Merkel cell carcinoma with squamous and sarcomatous differentiation.J Cutan Pathol. 2008 May 20.

Merkel cell carcinoma is an aggressive neuroendocrine tumor historically thought to arise from neural crest-derived cutaneous neuroendocrine cells. Recent evidence supports an epidermal origin. We present a case of Merkel cell carcinoma arising on the upper arm of a 94-year-old woman that had multiple morphologic patterns: small cells typical of Merkel cell carcinoma, malignant cells with squamous differentiation and malignant poorly differentiated spindle cells. Subsequent metastatic disease in regional lymph nodes showed only the small cells and the malignant spindle cells. To our knowledge, this is the first case of Merkel cell carcinoma showing these three patterns of differentiation at first presentation. This morphology raises the possibility that Merkel cell carcinomas may arise from epidermal stem cells that can differentiate along different lines.

Nuclear expression of survivin portends a poor prognosis in Merkel cell carcinoma.Mod Pathol. 2008 Jun;21(6):764-9. Epub 2008 Apr 18.

Inhibition of apoptosis is a critical step in tumorigenesis in many cancers, including Merkel cell carcinoma; however, the exact regulatory mechanisms are not fully understood. Survivin is an inhibitor of apoptosis that is undetectable in most terminally differentiated normal human tissues, strongly expressed in embryonic and fetal organs and is strongly expressed in many different human cancers. In this study, we investigated the expression of survivin in cutaneous Merkel cell carcinoma using immunohistochemistry and correlated the findings with long-term clinical follow-up. We collected and immunostained 19 cases of Merkel cell carcinoma with antibodies to survivin. The median patient age was 79 years, with an average follow-up of 17 months, and a male/female ratio of 7:11. All but one sample represented primary lesions and two cases were obtained from one patient. Clinical follow-up was obtained in 15 cases (79%). All 19 cases of Merkel cell carcinoma demonstrated strong immunoreactivity for survivin. Survivin protein was localized and classified into predominately nuclear (N=8) or cytoplasmic (N=4) compartments. A mixed pattern of survivin expression was also seen in three cases. Cases with a nuclear staining pattern were distinguished by an aggressive clinical course, with seven of eight patients developing metastases or dead of disease on follow-up. Furthermore, all of the cases with predominately cytoplasmic survivin localization (N=4) were free of disease on follow-up. Merkel cell carcinomas represent aggressive malignancies regulated by apoptotic pathways. We demonstrate that survivin, a protein with a dual role in inhibition of apoptosis and regulation of cellular proliferation is expressed in Merkel cell carcinoma. Moreover, nuclear subcellular localization of survivin in Merkel cell carcinomas may portend a poor prognosis and identification of these cases may assist clinical management.