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CD56 expression in basaloid anal squamous cell carcinoma - A potential diagnostic pitfall
Sepideh Madahian1, Richard Judelson1, Xiaoqin Zhu1
1Department of Pathology, University of Massachusetts, UMass Memorial Medical Center, 1 Innovation Dr., Biotech 3 Bldg., 2nd Floor, Worcester, MA, USA.
Annals of Diagnostic Pathology
|May 14, 2021
Summary
CD56 expression is uncommon in anal squamous cell carcinoma (SqCC) and does not indicate neuroendocrine differentiation. Pathologists should be aware of this potential diagnostic pitfall in basaloid SqCC.
Area of Science:
- Oncology
- Pathology
- Cancer Research
Background:
- Anal squamous cell carcinoma (SqCC) exhibits morphological heterogeneity.
- Basaloid and non-keratinizing SqCC can be misdiagnosed as neuroendocrine carcinoma due to overlapping morphology and poorly understood neuroendocrine marker expression.
Purpose of the Study:
- To investigate the expression of neuroendocrine markers (CD56, synaptophysin, chromogranin) in basaloid anal SqCC.
- To correlate marker expression with clinicopathologic features and human papillomavirus (HPV) status.
- To clarify the diagnostic significance of CD56 expression in anal SqCC.
Main Methods:
- Retrospective analysis of 48 basaloid anal SqCC cases.
- Immunohistochemical examination for CD56, synaptophysin, and chromogranin.
- HPV typing (HPV16, HPV33) and analysis of CTNNB1 mutations.
- Clinicopathologic correlation including stage and outcome.
Main Results:
- CD56 was expressed in 3 cases (6.3%), with varying intensity and morphology.
- Synaptophysin and chromogranin expression was not significant in any cases.
- All CD56-positive cases were HPV16-positive; one had a CTNNB1 mutation.
- No significant differences in clinicopathologic features were observed between CD56-positive and negative groups.
Conclusions:
- CD56 expression is infrequent in basaloid anal SqCC and does not signify neuroendocrine differentiation without co-expression of synaptophysin or chromogranin.
- CD56 expression in anal SqCC can be a diagnostic pitfall, mimicking neuroendocrine carcinoma or basal cell carcinoma.
- Awareness of CD56 expression in anal SqCC is crucial for accurate diagnosis.

