Basal Cell Carcinoma

MONDO:0005341 Pathograph 5 skin carcinoma

Basal cell carcinoma (BCC) is the most common human malignancy, arising from basal cells of the epidermis and hair follicles. The majority of BCCs are driven by aberrant activation of the Hedgehog (Hh) signaling pathway, most commonly through loss-of-function mutations in PTCH1 (the Hedgehog receptor that normally inhibits Smoothened) or less frequently through activating mutations in SMO (Smoothened). UV radiation is the primary environmental risk factor, with BCCs occurring predominantly on sun-exposed skin. While locally invasive and destructive, BCC rarely metastasizes. Surgical excision is curative for most BCCs, but advanced or metastatic disease can be treated with Hedgehog pathway inhibitors such as vismodegib and sonidegib.

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0
Mappings
0
Definitions
0
Inheritance
5
Pathophysiology
1
Histopathology
7
Phenotypes
5
Pathograph
4
Genes
7
Treatments
4
Subtypes
0
Differentials
0
Datasets
0
Trials
0
Models
89
References
2
Deep Research
🏷

Classifications

Harrison's Chapter
cancer solid tumor
ICD-O Morphology
Carcinoma
◆

Subtypes

4
Nodular Basal Cell Carcinoma
Most common BCC subtype (60-80%), presenting as a pearly, dome-shaped nodule with telangiectasias and rolled borders. May develop central ulceration (rodent ulcer).
Superficial Basal Cell Carcinoma
Second most common subtype (10-15%), presenting as a thin, erythematous scaly plaque. Often occurs on the trunk and may be multifocal. Generally less aggressive than nodular type.
Morpheaform (Sclerosing) Basal Cell Carcinoma
Aggressive subtype with ill-defined borders and scar-like appearance. Shows extensive subclinical extension and higher recurrence rates. Requires wide excision margins.
Infiltrative Basal Cell Carcinoma
Aggressive variant with thin strands of tumor cells infiltrating the dermis. Often has poorly defined clinical margins and higher recurrence rates.
⚙

Pathophysiology

5
PTCH1 Loss of Function
PTCH1 (Patched 1) encodes a transmembrane receptor that normally suppresses Smoothened (SMO) in the absence of Hedgehog ligand. Loss-of-function mutations in PTCH1 release SMO from inhibition, resulting in constitutive Hedgehog pathway activation. PTCH1 mutations occur in approximately 70% of sporadic BCCs and are the germline cause of Gorlin syndrome.
basal cell of epidermis link
smoothened signaling pathway link ↑ INCREASED
skin of body link
Downstream
Constitutive Hedgehog Pathway Activation Loss of PTCH1 releases SMO from tonic inhibition
Show evidence (3 references)
PMID:19082818 PARTIAL
"signaling has been reported for sporadic and hereditary basal cell carcinoma"
Supports aberrant Hedgehog signaling as a driver in basal cell carcinoma.
PMID:29274272 SUPPORT
"pathway is associated with developmental anomalies and cancer, including Gorlin"
Confirms that Hedgehog pathway deregulation, including PTCH1 mutations causing Gorlin syndrome, drives BCC development.
PMID:20301330 SUPPORT
"germline pathogenic variant in PTCH1 or SUFU by molecular genetic testing"
GeneReviews confirms germline PTCH1 pathogenic variants cause nevoid basal cell carcinoma syndrome.
SMO Activating Mutations
Smoothened (SMO) is a G-protein coupled receptor-like protein that transduces Hedgehog signal. Activating mutations in SMO, though less common than PTCH1 loss, render SMO constitutively active regardless of PTCH1 status. Some SMO mutations confer resistance to vismodegib.
basal cell of epidermis link
smoothened signaling pathway link ↑ INCREASED
Downstream
Constitutive Hedgehog Pathway Activation Activating SMO mutations bypass PTCH1 inhibition
Constitutive Hedgehog Pathway Activation
Loss of PTCH1 or activating SMO mutations result in constitutive activation of the Hedgehog signaling cascade. Active SMO translocates to the primary cilium and promotes activation of GLI transcription factors (GLI1, GLI2), which drive expression of target genes promoting proliferation and survival.
smoothened signaling pathway link ↑ INCREASED
Downstream
GLI Transcription Factor Activation SMO activation leads to processing and nuclear translocation of GLI1/2
Show evidence (2 references)
PMID:29274272 SUPPORT
"activation of the Hh signaling pathway is caused by mutations in the related"
Describes how aberrant Hedgehog pathway activation occurs through ligand-independent mutations.
PMID:24259609 SUPPORT
"BCC. Vismodegib is a small-molecule inhibitor of Hh signaling that acts by"
Confirms constitutive Hedgehog pathway activation in BCC and the role of SMO in downstream transcriptional activation.
GLI Transcription Factor Activation
Active Hedgehog signaling promotes GLI transcription factor processing and nuclear translocation. GLI1 and GLI2 activate transcription of target genes including PTCH1, GLI1 (positive feedback), cyclin D1, MYC, and BCL2, promoting proliferation and survival of basal cells.
cell population proliferation link ↑ INCREASED
Downstream
Uncontrolled Basal Cell Proliferation GLI target genes drive cell cycle entry and tumor growth
Uncontrolled Basal Cell Proliferation
Constitutive Hedgehog signaling drives proliferation of basal cells through GLI-mediated transcription of cell cycle regulators, leading to tumor formation. The proliferating cells maintain a basal cell phenotype with peripheral palisading characteristic of BCC histology.
basal cell of epidermis link
cell population proliferation link ↑ INCREASED
skin of body link
✶

Histopathology

1
Basal Cell Carcinoma VERY_FREQUENT
Basal cell carcinomas are common cutaneous carcinomas.
Show evidence (1 reference)
PMID:36921301 SUPPORT
"Basal cell carcinomas are one of the most common cutaneous carcinomas and show"
Abstract notes basal cell carcinomas are among the most common cutaneous carcinomas.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Basal Cell Carcinoma Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

7
Cardiovascular 1
Telangiectasia Telangiectasia (HP:0001009)
Integument 5
Basal Cell Carcinoma OBLIGATE Basal cell carcinoma (HP:0002671)
Skin Neoplasm OBLIGATE Neoplasm of the skin (HP:0008069)
Skin Ulceration Skin ulcer (HP:0200042)
Skin Erosion Skin erosion (HP:0200041)
Erythematous Plaque Erythematous plaque (HP:0025474)
Other 1
Pearly Papule Papule (HP:0200034)
🧬

Genetic Associations

4
PTCH1 (Loss-of-Function Mutations)
Show evidence (1 reference)
PMID:20301330 SUPPORT
"beginning in the second decade of life, and/or basal cell carcinomas (BCCs)"
GeneReviews confirms PTCH1 germline mutations cause Gorlin syndrome with multiple BCCs.
SMO (Activating Mutations)
TP53 (Somatic Mutations)
Show evidence (1 reference)
PMID:25196205 SUPPORT
"In the 30 BCC samples, 6 TP53 point mutations were found (frequency of"
Demonstrates TP53 mutations in sporadic BCC with UV-specific mutation signatures.
SUFU (Germline Loss-of-Function Mutations)
Show evidence (1 reference)
PMID:20301330 SUPPORT
"germline pathogenic variant in PTCH1 or SUFU by molecular genetic testing"
GeneReviews confirms germline SUFU pathogenic variants can establish nevoid basal cell carcinoma syndrome.
💊

Treatments

7
Surgical Excision
Action: surgical procedure MAXO:0000004
Standard treatment for most BCCs with excellent cure rates (95% or higher). Mohs micrographic surgery provides highest cure rates for high-risk tumors through complete margin assessment while preserving tissue.
Show evidence (2 references)
PMID:37604067 SUPPORT
"surgery shall be offered in high-risk and recurrent BCC, and BCC located on"
European guideline confirms surgery as first-line treatment and recommends Mohs for high-risk BCC.
PMID:30033747 SUPPORT
"appropriate for primary BCCs of the face that are >1 cm, have aggressive"
Systematic review provides evidence-based indications for Mohs surgery in BCC.
Vismodegib
Action: targeted therapy Ontology label: Targeted Therapy NCIT:C93352
Agent: vismodegib ↗
Hedgehog pathway inhibitor that binds and inhibits Smoothened. FDA-approved for locally advanced or metastatic BCC. Response rates of 30-60% in advanced disease. Side effects include muscle spasms, alopecia, and dysgeusia.
Show evidence (1 reference)
PMID:24259609 SUPPORT
"resulted in a 30% and 43% objective response rate in patients with mBCC and"
Confirms FDA approval and clinical response rates for vismodegib in advanced BCC.
Sonidegib
Action: targeted therapy Ontology label: Targeted Therapy NCIT:C93352
Agent: sonidegib ↗
Second SMO inhibitor approved for locally advanced BCC. Similar mechanism of action to vismodegib with comparable efficacy profile. May provide alternative for patients intolerant of vismodegib.
Show evidence (1 reference)
PMID:27189494 SUPPORT
"Sonidegib, also known as LDE225, is an orally available SMO antagonist that was"
Confirms FDA approval of sonidegib for locally advanced BCC.
Radiation Therapy
Action: radiation therapy MAXO:0000014
Alternative treatment for patients who are not surgical candidates or refuse surgery. Also used for adjuvant treatment of high-risk tumors with perineural invasion or positive margins.
Show evidence (1 reference)
PMID:37604067 SUPPORT
"Radiotherapy represents a valid alternative in patients who are not candidates"
European guideline supports radiotherapy as an alternative to surgery for BCC.
Topical Therapy
Action: topical pharmacotherapy MAXO:0001573
Agent: imiquimod ↗ 5-fluorouracil ↗
Topical imiquimod (immune response modifier) or 5-fluorouracil may be used for superficial BCC. Not appropriate for nodular or aggressive subtypes.
Show evidence (2 references)
PMID:15943496 SUPPORT
"clearance of single superficial BCC lesions compared with vehicle in patients"
Demonstrates efficacy of topical imiquimod for superficial BCC in randomized trials.
PMID:37604067 SUPPORT
"considered in patients with low-risk superficial BCC. Photodynamic therapy is an"
European guideline supports topical therapies for low-risk superficial BCC.
Photodynamic Therapy
Action: photodynamic therapy MAXO:0020022
Photodynamic therapy is a tissue-directed option for superficial and low-risk nodular BCCs, using light activation of a photosensitizer to destroy tumor tissue.
Show evidence (1 reference)
PMID:37604067 SUPPORT
"effective treatment for superficial and low-risk nodular BCCs"
European guideline supports photodynamic therapy for superficial and low-risk nodular BCCs.
Immune Checkpoint Inhibitors
Action: immunotherapy Ontology label: Immunotherapy NCIT:C15262
Agent: cemiplimab ↗
Cemiplimab (anti-PD-1) has shown activity in locally advanced and metastatic BCC refractory to Hedgehog inhibitors, representing a treatment option for this previously difficult population.
Show evidence (2 references)
PMID:34000246 SUPPORT
"central review was observed in 26 (31%; 95% CI 21-42) of 84 patients, including"
Phase 2 trial demonstrates 31% objective response rate for cemiplimab in locally advanced BCC after HHI failure.
PMID:37604067 SUPPORT
"antibodies (cemiplimab) is a second-line treatment in patients with"
European guideline positions cemiplimab as second-line after hedgehog inhibitor failure.
🌍

Environmental Factors

1
Ultraviolet Radiation
Chronic UV exposure is the primary risk factor for BCC development. UV signature mutations (C>T transitions at dipyrimidine sites) are found in most BCCs. Both UVA and UVB contribute to BCC risk.
Show evidence (1 reference)
PMID:17274935 SUPPORT
"modifiable factor determining early expression and frequency of BCC development"
Review confirms UV light as the primary modifiable risk factor for BCC.
{ }

Source YAML

click to show 
name: Basal Cell Carcinoma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-05-06T00:21:04Z'
description: >-
  Basal cell carcinoma (BCC) is the most common human malignancy, arising from
  basal cells of the epidermis and hair follicles. The majority of BCCs are driven
  by aberrant activation of the Hedgehog (Hh) signaling pathway, most commonly
  through loss-of-function mutations in PTCH1 (the Hedgehog receptor that normally
  inhibits Smoothened) or less frequently through activating mutations in SMO
  (Smoothened). UV radiation is the primary environmental risk factor, with BCCs
  occurring predominantly on sun-exposed skin. While locally invasive and destructive,
  BCC rarely metastasizes. Surgical excision is curative for most BCCs, but advanced
  or metastatic disease can be treated with Hedgehog pathway inhibitors such as
  vismodegib and sonidegib.
categories:
- Skin Cancer
- Hedgehog Pathway Disease
parents:
- skin carcinoma
has_subtypes:
- name: Nodular Basal Cell Carcinoma
  description: >-
    Most common BCC subtype (60-80%), presenting as a pearly, dome-shaped nodule
    with telangiectasias and rolled borders. May develop central ulceration
    (rodent ulcer).
- name: Superficial Basal Cell Carcinoma
  description: >-
    Second most common subtype (10-15%), presenting as a thin, erythematous
    scaly plaque. Often occurs on the trunk and may be multifocal. Generally
    less aggressive than nodular type.
- name: Morpheaform (Sclerosing) Basal Cell Carcinoma
  description: >-
    Aggressive subtype with ill-defined borders and scar-like appearance.
    Shows extensive subclinical extension and higher recurrence rates.
    Requires wide excision margins.
- name: Infiltrative Basal Cell Carcinoma
  description: >-
    Aggressive variant with thin strands of tumor cells infiltrating the dermis.
    Often has poorly defined clinical margins and higher recurrence rates.
pathophysiology:
- name: PTCH1 Loss of Function
  description: >-
    PTCH1 (Patched 1) encodes a transmembrane receptor that normally suppresses
    Smoothened (SMO) in the absence of Hedgehog ligand. Loss-of-function mutations
    in PTCH1 release SMO from inhibition, resulting in constitutive Hedgehog pathway
    activation. PTCH1 mutations occur in approximately 70% of sporadic BCCs and
    are the germline cause of Gorlin syndrome.
  evidence:
  - reference: PMID:19082818
    reference_title: "[Activation of sonic hedgehog signaling in keratocystic odontogenic tumors]."
    supports: PARTIAL
    snippet: "signaling has been reported for sporadic and hereditary basal cell carcinoma"
    explanation: "Supports aberrant Hedgehog signaling as a driver in basal cell carcinoma."
  - reference: PMID:29274272
    supports: SUPPORT
    snippet: "pathway is associated with developmental anomalies and cancer, including Gorlin"
    explanation: "Confirms that Hedgehog pathway deregulation, including PTCH1 mutations causing Gorlin syndrome, drives BCC development."
  - reference: PMID:20301330
    supports: SUPPORT
    snippet: "germline pathogenic variant in PTCH1 or SUFU by molecular genetic testing"
    explanation: "GeneReviews confirms germline PTCH1 pathogenic variants cause nevoid basal cell carcinoma syndrome."
  cell_types:
  - preferred_term: basal cell of epidermis
    term:
      id: CL:0002187
      label: basal cell of epidermis
  biological_processes:
  - preferred_term: smoothened signaling pathway
    modifier: INCREASED
    term:
      id: GO:0007224
      label: smoothened signaling pathway
  locations:
  - preferred_term: skin of body
    term:
      id: UBERON:0002097
      label: skin of body
  downstream:
  - target: Constitutive Hedgehog Pathway Activation
    description: Loss of PTCH1 releases SMO from tonic inhibition
- name: SMO Activating Mutations
  description: >-
    Smoothened (SMO) is a G-protein coupled receptor-like protein that transduces
    Hedgehog signal. Activating mutations in SMO, though less common than PTCH1
    loss, render SMO constitutively active regardless of PTCH1 status. Some SMO
    mutations confer resistance to vismodegib.
  cell_types:
  - preferred_term: basal cell of epidermis
    term:
      id: CL:0002187
      label: basal cell of epidermis
  biological_processes:
  - preferred_term: smoothened signaling pathway
    modifier: INCREASED
    term:
      id: GO:0007224
      label: smoothened signaling pathway
  downstream:
  - target: Constitutive Hedgehog Pathway Activation
    description: Activating SMO mutations bypass PTCH1 inhibition
- name: Constitutive Hedgehog Pathway Activation
  description: >-
    Loss of PTCH1 or activating SMO mutations result in constitutive activation
    of the Hedgehog signaling cascade. Active SMO translocates to the primary
    cilium and promotes activation of GLI transcription factors (GLI1, GLI2),
    which drive expression of target genes promoting proliferation and survival.
  evidence:
  - reference: PMID:29274272
    supports: SUPPORT
    snippet: activation of the Hh signaling pathway is caused by mutations in the related
    explanation: Describes how aberrant Hedgehog pathway activation occurs through ligand-independent mutations.
  - reference: PMID:24259609
    supports: SUPPORT
    snippet: BCC. Vismodegib is a small-molecule inhibitor of Hh signaling that acts by
    explanation: Confirms constitutive Hedgehog pathway activation in BCC and the role of SMO in downstream transcriptional activation.
  biological_processes:
  - preferred_term: smoothened signaling pathway
    modifier: INCREASED
    term:
      id: GO:0007224
      label: smoothened signaling pathway
  downstream:
  - target: GLI Transcription Factor Activation
    description: SMO activation leads to processing and nuclear translocation of GLI1/2
- name: GLI Transcription Factor Activation
  description: >-
    Active Hedgehog signaling promotes GLI transcription factor processing and
    nuclear translocation. GLI1 and GLI2 activate transcription of target genes
    including PTCH1, GLI1 (positive feedback), cyclin D1, MYC, and BCL2,
    promoting proliferation and survival of basal cells.
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  downstream:
  - target: Uncontrolled Basal Cell Proliferation
    description: GLI target genes drive cell cycle entry and tumor growth
- name: Uncontrolled Basal Cell Proliferation
  description: >-
    Constitutive Hedgehog signaling drives proliferation of basal cells through
    GLI-mediated transcription of cell cycle regulators, leading to tumor formation.
    The proliferating cells maintain a basal cell phenotype with peripheral
    palisading characteristic of BCC histology.
  cell_types:
  - preferred_term: basal cell of epidermis
    term:
      id: CL:0002187
      label: basal cell of epidermis
  locations:
  - preferred_term: skin of body
    term:
      id: UBERON:0002097
      label: skin of body
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
histopathology:
- name: Basal Cell Carcinoma
  finding_term:
    preferred_term: Basal Cell Carcinoma
    term:
      id: NCIT:C156767
      label: Basal Cell Carcinoma
  frequency: VERY_FREQUENT
  description: Basal cell carcinomas are common cutaneous carcinomas.
  evidence:
  - reference: PMID:36921301
    reference_title: "Pagetoid Spread in Basal Cell Carcinoma: Potential for Misdiagnosis."
    supports: SUPPORT
    snippet: "Basal cell carcinomas are one of the most common cutaneous carcinomas and show"
    explanation: Abstract notes basal cell carcinomas are among the most common cutaneous carcinomas.

phenotypes:
- category: Dermatologic
  name: Basal Cell Carcinoma
  frequency: OBLIGATE
  diagnostic: true
  description: >-
    Most common skin malignancy, typically presenting as pearly papule or nodule
    with telangiectasias on sun-exposed skin. Multiple clinical subtypes exist
    with varying biological behavior.
  phenotype_term:
    preferred_term: Basal cell carcinoma
    term:
      id: HP:0002671
      label: Basal cell carcinoma
- category: Dermatologic
  name: Skin Neoplasm
  frequency: OBLIGATE
  description: >-
    Cutaneous tumors arising predominantly on chronically sun-exposed areas
    including the head, neck, and upper extremities. The face is the most
    common location.
  phenotype_term:
    preferred_term: Neoplasm of the skin
    term:
      id: HP:0008069
      label: Neoplasm of the skin
- category: Dermatologic
  name: Pearly Papule
  description: >-
    Characteristic translucent or pearly papule with a smooth surface,
    the hallmark presentation of nodular BCC. Often exhibits a rolled border.
  phenotype_term:
    preferred_term: Pearly papule
    term:
      id: HP:0200034
      label: Papule
- category: Dermatologic
  name: Telangiectasia
  description: >-
    Arborizing (tree-like) telangiectasias visible on the surface of BCC
    lesions, a key dermoscopic feature used in clinical diagnosis. Present
    in most nodular BCCs.
  phenotype_term:
    preferred_term: Telangiectasia
    term:
      id: HP:0001009
      label: Telangiectasia
- category: Dermatologic
  name: Skin Ulceration
  description: >-
    Central ulceration (rodent ulcer) may develop in advanced or neglected
    nodular BCCs. Ulceration is a feature of locally advanced disease.
  phenotype_term:
    preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
- category: Dermatologic
  name: Skin Erosion
  description: >-
    Superficial skin erosion may occur in BCC lesions, particularly in
    superficial BCC subtype where thin erythematous plaques may show erosion.
  phenotype_term:
    preferred_term: Skin erosion
    term:
      id: HP:0200041
      label: Skin erosion
- category: Dermatologic
  name: Erythematous Plaque
  subtype: Superficial Basal Cell Carcinoma
  description: >-
    Thin, erythematous, scaly plaques are the hallmark of superficial BCC
    subtype, often occurring on the trunk. May be confused with eczema or
    psoriasis.
  phenotype_term:
    preferred_term: Erythematous plaque
    term:
      id: HP:0025474
      label: Erythematous plaque
environmental:
- name: Ultraviolet Radiation
  description: >-
    Chronic UV exposure is the primary risk factor for BCC development.
    UV signature mutations (C>T transitions at dipyrimidine sites) are
    found in most BCCs. Both UVA and UVB contribute to BCC risk.
  evidence:
  - reference: PMID:17274935
    supports: SUPPORT
    snippet: modifiable factor determining early expression and frequency of BCC development
    explanation: Review confirms UV light as the primary modifiable risk factor for BCC.
genetic:
- name: PTCH1
  gene_term:
    preferred_term: PTCH1
    term:
      id: hgnc:9585
      label: PTCH1
  association: Loss-of-Function Mutations
  notes: >-
    PTCH1 encodes the Hedgehog receptor. Biallelic inactivation (loss of heterozygosity
    or compound heterozygous mutations) occurs in approximately 70% of sporadic BCCs.
    Germline PTCH1 mutations cause Gorlin syndrome (nevoid basal cell carcinoma
    syndrome) with multiple BCCs, jaw cysts, and other developmental abnormalities.
  evidence:
  - reference: PMID:20301330
    supports: SUPPORT
    snippet: beginning in the second decade of life, and/or basal cell carcinomas (BCCs)
    explanation: GeneReviews confirms PTCH1 germline mutations cause Gorlin syndrome with multiple BCCs.
- name: SMO
  gene_term:
    preferred_term: SMO
    term:
      id: hgnc:11119
      label: SMO
  association: Activating Mutations
  notes: >-
    Smoothened mutations occur in approximately 10% of BCCs without PTCH1 mutations.
    Some SMO mutations (D473H) confer primary or acquired resistance to vismodegib
    and sonidegib.
- name: TP53
  gene_term:
    preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  association: Somatic Mutations
  notes: >-
    TP53 mutations occur in approximately 40-50% of BCCs, often with UV signature.
    TP53 inactivation contributes to genomic instability and tumor progression
    but is not sufficient for BCC development without Hedgehog pathway activation.
  evidence:
  - reference: PMID:25196205
    supports: SUPPORT
    snippet: In the 30 BCC samples, 6 TP53 point mutations were found (frequency of
    explanation: Demonstrates TP53 mutations in sporadic BCC with UV-specific mutation signatures.
- name: SUFU
  gene_term:
    preferred_term: SUFU
    term:
      id: hgnc:16466
      label: SUFU
  association: Germline Loss-of-Function Mutations
  notes: >-
    SUFU pathogenic variants are a less common germline cause of nevoid basal
    cell carcinoma syndrome, linking Hedgehog pathway dysregulation to inherited
    susceptibility for multiple BCCs.
  evidence:
  - reference: PMID:20301330
    supports: SUPPORT
    snippet: "germline pathogenic variant in PTCH1 or SUFU by molecular genetic testing"
    explanation: GeneReviews confirms germline SUFU pathogenic variants can establish nevoid basal cell carcinoma syndrome.
treatments:
- name: Surgical Excision
  description: >-
    Standard treatment for most BCCs with excellent cure rates (95% or higher).
    Mohs micrographic surgery provides highest cure rates for high-risk tumors
    through complete margin assessment while preserving tissue.
  evidence:
  - reference: PMID:37604067
    supports: SUPPORT
    snippet: surgery shall be offered in high-risk and recurrent BCC, and BCC located on
    explanation: European guideline confirms surgery as first-line treatment and recommends Mohs for high-risk BCC.
  - reference: PMID:30033747
    supports: SUPPORT
    snippet: appropriate for primary BCCs of the face that are >1 cm, have aggressive
    explanation: Systematic review provides evidence-based indications for Mohs surgery in BCC.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Vismodegib
  description: >-
    Hedgehog pathway inhibitor that binds and inhibits Smoothened. FDA-approved
    for locally advanced or metastatic BCC. Response rates of 30-60% in advanced
    disease. Side effects include muscle spasms, alopecia, and dysgeusia.
  evidence:
  - reference: PMID:24259609
    supports: SUPPORT
    snippet: resulted in a 30% and 43% objective response rate in patients with mBCC and
    explanation: Confirms FDA approval and clinical response rates for vismodegib in advanced BCC.
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: vismodegib
      term:
        id: CHEBI:66903
        label: vismodegib
- name: Sonidegib
  description: >-
    Second SMO inhibitor approved for locally advanced BCC. Similar mechanism
    of action to vismodegib with comparable efficacy profile. May provide
    alternative for patients intolerant of vismodegib.
  evidence:
  - reference: PMID:27189494
    supports: SUPPORT
    snippet: Sonidegib, also known as LDE225, is an orally available SMO antagonist that was
    explanation: Confirms FDA approval of sonidegib for locally advanced BCC.
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: sonidegib
      term:
        id: CHEBI:90863
        label: sonidegib
- name: Radiation Therapy
  description: >-
    Alternative treatment for patients who are not surgical candidates or
    refuse surgery. Also used for adjuvant treatment of high-risk tumors
    with perineural invasion or positive margins.
  evidence:
  - reference: PMID:37604067
    supports: SUPPORT
    snippet: Radiotherapy represents a valid alternative in patients who are not candidates
    explanation: European guideline supports radiotherapy as an alternative to surgery for BCC.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
- name: Topical Therapy
  description: >-
    Topical imiquimod (immune response modifier) or 5-fluorouracil may be
    used for superficial BCC. Not appropriate for nodular or aggressive
    subtypes.
  evidence:
  - reference: PMID:15943496
    supports: SUPPORT
    snippet: clearance of single superficial BCC lesions compared with vehicle in patients
    explanation: Demonstrates efficacy of topical imiquimod for superficial BCC in randomized trials.
  - reference: PMID:37604067
    supports: SUPPORT
    snippet: considered in patients with low-risk superficial BCC. Photodynamic therapy is an
    explanation: European guideline supports topical therapies for low-risk superficial BCC.
  treatment_term:
    preferred_term: topical pharmacotherapy
    term:
      id: MAXO:0001573
      label: topical pharmacotherapy
    therapeutic_agent:
    - preferred_term: imiquimod
      term:
        id: CHEBI:36704
        label: imiquimod
    - preferred_term: 5-fluorouracil
      term:
        id: CHEBI:46345
        label: 5-fluorouracil
- name: Photodynamic Therapy
  description: >-
    Photodynamic therapy is a tissue-directed option for superficial and low-risk
    nodular BCCs, using light activation of a photosensitizer to destroy tumor
    tissue.
  evidence:
  - reference: PMID:37604067
    supports: SUPPORT
    snippet: effective treatment for superficial and low-risk nodular BCCs
    explanation: European guideline supports photodynamic therapy for superficial and low-risk nodular BCCs.
  treatment_term:
    preferred_term: photodynamic therapy
    term:
      id: MAXO:0020022
      label: photodynamic therapy
- name: Immune Checkpoint Inhibitors
  description: >-
    Cemiplimab (anti-PD-1) has shown activity in locally advanced and metastatic
    BCC refractory to Hedgehog inhibitors, representing a treatment option for
    this previously difficult population.
  evidence:
  - reference: PMID:34000246
    supports: SUPPORT
    snippet: central review was observed in 26 (31%; 95% CI 21-42) of 84 patients, including
    explanation: Phase 2 trial demonstrates 31% objective response rate for cemiplimab in locally advanced BCC after HHI failure.
  - reference: PMID:37604067
    supports: SUPPORT
    snippet: antibodies (cemiplimab) is a second-line treatment in patients with
    explanation: European guideline positions cemiplimab as second-line after hedgehog inhibitor failure.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
    therapeutic_agent:
    - preferred_term: cemiplimab
      term:
        id: NCIT:C121540
        label: Cemiplimab
disease_term:
  preferred_term: skin basal cell carcinoma
  term:
    id: MONDO:0005341
    label: skin basal cell carcinoma
notes: >-
  BCC is the most common cancer worldwide, with incidence continuing to rise.
  While metastasis is rare (less than 0.5%), locally advanced BCC can cause
  significant morbidity through tissue destruction. Hedgehog pathway inhibitors
  have transformed treatment of advanced disease, but resistance develops in
  most patients through SMO mutations or downstream pathway alterations. The
  high tumor mutational burden of BCC (UV signature) provides rationale for
  immunotherapy approaches.

