Anal Canal Adenocarcinoma

📘

Definitions

1

Clinicopathologic definition

A primary adenocarcinoma arising in the anal canal mucosa, transitional zone, anal glands, or anorectal fistula region, diagnosed by biopsy and gland-forming histopathology with clinical and immunohistochemical exclusion of a downward-extending distal rectal adenocarcinoma or metastatic adenocarcinoma from another primary site.

CASE_DEFINITION Gastrointestinal oncology and surgical pathology definition

Show evidence (2 references)

PMID:29700411 SUPPORT Human Clinical

"Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis."

This multi-institutional cohort establishes anal canal adenocarcinoma as a rare aggressive gastrointestinal tumor and motivates subtype-aware pathologic classification.

PMID:34244243 SUPPORT Human Clinical

"A recent classification suggests that anal adenocarcinomas can be subdivided into two types: (1) colorectal from mucosa above the dentate line and (2) extramucosal from anorectal fistulae or anal glands."

This review supports classifying anal adenocarcinoma by colorectal-type mucosal origin versus extramucosal fistula or anal-gland origin.

◆

Subtypes

3

histologic and molecular

Anal gland/transitional-type anal canal adenocarcinoma

KRT7-positive, KRT20/CDX2-negative tumors interpreted as anal gland/transitional-type adenocarcinomas. In the Herfs cohort, this subtype had a subset of HPV16/18-associated tumors and a more prominent immune-checkpoint microenvironment than colorectal-type tumors.

Show evidence (1 reference)

PMID:29700411 SUPPORT Human Clinical

"Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma."

The 74-tumor molecular pathology cohort supports distinct region-specific subtypes within primary anal canal adenocarcinoma.

Colorectal-type anal canal adenocarcinoma

KRT20/CDX2-positive tumors interpreted as colorectal-type anal canal adenocarcinomas, resembling lower rectal or colorectal mucosal adenocarcinoma in lineage marker pattern and clinical management.

Show evidence (1 reference)

PMID:34244243 SUPPORT Human Clinical

"Differentiating between distal rectal adenocarcinoma with local spread and primary anal canal tumours is challenging."

This review highlights the diagnostic boundary between colorectal-type anal canal adenocarcinoma and distal rectal adenocarcinoma extending into the anal canal.

etiologic and histologic

Fistula-associated mucinous adenocarcinoma

Mucinous adenocarcinoma arising in a chronic anorectal fistula or perianal abscess/fistula tract, including Crohn disease-associated fistula cancers.

Show evidence (1 reference)

PMID:37695405 SUPPORT Human Clinical

"A biopsy taken from the tumor demonstrated mucinous adenocarcinoma; the tumor was diagnosed as FAMC."

This case report directly documents fistula-associated mucinous adenocarcinoma as an anal canal adenocarcinoma-related subtype.

⚙

Pathophysiology

3

Chronic fistula-associated mucinous carcinogenesis

Recurrent perianal abscess and anal fistula generate a chronic inflammatory epithelial tract. Dysplasia within the fistula lining can progress to poorly differentiated mucinous adenocarcinoma involving the dermis, epidermis, sphincter complex, or adjacent pelvic organs.

fistula tract glandular epithelial cell link

chronic inflammation-driven cell population proliferation link ↑ INCREASED

anal canal link

Downstream

Locally advanced pelvic invasion Fistula-associated mucinous tumors may infiltrate adjacent pelvic structures.

Show evidence (1 reference)

PMID:37695405 SUPPORT Human Clinical

"Histopathology showed highly dysplastic cells lining the lumen of the anal fistula and poorly differentiated mucinous adenocarcinoma proliferating in the dermis and epidermis in the distal aspect of the fistula."

The histopathology links dysplastic fistula lining to proliferating mucinous adenocarcinoma in the distal fistula tract.

Dualistic HPV-dependent and HPV-independent tumor lineages

Primary anal canal adenocarcinoma separates into at least two region-specific entities. Anal gland/transitional-type tumors can follow an HPV-dependent pathway with increased immune checkpoint expression, whereas colorectal-type tumors more often follow HPV-independent colorectal-lineage molecular programs.

glandular epithelial cell of anal canal link

immune response link ↕ DYSREGULATED cell surface receptor protein tyrosine kinase signaling pathway link ↕ DYSREGULATED

Downstream

PD-1/PD-L1-enriched immune microenvironment The anal gland/transitional subtype shows greater immune checkpoint expression.

KRAS/NRAS and PI3K pathway alteration Targetable gastrointestinal cancer genes vary across subtypes.

Show evidence (1 reference)

PMID:29700411 SUPPORT Human Clinical

"The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities."

The molecular cohort supports two mechanistically distinct entities separated by HPV status, immune contexture, checkpoint expression, and targetable mutation profile.

PD-1/PD-L1-enriched immune microenvironment

The anal gland/transitional-type subset has higher PD-1/PD-L1 expression and a different tumor-infiltrating lymphocyte profile than colorectal-type tumors, creating a biologic rationale for immune-checkpoint-directed clinical research while not establishing prospective efficacy for this rare tumor.

CD8-positive, alpha-beta T cell link regulatory T cell link

immune response link ↕ DYSREGULATED

Show evidence (1 reference)

PMID:29700411 SUPPORT Human Clinical

"anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1..."

This supports an immune-checkpoint-enriched microenvironment in the anal gland/transitional subtype relative to colorectal-type tumors.

✶

Histopathology

3

Primary anal canal adenocarcinoma

Primary anal canal adenocarcinoma is a glandular malignancy that requires histologic and immunophenotypic distinction from squamous carcinoma and from distal rectal adenocarcinoma extending into the anal canal.

Show evidence (1 reference)

PMID:29700411 SUPPORT Human Clinical

"The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels."

The Herfs cohort explicitly characterizes primary anal glandular neoplasms at the histologic level as part of subtype definition.

Mucinous fistula-associated adenocarcinoma

Fistula-associated tumors can show mucinous adenocarcinoma with dysplastic fistula epithelium and dermal or epidermal extension at the distal fistula tract.

Show evidence (1 reference)

PMID:37695405 SUPPORT Human Clinical

"Histopathology showed highly dysplastic cells lining the lumen of the anal fistula and poorly differentiated mucinous adenocarcinoma proliferating in the dermis and epidermis in the distal aspect of the fistula."

The case report provides direct histopathologic evidence for mucinous fistula-associated adenocarcinoma arising along the fistula tract.

CK7-positive and CK20/CDX2-negative immunophenotype

CK7-positive, CK20/CDX2-negative staining supports anal gland/transitional lineage in some tumors and helps distinguish primary anal adenocarcinoma from colorectal-type adenocarcinoma.

Show evidence (1 reference)

PMID:34244243 SUPPORT Human Clinical

"Immunohistological stains were positive for CK7 and negative for CK20, CDX2, SOX-10 consistent with adenocarcinoma."

The case report documents an immunophenotypic pattern used to support an anal adenocarcinoma diagnosis.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

Referential integrity issues (2):

Target 'Locally advanced pelvic invasion' (from 'Chronic fistula-associated mucinous carcinogenesis') not found in named elements
Target 'KRAS/NRAS and PI3K pathway alteration' (from 'Dualistic HPV-dependent and HPV-independent tumor lineages') not found in named elements

●

Phenotypes

3

Blood 1

Rectal bleeding or serosanguineous anal discharge Hematochezia (HP:0002573)

Show evidence (1 reference)

PMID:34244243 SUPPORT Human Clinical

"This case highlights the challenges of early diagnosis of anal malignancies and the importance of prompt evaluation of anorectal area by anoscopy and colonoscopy if symptoms of rectal bleeding or serosanguinous anal discharge are reported."

The review highlights rectal bleeding and serosanguineous discharge as symptoms that should trigger prompt anal and rectal evaluation.

Other 2

Anal pain with palpable tumor Anal pain (HP:0500005)

Show evidence (1 reference)

PMID:37695405 SUPPORT Human Clinical

"A 68-year-old woman was admitted to our hospital because of progressive anal pain and a palpable tumor."

Case-level evidence directly reports progressive anal pain and palpable tumor as presenting manifestations.

Anal stenosis from pelvic mass Anal stenosis (HP:0002025)

Show evidence (1 reference)

PMID:37962718 SUPPORT Human Clinical

"Computed tomography (CT) showed anal stenosis due to a pelvic mass."

This Crohn-associated anorectal fistula cancer case documents anal stenosis secondary to a pelvic mass.

🧬

Genetic Associations

2

KRAS and NRAS pathway mutation context (Somatic RAS pathway alterations and subtype-specific mutation burden)

Show evidence (1 reference)

PMID:29700411 SUPPORT Human Clinical

"anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS)"

The abstract identifies KRAS and NRAS as subtype-relevant downstream EGFR signaling effectors in primary anal canal adenocarcinoma.

