Mycosis Fungoides

Cancer MONDO:0009691 cutaneous T-cell lymphoma

Mycosis fungoides is the most common cutaneous T-cell lymphoma and is defined by malignant skin-homing T-cell clones infiltrating the skin. The disease typically evolves through patch, plaque, and tumor stages, while recognized WHO-EORTC clinicopathologic variants include folliculotropic mycosis fungoides, localized pagetoid reticulosis, and granulomatous slack skin. Current MF pathobiology centers on deregulated T-cell receptor/PLCG1 and JAK/STAT signaling, TNFR2-linked non-canonical NF-kappaB activation, transformation-associated RAS signaling, and progression-promoting stromal and macrophage remodeling in the tumor microenvironment. Early-stage disease is often managed with skin-directed therapy, whereas advanced or refractory disease can require radiotherapy and targeted systemic agents.

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1
Mappings
1
Definitions
8
Pathophys.
2
Histopath.
4
Phenotypes
4
Genes
5
Treatments
6
Subtypes
16
References
1
Deep Research
🔗

Mappings

MONDO
MONDO:0009691 mycosis fungoides
skos:exactMatch MONDO
Primary MONDO disease identifier for this disease-level mycosis fungoides entry.
📘

Definitions

1
Pathologic definition of mycosis fungoides
Mycosis fungoides is a cutaneous lymphoma characterized by infiltration of malignant T-cell clones into the skin.
CASE_DEFINITION General disease definition for the disease-level mycosis fungoides entry
Show evidence (1 reference)
PMID:40721285 SUPPORT Other
"Mycosis fungoides (MF) is the commonest subtype of cutaneous lymphoma, characterized by the infiltration of malignant T-cell clones into the skin."
This review provides a concise disease-level definition anchored to malignant T-cell infiltration of skin.
◆

Subtypes

6
clinicopathologic variant
Folliculotropic Mycosis Fungoides MONDO:0015808
Recognized WHO-EORTC clinicopathologic variant characterized by follicle-centered disease with distinct clinical and histologic spectrum; prognosis is heterogeneous and linked to its clinicopathologic subgroup.
Show evidence (1 reference)
PMID:29726638 SUPPORT Other
"Accepted by the WHO and EORTC as a variant of classic mycosis fungoides, folliculotropic (syn.: follicular or pilotropic) mycosis fungoides (FMF) is characterized by a broad clinical and histological spectrum with numerous differential diagnoses."
This review supports folliculotropic MF as a recognized clinicopathologic variant within the MF disease spectrum.
Localized Pagetoid Reticulosis MONDO:0015809
Woringer-Kolopp disease is a rare, usually localized, plaque-forming MF variant with prominent epidermotropism and generally indolent behavior.
Show evidence (1 reference)
PMID:35485962 SUPPORT Other
"Woringer-Kolopp disease (WKD), also known as localized pagetoid reticulosis, is a rare variant of mycosis fungoides as described by the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification system for cutaneous lymphomas."
This systematic review explicitly places localized pagetoid reticulosis as a rare MF variant in WHO-EORTC classification.
Granulomatous Slack Skin MONDO:0018031
Rare granulomatous cutaneous T-cell lymphoma phenotype that is best modeled as an MF-spectrum variant rather than a separate disease-level mechanism graph.
Show evidence (1 reference)
PMID:11411914 SUPPORT Human Clinical
"granulomatous mycosis fungoides, and suggests that these 2 disorders are only variants in the broad spectrum of a single disease."
This case-based pathology report supports granulomatous slack skin as part of the broader MF disease spectrum rather than a separate disease-level curation unit.
skin stage
Patch-Stage Mycosis Fungoides
Earliest clinical stage with patch lesions and often subtle histology, commonly requiring repeated clinicopathologic correlation for diagnosis.
Show evidence (1 reference)
PMID:40721285 SUPPORT Other
"MF has three distinct clinical stages - patch, plaque and tumour - presenting most commonly on the buttocks, trunk and breast."
This review identifies patch stage as one of the canonical MF clinical stages.
Plaque-Stage Mycosis Fungoides
Infiltrated plaque stage representing more established cutaneous disease and a transition point where progression-associated stromal and macrophage programs become more apparent.
Show evidence (1 reference)
PMID:40721285 SUPPORT Other
"MF has three distinct clinical stages - patch, plaque and tumour - presenting most commonly on the buttocks, trunk and breast."
This review identifies plaque stage as one of the canonical MF clinical stages.
Tumor-Stage Mycosis Fungoides
Advanced cutaneous stage with tumorous lesions and increased risk of extracutaneous progression and large-cell transformation-associated aggressive biology.
Show evidence (1 reference)
PMID:40721285 SUPPORT Other
"MF has three distinct clinical stages - patch, plaque and tumour - presenting most commonly on the buttocks, trunk and breast."
This review identifies tumor stage as one of the canonical MF clinical stages.
⚙