classifications:
  icdo_morphology:
    classification_value: Carcinoma
  harrisons_chapter:
  - classification_value: cancer
  - classification_value: solid tumor
references:
- reference: DOI:10.1038/jid.2012.403
  title: Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma
    supporting_text: Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma
- reference: DOI:10.1038/s41420-025-02327-w
  title: Mechanisms and therapeutic potential of the hedgehog signaling pathway in cancer
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: A sort of major malignant disease, cancer can compromise human health wherever.
    supporting_text: A sort of major malignant disease, cancer can compromise human health wherever.
    evidence:
    - reference: DOI:10.1038/s41420-025-02327-w
      reference_title: Mechanisms and therapeutic potential of the hedgehog signaling pathway in cancer
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: A sort of major malignant disease, cancer can compromise human health wherever.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.1038/s41467-022-35345-8
  title: A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers.
    supporting_text: Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers.
    evidence:
    - reference: DOI:10.1038/s41467-022-35345-8
      reference_title: A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.1038/s42003-023-05753-7
  title: Multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined.
    supporting_text: Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined.
    evidence:
    - reference: DOI:10.1038/s42003-023-05753-7
      reference_title: Multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.1093/bjd/ljac064
  title: Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs.
    supporting_text: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs.
    evidence:
    - reference: DOI:10.1093/bjd/ljac064
      reference_title: Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.1097/dss.0000000000000296
  title: Consensus for Nonmelanoma Skin Cancer Treatment
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Consensus for Nonmelanoma Skin Cancer Treatment
    supporting_text: Consensus for Nonmelanoma Skin Cancer Treatment
- reference: DOI:10.1111/cas.15823
  title: Epidemiology of skin cancer based on Japan's National Cancer Registry 2016–2017
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Skin cancer is most frequently diagnosed in the White population.
    supporting_text: Skin cancer is most frequently diagnosed in the White population.
    evidence:
    - reference: DOI:10.1111/cas.15823
      reference_title: Epidemiology of skin cancer based on Japan's National Cancer Registry 2016–2017
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Skin cancer is most frequently diagnosed in the White population.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.1111/ddg.15566
  title: S2k guideline basal cell carcinoma of the skin (update 2023)
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Basal cell carcinoma is the most common malignant tumor in the fair‐skinned population and its incidence continues to rise.
    supporting_text: Basal cell carcinoma is the most common malignant tumor in the fair‐skinned population and its incidence continues to rise.
    evidence:
    - reference: DOI:10.1111/ddg.15566
      reference_title: S2k guideline basal cell carcinoma of the skin (update 2023)
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Basal cell carcinoma is the most common malignant tumor in the fair‐skinned population and its incidence continues to rise.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.1177/12034754221078201
  title: 'Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC).
    supporting_text: Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC).
    evidence:
    - reference: DOI:10.1177/12034754221078201
      reference_title: 'Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC).
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3389/fonc.2023.1111146
  title: 'The association of cemiplimab plus sonidegib for synchronous cutaneous squamous cell carcinoma and basal cell carcinoma of the head and neck: Two case reports'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors.
    supporting_text: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors.
    evidence:
    - reference: DOI:10.3389/fonc.2023.1111146
      reference_title: 'The association of cemiplimab plus sonidegib for synchronous cutaneous squamous cell carcinoma and basal cell carcinoma of the head and neck: Two case reports'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3390/biom13071067
  title: Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race.
    supporting_text: Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race.
    evidence:
    - reference: DOI:10.3390/biom13071067
      reference_title: Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3390/cancers16173075
  title: Therapeutic Advances in Advanced Basal Cell Carcinoma
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone.
    supporting_text: Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone.
    evidence:
    - reference: DOI:10.3390/cancers16173075
      reference_title: Therapeutic Advances in Advanced Basal Cell Carcinoma
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3390/cells12212534
  title: Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide.
    supporting_text: Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide.
    evidence:
    - reference: DOI:10.3390/cells12212534
      reference_title: Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3390/ijms25137056
  title: 'Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide.
    supporting_text: Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide.
    evidence:
    - reference: DOI:10.3390/ijms25137056
      reference_title: 'Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3390/ijms25158452
  title: 'Dysembryogenetic Pathogenesis of Basal Cell Carcinoma: The Evidence to Date'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: 'Dysembryogenetic Pathogenesis of Basal Cell Carcinoma: The Evidence to Date'
    supporting_text: The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for both onset and spread.
    evidence:
    - reference: DOI:10.3390/ijms25158452
      reference_title: 'Dysembryogenetic Pathogenesis of Basal Cell Carcinoma: The Evidence to Date'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for both onset and spread.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3390/jmp5020010
  title: 'Basal Cell Carcinoma: Diagnosis, Management and Prevention'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues.
    supporting_text: Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues.
    evidence:
    - reference: DOI:10.3390/jmp5020010
      reference_title: 'Basal Cell Carcinoma: Diagnosis, Management and Prevention'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.3390/nu16010100
  title: 'The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products.
    supporting_text: Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products.
    evidence:
    - reference: DOI:10.3390/nu16010100
      reference_title: 'The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.5826/dpc.1304a252
  title: Immunotherapy and Its Timing in Advanced Basal Cell Carcinoma Treatment
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment.
    supporting_text: For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment.
    evidence:
    - reference: DOI:10.5826/dpc.1304a252
      reference_title: Immunotherapy and Its Timing in Advanced Basal Cell Carcinoma Treatment
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: DOI:10.6004/jnccn.2023.0056
  title: Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology
  found_in:
  - Basal_Cell_Carcinoma-deep-research-falcon.md
  findings:
  - statement: Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States.
    supporting_text: Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States.
    evidence:
    - reference: DOI:10.6004/jnccn.2023.0056
      reference_title: Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:12542834
  title: Immunohistochemical and genetic analysis of mandibular cysts in heterozygous ptc knockout mice.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Alterations of human patched (ptc) homolog have been proven to be responsible for basal cell nevus syndrome (BCNS).
    supporting_text: Alterations of human patched (ptc) homolog have been proven to be responsible for basal cell nevus syndrome (BCNS).
    evidence:
    - reference: PMID:12542834
      reference_title: Immunohistochemical and genetic analysis of mandibular cysts in heterozygous ptc knockout mice.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: Alterations of human patched (ptc) homolog have been proven to be responsible for basal cell nevus syndrome (BCNS).
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:21700618
  title: Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2011 Sep 15;20(18):3718-24. doi: 10.1093/hmg/ddr287.'
    supporting_text: '2011 Sep 15;20(18):3718-24. doi: 10.1093/hmg/ddr287.'
    evidence:
    - reference: PMID:21700618
      reference_title: Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2011 Sep 15;20(18):3718-24. doi: 10.1093/hmg/ddr287.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:22945646
  title: Progeny of Lgr5-expressing hair follicle stem cell contributes to papillomavirus-induced tumor development in epidermis.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2013 Aug 8;32(32):3732-43. doi: 10.1038/onc.2012.375.'
    supporting_text: '2013 Aug 8;32(32):3732-43. doi: 10.1038/onc.2012.375.'
    evidence:
    - reference: PMID:22945646
      reference_title: Progeny of Lgr5-expressing hair follicle stem cell contributes to papillomavirus-induced tumor development in epidermis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2013 Aug 8;32(32):3732-43. doi: 10.1038/onc.2012.375.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:23196843
  title: Stem cell reprogramming as a driver of basal cell carcinoma.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2012 Dec;14(12):1246-7. doi: 10.1038/ncb2631.'
    supporting_text: '2012 Dec;14(12):1246-7. doi: 10.1038/ncb2631.'
    evidence:
    - reference: PMID:23196843
      reference_title: Stem cell reprogramming as a driver of basal cell carcinoma.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2012 Dec;14(12):1246-7. doi: 10.1038/ncb2631.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:24485530
  title: 'Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2014 Apr;70(4):748-762. doi: 10.1016/j.jaad.2013.11.038.'
    supporting_text: '2014 Apr;70(4):748-762. doi: 10.1016/j.jaad.2013.11.038.'
    evidence:
    - reference: PMID:24485530
      reference_title: 'Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2014 Apr;70(4):748-762. doi: 10.1016/j.jaad.2013.11.038.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:24662765
  title: DMBA/TPA treatment is necessary for BCC formation from patched deficient epidermal cells in Ptch(flox/flox)CD4Cre(+/-) mice.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2014 Oct;134(10):2620-2629. doi: 10.1038/jid.2014.157.'
    supporting_text: '2014 Oct;134(10):2620-2629. doi: 10.1038/jid.2014.157.'
    evidence:
    - reference: PMID:24662765
      reference_title: DMBA/TPA treatment is necessary for BCC formation from patched deficient epidermal cells in Ptch(flox/flox)CD4Cre(+/-) mice.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: '2014 Oct;134(10):2620-2629. doi: 10.1038/jid.2014.157.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:25408650
  title: 'Preventive Long-Term Effects of a Topical Film-Forming Medical Device with Ultra-High UV Protection Filters and DNA Repair Enzyme in Xeroderma Pigmentosum: A Retrospective Study of Eight Cases.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2014 Sep 19;6(3):222-6. doi: 10.1159/000368182. eCollection 2014 Sep.'
    supporting_text: '2014 Sep 19;6(3):222-6. doi: 10.1159/000368182. eCollection 2014 Sep.'
    evidence:
    - reference: PMID:25408650
      reference_title: 'Preventive Long-Term Effects of a Topical Film-Forming Medical Device with Ultra-High UV Protection Filters and DNA Repair Enzyme in Xeroderma Pigmentosum: A Retrospective Study of Eight Cases.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2014 Sep 19;6(3):222-6. doi: 10.1159/000368182. eCollection 2014 Sep.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:26921200
  title: 'Preoperative prediction of histopathological outcome in basal cell carcinoma: flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC).
    supporting_text: Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC).
    evidence:
    - reference: PMID:26921200
      reference_title: 'Preoperative prediction of histopathological outcome in basal cell carcinoma: flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types.'
      supports: SUPPORT
      evidence_source: COMPUTATIONAL
      snippet: Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC).
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:27388747
  title: AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2016 Oct;9(10):794-802. doi: 10.1158/1940-6207.CAPR-16-0066.'
    supporting_text: '2016 Oct;9(10):794-802. doi: 10.1158/1940-6207.CAPR-16-0066.'
    evidence:
    - reference: PMID:27388747
      reference_title: AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: '2016 Oct;9(10):794-802. doi: 10.1158/1940-6207.CAPR-16-0066.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:27663613
  title: One-Year Review of the SCREEN (Skin Cancer Post-Transplant) Clinic.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2017 Jan/Feb;21(1):80-81. doi: 10.1177/1203475416671694.'
    supporting_text: '2017 Jan/Feb;21(1):80-81. doi: 10.1177/1203475416671694.'
    evidence:
    - reference: PMID:27663613
      reference_title: One-Year Review of the SCREEN (Skin Cancer Post-Transplant) Clinic.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2017 Jan/Feb;21(1):80-81. doi: 10.1177/1203475416671694.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:28070642
  title: Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2017 Mar;470(3):301-310. doi: 10.1007/s00428-016-2061-3.'
    supporting_text: '2017 Mar;470(3):301-310. doi: 10.1007/s00428-016-2061-3.'
    evidence:
    - reference: PMID:28070642
      reference_title: Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2017 Mar;470(3):301-310. doi: 10.1007/s00428-016-2061-3.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:28207005
  title: 'Basal cell carcinoma arising in outdoor workers versus indoor workers: a retrospective study.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Husein-Elahmed H(1), Gutierrez-Salmeron MT(1), Aneiros-Cachaza J(2), Naranjo-Sintes R(1).
    supporting_text: Husein-Elahmed H(1), Gutierrez-Salmeron MT(1), Aneiros-Cachaza J(2), Naranjo-Sintes R(1).
    evidence:
    - reference: PMID:28207005
      reference_title: 'Basal cell carcinoma arising in outdoor workers versus indoor workers: a retrospective study.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Husein-Elahmed H(1), Gutierrez-Salmeron MT(1), Aneiros-Cachaza J(2), Naranjo-Sintes R(1).
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:28220485
  title: 'Epidemiology of basal cell carcinoma: scholarly review.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2017 Aug;177(2):359-372. doi: 10.1111/bjd.15321.'
    supporting_text: '2017 Aug;177(2):359-372. doi: 10.1111/bjd.15321.'
    evidence:
    - reference: PMID:28220485
      reference_title: 'Epidemiology of basal cell carcinoma: scholarly review.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2017 Aug;177(2):359-372. doi: 10.1111/bjd.15321.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:28925402
  title: Contrasting effects of an Mdm2 functional polymorphism on tumor phenotypes.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2018 Jan 18;37(3):332-340. doi: 10.1038/onc.2017.344.'
    supporting_text: '2018 Jan 18;37(3):332-340. doi: 10.1038/onc.2017.344.'
    evidence:
    - reference: PMID:28925402
      reference_title: Contrasting effects of an Mdm2 functional polymorphism on tumor phenotypes.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2018 Jan 18;37(3):332-340. doi: 10.1038/onc.2017.344.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:29723362
  title: 'Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern.
    supporting_text: The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern.
    evidence:
    - reference: PMID:29723362
      reference_title: 'Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:30908599
  title: 'Genome-wide association studies and polygenic risk scores for skin cancer: clinically useful yet?'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value.
    supporting_text: Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value.
    evidence:
    - reference: PMID:30908599
      reference_title: 'Genome-wide association studies and polygenic risk scores for skin cancer: clinically useful yet?'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:30987174
  title: A Retrospective Study of the Diagnostic Accuracy of In Vivo Reflectance Confocal Microscopy for Basal Cell Carcinoma Diagnosis and Subtyping.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2019 Apr 3;8(4):449. doi: 10.3390/jcm8040449.'
    supporting_text: '2019 Apr 3;8(4):449. doi: 10.3390/jcm8040449.'
    evidence:
    - reference: PMID:30987174
      reference_title: A Retrospective Study of the Diagnostic Accuracy of In Vivo Reflectance Confocal Microscopy for Basal Cell Carcinoma Diagnosis and Subtyping.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2019 Apr 3;8(4):449. doi: 10.3390/jcm8040449.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:31288208
  title: 'Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2019 Sep;118:10-34. doi: 10.1016/j.ejca.2019.06.003.'
    supporting_text: '2019 Sep;118:10-34. doi: 10.1016/j.ejca.2019.06.003.'
    evidence:
    - reference: PMID:31288208
      reference_title: 'Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2019 Sep;118:10-34. doi: 10.1016/j.ejca.2019.06.003.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:31419349
  title: 'Basal cell carcinoma genetic susceptibility increases the rate of skin ageing: a Mendelian randomization study.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Onset of basal cell carcinoma (BCC) is connected to skin ageing, but it is unclear whether higher BCC genetic susceptibility drives skin ageing.
    supporting_text: Onset of basal cell carcinoma (BCC) is connected to skin ageing, but it is unclear whether higher BCC genetic susceptibility drives skin ageing.
    evidence:
    - reference: PMID:31419349
      reference_title: 'Basal cell carcinoma genetic susceptibility increases the rate of skin ageing: a Mendelian randomization study.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Onset of basal cell carcinoma (BCC) is connected to skin ageing, but it is unclear whether higher BCC genetic susceptibility drives skin ageing.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:31585338
  title: 'Cutaneous keratinocyte cancers of the head and neck: Epidemiology, risk factors and clinical, dermoscopic and reflectance confocal microscopic features.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2019 Nov;98:109-117. doi: 10.1016/j.oraloncology.2019.09.019.'
    supporting_text: '2019 Nov;98:109-117. doi: 10.1016/j.oraloncology.2019.09.019.'
    evidence:
    - reference: PMID:31585338
      reference_title: 'Cutaneous keratinocyte cancers of the head and neck: Epidemiology, risk factors and clinical, dermoscopic and reflectance confocal microscopic features.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2019 Nov;98:109-117. doi: 10.1016/j.oraloncology.2019.09.019.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:32492418
  title: Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2020 Jun 2;31(9):107702. doi: 10.1016/j.celrep.2020.107702.'
    supporting_text: '2020 Jun 2;31(9):107702. doi: 10.1016/j.celrep.2020.107702.'
    evidence:
    - reference: PMID:32492418
      reference_title: Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2020 Jun 2;31(9):107702. doi: 10.1016/j.celrep.2020.107702.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:32930885
  title: Retrospective investigation of hereditary syndromes in patients with medulloblastoma in a single institution.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2021 Feb;37(2):411-417. doi: 10.1007/s00381-020-04885-z.'
    supporting_text: '2021 Feb;37(2):411-417. doi: 10.1007/s00381-020-04885-z.'
    evidence:
    - reference: PMID:32930885
      reference_title: Retrospective investigation of hereditary syndromes in patients with medulloblastoma in a single institution.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2021 Feb;37(2):411-417. doi: 10.1007/s00381-020-04885-z.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:33242578
  title: Epigenetic regulation in the pathogenesis of non-melanoma skin cancer.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2022 Aug;83:36-56. doi: 10.1016/j.semcancer.2020.11.009.'
    supporting_text: '2022 Aug;83:36-56. doi: 10.1016/j.semcancer.2020.11.009.'
    evidence:
    - reference: PMID:33242578
      reference_title: Epigenetic regulation in the pathogenesis of non-melanoma skin cancer.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2022 Aug;83:36-56. doi: 10.1016/j.semcancer.2020.11.009.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:33420020
  title: Disease risk scores for skin cancers.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2021 Jan 8;12(1):160. doi: 10.1038/s41467-020-20246-5.'
    supporting_text: '2021 Jan 8;12(1):160. doi: 10.1038/s41467-020-20246-5.'
    evidence:
    - reference: PMID:33420020
      reference_title: Disease risk scores for skin cancers.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2021 Jan 8;12(1):160. doi: 10.1038/s41467-020-20246-5.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:34047380
  title: 'Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Basal cell carcinoma (BCC) is the most common skin cancer in the general population.
    supporting_text: Basal cell carcinoma (BCC) is the most common skin cancer in the general population.
    evidence:
    - reference: PMID:34047380
      reference_title: 'Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Basal cell carcinoma (BCC) is the most common skin cancer in the general population.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:35942364
  title: Management of patients with giant basal cell carcinoma during SARS COV2 outbreak in Italy.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2022 Aug;4(3):e202200009. doi: 10.1002/tbio.202200009.'
    supporting_text: '2022 Aug;4(3):e202200009. doi: 10.1002/tbio.202200009.'
    evidence:
    - reference: PMID:35942364
      reference_title: Management of patients with giant basal cell carcinoma during SARS COV2 outbreak in Italy.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2022 Aug;4(3):e202200009. doi: 10.1002/tbio.202200009.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:36169917
  title: Advances in Topical Treatments of Cutaneous Malignancies.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2023 Jan;24(1):69-80. doi: 10.1007/s40257-022-00731-x.'
    supporting_text: '2023 Jan;24(1):69-80. doi: 10.1007/s40257-022-00731-x.'
    evidence:
    - reference: PMID:36169917
      reference_title: Advances in Topical Treatments of Cutaneous Malignancies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2023 Jan;24(1):69-80. doi: 10.1007/s40257-022-00731-x.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:36451860
  title: Single-cell atlases link macrophages and CD8(+) T-cell subpopulations to disease progression and immunotherapy response in urothelial carcinoma.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2022 Nov 14;12(18):7745-7759. doi: 10.7150/thno.77281. eCollection 2022.'
    supporting_text: '2022 Nov 14;12(18):7745-7759. doi: 10.7150/thno.77281. eCollection 2022.'
    evidence:
    - reference: PMID:36451860
      reference_title: Single-cell atlases link macrophages and CD8(+) T-cell subpopulations to disease progression and immunotherapy response in urothelial carcinoma.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2022 Nov 14;12(18):7745-7759. doi: 10.7150/thno.77281. eCollection 2022.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:36785993
  title: 'The application of artificial intelligence in the detection of basal cell carcinoma: A systematic review.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2023 Jun;37(6):1160-1167. doi: 10.1111/jdv.18963.'
    supporting_text: '2023 Jun;37(6):1160-1167. doi: 10.1111/jdv.18963.'
    evidence:
    - reference: PMID:36785993
      reference_title: 'The application of artificial intelligence in the detection of basal cell carcinoma: A systematic review.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2023 Jun;37(6):1160-1167. doi: 10.1111/jdv.18963.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:37552752
  title: PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone.
    supporting_text: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone.
    evidence:
    - reference: PMID:37552752
      reference_title: PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:37788820
  title: 'Skin Cancer in Non-White Solid Organ Transplant Recipients: Mayo Clinic Experience.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2023 Oct;116(10):839-844. doi: 10.14423/SMJ.0000000000001605.'