MSI-high biomarker in individual case (Rare mismatch-repair-deficient or MSI-high biomarker context)

Show evidence (1 reference)

PMID:34244243 SUPPORT Human Clinical

"Subsequent tumour profiling demonstrated a high microsatellite instability and was KRAS/NRAS/BRAF wild type."

This case report supports MSI-high as a clinically relevant biomarker in at least a subset of anal adenocarcinoma patients.

💊

Treatments

3

Surgery for localized or resectable disease

Action: surgical procedure MAXO:0000004

Surgical resection is a major component of treatment for resectable anal canal adenocarcinoma and is associated with improved survival in SEER analyses.

Show evidence (1 reference)

PMID:32455011 SUPPORT Human Clinical

"Surgical intervention improved survival significantly as compared to patients who did not (116.7 months vs 42.7 months, p < 0.01)."

Population-based SEER analysis supports a survival association with surgery for anal canal adenocarcinoma.

Preoperative chemoradiation with surgical resection

Action: Chemoradiotherapy NCIT:C94626

For stage I-III anal adenocarcinoma, retrospective SEER data suggest that preoperative radiation or chemotherapy followed by surgery may maximize survival, especially for more advanced localized disease.

Show evidence (2 references)

PMID:32389595 SUPPORT Human Clinical

"Preoperative treatment with surgical resection may maximize the survival outcome."

The SEER stage I-III treatment study concludes that preoperative treatment with surgery may maximize survival.

PMID:32389595 SUPPORT Human Clinical

"Although chemoradiotherapy alone may be sufficient for early stages of disease, patients with advanced disease should be treated with a combination of surgical resection and chemoradiotherapy."

This supports combined surgery and chemoradiotherapy for advanced non-metastatic disease, while acknowledging possible sufficiency of chemoradiotherapy alone in early stages.

Pembrolizumab for MSI-high disease

Action: Pharmacotherapy NCIT:C15986

Agent: pembrolizumab ↗

Pembrolizumab is a biomarker-driven treatment consideration for MSI-high anal adenocarcinoma, but the direct disease-specific evidence is limited to case-level observation in the retrieved literature.

Show evidence (1 reference)

PMID:34244243 PARTIAL Human Clinical

"Over a year after diagnosis, the patient is alive and managed with pembrolizumab."

This single MSI-high case provides partial, case-level support for pembrolizumab in biomarker-selected anal adenocarcinoma.

🌍

Environmental Factors

2

Chronic anorectal fistula and perianal abscess history

Persistent anorectal fistula or perianal abscess/fistula inflammation can provide the substrate for fistula-associated mucinous adenocarcinoma.

Show evidence (1 reference)

PMID:37695405 SUPPORT Human Clinical

"A long-standing (over 10 years) anal fistula is considered a fundamental cause of fistula-associated mucinous adenocarcinoma (FAMC)."

The abstract identifies long-standing anal fistula as a fundamental cause of fistula-associated mucinous adenocarcinoma.

Crohn disease-associated anorectal fistula

Perianal Crohn disease with anorectal fistula can be complicated by mucinous anorectal fistula cancer with locally advanced invasion.

Show evidence (1 reference)

PMID:37962718 SUPPORT Human Clinical

"We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn's disease, which was curatively resected after preoperative chemoradiotherapy."

This case report supports Crohn disease-associated anorectal fistula as a context for locally advanced mucinous adenocarcinoma.

🔬

Clinical Trials

1

NCT05605873 NOT_APPLICABLE COMPLETED

Retrospective French cohort study designed to classify clinical, histologic, etiologic, and prognostic forms of adenocarcinoma of the anus.

Show evidence (1 reference)

clinicaltrials:NCT05605873 SUPPORT

"Adenocarcinoma of the anus is rare. It concerns less than 10% of anal cancers and its incidence is less than 0.2/100 000 inhabitants."

The ClinicalTrials.gov summary supports rarity and the rationale for studying clinical, histologic, and prognostic forms.