Pathophysiology

8
Cutaneous Homing of Malignant T-Cell Clones
Malignant skin-homing T-cell clones infiltrate the epidermis and dermis, establishing the defining cutaneous disease compartment of MF.
CD4-positive, alpha-beta T cell link
T cell migration link ↑ INCREASED
skin of body link
Show evidence (1 reference)
PMID:40721285 SUPPORT Other
"Mycosis fungoides (MF) is the commonest subtype of cutaneous lymphoma, characterized by the infiltration of malignant T-cell clones into the skin."
This disease-definition statement directly supports cutaneous infiltration by malignant T-cell clones as the core pathobiology of MF.
TCR/PLCG1 Signaling Deregulation
Recurrent molecular alterations in MF converge on pathologic activation of the T-cell receptor and PLCG1 signaling axis.
CD4-positive, alpha-beta T cell link
T cell receptor signaling pathway link ↑ INCREASED
Show evidence (1 reference)
PMID:33923722 SUPPORT Other
"These seem to make up an orchestrated constellation of genomic and environmental alterations generated around deregulated T-cell receptor (TCR)/phospholipase C, gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of transcription (JAK/STAT) activities"
This integrative review identifies deregulated TCR/PLCG1 signaling as a core molecular driver axis in MF.
JAK/STAT Signaling Activation
JAK/STAT pathway activation is a recurrent MF driver axis and remains prominent in contemporary mutational studies of the disease.
CD4-positive, alpha-beta T cell link
cell surface receptor signaling pathway via JAK-STAT link ↑ INCREASED
Show evidence (2 references)
PMID:33923722 SUPPORT Other
"These seem to make up an orchestrated constellation of genomic and environmental alterations generated around deregulated T-cell receptor (TCR)/phospholipase C, gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of transcription (JAK/STAT) activities"
This review identifies JAK/STAT activity as one of the central driver axes in MF pathobiology.
PMID:41008827 SUPPORT Human Clinical
"Recurrent alterations included FAT1 (28.2%), KMT2D (19.2%), TP53 (13.5%), JAK3 (11.5%), and SETBP1 (11.5%), highlighting the role of Wnt signaling, epigenetic dysregulation, the p53 pathway, and JAK/STAT signaling in MF pathogenesis."
This national genomics analysis independently supports recurrent JAK/STAT pathway involvement in MF.
TNFR2-Driven Non-Canonical NF-kappaB Signaling
Recurrent TNFRSF1B alterations augment TNFR2 signaling and activate the non-canonical NF-kappaB pathway in malignant T cells.
CD4-positive, alpha-beta T cell link
non-canonical NF-kappaB signal transduction link ↑ INCREASED
Show evidence (2 references)
PMID:26258847 SUPPORT Human Clinical
"Here we report recurrent point mutations and genomic gains of TNFRSF1B, encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with mycosis fungoides and Sézary syndrome."
This genomic study identifies recurrent TNFRSF1B alterations in MF/SS, supporting TNFR2 as a disease-relevant driver.
PMID:26258847 SUPPORT Human Clinical
"Expression of the recurrent TNFR2 Thr377Ile mutant in T cells leads to enhanced non-canonical NF-κB signaling"
This study directly links recurrent TNFR2 mutation to enhanced non-canonical NF-kappaB signaling.
Cancer-Associated Fibroblast Matrix Remodeling
Progressive MF lesions develop a fibroblast-rich stromal program marked by increased collagen fibril organization and enrichment of cancer-associated fibroblasts.
fibroblast link
collagen fibril organization link ↑ INCREASED
Show evidence (2 references)
PMID:40163757 SUPPORT Human Clinical
"genes linked to collagen fibril assembly and regulation of interleukin-4 were upregulated as the disease progressed from patch- to plaque-stage MF."
This spatial transcriptomic study links MF progression to a collagen remodeling program in advancing lesions.
PMID:40163757 SUPPORT Human Clinical
"Patients with stage I MF with high-progression signatures showed significantly increased cancer-associated fibroblast (CAF; P = .008)"
This study directly connects high-progression MF to enrichment of cancer-associated fibroblasts.
Interleukin-4 Program Activation
Progression from patch-stage to plaque-stage MF is accompanied by an interleukin-4-associated transcriptional program.
regulation of interleukin-4 production link ↑ INCREASED
Show evidence (1 reference)
PMID:40163757 SUPPORT Human Clinical
"genes linked to collagen fibril assembly and regulation of interleukin-4 were upregulated as the disease progressed from patch- to plaque-stage MF."
This spatial transcriptomic study directly supports increased IL-4 regulatory programs during early MF progression.
M2 Macrophage-Mediated Immune Suppression
Progressing MF lesions accumulate M2 macrophages and exhaustion-associated immune programs that suppress effective antitumor T-cell immunity.
M2 macrophage link
negative regulation of T cell mediated immunity link ↑ INCREASED
Show evidence (2 references)
PMID:40163757 SUPPORT Human Clinical
"Furthermore, M2 macrophages significantly increased in lymphoma cell areas (P < .001) and immune cell areas (P = .031) in plaque-stage MF compared with patch-stage MF."
This study directly demonstrates enrichment of M2 macrophages in progressing MF lesions.
PMID:40163757 SUPPORT Human Clinical
"CD163 expression was significantly correlated with most of the progression signatures and T-cell exhaustion markers"
Correlation between CD163 and exhaustion markers supports an immunosuppressive macrophage-centered microenvironment in progressive MF.
Large-Cell Transformation-Associated RAS Signaling
Large-cell transformation in MF is a progression state marked by acquired oncogenic RAS/MAPK lesions and broader mutation accumulation, rather than a separate disease-level mechanism graph.
Ras protein signal transduction link ↑ INCREASED
Show evidence (2 references)
PMID:34771672 SUPPORT Human Clinical
"Oncogenic RAS mutations were exclusively detected in patients with LCT."
This targeted sequencing study directly links oncogenic RAS mutations to large-cell transformation in MF.
PMID:34771672 SUPPORT Human Clinical
"In particular, the activation of RAS signaling-together with epigenetic dysregulation-may crucially contribute to the molecular pathogenesis of the LCT phenotype, thus conveying its adverse clinical behavior."
This conclusion supports RAS signaling as a mechanistic contributor to transformation-associated aggressive MF biology.
✶

Histopathology

2
Epidermotropic Small-to-Medium Lymphoid Infiltrate VERY_FREQUENT
Early MF commonly shows an epidermotropic infiltrate of small-to-medium lymphocytes that may require repeated biopsy for recognition.
Show evidence (1 reference)
PMID:40721285 SUPPORT Other
"Patients may require multiple skin biopsies, especially at the patch stage, to identify the characteristic epidermotropic infiltrates of small-to-medium-sized lymphocytes."
This review supports the characteristic epidermotropic small-to-medium lymphoid infiltrate of MF.
Folliculotropism
Folliculotropism is a histopathologic pattern associated with the folliculotropic MF variant and poorer prognosis in infiltrated head and neck plaques or tumors.
Show evidence (1 reference)
PMID:37124514 SUPPORT Other
"Besides advanced stage, other factors associated with poorer prognosis are advanced age, male gender, folliculotropism in histopathology of patients with infiltrated plaques and tumors in the head and neck region, large cell transformation, and elevated lactate dehydrogenase."
This review identifies folliculotropism as a clinically important histopathologic pattern within MF.
●

Phenotypes

4
Immune 1
Erythroderma OCCASIONAL Erythroderma (HP:0001019)
Show evidence (1 reference)
PMID:34541796 SUPPORT Other
"MF presents clinically with patch, plaque and/or tumor stages, but can also evolve as erythroderma"
This review supports erythrodermic evolution as part of the MF clinical spectrum.
Integument 3
Patch/Plaque/Tumor Skin Lesions VERY_FREQUENT Abnormal skin morphology (HP:0011121)
Show evidence (1 reference)
PMID:34541796 SUPPORT Other
"MF presents clinically with patch, plaque and/or tumor stages, but can also evolve as erythroderma"
This review directly supports the characteristic patch/plaque/tumor lesion spectrum of MF.
Skin Plaque FREQUENT Skin plaque (HP:0200035)
Show evidence (1 reference)
PMID:40721285 SUPPORT Other
"MF has three distinct clinical stages - patch, plaque and tumour - presenting most commonly on the buttocks, trunk and breast."
This review explicitly identifies plaque lesions as a canonical MF clinical stage.
Pruritus Pruritus (HP:0000989)
Show evidence (1 reference)
PMID:17577020 SUPPORT Human Clinical
"Overall, 32% of patients had pruritus relief."
Relief of pruritus in a refractory MF/SS trial supports pruritus as a clinically meaningful symptomatic phenotype in MF-spectrum disease.
🧬

Genetic Associations

4
TNFRSF1B (TNFR2) (Recurrent Somatic Alteration)
Show evidence (1 reference)
PMID:26258847 SUPPORT Human Clinical
"Here we report recurrent point mutations and genomic gains of TNFRSF1B, encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with mycosis fungoides and Sézary syndrome."
This genomic study establishes TNFRSF1B as a recurrent somatic driver in MF/SS.
CTLA4-CD28 Fusion (Fusion Oncogene)
Show evidence (1 reference)
PMID:26258847 SUPPORT Human Clinical
"Using an integrative genomic approach, we additionally discovered a recurrent CTLA4-CD28 fusion"
This genomic study directly identifies CTLA4-CD28 as a recurrent fusion event in MF/SS.
FAT1, KMT2D, TP53, and JAK3 Alterations (Recurrent Somatic Mutation)
Show evidence (1 reference)
PMID:41008827 SUPPORT Human Clinical
"Recurrent alterations included FAT1 (28.2%), KMT2D (19.2%), TP53 (13.5%), JAK3 (11.5%), and SETBP1 (11.5%), highlighting the role of Wnt signaling, epigenetic dysregulation, the p53 pathway, and JAK/STAT signaling in MF pathogenesis."
This national genomics study supports a recurrent mutation profile spanning Wnt, epigenetic, p53, and JAK/STAT axes in MF.
RAS Mutations (Large-Cell Transformation-Associated Mutation)
Show evidence (1 reference)
PMID:34771672 SUPPORT Human Clinical
"Oncogenic RAS mutations were exclusively detected in patients with LCT."
This sequencing study links RAS mutations specifically to transformed, aggressive MF.
💊

Treatments

5
Narrowband UVB Phototherapy
Action: UV light therapy Ontology label: UV Light Therapy NCIT:C15344
Narrowband UVB is a skin-directed option for early-stage MF, particularly stage IA-IB patch or plaque disease.
Show evidence (1 reference)
PMID:17986058 SUPPORT Human Clinical
"This study provides evidence that NB-UVB might be an efficient option for stage IA and IB MF patients."
This early-stage MF cohort supports narrowband UVB as an effective skin-directed therapy.
Total Skin Electron Beam Radiation Therapy
Action: total skin electron beam radiation therapy Ontology label: Total Skin Electron Beam Radiation Therapy NCIT:C93341
Total skin electron beam therapy is used for diffuse cutaneous disease and remains a core MF radiotherapeutic modality.
Show evidence (1 reference)
PMID:16207183 SUPPORT Human Clinical
"Total skin electron irradiation (TSEI) therapy is the treatment of choice for mycosis fungoides."
This clinical series identifies total skin electron irradiation as a central therapeutic modality for MF.
Mogamulizumab
Action: immunotherapy Ontology label: Immunotherapy NCIT:C15262
Agent: mogamulizumab ↗
CCR4-directed antibody therapy that improves progression-free survival in previously treated cutaneous T-cell lymphoma and is relevant to relapsed/refractory MF.
Show evidence (1 reference)
PMID:30100375 SUPPORT Human Clinical
"Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides"
The MAVORIC phase 3 trial supports mogamulizumab as an active systemic option in previously treated CTCL including MF.
Brentuximab Vedotin
Action: immunotherapy Ontology label: Immunotherapy NCIT:C15262
Agent: brentuximab vedotin ↗
CD30-directed antibody-drug conjugate with superior durable response over physician's choice in previously treated CD30-positive cutaneous T-cell lymphoma.
Show evidence (1 reference)
PMID:28600132 SUPPORT Human Clinical
"the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice"
The ALCANZA phase 3 trial supports brentuximab vedotin as an effective systemic therapy for CD30-positive MF-spectrum CTCL.
Vorinostat
Action: Pharmacotherapy NCIT:C15986
Agent: vorinostat ↗
Histone deacetylase inhibition with vorinostat provides disease control and symptom relief in persistent, progressive, or treatment-refractory MF.
Show evidence (1 reference)
PMID:17577020 SUPPORT Human Clinical
"Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile."
This phase IIb study supports vorinostat as an active systemic therapy in refractory MF/SS.
{ }

Source YAML

click to show 
name: Mycosis Fungoides
creation_date: "2026-04-13T05:44:53Z"
updated_date: "2026-04-22T20:13:21Z"
category: Cancer
categories:
- Hematologic Malignancy
- T-Cell Lymphoma
- Cutaneous Lymphoma
synonyms:
- MF
description: >-
  Mycosis fungoides is the most common cutaneous T-cell lymphoma and is defined
  by malignant skin-homing T-cell clones infiltrating the skin. The disease
  typically evolves through patch, plaque, and tumor stages, while recognized
  WHO-EORTC clinicopathologic variants include folliculotropic mycosis
  fungoides, localized pagetoid reticulosis, and granulomatous slack skin.
  Current MF pathobiology centers on deregulated T-cell receptor/PLCG1 and
  JAK/STAT signaling, TNFR2-linked non-canonical NF-kappaB activation,
  transformation-associated RAS signaling, and progression-promoting stromal and
  macrophage remodeling in the tumor microenvironment. Early-stage disease is
  often managed with skin-directed therapy, whereas advanced or refractory
  disease can require radiotherapy and targeted systemic agents.
definitions:
- name: Pathologic definition of mycosis fungoides
  definition_type: CASE_DEFINITION
  description: >-
    Mycosis fungoides is a cutaneous lymphoma characterized by infiltration of
    malignant T-cell clones into the skin.
  scope: General disease definition for the disease-level mycosis fungoides entry
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Mycosis fungoides (MF) is the commonest subtype of cutaneous lymphoma,
      characterized by the infiltration of malignant T-cell clones into the skin.
    explanation: >-
      This review provides a concise disease-level definition anchored to
      malignant T-cell infiltration of skin.
prevalence:
- population: All cutaneous T-cell lymphoma diagnoses
  percentage: 60
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It accounts for approximately 60% of all cutaneous T-cell lymphoma diagnoses.
    explanation: >-
      This review quantifies the share of cutaneous T-cell lymphomas
      represented by mycosis fungoides.
disease_term:
  preferred_term: mycosis fungoides
  term:
    id: MONDO:0009691
    label: mycosis fungoides
parents:
- cutaneous T-cell lymphoma
has_subtypes:
- name: Folliculotropic
  display_name: Folliculotropic Mycosis Fungoides
  subtype_term:
    preferred_term: folliculotropic mycosis fungoides
    term:
      id: MONDO:0015808
      label: folliculotropic mycosis fungoides
  description: >-
    Recognized WHO-EORTC clinicopathologic variant characterized by
    follicle-centered disease with distinct clinical and histologic spectrum;
    prognosis is heterogeneous and linked to its clinicopathologic subgroup.
  classification: clinicopathologic_variant
  evidence:
  - reference: PMID:29726638
    reference_title: "Folliculotropic mycosis fungoides."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Accepted by the WHO and EORTC as a variant of classic mycosis fungoides,
      folliculotropic (syn.: follicular or pilotropic) mycosis fungoides (FMF) is
      characterized by a broad clinical and histological spectrum with numerous
      differential diagnoses.
    explanation: >-
      This review supports folliculotropic MF as a recognized
      clinicopathologic variant within the MF disease spectrum.
- name: Localized Pagetoid Reticulosis
  display_name: Localized Pagetoid Reticulosis
  subtype_term:
    preferred_term: localized pagetoid reticulosis
    term:
      id: MONDO:0015809
      label: localized pagetoid reticulosis
  description: >-
    Woringer-Kolopp disease is a rare, usually localized, plaque-forming MF
    variant with prominent epidermotropism and generally indolent behavior.
  classification: clinicopathologic_variant
  evidence:
  - reference: PMID:35485962
    reference_title: "Woringer-Kolopp disease (localized pagetoid reticulosis): a systematic review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Woringer-Kolopp disease (WKD), also known as localized pagetoid reticulosis,
      is a rare variant of mycosis fungoides as described by the World
      Health Organization-European Organization for Research and Treatment of Cancer
      (WHO-EORTC) classification system for cutaneous lymphomas.
    explanation: >-
      This systematic review explicitly places localized pagetoid reticulosis
      as a rare MF variant in WHO-EORTC classification.
- name: Granulomatous Slack Skin
  display_name: Granulomatous Slack Skin
  subtype_term:
    preferred_term: granulomatous slack skin disease
    term:
      id: MONDO:0018031
      label: granulomatous slack skin disease
  description: >-
    Rare granulomatous cutaneous T-cell lymphoma phenotype that is best
    modeled as an MF-spectrum variant rather than a separate disease-level
    mechanism graph.
  classification: clinicopathologic_variant
  evidence:
  - reference: PMID:11411914
    reference_title: "Granulomatous slack skin: a distinct disorder or a variant of mycosis fungoides?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      granulomatous mycosis fungoides, and suggests that these 2 disorders are only
      variants in the broad spectrum of a single disease.
    explanation: >-
      This case-based pathology report supports granulomatous slack skin as
      part of the broader MF disease spectrum rather than a separate
      disease-level curation unit.
- name: Patch Stage
  display_name: Patch-Stage Mycosis Fungoides
  description: >-
    Earliest clinical stage with patch lesions and often subtle histology,
    commonly requiring repeated clinicopathologic correlation for diagnosis.
  classification: skin_stage
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MF has three distinct clinical stages - patch, plaque and tumour - presenting most
      commonly on the buttocks, trunk and breast.
    explanation: >-
      This review identifies patch stage as one of the canonical MF clinical
      stages.
- name: Plaque Stage
  display_name: Plaque-Stage Mycosis Fungoides
  description: >-
    Infiltrated plaque stage representing more established cutaneous disease
    and a transition point where progression-associated stromal and macrophage
    programs become more apparent.
  classification: skin_stage
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MF has three distinct clinical stages - patch, plaque and tumour - presenting most
      commonly on the buttocks, trunk and breast.
    explanation: >-
      This review identifies plaque stage as one of the canonical MF
      clinical stages.
- name: Tumor Stage
  display_name: Tumor-Stage Mycosis Fungoides
  description: >-
    Advanced cutaneous stage with tumorous lesions and increased risk of
    extracutaneous progression and large-cell transformation-associated
    aggressive biology.
  classification: skin_stage
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MF has three distinct clinical stages - patch, plaque and tumour - presenting most
      commonly on the buttocks, trunk and breast.
    explanation: >-
      This review identifies tumor stage as one of the canonical MF clinical
      stages.
diagnosis:
- name: Skin Biopsy with Histopathology and Immunohistochemistry
  description: >-
    Diagnosis requires skin biopsy interpreted with clinicopathologic
    correlation and immunohistochemical analysis, especially in subtle early
    lesions.
  evidence:
  - reference: PMID:37124514
    reference_title: "Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Skin biopsy for histopathology and immunohistochemical analysis is imperative
      to confirm the diagnosis of MF/SS.
    explanation: >-
      This review supports skin biopsy with histopathology and
      immunohistochemistry as an essential diagnostic step for MF.
pathophysiology:
- name: Cutaneous Homing of Malignant T-Cell Clones
  description: >-
    Malignant skin-homing T-cell clones infiltrate the epidermis and dermis,
    establishing the defining cutaneous disease compartment of MF.
  cell_types:
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: T cell migration
    modifier: INCREASED
    term:
      id: GO:0072678
      label: T cell migration
  locations:
  - preferred_term: skin of body
    term:
      id: UBERON:0002097
      label: skin of body
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Mycosis fungoides (MF) is the commonest subtype of cutaneous lymphoma,
      characterized by the infiltration of malignant T-cell clones into the skin.
    explanation: >-
      This disease-definition statement directly supports cutaneous
      infiltration by malignant T-cell clones as the core pathobiology of MF.
- name: TCR/PLCG1 Signaling Deregulation
  description: >-
    Recurrent molecular alterations in MF converge on pathologic activation of
    the T-cell receptor and PLCG1 signaling axis.
  cell_types:
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: T cell receptor signaling pathway
    modifier: INCREASED
    term:
      id: GO:0050852
      label: T cell receptor signaling pathway
  evidence:
  - reference: PMID:33923722
    reference_title: "Mycosis Fungoides and Sezary Syndrome: An Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      These seem to make up an orchestrated constellation of genomic and environmental
      alterations generated around deregulated T-cell receptor (TCR)/phospholipase C,
      gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of
      transcription (JAK/STAT) activities
    explanation: >-
      This integrative review identifies deregulated TCR/PLCG1 signaling as
      a core molecular driver axis in MF.
- name: JAK/STAT Signaling Activation
  description: >-
    JAK/STAT pathway activation is a recurrent MF driver axis and remains
    prominent in contemporary mutational studies of the disease.
  cell_types:
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: cell surface receptor signaling pathway via JAK-STAT
    modifier: INCREASED
    term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
  evidence:
  - reference: PMID:33923722
    reference_title: "Mycosis Fungoides and Sezary Syndrome: An Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      These seem to make up an orchestrated constellation of genomic and environmental
      alterations generated around deregulated T-cell receptor (TCR)/phospholipase C,
      gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of
      transcription (JAK/STAT) activities
    explanation: >-
      This review identifies JAK/STAT activity as one of the central driver
      axes in MF pathobiology.
  - reference: PMID:41008827
    reference_title: "Integrative Mutational Landscape of Mycosis Fungoides Using a National Genomics Repository."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Recurrent alterations included FAT1 (28.2%), KMT2D (19.2%), TP53
      (13.5%), JAK3 (11.5%), and SETBP1 (11.5%), highlighting the role of Wnt
      signaling, epigenetic dysregulation, the p53 pathway, and JAK/STAT signaling in
      MF pathogenesis.
    explanation: >-
      This national genomics analysis independently supports recurrent JAK/STAT
      pathway involvement in MF.
- name: TNFR2-Driven Non-Canonical NF-kappaB Signaling
  description: >-
    Recurrent TNFRSF1B alterations augment TNFR2 signaling and activate the
    non-canonical NF-kappaB pathway in malignant T cells.
  cell_types:
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: non-canonical NF-kappaB signal transduction
    modifier: INCREASED
    term:
      id: GO:0038061
      label: non-canonical NF-kappaB signal transduction
  evidence:
  - reference: PMID:26258847
    reference_title: "Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here we report recurrent point mutations and genomic gains of TNFRSF1B,
      encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with
      mycosis fungoides and Sézary syndrome.
    explanation: >-
      This genomic study identifies recurrent TNFRSF1B alterations in MF/SS,
      supporting TNFR2 as a disease-relevant driver.
  - reference: PMID:26258847
    reference_title: "Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Expression of the recurrent TNFR2 Thr377Ile mutant in T cells leads to
      enhanced non-canonical NF-κB signaling
    explanation: >-
      This study directly links recurrent TNFR2 mutation to enhanced
      non-canonical NF-kappaB signaling.
- name: Cancer-Associated Fibroblast Matrix Remodeling
  description: >-
    Progressive MF lesions develop a fibroblast-rich stromal program marked by
    increased collagen fibril organization and enrichment of
    cancer-associated fibroblasts.
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: collagen fibril organization
    modifier: INCREASED
    term:
      id: GO:0030199
      label: collagen fibril organization
  evidence:
  - reference: PMID:40163757
    reference_title: "Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      genes linked to collagen fibril assembly and regulation of interleukin-4 were
      upregulated as the disease progressed from patch- to plaque-stage MF.
    explanation: >-
      This spatial transcriptomic study links MF progression to a collagen
      remodeling program in advancing lesions.
  - reference: PMID:40163757
    reference_title: "Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients with stage I MF with high-progression signatures showed significantly
      increased cancer-associated fibroblast (CAF; P = .008)
    explanation: >-
      This study directly connects high-progression MF to enrichment of
      cancer-associated fibroblasts.
- name: Interleukin-4 Program Activation
  description: >-
    Progression from patch-stage to plaque-stage MF is accompanied by an
    interleukin-4-associated transcriptional program.
  biological_processes:
  - preferred_term: regulation of interleukin-4 production
    modifier: INCREASED
    term:
      id: GO:0032673
      label: regulation of interleukin-4 production
  evidence:
  - reference: PMID:40163757
    reference_title: "Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      genes linked to collagen fibril assembly and regulation of interleukin-4 were
      upregulated as the disease progressed from patch- to plaque-stage MF.
    explanation: >-
      This spatial transcriptomic study directly supports increased IL-4
      regulatory programs during early MF progression.
- name: M2 Macrophage-Mediated Immune Suppression
  description: >-
    Progressing MF lesions accumulate M2 macrophages and exhaustion-associated
    immune programs that suppress effective antitumor T-cell immunity.
  cell_types:
  - preferred_term: M2 macrophage
    term:
      id: CL:0000890
      label: M2 macrophage
  biological_processes:
  - preferred_term: negative regulation of T cell mediated immunity
    modifier: INCREASED
    term:
      id: GO:0002710
      label: negative regulation of T cell mediated immunity
  evidence:
  - reference: PMID:40163757
    reference_title: "Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Furthermore, M2 macrophages significantly increased in lymphoma cell areas (P <
      .001) and immune cell areas (P = .031) in plaque-stage MF compared with
      patch-stage MF.
    explanation: >-
      This study directly demonstrates enrichment of M2 macrophages in
      progressing MF lesions.
  - reference: PMID:40163757
    reference_title: "Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CD163 expression was significantly correlated with most of the progression
      signatures and T-cell exhaustion markers
    explanation: >-
      Correlation between CD163 and exhaustion markers supports an
      immunosuppressive macrophage-centered microenvironment in progressive MF.
- name: Large-Cell Transformation-Associated RAS Signaling
  description: >-
    Large-cell transformation in MF is a progression state marked by acquired
    oncogenic RAS/MAPK lesions and broader mutation accumulation, rather than
    a separate disease-level mechanism graph.
  biological_processes:
  - preferred_term: Ras protein signal transduction
    modifier: INCREASED
    term:
      id: GO:0007265
      label: Ras protein signal transduction
  evidence:
  - reference: PMID:34771672
    reference_title: "Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oncogenic RAS mutations were exclusively detected in patients with LCT.
    explanation: >-
      This targeted sequencing study directly links oncogenic RAS mutations to
      large-cell transformation in MF.
  - reference: PMID:34771672
    reference_title: "Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In particular, the activation of RAS signaling-together with epigenetic
      dysregulation-may crucially contribute to the molecular pathogenesis of the LCT
      phenotype, thus conveying its adverse clinical behavior.
    explanation: >-
      This conclusion supports RAS signaling as a mechanistic contributor to
      transformation-associated aggressive MF biology.
histopathology:
- name: Epidermotropic Small-to-Medium Lymphoid Infiltrate
  finding_term:
    preferred_term: epidermotropic infiltrate of small-to-medium-sized lymphocytes
    # NTR: no specific HPO term found for epidermotropism

