The clinicopathologic spectrum and genomic landscape of de-/trans-differentiated melanoma.

Autor: Ferreira I; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.; Université Libre de Bruxelles, Brussels, Belgium., Droop A; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK., Edwards O; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK., Wong K; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK., Harle V; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK., Habeeb O; Department of Anatomic Pathology, Middlemore Hospital, Auckland, NZ, New Zealand., Gharpuray-Pandit D; Department of Cellular Pathology, Royal Preston Hospital, Preston, UK., Houghton J; Department of Pathology, Royal Victoria Hospital, Belfast, Ireland., Wiedemeyer K; Department of Dermatology, University of Heidelberg, Heidelberg, Germany.; Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Mentzel T; Dermatopathology Friedrichshafen, Friedrichshafen, Germany., Billings SD; Department of Pathology, Cleveland Clinic, Cleveland, OH, USA., Ko JS; Department of Pathology, Cleveland Clinic, Cleveland, OH, USA., Füzesi L; Center for Pathology, Robert-Weixler-Straße 48a, Kempten, Germany., Mulholland K; Department of Pathology, Altnagelvin Area Hospital, Londonderry, UK., Prusac IK; Department of Pathology, University Hospital Split and Split University School of Medicine, Split, Croatia., Liegl-Atzwanger B; Diagnostic and Research Centre for Molecular Biomedicine, Diagnostic and Research Centre for Pathology, Translational Sarcoma Pathology, Comprehensive Cancer Centre Subunit Sarcoma, Medical University Graz, Graz, Austria., de Saint Aubain N; Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Caldwell H; Division of Pathology, Cancer Research UK Edinburgh Centre, The University of Edinburgh, Institute of Genetics and Cancer, Edinburgh, UK., Riva L; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK., van der Weyden L; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK., Arends MJ; Division of Pathology, Cancer Research UK Edinburgh Centre, The University of Edinburgh, Institute of Genetics and Cancer, Edinburgh, UK., Brenn T; Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. thomas.brenn@ucalgary.ca.; Division of Pathology, Cancer Research UK Edinburgh Centre, The University of Edinburgh, Institute of Genetics and Cancer, Edinburgh, UK. thomas.brenn@ucalgary.ca.; The Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. thomas.brenn@ucalgary.ca., Adams DJ; Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Jazyk: angličtina
Zdroj: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2021 Nov; Vol. 34 (11), pp. 2009-2019. Date of Electronic Publication: 2021 Jun 21.
DOI: 10.1038/s41379-021-00857-z
Abstrakt: Dedifferentiation and transdifferentiation are rare and only poorly understood phenomena in cutaneous melanoma. To study this disease more comprehensively we have retrieved 11 primary cutaneous melanomas from our pathology archives showing biphasic features characterized by a conventional melanoma and additional areas of de-/trans-differentiation as defined by a lack of immunohistochemical expression of all conventional melanocytic markers (S-100 protein, SOX10, Melan-A, and HMB-45). The clinical, histologic, and immunohistochemical findings were recorded and follow-up was obtained. The patients were mostly elderly (median: 81 years; range: 42-86 years) without significant gender predilection, and the sun-exposed skin of the head and neck area was most commonly affected. The tumors were deeply invasive with a mean depth of 7 mm (range: 4-80 mm). The dedifferentiated component showed atypical fibroxanthoma-like features in the majority of cases (7), while additional rhabdomyosarcomatous and epithelial transdifferentiation was noted histologically and/or immunohistochemically in two tumors each. The background conventional melanoma component was of desmoplastic (4), superficial spreading (3), nodular (2), lentigo maligna (1), or spindle cell (1) types. For the seven patients with available follow-up data (median follow-up period of 25 months; range: 8-36 months), two died from their disease, and three developed metastases. Next-generation sequencing of the cohort revealed somatic mutations of established melanoma drivers including mainly NF1 mutations (5) in the conventional component, which was also detected in the corresponding de-/trans-differentiated component. In summary, the diagnosis of primary cutaneous de-/trans-differentiated melanoma is challenging and depends on the morphologic identification of conventional melanoma. Molecular analysis is diagnostically helpful as the mutated gene profile is shared between the conventional and de-/trans-differentiated components. Importantly, de-/trans-differentiation does not appear to confer a more aggressive behavior.
(© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)
Databáze: MEDLINE
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