{ }

Source YAML

click to show

name: Anal Canal Adenocarcinoma
creation_date: "2026-05-14T18:23:55Z"
updated_date: "2026-05-14T18:23:55Z"
synonyms:
- Anal adenocarcinoma
- Adenocarcinoma of the anal canal
- Adenocarcinoma arising in anal mucosa
- Fistula-associated mucinous adenocarcinoma
description: >-
  Anal canal adenocarcinoma is a rare, aggressive gland-forming malignancy of
  the anal canal region. It is biologically heterogeneous: some tumors resemble
  colorectal-type adenocarcinoma, some arise from anal gland or transitional
  epithelium, and fistula-associated mucinous tumors can emerge in chronic
  anorectal inflammatory tracts. The evidence base is dominated by population
  registry cohorts, retrospective treatment studies, molecular cohort profiling,
  and case reports rather than randomized disease-specific trials.
categories:
- Gastrointestinal Malignancy
- Adenocarcinoma
- Solid Tumor
- Rare Cancer
parents:
- anus adenocarcinoma
- anal canal carcinoma
- adenocarcinoma
disease_term:
  preferred_term: anal canal adenocarcinoma
  term:
    id: MONDO:0002735
    label: anal canal adenocarcinoma
definitions:
- name: Clinicopathologic definition
  definition_type: CASE_DEFINITION
  description: >-
    A primary adenocarcinoma arising in the anal canal mucosa, transitional
    zone, anal glands, or anorectal fistula region, diagnosed by biopsy and
    gland-forming histopathology with clinical and immunohistochemical exclusion
    of a downward-extending distal rectal adenocarcinoma or metastatic
    adenocarcinoma from another primary site.
  scope: Gastrointestinal oncology and surgical pathology definition
  evidence:
  - reference: PMID:29700411
    reference_title: "A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis."
    explanation: >-
      This multi-institutional cohort establishes anal canal adenocarcinoma as a
      rare aggressive gastrointestinal tumor and motivates subtype-aware
      pathologic classification.
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A recent classification suggests that anal adenocarcinomas can be subdivided into two types: (1) colorectal from mucosa above the dentate line and (2) extramucosal from anorectal fistulae or anal glands."
    explanation: >-
      This review supports classifying anal adenocarcinoma by colorectal-type
      mucosal origin versus extramucosal fistula or anal-gland origin.
has_subtypes:
- name: Anal Gland/Transitional Type
  display_name: Anal gland/transitional-type anal canal adenocarcinoma
  classification: histologic and molecular
  description: >-
    KRT7-positive, KRT20/CDX2-negative tumors interpreted as anal
    gland/transitional-type adenocarcinomas. In the Herfs cohort, this subtype
    had a subset of HPV16/18-associated tumors and a more prominent
    immune-checkpoint microenvironment than colorectal-type tumors.
  evidence:
  - reference: PMID:29700411
    reference_title: "A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma."
    explanation: >-
      The 74-tumor molecular pathology cohort supports distinct
      region-specific subtypes within primary anal canal adenocarcinoma.
- name: Colorectal Type
  display_name: Colorectal-type anal canal adenocarcinoma
  classification: histologic and molecular
  description: >-
    KRT20/CDX2-positive tumors interpreted as colorectal-type anal canal
    adenocarcinomas, resembling lower rectal or colorectal mucosal
    adenocarcinoma in lineage marker pattern and clinical management.
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Differentiating between distal rectal adenocarcinoma with local spread and primary anal canal tumours is challenging."
    explanation: >-
      This review highlights the diagnostic boundary between colorectal-type
      anal canal adenocarcinoma and distal rectal adenocarcinoma extending into
      the anal canal.
- name: Fistula-Associated Mucinous Type
  display_name: Fistula-associated mucinous adenocarcinoma
  classification: etiologic and histologic
  description: >-
    Mucinous adenocarcinoma arising in a chronic anorectal fistula or perianal
    abscess/fistula tract, including Crohn disease-associated fistula cancers.
  evidence:
  - reference: PMID:37695405
    reference_title: "A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A biopsy taken from the tumor demonstrated mucinous adenocarcinoma; the tumor was diagnosed as FAMC."
    explanation: >-
      This case report directly documents fistula-associated mucinous
      adenocarcinoma as an anal canal adenocarcinoma-related subtype.
environmental:
- name: Chronic anorectal fistula and perianal abscess history
  description: >-
    Persistent anorectal fistula or perianal abscess/fistula inflammation can
    provide the substrate for fistula-associated mucinous adenocarcinoma.
  effect: HARMFUL
  evidence:
  - reference: PMID:37695405
    reference_title: "A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A long-standing (over 10 years) anal fistula is considered a fundamental cause of fistula-associated mucinous adenocarcinoma (FAMC)."
    explanation: >-
      The abstract identifies long-standing anal fistula as a fundamental cause
      of fistula-associated mucinous adenocarcinoma.
- name: Crohn disease-associated anorectal fistula
  description: >-
    Perianal Crohn disease with anorectal fistula can be complicated by
    mucinous anorectal fistula cancer with locally advanced invasion.
  effect: HARMFUL
  evidence:
  - reference: PMID:37962718
    reference_title: "Resection of anorectal fistula cancer associated with Crohn's disease after preoperative chemoradiotherapy: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn's disease, which was curatively resected after preoperative chemoradiotherapy."
    explanation: >-
      This case report supports Crohn disease-associated anorectal fistula as a
      context for locally advanced mucinous adenocarcinoma.
pathophysiology:
- name: Chronic fistula-associated mucinous carcinogenesis
  description: >-
    Recurrent perianal abscess and anal fistula generate a chronic
    inflammatory epithelial tract. Dysplasia within the fistula lining can
    progress to poorly differentiated mucinous adenocarcinoma involving the
    dermis, epidermis, sphincter complex, or adjacent pelvic organs.
  cell_types:
  - preferred_term: fistula tract glandular epithelial cell
    term:
      id: CL:0000066
      label: epithelial cell
  locations:
  - preferred_term: anal canal
    term:
      id: UBERON:0000159
      label: anal canal
  biological_processes:
  - preferred_term: chronic inflammation-driven cell population proliferation
    term:
      id: GO:0008283
      label: cell population proliferation
    modifier: INCREASED
  evidence:
  - reference: PMID:37695405
    reference_title: "A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Histopathology showed highly dysplastic cells lining the lumen of the anal fistula and poorly differentiated mucinous adenocarcinoma proliferating in the dermis and epidermis in the distal aspect of the fistula."
    explanation: >-
      The histopathology links dysplastic fistula lining to proliferating
      mucinous adenocarcinoma in the distal fistula tract.
  downstream:
  - target: Locally advanced pelvic invasion
    description: Fistula-associated mucinous tumors may infiltrate adjacent pelvic structures.
- name: Dualistic HPV-dependent and HPV-independent tumor lineages
  description: >-
    Primary anal canal adenocarcinoma separates into at least two
    region-specific entities. Anal gland/transitional-type tumors can follow an
    HPV-dependent pathway with increased immune checkpoint expression, whereas
    colorectal-type tumors more often follow HPV-independent colorectal-lineage
    molecular programs.
  cell_types:
  - preferred_term: glandular epithelial cell of anal canal
    term:
      id: CL:0000066
      label: epithelial cell
  biological_processes:
  - preferred_term: immune response
    term:
      id: GO:0006955
      label: immune response
    modifier: DYSREGULATED
  - preferred_term: cell surface receptor protein tyrosine kinase signaling pathway
    term:
      id: GO:0007169
      label: cell surface receptor protein tyrosine kinase signaling pathway
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:29700411
    reference_title: "A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities."
    explanation: >-
      The molecular cohort supports two mechanistically distinct entities
      separated by HPV status, immune contexture, checkpoint expression, and
      targetable mutation profile.
    images:
    - Anal_Canal_Adenocarcinoma-deep-research-falcon_artifacts/image-1.png
  downstream:
  - target: PD-1/PD-L1-enriched immune microenvironment
    description: The anal gland/transitional subtype shows greater immune checkpoint expression.
  - target: KRAS/NRAS and PI3K pathway alteration
    description: Targetable gastrointestinal cancer genes vary across subtypes.
- name: PD-1/PD-L1-enriched immune microenvironment
  description: >-
    The anal gland/transitional-type subset has higher PD-1/PD-L1 expression
    and a different tumor-infiltrating lymphocyte profile than colorectal-type
    tumors, creating a biologic rationale for immune-checkpoint-directed
    clinical research while not establishing prospective efficacy for this rare
    tumor.
  cell_types:
  - preferred_term: CD8-positive, alpha-beta T cell
    term:
      id: CL:0000625
      label: CD8-positive, alpha-beta T cell
  - preferred_term: regulatory T cell
    term:
      id: CL:0000815
      label: regulatory T cell
  biological_processes:
  - preferred_term: immune response
    term:
      id: GO:0006955
      label: immune response
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:29700411
    reference_title: "A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligand-receptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa."
    explanation: >-
      This supports an immune-checkpoint-enriched microenvironment in the anal
      gland/transitional subtype relative to colorectal-type tumors.
phenotypes:
- name: Anal pain with palpable tumor
  category: Gastrointestinal
  description: >-
    Anal or perianal pain with a palpable tumor can be a presenting feature,
    especially in fistula-associated mucinous adenocarcinoma.
  phenotype_term:
    preferred_term: anal pain
    term:
      id: HP:0500005
      label: Anal pain
  evidence:
  - reference: PMID:37695405
    reference_title: "A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 68-year-old woman was admitted to our hospital because of progressive anal pain and a palpable tumor."
    explanation: >-
      Case-level evidence directly reports progressive anal pain and palpable
      tumor as presenting manifestations.
- name: Rectal bleeding or serosanguineous anal discharge
  category: Gastrointestinal
  description: >-
    Bleeding or serosanguineous drainage may prompt anorectal examination even
    when prior colorectal screening was normal.
  phenotype_term:
    preferred_term: rectal bleeding
    term:
      id: HP:0002573
      label: Hematochezia
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This case highlights the challenges of early diagnosis of anal malignancies and the importance of prompt evaluation of anorectal area by anoscopy and colonoscopy if symptoms of rectal bleeding or serosanguinous anal discharge are reported."
    explanation: >-
      The review highlights rectal bleeding and serosanguineous discharge as
      symptoms that should trigger prompt anal and rectal evaluation.
- name: Anal stenosis from pelvic mass
  category: Gastrointestinal
  description: >-
    Locally advanced anorectal fistula cancer can present with anal stenosis
    caused by a pelvic mass and may be associated with abdominal pain and
    diarrhea in Crohn disease.
  phenotype_term:
    preferred_term: Anal stenosis
    term:
      id: HP:0002025
      label: Anal stenosis
  evidence:
  - reference: PMID:37962718
    reference_title: "Resection of anorectal fistula cancer associated with Crohn's disease after preoperative chemoradiotherapy: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Computed tomography (CT) showed anal stenosis due to a pelvic mass."
    explanation: >-
      This Crohn-associated anorectal fistula cancer case documents anal
      stenosis secondary to a pelvic mass.
histopathology:
- name: Primary anal canal adenocarcinoma
  finding_term:
    preferred_term: Anal Canal Adenocarcinoma
    term:
      id: NCIT:C7471
      label: Anal Canal Adenocarcinoma
  description: >-
    Primary anal canal adenocarcinoma is a glandular malignancy that requires
