title: Study of EWS/FLI-1 rearrangement in 18 cases of CK20+/CM2B4+ Merkel cell carcinoma using FISH and correlation to the differential diagnosis of Ewing sarcoma/peripheral neuroectodermal tumor.
abstract: Merkel cell carcinoma (MCC) and primary cutaneous Ewing sarcoma/primitive neuroectodermal tumors (PCES/PNET) pose a challenging morphologic differential diagnosis. Approximately 90% of Ewing sarcoma/primitive neuroectodermal tumors (PNETs) have a specific translocation, t(11;22) (q24;q12). The EWS-friend leukemia integration-1 (FLI-1) fusion results in FLI-1 overexpression. EWS/FLI-1 rearrangement has been suggested as a useful tool in the diagnosis of PCES/PNET. In contrast, Merkel cell polyomavirus was found to be an infective agent related to the pathogenesis of MCC. Merkel cell polyomavirus can be immunohistochemically detected with the antibody CM2B4. To the best of our knowledge, there is no case of any cytokeratin (CK)20-/CM2B4+ PNET. The goal of our study was to investigate whether EWS/FLI-1 rearrangement was present in cases of MCC. We have studied 18 cases of MCC. To make sure that the cases investigated by fluorescent in situ hybridization were genuine MCC, we considered only CK20+/CM2B4+ cases. Six cases met this criterion. EWS/FLI-1 rearrangement was not evidenced in any of the 18 cases (including the 6 "genuine" cases of MCC). Although our findings were somewhat expected, we think that they fill a gap in the literature: the confirmation that MCC is devoid of the EWS/FLI-1 rearrangement.
authors.affiliation: *Service of Cellular Pathology, Clinica Ponferrada, Ponferrada †Service of Anatomic Pathology, Complejo Hospitalario Universitario Santiago de Compostela ‡Department of Medicine, University of Santiago de Compostela, Galicia §Department of Anatomic Pathology, Hospital Universitario de Guadalajara, Guadalajara, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Fernandez-Flores
authors.forename: Jose M
authors.initials: JM
authors.lastname: Suarez-Peñaranda
authors.forename: Soledad
authors.initials: S
authors.lastname: Alonso
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000175:diagnosis* / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053554:Keratin-20 / Q000276:immunology / Q000378:metabolism; D008297:Male; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000175:diagnosis*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011051:Poliomyelitis / Q000175:diagnosis / Q000473:pathology; D017955:Poliovirus / Q000276:immunology / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics*; D034802:RNA-Binding Protein EWS / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000175:diagnosis; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D000956:Antigens, Viral; C106031:EWS-FLI fusion protein; D053554:Keratin-20; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS