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High-Risk HPV-Associated Anal Basaloid Squamous Carcinoma

Posted on July 09 2014

Case Study

Accurate recognition of anal basaloid squamous cell carcinomas (problematically called cloacogentic or transitional in the past), especially their distinction from poorly differentiated adenocarcinoma, urothelial carcinoma and neuroendocrine (oat cell) carcinoma can be difficult. Tumors with this histology can arise in the high anal transition zone (ATZ), which can be difficult to anatomically distinguish from the low-rectum. Therefore, confirmation of this diagnosis requires careful clinical-anatomic correlation in support of ATZ origin.

History

A 72 year-old female presented with what was believed to be a right lateral rectal mass.

Morphology

Mucosal architecture is effaced by a nested, nonkeratinizing, non-gland forming basaloid proliferation without obvious squamous or neuroendocrine differentiation. Scant benign surface glandular epithelium is present without detectable mature surface squamous epithelium.

Special Studies

  • Immunohistochemistry. Paraffin immunostains highlight uniform, strong block-like p16, positive AE1/3, negative-to-dim+ p63, negative with rare dim+ CK5/6, negative CD56, and negative CK20- staining.

H&E

AE1/3+

p16++

P63(dim)+

CK5-/6(partial dim)+

CD56-

CK20-

Differential Diagnosis

Poorly differentiated rectal adenocarcinoma vs. neuroendocrine carcinoma vs. high-risk HPV-associated anal basaloid squamous carcinoma.

Diagnosis

High-risk HPV-associated anal basaloid squamous carcinoma.

Educational comments

Despite the clinical impression of rectal origin, the constellation of pathologic findings are more compatible with anal carcinoma. Accurate recognition of anal basaloid squamous cell carcinomas (problematically called cloacogentic or transitional in the past), especially their distinction from poorly differentiated adenocarcinoma, urothelial carcinoma and neuroendocrine (oat cell) carcinoma can be difficult. Tumors with this histology can arise in the high anal transition zone (ATZ), which can be difficult to anatomically distinguish from the low-rectum. Therefore, confirmation of this diagnosis requires careful clinical-anatomic correlation in support of ATZ origin.

Although one study reports very high sensitivity of p63 and CK5/6 staining and specificity of p63 for distinguishing anal SCCA from colorectal adenocarcinoma [1], another smaller study reports some variability in both p63 and CK5/6 staining of anal squamous carcinomas [2], which is seen in this biopsy. Overall, in this biopsy the p16(strong block-like)++ p63(dim)+ CK5/6-/(partial dim)+ CK20- CD56- AE1/3+ immunophenotype much more strongly supports basaloid squamous carcinoma and argues against neuroendocrine and rectal-adenocarcinoma. Strong block like p16+ tumor staining indirectly suggests high-risk HPV mediated disease.

References

  1. Owens SR, Greenson JK, 2007. Immunohistochemcial staining for p63 is useful in the diagnosis of anal squamous cell carcinoma. Am J Surg Pathol. 31(2):285-90
  2. Kaufmann O1, Fietze E, Mengs J, Dietel M 2001. Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol.116(6):823-30.

Case study by Guy E. Nichols MD, PhD


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