Cytokeratin 20-Negative Merkel Cell Carcinoma: A Case Series and Discussion of Diagnostic Strategies

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma of the skin. MCC can present a diagnostic challenge, especially in cases where Cytokeratin 20 (CK20) is negative or focally positive. CK20-negative MCC accounts for about 5% of MCCs. This case series describes five cases of CK20-negative or focally positive MCC at an academic medical center. All cases were biopsies of cutaneous lesions. Histopathological investigation with hematoxylin and eosin staining revealed characteristic aggregates of small blue cell tumor morphology in all cases. CK20 staining was absent in three cases and focally positive in two, defined as less than 5% of tumor cells. All cases demonstrated pancytokeratin (PanCK) positivity in the paranuclear dot-like pattern. Thyroid transcription factor 1 (TTF-1) was negative in all instances, supporting the diagnosis of MCC. This case series illustrates the diagnostic value and limitations of PanCK and TTF-1 staining in MCC in cases where CK20 is negative and discusses strategies for diagnosing this rare variant of MCC.