Merkel cell carcinoma (MCC) has a small cell variant, indistinguishable in hematoxylin-eosin sections from metastatic small cell carcinoma of the lung (SCCL). To investigate whether intermediate filament expression is helpful in this distinction, 17 MCCs of the small cell type were examined for cytokeratin, as well as neurofilament protein immunostaining, and compared with 59 intermediate-type MCCs and 22 SCCL. With a pan-cytokeratin cocktail (cytokeratin 1-8, 10, 13-16, 19), most (39 of 55) intermediate-type tumors and, more important, 11 of 16 cases of the small cell variant exhibited focal paranuclear staining with dot-like positivity, crescentic positivity, or both. A combined focal (dot-like/crescentic) and diffuse cytoplasmic pan-cytokeratin staining was seen in additional 8 of 55 intermediate and 4 of 16 small cell MCCs. Cytokeratin 20 also evoked focal cytoplasmic staining and occasionally focal and diffuse positivity in the MCCs, irrespective of the subtype. Exclusively diffuse cytokeratin 20 patterns did not occur. Conversely, most SCCL showed a diffuse expression of pancytokeratin, and all cases remained cytokeratin 20 negative. When neurofilament protein was applied, approximately half of the MCCs (25 of 40), including 7 of 11 of the small cell variant, were positive, whereas all SCCL were negative. In conclusion, the cytokeratin and neurofilament protein patterns of small cell MCCs are identical to the pattern of intermediate MCCs but differ from the profile of SCCL, which may help in the differential diagnosis.
Dot-like positivities for CK-20 or NF are important to prove MCC and to exclude SCCL in clinically and morphologically doubtful cases. Dot-like positivities for pan-CK favor MCC, but do not always exclude SCCL. NSE and CHR are of no value for the differential diagnosis of MCC and SCCL. Melanoma and lymphoma are ruled out by negativity for S100 and pan-CK, respectively.
Our data strongly implicate that prognostic classification of chronic-phase Ph(1+) CML can be significantly improved by the inclusion of morphologic parameters. The variables of the presented scoring system may be easily assessed by routinely processed aspirates and bone marrow trephines.
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