    supporting_text: '2023 Oct;116(10):839-844. doi: 10.14423/SMJ.0000000000001605.'
    evidence:
    - reference: PMID:37788820
      reference_title: 'Skin Cancer in Non-White Solid Organ Transplant Recipients: Mayo Clinic Experience.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2023 Oct;116(10):839-844. doi: 10.14423/SMJ.0000000000001605.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:37887285
  title: Immunity against Non-Melanoma Skin Cancer and the Effect of Immunosuppressive Medication on Non-Melanoma Skin Cancer Risk in Solid Organ Transplant Recipients.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2023 Oct 11;12(20):2441. doi: 10.3390/cells12202441.'
    supporting_text: '2023 Oct 11;12(20):2441. doi: 10.3390/cells12202441.'
    evidence:
    - reference: PMID:37887285
      reference_title: Immunity against Non-Melanoma Skin Cancer and the Effect of Immunosuppressive Medication on Non-Melanoma Skin Cancer Risk in Solid Organ Transplant Recipients.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2023 Oct 11;12(20):2441. doi: 10.3390/cells12202441.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:37964400
  title: 'Oral mucosa involvement in pediatric patients with xeroderma pigmentosum: a comprehensive review.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage.
    supporting_text: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage.
    evidence:
    - reference: PMID:37964400
      reference_title: 'Oral mucosa involvement in pediatric patients with xeroderma pigmentosum: a comprehensive review.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:38067338
  title: A Review of Recent Advances in Computer-Aided Detection Methods Using Hyperspectral Imaging Engineering to Detect Skin Cancer.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2023 Nov 29;15(23):5634. doi: 10.3390/cancers15235634.'
    supporting_text: '2023 Nov 29;15(23):5634. doi: 10.3390/cancers15235634.'
    evidence:
    - reference: PMID:38067338
      reference_title: A Review of Recent Advances in Computer-Aided Detection Methods Using Hyperspectral Imaging Engineering to Detect Skin Cancer.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2023 Nov 29;15(23):5634. doi: 10.3390/cancers15235634.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:38282244
  title: 'Exposome and basal cell carcinoma: a multicenter case-control study.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: 'Exposome and basal cell carcinoma: a multicenter case-control study'
    supporting_text: While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute.
    evidence:
    - reference: PMID:38282244
      reference_title: 'Exposome and basal cell carcinoma: a multicenter case-control study.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:38643380
  title: Representation of skin carcinomas in public awareness - Awareness worldwide and in Germany.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Jun;22(6):794-800. doi: 10.1111/ddg.15406.'
    supporting_text: '2024 Jun;22(6):794-800. doi: 10.1111/ddg.15406.'
    evidence:
    - reference: PMID:38643380
      reference_title: Representation of skin carcinomas in public awareness - Awareness worldwide and in Germany.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2024 Jun;22(6):794-800. doi: 10.1111/ddg.15406.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:38672604
  title: What Have We Learned about the Prevention of NMSC from Albino Patients from Malawi? Secondary Prevention Maintained over Time.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi.
    supporting_text: We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi.
    evidence:
    - reference: PMID:38672604
      reference_title: What Have We Learned about the Prevention of NMSC from Albino Patients from Malawi? Secondary Prevention Maintained over Time.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:38987869
  title: 'Skin cancer risk after hematopoietic stem cell transplantation: a systematic review and meta-analysis.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Dec;63(12):1691-1700. doi: 10.1111/ijd.17371.'
    supporting_text: '2024 Dec;63(12):1691-1700. doi: 10.1111/ijd.17371.'
    evidence:
    - reference: PMID:38987869
      reference_title: 'Skin cancer risk after hematopoietic stem cell transplantation: a systematic review and meta-analysis.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2024 Dec;63(12):1691-1700. doi: 10.1111/ijd.17371.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39404378
  title: Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC).
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Sep 26;13(19):1615. doi: 10.3390/cells13191615.'
    supporting_text: '2024 Sep 26;13(19):1615. doi: 10.3390/cells13191615.'
    evidence:
    - reference: PMID:39404378
      reference_title: Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC).
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2024 Sep 26;13(19):1615. doi: 10.3390/cells13191615.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39422527
  title: 'Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Oct;159(5):530-542. doi: 10.23736/S2784-8671.24.07993-3.'
    supporting_text: '2024 Oct;159(5):530-542. doi: 10.23736/S2784-8671.24.07993-3.'
    evidence:
    - reference: PMID:39422527
      reference_title: 'Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2024 Oct;159(5):530-542. doi: 10.23736/S2784-8671.24.07993-3.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39581763
  title: Analysis of Germline and Somatic Mutation in Patients With Developmental Odontogenic Cysts Using Targeted Gene Panel.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway.
    supporting_text: Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway.
    evidence:
    - reference: PMID:39581763
      reference_title: Analysis of Germline and Somatic Mutation in Patients With Developmental Odontogenic Cysts Using Targeted Gene Panel.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39697716
  title: 'Immunotherapy for locally advanced and metastatic basal cell carcinoma: a narrative review.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Nov 30;13(11):6565-6575. doi: 10.21037/tcr-24-742.'
    supporting_text: '2024 Nov 30;13(11):6565-6575. doi: 10.21037/tcr-24-742.'
    evidence:
    - reference: PMID:39697716
      reference_title: 'Immunotherapy for locally advanced and metastatic basal cell carcinoma: a narrative review.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2024 Nov 30;13(11):6565-6575. doi: 10.21037/tcr-24-742.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39702585
  title: Systematic proteome-wide Mendelian randomization to prioritize causal plasma proteins for skin cancers.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Dec 19;7(1):1681. doi: 10.1038/s42003-024-07403-y.'
    supporting_text: '2024 Dec 19;7(1):1681. doi: 10.1038/s42003-024-07403-y.'
    evidence:
    - reference: PMID:39702585
      reference_title: Systematic proteome-wide Mendelian randomization to prioritize causal plasma proteins for skin cancers.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2024 Dec 19;7(1):1681. doi: 10.1038/s42003-024-07403-y.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39708578
  title: 'Prevalence, incidence and trends of keratinocyte carcinoma in Denmark 2007-2021: A population-based register study.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Feb;94:102732. doi: 10.1016/j.canep.2024.102732.'
    supporting_text: '2025 Feb;94:102732. doi: 10.1016/j.canep.2024.102732.'
    evidence:
    - reference: PMID:39708578
      reference_title: 'Prevalence, incidence and trends of keratinocyte carcinoma in Denmark 2007-2021: A population-based register study.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Feb;94:102732. doi: 10.1016/j.canep.2024.102732.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39719956
  title: 'Surface mold brachytherapy for head and neck non-melanoma skin cancer - local control rates and survival: A retrospective analysis.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Oct;16(5):323-334. doi: 10.5114/jcb.2024.144703.'
    supporting_text: '2024 Oct;16(5):323-334. doi: 10.5114/jcb.2024.144703.'
    evidence:
    - reference: PMID:39719956
      reference_title: 'Surface mold brachytherapy for head and neck non-melanoma skin cancer - local control rates and survival: A retrospective analysis.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2024 Oct;16(5):323-334. doi: 10.5114/jcb.2024.144703.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39777366
  title: Image Guidance is Associated with Improved Freedom From Recurrence After Superficial Radiation Therapy for Nonmelanoma Skin Cancer.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2024 Feb 9;9(12):101463. doi: 10.1016/j.adro.2024.101463. eCollection 2024 Dec.'
    supporting_text: '2024 Feb 9;9(12):101463. doi: 10.1016/j.adro.2024.101463. eCollection 2024 Dec.'
    evidence:
    - reference: PMID:39777366
      reference_title: Image Guidance is Associated with Improved Freedom From Recurrence After Superficial Radiation Therapy for Nonmelanoma Skin Cancer.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2024 Feb 9;9(12):101463. doi: 10.1016/j.adro.2024.101463. eCollection 2024 Dec.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39791512
  title: '10 Years of Mohs Micrographic Surgery in Denmark: Results from a Nationwide Cohort.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Jan 10;105:adv41118. doi: 10.2340/actadv.v105.41118.'
    supporting_text: '2025 Jan 10;105:adv41118. doi: 10.2340/actadv.v105.41118.'
    evidence:
    - reference: PMID:39791512
      reference_title: '10 Years of Mohs Micrographic Surgery in Denmark: Results from a Nationwide Cohort.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2025 Jan 10;105:adv41118. doi: 10.2340/actadv.v105.41118.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39949752
  title: 'Case report: Complete response of recurrent locally advanced basal cell carcinoma following addition of vismodegib to neoadjuvant cemiplimab therapy.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Jan 30;15:1500785. doi: 10.3389/fonc.2025.1500785. eCollection 2025.'
    supporting_text: '2025 Jan 30;15:1500785. doi: 10.3389/fonc.2025.1500785. eCollection 2025.'
    evidence:
    - reference: PMID:39949752
      reference_title: 'Case report: Complete response of recurrent locally advanced basal cell carcinoma following addition of vismodegib to neoadjuvant cemiplimab therapy.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Jan 30;15:1500785. doi: 10.3389/fonc.2025.1500785. eCollection 2025.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39966563
  title: 'Global, regional, and national trends in the burden of melanoma and non-melanoma skin cancer: insights from the global burden of disease study 1990-2021.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Feb 18;15(1):5996. doi: 10.1038/s41598-025-90485-3.'
    supporting_text: '2025 Feb 18;15(1):5996. doi: 10.1038/s41598-025-90485-3.'
    evidence:
    - reference: PMID:39966563
      reference_title: 'Global, regional, and national trends in the burden of melanoma and non-melanoma skin cancer: insights from the global burden of disease study 1990-2021.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Feb 18;15(1):5996. doi: 10.1038/s41598-025-90485-3.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:39979629
  title: 'Non-melanoma skin cancer of the external auditory canal: long-term outcomes of a tertiary head and neck unit.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Jul;282(7):3657-3667. doi: 10.1007/s00405-025-09274-3.'
    supporting_text: '2025 Jul;282(7):3657-3667. doi: 10.1007/s00405-025-09274-3.'
    evidence:
    - reference: PMID:39979629
      reference_title: 'Non-melanoma skin cancer of the external auditory canal: long-term outcomes of a tertiary head and neck unit.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Jul;282(7):3657-3667. doi: 10.1007/s00405-025-09274-3.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40043261
  title: 'Neoadjuvant Sonidegib for the Management of Locally Advanced Basal Cell Carcinoma: A Case Report.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Mar 1;24(3):329-331. doi: 10.36849/JDD.8329.'
    supporting_text: '2025 Mar 1;24(3):329-331. doi: 10.36849/JDD.8329.'
    evidence:
    - reference: PMID:40043261
      reference_title: 'Neoadjuvant Sonidegib for the Management of Locally Advanced Basal Cell Carcinoma: A Case Report.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2025 Mar 1;24(3):329-331. doi: 10.36849/JDD.8329.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40167057
  title: "Frozen Section Mohs: A Hybrid Technique and One Plastic Surgeon's Experience With 1714 Consecutive Skin Cancer Removals."
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Apr 1;94(4S Suppl 2):S121-S125. doi: 10.1097/SAP.0000000000004254.'
    supporting_text: '2025 Apr 1;94(4S Suppl 2):S121-S125. doi: 10.1097/SAP.0000000000004254.'
    evidence:
    - reference: PMID:40167057
      reference_title: "Frozen Section Mohs: A Hybrid Technique and One Plastic Surgeon's Experience With 1714 Consecutive Skin Cancer Removals."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Apr 1;94(4S Suppl 2):S121-S125. doi: 10.1097/SAP.0000000000004254.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40370729
  title: Correlation of dermoscopic and histopathological features in basal cell carcinoma using computerized image analysis.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Basal cell carcinoma (BCC) is the most common skin cancer, exhibiting local invasiveness despite its low metastatic potential.
    supporting_text: Basal cell carcinoma (BCC) is the most common skin cancer, exhibiting local invasiveness despite its low metastatic potential.
    evidence:
    - reference: PMID:40370729
      reference_title: Correlation of dermoscopic and histopathological features in basal cell carcinoma using computerized image analysis.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Basal cell carcinoma (BCC) is the most common skin cancer, exhibiting local invasiveness despite its low metastatic potential.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40397469
  title: Burden of Skin Cancer in Older Adults From 1990 to 2021 and Modelled Projection to 2050.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Jul 1;161(7):715-722. doi: 10.1001/jamadermatol.2025.1276.'
    supporting_text: '2025 Jul 1;161(7):715-722. doi: 10.1001/jamadermatol.2025.1276.'
    evidence:
    - reference: PMID:40397469
      reference_title: Burden of Skin Cancer in Older Adults From 1990 to 2021 and Modelled Projection to 2050.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Jul 1;161(7):715-722. doi: 10.1001/jamadermatol.2025.1276.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40432222
  title: Cemiplimab in the treatment of metastatic basal cell carcinoma.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Jul;21(16):1999-2005. doi: 10.1080/14796694.2025.2511568.'
    supporting_text: '2025 Jul;21(16):1999-2005. doi: 10.1080/14796694.2025.2511568.'
    evidence:
    - reference: PMID:40432222
      reference_title: Cemiplimab in the treatment of metastatic basal cell carcinoma.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Jul;21(16):1999-2005. doi: 10.1080/14796694.2025.2511568.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40449860
  title: A comparative analysis of Mohs micrographic surgery with or without photodynamic therapy for locally advanced basal cell carcinoma.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Locally advanced basal cell carcinoma (laBCC) is a more severe subtype of BCC, characterized by large, deeply invasive tumors that often occur in cosmetically or functionally sensitive areas.
    supporting_text: Locally advanced basal cell carcinoma (laBCC) is a more severe subtype of BCC, characterized by large, deeply invasive tumors that often occur in cosmetically or functionally sensitive areas.
    evidence:
    - reference: PMID:40449860
      reference_title: A comparative analysis of Mohs micrographic surgery with or without photodynamic therapy for locally advanced basal cell carcinoma.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Locally advanced basal cell carcinoma (laBCC) is a more severe subtype of BCC, characterized by large, deeply invasive tumors that often occur in cosmetically or functionally sensitive areas.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40522768
  title: 'Prevalence of genetic alterations in basal cell carcinoma patients resistant to Hedgehog pathway inhibitors: a systematic review.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Dec;57(1):2516701. doi: 10.1080/07853890.2025.2516701.'
    supporting_text: '2025 Dec;57(1):2516701. doi: 10.1080/07853890.2025.2516701.'
    evidence:
    - reference: PMID:40522768
      reference_title: 'Prevalence of genetic alterations in basal cell carcinoma patients resistant to Hedgehog pathway inhibitors: a systematic review.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Dec;57(1):2516701. doi: 10.1080/07853890.2025.2516701.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40559089
  title: 'Advanced Basal Cell Carcinoma: A Narrative Review on Current Systemic Treatments and the Neoadjuvant Approach.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Jun 1;15(6):226. doi: 10.3390/jpm15060226.'
    supporting_text: '2025 Jun 1;15(6):226. doi: 10.3390/jpm15060226.'
    evidence:
    - reference: PMID:40559089
      reference_title: 'Advanced Basal Cell Carcinoma: A Narrative Review on Current Systemic Treatments and the Neoadjuvant Approach.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Jun 1;15(6):226. doi: 10.3390/jpm15060226.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:40834113
  title: 'Management of advanced basal cell carcinoma with hedgehog inhibitors: a real-world prospective comparative study.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Hedgehog inhibitors (HHIs) should be offered to patients with advanced basal cell carcinoma (BCC) as a first-line treatment.
    supporting_text: Hedgehog inhibitors (HHIs) should be offered to patients with advanced basal cell carcinoma (BCC) as a first-line treatment.
    evidence:
    - reference: PMID:40834113
      reference_title: 'Management of advanced basal cell carcinoma with hedgehog inhibitors: a real-world prospective comparative study.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Hedgehog inhibitors (HHIs) should be offered to patients with advanced basal cell carcinoma (BCC) as a first-line treatment.
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41039887
  title: Clinical Features and Outcomes of Locally Advanced and Metastatic Basal Cell Carcinoma.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Oct 2;105:adv43240. doi: 10.2340/actadv.v105.43240.'
    supporting_text: '2025 Oct 2;105:adv43240. doi: 10.2340/actadv.v105.43240.'
    evidence:
    - reference: PMID:41039887
      reference_title: Clinical Features and Outcomes of Locally Advanced and Metastatic Basal Cell Carcinoma.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Oct 2;105:adv43240. doi: 10.2340/actadv.v105.43240.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41053641
  title: 'Vismodegib treatment in locally advanced basal cell carcinoma limited to the facial region: a single-center experience.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Oct 6;25(1):1514. doi: 10.1186/s12885-025-14914-2.'
    supporting_text: '2025 Oct 6;25(1):1514. doi: 10.1186/s12885-025-14914-2.'
    evidence:
    - reference: PMID:41053641
      reference_title: 'Vismodegib treatment in locally advanced basal cell carcinoma limited to the facial region: a single-center experience.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Oct 6;25(1):1514. doi: 10.1186/s12885-025-14914-2.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41240053
  title: Does Basal Cell Carcinoma Arise from a Precursor Lesion?
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2026 Apr;146(4):905-913. doi: 10.1016/j.jid.2025.09.381.'
    supporting_text: '2026 Apr;146(4):905-913. doi: 10.1016/j.jid.2025.09.381.'
    evidence:
    - reference: PMID:41240053
      reference_title: Does Basal Cell Carcinoma Arise from a Precursor Lesion?
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2026 Apr;146(4):905-913. doi: 10.1016/j.jid.2025.09.381.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41495244
  title: '[Chronic skin damage from UV radiation].'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2026 Feb;77(2):80-89. doi: 10.1007/s00105-025-05621-x.'
    supporting_text: '2026 Feb;77(2):80-89. doi: 10.1007/s00105-025-05621-x.'
    evidence:
    - reference: PMID:41495244
      reference_title: '[Chronic skin damage from UV radiation].'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2026 Feb;77(2):80-89. doi: 10.1007/s00105-025-05621-x.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41515948
  title: 'Resistance to SMO Inhibitors in Advanced Basal Cell Carcinoma: A Case Highlighting the Role of Molecular Tumor Profiling.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2025 Dec 21;27(1):68. doi: 10.3390/ijms27010068.'
    supporting_text: '2025 Dec 21;27(1):68. doi: 10.3390/ijms27010068.'
    evidence:
    - reference: PMID:41515948
      reference_title: 'Resistance to SMO Inhibitors in Advanced Basal Cell Carcinoma: A Case Highlighting the Role of Molecular Tumor Profiling.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2025 Dec 21;27(1):68. doi: 10.3390/ijms27010068.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41543881
  title: Alcian blue-positive stromal phenotype in basal cell carcinoma is associated with progression on first-line hedgehog inhibitors.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2026 Jan;12(1):e70074. doi: 10.1002/2056-4538.70074.'
    supporting_text: '2026 Jan;12(1):e70074. doi: 10.1002/2056-4538.70074.'
    evidence:
    - reference: PMID:41543881
      reference_title: Alcian blue-positive stromal phenotype in basal cell carcinoma is associated with progression on first-line hedgehog inhibitors.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2026 Jan;12(1):e70074. doi: 10.1002/2056-4538.70074.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41685950
  title: 'Improving Basal Cell Carcinoma Subtype Diagnosis with Dermoscopy and Reflectance Confocal Microscopy: A Multicenter Prospective Study.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2026 Feb 13:llag037. doi: 10.1093/ced/llag037.'
    supporting_text: '2026 Feb 13:llag037. doi: 10.1093/ced/llag037.'
    evidence:
    - reference: PMID:41685950
      reference_title: 'Improving Basal Cell Carcinoma Subtype Diagnosis with Dermoscopy and Reflectance Confocal Microscopy: A Multicenter Prospective Study.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2026 Feb 13:llag037. doi: 10.1093/ced/llag037.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41703999
  title: Evolving paradigms in the management of basal cell carcinoma.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2026 Mar 1;38(2):107-113. doi: 10.1097/CCO.0000000000001223.'
    supporting_text: '2026 Mar 1;38(2):107-113. doi: 10.1097/CCO.0000000000001223.'
    evidence:
    - reference: PMID:41703999
      reference_title: Evolving paradigms in the management of basal cell carcinoma.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2026 Mar 1;38(2):107-113. doi: 10.1097/CCO.0000000000001223.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:41884741
  title: Genetic Insight into Gorlin-Goltz Syndrome.
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2026 Mar-Apr;71(2):87-93. doi: 10.4103/ijd.ijd_1165_23.'
    supporting_text: '2026 Mar-Apr;71(2):87-93. doi: 10.4103/ijd.ijd_1165_23.'
    evidence:
    - reference: PMID:41884741
      reference_title: Genetic Insight into Gorlin-Goltz Syndrome.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: '2026 Mar-Apr;71(2):87-93. doi: 10.4103/ijd.ijd_1165_23.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:42023819
  title: 'Characteristics and prognosis of skin cancer arising from burn scars: a systematic review.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: Burn scars are recognized risk factors for malignant skin transformation, most notably Marjolin's ulcer (MU).
    supporting_text: Burn scars are recognized risk factors for malignant skin transformation, most notably Marjolin's ulcer (MU).
    evidence:
    - reference: PMID:42023819
      reference_title: 'Characteristics and prognosis of skin cancer arising from burn scars: a systematic review.'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Burn scars are recognized risk factors for malignant skin transformation, most notably Marjolin's ulcer (MU).
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
- reference: PMID:42074595
  title: 'The Epigenetic Landscape and Exposome of Non-Melanoma Skin Cancer: Mechanisms, Biomarkers, and Therapeutic Perspectives.'
  found_in:
  - Basal_Cell_Carcinoma-deep-research-openscientist.md
  findings:
  - statement: '2026 Apr 17;17(4):477. doi: 10.3390/genes17040477.'
    supporting_text: '2026 Apr 17;17(4):477. doi: 10.3390/genes17040477.'
    evidence:
    - reference: PMID:42074595
      reference_title: 'The Epigenetic Landscape and Exposome of Non-Melanoma Skin Cancer: Mechanisms, Biomarkers, and Therapeutic Perspectives.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: '2026 Apr 17;17(4):477. doi: 10.3390/genes17040477.'
      explanation: Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
📚

References & Deep Research

References

89
DOI:10.1038/jid.2012.403
Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma
1 finding
Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma
"Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma"
DOI:10.1038/s41420-025-02327-w
Mechanisms and therapeutic potential of the hedgehog signaling pathway in cancer
1 finding
A sort of major malignant disease, cancer can compromise human health wherever.
"A sort of major malignant disease, cancer can compromise human health wherever."
Show evidence (1 reference)
DOI:10.1038/s41420-025-02327-w SUPPORT Human Clinical
"A sort of major malignant disease, cancer can compromise human health wherever."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.1038/s41467-022-35345-8
A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
1 finding
Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers.
"Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers."
Show evidence (1 reference)
DOI:10.1038/s41467-022-35345-8 SUPPORT Human Clinical
"Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.1038/s42003-023-05753-7
Multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma
1 finding
Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined.
"Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined."
Show evidence (1 reference)
DOI:10.1038/s42003-023-05753-7 SUPPORT Other
"Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.1093/bjd/ljac064
Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017
1 finding
Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs.
"Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs."
Show evidence (1 reference)
DOI:10.1093/bjd/ljac064 SUPPORT Human Clinical
"Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.1097/dss.0000000000000296
Consensus for Nonmelanoma Skin Cancer Treatment
1 finding
Consensus for Nonmelanoma Skin Cancer Treatment
"Consensus for Nonmelanoma Skin Cancer Treatment"
DOI:10.1111/cas.15823
Epidemiology of skin cancer based on Japan's National Cancer Registry 2016–2017
1 finding
Skin cancer is most frequently diagnosed in the White population.
"Skin cancer is most frequently diagnosed in the White population."
Show evidence (1 reference)
DOI:10.1111/cas.15823 SUPPORT Human Clinical
"Skin cancer is most frequently diagnosed in the White population."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.1111/ddg.15566
S2k guideline basal cell carcinoma of the skin (update 2023)
1 finding
Basal cell carcinoma is the most common malignant tumor in the fair‐skinned population and its incidence continues to rise.
"Basal cell carcinoma is the most common malignant tumor in the fair‐skinned population and its incidence continues to rise."
Show evidence (1 reference)
DOI:10.1111/ddg.15566 SUPPORT Other
"Basal cell carcinoma is the most common malignant tumor in the fair‐skinned population and its incidence continues to rise."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.1177/12034754221078201
Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis
1 finding
Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC).
"Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC)."
Show evidence (1 reference)
DOI:10.1177/12034754221078201 SUPPORT Other
"Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC)."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3389/fonc.2023.1111146
The association of cemiplimab plus sonidegib for synchronous cutaneous squamous cell carcinoma and basal cell carcinoma of the head and neck: Two case reports
1 finding
Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors.
"Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors."
Show evidence (1 reference)
DOI:10.3389/fonc.2023.1111146 SUPPORT Human Clinical
"Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3390/biom13071067
Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer
1 finding
Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race.
"Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race."
Show evidence (1 reference)
DOI:10.3390/biom13071067 SUPPORT Human Clinical
"Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3390/cancers16173075
Therapeutic Advances in Advanced Basal Cell Carcinoma
1 finding
Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone.
"Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone."
Show evidence (1 reference)
DOI:10.3390/cancers16173075 SUPPORT Human Clinical
"Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3390/cells12212534
Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma
1 finding
Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide.
"Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide."
Show evidence (1 reference)
DOI:10.3390/cells12212534 SUPPORT Human Clinical
"Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3390/ijms25137056
Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities
1 finding
Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide.
"Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide."
Show evidence (1 reference)
DOI:10.3390/ijms25137056 SUPPORT Human Clinical
"Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3390/ijms25158452
Dysembryogenetic Pathogenesis of Basal Cell Carcinoma: The Evidence to Date
1 finding
Dysembryogenetic Pathogenesis of Basal Cell Carcinoma: The Evidence to Date
"The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for..."
Show evidence (1 reference)
DOI:10.3390/ijms25158452 SUPPORT Other
"The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for..."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3390/jmp5020010
Basal Cell Carcinoma: Diagnosis, Management and Prevention
1 finding
Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues.
"Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues."
Show evidence (1 reference)
DOI:10.3390/jmp5020010 SUPPORT Other
"Basal cell carcinoma (BCC) is a slow-growing, locally aggressive, rarely metastasizing, low-grade cutaneous neoplasm that arises from the epidermal basal layer and invades the adjoining tissues."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.3390/nu16010100
The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis
1 finding
Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products.
"Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products."
Show evidence (1 reference)
DOI:10.3390/nu16010100 SUPPORT Other
"Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.5826/dpc.1304a252
Immunotherapy and Its Timing in Advanced Basal Cell Carcinoma Treatment
1 finding
For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment.
"For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment."
Show evidence (1 reference)
DOI:10.5826/dpc.1304a252 SUPPORT Human Clinical
"For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
DOI:10.6004/jnccn.2023.0056
Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology
1 finding
Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States.
"Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States."
Show evidence (1 reference)
DOI:10.6004/jnccn.2023.0056 SUPPORT Other
"Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:12542834
Immunohistochemical and genetic analysis of mandibular cysts in heterozygous ptc knockout mice.
1 finding
Alterations of human patched (ptc) homolog have been proven to be responsible for basal cell nevus syndrome (BCNS).
"Alterations of human patched (ptc) homolog have been proven to be responsible for basal cell nevus syndrome (BCNS)."
Show evidence (1 reference)
PMID:12542834 SUPPORT Model Organism
"Alterations of human patched (ptc) homolog have been proven to be responsible for basal cell nevus syndrome (BCNS)."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:21700618
Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma.
1 finding
2011 Sep 15;20(18):3718-24. doi: 10.1093/hmg/ddr287.
"2011 Sep 15;20(18):3718-24. doi: 10.1093/hmg/ddr287."
Show evidence (1 reference)
PMID:21700618 SUPPORT Human Clinical
"2011 Sep 15;20(18):3718-24. doi: 10.1093/hmg/ddr287."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:22945646
Progeny of Lgr5-expressing hair follicle stem cell contributes to papillomavirus-induced tumor development in epidermis.
1 finding
2013 Aug 8;32(32):3732-43. doi: 10.1038/onc.2012.375.
"2013 Aug 8;32(32):3732-43. doi: 10.1038/onc.2012.375."
Show evidence (1 reference)
PMID:22945646 SUPPORT Human Clinical
"2013 Aug 8;32(32):3732-43. doi: 10.1038/onc.2012.375."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:23196843
Stem cell reprogramming as a driver of basal cell carcinoma.
1 finding
2012 Dec;14(12):1246-7. doi: 10.1038/ncb2631.
"2012 Dec;14(12):1246-7. doi: 10.1038/ncb2631."
Show evidence (1 reference)
PMID:23196843 SUPPORT Other
"2012 Dec;14(12):1246-7. doi: 10.1038/ncb2631."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:24485530
Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public.
1 finding
2014 Apr;70(4):748-762. doi: 10.1016/j.jaad.2013.11.038.
"2014 Apr;70(4):748-762. doi: 10.1016/j.jaad.2013.11.038."
Show evidence (1 reference)
PMID:24485530 SUPPORT Human Clinical
"2014 Apr;70(4):748-762. doi: 10.1016/j.jaad.2013.11.038."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:24662765
DMBA/TPA treatment is necessary for BCC formation from patched deficient epidermal cells in Ptch(flox/flox)CD4Cre(+/-) mice.
1 finding
2014 Oct;134(10):2620-2629. doi: 10.1038/jid.2014.157.
"2014 Oct;134(10):2620-2629. doi: 10.1038/jid.2014.157."
Show evidence (1 reference)
PMID:24662765 SUPPORT Model Organism
"2014 Oct;134(10):2620-2629. doi: 10.1038/jid.2014.157."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:25408650
Preventive Long-Term Effects of a Topical Film-Forming Medical Device with Ultra-High UV Protection Filters and DNA Repair Enzyme in Xeroderma Pigmentosum: A Retrospective Study of Eight Cases.
1 finding
2014 Sep 19;6(3):222-6. doi: 10.1159/000368182. eCollection 2014 Sep.
"2014 Sep 19;6(3):222-6. doi: 10.1159/000368182. eCollection 2014 Sep."
Show evidence (1 reference)
PMID:25408650 SUPPORT Human Clinical
"2014 Sep 19;6(3):222-6. doi: 10.1159/000368182. eCollection 2014 Sep."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:26921200
Preoperative prediction of histopathological outcome in basal cell carcinoma: flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types.
1 finding
Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC).
"Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC)."
Show evidence (1 reference)
PMID:26921200 SUPPORT Computational
"Prediction of the histopathological subtype of basal cell carcinoma (BCC) is important for tailoring optimal treatment, especially in patients with suspected superficial BCC (sBCC)."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:27388747
AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome.
1 finding
2016 Oct;9(10):794-802. doi: 10.1158/1940-6207.CAPR-16-0066.
"2016 Oct;9(10):794-802. doi: 10.1158/1940-6207.CAPR-16-0066."
Show evidence (1 reference)
PMID:27388747 SUPPORT Model Organism
"2016 Oct;9(10):794-802. doi: 10.1158/1940-6207.CAPR-16-0066."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:27663613
One-Year Review of the SCREEN (Skin Cancer Post-Transplant) Clinic.
1 finding
2017 Jan/Feb;21(1):80-81. doi: 10.1177/1203475416671694.
"2017 Jan/Feb;21(1):80-81. doi: 10.1177/1203475416671694."
Show evidence (1 reference)
PMID:27663613 SUPPORT Human Clinical
"2017 Jan/Feb;21(1):80-81. doi: 10.1177/1203475416671694."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:28070642
Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors.
1 finding
2017 Mar;470(3):301-310. doi: 10.1007/s00428-016-2061-3.
"2017 Mar;470(3):301-310. doi: 10.1007/s00428-016-2061-3."
Show evidence (1 reference)
PMID:28070642 SUPPORT Human Clinical
"2017 Mar;470(3):301-310. doi: 10.1007/s00428-016-2061-3."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:28207005
Basal cell carcinoma arising in outdoor workers versus indoor workers: a retrospective study.
1 finding
Husein-Elahmed H(1), Gutierrez-Salmeron MT(1), Aneiros-Cachaza J(2), Naranjo-Sintes R(1).
"Husein-Elahmed H(1), Gutierrez-Salmeron MT(1), Aneiros-Cachaza J(2), Naranjo-Sintes R(1)."
Show evidence (1 reference)
PMID:28207005 SUPPORT Human Clinical
"Husein-Elahmed H(1), Gutierrez-Salmeron MT(1), Aneiros-Cachaza J(2), Naranjo-Sintes R(1)."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:28220485
Epidemiology of basal cell carcinoma: scholarly review.
1 finding
2017 Aug;177(2):359-372. doi: 10.1111/bjd.15321.
"2017 Aug;177(2):359-372. doi: 10.1111/bjd.15321."
Show evidence (1 reference)
PMID:28220485 SUPPORT Human Clinical
"2017 Aug;177(2):359-372. doi: 10.1111/bjd.15321."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:28925402
Contrasting effects of an Mdm2 functional polymorphism on tumor phenotypes.
1 finding
2018 Jan 18;37(3):332-340. doi: 10.1038/onc.2017.344.
"2018 Jan 18;37(3):332-340. doi: 10.1038/onc.2017.344."
Show evidence (1 reference)
PMID:28925402 SUPPORT Other
"2018 Jan 18;37(3):332-340. doi: 10.1038/onc.2017.344."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:29723362
Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.
1 finding
The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern.
"The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern."
Show evidence (1 reference)
PMID:29723362 SUPPORT Other
"The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:30908599
Genome-wide association studies and polygenic risk scores for skin cancer: clinically useful yet?
1 finding
Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value.
"Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value."
Show evidence (1 reference)
PMID:30908599 SUPPORT Other
"Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:30987174
A Retrospective Study of the Diagnostic Accuracy of In Vivo Reflectance Confocal Microscopy for Basal Cell Carcinoma Diagnosis and Subtyping.
1 finding
2019 Apr 3;8(4):449. doi: 10.3390/jcm8040449.
"2019 Apr 3;8(4):449. doi: 10.3390/jcm8040449."
Show evidence (1 reference)
PMID:30987174 SUPPORT Other
"2019 Apr 3;8(4):449. doi: 10.3390/jcm8040449."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:31288208
Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines.
1 finding
2019 Sep;118:10-34. doi: 10.1016/j.ejca.2019.06.003.
"2019 Sep;118:10-34. doi: 10.1016/j.ejca.2019.06.003."
Show evidence (1 reference)
PMID:31288208 SUPPORT Other
"2019 Sep;118:10-34. doi: 10.1016/j.ejca.2019.06.003."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:31419349
Basal cell carcinoma genetic susceptibility increases the rate of skin ageing: a Mendelian randomization study.
1 finding
Onset of basal cell carcinoma (BCC) is connected to skin ageing, but it is unclear whether higher BCC genetic susceptibility drives skin ageing.
"Onset of basal cell carcinoma (BCC) is connected to skin ageing, but it is unclear whether higher BCC genetic susceptibility drives skin ageing."
Show evidence (1 reference)
PMID:31419349 SUPPORT Human Clinical
"Onset of basal cell carcinoma (BCC) is connected to skin ageing, but it is unclear whether higher BCC genetic susceptibility drives skin ageing."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:31585338
Cutaneous keratinocyte cancers of the head and neck: Epidemiology, risk factors and clinical, dermoscopic and reflectance confocal microscopic features.
1 finding
2019 Nov;98:109-117. doi: 10.1016/j.oraloncology.2019.09.019.
"2019 Nov;98:109-117. doi: 10.1016/j.oraloncology.2019.09.019."
Show evidence (1 reference)
PMID:31585338 SUPPORT Human Clinical
"2019 Nov;98:109-117. doi: 10.1016/j.oraloncology.2019.09.019."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:32492418
Regional Variation in Epidermal Susceptibility to UV-Induced Carcinogenesis Reflects Proliferative Activity of Epidermal Progenitors.
1 finding
2020 Jun 2;31(9):107702. doi: 10.1016/j.celrep.2020.107702.
"2020 Jun 2;31(9):107702. doi: 10.1016/j.celrep.2020.107702."
Show evidence (1 reference)
PMID:32492418 SUPPORT Other
"2020 Jun 2;31(9):107702. doi: 10.1016/j.celrep.2020.107702."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:32930885
Retrospective investigation of hereditary syndromes in patients with medulloblastoma in a single institution.
1 finding
2021 Feb;37(2):411-417. doi: 10.1007/s00381-020-04885-z.
"2021 Feb;37(2):411-417. doi: 10.1007/s00381-020-04885-z."
Show evidence (1 reference)
PMID:32930885 SUPPORT Human Clinical
"2021 Feb;37(2):411-417. doi: 10.1007/s00381-020-04885-z."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:33242578
Epigenetic regulation in the pathogenesis of non-melanoma skin cancer.
1 finding
2022 Aug;83:36-56. doi: 10.1016/j.semcancer.2020.11.009.
"2022 Aug;83:36-56. doi: 10.1016/j.semcancer.2020.11.009."
Show evidence (1 reference)
PMID:33242578 SUPPORT Human Clinical
"2022 Aug;83:36-56. doi: 10.1016/j.semcancer.2020.11.009."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:33420020
Disease risk scores for skin cancers.
1 finding
2021 Jan 8;12(1):160. doi: 10.1038/s41467-020-20246-5.
"2021 Jan 8;12(1):160. doi: 10.1038/s41467-020-20246-5."
Show evidence (1 reference)
PMID:33420020 SUPPORT Other
"2021 Jan 8;12(1):160. doi: 10.1038/s41467-020-20246-5."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:34047380
Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.
1 finding
Basal cell carcinoma (BCC) is the most common skin cancer in the general population.
"Basal cell carcinoma (BCC) is the most common skin cancer in the general population."
Show evidence (1 reference)
PMID:34047380 SUPPORT Human Clinical
"Basal cell carcinoma (BCC) is the most common skin cancer in the general population."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:35942364
Management of patients with giant basal cell carcinoma during SARS COV2 outbreak in Italy.
1 finding
2022 Aug;4(3):e202200009. doi: 10.1002/tbio.202200009.
"2022 Aug;4(3):e202200009. doi: 10.1002/tbio.202200009."
Show evidence (1 reference)
PMID:35942364 SUPPORT Other
"2022 Aug;4(3):e202200009. doi: 10.1002/tbio.202200009."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:36169917
Advances in Topical Treatments of Cutaneous Malignancies.
1 finding
2023 Jan;24(1):69-80. doi: 10.1007/s40257-022-00731-x.
"2023 Jan;24(1):69-80. doi: 10.1007/s40257-022-00731-x."
Show evidence (1 reference)
PMID:36169917 SUPPORT Human Clinical
"2023 Jan;24(1):69-80. doi: 10.1007/s40257-022-00731-x."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:36451860
Single-cell atlases link macrophages and CD8(+) T-cell subpopulations to disease progression and immunotherapy response in urothelial carcinoma.
1 finding
2022 Nov 14;12(18):7745-7759. doi: 10.7150/thno.77281. eCollection 2022.
"2022 Nov 14;12(18):7745-7759. doi: 10.7150/thno.77281. eCollection 2022."
Show evidence (1 reference)
PMID:36451860 SUPPORT Other
"2022 Nov 14;12(18):7745-7759. doi: 10.7150/thno.77281. eCollection 2022."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:36785993
The application of artificial intelligence in the detection of basal cell carcinoma: A systematic review.
1 finding
2023 Jun;37(6):1160-1167. doi: 10.1111/jdv.18963.
"2023 Jun;37(6):1160-1167. doi: 10.1111/jdv.18963."
Show evidence (1 reference)
PMID:36785993 SUPPORT Other
"2023 Jun;37(6):1160-1167. doi: 10.1111/jdv.18963."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:37552752
PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.
1 finding
Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone.
"Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone."
Show evidence (1 reference)
PMID:37552752 SUPPORT In Vitro
"Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:37788820
Skin Cancer in Non-White Solid Organ Transplant Recipients: Mayo Clinic Experience.
1 finding
2023 Oct;116(10):839-844. doi: 10.14423/SMJ.0000000000001605.
"2023 Oct;116(10):839-844. doi: 10.14423/SMJ.0000000000001605."
Show evidence (1 reference)
PMID:37788820 SUPPORT Human Clinical
"2023 Oct;116(10):839-844. doi: 10.14423/SMJ.0000000000001605."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:37887285
Immunity against Non-Melanoma Skin Cancer and the Effect of Immunosuppressive Medication on Non-Melanoma Skin Cancer Risk in Solid Organ Transplant Recipients.
1 finding
2023 Oct 11;12(20):2441. doi: 10.3390/cells12202441.
"2023 Oct 11;12(20):2441. doi: 10.3390/cells12202441."
Show evidence (1 reference)
PMID:37887285 SUPPORT Other
"2023 Oct 11;12(20):2441. doi: 10.3390/cells12202441."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:37964400
Oral mucosa involvement in pediatric patients with xeroderma pigmentosum: a comprehensive review.
1 finding
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage.
"Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage."
Show evidence (1 reference)
PMID:37964400 SUPPORT Human Clinical
"Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV-induced DNA damage."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:38067338
A Review of Recent Advances in Computer-Aided Detection Methods Using Hyperspectral Imaging Engineering to Detect Skin Cancer.
1 finding
2023 Nov 29;15(23):5634. doi: 10.3390/cancers15235634.
"2023 Nov 29;15(23):5634. doi: 10.3390/cancers15235634."
Show evidence (1 reference)
PMID:38067338 SUPPORT Other
"2023 Nov 29;15(23):5634. doi: 10.3390/cancers15235634."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:38282244
Exposome and basal cell carcinoma: a multicenter case-control study.
1 finding
Exposome and basal cell carcinoma: a multicenter case-control study
"While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute."
Show evidence (1 reference)
PMID:38282244 SUPPORT Human Clinical
"While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:38643380
Representation of skin carcinomas in public awareness - Awareness worldwide and in Germany.
1 finding
2024 Jun;22(6):794-800. doi: 10.1111/ddg.15406.
"2024 Jun;22(6):794-800. doi: 10.1111/ddg.15406."
Show evidence (1 reference)
PMID:38643380 SUPPORT Human Clinical
"2024 Jun;22(6):794-800. doi: 10.1111/ddg.15406."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:38672604
What Have We Learned about the Prevention of NMSC from Albino Patients from Malawi? Secondary Prevention Maintained over Time.
1 finding
We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi.
"We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi."
Show evidence (1 reference)
PMID:38672604 SUPPORT Other
"We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:38987869
Skin cancer risk after hematopoietic stem cell transplantation: a systematic review and meta-analysis.
1 finding
2024 Dec;63(12):1691-1700. doi: 10.1111/ijd.17371.
"2024 Dec;63(12):1691-1700. doi: 10.1111/ijd.17371."
Show evidence (1 reference)
PMID:38987869 SUPPORT Other
"2024 Dec;63(12):1691-1700. doi: 10.1111/ijd.17371."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39404378
Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC).
1 finding
2024 Sep 26;13(19):1615. doi: 10.3390/cells13191615.
"2024 Sep 26;13(19):1615. doi: 10.3390/cells13191615."
Show evidence (1 reference)
PMID:39404378 SUPPORT Other
"2024 Sep 26;13(19):1615. doi: 10.3390/cells13191615."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39422527
Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors.
1 finding
2024 Oct;159(5):530-542. doi: 10.23736/S2784-8671.24.07993-3.
"2024 Oct;159(5):530-542. doi: 10.23736/S2784-8671.24.07993-3."
Show evidence (1 reference)
PMID:39422527 SUPPORT Human Clinical
"2024 Oct;159(5):530-542. doi: 10.23736/S2784-8671.24.07993-3."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39581763
Analysis of Germline and Somatic Mutation in Patients With Developmental Odontogenic Cysts Using Targeted Gene Panel.
1 finding
Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway.
"Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway."
Show evidence (1 reference)
PMID:39581763 SUPPORT Human Clinical
"Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39697716
Immunotherapy for locally advanced and metastatic basal cell carcinoma: a narrative review.
1 finding
2024 Nov 30;13(11):6565-6575. doi: 10.21037/tcr-24-742.
"2024 Nov 30;13(11):6565-6575. doi: 10.21037/tcr-24-742."
Show evidence (1 reference)
PMID:39697716 SUPPORT Other
"2024 Nov 30;13(11):6565-6575. doi: 10.21037/tcr-24-742."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39702585
Systematic proteome-wide Mendelian randomization to prioritize causal plasma proteins for skin cancers.
1 finding
2024 Dec 19;7(1):1681. doi: 10.1038/s42003-024-07403-y.
"2024 Dec 19;7(1):1681. doi: 10.1038/s42003-024-07403-y."
Show evidence (1 reference)
PMID:39702585 SUPPORT Other
"2024 Dec 19;7(1):1681. doi: 10.1038/s42003-024-07403-y."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39708578
Prevalence, incidence and trends of keratinocyte carcinoma in Denmark 2007-2021: A population-based register study.
1 finding
2025 Feb;94:102732. doi: 10.1016/j.canep.2024.102732.
"2025 Feb;94:102732. doi: 10.1016/j.canep.2024.102732."
Show evidence (1 reference)
PMID:39708578 SUPPORT Other
"2025 Feb;94:102732. doi: 10.1016/j.canep.2024.102732."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39719956
Surface mold brachytherapy for head and neck non-melanoma skin cancer - local control rates and survival: A retrospective analysis.
1 finding
2024 Oct;16(5):323-334. doi: 10.5114/jcb.2024.144703.
"2024 Oct;16(5):323-334. doi: 10.5114/jcb.2024.144703."
Show evidence (1 reference)
PMID:39719956 SUPPORT Other
"2024 Oct;16(5):323-334. doi: 10.5114/jcb.2024.144703."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39777366
Image Guidance is Associated with Improved Freedom From Recurrence After Superficial Radiation Therapy for Nonmelanoma Skin Cancer.
1 finding
2024 Feb 9;9(12):101463. doi: 10.1016/j.adro.2024.101463. eCollection 2024 Dec.
"2024 Feb 9;9(12):101463. doi: 10.1016/j.adro.2024.101463. eCollection 2024 Dec."
Show evidence (1 reference)
PMID:39777366 SUPPORT Other
"2024 Feb 9;9(12):101463. doi: 10.1016/j.adro.2024.101463. eCollection 2024 Dec."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39791512
10 Years of Mohs Micrographic Surgery in Denmark: Results from a Nationwide Cohort.
1 finding
2025 Jan 10;105:adv41118. doi: 10.2340/actadv.v105.41118.
"2025 Jan 10;105:adv41118. doi: 10.2340/actadv.v105.41118."
Show evidence (1 reference)
PMID:39791512 SUPPORT Human Clinical
"2025 Jan 10;105:adv41118. doi: 10.2340/actadv.v105.41118."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39949752
Case report: Complete response of recurrent locally advanced basal cell carcinoma following addition of vismodegib to neoadjuvant cemiplimab therapy.
1 finding
2025 Jan 30;15:1500785. doi: 10.3389/fonc.2025.1500785. eCollection 2025.
"2025 Jan 30;15:1500785. doi: 10.3389/fonc.2025.1500785. eCollection 2025."
Show evidence (1 reference)
PMID:39949752 SUPPORT Other
"2025 Jan 30;15:1500785. doi: 10.3389/fonc.2025.1500785. eCollection 2025."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39966563
Global, regional, and national trends in the burden of melanoma and non-melanoma skin cancer: insights from the global burden of disease study 1990-2021.
1 finding
2025 Feb 18;15(1):5996. doi: 10.1038/s41598-025-90485-3.
"2025 Feb 18;15(1):5996. doi: 10.1038/s41598-025-90485-3."
Show evidence (1 reference)
PMID:39966563 SUPPORT Other
"2025 Feb 18;15(1):5996. doi: 10.1038/s41598-025-90485-3."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:39979629
Non-melanoma skin cancer of the external auditory canal: long-term outcomes of a tertiary head and neck unit.
1 finding
2025 Jul;282(7):3657-3667. doi: 10.1007/s00405-025-09274-3.
"2025 Jul;282(7):3657-3667. doi: 10.1007/s00405-025-09274-3."
Show evidence (1 reference)
PMID:39979629 SUPPORT Other
"2025 Jul;282(7):3657-3667. doi: 10.1007/s00405-025-09274-3."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40043261
Neoadjuvant Sonidegib for the Management of Locally Advanced Basal Cell Carcinoma: A Case Report.
1 finding
2025 Mar 1;24(3):329-331. doi: 10.36849/JDD.8329.
"2025 Mar 1;24(3):329-331. doi: 10.36849/JDD.8329."
Show evidence (1 reference)
PMID:40043261 SUPPORT Human Clinical
"2025 Mar 1;24(3):329-331. doi: 10.36849/JDD.8329."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40167057
Frozen Section Mohs: A Hybrid Technique and One Plastic Surgeon's Experience With 1714 Consecutive Skin Cancer Removals.
1 finding
2025 Apr 1;94(4S Suppl 2):S121-S125. doi: 10.1097/SAP.0000000000004254.
"2025 Apr 1;94(4S Suppl 2):S121-S125. doi: 10.1097/SAP.0000000000004254."
Show evidence (1 reference)
PMID:40167057 SUPPORT Other
"2025 Apr 1;94(4S Suppl 2):S121-S125. doi: 10.1097/SAP.0000000000004254."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40370729
Correlation of dermoscopic and histopathological features in basal cell carcinoma using computerized image analysis.
1 finding
Basal cell carcinoma (BCC) is the most common skin cancer, exhibiting local invasiveness despite its low metastatic potential.
"Basal cell carcinoma (BCC) is the most common skin cancer, exhibiting local invasiveness despite its low metastatic potential."
Show evidence (1 reference)
PMID:40370729 SUPPORT Other
"Basal cell carcinoma (BCC) is the most common skin cancer, exhibiting local invasiveness despite its low metastatic potential."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40397469
Burden of Skin Cancer in Older Adults From 1990 to 2021 and Modelled Projection to 2050.
1 finding
2025 Jul 1;161(7):715-722. doi: 10.1001/jamadermatol.2025.1276.
"2025 Jul 1;161(7):715-722. doi: 10.1001/jamadermatol.2025.1276."
Show evidence (1 reference)
PMID:40397469 SUPPORT Other
"2025 Jul 1;161(7):715-722. doi: 10.1001/jamadermatol.2025.1276."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40432222
Cemiplimab in the treatment of metastatic basal cell carcinoma.
1 finding
2025 Jul;21(16):1999-2005. doi: 10.1080/14796694.2025.2511568.
"2025 Jul;21(16):1999-2005. doi: 10.1080/14796694.2025.2511568."
Show evidence (1 reference)
PMID:40432222 SUPPORT Other
"2025 Jul;21(16):1999-2005. doi: 10.1080/14796694.2025.2511568."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40449860
A comparative analysis of Mohs micrographic surgery with or without photodynamic therapy for locally advanced basal cell carcinoma.
1 finding
Locally advanced basal cell carcinoma (laBCC) is a more severe subtype of BCC, characterized by large, deeply invasive tumors that often occur in cosmetically or functionally sensitive areas.
"Locally advanced basal cell carcinoma (laBCC) is a more severe subtype of BCC, characterized by large, deeply invasive tumors that often occur in cosmetically or functionally sensitive areas."
Show evidence (1 reference)
PMID:40449860 SUPPORT Other
"Locally advanced basal cell carcinoma (laBCC) is a more severe subtype of BCC, characterized by large, deeply invasive tumors that often occur in cosmetically or functionally sensitive areas."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40522768
Prevalence of genetic alterations in basal cell carcinoma patients resistant to Hedgehog pathway inhibitors: a systematic review.
1 finding
2025 Dec;57(1):2516701. doi: 10.1080/07853890.2025.2516701.
"2025 Dec;57(1):2516701. doi: 10.1080/07853890.2025.2516701."
Show evidence (1 reference)
PMID:40522768 SUPPORT Other
"2025 Dec;57(1):2516701. doi: 10.1080/07853890.2025.2516701."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40559089
Advanced Basal Cell Carcinoma: A Narrative Review on Current Systemic Treatments and the Neoadjuvant Approach.
1 finding
2025 Jun 1;15(6):226. doi: 10.3390/jpm15060226.
"2025 Jun 1;15(6):226. doi: 10.3390/jpm15060226."
Show evidence (1 reference)
PMID:40559089 SUPPORT Other
"2025 Jun 1;15(6):226. doi: 10.3390/jpm15060226."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:40834113
Management of advanced basal cell carcinoma with hedgehog inhibitors: a real-world prospective comparative study.
1 finding
Hedgehog inhibitors (HHIs) should be offered to patients with advanced basal cell carcinoma (BCC) as a first-line treatment.
"Hedgehog inhibitors (HHIs) should be offered to patients with advanced basal cell carcinoma (BCC) as a first-line treatment."
Show evidence (1 reference)
PMID:40834113 SUPPORT Human Clinical
"Hedgehog inhibitors (HHIs) should be offered to patients with advanced basal cell carcinoma (BCC) as a first-line treatment."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41039887
Clinical Features and Outcomes of Locally Advanced and Metastatic Basal Cell Carcinoma.
1 finding
2025 Oct 2;105:adv43240. doi: 10.2340/actadv.v105.43240.
"2025 Oct 2;105:adv43240. doi: 10.2340/actadv.v105.43240."
Show evidence (1 reference)
PMID:41039887 SUPPORT Other
"2025 Oct 2;105:adv43240. doi: 10.2340/actadv.v105.43240."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41053641
Vismodegib treatment in locally advanced basal cell carcinoma limited to the facial region: a single-center experience.
1 finding
2025 Oct 6;25(1):1514. doi: 10.1186/s12885-025-14914-2.
"2025 Oct 6;25(1):1514. doi: 10.1186/s12885-025-14914-2."
Show evidence (1 reference)
PMID:41053641 SUPPORT Other
"2025 Oct 6;25(1):1514. doi: 10.1186/s12885-025-14914-2."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41240053
Does Basal Cell Carcinoma Arise from a Precursor Lesion?
1 finding
2026 Apr;146(4):905-913. doi: 10.1016/j.jid.2025.09.381.
"2026 Apr;146(4):905-913. doi: 10.1016/j.jid.2025.09.381."
Show evidence (1 reference)
PMID:41240053 SUPPORT Other
"2026 Apr;146(4):905-913. doi: 10.1016/j.jid.2025.09.381."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41495244
[Chronic skin damage from UV radiation].
1 finding
2026 Feb;77(2):80-89. doi: 10.1007/s00105-025-05621-x.
"2026 Feb;77(2):80-89. doi: 10.1007/s00105-025-05621-x."
Show evidence (1 reference)
PMID:41495244 SUPPORT Other
"2026 Feb;77(2):80-89. doi: 10.1007/s00105-025-05621-x."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41515948
Resistance to SMO Inhibitors in Advanced Basal Cell Carcinoma: A Case Highlighting the Role of Molecular Tumor Profiling.
1 finding
2025 Dec 21;27(1):68. doi: 10.3390/ijms27010068.
"2025 Dec 21;27(1):68. doi: 10.3390/ijms27010068."
Show evidence (1 reference)
PMID:41515948 SUPPORT Other
"2025 Dec 21;27(1):68. doi: 10.3390/ijms27010068."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41543881
Alcian blue-positive stromal phenotype in basal cell carcinoma is associated with progression on first-line hedgehog inhibitors.
1 finding
2026 Jan;12(1):e70074. doi: 10.1002/2056-4538.70074.
"2026 Jan;12(1):e70074. doi: 10.1002/2056-4538.70074."
Show evidence (1 reference)
PMID:41543881 SUPPORT Human Clinical
"2026 Jan;12(1):e70074. doi: 10.1002/2056-4538.70074."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41685950
Improving Basal Cell Carcinoma Subtype Diagnosis with Dermoscopy and Reflectance Confocal Microscopy: A Multicenter Prospective Study.
1 finding
2026 Feb 13:llag037. doi: 10.1093/ced/llag037.
"2026 Feb 13:llag037. doi: 10.1093/ced/llag037."
Show evidence (1 reference)
PMID:41685950 SUPPORT Human Clinical
"2026 Feb 13:llag037. doi: 10.1093/ced/llag037."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41703999
Evolving paradigms in the management of basal cell carcinoma.
1 finding
2026 Mar 1;38(2):107-113. doi: 10.1097/CCO.0000000000001223.
"2026 Mar 1;38(2):107-113. doi: 10.1097/CCO.0000000000001223."
Show evidence (1 reference)
PMID:41703999 SUPPORT Human Clinical
"2026 Mar 1;38(2):107-113. doi: 10.1097/CCO.0000000000001223."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:41884741
Genetic Insight into Gorlin-Goltz Syndrome.
1 finding
2026 Mar-Apr;71(2):87-93. doi: 10.4103/ijd.ijd_1165_23.
"2026 Mar-Apr;71(2):87-93. doi: 10.4103/ijd.ijd_1165_23."
Show evidence (1 reference)
PMID:41884741 SUPPORT Other
"2026 Mar-Apr;71(2):87-93. doi: 10.4103/ijd.ijd_1165_23."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:42023819
Characteristics and prognosis of skin cancer arising from burn scars: a systematic review.
1 finding
Burn scars are recognized risk factors for malignant skin transformation, most notably Marjolin's ulcer (MU).
"Burn scars are recognized risk factors for malignant skin transformation, most notably Marjolin's ulcer (MU)."
Show evidence (1 reference)
PMID:42023819 SUPPORT Other
"Burn scars are recognized risk factors for malignant skin transformation, most notably Marjolin's ulcer (MU)."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.
PMID:42074595
The Epigenetic Landscape and Exposome of Non-Melanoma Skin Cancer: Mechanisms, Biomarkers, and Therapeutic Perspectives.
1 finding
2026 Apr 17;17(4):477. doi: 10.3390/genes17040477.
"2026 Apr 17;17(4):477. doi: 10.3390/genes17040477."
Show evidence (1 reference)
PMID:42074595 SUPPORT Human Clinical
"2026 Apr 17;17(4):477. doi: 10.3390/genes17040477."
Deep research cited this publication as relevant literature for Basal Cell Carcinoma.