  frequency: VERY_FREQUENT
  diagnostic: true
  description: >-
    Early MF commonly shows an epidermotropic infiltrate of small-to-medium
    lymphocytes that may require repeated biopsy for recognition.
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Patients may require multiple skin biopsies, especially at the patch stage, to
      identify the characteristic epidermotropic infiltrates of
      small-to-medium-sized lymphocytes.
    explanation: >-
      This review supports the characteristic epidermotropic small-to-medium
      lymphoid infiltrate of MF.
- name: Folliculotropism
  finding_term:
    preferred_term: folliculotropism
    # NTR: no specific HPO term found for folliculotropism

  description: >-
    Folliculotropism is a histopathologic pattern associated with the
    folliculotropic MF variant and poorer prognosis in infiltrated head and
    neck plaques or tumors.
  evidence:
  - reference: PMID:37124514
    reference_title: "Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Besides advanced stage, other factors associated with poorer prognosis are
      advanced age, male gender, folliculotropism in histopathology of patients with
      infiltrated plaques and tumors in the head and neck region, large cell
      transformation, and elevated lactate dehydrogenase.
    explanation: >-
      This review identifies folliculotropism as a clinically important
      histopathologic pattern within MF.
phenotypes:
- category: Dermatologic
  name: Patch/Plaque/Tumor Skin Lesions
  frequency: VERY_FREQUENT
  description: >-
    MF classically presents with a progression spectrum of patch, plaque, and
    tumor skin lesions.
  phenotype_term:
    preferred_term: Abnormal skin morphology
    term:
      id: HP:0011121
      label: Abnormal skin morphology
  evidence:
  - reference: PMID:34541796
    reference_title: "Mycosis fungoides and Sézary syndrome."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MF presents clinically with patch, plaque and/or tumor stages, but can also
      evolve as erythroderma
    explanation: >-
      This review directly supports the characteristic patch/plaque/tumor
      lesion spectrum of MF.
- category: Dermatologic
  name: Skin Plaque
  frequency: FREQUENT
  description: >-
    Plaques are one of the canonical morphologic lesion types of MF and
    represent an established clinical stage.
  phenotype_term:
    preferred_term: Skin plaque
    term:
      id: HP:0200035
      label: Skin plaque
  evidence:
  - reference: PMID:40721285
    reference_title: "Mycosis fungoides: a review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MF has three distinct clinical stages - patch, plaque and tumour - presenting most
      commonly on the buttocks, trunk and breast.
    explanation: >-
      This review explicitly identifies plaque lesions as a canonical MF
      clinical stage.
- category: Dermatologic
  name: Erythroderma
  frequency: OCCASIONAL
  description: >-
    Some MF cases evolve to erythroderma during disease progression, although
    diffuse erythroderma is more typical of Sézary syndrome.
  phenotype_term:
    preferred_term: Erythroderma
    term:
      id: HP:0001019
      label: Erythroderma
  evidence:
  - reference: PMID:34541796
    reference_title: "Mycosis fungoides and Sézary syndrome."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      MF presents clinically with patch, plaque and/or tumor stages, but can also
      evolve as erythroderma
    explanation: >-
      This review supports erythrodermic evolution as part of the MF clinical
      spectrum.
- category: Constitutional
  name: Pruritus
  description: >-
    Pruritus is a common symptomatic burden in MF and is frequently tracked as
    a patient-relevant treatment outcome in refractory disease.
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
  evidence:
  - reference: PMID:17577020
    reference_title: "Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall, 32% of patients had pruritus relief.
    explanation: >-
      Relief of pruritus in a refractory MF/SS trial supports pruritus as a
      clinically meaningful symptomatic phenotype in MF-spectrum disease.
genetic:
- name: TNFRSF1B (TNFR2)
  association: Recurrent Somatic Alteration
  notes: >-
    Recurrent point mutations and genomic gains of TNFRSF1B define a
    disease-relevant MF driver axis linked to TNFR2 signaling.
  evidence:
  - reference: PMID:26258847
    reference_title: "Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here we report recurrent point mutations and genomic gains of TNFRSF1B,
      encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with
      mycosis fungoides and Sézary syndrome.
    explanation: >-
      This genomic study establishes TNFRSF1B as a recurrent somatic driver
      in MF/SS.
- name: CTLA4-CD28 Fusion
  association: Fusion Oncogene
  notes: >-
    Recurrent CTLA4-CD28 fusion provides an additional immune-signaling driver
    lesion within the MF/SS genomic landscape.
  evidence:
  - reference: PMID:26258847
    reference_title: "Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Using an integrative genomic approach, we additionally discovered a recurrent
      CTLA4-CD28 fusion
    explanation: >-
      This genomic study directly identifies CTLA4-CD28 as a recurrent fusion
      event in MF/SS.
- name: FAT1, KMT2D, TP53, and JAK3 Alterations
  association: Recurrent Somatic Mutation
  notes: >-
    Contemporary genomic profiling of MF identifies recurrent alterations in
    Wnt, epigenetic, p53, and JAK/STAT pathway genes, broadening the known
    mutational spectrum beyond earlier targeted studies.
  evidence:
  - reference: PMID:41008827
    reference_title: "Integrative Mutational Landscape of Mycosis Fungoides Using a National Genomics Repository."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Recurrent alterations included FAT1 (28.2%), KMT2D (19.2%), TP53
      (13.5%), JAK3 (11.5%), and SETBP1 (11.5%), highlighting the role of Wnt
      signaling, epigenetic dysregulation, the p53 pathway, and JAK/STAT signaling in
      MF pathogenesis.
    explanation: >-
      This national genomics study supports a recurrent mutation profile
      spanning Wnt, epigenetic, p53, and JAK/STAT axes in MF.
- name: RAS Mutations
  association: Large-Cell Transformation-Associated Mutation
  notes: >-
    Oncogenic RAS mutations are linked to aggressive MF with large-cell
    transformation and should be interpreted as progression biology within MF
    rather than justification for a separate disease page.
  evidence:
  - reference: PMID:34771672
    reference_title: "Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oncogenic RAS mutations were exclusively detected in patients with LCT.
    explanation: >-
      This sequencing study links RAS mutations specifically to transformed,
      aggressive MF.
treatments:
- name: Narrowband UVB Phototherapy
  description: >-
    Narrowband UVB is a skin-directed option for early-stage MF, particularly
    stage IA-IB patch or plaque disease.
  treatment_term:
    preferred_term: UV light therapy
    term:
      id: NCIT:C15344
      label: UV Light Therapy
  evidence:
  - reference: PMID:17986058
    reference_title: "Narrow-band ultraviolet therapy in early-stage mycosis fungoides: study on 20 patients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This study provides evidence that NB-UVB might be an efficient option for
      stage IA and IB MF patients.
    explanation: >-
      This early-stage MF cohort supports narrowband UVB as an effective
      skin-directed therapy.
- name: Total Skin Electron Beam Radiation Therapy
  description: >-
    Total skin electron beam therapy is used for diffuse cutaneous disease and
    remains a core MF radiotherapeutic modality.
  treatment_term:
    preferred_term: total skin electron beam radiation therapy
    term:
      id: NCIT:C93341
      label: Total Skin Electron Beam Radiation Therapy
  evidence:
  - reference: PMID:16207183
    reference_title: "Total skin electron irradiation therapy in mycosis fungoides using high-dose rate mode: a preliminary experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Total skin electron irradiation (TSEI) therapy is the treatment of choice for
      mycosis fungoides.
    explanation: >-
      This clinical series identifies total skin electron irradiation as a
      central therapeutic modality for MF.
- name: Mogamulizumab
  description: >-
    CCR4-directed antibody therapy that improves progression-free survival in
    previously treated cutaneous T-cell lymphoma and is relevant to
    relapsed/refractory MF.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
    therapeutic_agent:
    - preferred_term: mogamulizumab
      term:
        id: NCIT:C62510
        label: Mogamulizumab
  evidence:
  - reference: PMID:30100375
    reference_title: "Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mogamulizumab significantly prolonged progression-free survival
      compared with vorinostat, and could provide a new, effective treatment for
      patients with mycosis fungoides
    explanation: >-
      The MAVORIC phase 3 trial supports mogamulizumab as an active systemic
      option in previously treated CTCL including MF.
- name: Brentuximab Vedotin
  description: >-
    CD30-directed antibody-drug conjugate with superior durable response over
    physician's choice in previously treated CD30-positive cutaneous T-cell
    lymphoma.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
    therapeutic_agent:
    - preferred_term: brentuximab vedotin
      term:
        id: NCIT:C66944
        label: Brentuximab Vedotin
  evidence:
  - reference: PMID:28600132
    reference_title: "Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the proportion of patients achieving an objective global response lasting at
      least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin
      versus 12·5% (eight of 64) with physician's choice
    explanation: >-
      The ALCANZA phase 3 trial supports brentuximab vedotin as an effective
      systemic therapy for CD30-positive MF-spectrum CTCL.
- name: Vorinostat
  description: >-
    Histone deacetylase inhibition with vorinostat provides disease control and
    symptom relief in persistent, progressive, or treatment-refractory MF.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: vorinostat
      term:
        id: NCIT:C1796
        label: Vorinostat
  evidence:
  - reference: PMID:17577020
    reference_title: "Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oral vorinostat was effective in treatment refractory MF/SS with an
      acceptable safety profile.
    explanation: >-
      This phase IIb study supports vorinostat as an active systemic therapy
      in refractory MF/SS.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0009691
      label: mycosis fungoides
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease identifier for this disease-level mycosis fungoides entry.
references:
- reference: PMID:11411914
  title: "Granulomatous slack skin: a distinct disorder or a variant of mycosis fungoides?"
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:16207183
  title: "Total skin electron irradiation therapy in mycosis fungoides using high-dose rate mode: a preliminary experience."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:17577020
  title: "Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:17986058
  title: "Narrow-band ultraviolet therapy in early-stage mycosis fungoides: study on 20 patients."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:26258847
  title: Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2.
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:28600132
  title: "Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:29726638
  title: Folliculotropic mycosis fungoides.
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:30100375
  title: "Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:33923722
  title: "Mycosis Fungoides and Sézary Syndrome: An Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:34541796
  title: Mycosis fungoides and Sézary syndrome.
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:34771672
  title: Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation.
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:35485962
  title: "Woringer-Kolopp disease (localized pagetoid reticulosis): a systematic review."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:37124514
  title: "Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:40163757
  title: Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides.
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:40721285
  title: "Mycosis fungoides: a review."
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
- reference: PMID:41008827
  title: Integrative Mutational Landscape of Mycosis Fungoides Using a National Genomics Repository.
  found_in:
  - Mycosis_Fungoides-deep-research-openai.md
  findings: []
📚

References & Deep Research

References

16
PMID:11411914
Granulomatous slack skin: a distinct disorder or a variant of mycosis fungoides?
No top-level findings curated for this source.
PMID:16207183
Total skin electron irradiation therapy in mycosis fungoides using high-dose rate mode: a preliminary experience.
No top-level findings curated for this source.
PMID:17577020
Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.
No top-level findings curated for this source.
PMID:17986058
Narrow-band ultraviolet therapy in early-stage mycosis fungoides: study on 20 patients.
No top-level findings curated for this source.
PMID:26258847
Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2.
No top-level findings curated for this source.
PMID:28600132
Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.
No top-level findings curated for this source.
PMID:29726638
Folliculotropic mycosis fungoides.
No top-level findings curated for this source.
PMID:30100375
Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial.
No top-level findings curated for this source.
PMID:33923722
Mycosis Fungoides and Sézary Syndrome: An Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy.
No top-level findings curated for this source.
PMID:34541796
Mycosis fungoides and Sézary syndrome.
No top-level findings curated for this source.
PMID:34771672
Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation.
No top-level findings curated for this source.
PMID:35485962
Woringer-Kolopp disease (localized pagetoid reticulosis): a systematic review.
No top-level findings curated for this source.
PMID:37124514
Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management.
No top-level findings curated for this source.
PMID:40163757
Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides.
No top-level findings curated for this source.
PMID:40721285
Mycosis fungoides: a review.
No top-level findings curated for this source.
PMID:41008827
Integrative Mutational Landscape of Mycosis Fungoides Using a National Genomics Repository.
No top-level findings curated for this source.

Deep Research

1
OpenAI ▸
Mycosis Fungoides Deep Research
gpt-5.4

Mycosis Fungoides Deep Research

Modeling choices

This curation follows the cancer-modeling guidance from dismech issue #1198. The dismech page is the disease-level mechanism graph for Mycosis_Fungoides, not a page-per-subclass decomposition. I kept the disease anchor MONDO-first at MONDO:0009691 and treated WHO-EORTC-recognized variants as flat subtype facets rather than separate disease pages. That means folliculotropic mycosis fungoides, localized pagetoid reticulosis, and granulomatous slack skin are represented as subtype values under one MF entry. Large-cell transformation was modeled as progression biology within MF rather than as a separate disease file.

NCIT was used where it adds oncology-specific value under the current schema, especially for histopathology and treatment terms. I did not add disease-level or subtype-level NCIT mappings because the present schema exposes MONDO disease mapping slots but not a parallel ncit_mappings structure for disease/subtype anchors.

Disease identity and subtype structure

Recent reviews consistently describe MF as the most common cutaneous T-cell lymphoma and as a disease centered on malignant T-cell infiltration of skin (PMID:40721285, PMID:37124514). Clinical staging remains the core disease axis: patch, plaque, and tumor stages are explicit in recent reviews (PMID:40721285, PMID:34541796). WHO-EORTC-recognized clinicopathologic variants include folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin (PMID:37124514, PMID:29726638, PMID:35485962, PMID:11411914).

The resulting subtype model in YAML is intentionally flat:

  • classification: clinicopathologic_variant
  • classification: skin_stage

This preserves clinically meaningful subtype structure without implying that every ontology subclass needs its own dismech page.

Histopathology and diagnosis

The strongest disease-level histopathology signal available in recent MF review abstracts is the characteristic epidermotropic infiltrate of small-to-medium lymphocytes, especially in early patch-stage disease, alongside the need for repeated biopsies and careful clinicopathologic correlation (PMID:40721285, PMID:34541796). Folliculotropism is clinically important because it is tied to recognized variant structure and poorer prognosis in infiltrated head/neck plaques and tumors (PMID:37124514). Diagnostic workflow is anchored to skin biopsy with histopathology and immunohistochemistry (PMID:37124514).

Pathophysiology

I kept the mechanistic graph atomic and avoided bundled nodes. The main disease mechanisms supported by the literature are:

  1. Cutaneous homing and accumulation of malignant T-cell clones in skin (PMID:40721285).
  2. Deregulated TCR/PLCG1 signaling as a core driver axis (PMID:33923722).
  3. Recurrent JAK/STAT activation supported both by integrative review and contemporary MF genomics (PMID:33923722, PMID:41008827).
  4. TNFRSF1B/TNFR2-driven non-canonical NF-kappaB signaling as a recurrent human genomic mechanism (PMID:26258847).
  5. Cancer-associated fibroblast and collagen-remodeling programs during early progression (PMID:40163757).
  6. Interleukin-4-associated transcriptional activation during patch-to-plaque evolution (PMID:40163757).
  7. M2 macrophage enrichment and exhaustion-linked immune suppression in progressive lesions (PMID:40163757).
  8. RAS-signaling acquisition in large-cell transformation, modeled as MF progression rather than a new disease anchor (PMID:34771672).

Genetics

The genetics section emphasizes lesions that help explain MF mechanism or progression:

  • TNFRSF1B recurrent mutation/gain and TNFR2 signaling (PMID:26258847)
  • CTLA4-CD28 fusion (PMID:26258847)
  • recurrent FAT1, KMT2D, TP53, and JAK3 alterations in a 2025 national genomics analysis (PMID:41008827)
  • transformation-associated RAS mutations in aggressive large-cell transformation (PMID:34771672)

This keeps the disease page focused on driver axes rather than turning the entry into an exhaustive mutation inventory.

Phenotypes

The phenotype set emphasizes disease-defining cutaneous morphology and clinically important symptom burden:

  • patch/plaque/tumor lesion spectrum (PMID:34541796)
  • plaque lesions as a canonical stage feature (PMID:40721285)
  • erythrodermic evolution in some MF cases (PMID:34541796)
  • pruritus as a patient-relevant symptom tracked in therapeutic studies (PMID:17577020)

Treatments

The treatment section was kept disease-relevant and ontology-grounded, with NCIT preferred when it gives materially better oncology specificity:

  • narrowband UVB under NCIT:C15344 UV Light Therapy (PMID:17986058)
  • total skin electron beam radiation therapy with the exact NCIT procedure term NCIT:C93341 (PMID:16207183)
  • mogamulizumab (PMID:30100375)
  • brentuximab vedotin (PMID:28600132)
  • vorinostat (PMID:17577020)

This avoids mixing in very broad generic MAXO treatment labels when a more oncology-specific NCIT procedure is available, while still using MAXO:0000058 for systemic pharmacotherapy actions paired with specific antineoplastic agents.