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Merkel-Zell-Karzinom

Merkel cell carcinoma

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Zusammenfassung

Das Merkel-Zell-Karzinom (MCC; kutanes neuroendokrines Karzinom) ist ein seltener Tumor unklarer Histogenese, der vorwiegend an sonnenexponierten Arealen bei älteren Patienten auftritt. Eine höhere Inzidenz und Auftreten in jüngerem Alter finden sich vorwiegend bei immunsupprimierten Personen, weshalb neben der ultravioletten(UV)-Strahlung auch der Immunsuppression eine pathogenetische Rolle zugesprochen wird. Zusätzlich konnte in 80 % der Fälle ein klonal integriertes Polyomavirus (Merkel-Zell-Polyomavirus, MCPyV) nachgewiesen werden. Klinisch stellt das MCC einen uncharakteristischen Tumor dar. Histopathologisch finden sich monomorphe dermale und/oder subkutane Knoten aus runden bis ovalen mittelgroßen Zellen mit vesikulärem Nukleus und spärlichem Zytoplasma. Die neoplastischen Zellen des MCC exprimieren Zytokeratin (CK) 20 mit punktförmiger („dot-like“) perinukleärer Betonung. Außerdem sind immunhistochemisch pan-CK, neuroendokrine Marker (u. a. Chromogranin A und Synaptophysin), Neurofilamentproteine, CD56, CD57, Bcl-2, TdT und PAX-5 positiv. Die meisten Fälle zeigen auch eine Positivität auf CM2B4, einen gegen MCPyV gerichteten Antikörper. Eine p63-Expression wird bei einem Teil der Fälle beobachtet und war in einigen Studien mit einer günstigen Prognose assoziiert. Die Marker thyroidaler Transkriptionsfaktor-1, „mammalian achaete-scute complex-like 1“, Vimentin, S-100 und CK7 werden beim MCC gewöhnlich nicht exprimiert. Die Prognose ist vorwiegend von der Tumorgröße und dem Lymphknotenstatus abhängig. Das Vorliegen intralymphatischer Tumorkomplexe ist mit einer höheren Rate an Lokalrezidiven und Lymphknotenmetastasen assoziiert. Eine größere Anzahl intratumoraler zytotoxischer T-Lymphozyten ist mit günstiger Prognose, das Vorliegen von > 50 % K-67+-neoplastischer Zellen mit schlechter Prognose vergesellschaftet. Weitere hinsichtlich ihrer prognostischen Relevanz untersuchte morphologische, phänotypische und genetische Faktoren wurden bisher nicht in größeren Kohorten validiert.

Abstract

Merkel cell carcinoma (MCC, cutaneous neuroendocrine carcinoma) is a rare form of tumor of unclear histogenesis which predominantly occurs in elderly patients on areas exposed to the sun. A higher incidence and occurrence in younger people is predominantly found in immunosuppressed persons which is why a pathogenetic role is also attributed to immunosuppression in addition to ultraviolet (UV) radiation. Additionally, in 80% of cases clonally integrated polyomavirus (Merkel cell polyomavirus, MCPyV) could be detected. Clinically MCC represents an uncharacteristic tumor. Histopathologically, monomorphic dermal and/or subcutaneous nodes are found consisting of round or oval medium sized cells with a vesicular nucleus and sparse cytoplasm. The neoplastic cells of MCC express cytokeratin (CK) 20 with a dot-like perinuclear accentuation. In addition, pan-CK, neuroendocrine markers (e.g. chromogranin A and synaptophysin), neurofilament proteins, CD56, CD57, Bcl-2, TdT and PAX-5 are immunohistochemically positive. In most cases CM2B4, an antibody against MCPyV is also positive. Expression of p63 has been observed in some of the cases and in some studies was associated with a favorable prognosis. The markers thyroid transcription factor 1, mammalian achaete scute complex like 1, vimentin, S-100 and CK7 are not normally expressed by MCC. The prognosis is primarily dependent on tumor size and the lymph node status. The presence of intralymphatic tumor complexes is associated with a higher rate of local recurrence and lymph node metastasis. A larger number of intratumoral cytotoxic T-lymphocytes is accompanied by a favorable prognosis and the presence of > 50 % of K-67+ neoplastic cells with an unfavorable prognosis. Further morphological, phenotypical and genetic factors have not yet been validated in larger cohorts with respect to the prognostic relevance.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. L. Cerroni und I. Fried geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Forschungseinheit für Dermatopathologie, Klinik für Dermatologie und Venerologie, Medizinische Universität Graz, Auenbruggerplatz 8, 8036, Graz, Österreich

    I. Fried &  L. Cerroni

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Correspondence to L. Cerroni.

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Fried, I., Cerroni, L. Merkel-Zell-Karzinom. Pathologe 35, 467–475 (2014). https://doi.org/10.1007/s00292-014-1935-x

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