Well-Differentiated Neuroendocrine Tumors in Skin: Terminology and Diagnostic Utility of Cytokeratin 5/6 and p63

Abstract

Background

Well-differentiated neuroendocrine tumors (WDNETs) in skin include metastases from visceral primary sites and very uncommonly, primary cutaneous carcinoid tumors. Cutaneous WDNET may present a diagnostic challenge and in particular can be mistaken for a benign skin adnexal tumor. In contrast to cutaneous adnexal tumors, metastatic adenocarcinomas to the skin are cytokeratin 5/6 (CK 5/6) and p63 negative in the majority of cases. It is unclear if failure to stain with CK 5/6 and p63 would be helpful in differentiating WDNETs from cutaneous adnexal neoplasms.

Methods

We reviewed ten cases of cutaneous WDNETs (8 cases of metastatic disease and 2 presumed primary carcinoid tumors of the skin) and performed immunohistochemical stains for CK 5/6 and p63 on all cases.

Results

All ten cases were negative with both CK 5/6 and p63.

Conclusion

Negative staining for cytokeratin 5/6 and p63 can be helpful to distinguish WDNETs from cutaneous adnexal neoplasms. It is important to consider WDNETs in the differential diagnosis of cutaneous adnexal neoplasms as low grade tumors may be first sign of aggressive metastatic disease.

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