Deep Research

2
Falcon ▸
1. Disease Information
Edison Scientific Literature 59 citations 2026-04-05T14:01:25.652232

1. Disease Information

1.1 Definition and current understanding

BCC is described in recent guidelines and reviews as a slow-growing, locally aggressive cutaneous neoplasm arising from the basal layer of the epidermis, with rare metastasis. (lang2024s2kguidelinebasal pages 1-2, schmults2023basalcellskin pages 2-4, sol2024therapeuticapproachesfor pages 7-8)

1.2 Key identifiers and classifications

Because many registries do not systematically record BCC, identifiers are often used indirectly in observational and genetic studies.

  • ICD-10 (commonly used for EHR/claims phenotyping): A large 2024 GWAS meta-analysis defined BCC cases in one cohort using ICD-10 codes C44.01–C44.91. (choquet2024multiancestrygenomewidemetaanalysis pages 7-7)
  • ICD-O-3 topography (registry-based definition): Japan’s National Cancer Registry analysis defined skin cancers using ICD-O-3 topography codes including C44 (skin) (and additional genital skin topographies), with in situ lesions included. (ogata2023epidemiologyofskin pages 1-2)
  • MeSH / MONDO / ICD-11: Not extractable from the retrieved full-text evidence in this run; therefore not asserted here.

1.3 Common synonyms / alternative names

  • Basal cell carcinoma of the skin
  • Basal cell skin cancer (NCCN nomenclature) (schmults2023basalcellskin pages 2-4)
  • Keratinocyte cancer / keratinocyte carcinoma (umbrella term often including BCC and cSCC) (vallini2023signalingpathwaysand pages 1-2, yang2023trendsinkeratinocyte pages 1-8)

1.4 Evidence sources (patient-level vs aggregated)

  • Aggregated resources/guidelines: NCCN Clinical Practice Guideline (Version 2.2024; published 2023) and German S2k guideline update 2023 (published 2024). (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2)
  • Population-level registry data: Japan National Cancer Registry 2016–2017. (ogata2023epidemiologyofskin pages 1-2)
  • Patient-level cohorts: Prospective recurrence cohort (treated tumors followed for recurrence). (chren2013tumorrecurrence5 pages 1-2)

2. Etiology

2.1 Disease causal factors

Ultraviolet (UV) radiation is consistently highlighted as a principal causal factor, with additional contributions from ionizing radiation and genetic predisposition. (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2, vallini2023signalingpathwaysand pages 2-3)

2.2 Risk factors

  • UV exposure (including indoor tanning) and ionizing radiation (including prior radiotherapy) are key environmental risk factors. (schmults2023basalcellskin pages 2-4, vallini2023signalingpathwaysand pages 2-3)
  • Phenotype and demographics: fair skin, red/blond hair, light eye color; older age; male sex. (schmults2023basalcellskin pages 2-4, dessinioti2023immunotherapyandits pages 1-2)
  • Immunosuppression: increased risk in solid-organ transplant recipients; one 2023 review reported BCC risk elevated 6- to 16-fold vs the general population in transplant recipients in summarized literature. (vallini2023signalingpathwaysand pages 2-3)
  • Genetic predisposition / genodermatoses: basal cell carcinoma syndrome (Gorlin/NBCCS), xeroderma pigmentosum (XP). (lang2024s2kguidelinebasal pages 1-2, schmults2023basalcellskin pages 2-4)
  • Arsenic exposure: chronic arsenic exposure is listed as a risk factor in the German guideline and is also addressed in molecular profiling work in arsenic-exposed populations. (lang2024s2kguidelinebasal pages 1-2, alkassis2024therapeuticadvancesin pages 2-4)

2.3 Protective factors

  • Photoprotection/UV avoidance: emphasized as the primary prevention strategy for non-melanoma skin cancers. (hyeraci2023systemicphotoprotectionin pages 1-2)
  • Systemic photoprotection agents: A 2023 review states that among multiple oral photoprotective agents, only a few have demonstrated effectiveness in trials and have been incorporated into international guidance for NMSC prevention, including nicotinamide and retinoids. (hyeraci2023systemicphotoprotectionin pages 1-2)

2.4 Gene–environment interactions

The dominant conceptual interaction is UV-induced DNA damage superimposed on inherited or acquired susceptibility (e.g., pigmentary traits, DNA repair capacity, immune status), consistent with high UV-signature mutational patterns and known susceptibility loci; however, specific interaction effect sizes were not extractable from the retrieved texts. (vallini2023signalingpathwaysand pages 2-3, choquet2024multiancestrygenomewidemetaanalysis pages 7-7)

3. Phenotypes

3.1 Typical clinical phenotypes and presentation

BCC shows clinical heterogeneity; common subtypes include nodular and superficial BCC, with high-risk subtypes including morpheaform/sclerosing and infiltrative patterns. (alkassis2024therapeuticadvancesin pages 2-4, lang2024s2kguidelinebasal pages 1-2)

A structured phenotype/HPO mapping table is provided below.

Clinical feature Description Suggested HPO term(s) Notes/frequency (if in evidence) Evidence source (author year) URL
Nodular basal cell carcinoma Classic pearly/translucent papule or nodule, often with surface telangiectasia; may ulcerate as it enlarges HP:0009726 Skin nodule; HP:0000975 Hyperpigmentation of the skin (if pigmented); HP:0008066 Telangiectasia; HP:0000979 Skin ulcer Low-risk subtype; reported as the commonest subtype, about 60-80% of BCCs; usually slow-growing and locally invasive rather than metastatic (alkassis2024therapeuticadvancesin pages 2-4, lang2024s2kguidelinebasal pages 1-2) Alkassis 2024; Lang 2024 https://doi.org/10.3390/cancers16173075 ; https://doi.org/10.1111/ddg.15566
Superficial basal cell carcinoma Thin erythematous or scaly patch/plaque, often on trunk; can mimic inflammatory dermatoses HP:0000989 Pruritic rash; HP:0200034 Erythematous plaque; HP:0001075 Scaly skin Low-risk subtype; about 20% in one recent review; commonly on trunk and other sun-exposed skin (alkassis2024therapeuticadvancesin pages 2-4, lang2024s2kguidelinebasal pages 1-2) Alkassis 2024; Lang 2024 https://doi.org/10.3390/cancers16173075 ; https://doi.org/10.1111/ddg.15566
Pigmented basal cell carcinoma Brown/black/blue pigmented lesion, sometimes clinically resembling melanoma HP:0000953 Hypermelanotic macule; HP:0000975 Hyperpigmentation of the skin Particularly relevant in East Asian populations; Japanese guideline notes 88.3% of BCCs in Japanese patients are pigmented (lang2024s2kguidelinebasal pages 1-2) Lang 2024 https://doi.org/10.1111/ddg.15566
Morpheaform / sclerosing BCC Scar-like, indurated, ill-defined plaque with infiltrative growth pattern HP:0010783 Scar; HP:0002263 Facial asymmetry (if destructive facial growth); HP:0200034 Plaque High-risk histologic subtype with greater subclinical extension and recurrence risk; often requires Mohs surgery or wider margin control (alkassis2024therapeuticadvancesin pages 2-4, schmults2023basalcellskin media 73ba3136) Alkassis 2024; Schmults 2023 https://doi.org/10.3390/cancers16173075 ; https://doi.org/10.6004/jnccn.2023.0056
Infiltrative / micronodular / basosquamous high-risk BCC More aggressive growth patterns with deeper tissue infiltration and less obvious borders HP:0000951 Abnormality of the skin; HP:0008064 Neoplasm of the skin Considered high-risk subtypes; associated with greater local recurrence risk and need for margin-controlled surgery (alkassis2024therapeuticadvancesin pages 2-4, schmults2023basalcellskin media 73ba3136) Alkassis 2024; Schmults 2023 https://doi.org/10.3390/cancers16173075 ; https://doi.org/10.6004/jnccn.2023.0056
Nonhealing lesion Persistent lesion that fails to resolve over time HP:0033677 Nonhealing skin ulcer Common presentation in review literature; clinical suspicion should prompt biopsy (lang2024s2kguidelinebasal pages 1-2) Baba 2024 https://doi.org/10.3390/jmp5020010
Bleeding / friable lesion Lesion may bleed intermittently, especially after minor trauma HP:0025337 Cutaneous bleeding Review notes BCC may present as a nonhealing lesion that occasionally bleeds (lang2024s2kguidelinebasal pages 1-2) Baba 2024 https://doi.org/10.3390/jmp5020010
Pruritic lesion Itching can occur, although many lesions are asymptomatic HP:0000989 Pruritus Review notes BCC may present as a pruritic lesion with otherwise few symptoms (lang2024s2kguidelinebasal pages 1-2) Baba 2024 https://doi.org/10.3390/jmp5020010
Ulcerated lesion (“rodent ulcer”) Central ulceration developing in a locally destructive lesion HP:0000979 Skin ulcer Ulceration is part of the classic clinical heterogeneity described in guidelines; can indicate larger or neglected tumor (lang2024s2kguidelinebasal pages 1-2) Lang 2024 https://doi.org/10.1111/ddg.15566
Head and neck distribution Predominant anatomic distribution on chronically sun-exposed skin, especially face/head/neck HP:0000286 Epicanthus?; HP:0000154 Abnormality of the neck skin; HP:0011274 Abnormality of the skin of the face Most BCCs arise on head/neck; S2k guideline states BCCs occur mostly on head/neck, trunk, extremities; review notes lesions usually occur above line joining tragus to angle of mouth (lang2024s2kguidelinebasal pages 1-2) Lang 2024; Baba 2024 https://doi.org/10.1111/ddg.15566 ; https://doi.org/10.3390/jmp5020010
Truncal distribution Especially common for superficial BCC HP:0011122 Abnormality of skin of trunk Face, neck, and trunk are common sites in recent review (sol2024therapeuticapproachesfor pages 7-8) Sol 2024 https://doi.org/10.3390/ijms25137056
Adult / older-adult onset Usually presents later in life rather than childhood, except in hereditary syndromes HP:0003581 Adult onset; HP:0003596 Middle age onset; HP:0003584 Late onset Mean age of onset in German guideline ~73 years in men and 71 years in women (lang2024s2kguidelinebasal pages 1-2) Lang 2024 https://doi.org/10.1111/ddg.15566
Locally aggressive growth Slow-growing but capable of substantial local invasion, tissue destruction, disfigurement, and functional impairment HP:0000951 Abnormality of the skin; HP:0012252 Abnormality of facial soft tissue NCCN: less aggressive than melanoma/SCC but local destruction can cause disfigurement and limitation of function; advanced lesions behave aggressively (schmults2023basalcellskin pages 2-4, alkassis2024therapeuticadvancesin pages 1-2) Schmults 2023; Alkassis 2024 https://doi.org/10.6004/jnccn.2023.0056 ; https://doi.org/10.3390/cancers16173075
Very low metastatic potential Metastatic spread is exceptional compared with other skin cancers HP:0003002 Neoplasm of the skin?; HP:0002664 Neoplasm metastasis Metastasis estimated at <0.1% in NCCN and 0.0028%-0.55% in guideline/review estimates (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2, sol2024therapeuticapproachesfor pages 7-8) Schmults 2023; Lang 2024; Sol 2024 https://doi.org/10.6004/jnccn.2023.0056 ; https://doi.org/10.1111/ddg.15566 ; https://doi.org/10.3390/ijms25137056
Diagnostic confirmation by biopsy Histopathology is required to confirm diagnosis and subtype; deep reticular dermis sampling preferred when possible HP:0034335 Abnormal skin morphology NCCN recommends biopsy including deep reticular dermis; Baba review states all suspicious lesions should be biopsied (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2) Schmults 2023; Baba 2024 https://doi.org/10.6004/jnccn.2023.0056 ; https://doi.org/10.3390/jmp5020010
Diagnostic total-body skin examination Full skin exam at diagnosis to detect additional keratinocyte cancers or melanoma HP:0000951 Abnormality of the skin NCCN states patients are at increased risk for additional lesions and cutaneous melanoma; total-body skin exam recommended (schmults2023basalcellskin pages 2-4) Schmults 2023 https://doi.org/10.6004/jnccn.2023.0056
Imaging for suspected deep extension MRI preferred for perineural disease; CT preferred for possible bone involvement HP:0012790 Perineural invasion; HP:0000938 Osteolysis Imaging not routine for all BCC; used when clinical exam is insufficient or advanced extension suspected (schmults2023basalcellskin pages 2-4, schmults2023basalcellskin media 73ba3136) Schmults 2023 https://doi.org/10.6004/jnccn.2023.0056

Table: This table summarizes common clinical presentations and diagnostic features of basal cell carcinoma, with best-effort HPO mappings and key notes on distribution, aggressiveness, and metastatic rarity. It is useful for phenotype annotation and disease knowledge-base curation.

3.2 Age of onset, severity, progression

  • Age of onset: German S2k guideline reports mean age of onset ~73 years (men) and 71 years (women). (lang2024s2kguidelinebasal pages 1-2)
  • Course: typically slow-growing and locally invasive; metastasis is rare. (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2)

3.3 Quality-of-life impact

Guidelines emphasize that because local therapies (surgery and/or radiotherapy) are common, disfigurement and limitation of function are central morbidity concerns. (schmults2023basalcellskin pages 2-4)

4. Genetic/Molecular Information

4.1 Causal genes and key molecular drivers (current consensus)

BCC pathogenesis is strongly linked to Hedgehog (HH) pathway activation, typically via inactivation of pathway repressors (e.g., PTCH1) or activating alterations in SMO, resulting in downstream activation of GLI transcription factors. (lang2024s2kguidelinebasal pages 1-2, vallini2023signalingpathwaysand pages 2-3, alkassis2024therapeuticadvancesin pages 2-4)

A structured gene/pathway summary is provided below.

Mechanism/Pathway Key genes/proteins Typical alteration (somatic vs germline) Approx frequency/range in BCC (as stated) Notes (UV signature, resistance) Evidence source (author year) URL
Hedgehog pathway activation PTCH1, SMO, SUFU, GLI1/2/3 Mostly somatic in sporadic BCC; germline PTCH1 in Gorlin syndrome/NBCCS ~85% of sporadic BCCs carry Hedgehog-pathway mutations; PTCH LOF ~73%, SMO GOF ~20%, SUFU LOF ~8% (vallini2023signalingpathwaysand pages 2-3) Central driver pathway; basis for SMO-targeted therapy; resistance/toxicity limits long-term HHI use (vallini2023signalingpathwaysand pages 2-3, vallini2023signalingpathwaysand pages 1-2) Vallini 2023 https://doi.org/10.3390/cells12212534
Hedgehog pathway activation PTCH1, SMO Somatic in sporadic BCC; germline predisposition in syndromic disease PTCH1 mutations ~30%–90% of sporadic BCCs; SMO activating mutations ~10% of sporadic BCCs (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2) NCCN and S2k both identify sonic hedgehog signaling as pivotal in BCC pathogenesis (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2) Schmults 2023; Lang 2024 https://doi.org/10.6004/jnccn.2023.0056; https://doi.org/10.1111/ddg.15566
Hedgehog pathway dysregulation in advanced BCC PTCH1, SMO, GLI TFs Somatic PTCH1 LOF up to 75%; SMO activating mutations 10%–20% (alkassis2024therapeuticadvancesin pages 2-4) Advanced disease remains Hh-driven; HH inhibitors are effective but resistance emerges clinically (alkassis2024therapeuticadvancesin pages 2-4, alkassis2024therapeuticadvancesin pages 1-2) Alkassis 2024 https://doi.org/10.3390/cancers16173075
UV-induced DNA damage / tumor suppressor disruption TP53, PTCH1 Somatic TP53 altered in 61% in one study summarized by S2k; UV-signature mutations common in p53 and PTCH (lang2024s2kguidelinebasal pages 1-2, vallini2023signalingpathwaysand pages 2-3) Canonical C>T / CC>TT UV-signature mutagenesis; UVB is the dominant environmental trigger (vallini2023signalingpathwaysand pages 2-3, schmults2023basalcellskin pages 2-4) Lang 2024; Vallini 2023 https://doi.org/10.1111/ddg.15566; https://doi.org/10.3390/cells12212534
High tumor mutational burden / immunogenicity PD-L1, MHC-I, neoantigen burden Somatic tumor feature TMB reported as 47.3 mutations/Mb; PD-L1 expression in one study: 22% of tumor cells and 82% of tumor-infiltrating immune cells (vallini2023signalingpathwaysand pages 2-3, dessinioti2023immunotherapyandits pages 1-2) Provides rationale for PD-1 blockade after HHI failure; predictive biomarkers remain unsettled (dessinioti2023immunotherapyandits pages 1-2, alkassis2024therapeuticadvancesin pages 10-12) Vallini 2023; Dessinioti 2023 https://doi.org/10.3390/cells12212534; https://doi.org/10.5826/dpc.1304a252
UV-associated promoter/non-Hedgehog mutations TERT, DPH3-OXNAD1 Somatic TERT 39%–74%; DPH3-OXNAD1 42% (alkassis2024therapeuticadvancesin pages 2-4) Reported as UV-associated alterations complementing Hedgehog and TP53 pathway disruption (alkassis2024therapeuticadvancesin pages 2-4) Alkassis 2024 https://doi.org/10.3390/cancers16173075
Additional driver/modifier landscape NOTCH1/2, RAS family, MYCN, CSMD1/2, IFIH1, CCR5, TPCN2, FADS2, CDKL1 Mostly somatic for tumor drivers; germline susceptibility loci from GWAS 122 BCC-associated loci identified in multi-ancestry GWAS; 36 novel loci (choquet2024multiancestrygenomewidemetaanalysis pages 7-7). Earlier multi-phenotype analysis identified 78 BCC risk loci, including 19 previously unknown (from search results summary) Supports polygenic susceptibility, pigmentation/immune pathway overlap, and risk stratification beyond HH alone (choquet2024multiancestrygenomewidemetaanalysis pages 7-7) Choquet 2024; Seviiri 2022 https://doi.org/10.1038/s42003-023-05753-7; https://doi.org/10.1038/s41467-022-35345-8
Immunosuppressive tumor microenvironment Tregs, CAFs, IL-6, IL-10, CCL22, LAG-3, PD-1, macrophages, γδ T cells Tumor microenvironmental state No single uniform frequency; checkpoint markers LAG-3 and PD-1 expressed on >1% of TILs in profiled tumors (alkassis2024therapeuticadvancesin pages 2-4) Advanced BCC shows macrophage-driven inflammation; low-risk lesions enriched for γδ T cells; supports immunotherapy combinations (alkassis2024therapeuticadvancesin pages 2-4) Alkassis 2024 https://doi.org/10.3390/cancers16173075
Cell of origin / developmental programs Hair follicle stem cells, interfollicular epidermis, bulge stem cells, SHH/SMO Experimental models; developmental lineage mechanisms Not a mutation frequency; lineage evidence indicates superficial BCC may arise from interfollicular epidermis, nodular BCC from hair follicle stem cells (nicoletti2024dysembryogeneticpathogenesisof pages 8-10, nicoletti2024dysembryogeneticpathogenesisof pages 11-12) Mouse and xenograft models support Hedgehog-driven reprogramming; relevant for understanding subtype biology rather than diagnosis (nicoletti2024dysembryogeneticpathogenesisof pages 8-10, cong2025mechanismsandtherapeutic pages 4-5) Nicoletti 2024; Cong 2025 https://doi.org/10.3390/ijms25158452; https://doi.org/10.1038/s41420-025-02327-w
Therapeutic resistance axis SMO, downstream GLI signaling, non-canonical RAS-RAF-MEK-ERK inputs Acquired somatic/drug-resistance biology No fixed frequency stated in retrieved text HHI benefit can be limited by adverse events and resistance; non-canonical GLI activation via MAPK signaling is a proposed bypass mechanism (vallini2023signalingpathwaysand pages 2-3, vallini2023signalingpathwaysand pages 1-2) Vallini 2023 https://doi.org/10.3390/cells12212534

Table: This table summarizes the core molecular pathways, genes, and mechanistic features implicated in basal cell carcinoma, with frequencies and notes drawn from the retrieved evidence. It is useful for linking clinical BCC biology to driver alterations, mutational processes, and treatment resistance.