    histologic and immunophenotypic distinction from squamous carcinoma and
    from distal rectal adenocarcinoma extending into the anal canal.
  evidence:
  - reference: PMID:29700411
    reference_title: "A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels."
    explanation: >-
      The Herfs cohort explicitly characterizes primary anal glandular neoplasms
      at the histologic level as part of subtype definition.
- name: Mucinous fistula-associated adenocarcinoma
  description: >-
    Fistula-associated tumors can show mucinous adenocarcinoma with dysplastic
    fistula epithelium and dermal or epidermal extension at the distal fistula
    tract.
  evidence:
  - reference: PMID:37695405
    reference_title: "A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Histopathology showed highly dysplastic cells lining the lumen of the anal fistula and poorly differentiated mucinous adenocarcinoma proliferating in the dermis and epidermis in the distal aspect of the fistula."
    explanation: >-
      The case report provides direct histopathologic evidence for mucinous
      fistula-associated adenocarcinoma arising along the fistula tract.
- name: CK7-positive and CK20/CDX2-negative immunophenotype
  description: >-
    CK7-positive, CK20/CDX2-negative staining supports anal gland/transitional
    lineage in some tumors and helps distinguish primary anal adenocarcinoma
    from colorectal-type adenocarcinoma.
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Immunohistological stains were positive for CK7 and negative for CK20, CDX2, SOX-10 consistent with adenocarcinoma."
    explanation: >-
      The case report documents an immunophenotypic pattern used to support an
      anal adenocarcinoma diagnosis.
genetic:
- name: KRAS and NRAS pathway mutation context
  association: Somatic RAS pathway alterations and subtype-specific mutation burden
  variant_origin: SOMATIC
  gene_term:
    preferred_term: KRAS
    term:
      id: hgnc:6407
      label: KRAS
  notes: >-
    Herfs et al. profiled clinically relevant gastrointestinal cancer genes and
    found subtype-specific differences in downstream EGFR signaling effectors,
    including KRAS and NRAS.
  evidence:
  - reference: PMID:29700411
    reference_title: "A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "anal gland/transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS)"
    explanation: >-
      The abstract identifies KRAS and NRAS as subtype-relevant downstream EGFR
      signaling effectors in primary anal canal adenocarcinoma.
- name: MSI-high biomarker in individual case
  association: Rare mismatch-repair-deficient or MSI-high biomarker context
  variant_origin: SOMATIC
  notes: >-
    MSI-high status appears uncommon in the Herfs cohort but was reported in a
    BMJ Open Gastroenterology case treated with pembrolizumab.
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Subsequent tumour profiling demonstrated a high microsatellite instability and was KRAS/NRAS/BRAF wild type."
    explanation: >-
      This case report supports MSI-high as a clinically relevant biomarker in
      at least a subset of anal adenocarcinoma patients.
epidemiology:
- name: United States SEER incidence and demographics
  description: >-
    In SEER data from 1973-2015, anal canal adenocarcinoma was uncommon,
    diagnosed at mean age 68.12 years, and showed a modest male predominance.
  unit: population registry cases
  evidence:
  - reference: PMID:32455011
    reference_title: "Clinicopathologic Features and Outcome of Adenocarcinoma of the Anal Canal: A Population-Based Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The mean age for diagnosis of AA was 68.12 ± 14.02 years. Males outnumbered females by 54.8 to 45.2%."
    explanation: >-
      The SEER-based population study gives age and sex distribution for anal
      canal adenocarcinoma in the United States.
- name: Anal adenocarcinoma proportion among anal cancers
  description: >-
    Anal adenocarcinoma represents a minority of anal cancers, substantially
    less common than anal squamous cell carcinoma.
  unit: percent of anal cancer
  evidence:
  - reference: PMID:32389595
    reference_title: "Survival Outcomes After Initial Treatment for Anal Adenocarcinoma: A Population-Based Cohort Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Anal adenocarcinoma (AA) is reported to represent 5% to 10% of all anal cancer."
    explanation: >-
      The treatment-outcomes cohort frames AA as a rare minority histology among
      anal cancers.
stages:
- name: SEER stage distribution at diagnosis
  description: >-
    SEER data show that localized disease is the most common presentation, with
    substantial regional and distant disease at diagnosis.
  evidence:
  - reference: PMID:32455011
    reference_title: "Clinicopathologic Features and Outcome of Adenocarcinoma of the Anal Canal: A Population-Based Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Tumors were mostly localized on presentation (44.4%) and moderately differentiated (41.1%)."
    explanation: >-
      This supports localized disease as the most common SEER presentation and
      provides tumor grade context.
diagnosis:
- name: Biopsy with histopathology and immunohistochemistry
  description: >-
    Diagnosis requires tissue confirmation of adenocarcinoma and careful
    pathologic distinction from distal rectal adenocarcinoma, including CK7,
    CK20, CDX2, and other immunohistochemical markers when clinically needed.
  diagnosis_term:
    preferred_term: Biopsy Procedure
    term:
      id: NCIT:C15189
      label: Biopsy Procedure
  results: Invasive anal canal adenocarcinoma histology and subtype classification.
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Immunohistological stains were positive for CK7 and negative for CK20, CDX2, SOX-10 consistent with adenocarcinoma."
    explanation: >-
      The case report illustrates immunohistochemical workup used to support
      anal adenocarcinoma diagnosis.
  - reference: PMID:29700411
    reference_title: "A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels."
    explanation: >-
      Herfs et al. support integrated histologic, immunologic, genomic, and
      epidemiologic characterization of anal glandular neoplasms.
- name: Staging imaging for local and metastatic disease
  description: >-
    Cross-sectional imaging and PET can identify pelvic lymphadenopathy, local
    rectal/anal extension, and distant lesions during staging.
  diagnosis_term:
    preferred_term: Imaging Procedure
    term:
      id: NCIT:C17369
      label: Imaging Procedure
  results: Local extent, nodal involvement, and distant metastasis assessment.
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "PET scan revealed hypermetabolic uptake at the rectum extending to the anal verge, gluteal fold, posterior scrotal sac, lymphadenopathy in the abdomen and pelvis from the iliac chain to external femoral nodes, and a hepatic lesion suspicious for metastatic disease."
    explanation: >-
      This case demonstrates PET-based staging of local extension, nodal
      disease, and suspected distant metastasis.
treatments:
- name: Surgery for localized or resectable disease
  description: >-
    Surgical resection is a major component of treatment for resectable anal
    canal adenocarcinoma and is associated with improved survival in SEER
    analyses.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence:
  - reference: PMID:32455011
    reference_title: "Clinicopathologic Features and Outcome of Adenocarcinoma of the Anal Canal: A Population-Based Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Surgical intervention improved survival significantly as compared to patients who did not (116.7 months vs 42.7 months, p < 0.01)."
    explanation: >-
      Population-based SEER analysis supports a survival association with
      surgery for anal canal adenocarcinoma.
- name: Preoperative chemoradiation with surgical resection
  description: >-
    For stage I-III anal adenocarcinoma, retrospective SEER data suggest that
    preoperative radiation or chemotherapy followed by surgery may maximize
    survival, especially for more advanced localized disease.
  treatment_term:
    preferred_term: Chemoradiotherapy
    term:
      id: NCIT:C94626
      label: Chemoradiotherapy
  evidence:
  - reference: PMID:32389595
    reference_title: "Survival Outcomes After Initial Treatment for Anal Adenocarcinoma: A Population-Based Cohort Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Preoperative treatment with surgical resection may maximize the survival outcome."
    explanation: >-
      The SEER stage I-III treatment study concludes that preoperative
      treatment with surgery may maximize survival.
  - reference: PMID:32389595
    reference_title: "Survival Outcomes After Initial Treatment for Anal Adenocarcinoma: A Population-Based Cohort Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although chemoradiotherapy alone may be sufficient for early stages of disease, patients with advanced disease should be treated with a combination of surgical resection and chemoradiotherapy."
    explanation: >-
      This supports combined surgery and chemoradiotherapy for advanced
      non-metastatic disease, while acknowledging possible sufficiency of
      chemoradiotherapy alone in early stages.
- name: Pembrolizumab for MSI-high disease
  description: >-
    Pembrolizumab is a biomarker-driven treatment consideration for MSI-high
    anal adenocarcinoma, but the direct disease-specific evidence is limited to
    case-level observation in the retrieved literature.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: pembrolizumab
      term:
        id: NCIT:C106432
        label: Pembrolizumab
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Over a year after diagnosis, the patient is alive and managed with pembrolizumab."
    explanation: >-
      This single MSI-high case provides partial, case-level support for
      pembrolizumab in biomarker-selected anal adenocarcinoma.
clinical_trials:
- name: NCT05605873
  phase: NOT_APPLICABLE
  status: COMPLETED
  description: >-
    Retrospective French cohort study designed to classify clinical,
    histologic, etiologic, and prognostic forms of adenocarcinoma of the anus.
  evidence:
  - reference: clinicaltrials:NCT05605873
    supports: SUPPORT
    snippet: "Adenocarcinoma of the anus is rare. It concerns less than 10% of anal cancers and its incidence is less than 0.2/100 000 inhabitants."
    explanation: >-
      The ClinicalTrials.gov summary supports rarity and the rationale for
      studying clinical, histologic, and prognostic forms.
progression:
- phase: Poor overall prognosis
  notes: >-
    Anal adenocarcinoma has worse survival than rectal adenocarcinoma and anal
    squamous cell carcinoma in comparative SEER analysis.
  evidence:
  - reference: PMID:34244243
    reference_title: "Anal adenocarcinoma: case report, literature review and comparative survival analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Survival analysis showed that anal adenocarcinoma is associated with worse outcomes compared with rectal adenocarcinoma and anal squamous cell carcinoma."
    explanation: >-
      Comparative SEER survival analysis supports worse outcomes for anal
      adenocarcinoma than the two major comparator malignancies.
- phase: Stage- and surgery-associated survival differences
  notes: >-
    Survival is better for localized and well-differentiated tumors and is
    improved among surgically treated patients in a SEER population-based study.
  evidence:
  - reference: PMID:32455011
    reference_title: "Clinicopathologic Features and Outcome of Adenocarcinoma of the Anal Canal: A Population-Based Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with localized disease and well-differentiated tumors showed better survival outcomes."
    explanation: >-
      This population-based analysis supports stage and differentiation as
      clinically relevant prognostic factors.
- phase: Bimodal poor survival pattern
  notes: >-
    SEER analysis reported poor cancer-free survival in younger and older
    patient groups, reinforcing that this rare histology has clinically
    important prognosis across age strata.
  evidence:
  - reference: PMID:32455011
    reference_title: "Clinicopathologic Features and Outcome of Adenocarcinoma of the Anal Canal: A Population-Based Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Anal canal adenocarcinoma demonstrated a poor bimodal cancer-free survival in both younger and older patient groups."
    explanation: >-
      The SEER cohort conclusion supports a poor bimodal cancer-free survival
      pattern in both younger and older patients.

