CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: magic bullet, diagnostic pitfall, or both?

Background: Antibodies to CD56 label natural killer (NK) cell lymphomas and neuroendocrine tumors such as Merkel cell carcinoma (MCC). In MCC altered by crush artifact or obscured by lymphocytes, the histologic features coupled with CD56 positivity can lead to an erroneous impression of NK-cell lymphoma. Methods: Eighteen cases of MCC were stained for CD56, CK20, MNF116, and pankeratin. The results were compared to histologic features and CD56 staining pattern of three NK-cell lymphomas. Results: Three of 18 cases of MCC histologically resembled lymphoma, and CD56 positivity with CD3 and CD20 negativity initially raised the possibility of NK-cell lymphoma. Two additional cases were obscured by dense inflammation, again suggesting the diagnosis of lymphoma. Seventeen of 18 MCC labeled for CD56 and an equal number stained for CK20. All MCC tested were positive for CAM5.2 (14/14) and MNF116 (17/17). Antibodies to pankeratin labeled only one of 18 MCC. Staining for CD56 was stronger in MCC than NK-cell lymphomas. Conclusions: CD56 is a sensitive marker for MCC as well as for NK-cell lymphoma, but is not specific. Importantly, CD56 positivity in crushed or inflamed biopsies of MCC may lead to an erroneous impression of NK lymphoma. Awareness of this potential pitfall will prevent misdiagnosis.