4.2 Pathogenic variants and somatic vs germline

  • Somatic drivers (sporadic BCC): Hedgehog-pathway mutations are common; one 2023 advanced BCC review summarizes that ~85% of sporadic BCCs carry HH-pathway mutations (~73% PTCH loss-of-function, ~20% SMO gain-of-function, ~8% SUFU loss-of-function). (vallini2023signalingpathwaysand pages 2-3)
  • Germline predisposition: Gorlin syndrome/NBCCS is linked to germline PTCH1; a 2023 review reports a small fraction of BCC is linked to Gorlin syndrome. (vallini2023signalingpathwaysand pages 2-3)

4.3 Epigenetic, chromosomal, and multi-omics

The retrieved evidence base emphasizes mutational and transcriptomic/tumor-microenvironment features rather than a consistent epigenetic signature; therefore, no specific DNA methylation/histone-modification markers are asserted here.

5. Environmental Information

5.1 Environmental and lifestyle factors

  • UV radiation (sunlight and indoor tanning) and ionizing radiation are consistently cited contributors to BCC development. (schmults2023basalcellskin pages 2-4, vallini2023signalingpathwaysand pages 2-3)
  • Arsenic exposure is listed as a risk factor in guideline/review evidence and is associated with NMSC molecular profiling in an arsenic-exposed population. (lang2024s2kguidelinebasal pages 1-2, alkassis2024therapeuticadvancesin pages 2-4)

5.2 Infectious agents

No specific infectious agent is established as a direct cause of BCC in the retrieved evidence.

6. Mechanism / Pathophysiology

6.1 Causal chain (high-level)

  1. Trigger/exposure: chronic UV exposure and/or ionizing radiation (and other modifiers such as immunosuppression). (schmults2023basalcellskin pages 2-4, vallini2023signalingpathwaysand pages 2-3)
  2. DNA damage and mutation acquisition: UV-signature mutations commonly affect tumor suppressors (e.g., TP53) and Hedgehog pathway components (e.g., PTCH). (schmults2023basalcellskin pages 2-4, lang2024s2kguidelinebasal pages 1-2)
  3. Pathway dysregulation: loss of PTCH-mediated repression of SMO → activation of GLI transcriptional programs → keratinocyte proliferation and tumor growth. (sol2024therapeuticapproachesfor pages 2-3, vallini2023signalingpathwaysand pages 2-3)
  4. Local invasion and immune modulation: BCC can show high tumor mutational burden with an “immune excluded”/immunosuppressive microenvironment, providing a rationale for immune checkpoint blockade in advanced disease. (dessinioti2023immunotherapyandits pages 1-2, alkassis2024therapeuticadvancesin pages 2-4)

6.2 Suggested ontology mappings

  • GO biological processes (examples):
  • Hedgehog signaling pathway (GO:0007224)
  • Regulation of cell proliferation (GO:0042127)
  • DNA damage response (GO:0006974)
  • Keratinocyte differentiation (GO:0030216)
  • Cell Ontology (examples):
  • Keratinocyte (CL:0000312)
  • Epidermal basal cell (best-effort; basal keratinocyte subtype)
  • Hair follicle stem cell (best-effort; stem/progenitor niche implicated in models) (nicoletti2024dysembryogeneticpathogenesisof pages 8-10)

7. Anatomical Structures Affected

7.1 Organ/tissue level

  • Primary organ: skin (epidermis and adnexal structures), with most lesions on sun-exposed sites (face/head/neck; also trunk). (lang2024s2kguidelinebasal pages 1-2, sol2024therapeuticapproachesfor pages 7-8)

7.2 Cell level

  • Primary affected cell type: keratinocytes/basal epidermal lineage. (sol2024therapeuticapproachesfor pages 7-8, sol2024therapeuticapproachesfor pages 2-3)
  • Cell(s) of origin (model-based): evidence supports contributions from interfollicular epidermis (superficial BCC) and hair follicle stem cells (nodular BCC) in experimental contexts. (nicoletti2024dysembryogeneticpathogenesisof pages 8-10)

7.3 UBERON suggestions (best-effort)

  • Skin (UBERON:0002097)
  • Epidermis (UBERON:0001003)
  • Hair follicle (UBERON:0002074)

8. Temporal Development

  • Onset pattern: typically chronic/insidious in older adults; rapid growth and recurrence characterize the minority “difficult-to-treat” subset. (alkassis2024therapeuticadvancesin pages 1-2, lang2024s2kguidelinebasal pages 1-2)
  • Progression: Most cases are “easy-to-treat”; a review-derived classification estimates ~95% are easy-to-treat, with locally advanced and metastatic disease estimated at 0.8% and 0.0028–0.55%, respectively. (sol2024therapeuticapproachesfor pages 7-8)

9. Inheritance and Population

9.1 Epidemiology (selected recent statistics)

A data-rich summary table is provided below.

Metric Value Population/Setting Source (first author year) PMID if known URL if available
US annual BCC cases estimate 2 million Americans annually United States; estimated annual incidence in NCCN guideline Schmults 2023 (schmults2023basalcellskin pages 2-4) https://doi.org/10.6004/jnccn.2023.0056
US annual BCC cases estimate 3.6 million cases diagnosed annually United States; review estimate Alkassis 2024 (alkassis2024therapeuticadvancesin pages 1-2) https://doi.org/10.3390/cancers16173075
Germany incidence ≥200 per 100,000/year Germany Lang 2024 (lang2024s2kguidelinebasal pages 1-2) https://doi.org/10.1111/ddg.15566
Lifetime prevalence >10% Central/Northern European groups Lang 2024 (lang2024s2kguidelinebasal pages 1-2) https://doi.org/10.1111/ddg.15566
Japan BCC share of skin cancers 37.2% Japan National Cancer Registry 2016–2017 Ogata 2023 (ogata2023epidemiologyofskin pages 1-2) https://doi.org/10.1111/cas.15823
Japan BCC incidence 3.63 per 100,000 Japan; WHO standard population model Ogata 2023 (ogata2023epidemiologyofskin pages 1-2) https://doi.org/10.1111/cas.15823
Metastatic rate / incidence <0.1% General BCC; NCCN summary Schmults 2023 (schmults2023basalcellskin pages 2-4) https://doi.org/10.6004/jnccn.2023.0056
Metastatic rate / incidence 0.0028%–0.55% General BCC; guideline/review estimates Lang 2024 (lang2024s2kguidelinebasal pages 1-2) https://doi.org/10.1111/ddg.15566
Progression to advanced disease 1%–10% BCC overall progressing to advanced stage Alkassis 2024 (alkassis2024therapeuticadvancesin pages 1-2) https://doi.org/10.3390/cancers16173075
laBCC incidence 0.8% Difficult-to-treat BCC classification Sol 2024 (sol2024therapeuticapproachesfor pages 7-8) https://doi.org/10.3390/ijms25137056
mBCC incidence 0.0028%–0.55% Difficult-to-treat BCC classification Sol 2024 (sol2024therapeuticapproachesfor pages 7-8) https://doi.org/10.3390/ijms25137056
5-year recurrence after Mohs surgery (primary BCC) 1.0% Systematic review-weighted average Schmults 2023 (schmults2023basalcellskin pages 7-9) https://doi.org/10.6004/jnccn.2023.0056
5-year recurrence after Mohs surgery (recurrent BCC) 5.6% Systematic review-weighted average Schmults 2023 (schmults2023basalcellskin pages 7-9) https://doi.org/10.6004/jnccn.2023.0056
5-year recurrence after standard excision (primary BCC) 10.1% Comparative analyses cited in NCCN Schmults 2023 (schmults2023basalcellskin pages 7-9) https://doi.org/10.6004/jnccn.2023.0056
5-year recurrence after standard excision (recurrent BCC) 17.4% Comparative analyses cited in NCCN Schmults 2023 (schmults2023basalcellskin pages 7-9) https://doi.org/10.6004/jnccn.2023.0056
5-year recurrence after destruction/C&E 1.2%–40% Reported range; varies by risk/anatomic site/subtype Schmults 2023 (schmults2023basalcellskin pages 7-9) https://doi.org/10.6004/jnccn.2023.0056
5-year recurrence after destruction 4.9% (95% CI 2.3–7.4) Prospective cohort of primary NMSC (BCC+SCC) Chren 2013 (chren2013tumorrecurrence5 pages 1-2) https://doi.org/10.1038/jid.2012.403
5-year recurrence after excision 3.5% (95% CI 1.8–5.2) Prospective cohort of primary NMSC (BCC+SCC) Chren 2013 (chren2013tumorrecurrence5 pages 1-2) https://doi.org/10.1038/jid.2012.403
5-year recurrence after Mohs surgery 2.1% (95% CI 0.6–3.5) Prospective cohort of primary NMSC (BCC+SCC) Chren 2013 (chren2013tumorrecurrence5 pages 1-2) https://doi.org/10.1038/jid.2012.403
Adjusted 5-year recurrence after destruction 3.8% (95% CI 1.4–6.1) Prospective cohort of primary NMSC (BCC+SCC) Chren 2013 (chren2013tumorrecurrence5 pages 3-4) https://doi.org/10.1038/jid.2012.403
Adjusted 5-year recurrence after excision 3.3% (95% CI 1.6–4.9) Prospective cohort of primary NMSC (BCC+SCC) Chren 2013 (chren2013tumorrecurrence5 pages 3-4) https://doi.org/10.1038/jid.2012.403
Adjusted 5-year recurrence after Mohs surgery 1.7% (95% CI 0.4–3.0) Prospective cohort of primary NMSC (BCC+SCC) Chren 2013 (chren2013tumorrecurrence5 pages 3-4) https://doi.org/10.1038/jid.2012.403
Cemiplimab ORR after prior HHI 31% (26/84); CR 6%, PR 25% Locally advanced BCC after hedgehog inhibitor therapy Stratigos 2021 (stratigos2021cemiplimabinlocally pages 5-6, stratigos2021cemiplimabinlocally pages 1-1) https://doi.org/10.1016/S1470-2045(21)00126-1
Cemiplimab median PFS 19 months (95% CI 9–not evaluable) Locally advanced BCC after hedgehog inhibitor therapy Stratigos 2021 (stratigos2021cemiplimabinlocally pages 5-6) https://doi.org/10.1016/S1470-2045(21)00126-1
Cemiplimab median duration of response Not reached; 91% in response at 6 months, 85% at 12 months Responders with locally advanced BCC after hedgehog inhibitor therapy Stratigos 2021 (stratigos2021cemiplimabinlocally pages 5-6) https://doi.org/10.1016/S1470-2045(21)00126-1

Table: This table compiles high-yield epidemiology, progression, metastasis, recurrence, and systemic therapy outcome statistics for basal cell carcinoma from the gathered evidence. It is designed to support rapid comparison of population burden and clinically relevant outcome benchmarks.

Key points from recent guidelines and registry analyses: - NCCN estimates ~2 million Americans affected annually (acknowledging under-registration). (schmults2023basalcellskin pages 2-4) - German S2k guideline reports ≥200/100,000/year incidence in Germany and lifetime prevalence >10% in central/northern Europe. (lang2024s2kguidelinebasal pages 1-2) - Japan registry analysis (2016–2017) reports BCC incidence 3.63/100,000 (WHO model). (ogata2023epidemiologyofskin pages 1-2)

9.2 Genetic architecture

  • Rare high-penetrance syndromes (e.g., Gorlin/NBCCS, XP) contribute to susceptibility. (lang2024s2kguidelinebasal pages 1-2, vallini2023signalingpathwaysand pages 2-3)
  • Common-variant susceptibility is polygenic; a multi-ancestry GWAS meta-analysis (50,531 cases; 762,234 controls) identified 122 BCC-associated loci (36 novel). (choquet2024multiancestrygenomewidemetaanalysis pages 7-7)

10. Diagnostics

10.1 Core diagnostic approach

  • Clinical exam + biopsy confirmation: NCCN recommends biopsy that includes deep reticular dermis; total body skin exam is recommended because patients are at increased risk of additional lesions and melanoma. (schmults2023basalcellskin pages 2-4)
  • Imaging in selected cases: MRI preferred for suspected perineural disease; CT preferred for suspected bony involvement. (schmults2023basalcellskin pages 2-4)

10.2 Risk stratification and real-world clinical algorithms

NCCN provides operational risk stratification (low vs high risk) based on clinical and pathologic features and provides a treatment flowchart that escalates to Mohs surgery or margin-controlled approaches for high-risk tumors.

  • NCCN risk stratification table and treatment algorithms (visual evidence): (schmults2023basalcellskin media 73ba3136, schmults2023basalcellskin media 96ea4de3, schmults2023basalcellskin media e102265c)

10.3 Differential diagnosis

Not systematically extracted from the retrieved evidence; in practice includes melanoma (especially for pigmented lesions), SCC, sebaceous hyperplasia, adnexal tumors, inflammatory dermatoses (for superficial BCC), and benign ulcer etiologies.

11. Outcome / Prognosis

11.1 Metastasis and advanced disease

  • NCCN describes metastatic rate as <0.1%. (schmults2023basalcellskin pages 2-4)
  • German guideline gives metastatic incidence estimates 0.0028%–0.55%. (lang2024s2kguidelinebasal pages 1-2)

11.2 Local control / recurrence benchmarks

Evidence for 5-year recurrence varies depending on case-mix and treatment selection. Two complementary evidence types are useful:

1) Prospective cohort (NMSC overall) with CIs: unadjusted 5-year recurrence after Mohs 2.1% (95% CI 0.6–3.5), excision 3.5% (1.8–5.2), destruction 4.9% (2.3–7.4). (chren2013tumorrecurrence5 pages 1-2)

2) Systematic-review weighted averages emphasizing BCC recurrence (commonly cited in practice): 5-year recurrence for primary BCC 1.0% after Mohs vs 10.1% after excision; recurrent BCC 5.6% after Mohs vs 17.4% after excision. (schmults2023basalcellskin pages 7-9, kauvar2015consensusfornonmelanoma pages 7-8)

12. Treatment

12.1 Treatment landscape and real-world implementation

A structured treatment table (including MAXO suggestions) is provided below.

Treatment modality Indication (low-risk/high-risk/locally advanced/metastatic) Mechanism/approach Key outcome stats (recurrence or ORR/PFS where available) Key adverse events/limitations (if stated in evidence) Suggested MAXO term (best-effort) Evidence source (author year) URL
Standard surgical excision Primarily low-risk; also selected high-risk lesions with margin control Elliptical excision with histopathologic margin assessment 5-year recurrence for primary BCC reported as 10.1%; recurrent BCC 17.4% in comparative analyses; in a prospective NMSC cohort, unadjusted 5-year recurrence 3.5% (95% CI 1.8-5.2), adjusted 3.3% (95% CI 1.6-4.9) (schmults2023basalcellskin pages 7-9, chren2013tumorrecurrence5 pages 1-2, chren2013tumorrecurrence5 pages 3-4) Incomplete excision rates reported 3.2%-61.5% depending on site/subtype/provider; may be suboptimal for high-risk facial tumors (schmults2023basalcellskin pages 7-9) MAXO: surgical excision Schmults 2023; Chren 2013 https://doi.org/10.6004/jnccn.2023.0056 ; https://doi.org/10.1038/jid.2012.403
Mohs micrographic surgery (MMS) High-risk, recurrent, tissue-sparing critical sites; many head/neck tumors Stage-wise excision with complete peripheral/deep margin assessment 5-year recurrence 1.0% for primary BCC and 5.6% for recurrent BCC in NCCN-cited meta-analyses; prospective cohort unadjusted 2.1% (95% CI 0.6-3.5), adjusted 1.7% (95% CI 0.4-3.0); Denmark nationwide cohort: overall 5-year recurrence 3.8%, primary 3.1%, recurrent 5.3% (schmults2023basalcellskin pages 7-9, chren2013tumorrecurrence5 pages 1-2, chren2013tumorrecurrence5 pages 3-4) Resource-intensive; generally reserved for high-risk or anatomically critical tumors (schmults2023basalcellskin media 73ba3136, schmults2023basalcellskin media 96ea4de3, schmults2023basalcellskin media e102265c) MAXO: Mohs micrographic surgery Schmults 2023; Chren 2013 https://doi.org/10.6004/jnccn.2023.0056 ; https://doi.org/10.1038/jid.2012.403
Curettage and electrodesiccation (C&E) / destruction Selected low-risk superficial or nodular lesions Physical tumor destruction by curettage plus electrodessication 5-year recurrence range 1.2%-40% depending on risk/site/subtype; prospective cohort unadjusted 4.9% (95% CI 2.3-7.4), adjusted 3.8% (95% CI 1.4-6.1) for NMSC overall (schmults2023basalcellskin pages 7-9, chren2013tumorrecurrence5 pages 1-2, chren2013tumorrecurrence5 pages 3-4) No histologic margin assessment; higher recurrence in high-risk locations/aggressive histology; not preferred in terminal hair-bearing sites (schmults2023basalcellskin pages 7-9) MAXO: curettage of skin lesion; electrodesiccation Schmults 2023; Chren 2013 https://doi.org/10.6004/jnccn.2023.0056 ; https://doi.org/10.1038/jid.2012.403
Radiotherapy Alternative for unresectable tumors, positive margins when re-excision not feasible, or patients unsuitable for surgery; recurrent/high-risk in selected settings Local ionizing radiation for tumor control Meta-analytic/guide-level evidence suggests recurrence can be comparable to surgery in selected cases; NCCN and S2k list RT as a major modality, especially when surgery is not feasible (alkassis2024therapeuticadvancesin pages 1-2, lang2024s2kguidelinebasal pages 1-2, sol2024therapeuticapproachesfor pages 7-8) Cosmetic/functional trade-offs; generally not first choice for most operable cases (alkassis2024therapeuticadvancesin pages 1-2, lang2024s2kguidelinebasal pages 1-2) MAXO: radiation therapy Alkassis 2024; Lang 2024; Sol 2024 https://doi.org/10.3390/cancers16173075 ; https://doi.org/10.1111/ddg.15566 ; https://doi.org/10.3390/ijms25137056
Topical imiquimod Selected superficial low-risk BCC Immune response modifier (TLR7 agonist) Included as topical option in guidelines/reviews for appropriately selected superficial disease; no robust recurrence statistic extracted from retrieved texts (alkassis2024therapeuticadvancesin pages 2-4, lang2024s2kguidelinebasal pages 1-2) Limited to selected superficial lesions; not appropriate for many high-risk tumors (alkassis2024therapeuticadvancesin pages 2-4, lang2024s2kguidelinebasal pages 1-2) MAXO: topical immune response modifier therapy Alkassis 2024; Lang 2024 https://doi.org/10.3390/cancers16173075 ; https://doi.org/10.1111/ddg.15566
Topical 5-fluorouracil Selected superficial low-risk BCC Topical antimetabolite chemotherapy Listed in guidelines/reviews for superficial disease; no extracted pooled recurrence number in retrieved evidence (alkassis2024therapeuticadvancesin pages 2-4, lang2024s2kguidelinebasal pages 1-2) Limited role outside superficial disease; lacks margin control (alkassis2024therapeuticadvancesin pages 2-4) MAXO: topical antimetabolite therapy Alkassis 2024; Lang 2024 https://doi.org/10.3390/cancers16173075 ; https://doi.org/10.1111/ddg.15566
Photodynamic therapy (PDT) Selected superficial facial/scalp or other low-risk superficial BCC Photosensitizer plus activating light causing local cytotoxicity Used in real-world management of superficial lesions; no trial-level recurrence figure extracted here (alkassis2024therapeuticadvancesin pages 2-4) Best suited to superficial disease; not a standard approach for deeply invasive/high-risk BCC (alkassis2024therapeuticadvancesin pages 2-4) MAXO: photodynamic therapy Alkassis 2024 https://doi.org/10.3390/cancers16173075
Vismodegib Locally advanced/metastatic BCC not amenable to curative surgery/RT; first-line systemic Small-molecule SMO inhibitor targeting Hedgehog pathway Guideline-supported first-line systemic option for advanced BCC; advanced disease estimates: laBCC ~0.8%, mBCC 0.0028%-0.55%; no ORR extracted from retrieved primary text here (sol2024therapeuticapproachesfor pages 7-8, lang2024s2kguidelinebasal pages 1-2, dessinioti2023immunotherapyandits pages 1-2) High discontinuation burden across HHIs: vismodegib discontinuation 88%-92%, with about half stopping after ~8-12 months (dessinioti2023immunotherapyandits pages 1-2) MAXO: Hedgehog pathway inhibitor therapy Sol 2024; Lang 2024; Dessinioti 2023 https://doi.org/10.3390/ijms25137056 ; https://doi.org/10.1111/ddg.15566 ; https://doi.org/10.5826/dpc.1304a252
Sonidegib Locally advanced/metastatic BCC not amenable to curative surgery/RT; first-line systemic alternative Small-molecule SMO inhibitor targeting Hedgehog pathway Guideline-supported first-line systemic option for advanced BCC; no ORR extracted from retrieved primary text here (dessinioti2023immunotherapyandits pages 1-2, lang2024s2kguidelinebasal pages 1-2) Approximate discontinuation ~92%; resistance and tolerability issues limit long-term use (dessinioti2023immunotherapyandits pages 1-2, vallini2023signalingpathwaysand pages 2-3) MAXO: Hedgehog pathway inhibitor therapy Dessinioti 2023; Lang 2024; Vallini 2023 https://doi.org/10.5826/dpc.1304a252 ; https://doi.org/10.1111/ddg.15566 ; https://doi.org/10.3390/cells12212534
Cemiplimab Locally advanced or metastatic BCC after HHI intolerance/progression; second-line systemic Anti-PD-1 immune checkpoint inhibitor Phase 2 laBCC after HHI: ORR 31% (26/84; 95% CI 21-42), CR 6%, PR 25%; median time to response 4.3 months; median PFS 19 months (95% CI 9-NE); median DOR not reached, 91% in response at 6 months and 85% at 12 months; median DOR 26.2 months reported in later review summary (stratigos2021cemiplimabinlocally pages 5-6, stratigos2021cemiplimabinlocally pages 1-1, dessinioti2023immunotherapyandits pages 4-6) Grade 3-4 treatment-emergent AEs in 48%; immune-related AEs in 25%, hypothyroidism 10%; discontinuation commonly due to progression or AEs (stratigos2021cemiplimabinlocally pages 1-1, dessinioti2023immunotherapyandits pages 4-6) MAXO: PD-1 inhibitor immunotherapy Stratigos 2021; Dessinioti 2023 https://doi.org/10.1016/S1470-2045(21)00126-1 ; https://doi.org/10.5826/dpc.1304a252
Nivolumab (investigational) Advanced BCC in clinical trials Anti-PD-1 immunotherapy Phase II signal: ORR 50% in 10 patients with nivolumab monotherapy; 10% in 6 patients with nivolumab + relatlimab in one review summary (alkassis2024therapeuticadvancesin pages 10-12) Early-phase/investigational; very small cohorts (alkassis2024therapeuticadvancesin pages 10-12) MAXO: PD-1 inhibitor immunotherapy Alkassis 2024 https://doi.org/10.3390/cancers16173075
Combined cemiplimab + sonidegib (case-report implementation) Synchronous advanced cSCC/BCC of head and neck; individualized multidisciplinary use Combined PD-1 blockade plus SMO inhibition Two reported cases achieved remarkable clinical benefit and long-term responses without major adverse events (sol2024therapeuticapproachesfor pages 7-8) Limited to case reports; not standard guideline algorithm (sol2024therapeuticapproachesfor pages 7-8) MAXO: combination immunotherapy and targeted therapy Colombo 2023 https://doi.org/10.3389/fonc.2023.1111146

Table: This table summarizes major basal cell carcinoma treatment options across low-risk, high-risk, and advanced disease, emphasizing real-world implementation and quantitative outcomes where available. It is useful for comparing local therapies, systemic Hedgehog inhibitors, and immunotherapy in a single evidence-linked view.

12.2 Surgery and local therapies

  • Surgery is widely described as first-line for most BCCs; Mohs is prioritized for high-risk lesions to minimize recurrence and preserve tissue. (lang2024s2kguidelinebasal pages 1-2, schmults2023basalcellskin media 73ba3136)

12.3 Targeted therapy: Hedgehog pathway inhibitors (HHIs)

For locally advanced/metastatic BCC not amenable to curative surgery/radiation, vismodegib and sonidegib are first-line systemic options. High discontinuation rates are emphasized in 2023 expert review evidence: 88–92% discontinuation for vismodegib and approximately 92% for sonidegib, with about half discontinuing after ~8–12 months. (dessinioti2023immunotherapyandits pages 1-2)

12.4 Immunotherapy: PD-1 blockade

For advanced BCC after HHI failure/intolerance, cemiplimab is supported by phase 2 evidence. In the locally advanced cohort (n=84), independent central review ORR was 31% (26/84; 95% CI 21–42) with 6% complete and 25% partial responses, and median PFS 19 months (95% CI 9–not evaluable). (stratigos2021cemiplimabinlocally pages 1-1, stratigos2021cemiplimabinlocally pages 5-6)

Direct efficacy statement from the trial excerpt (data): ORR and response composition are reported numerically as above; median time to response was 4.3 months (IQR 4.2–7.2), and median duration of response was not reached, with 85% remaining in response at 12 months (Kaplan–Meier). (stratigos2021cemiplimabinlocally pages 5-6)

13. Prevention

13.1 Primary prevention (UV/radiation)

Photoprotection is emphasized as the first-choice prevention strategy for non-melanoma skin cancers given UV’s central role. (hyeraci2023systemicphotoprotectionin pages 1-2)

13.2 Chemoprevention (nicotinamide)

Evidence is mixed depending on population and pooling strategy: - Mainville et al. meta-analysis (2022): oral nicotinamide associated with reduced new skin cancers overall (rate ratio 0.50; 95% CI 0.29–0.85) and the authors report significant reduction in BCC and cSCC. (mainville2022effectofnicotinamide pages 1-2) - Tosti et al. meta-analysis (2023): pooled estimates were not statistically significant for BCC (RR 0.88; 95% CI 0.50–1.55) when combining immunocompetent and immunosuppressed cohorts; authors conclude insufficient evidence for significant reduction. (tosti2023theroleof pages 1-2) - Guideline inclusion statement (systemic photoprotection review 2023): only a few oral agents have shown efficacy in trials and have been incorporated into international guidance for NMSC prevention, including nicotinamide and retinoids. (hyeraci2023systemicphotoprotectionin pages 1-2)

13.3 Secondary prevention (screening/early detection)

  • NCCN emphasizes total body skin examination and careful follow-up due to increased risk of additional keratinocyte cancers and melanoma. (schmults2023basalcellskin pages 2-4)

14. Other Species / Natural Disease

The retrieved evidence focused on mechanistic model systems rather than naturally occurring BCC in non-human populations; therefore, naturally occurring veterinary BCC epidemiology is not asserted here.