📚

References & Deep Research

Deep Research

1

Falcon ▸

1. Disease Information

Edison Scientific Literature 23 citations 2026-05-14T14:42:27.745702

1. Disease Information

Overview (definition; current understanding)

Anal canal adenocarcinoma is a rare malignant epithelial tumor with gland-forming histology arising in the anal canal region and/or adjacent transitional zone, with heterogeneous biology and clinical behavior. Registry-based studies emphasize its rarity and historically limited evidence base for guidelines. (gogna2020clinicopathologicfeaturesand pages 1-2, park2020survivaloutcomesafter pages 1-2)

Key identifiers and coding (available from retrieved sources)

SEER-based studies identify anal canal adenocarcinoma using ICD-O-3 site codes for the anal canal region—C21.0 (anus, NOS), C21.1 (anal canal), C21.2 (cloacogenic zone)—and exclude “overlapping lesion of rectum, anus and anal canal” (C21.8) to avoid misclassification with rectal primaries. (gogna2020clinicopathologicfeaturesand pages 2-3)

Synonyms / alternative names (from literature)

Anal adenocarcinoma (used interchangeably in case series and registry studies) (tsay2021analadenocarcinomacase pages 2-3, park2020survivaloutcomesafter pages 1-2)
Fistula-associated mucinous adenocarcinoma (subset arising in chronic anorectal fistula tracts) (koizumi2023acasereport pages 1-3, inoue2023resectionofanorectal pages 1-3)
Extramucosal anal adenocarcinoma (from anal glands or fistulae) vs colorectal-type (above dentate line) (tsay2021analadenocarcinomacase pages 2-3)

Evidence source type

Most available evidence is aggregated (SEER population registry) and case-based/observational literature due to rarity; prospective randomized data are minimal. (gogna2020clinicopathologicfeaturesand pages 1-2, park2020survivaloutcomesafter pages 1-2, NCT05605873 chunk 1)

2. Etiology

Disease causal factors / mechanistic contexts

Anal canal adenocarcinoma is etiologically heterogeneous and can arise through distinct pathways depending on subtype.

Chronic inflammation and fistula-associated carcinogenesis (mucinous subtype) - A 2023 fistula-associated mucinous adenocarcinoma case report states: “Chronic inflammation in organs is one of the causes of cancer development and proliferation.” (Koizumi et al., Surgical Case Reports, published 2023-09; https://doi.org/10.1186/s40792-023-01743-3). (koizumi2023acasereport pages 1-3) - The same report emphasizes that “A long-standing (over 10 years) anal fistula is considered an etiology of fistula-associated mucinous adenocarcinoma (FAMC)” and notes that malignant transformation may occur faster than expected: “FAMC can develop within fewer than 3 years after the development of a perianal abscess and anal fistula.” (koizumi2023acasereport pages 1-3)

Crohn’s disease and anorectal fistula cancer context A 2023 Crohn’s disease-associated case report highlights diagnostic difficulty and late presentation in anorectal fistula cancers, commonly mucinous histology, and reports that symptom changes (mucus discharge, bleeding, stricture) often trigger diagnosis. (Inoue et al., Surgical Case Reports, published 2023-11; https://doi.org/10.1186/s40792-023-01778-6). (inoue2023resectionofanorectal pages 1-3)

Infectious agents (HPV) and current evidence

Evidence for HPV differs by subtype: - A 2021 literature review/case report states that, unlike anal squamous cell carcinoma, “no such association with anal adenocarcinoma has been established” for HPV. (Tsay et al., BMJ Open Gastroenterology, 2021-07; https://doi.org/10.1136/bmjgast-2021-000661). (tsay2021analadenocarcinomacase pages 2-3) - In contrast, molecular profiling of primary anal canal adenocarcinoma supports HPV-dependent and HPV-independent pathways and reports HPV16/18 restricted to an anal gland/transitional-type subset (see Molecular section). (herfs2018adualisticmodel pages 1-2, herfs2018adualisticmodel pages 8-9)

Risk factors (human clinical evidence)

Immunosuppression, perianal Crohn’s disease, and older age are proposed/recognized risk factors, though “poorly studied” due to small sample sizes. (tsay2021analadenocarcinomacase pages 2-3)
Chronic anal fistula / perianal abscess → fistula-associated mucinous adenocarcinoma is supported by case-based evidence and recognized as an etiologic substrate in reviews of extramucosal tumors. (koizumi2023acasereport pages 1-3, tsay2021analadenocarcinomacase pages 2-3, inoue2023resectionofanorectal pages 1-3)

Protective factors / gene–environment interactions

No protective factors or gene–environment interaction evidence specific to anal canal adenocarcinoma were retrievable in the current corpus.

3. Phenotypes

Common clinical presentation (symptoms/signs)

Case reports and fistula-associated cancer reports describe symptomatic presentation including: - Anal pain and palpable perianal/anal mass (koizumi2023acasereport pages 1-3) - Mucus discharge, anal bleeding, and stricturing/stenosis in fistula-cancer contexts (inoue2023resectionofanorectal pages 1-3) - Perianal nodules/papules and chronic anal drainage in an anal adenocarcinoma case report (tsay2021analadenocarcinomacase pages 1-1)

Stage at presentation / temporal development

In a SEER population analysis (1973–2015), anal canal adenocarcinoma presented as: - In situ 6.7%, localized 44.4%, regional 25.8%, distant 13.5% (gogna2020clinicopathologicfeaturesand pages 1-2) This distribution supports a substantial proportion diagnosed beyond localized disease, consistent with diagnostic delay in fistula-associated forms. (inoue2023resectionofanorectal pages 1-3)

Phenotype characteristics and frequencies

Beyond SEER stage distributions, robust phenotype frequency estimates (e.g., percent with bleeding/pain) were not available in retrieved texts.

Suggested HPO terms (non-exhaustive)

Anal pain — HP:0002043 (mapping suggestion; not validated from retrieved text)
Hematochezia/rectal bleeding — HP:0002240 (mapping suggestion)
Tenesmus — HP:0031052 (mapping suggestion)
Anal fistula — HP:0001930 (mapping suggestion)
Anal mass — could map to HP:0031976 (mass) with anatomic qualifier (mapping suggestion)

Quality of life impact

Crohn’s-related perianal disease and fistulizing disease is described as disabling with significant quality-of-life impairment in contemporary reviews of perianal IBD, but disease-specific QoL quantification for anal adenocarcinoma itself was not retrievable. (inoue2023resectionofanorectal pages 1-3)

4. Genetic / Molecular Information

Molecular subtypes and lineage markers (primary human tumor profiling)

A multi-institutional cohort study (n=74 primary anal canal adenocarcinomas) supports a dualistic model with two region-specific entities: - Anal gland/transitional-type: 26/74 (35.1%), characterized by diffuse Krt7 expression and absence of Krt20/CDX2 (herfs2018adualisticmodel pages 4-5) - Colorectal-type: 48/74 (64.9%), characterized by Krt20/CDX2 positivity and not Krt7 (herfs2018adualisticmodel pages 4-5)

HPV status and p16INK4a

HPV16/18 infection was detected in an anal gland/transitional subset: 11/26 (42.3%) (herfs2018adualisticmodel pages 8-9)
Among HPV-infected tumors, 5/11 (45.5%) had patches of p16 negativity and some showed CDKN2A promoter hypermethylation (herfs2018adualisticmodel pages 9-10, herfs2018adualisticmodel pages 8-9)

Mismatch repair deficiency / MSI

Mismatch repair deficiency/MSI-high appears rare in this tumor type: 1/74 (1.4%) MSI-high reported in the dualistic cohort. (herfs2018adualisticmodel pages 8-9)

Immune microenvironment and checkpoints

Anal gland/transitional-type tumors show greater immune infiltration and higher checkpoint expression; the study highlights higher PD-1/PD-L1 expression and T-cell infiltration relative to colorectal-type tumors. Visual summary of immune-marker differences (PD-L1 tumor cell scoring; PD-1+ immune infiltration) is provided in the retrieved figures. (herfs2018adualisticmodel pages 9-10, herfs2018adualisticmodel media 4416b428)

Actionable alterations and pathway context

In the 74-case dualistic cohort: - EGFR protein detected by IHC in 64/74 (86.5%) tumors (herfs2018adualisticmodel pages 7-8) - Somatic mutation frequencies included KRAS 47.1%, NRAS 5.9%, PIK3CA 7.6%, PTEN 2.9%, BRAF 1.5%; EGFR, HER2, KIT, PDGFRA, DDR2 mutations were absent in this dataset (herfs2018adualisticmodel pages 7-8) - The subtype comparison and mutation landscape are summarized visually in retrieved figures (heatmap and prevalence plots). (herfs2018adualisticmodel media 502e33fe)

Example case molecular features

A 2021 case report described MSI-high status and KRAS/NRAS/BRAF wild type tumor profiling in an individual patient. (tsay2021analadenocarcinomacase pages 1-2)

Suggested gene/pathway ontologies

HGNC gene symbols: KRAS, NRAS, PIK3CA, PTEN, BRAF, EGFR, CDKN2A (herfs2018adualisticmodel pages 7-8, herfs2018adualisticmodel pages 8-9)
Suggested GO biological process terms (mapping suggestions):
GO:0008285 negative regulation of cell proliferation (cancer hallmark)
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway (EGFR axis)
GO:0045087 innate immune response / GO:0006955 immune response (immune infiltration/checkpoints)

