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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

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
    • 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
Teri A Longacre MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

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

Squamous Carcinoma of the Anus Colorectal Squamous Carcinoma
Must involve anal canal Must not involve the anal squamous mucosa
Some require that colorectal SCC be at least 5-7 cm from the anus

 

Squamous Carcinoma of the Anus Perianal Squamous Carcinoma
Must involve anal canal ≤5 cm from anal verge and entirely visible outside the anal canal on clinical examination
  • Perianal carcinomas have a better prognosis of 85-90% 5 year survival vs. 65-80% for anal squamous carcinomas
  • High risk HPV may be seen in both
  •  

    Squamous Carcinoma of the Anus, Predominantly Basaloid Basal Cell Carcinoma of Perianal Skin
    Involves anal canal Extremely rarely involves anal canal
    May have adjacent squamous carcinoma in situ No relationship to carcinoma in situ
    Frequent necrosis Necrosis infrequent
    BerEp4 and smooth muscle actin negative BerEp4 and smooth muscle actin positive reported up to 100%
    AE1, CK22, CEA, EMA positive 80-100% AE1, CK22, CEA, EMA negative

     

    Squamous Carcinoma of the Anus, Predominantly Basaloid Adenocarcinoma of the Anus, Poorly Differentiated
    CK5/6 and p63 virtually always positive CK5/6 and p63 negative
    CK20 negative CK20 positive if rectal type; negative if perianal gland type
    High risk HPV may be seen in both

     

    Verrucous Carcinoma of the Anus Usual Squamous Carcinoma of the Anus
    Only blunt pushing invasion Jagged invasion
    No more than mild dysplasia Usually significant dysplasia
    Mitotic figures confined to basal layer unless inflamed Mitotic figures may be present at all levels
    No vascular or perineural invasion May have vascular or perineural invasion
    Does not metastasize May metastasize
  • Note that usual squamous carcinoma can develop in verrucous carcinoma
  •  

    Squamous Carcinoma of the Anus Poorly Differentiated Neuroendocrine Carcinoma, Small Cell (Undifferentiated) Type
    CK5/6 and p63 virtually always positive CK5/6 and p63 negative
    CK7 variably positive CK7 negative

     

    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

    Extension from rectal lesions must be ruled out

    Bibliography

    • Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
    • Williams GR, Talbot IC. Anal carcinoma--a histological review. Histopathology. 1994 Dec;25(6):507-16.
    • Longacre TA, Kong CS, Welton ML. Diagnostic problems in anal pathology. Adv Anat Pathol. 2008 Sep;15(5):263-78.
    • Shepherd NA, Scholefield JH, Love SB, England J, Northover JM. Prognostic factors in anal squamous carcinoma: a multivariate analysis of clinical, pathological and flow cytometric parameters in 235 cases. Histopathology. 1990 Jun;16(6):545-55.
    • Friberg B, Svensson C, Goldman S, Glimelius B. The Swedish National Care Programme for Anal Carcinoma--implementation and overall results. Acta Oncol. 1998;37(1):25-32.
    • Pang LS, Morson BC. Basaloid carcinoma of the anal canal. J Clin Pathol. 1967 Mar;20(2):128-35.
    • Nahas CS, Shia J, Joseph R, Schrag D, Minsky BD, Weiser MR, Guillem JG, Paty PB, Klimstra DS, Tang LH, Wong WD, Temple LK. Squamous-cell carcinoma of the rectum: a rare but curable tumor. Dis Colon Rectum. 2007 Sep;50(9):1393-400.
    • Roohipour R, Patil S, Goodman KA, Minsky BD, Wong WD, Guillem JG, Paty PB, Weiser MR, Neuman HB, Shia J, Schrag D, Temple LK. Squamous-cell carcinoma of the anal canal: predictors of treatment outcome. Dis Colon Rectum. 2008 Feb;51(2):147-53. Erratum in: Dis Colon Rectum. 2008 May;51(5):620.
    • Khanfir K, Ozsahin M, Bieri S, Cavuto C, Mirimanoff RO, Zouhair A. Patterns of failure and outcome in patients with carcinoma of the anal margin. Ann Surg Oncol. 2008 Apr;15(4):1092-8.
    • Owens SR, Greenson JK. Immunohistochemical staining for p63 is useful in the diagnosis of anal squamous cell carcinomas. Am J Surg Pathol. 2007 Feb;31(2):285-90.
    • Balachandra B, Marcus V, Jass JR. Poorly differentiated tumours of the anal canal: a diagnostic strategy for the surgical pathologist. Histopathology. 2007 Jan;50(1):163-74.
    • Behrendt GC, Hansmann ML. Carcinomas of the anal canal and anal margin differ in their expression of cadherin, cytokeratins and p53. Virchows Arch. 2001 Dec;439(6):782-6.
    • Kacerovska D, Szepe P, Vanecek T, Nemcova J, Michal M, Mukensnabl P, Kazakov DV. Spiradenocylindroma-like basaloid carcinoma of the anus and rectum: case report, including HPV studies and analysis of the CYLD gene mutations. Am J Dermatopathol. 2008 Oct;30(5):472-6.
    • Chetty R, Serra S, Hsieh E. Basaloid squamous carcinoma of the anal canal with an adenoid cystic pattern: histologic and immunohistochemical reappraisal of an unusual variant. Am J Surg Pathol. 2005 Dec;29(12):1668-72.
    • Fenger C, Frisch M, Jass JJ, Williams GT, Hilden J. Anal cancer subtype reproducibility study. Virchows Arch. 2000 Mar;436(3):229-33.
    • Alvarez-Cañas MC, Fernández FA, Rodilla IG, Val-Bernal JF. Perianal basal cell carcinoma: a comparative histologic, immunohistochemical, and flow cytometric study with basaloid carcinoma of the anus. Am J Dermatopathol. 1996 Aug;18(4):371-9.
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