15. Model Organisms

Evidence supports several established experimental approaches: - Transgenic mouse models overexpressing HH mediators (SHH, GLI1/2, oncogenic SMO) develop BCC-like tumors. (cong2025mechanismsandtherapeutic pages 4-5) - Human keratinocyte xenograft models: engineered keratinocytes expressing SHH grafted onto nude mice generate BCC-like structures. (cong2025mechanismsandtherapeutic pages 4-5) - Lineage/cell-of-origin models: data support contributions of interfollicular epidermis vs hair follicle stem cells for different clinical subtypes; neural niche contributions are also described in mouse studies summarized in a 2024 review. (nicoletti2024dysembryogeneticpathogenesisof pages 8-10) - Ex vivo models: ex vivo skin explant culture models are noted as practical for testing therapies when primary BCC cultures are hard to maintain. (vallini2023signalingpathwaysand pages 13-14)

Notes on evidence gaps and compliance with requested identifiers

  • PMIDs: Many of the retrieved recent guideline/review PDFs did not expose PMID fields in the tool outputs; therefore PMID annotation is incomplete in this run.
  • ICD-11/MONDO/MeSH official IDs: Not available directly in retrieved full texts; therefore not asserted.

Key NCCN algorithm figures (visual evidence)

  • NCCN risk stratification table, initial risk categorization flowchart, and high-risk treatment algorithm were extracted as images from the NCCN guideline PDF. (schmults2023basalcellskin media 73ba3136, schmults2023basalcellskin media 96ea4de3, schmults2023basalcellskin media e102265c)

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OpenScientist ▸
1. Disease Information
openscientist-autonomous 70 citations 2026-05-06T00:20:20.473762+00:00

1. Disease Information

Overview

Basal cell carcinoma is a malignant neoplasm arising from basal cells of the epidermis and hair follicle structures. It is the single most common cancer in humans, particularly prevalent among fair-skinned populations. BCC is characterized by slow growth, local invasiveness, and an extremely low rate of metastasis (<0.1%), yet untreated lesions can cause significant tissue destruction and functional impairment (PMID: 31585338; PMID: 41515948).

As noted in a comprehensive epidemiological review: "Basal cell carcinomas (BCC) are the most common, comprising 80% of keratinocyte cancers, but have a very low rate of metastases and low mortality" (PMID: 31585338).

Key Identifiers

Database Identifier
MONDO MONDO:0004972
OMIM 605462 (BCC1); 613294 (BCC, susceptibility to)
ICD-10 C44 (Other malignant neoplasms of skin)
ICD-11 2C32.0 (Basal cell carcinoma of skin)
MeSH D002280 (Carcinoma, Basal Cell)
Orphanet ORPHA:48 (Basal cell carcinoma)
SNOMED CT 254701007 (Basal cell carcinoma of skin)

Synonyms and Alternative Names

  • Basal cell epithelioma
  • Basalioma
  • Rodent ulcer
  • BCC
  • Basaloid carcinoma
  • Jacob's ulcer

Information Sources

This report synthesizes information from aggregated disease-level resources (OMIM, Orphanet, GWAS Catalog, COSMIC, GBD), clinical trial data, population-based registries (SEER, Danish national databases), and primary literature (100 papers reviewed from PubMed).

2. Etiology

Disease Causal Factors

BCC is a multifactorial disease resulting from the convergence of genetic, environmental, and epigenetic factors. The central molecular driver is constitutive activation of the Hedgehog signaling pathway:

"Basal cell carcinoma (BCC) is driven in nearly all cases by mutations that constitutively activate upstream Hedgehog (HH) signaling, either through loss-of-function mutations in PTCH1 or gain-of-function mutations in SMO" (PMID: 41240053).

The disease represents a complex interplay: "BCC is a complex disease, in which the interplay between UVR, phenotype (UVR-sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis" (PMID: 28220485).

Risk Factors

Genetic Risk Factors

  • PTCH1 mutations (9q22.32): Loss-of-function mutations in the Hedgehog receptor PTCH1 are found in ~73% of sporadic BCCs (OMIM: 601309). These are predominantly somatic, though germline mutations cause Gorlin syndrome.
  • SMO mutations (7q32.1): Gain-of-function mutations in the Smoothened receptor occur in ~10–20% of cases (OMIM: 601500).
  • TP53 mutations: Found in approximately 50% of BCCs, typically UV-signature C>T transitions.
  • Pigmentation gene variants (GWAS-identified susceptibility loci):
  • MC1R (rs1805007, Arg151Cys) — strongest association with BCC risk; OR = 1.55 (95% CI: 1.45–1.66; P = 4.3 x 10^-17) (PMID: 21700618)
  • ASIP/RALY — associated with agouti signaling and melanogenesis
  • IRF4 — interferon regulatory factor 4
  • OCA2 — oculocutaneous albinism type 2
  • SLC45A2 — solute carrier family 45 member 2
  • TYR — tyrosinase
  • Novel susceptibility loci: 6p25 near EXOC2 (rs12210050; OR = 1.24, P = 9.9 x 10^-10) and 13q32 near UBAC2 (rs7335046; OR = 1.26, P = 2.9 x 10^-8) (PMID: 21700618)

Six pigmentation loci overlap between BCC, SCC, and melanoma: ASIP/RALY, IRF4, MC1R, OCA2, SLC45A2, and TYR (PMID: 30908599).

Environmental Risk Factors

  • Ultraviolet radiation (UVR): The dominant environmental risk factor. "Chronic ultraviolet radiation (UVR), the dominant risk factor, induces DNA damage and inflammation that dysregulate epigenetic enzymes (e.g., DNMTs, HDACs)" (PMID: 42074595). Both UVA and UVB contribute to BCC through direct DNA damage (cyclobutane pyrimidine dimers) and indirect oxidative stress.
  • Immunosuppression: Solid organ transplant recipients have markedly increased risk; SIR for skin cancer post-HSCT was 7.21 (95% CI: 3.98–13.08), with allogeneic HSCT SIR of 10.18 (PMID: 38987869).
  • Fair skin/Fitzpatrick type I-II: UV-sensitive phenotype strongly predisposes.
  • Age: Incidence increases markedly with age; median age at diagnosis ~67–72 years.
  • Sex: Males are affected more frequently than females.
  • Family history: First-degree relatives with BCC confer increased risk.
  • Ionizing radiation exposure: History of radiation therapy.
  • Arsenic exposure: Environmental or occupational arsenic.
  • Certain medications: Hydrochlorothiazide, statins, ACE inhibitors, and omeprazole have been associated with increased BCC risk (PMID: 38282244).
  • Burns/scars: Burn scars are recognized risk factors for skin cancer (Marjolin's ulcer) (PMID: 42023819).

Hereditary Syndromes

  • Gorlin syndrome (Basal cell nevus syndrome, BCNS): Autosomal dominant, caused by germline heterozygous mutations in PTCH1, SUFU, SMO, or PTCH2. "Gorlin-Goltz syndrome... is a rare, inherited, autosomal dominant genodermatoses, with variable expression and complete penetrance, characterized by the occurrence of multiple basal cell carcinomas (BCCs) at a young age, palmoplantar pits, keratocystic odontogenic tumors, intracranial ectopic calcifications, facial dysmorphism, and ocular and skeletal anomalies" (PMID: 41884741).
  • Xeroderma pigmentosum (XP): Defective nucleotide excision repair leads to extreme UV sensitivity and markedly elevated skin cancer risk (PMID: 37964400).

Protective Factors

Genetic Protective Factors

  • MC1R wild-type alleles: Associated with darker pigmentation and reduced BCC risk.
  • CTSS (Cathepsin S): Mendelian randomization identified CTSS as significantly associated with decreased BCC risk (PMID: 39702585).
  • Darker skin pigmentation genes: Higher melanin content provides natural UV protection.

Environmental Protective Factors

  • Sunscreen use: Higher SPF use 15 years prior was associated with reduced BCC risk (P = 0.04) (PMID: 38282244).
  • Coffee consumption: Higher coffee intake was inversely associated with BCC (PMID: 38282244).
  • Relaxation activities/stress reduction: Associated with reduced risk (PMID: 38282244).
  • Photoprotective clothing: Consistent textile sun protection.
  • DNA repair enzymes (topical): Topical photolyase with UV filters reduced new BCC incidence by 56% in XP patients (PMID: 25408650).

Gene-Environment Interactions

The interaction between UV exposure and genetic susceptibility is central to BCC pathogenesis. Individuals with MC1R variants (red hair, fair skin) who have chronic UV exposure show multiplicative risk increases. UV radiation induces characteristic C>T and CC>TT transitions ("UV signature mutations") in PTCH1 and TP53, linking environmental exposure directly to the genetic driver events. Additionally, chronic UVR dysregulates epigenetic enzymes including DNMTs and HDACs, creating epigenomic reprogramming that contributes to carcinogenesis (PMID: 42074595).

3. Phenotypes

Clinical Subtypes and Presentations

Subtype Frequency Clinical Features HPO Term
Nodular BCC ~60–80% Pearly, translucent papule/nodule with telangiectasias; may ulcerate centrally HP:0002671
Superficial BCC ~10–30% Erythematous, scaly patch or plaque; flat surface with multiple small erosions HP:0002671
Infiltrative/morpheaform (sclerodermiform) BCC ~5–10% Scar-like, ill-defined, indurated plaque; white/ivory color HP:0002671
Basosquamous (metatypical) BCC ~1–2% Features of both BCC and SCC; more aggressive behavior HP:0002671

Relevant HPO Terms: - HP:0002671 — Basal cell carcinoma - HP:0008069 — Neoplasm of the skin - HP:0001000 — Abnormality of skin pigmentation - HP:0007565 — Multiple basal cell carcinomas (Gorlin syndrome)

Phenotype Characteristics

  • Age of onset: Predominantly adult-onset (median ~67–72 years); younger onset in Gorlin syndrome and XP. Outdoor workers develop BCC at older ages than indoor workers (PMID: 28207005).
  • Severity: Variable; ranges from indolent superficial lesions to locally destructive advanced tumors. Sclerodermiform BCCs are diagnosed on average 3.52 years later than non-aggressive subtypes (PMID: 29723362).
  • Progression: Typically slow-growing (months to years); infiltrative subtypes progress more rapidly.
  • Location: ~75% occur on the head and neck; nose is the most common site (42.9%), followed by cheek (14.3%) and upper lip (11.9%) (PMID: 40370729).
  • Frequency: The most common human cancer; lifetime risk 33–39% for men and 23–28% for women in white populations (PMID: 35942364).

Dermoscopic Features by Subtype

  • Superficial BCC: Brown globules, shiny white-red structureless areas, flat surface, multiple small erosions (PMID: 41685950; PMID: 26921200)
  • Nodular BCC: Blue structures, arborizing telangiectasias, ulceration, large tumor islands (PMID: 41685950)
  • Infiltrative BCC: White porcelain areas, lack of pigmentation, elongated hyporeflective tumor strands ("shoal of fish" pattern on LC-OCT) (PMID: 41685950; PMID: 34047380)

Quality of Life Impact

BCC can significantly impact quality of life, particularly when located in cosmetically sensitive areas (face, nose, periorbital region). Surgical treatment may result in scarring, disfigurement, and functional impairment. Advanced BCC treatment with HH inhibitors causes substantial side effects including muscle spasms, alopecia, and dysgeusia that affect daily functioning. Superficial BCCs and small nodular BCCs on the trunk have relatively minimal QOL impact.

4. Genetic/Molecular Information

Causal Genes

Gene OMIM HGNC Role Mutation Frequency
PTCH1 601309 HGNC:9585 Tumor suppressor; HH pathway receptor ~73% of sporadic BCCs
SMO 601500 HGNC:11119 Proto-oncogene; HH signal transducer ~10–20% of sporadic BCCs
TP53 191170 HGNC:11998 Tumor suppressor; genome guardian ~50% of sporadic BCCs
SUFU 607035 HGNC:16466 Negative regulator of HH pathway Germline in some Gorlin cases
PTCH2 603673 HGNC:9586 HH pathway receptor paralog Germline in rare Gorlin cases

"It occurs due to a defective hedgehog cell signaling pathway, caused by heterozygous germ-line mutations in either Patched 1 (PTCH1), Suppressor of fused (SUFU), Smoothened (SMO), or Patched 2 (PTCH2) genes, leading to tumorigenesis and various developmental anomalies" (PMID: 41884741).

Pathogenic Variants

  • PTCH1: Loss-of-function mutations include nonsense, frameshift, splice-site, and missense variants. UV-signature C>T transitions are common in sporadic BCC. Somatic loss of heterozygosity (LOH) at 9q22 is frequent. In Gorlin syndrome, germline heterozygous mutations with second-hit somatic inactivation follow the Knudson two-hit model. Specific variants such as PTCH1 c.3499G>A (p.G1167R) promote proliferation and may confer resistance to vismodegib (PMID: 37552752).
  • SMO: Gain-of-function mutations (e.g., SMO c.2081C>G, p.P694R) constitutively activate HH signaling independent of ligand. SMO mutations are also the most common mechanism of acquired resistance to HH inhibitors (PMID: 40522768; PMID: 37552752).
  • TP53: UV-signature mutations, primarily somatic.
  • Classification: Most PTCH1 mutations in sporadic BCC are somatic. Germline PTCH1 mutations in Gorlin syndrome are classified as pathogenic per ACMG/AMP guidelines in ClinVar. SMO activating variants are primarily somatic (COSMIC).

Modifier Genes

  • MC1R: Red hair color variants modify BCC susceptibility independent of UV response.
  • MDM2 SNP309G: Functional polymorphism that elevates MDM2 levels, decreasing p53 activity and potentially modifying tumor phenotype (PMID: 28925402).
  • AKT1: Activation is obligatory for spontaneous BCC tumor growth in murine models (PMID: 27388747).

Epigenetic Information

Epigenetic dysregulation plays a significant role in BCC pathogenesis. Chronic UV exposure dysregulates DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), creating an altered epigenomic landscape that promotes tumorigenesis (PMID: 42074595). Key epigenetic features include:

  • DNA methylation: Promoter hypermethylation of tumor suppressor genes
  • Histone modifications: Altered histone acetylation patterns
  • Non-coding RNAs: Dysregulation of long non-coding RNAs (lncRNAs), circular RNAs, and miRNAs (PMID: 33242578)
  • Chromatin remodeling: UV-induced changes in chromatin accessibility

Chromosomal Abnormalities

  • Loss of heterozygosity (LOH) at 9q22: The most common chromosomal alteration, encompassing the PTCH1 locus.
  • Additional LOH regions: 1q, 2q, 9p, and 17p (TP53 locus).
  • Copy number alterations: Gains at 6p and losses at 9q are recurrent.

5. Environmental Information

Environmental Factors

  • Ultraviolet radiation: The primary etiological agent. UVR is the dominant risk factor, recognized as a Group 1 carcinogen (IARC). Both acute intermittent (sunburn) and chronic cumulative exposure contribute. "Ultraviolet (UV) radiation is the primary risk factor for the development of both melanocytic and nonmelanocytic skin cancer" (PMID: 41495244).
  • Ionizing radiation: Therapeutic radiation exposure increases BCC risk in the irradiated field.
  • Arsenic: Environmental contamination (drinking water) and occupational exposure.
  • Coal tar and petroleum products: Occupational carcinogens.
  • Psoralen + UVA (PUVA): Phototherapy treatment for psoriasis increases risk.

Lifestyle Factors

  • Outdoor occupation: Outdoor workers are more likely to develop nodular BCC, but BCC onset is actually older in outdoor workers than indoor workers, suggesting other factors contribute to early-onset BCC (PMID: 28207005).
  • Indoor tanning: Artificial UV exposure significantly increases risk.
  • Sunscreen use: Regular high-SPF sunscreen use is protective (PMID: 38282244).
  • Diet: Higher linolenic acid intake associated with BCC; higher coffee consumption protective (PMID: 38282244).

Infectious Agents

  • BCC is not directly caused by infectious agents in most cases.
  • Human papillomavirus (HPV): Some studies suggest a possible cofactor role, though evidence is limited for BCC specifically. HPV has a clearer role in SCC pathogenesis.

6. Mechanism / Pathophysiology

Molecular Pathways

Hedgehog (HH) Signaling Pathway — The Central Driver

The Hedgehog pathway is the principal oncogenic driver in BCC. In normal physiology, the transmembrane receptor PTCH1 inhibits the signal transducer SMO. Binding of HH ligands (SHH, IHH, DHH) to PTCH1 relieves this inhibition, allowing SMO activation and subsequent nuclear translocation of GLI transcription factors (GLI1, GLI2, GLI3), which activate target gene expression.

Causal chain in BCC:

UV Radiation --> PTCH1 Loss-of-Function Mutation (or SMO Gain-of-Function)
    --> Constitutive SMO Activation
    --> GLI1/GLI2 Nuclear Translocation
    --> Transcription of Target Genes (CCND1, MYC, BCL2, PTCH1, GLI1)
    --> Proliferation UP, Apoptosis DOWN, Stem Cell Self-Renewal UP
    --> BCC Formation

GO terms: GO:0007224 (smoothened signaling pathway), GO:0061371 (determination of heart left/right asymmetry — embryonic HH function)

Wnt/Beta-Catenin Pathway

Concomitant Wnt pathway activation is required for BCC initiation. Studies demonstrate that BCC formation requires "reprogramming of interfollicular epidermal cells to an embryonic hair follicle progenitor-like fate, with concomitant Wnt pathway activation" (PMID: 23196843).

GO term: GO:0016055 (Wnt signaling pathway)

p53 Pathway

TP53 mutations occur in ~50% of BCCs, contributing to impaired DNA damage response and apoptosis evasion. MDM2 overexpression further attenuates p53 activity in some cases.

GO term: GO:0006915 (apoptotic process)

PI3K/AKT/mTOR Pathway

AKT1 activation has been shown to be obligatory for spontaneous BCC tumor growth in murine models mimicking Gorlin syndrome (PMID: 27388747).

GO term: GO:0043491 (protein kinase B signaling)

Cellular Processes

  • Aberrant proliferation: Constitutive HH signaling drives uncontrolled basal cell division (GO:0008283, cell proliferation)
  • Apoptosis resistance: BCL2 upregulation through GLI-mediated transcription (GO:0043066, negative regulation of apoptotic process)
  • Stem cell reprogramming: Interfollicular epidermal cells are reprogrammed to embryonic hair follicle progenitor-like cells (PMID: 23196843) (GO:0048863, stem cell differentiation)
  • DNA damage and repair failure: UV-induced CPDs and 6-4PPs, impaired nucleotide excision repair (GO:0006289, nucleotide-excision repair)
  • Epigenomic reprogramming: UV-induced dysregulation of DNMTs and HDACs (PMID: 42074595)

Cell of Origin

BCC originates from interfollicular epidermal progenitor cells and hair follicle stem cells. Lineage-tracing studies show that BCC-initiating cells are reprogrammed to hair follicle progenitor-like fate. BCC patches are more frequent, larger, and more invasive near hair follicles (HFs), and proliferation of basal epidermal cells within 60 micrometers of HF openings is elevated upon UV exposure (PMID: 32492418). LGR5-expressing hair follicle stem cells and their progeny contribute to tumor development (PMID: 28070642; PMID: 22945646).

Cell Ontology terms: CL:0000312 (keratinocyte), CL:0002559 (hair follicle cell), CL:0000646 (basal cell)

Immune System Involvement

BCC is characterized by low immunogenicity, which contributes to immune evasion. Key features include:

  • PD-L1 expression: Present in tumor cells and microenvironment, enabling immune checkpoint evasion
  • Tumor-infiltrating lymphocytes (TILs): Generally sparse in BCC compared to SCC
  • Regulatory T cells (Tregs): Enriched in the tumor microenvironment
  • Tumor-associated macrophages (TAMs): CD68+ and CD163+ macrophages in the BCC microenvironment; single-cell atlases link macrophages and CD8+ T cells to BCC biology (PMID: 36451860)
  • Myeloid-derived suppressor cells (MDSCs): Contribute to immunosuppressive milieu (PMID: 39404378)

Stromal Microenvironment

The BCC stroma plays a critical role in disease behavior. Alcian blue (AB)-positive stroma — indicating mucin-rich, desmoplastic extracellular matrix remodeling — has been identified as a candidate biomarker for HH inhibitor resistance, with multivariable hazard ratio = 23.8 (95% CI: 4.02–141.3; P < 0.001) for shorter progression-free survival (PMID: 41543881).

Potential Prognostic Biomarkers

  • SOX2: Expression levels as potential prognostic biomarker
  • Matrix metalloproteinases (MMPs): Emerging as prognostic indicators and therapeutic targets (PMID: 39697716)
  • ASIP (Agouti signaling protein): Mendelian randomization confirmed association with increased BCC and melanoma risk (PMID: 39702585)

7. Anatomical Structures Affected

Organ Level

  • Primary organ: Skin (UBERON:0002097)
  • Body system: Integumentary system
  • Secondary involvement: In advanced/metastatic disease — regional lymph nodes, lung, bone, liver (rare)

Tissue and Cell Level

  • Tissue types: Epidermis (UBERON:0001003), dermis (UBERON:0002067)
  • Specific cell populations:
  • Basal keratinocytes (CL:0000312)
  • Hair follicle stem cells (CL:0002559)
  • Interfollicular epidermal progenitors (CL:0000646)
  • LGR5+ hair follicle stem cells
  • LGR6+ stem cells (PMID: 28070642)

Subcellular Level

  • Nucleus: Site of GLI transcription factor activity; DNA damage accumulation (GO:0005634)
  • Primary cilium: Essential organelle for HH signal transduction (GO:0005929)
  • Cell membrane: PTCH1/SMO receptor complex (GO:0005886)
  • Cytoplasm: SMO trafficking and SUFU-GLI complex (GO:0005737)

Localization

  • Head and neck: ~75% of all BCCs (UBERON:0000974, neck; UBERON:0000033, head)
  • Nose: Most common site (~43%) (UBERON:0000004)
  • Cheek (~14%) (UBERON:0001567)
  • Periorbital region
  • Ears (including external auditory canal) (PMID: 39979629)
  • Trunk: More common in indoor workers, suggesting non-UV etiological factors (PMID: 28207005)
  • Extremities: Less common
  • Lateralization: No consistent lateralization; distribution follows sun-exposed surfaces

8. Temporal Development

Onset

  • Typical age of onset: Adult to geriatric (median ~67–72 years); incidence increases sharply with age
  • Early onset: In Gorlin syndrome (childhood/adolescence) and xeroderma pigmentosum
  • Onset pattern: Insidious/chronic; typically grows slowly over months to years
  • Trend: Increasing incidence in younger age groups noted (PMID: 39422527)

Progression

  • Disease stages (EADO staging for advanced BCC):
  • Stage I: Superficial, small, low-risk
  • Stage II: Larger, higher-risk subtypes
  • Stage III: Locally advanced (laBCC) — significant tissue invasion

  • Stage IV: Metastatic (mBCC) — extremely rare (<0.1%)

  • Progression rate: Generally slow; infiltrative/sclerodermiform subtypes may progress more rapidly and invade deeper structures.

  • Disease course: Progressive if untreated; does not spontaneously resolve in most cases. Chronic lifelong surveillance needed due to recurrence risk and risk of new primary tumors.
  • Advanced disease characteristics: Median size of laBCC was 73 mm (IQR 110; range 15–400 mm), with 71% measuring 5 cm or larger; 59% showed infiltration beyond subcutaneous fat; 12% had bone infiltration (PMID: 41039887).

Patterns

  • Recurrence: 44% of laBCC experienced local recurrence after resection. Median time to metastasis was 33 months (PMID: 41039887).
  • Multiple primaries: Patients with one BCC have ~50% chance of developing another within 5 years. Risk prediction scores can identify individuals at risk of multiple keratinocyte cancers, with top percentile DRS associated with up to 13-fold risk increase (PMID: 33420020).
  • Critical periods: Cumulative childhood UV exposure is a critical window; photoprotection in early life significantly reduces lifetime BCC risk.

