Anus & perianal area

• Primary squamous cell carcinoma of the anus

• WHO officially only recognizes squamous cell carcinoma
• Basaloid variant has also been termed cloacogenic or transitional
• Mucoepidermoid carcinoma may be used for tumors with prominent mucinous features, although the biology may be different (J Gastroenterol 2001;36:508)

• Tumors above dentate line: more common in women; usually diagnosed in sixth decade
• Tumors below dentate line: more common in men; usually diagnosed in third decade

• Presenting symptoms include rectal bleeding, pain, mass

• Prognosis depends on AJCC stage of tumor
• Distal tumors have a better prognosis (slower growth, earlier detection)
• Better prognosis with higher radiation dose and no / shorter treatment interruptions (Gastrointest Cancer Res 2008;2:10)
• Worse prognosis if older, male or with HIV (Dis Colon Rectum 2009;52:624, Dis Colon Rectum 2001;44:1496)
• HPV and p53 status can stratify prognosis (worst prognosis: HPV negative, p53 aberrant staining) (Mod Pathol 2021;34:1017)

• Surgery with chemoradiation

• Anal canal tumors are nodular, ulcerated, ≥ 3 - 4 cm
• Invade deeply into wall and spread proximally and distally into submucosa of the distal rectum and proximal anus

• Resembles squamous cell carcinoma as seen elsewhere in body
• Tumors often display multiple morphologic patterns, calling into question the utility of subdividing the entity
• May be keratinizing (usually below the dentate line) or nonkeratinizing (anywhere, although tumors above the dentate line are usually nonkeratinizing)
• Uncommon basaloid subtype shows plexiform pattern and palisading of small undifferentiated cells around the border, with central necrosis of tumor nodules (also mitotic figures, invasion, desmoplastic stroma) (Am J Surg Pathol 2016;40:354)
• May have massive eosinophilic infiltration, mucoepidermoid features (with mucinous microcysts) or poorly differentiated morphology
• Can show small cell anaplastic features (but without evidence of neuroendocrine differentiation)
• Often replaces crypts of adjacent rectal mucosa
• May show overlying / adjacent dysplastic changes (anal intraepithelial neoplasia)

Contributed by Raul S. Gonzalez, M.D.

Which of the following statements is true about anal squamous cell carcinoma?

1. Cases above the dentate line are more common in men
2. Cases below the dentate line are more common in elderly patients
3. Patients with HIV have a worse prognosis
4. Vast majority are purely basaloid

C. Patients with HIV have a worse prognosis. Poor prognostic factors in anal squamous cell carcinoma include older age, male sex and HIV positivity. Cases above the dentate line are more common in older women and cases below the dentate line are more common in younger men. Most cases are squamous cell carcinoma, NOS; basaloid examples are uncommon.

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Reference: Squamous cell carcinoma

Which of the following etiologic subtypes of anal squamous cell carcinoma has the worst prognosis?

1. HPV negative, p53 aberrant staining
2. HPV negative, p53 wild type staining
3. HPV positive, p53 aberrant staining
4. HPV positive, p53 wild type staining

A. HPV negative, p53 aberrant staining. Patients with this subtype have the worst prognosis. HPV positive cancers with p53 wild type staining confer the best prognosis and the other choices have an intermediate prognosis.

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Reference: Squamous cell carcinoma