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Merkelzellkarzinom

Merkel-cell carcinoma

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Zusammenfassung

Das Merkelzellkarzinom (MCC) ist ein seltenes, neuroendokrines Karzinom, das wegen ultrastruktureller Gemeinsamkeiten mit der Merkel-Zelle als MCC bezeichnet wird. Die neuroendokrine Merkel-Zelle wurde als Ursprungszelle favorisiert, was jedoch aufgrund ihrer postmitotischen Natur wahrscheinlich nicht zutrifft. Sie entsteht aus einer epidermalen Stammzelle, die auch die Ursprungszelle des Merkelzellkarzinoms darstellen könnte. Andere mögliche Ursprungszellen sind dermale Stammzellen oder Prä-/Pro-B-Zellen. Letztere zeigen mit dem MCC gemeinsam die Expressionen verschiedener Marker (u. a. PAX5).

MCC werden in ca. 80 % der Fälle durch spezielle Integration des Merkelzell-Polyomavirus (MCPyV) in das Genom induziert, in ca. 20 % durch typische UV-induzierte Mutationen in zahlreichen Genen (u. a. TP53, RB1). Histopathologisch ist das MCC ein monomorpher Tumor, der immunhistochemisch durch den Nachweis von CK20 in paranukleären Plaques, von Neurofilamenten und von Chromogranin A diagnostiziert wird. Viruspositive und virusnegative Fälle sind histologisch nicht zu differenzieren.

UV-induzierte und virale Neoantigene bedingen die hohe Immunogenität des MCC. In neuester Zeit wurden PD‑1 und PD-L1 in Tumorzellen und Immunzellen nachgewiesen. Die entsprechenden Checkpoint-Inhibitoren Avelumab und Pembrolizumab sind effektiv in der Therapie und sprechen bei ca. der Hälfte der Fälle unabhängig vom Virusstatus gut an. Disseminierte Tumorzellen (CTCs) sind geeignet für die Verlaufskontrollen. Weitere immunologische und molekulare Studien sind nötig, um individualisierte Therapien, auch für immuninkompetente Patienten zu ermöglichen.

Abstract

Merkel-cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma named for its Merkel-cell-like ultrastructure. The neuroendocrine Merkel cell was previously believed to be the cell of origin. However, Merkel cells are postmitotic and thus probably not the cell of origin of MCC. It is derived from an epidermal stem cell, which also might represent the cell of origin of MCC. Further putative cells of origin are dermal stem cells and pre/pro‑B cells, the latter showing some similar markers (e.g. PAX5).

About 80% of MCCs are induced by the integration of DNA of the Merkel cell polyoma virus (MCPyV) into the genome. On the other hand, about 20% of MCCs show UV-induced mutations in numerous genes (e.g. TP53, RB1). In routine histology, MCC appears monomorphic and the diagnosis is confirmed by immunohistochemistry showing CK20 arranged in typical paranuclear plaques, together with the presence of neurofilaments and chromogranin A. Virus-positive and virus-negative MCC are not different histologically.

UV-induced and viral neoantigens cause the strong immunogenicity of MCC. Moreover, over the last few years, the presence of PD-1 and PD-L1 has been demonstrated within tumor and immune cells. For the checkpoint inhibitors pembrolizumab and avelumab, responses of about 50% have been shown, independent of virus state. Circulating tumor cells (CTCs) seem to be helpful in tumor tracking. Further immunological and molecular studies are necessary for future individual therapies, also concerning immunocompromised patients.

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  1. DermatoMed Hamburg, Facharztzentrum an der Kampnagelfabrik, Jarrestraße 2–6, 22303, Hamburg, Deutschland

    I. Moll

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I. Moll gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Moll, I. Merkelzellkarzinom. Pathologe 40 (Suppl 3), 350–354 (2019). https://doi.org/10.1007/s00292-019-00705-7

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