9. Inheritance and Population

Epidemiology

Metric Value Source
Global incidence (>=65 years) 371.97 per 100,000 (95% UI: 310.75–439.58) in 2021 PMID: 40397469
ASIR trend EAPC = 1.94% (1990–2021) PMID: 39966563
Denmark BCC incidence 252 to 338 per 100,000 (2007–2021), age-adjusted PMID: 39708578
Lifetime risk (white population) Men: 33–39%; Women: 23–28% PMID: 35942364
Proportion of keratinocyte cancers ~80% PMID: 31585338

Genetic Etiology

  • Sporadic BCC: Multifactorial/polygenic inheritance with strong environmental contribution
  • Gorlin syndrome: Autosomal dominant, complete penetrance, variable expressivity (PMID: 41884741)
  • Polygenic risk scores: PRS associated with ~3-fold increases in BCC risk; BCC genetic susceptibility also accelerates skin aging by 0.88 years perceived age increase per genetic risk score unit (PMID: 31419349; PMID: 30908599)

Population Demographics

  • Most affected populations: Fair-skinned Caucasians (Fitzpatrick skin types I–II); particularly prevalent in Australia, Northern Europe, and North America
  • Sex ratio: Male predominance; males > females (~1.5:1 to 2:1)
  • Ethnic variation: Significantly lower incidence in people of color; in non-white SOTRs, BCC occurs in 46.9% of skin cancer cases (PMID: 37788820)
  • Geographic distribution: Higher incidence at lower latitudes (greater UV exposure); highest rates in Australia; burden disproportionately higher in countries with higher sociodemographic index (PMID: 40397469)
  • Age distribution: Sharply increasing incidence after age 50; global burden greatest in adults >=65 years; population growth is the primary driver of increasing burden (PMID: 40397469)

10. Diagnostics

Clinical Examination and Dermoscopy

  • Clinical diagnosis: Based on characteristic morphology — pearly, translucent papule/nodule with telangiectasias on sun-exposed skin
  • Dermoscopy: Essential tool for BCC diagnosis. Sensitivity 97.1% (95% CI: 91.80–99.40) and specificity 78.95% (95% CI: 54.43–93.95) for BCC detection using reflectance confocal microscopy (PMID: 30987174). Integration of dermoscopy and RCM improves diagnostic accuracy, with AUC reaching 0.899 for superficial BCC (PMID: 41685950).

Imaging Studies

  • Line-field confocal OCT (LC-OCT): Overall BCC subtype agreement with histology was 90.4% (95% CI: 79.0–96.8) (PMID: 34047380)
  • Reflectance confocal microscopy (RCM): Non-invasive in vivo imaging with high sensitivity for BCC detection
  • Hyperspectral imaging (HSI): Emerging computer-aided detection method (PMID: 38067338)
  • CT/MRI: For advanced BCC to assess extent of invasion, perineural spread, or metastasis

Biopsy and Histopathology

  • Biopsy: Mandatory for histological confirmation, especially in ambiguous lesions and high-risk areas (PMID: 31288208)
  • Histopathological features: Basaloid cell nests with peripheral palisading, retraction artifact (clefting), mucinous stroma
  • Immunohistochemistry: BerEP4 positive, BCL2 positive, CK5/6 positive; helps differentiate from SCC and trichoepithelioma
  • Subtyping: Critical for treatment planning — nodular, superficial, infiltrative/morpheaform, basosquamous

Genetic Testing

  • Gorlin syndrome: Panel testing for PTCH1, PTCH2, SMO, and SUFU recommended for patients presenting with multiple BCCs at young age or syndromic features (PMID: 39581763)
  • Sporadic BCC: Genetic testing not routinely performed; molecular profiling may guide therapy in advanced cases resistant to HH inhibitors
  • Tumor molecular profiling: Useful for identifying resistance mechanisms (SMO mutations, GLI amplification) in HHI-resistant cases (PMID: 41515948; PMID: 40522768)

Artificial Intelligence

AI-based diagnostic tools are being developed for BCC detection in dermoscopy, OCT, and RCM images, showing promising results for automated detection and classification (PMID: 36785993; PMID: 40370729).

Differential Diagnosis

Condition Distinguishing Features
Squamous cell carcinoma Keratinization, more infiltrative, higher metastatic potential
Trichoepithelioma Benign; LGR6+ stromal cells present (absent in BCC)
Melanoma (amelanotic) S100/Melan-A positive; lacks palisading
Sebaceous hyperplasia Central umbilication, yellowish color
Dermatofibroma Firm papule, dimple sign
Merkel cell carcinoma Rapidly growing, violaceous nodule

Screening

  • Full-body skin examination: Recommended for high-risk individuals (fair skin, history of skin cancer, immunosuppression)
  • SCREEN clinic model: Integrated skin cancer screening in transplant clinics identifies at-risk patients (PMID: 27663613)
  • No population-wide newborn or genetic screening for sporadic BCC

11. Outcome/Prognosis

Survival and Mortality

Stage 5-Year Disease-Specific Survival Source
Early/localized BCC >95–99% Multiple sources
Locally advanced BCC 79% PMID: 41039887
Metastatic BCC 30% PMID: 41039887
  • Mortality: Very low overall; death is uncommon and decreasing due to earlier diagnosis (PMID: 35942364). In one 32-year single-center study, 12% of patients with laBCC died of their disease (PMID: 41039887).

Morbidity

  • Local tissue destruction: Untreated BCC can cause significant cosmetic and functional impairment
  • Treatment morbidity: Surgical scarring, HHI side effects (muscle spasms, alopecia, dysgeusia)
  • Multiple BCCs: Patients are at substantial risk of developing subsequent primary BCCs; high DRSA scores associated with earlier diagnosis by up to 14 years and more recurrent forms (PMID: 33420020)

Prognostic Factors

  • Tumor subtype: Infiltrative/morpheaform and basosquamous subtypes carry higher recurrence and metastatic risk
  • Tumor size: Larger tumors have worse outcomes
  • Location: Head/neck tumors, particularly periorbital and nasal, carry higher surgical complexity
  • Perineural/perivascular invasion: Associated with higher recurrence and metastatic risk
  • Immunosuppression status: Transplant recipients have higher recurrence and more aggressive disease
  • Alcian blue-positive stroma: Candidate biomarker for HHI resistance (HR = 23.8) (PMID: 41543881)
  • ECOG performance status: Significant predictor of overall survival in vismodegib-treated patients (PMID: 41053641)

12. Treatment

Surgical Treatment (MAXO:0000004 — surgical procedure)

Mohs Micrographic Surgery (Gold Standard for High-Risk BCC)

  • 5-year recurrence rate: 3.8% overall (95% CI: 2.8–5.0); 3.1% for primary BCC; 5.3% for recurrent BCC — from a Danish nationwide cohort of 2,203 patients (PMID: 39791512)
  • Cure rates: Up to 99–100% reported (PMID: 40167057)
  • Indications: High-risk BCC, recurrent BCC, cosmetically sensitive areas

Standard Surgical Excision

  • First-line for most "easy-to-treat" BCCs
  • Complete excision with histologically confirmed margins
  • MAXO:0000601 — wide excision

Other Destructive Techniques

  • Electrodesiccation and curettage: For low-risk, superficial BCC
  • Cryotherapy: For low-risk superficial BCC
  • Laser ablation: Select superficial cases

Pharmacotherapy

Hedgehog Pathway Inhibitors (MAXO:0001298 — targeted therapy)

Drug Indication ORR CR Key Side Effects
Vismodegib laBCC, mBCC 65% (real-world) 28% Muscle spasms, alopecia, dysgeusia
Sonidegib laBCC 89% (real-world) 37% Muscle spasms, alopecia, dysgeusia

"Updated evidence confirms Hedgehog pathway inhibitors (HHIs) as the standard first-line therapy for advanced BCC, while programmed death-1 (PD-1) blockade with cemiplimab has established durable responses after HHI failure" (PMID: 41703999).

Vismodegib median PFS was 15.1 months and median OS was 37.5 months in a facial laBCC cohort (PMID: 41053641). Sonidegib showed superior real-world efficacy compared to pivotal trial data (ORR 89% vs. 60.6%) (PMID: 40834113). Sequential HHI therapy (switching from vismodegib to sonidegib) achieved ORR of 71% with CR of 43% (PMID: 40834113).

Resistance mechanisms: Mutations in SMO (drug-binding site alterations), GLI2 amplification, activation of alternative pathways (PI3K/AKT). SMO c.2081C>G (p.P694R) may confer resistance to vismodegib but sensitivity to downstream inhibitor GANT61 (PMID: 37552752).

Immunotherapy (MAXO:0000750 — immunotherapy)

  • Cemiplimab (anti-PD-1): FDA-approved for patients with laBCC or mBCC who have progressed on or are intolerant to HHI therapy. "Cemiplimab is the first immune checkpoint inhibitor (ICI) approved by the Food and Drug Administration for refractory BCC, marking a major breakthrough in BCC immunotherapy" (PMID: 39697716). Response rate ~21% in mBCC, with durable disease control (PMID: 40432222).
  • Combination therapy: Cemiplimab + vismodegib shows promise — a case report demonstrated pathologic complete response with combination neoadjuvant therapy (PMID: 39949752).

Topical Therapies (MAXO:0001058 — topical medication)

"For the treatment of superficial BCC, complete clearance rates ranged from 90 to 93% for 5% 5-fluorouracil (5-FU) and 71 to 76% for imiquimod (IMQ)" (PMID: 36169917).

Agent Indication Clearance Rate
5-Fluorouracil 5% Superficial BCC 90–93%
Imiquimod 5% Superficial BCC 71–76%
Imiquimod 5% Giant superficial BCC Effective (case series)

Photodynamic Therapy (MAXO:0000940)

Effective for superficial BCC and thin nodular BCC. PDT combined with Mohs surgery may offer advantages for non-aggressive laBCC subtypes (PMID: 40449860).

Radiation Therapy (MAXO:0000014 — radiation therapy)

  • Superficial radiation therapy (SRT): IGSRT showed 2-year freedom from recurrence of 99.23% across all NMSC types; BCC recurrence 1.1% (PMID: 39777366)
  • Surface mold brachytherapy: Effective alternative for inoperable patients (PMID: 39719956)
  • Valid alternative to surgery for facial BCC in elderly patients (PMID: 31288208)

Neoadjuvant Approaches

HHI neoadjuvant therapy before surgery is emerging as a strategy to reduce tumor burden before definitive excision, particularly in cosmetically sensitive areas (PMID: 40043261; PMID: 40559089).

Treatment Algorithm

BCC Diagnosis
|-- Low-risk / "Easy-to-treat"
|   |-- Superficial --> Topical (5-FU, imiquimod), PDT, or surgery
|   +-- Nodular --> Surgical excision +/- Mohs
|-- High-risk / "Difficult-to-treat"
|   |-- Recurrent / cosmetically sensitive --> Mohs micrographic surgery
|   +-- Locally advanced (laBCC)
|       |-- Resectable --> Neoadjuvant HHI --> Surgery
|       +-- Unresectable --> HHI (vismodegib/sonidegib)
|           |-- Response --> Continue / Surgery
|           +-- Progression/Intolerance --> Cemiplimab (anti-PD-1)
|               +-- Progression --> Clinical trials / Combination therapy
+-- Metastatic (mBCC) --> HHI --> Cemiplimab --> Clinical trials

13. Prevention

Primary Prevention

  • UV avoidance: Limiting sun exposure, especially during peak hours (10 AM–4 PM)
  • Sunscreen: Regular use of broad-spectrum SPF 30+ sunscreen; higher SPF use associated with reduced risk (PMID: 38282244)
  • Protective clothing: Hats, long sleeves, UV-protective textiles; particularly important in resource-limited settings (PMID: 38672604)
  • Avoidance of indoor tanning: Critical public health measure
  • Topical DNA repair enzymes: Photolyase-containing sunscreens reduced BCC incidence by 56% in XP patients (PMID: 25408650)
  • Public health education: Skin Cancer Awareness Month (May) shows seasonal increases in search interest; targeted campaigns needed for communities of color (PMID: 38643380; PMID: 24485530)

MAXO:0000150 — sun protective behavior counseling

Secondary Prevention

  • Full-body skin examination: Regular dermatological screening for high-risk individuals
  • Dermoscopy-assisted screening: Improves accuracy of BCC subtype identification, particularly for superficial BCC (PMID: 26921200)
  • Integrated transplant screening clinics: SCREEN clinic model for organ transplant recipients (PMID: 27663613)
  • Disease risk scores: Polygenic risk scores can identify high-risk individuals and predict when they are likely to develop skin cancer, with high scores associated with earlier diagnosis by up to 14 years (PMID: 33420020)

Tertiary Prevention

  • Long-term follow-up: Recommended for all patients with BCC, especially high-risk subtypes
  • Surveillance protocols: Close monitoring for Gorlin syndrome patients to diagnose and treat BCCs at early stage (PMID: 31288208)
  • Immunosuppression management: Switching from calcineurin inhibitors to mTOR inhibitors in transplant recipients may reduce NMSC incidence (PMID: 37887285)

Genetic Counseling

  • Recommended for patients with multiple BCCs at young age or features suggesting Gorlin syndrome
  • Family screening for PTCH1 mutations in confirmed Gorlin kindreds
  • Prenatal testing available for known pathogenic variants

14. Other Species / Natural Disease

Taxonomy of Affected Species

BCC and BCC-like tumors have been documented in several species:

  • Mus musculus (mouse; NCBI Taxon: 10090): Primary model organism for BCC research
  • Rattus norvegicus (rat; NCBI Taxon: 10116): Less commonly used
  • Felis catus (domestic cat): Rare spontaneous BCC reported
  • Canis lupus familiaris (domestic dog): Rare basal cell tumors (generally more benign than human BCC)
  • Equus caballus (horse): Occasionally reported

Orthologous Genes

Human Gene Mouse Ortholog NCBI Gene ID (Mouse)
PTCH1 Ptch1 19206
SMO Smo 319757
SUFU Sufu 24069
GLI1 Gli1 14632
GLI2 Gli2 14633

Comparative Biology

The Hedgehog signaling pathway is highly conserved across vertebrates. Ptch1+/- heterozygous knockout mice develop mandibular cysts that histologically resemble keratocystic odontogenic tumors of Gorlin syndrome, with parakeratotic stratified squamous epithelium and keratinized contents (PMID: 12542834). The conservation of HH pathway components across species validates the use of animal models for studying BCC biology and testing therapeutics.

15. Model Organisms

Mouse Models

Ptch1+/- Heterozygous Knockout Mouse

  • Type: Genetically engineered (knockout)
  • Background: Mimics Gorlin syndrome with heterozygous Ptch1 inactivation
  • Phenotype recapitulation: Develops medulloblastoma, rhabdomyosarcoma, and mandibular cysts; BCC development requires additional stimuli (UV or chemical carcinogenesis)
  • Mandibular cysts: Found in 25.4% of Ptch1+/- mice, lined by thin parakeratotic squamous epithelium resembling keratocystic odontogenic tumors of Gorlin syndrome (PMID: 12542834)

SKH1-Ptch1+/- Mouse (UV-Inducible BCC Model)

  • Type: Conditional/hairless variant
  • Features: AKT1 activation is obligatory for spontaneous BCC growth; vismodegib can ablate tumors but they recur upon drug discontinuation (PMID: 27388747)

Ptch(flox/flox)CD4Cre+/- Mouse

  • Type: Conditional knockout
  • Key finding: Biallelic loss of Ptch in CD4+ cells does not suffice for BCC formation alone; a second stimulus (DMBA/TPA) is required. BCCs originate from rare Ptch-deficient stem cell-like cells expressing CD4 (PMID: 24662765)

UV-Inducible Murine BCC Model (Multicolor Lineage Tracing)

  • Key finding: BCC patches are more frequent, larger, and more invasive near hair follicles. Chronic UV irradiation promotes proliferation of basal epidermal cells within 60 micrometers of HF openings (PMID: 32492418)

Model Limitations

  • Mouse skin differs from human skin in thickness, hair cycling, and immune composition
  • Ptch1+/- mice more commonly develop medulloblastoma than BCC without additional stimuli
  • UV-induced murine BCCs may not fully recapitulate the mutational spectrum of human BCCs
  • Drug metabolism differences between mice and humans affect pharmacokinetic modeling
  • Immune microenvironment differs between species

Model Resources

  • Mouse Genome Informatics (MGI): Comprehensive Ptch1 allele database
  • International Mouse Phenotyping Consortium (IMPC): Ptch1 knockout phenotyping data
  • Jackson Laboratory (JAX): Repository for BCC-relevant mouse strains
  • IMSR (International Mouse Strain Resource): Strain availability database

Key Findings — Detailed Evidence

Finding 1: BCC is the Most Common Human Malignancy Driven by Hedgehog Pathway Dysregulation

BCC accounts for approximately 80% of all keratinocyte cancers and is the single most common cancer in fair-skinned populations. The disease is driven in virtually all cases by constitutive activation of the Hedgehog signaling pathway, predominantly through loss-of-function mutations in PTCH1 or gain-of-function mutations in SMO. The global burden is substantial and rising — the age-standardized incidence rate in adults >=65 was 371.97 per 100,000 (95% UI: 310.75–439.58) in 2021, with an EAPC of 1.94% from 1990 to 2021. In Denmark alone, 183,338 first-time BCC cases were recorded from 2007 to 2021, with age-adjusted incidence rising from 252 to 338 per 100,000.

Finding 2: Gorlin Syndrome Demonstrates Germline Hedgehog Pathway Mutations Cause Hereditary BCC

Gorlin-Goltz syndrome (BCNS) provides the genetic proof-of-concept that Hedgehog pathway mutations are causal for BCC. This autosomal dominant syndrome with complete penetrance and variable expression is caused by heterozygous germline mutations in PTCH1, SUFU, SMO, or PTCH2. Affected individuals develop multiple BCCs at a young age alongside palmoplantar pits, keratocystic odontogenic tumors, intracranial calcifications, and skeletal anomalies. Patients with SHH-subgroup medulloblastoma should undergo routine genetic testing for Gorlin-associated mutations, as early identification changes management — notably, whole craniospinal irradiation should be avoided due to risk of radiation-induced BCCs (PMID: 32930885).

Finding 3: Comprehensive Treatment Paradigm — Surgery, HH Inhibitors, Immunotherapy, and Topical Therapies

The treatment landscape for BCC is well-defined and expanding. Mohs micrographic surgery remains the gold standard for high-risk BCC with a 5-year recurrence rate of 3.8% (nationwide Danish cohort). For locally advanced disease, HH inhibitors provide high response rates — vismodegib ORR 65% with 28% CR; sonidegib ORR 89% with 37% CR in real-world settings. Cemiplimab has emerged as a transformative option after HHI failure, providing durable responses. Topical therapies (5-FU 90–93% clearance; imiquimod 71–76% clearance) remain effective for superficial BCC.

Finding 4: UV Radiation is the Dominant Environmental Risk Factor Through DNA Damage and Epigenomic Reprogramming

Ultraviolet radiation is the primary environmental driver of BCC through a dual mechanism of direct DNA damage (UV-signature mutations in PTCH1, TP53) and chronic dysregulation of epigenetic machinery (DNMTs, HDACs). The interplay between UVR, UV-sensitive phenotype, and genotype is central to BCC etiopathogenesis. Immunosuppression dramatically amplifies risk — stem cell transplant recipients have a 7.21-fold increased skin cancer risk. GWAS have identified multiple susceptibility loci in pigmentation genes that modify UV sensitivity and BCC risk.

Mechanistic Model

The pathogenesis of BCC can be understood as a multi-step process with converging genetic and environmental inputs:

INITIATION
===========
  Chronic UV Exposure (UVB > UVA)
      |
      v
  DNA Damage: CPDs, 6-4PPs, oxidative lesions
      |
      +---> UV-signature mutations (C>T, CC>TT)
      |         |
      |         +---> PTCH1 loss-of-function (~73%)
      |         +---> TP53 inactivation (~50%)
      |         +---> SMO gain-of-function (~10-20%)
      |
      +---> Epigenomic Reprogramming
|
+---> DNMT/HDAC dysregulation
+---> Promoter methylation changes
+---> ncRNA dysregulation

PROMOTION
==========
  Constitutive HH Pathway Activation
      |
      v
  SMO Activation --> GLI1/GLI2 Nuclear Translocation
      |
      +---> Target gene transcription: CCND1, MYC, BCL2
      +---> Wnt pathway co-activation (required)
      +---> Stem cell reprogramming to HF progenitor fate
      |
  AKT/PI3K Pathway Activation (required for growth)
      |
      v
  Cell Proliferation UP + Apoptosis DOWN

PROGRESSION
============
  Clonal Expansion from Hair Follicle-Proximal Stem Cells
      |
      +---> Nodular BCC (most common)
      +---> Superficial BCC
      +---> Infiltrative/Morpheaform BCC (desmoplastic stroma)
      +---> Basosquamous BCC (mixed differentiation)
      |
  Immune Evasion (PD-L1, Tregs, TAMs, low TILs)
      |
      v
  Locally Advanced BCC (rare: Metastatic BCC)

Evidence Base

Landmark References

PMID Title/Topic Key Contribution
41240053 BCC precursor lesion Established that nearly all BCCs are driven by HH pathway mutations
28220485 Epidemiology review Confirmed BCC as most common cancer in white-skinned individuals
41884741 Gorlin-Goltz syndrome genetics Comprehensive description of BCNS genetics and features
41703999 Evolving BCC treatment paradigms Established current HHI to PD-1 treatment algorithm
39791512 Mohs surgery nationwide cohort Definitive recurrence data from Danish national registry
42074595 Epigenetic landscape of NMSC Linked UV to epigenomic reprogramming via DNMT/HDAC dysregulation
40397469 Burden of skin cancer in older adults Comprehensive global burden data and projections to 2050
36169917 Topical treatment advances Clearance rates for 5-FU and imiquimod in superficial BCC
38987869 Skin cancer post-HSCT meta-analysis Quantified immunosuppression as risk factor (SIR = 7.21)
41543881 AB-positive stroma and HHI resistance Novel prognostic biomarker for HHI treatment outcome
23196843 Stem cell reprogramming in BCC Established Wnt co-activation and HF progenitor reprogramming
32492418 UV and hair follicle-proximal carcinogenesis BCC preferentially initiates near hair follicles
21700618 GWAS for BCC and SCC Identified MC1R, 6p25, and 13q32 susceptibility loci
31288208 European BCC guidelines Consensus diagnostic and treatment recommendations
33420020 Disease risk scores for skin cancers PRS predict BCC risk and timing of onset

Limitations and Knowledge Gaps

  1. Incomplete epidemiological data: BCC is often not reported to cancer registries, making true global incidence difficult to ascertain. The GBD data may underestimate the burden.

  2. Limited data in non-white populations: Most BCC research focuses on Caucasian populations. Characterization in people of color, where BCC presents differently and may be diagnosed later, remains insufficient (PMID: 37788820; PMID: 24485530).

  3. Biomarker validation: Promising biomarkers such as AB-positive stroma, SOX2, and MMPs require prospective validation in larger cohorts.

  4. HHI resistance mechanisms: While SMO mutations are the best-characterized resistance mechanism, the full landscape of resistance pathways (including non-HH pathway activation) remains incompletely understood.

  5. Optimal combination therapy: The sequencing and combination of HH inhibitors with immunotherapy is being explored but lacks phase III trial data.

  6. Prevention in high-risk populations: Optimal prevention strategies for transplant recipients and Gorlin syndrome patients need further refinement.

  7. Epigenetic mechanisms: While UV-induced epigenomic reprogramming is established, specific therapeutic targeting of epigenetic alterations in BCC remains in preclinical stages.

  8. Single-cell and spatial profiling: The cellular heterogeneity of BCC and its microenvironment, particularly regarding therapy resistance, requires further characterization with modern single-cell and spatial transcriptomic approaches.

Proposed Follow-up Experiments/Actions

  1. Prospective biomarker validation study: Validate AB-positive stroma as a predictive biomarker for HHI resistance in a multicenter prospective cohort, potentially enabling treatment stratification before initiating systemic therapy.

  2. Combination therapy clinical trials: Design randomized trials of cemiplimab + vismodegib/sonidegib versus sequential therapy for laBCC to determine optimal treatment strategy for advanced disease.

  3. Single-cell atlas of BCC subtypes: Comprehensive single-cell RNA-seq profiling of nodular, superficial, infiltrative, and basosquamous BCC subtypes to characterize cellular heterogeneity, immune microenvironment, and identify subtype-specific therapeutic vulnerabilities.

  4. Epigenetic therapeutic targeting: Preclinical and early-phase clinical studies of DNMT inhibitors and HDAC inhibitors in BCC, particularly in combination with HHI therapy to address resistance.

  5. Polygenic risk score implementation study: Clinical validation trial evaluating whether incorporation of BCC PRS into primary care screening protocols improves early detection rates and reduces advanced-stage presentation.

  6. Non-white population epidemiology: Large prospective cohort studies of BCC incidence, characteristics, and outcomes in diverse populations to address existing data gaps.

  7. CRISPR functional genomics: Systematic CRISPR screens in BCC cell lines and organoids to identify synthetic lethal interactions with HH pathway activation, potentially revealing new therapeutic targets for HHI-resistant disease.

  8. Liquid biopsy development: Development and validation of circulating tumor DNA (ctDNA) assays for monitoring treatment response and detecting early recurrence in advanced BCC.

Ontology Summary

Key Ontology Terms for Knowledge Base Entry

Category Term ID
Disease Basal cell carcinoma MONDO:0004972
Phenotype Basal cell carcinoma HP:0002671
Phenotype Multiple basal cell carcinomas HP:0007565
Gene PTCH1 HGNC:9585
Gene SMO HGNC:11119
Gene TP53 HGNC:11998
Gene MC1R HGNC:6929
Gene SUFU HGNC:16466
Biological Process Smoothened signaling pathway GO:0007224
Biological Process Wnt signaling pathway GO:0016055
Biological Process Apoptotic process GO:0006915
Biological Process Cell proliferation GO:0008283
Cellular Component Primary cilium GO:0005929
Cell Type Keratinocyte CL:0000312
Cell Type Basal cell of epidermis CL:0000646
Cell Type Hair follicle cell CL:0002559
Anatomy Skin of body UBERON:0002097
Anatomy Epidermis UBERON:0001003
Anatomy External nose UBERON:0000004
Anatomy Head UBERON:0000033
Chemical Vismodegib CHEBI:66903
Chemical 5-Fluorouracil CHEBI:46345
Treatment Surgical procedure MAXO:0000004
Treatment Targeted therapy MAXO:0001298
Treatment Immunotherapy MAXO:0000750
Treatment Radiation therapy MAXO:0000014
Treatment Sun protective counseling MAXO:0000150

Report generated: 2026-05-05 | Based on systematic review of 100 primary literature sources | All citations verified against PubMed abstracts