Squamous Carcinoma of the Anus

Definition

• Squamous carcinoma, of varying levels of differentiation, involving the anal canal

Alternate/Historical names

• Basaloid carcinoma
• Basaloid squamous carcinoma
• Cloacogenic carcinoma
• Epidermoid carcinoma
• Mucoepidermoid carcinoma (referring to the mucinous microcystic variant)
• Non-keratinizing squamous carcinoma
• Transitional carcinoma

Covered separately

• Rectal squamous cell carcinoma
• Verrucous carcinoma

Diagnostic Criteria

• Must involve the anal canal
• Best determined clinically
• Lesion must not be entirely visible outside the anal canal on clinical examination
• Variable degrees of differentiation and patterns
• Often varies within the same tumor
• Biopsy may not be representative of entire lesion
• Clear squamous differentiation with keratinization and intercellular bridges
• Present to some degree in >90% of cases
• Basaloid, poorly differentiated carcinoma
• Present to some degree in 65% of cases
• Small to moderate amounts of cytoplasm
• Frequent peripheral palisading
• Frequent retraction artifact
• Frequent eosinophilic necrosis in center of nests
• Small cell (anaplastic) carcinoma
• Included by WHO as a variant but not identified in modern studies
• Similar to basaloid pattern (above), but with the following features
  • Lack of palisading
  • Lack of cohesion
  • Diffuse infiltration
  • Increased mitotic rate and apoptosis
  • In spite of the similar name, this does not refer to small cell (high grade endocrine) carcinoma
• Microcystic (mucoepidermoid) pattern
  • Present to some degree in 25% of cases
  • Varies from poorly defined to well formed glands
  • May contain central stainable mucin
• Prominent basement membrane surrounding and within tumor nodules reminiscent of skin adnexal and salivary gland neoplasms
  • Has been given several names
    • Cylindroma
    • Adenoid cystic carcinoma
    • Spiradenocylindroma
  • Lacks any myoepithelial layer
  • Rare as a dominant pattern
• No clear clinical difference has been demonstrated for any of these types and patterns of differentiation or degrees of differentiation with modern therapy
  • Diagnosis should simply be Squamous Carcinoma
    • Descriptive features may be included in a comment
• A few studies from the pre-modern therapy era suggested that the mucinous microcystic pattern and the small cell (anaplastic) carcinoma had a worse outcome
• Old version of WHO classification is no longer followed:
• Large cell keratinizing, large cell non-keratinizing and basaloid
• The classification shows poor reproducibility and is not clinically relevant

Original posting/updates : 10/7/10, 11/13/11

Supplemental studies

Immunohistology

• Usually positive:
  • p63
  • High molecular weight keratins (CK5/6, 34BE12)
  • AE1 (CK 10,14 15, 16, 19)
• Variable reports for CK7
• Usually negative markers
  • CAM5.2 (CK 8, 18) (one report)
  • CK20

Genetic analysis

• High risk human papilloma virus (HPV) can be demonstrated in >90% of cases

Differential Diagnosis

• Colorectal squamous carcinoma
• Perianal squamous carcinoma
• Perianal basal cell carcinoma
• Anal adenocarcinoma, poorly differentiated
• Verrucous carcinoma
• Small cell high grade endocrine carcinoma
• Large cell high grade endocrine carcinoma
• Anal melanoma

Squamous Carcinoma of the Anus	Poorly Differentiated Neuroendocrine Carcinoma, Large Cell Type
CK5/6 and p63 virtually always positive	CK5/6 and p63 negative
At most, scattered neuroendocrine marker positivity	Synaptophysin, chromogranin or CD56 extensively positive
Nests of cells with peripheral palisading	At least focal trabeculae, rosettes and/or stippled chromatin

Clinical

• Classically presents in 50-70 age range
  • Also presents in younger patients in the setting of AIDS and other immunodeficiencies
• Therapy generally centered on radiation and chemotherapy followed by local excision if there is a residual lesion
  • Produces cures in the range of 65-80%
• Biopsy is generally preferred over excision for initial diagnosis
  • Permits radiation and chemotherapy without a delay for wound healing

Grading / Staging / Report

Grading

• Degree of differentiation may correlate with natural history of metastasis, recurrence and death
• There is no clear evidence that pattern or type of differentiation affects prognosis with modern therapy

Staging

• Use TNM staging

Report

• Preferred diagnosis is simply Squamous Carcinoma
  • Text of report may include pattern or degree/type of differentiation and other features
• Margins should be reported on resection specimens
• Give site and degree of involvement

Classification / Lists

Anal Tumors and Neoplasms

• Adenocarcinoma
• Condyloma
• Dysplasia / HSIL / LSIL
• Extramammary Paget disease
• Fibroepithelial polyp / skin tag
• Melanoma
• Squamous carcinoma
• Verrucous carcinoma

Extension from rectal lesions must be ruled out

Bibliography

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