Suggested CL (cell types) for mechanism annotation (mapping suggestions)

CD8+ T cell — CL:0000625 (supported conceptually by T-cell infiltration measures) (herfs2018adualisticmodel pages 9-10)
Regulatory T cell (Foxp3+) — CL:0000815 (herfs2018adualisticmodel pages 9-10)
Epithelial cell (glandular) — CL:0000066 (tumor origin) (herfs2018adualisticmodel pages 4-5)

5. Environmental Information

Direct environmental toxin/radiation/lifestyle risk factor quantification specific to anal canal adenocarcinoma was not retrievable in the current corpus. The most consistently described non-genetic drivers relate to chronic inflammation (fistula, IBD) rather than classic environmental exposures. (koizumi2023acasereport pages 1-3, inoue2023resectionofanorectal pages 1-3)

6. Mechanism / Pathophysiology

Causal chains (current evidence-supported models)

Pathway A: Chronic fistula/inflammation → mucinous adenocarcinoma Perianal abscess and fistula represent chronic infectious/inflammatory processes; persistent inflammation and epithelial dysplasia within fistula tracts can progress to mucinous adenocarcinoma, often recognized only after symptom change or mass formation. (koizumi2023acasereport pages 1-3, inoue2023resectionofanorectal pages 1-3)

Pathway B: Dualistic anal canal adenocarcinoma model (HPV-dependent vs independent) Primary anal canal adenocarcinoma comprises at least two lineages with distinct etiologies and immune/mutational features. Anal gland/transitional tumors can be HPV16/18-associated and show increased PD-1/PD-L1 and T-cell infiltration, while colorectal-type tumors more closely resemble colorectal mucosal cancers and show different mutation patterns. (herfs2018adualisticmodel pages 1-2, herfs2018adualisticmodel pages 8-9)

Upstream vs downstream processes

Upstream: chronic inflammation (fistula/IBD), HPV infection in a subset (koizumi2023acasereport pages 1-3, herfs2018adualisticmodel pages 8-9)
Downstream: oncogenic signaling alterations (KRAS/PI3K axis), immune evasion via PD-1/PD-L1, invasion and metastatic spread (herfs2018adualisticmodel pages 7-8, herfs2018adualisticmodel media 4416b428)

7. Anatomical Structures Affected

Primary site

Anal canal / cloacogenic/transitional zone region (ICD-O-3 C21.1/C21.2 context; anal canal strict localization in molecular cohort) (gogna2020clinicopathologicfeaturesand pages 2-3, herfs2018adualisticmodel pages 7-8)

Suggested UBERON terms (mapping suggestions)

Anal canal — UBERON:0001052 (mapping suggestion)
Anus — UBERON:0001245 (mapping suggestion)
Rectum (lower rectum interface) — UBERON:0001052? (rectum has separate UBERON ID; mapping suggestion)

Local invasion patterns (case evidence)

Advanced fistula-associated tumors may infiltrate adjacent pelvic structures (e.g., prostate/levator ani/internal obturator described in Crohn’s-associated fistula cancer report). (inoue2023resectionofanorectal pages 1-3)

8. Temporal Development

Typical age of onset

Mean age at diagnosis in a SEER analysis was 68.12 ± 14.02 years. (gogna2020clinicopathologicfeaturesand pages 1-2)

Course/progression patterns

Fistula-associated cancers can emerge after long-standing disease (>10 years) but may also develop within a few years after perianal abscess/fistula in some cases, emphasizing variable latency. (koizumi2023acasereport pages 1-3)

9. Inheritance and Population

Epidemiology (registry-based)

A SEER population-based study (1973–2015; n=2,090) reports: - Estimated prevalence 0.0011% (gogna2020clinicopathologicfeaturesand pages 1-2) - Incidence trend: +4.03%/year (1973–1985) followed by −0.32%/year (1986–2015) (gogna2020clinicopathologicfeaturesand pages 2-3) - Sex distribution: 54.8% male, 45.2% female (gogna2020clinicopathologicfeaturesand pages 1-2)

No Mendelian inheritance pattern is established; this is primarily a sporadic malignancy with somatic alterations and inflammatory/viral etiologies in subsets. (herfs2018adualisticmodel pages 1-2, herfs2018adualisticmodel pages 7-8)

10. Diagnostics

Clinical and pathology diagnosis

Diagnosis typically relies on anorectal exam, endoscopic evaluation, and biopsy with histopathology and immunohistochemistry to distinguish anal gland/transitional vs colorectal-type tumors.

Histopathology / IHC (subtype assignment) - The dualistic model uses keratin/CDX2 patterns: Krt7 (anal gland/transitional) vs Krt20/CDX2 (colorectal-type). (herfs2018adualisticmodel pages 4-5)

Imaging Case reports use cross-sectional imaging and/or PET for staging and metastatic evaluation. (tsay2021analadenocarcinomacase pages 1-1)

Molecular testing Somatic profiling may include KRAS/NRAS/BRAF testing and MSI/MMR assessment (MSI-high is rare but clinically actionable for immunotherapy in many GI cancers). (tsay2021analadenocarcinomacase pages 1-2, herfs2018adualisticmodel pages 8-9)

Differential diagnosis

A recurring challenge is distinguishing primary anal canal adenocarcinoma from distal rectal adenocarcinoma extending into the anal canal and from fistula-associated extramucosal lesions. (tsay2021analadenocarcinomacase pages 2-3)

11. Outcome / Prognosis

Survival statistics (SEER population data)

In SEER (n=2,090), overall survival at: - 1 year 76.1%, 2 years 63.4%, 3 years 52.6%, 4 years 47.9%, 5 years 39.6% (gogna2020clinicopathologicfeaturesand pages 2-3) Prognosis varies strongly by stage and grade; metastatic disease showed markedly higher mortality (HR ~6). (gogna2020clinicopathologicfeaturesand pages 2-3)

Prognostic factors

Older age strongly predicts worse survival (e.g., age >81 mean survival 30.14 ± 1.84 months, HR 3.79). (gogna2020clinicopathologicfeaturesand pages 2-3)
Localized disease is associated with better survival than distant disease. (gogna2020clinicopathologicfeaturesand pages 2-3)
In the dualistic molecular cohort, anal gland/transitional-type tumors tended toward worse 5-year DFS/OS than colorectal-type tumors (5-year OS 27.8% vs 50.4%). (herfs2018adualisticmodel pages 7-8)

12. Treatment

Current applications / real-world implementations (population-based evidence)

Because of limited disease-specific guidelines, management often extrapolates from rectal adenocarcinoma paradigms and/or multimodality strategies.

Surgery In a SEER analysis, surgery was associated with longer survival (116.7 months vs 42.7 months, p<0.01). (gogna2020clinicopathologicfeaturesand pages 1-2)

Chemoradiation and combined modality In a SEER cohort of stage I–III patients (2010–2016; n=393), 3-year cause-specific survival differed by initial approach: - RT+CTx 63.9% - RT or CTx 35.7% - Surgery alone 77.7% - Preoperative RT/CTx + surgery 80.3% - Postoperative RT/CTx + surgery 65.8% (P<.001). (Park 2020; https://doi.org/10.1016/j.clcc.2020.04.001). (park2020survivaloutcomesafter pages 1-2) Preoperative RT/CTx plus surgery remained associated with improved cause-specific survival (multivariable P=0.024). (park2020survivaloutcomesafter pages 1-2)

Immunotherapy (evidence level: case-based; biomarker-driven) A 2021 case report described pembrolizumab use in an MSI-high anal adenocarcinoma patient with >1-year survival in follow-up narrative. (tsay2021analadenocarcinomacase pages 1-2) For anal adenocarcinoma overall, immune checkpoint relevance is biologically supported by elevated PD-1/PD-L1 in anal gland/transitional tumors, but prospective efficacy data are not established in the retrieved corpus. (herfs2018adualisticmodel pages 9-10, herfs2018adualisticmodel media 4416b428)

Ongoing / recent clinical research (clinicaltrials.gov)

NCT05605873 (ProCHADA): Retrospective observational cohort (France), enrollment 46; aims to classify forms of anal adenocarcinoma and estimate prognosis; endpoints include 1-year and 5-year mortality; start date 2022-09-16, estimated completion 2023-12-31. (ClinicalTrials.gov record). (NCT05605873 chunk 1)

Suggested MAXO terms (mapping suggestions)

Abdominoperineal resection — MAXO:0000445 (mapping suggestion)
Chemoradiotherapy — MAXO:0000602 (mapping suggestion)
External beam radiotherapy — MAXO:0000014 (mapping suggestion)
Immune checkpoint inhibitor therapy — MAXO:0001025 (mapping suggestion)

13. Prevention

Evidence specific to adenocarcinoma prevention is limited in retrieved sources. - For fistula-associated cancers, case literature suggests heightened clinical suspicion and early biopsy when chronic fistula symptoms change or masses develop, as delayed diagnosis contributes to advanced presentation. (koizumi2023acasereport pages 1-3, inoue2023resectionofanorectal pages 1-3) - HPV vaccination and anal cancer screening guidelines are largely developed for anal squamous cell carcinoma risk contexts and cannot be directly assumed for adenocarcinoma, especially given mixed HPV evidence by subtype. (tsay2021analadenocarcinomacase pages 2-3, herfs2018adualisticmodel pages 8-9)

14. Other Species / Natural Disease

No directly analogous naturally occurring non-human disease models of anal canal adenocarcinoma were identified in the retrieved evidence. A canine condition, apocrine gland anal sac adenocarcinoma, is anatomically and biologically distinct (anal sac origin) and should not be treated as a direct model for human anal canal adenocarcinoma. (gogna2020clinicopathologicfeaturesand pages 1-2)

15. Model Organisms

No validated, disease-specific model organism systems (mouse, zebrafish, organoid platforms uniquely representing anal canal adenocarcinoma subtypes) were retrieved from the current corpus.

