Stanford School of Medicine

Surgical Pathology Criteria

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Adenocarcinoma of the Anus


  • Adenocarcinoma arising in the anal canal or in adjacent deep tissues

Alternate/Historical names:

  • Perianal adenocarcinoma (for extra-mucosal adenocarcinoma)
  • Perianal gland adenocarcinoma (for extra-mucosal adenocarcinoma)

Diagnostic Criteria

  • Must primarily involve the anal canal
  • Two basic types of anal adenocarcinoma
    • Colorectal type
      • Originates in mucosa
        • May have a residual mucosal lesion
      • Histologically identical to colorectal adenocarcinoma
    • Extra-mucosal, fistula / anal gland type
      • No overlying mucosal lesion
        • May ulcerate
      • Most cases associated with chronic anorectal fistula
      • Most cases are mucinous
        • >50% of tumor volume is mucin
        • Ductal / tubular differentiation may be seen
  • Paget disease may be present
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


  Colorectal Type Extramucosal Type
p63 Negative Negative
CK5/6 Negative Negative
CDX2 Positive Negative
CK7 Occasionally positive Positive
CK20 Positive Negative
No specific studies reported of anal carcinomas of colorectal type; phenotype given is that of colorectal adenocarcinoma; extramucosal data from Lisovsky 2007

Genetic analysis

  • High risk human papilloma virus (HPV18) has been demonstrated in 2/6 anal adenocarcinomas of unstated type (Koulos 1991)


Differential Diagnosis

Colorectal Type Adenocarcinoma of the Anus Extra-mucosal (Fistula/Anal Gland) Type Adenocarcinoma of the Anus
Usually has identifiable surface component No surface mucosal component
No association with chronic fistula Most case associated with chronic fistula
CK7 variably positive CK7 positive
CK20 positive CK20 negative
CDX2 positive CDX2 negative
Small numbers of cases have been tested


Squamous Carcinoma of the Anus Poorly Differentiated Adenocarcinoma of the Anus
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


  • Melanoma should be ruled out before the diagnosis of poorly differentiated adenocarcinoma is made
    • S100/HMB45 and keratin immunohistochemistry distinguishes the two


    • Classically, extra-mucosal type has a poor prognosis
      • <20% 5 year survival
      • Recent reports indicate improved survival with adjuvant chemo- and radiation therapy

    Grading / Staging

    • Grading same as for colorectal adenocarcinoma
      • Grading based on worst area
        • Leading front of invasion excluded from grading
        • Criteria for mucinous and signet ring apply to the entire lesion
      • Low grade
        • Well differentiated
          • >95% gland forming
        • Moderately differentiated
          • 50-95% gland forming
      • High grade
        • Poorly differentiated
          • 5-50% gland forming
          • Mucinous carcinoma (>50% of carcinomatous lesion is mucin)
          • Signet ring (>50% of cells signet ring)
        • Undifferentiated
          • <5% gland forming
    • Use TNM staging for anal adenocarcinoma

    Classification / Lists

    Anal Tumors and Neoplasms

    Extension from rectal lesions must be ruled out


    • Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
    • Longacre TA, Kong CS, Welton ML. Diagnostic problems in anus pathology. Adv Anat Pathol. 2008 Sep;15(5):263-78.
    • Balachandra B, Marcus V, Jass JR. Poorly differentiated tumours of the anus canus: a diagnostic strategy for the surgical pathologist. Histopathology. 2007 Jan;50(1):163-74.
    • Lisovsky M, Patel K, Cymes K, Chase D, Bhuiya T, Morgenstern N. Immunophenotypic characterization of anus gland carcinoma: loss of p63 and cytokeratin 5/6. Arch Pathol Lab Med. 2007 Aug;131(8):1304-11.
    • Anthony T, Simmang C, Lee EL, Turnage RH. Perianus mucinous adenocarcinoma. J Surg Oncol. 1997 Mar;64(3):218-21.
    • Gaertner WB, Hagerman GF, Finne CO, Alavi K, Jessurun J, Rothenberger DA, Madoff RD. Fistula-associated anus adenocarcinoma: good results with aggressive therapy. Dis Colon Rectum. 2008 Jul;51(7):1061-7.
    • Koulos J, Symmans F, Chumas J, Nuovo G. Human papillomavirus detection in adenocarcinoma of the anus. Mod Pathol. 1991 Jan;4(1):58-61.
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