Key quantitative evidence map

The table below compiles the most actionable numeric findings for knowledge-base fields (epidemiology, stage distribution, survival, subtype proportions, HPV/MMR, and mutation frequencies).

Domain	Key finding (with numbers)	Population/cohort	Study (first author year)	Publication date	URL/DOI	Evidence citation ID
Epidemiology	Estimated prevalence in SEER: 0.0011%; incidence increased 4.03%/year (1973-1985), then declined 0.32%/year (1986-2015)	2,090 anal canal adenocarcinoma cases from SEER (1973-2015)	Gogna 2020	2020-05-13	https://doi.org/10.1155/2020/5139236	(gogna2020clinicopathologicfeaturesand pages 1-2, gogna2020clinicopathologicfeaturesand pages 2-3)
Epidemiology	Mean age at diagnosis 68.12 ± 14.02 years; 54.8% male; presentation: 44.4% localized, 25.8% regional, 13.5% distant, 6.7% in situ	2,090 SEER cases	Gogna 2020	2020-05-13	https://doi.org/10.1155/2020/5139236	(gogna2020clinicopathologicfeaturesand pages 1-2, gogna2020clinicopathologicfeaturesand pages 2-3)
Survival	Overall survival rates at 1, 2, 3, 4, 5 years: 76.1%, 63.4%, 52.6%, 47.9%, 39.6%	2,090 SEER cases	Gogna 2020	2020-05-13	https://doi.org/10.1155/2020/5139236	(gogna2020clinicopathologicfeaturesand pages 2-3)
Survival	Surgery associated with markedly longer survival: 116.7 months vs 42.7 months without surgery (p < 0.01)	2,090 SEER cases	Gogna 2020	2020-05-13	https://doi.org/10.1155/2020/5139236	(gogna2020clinicopathologicfeaturesand pages 1-2)
Survival	Age >81 years associated with poorer outcome: mean survival 30.14 ± 1.84 months; HR 3.79 (95% CI 2.65-5.41)	2,090 SEER cases	Gogna 2020	2020-05-13	https://doi.org/10.1155/2020/5139236	(gogna2020clinicopathologicfeaturesand pages 2-3)
Survival	Metastatic disease associated with ~6-fold higher mortality: HR 6.02 (95% CI 4.55-7.99)	2,090 SEER cases	Gogna 2020	2020-05-13	https://doi.org/10.1155/2020/5139236	(gogna2020clinicopathologicfeaturesand pages 2-3)
Treatment	3-year cause-specific survival by initial treatment: 63.9% (RT+CTx), 35.7% (RT or CTx), 77.7% (surgery alone), 80.3% (preop RT/CTx + surgery), 65.8% (postop RT/CTx + surgery); P < .001	393 stage I-III cases in SEER (2010-2016)	Park 2020	2020-09	https://doi.org/10.1016/j.clcc.2020.04.001	(park2020survivaloutcomesafter pages 1-2)
Treatment	Preoperative RT/CTx plus surgery associated with improved cause-specific survival on multivariable analysis (P = .024)	393 stage I-III SEER cases	Park 2020	2020-09	https://doi.org/10.1016/j.clcc.2020.04.001	(park2020survivaloutcomesafter pages 1-2)
Molecular subtype	Two subtypes identified: anal gland/transitional-type 26/74 (35.1%) vs colorectal-type 48/74 (64.9%)	74 primary anal canal adenocarcinomas	Herfs 2018	2018	Not available in retrieved metadata	(herfs2018adualisticmodel pages 4-5)
HPV/MMR	HPV16/18 detected only in anal gland/transitional tumors: 11/26 (42.3%); p16 strong/diffuse staining in 12/26 (46.2%) Krt7-positive tumors	74 tumors; subtype analysis within 26 gland/transitional tumors	Herfs 2018	2018	Not available in retrieved metadata	(herfs2018adualisticmodel pages 8-9, herfs2018adualisticmodel pages 4-5)
HPV/MMR	Among HPV-infected tumors, 5/11 (45.5%) showed patches of p16 negativity; MSI-high/MMR-deficient phenotype observed in only 1/74 (1.4%) tumors	74 tumors	Herfs 2018	2018	Not available in retrieved metadata	(herfs2018adualisticmodel pages 9-10, herfs2018adualisticmodel pages 8-9)
Mutations	EGFR protein detected in 64/74 (86.5%) cancers	74 tumors	Herfs 2018	2018	Not available in retrieved metadata	(herfs2018adualisticmodel pages 9-10, herfs2018adualisticmodel pages 7-8)
Mutations	Mutation frequencies: KRAS 47.1%, NRAS 5.9%, PIK3CA 7.6%, PTEN 2.9%, BRAF 1.5%; EGFR, HER2, KIT, PDGFRA, DDR2 mutations absent	74 tumors	Herfs 2018	2018	Not available in retrieved metadata	(herfs2018adualisticmodel pages 7-8, herfs2018adualisticmodel media 502e33fe)
Immune microenvironment	Anal gland/transitional-type tumors showed higher PD-1/PD-L1 expression and more prominent T-cell infiltration than colorectal-type counterparts	74 tumors	Herfs 2018	2018	Not available in retrieved metadata	(herfs2018adualisticmodel pages 9-10, herfs2018adualisticmodel pages 1-2, herfs2018adualisticmodel media 4416b428)
Prognosis by subtype	In survival subset, 65/74 (87.8%) evaluable; 9/74 (12.2%) metastatic at diagnosis; recurrence 10/24 (41.7%) in anal gland/transitional vs 13/41 (31.7%) in colorectal-type; 5-year DFS 33.1% vs 52.6% and 5-year OS 27.8% vs 50.4%	65 evaluable for OS/DFS within a 74-case cohort	Herfs 2018	2018	Not available in retrieved metadata	(herfs2018adualisticmodel pages 7-8)
Comparative prognosis	Anal adenocarcinoma represented 5%-10% of anal canal malignancies and had worse prognosis than rectal adenocarcinoma and anal squamous carcinoma in comparative SEER analysis	SEER comparative cohort; anal adenocarcinoma subset noted as 1,660 in excerpted review	Tsay 2021	2021-07	https://doi.org/10.1136/bmjgast-2021-000661	(tsay2021analadenocarcinomacase pages 2-3, tsay2021analadenocarcinomacase pages 1-1)

Table: This table compiles key numeric findings for anal canal adenocarcinoma across epidemiology, survival, molecular subtype, HPV/MMR status, mutations, and treatment outcomes. It is useful as a quick-reference evidence map for populating structured disease knowledge base fields.

Visual evidence (molecular landscape)

Figures from the dualistic model cohort summarize mutation prevalence by subtype and PD-1/PD-L1/T-cell infiltration patterns. - Mutation/subtype overview: (herfs2018adualisticmodel media 502e33fe) - PD-L1 and immune infiltration overview: (herfs2018adualisticmodel media 4416b428)

Expert synthesis and analysis (authoritative interpretation)

Anal canal adenocarcinoma is not a single entity: evidence supports at least two biologically distinct subtypes (anal gland/transitional vs colorectal-type) with different HPV associations, immune contexture, and mutational landscapes, which implies that “one-size-fits-all” extrapolation from rectal adenocarcinoma or anal squamous carcinoma is likely suboptimal. (herfs2018adualisticmodel pages 1-2, herfs2018adualisticmodel pages 4-5)
Inflammation-associated disease contexts (Crohn’s/fistula) are clinically important for a subset of tumors (often mucinous), with notable diagnostic delay; surveillance strategies for high-risk fistulizing disease remain an evidence gap requiring prospective evaluation. (koizumi2023acasereport pages 1-3, inoue2023resectionofanorectal pages 1-3)
Precision oncology opportunities exist but are constrained by KRAS prevalence (~47% in one cohort), which may limit anti-EGFR strategies in many patients; conversely, PD-1/PD-L1–high immune phenotypes in anal gland/transitional tumors provide a biologic rationale for immunotherapy trials, though MSI-high appears rare (~1.4%). (herfs2018adualisticmodel pages 7-8, herfs2018adualisticmodel pages 8-9, herfs2018adualisticmodel media 4416b428)

Limitations of this report (evidence availability)

Ontology identifiers (MONDO/MeSH/ICD-10/ICD-11/Orphanet) were not retrievable using available tools and texts; only ICD-O-3 site codes used in SEER studies are provided. (gogna2020clinicopathologicfeaturesand pages 2-3)
Most adenocarcinoma-specific clinical guidance is based on retrospective cohorts and case reports; several potentially relevant 2024 adenocarcinoma studies were listed as unobtainable in tool search results and thus could not be cited.

References

(gogna2020clinicopathologicfeaturesand pages 2-3): Shekhar Gogna, Roberto Bergamaschi, Agon Kajmolli, Mahir Gachabayov, Aram Rojas, David Samson, Rifat Latifi, and Xiang Da Dong. Clinicopathologic features and outcome of adenocarcinoma of the anal canal: a population-based study. International Journal of Surgical Oncology, 2020:1-6, May 2020. URL: https://doi.org/10.1155/2020/5139236, doi:10.1155/2020/5139236. This article has 7 citations.
(gogna2020clinicopathologicfeaturesand pages 1-2): Shekhar Gogna, Roberto Bergamaschi, Agon Kajmolli, Mahir Gachabayov, Aram Rojas, David Samson, Rifat Latifi, and Xiang Da Dong. Clinicopathologic features and outcome of adenocarcinoma of the anal canal: a population-based study. International Journal of Surgical Oncology, 2020:1-6, May 2020. URL: https://doi.org/10.1155/2020/5139236, doi:10.1155/2020/5139236. This article has 7 citations.
(park2020survivaloutcomesafter pages 1-2): Hyojung Park. Survival outcomes after initial treatment for anal adenocarcinoma: a population-based cohort study. Clinical Colorectal Cancer, 19:e75-e82, Sep 2020. URL: https://doi.org/10.1016/j.clcc.2020.04.001, doi:10.1016/j.clcc.2020.04.001. This article has 6 citations and is from a peer-reviewed journal.
(tsay2021analadenocarcinomacase pages 2-3): Cynthia J Tsay, Thomas Pointer, Jocelyn B Chandler, Anil B Nagar, and Petr Protiva. Anal adenocarcinoma: case report, literature review and comparative survival analysis. BMJ Open Gastroenterology, 8:e000661, Jul 2021. URL: https://doi.org/10.1136/bmjgast-2021-000661, doi:10.1136/bmjgast-2021-000661. This article has 6 citations and is from a peer-reviewed journal.
(koizumi2023acasereport pages 1-3): Michihiro Koizumi, Akihisa Matsuda, Takeshi Yamada, Koji Morimoto, Itaru Kubota, Yawara Kubota, Shuzo Tamura, Kenta Tominaga, Takashi Sakatani, and Hiroshi Yoshida. A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess. Surgical Case Reports, Sep 2023. URL: https://doi.org/10.1186/s40792-023-01743-3, doi:10.1186/s40792-023-01743-3. This article has 15 citations.
(inoue2023resectionofanorectal pages 1-3): Takuya Inoue, Yuki Sekido, Takayuki Ogino, Tsuyoshi Hata, Norikatsu Miyoshi, Hidekazu Takahashi, Mamoru Uemura, Tsunekazu Mizushima, Yuichiro Doki, and Hidetoshi Eguchi. Resection of anorectal fistula cancer associated with crohn’s disease after preoperative chemoradiotherapy: a case report. Surgical Case Reports, Nov 2023. URL: https://doi.org/10.1186/s40792-023-01778-6, doi:10.1186/s40792-023-01778-6. This article has 10 citations.
(NCT05605873 chunk 1): Clinical, Histological and Prognostic Forms of Adenocarcinoma of the Anus. Fondation Hôpital Saint-Joseph. 2022. ClinicalTrials.gov Identifier: NCT05605873
(herfs2018adualisticmodel pages 1-2): M Herfs, P Roncarati, B Koopmansch, O Peulen, D Bruyere, A Lebeau, E Hendrick, and P Hubert. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures …. Unknown journal, 2018.
(herfs2018adualisticmodel pages 8-9): M Herfs, P Roncarati, B Koopmansch, O Peulen, D Bruyere, A Lebeau, E Hendrick, and P Hubert. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures …. Unknown journal, 2018.
(tsay2021analadenocarcinomacase pages 1-1): Cynthia J Tsay, Thomas Pointer, Jocelyn B Chandler, Anil B Nagar, and Petr Protiva. Anal adenocarcinoma: case report, literature review and comparative survival analysis. BMJ Open Gastroenterology, 8:e000661, Jul 2021. URL: https://doi.org/10.1136/bmjgast-2021-000661, doi:10.1136/bmjgast-2021-000661. This article has 6 citations and is from a peer-reviewed journal.
(herfs2018adualisticmodel pages 4-5): M Herfs, P Roncarati, B Koopmansch, O Peulen, D Bruyere, A Lebeau, E Hendrick, and P Hubert. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures …. Unknown journal, 2018.
(herfs2018adualisticmodel pages 9-10): M Herfs, P Roncarati, B Koopmansch, O Peulen, D Bruyere, A Lebeau, E Hendrick, and P Hubert. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures …. Unknown journal, 2018.
(herfs2018adualisticmodel media 4416b428): M Herfs, P Roncarati, B Koopmansch, O Peulen, D Bruyere, A Lebeau, E Hendrick, and P Hubert. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures …. Unknown journal, 2018.
(herfs2018adualisticmodel pages 7-8): M Herfs, P Roncarati, B Koopmansch, O Peulen, D Bruyere, A Lebeau, E Hendrick, and P Hubert. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures …. Unknown journal, 2018.
(herfs2018adualisticmodel media 502e33fe): M Herfs, P Roncarati, B Koopmansch, O Peulen, D Bruyere, A Lebeau, E Hendrick, and P Hubert. A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures …. Unknown journal, 2018.
(tsay2021analadenocarcinomacase pages 1-2): Cynthia J Tsay, Thomas Pointer, Jocelyn B Chandler, Anil B Nagar, and Petr Protiva. Anal adenocarcinoma: case report, literature review and comparative survival analysis. BMJ Open Gastroenterology, 8:e000661, Jul 2021. URL: https://doi.org/10.1136/bmjgast-2021-000661, doi:10.1136/bmjgast-2021-000661. This article has 6 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Ask OpenScientist

OpenScientist Report

Definitions

Subtypes

Pathophysiology

Histopathology

Pathograph

Phenotypes

Genetic Associations

Treatments

Environmental Factors

Clinical Trials

Source YAML

References & Deep Research

Deep Research

1. Disease Information

Overview (definition; current understanding)

Key identifiers and coding (available from retrieved sources)

Synonyms / alternative names (from literature)

Evidence source type

2. Etiology

Disease causal factors / mechanistic contexts

Infectious agents (HPV) and current evidence

Risk factors (human clinical evidence)

Protective factors / gene–environment interactions

3. Phenotypes

Common clinical presentation (symptoms/signs)

Stage at presentation / temporal development

Phenotype characteristics and frequencies

Suggested HPO terms (non-exhaustive)

Quality of life impact

4. Genetic / Molecular Information

Molecular subtypes and lineage markers (primary human tumor profiling)

HPV status and p16INK4a

Mismatch repair deficiency / MSI

Immune microenvironment and checkpoints

Actionable alterations and pathway context

Example case molecular features

Suggested gene/pathway ontologies

Suggested CL (cell types) for mechanism annotation (mapping suggestions)

5. Environmental Information

6. Mechanism / Pathophysiology

Causal chains (current evidence-supported models)

Upstream vs downstream processes

7. Anatomical Structures Affected

Primary site

Suggested UBERON terms (mapping suggestions)

Local invasion patterns (case evidence)

8. Temporal Development

Typical age of onset

Course/progression patterns

9. Inheritance and Population

Epidemiology (registry-based)

10. Diagnostics

Clinical and pathology diagnosis

Differential diagnosis

11. Outcome / Prognosis

Survival statistics (SEER population data)

Prognostic factors

12. Treatment

Current applications / real-world implementations (population-based evidence)

Ongoing / recent clinical research (clinicaltrials.gov)

Suggested MAXO terms (mapping suggestions)

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Key quantitative evidence map

Visual evidence (molecular landscape)

Expert synthesis and analysis (authoritative interpretation)

Limitations of this report (evidence availability)

Artifacts