Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases.

Autor: Legrand M; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France., Louveau B; Department of Tumour Genomics and Pharmacology, Hôpital Saint Louis, Université Paris Cité, Human Immunology Pathophysiology and Immunotherapy (HIPI), Paris, France., Macagno N; CARADERM Network, Fédération de Recherche Clinique, Lille, France.; Department of Pathology, Aix Marseille University, La Timone Hospital, Marseille, France., Mancini M; Department of Tumour Genomics and Pharmacology, Hôpital Saint Louis, Université Paris Cité, Human Immunology Pathophysiology and Immunotherapy (HIPI), Paris, France., Kazakov DV; IDP Dermatohistopathologie Institut, Pathologie Institut Enge, Zurich, Switzerland., Pissaloux D; Department of Biopathology, Center Léon Bérard, Lyon, France., Tirode F; Department of Biopathology, Center Léon Bérard, Lyon, France.; Université de Lyon, Université Claude Bernard Lyon 1, Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France., Tallet A; Platform of Somatic Tumour Molecular Genetics, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France., Mourah S; Department of Tumour Genomics and Pharmacology, Hôpital Saint Louis, Université Paris Cité, Human Immunology Pathophysiology and Immunotherapy (HIPI), Paris, France., Lepiller Q; French National Papillomavirus Reference Center, CHU de Besançon, Université de Franche-Comté, Besançon, France., de la Fouchardière A; Department of Biopathology, Center Léon Bérard, Lyon, France.; Université de Lyon, Université Claude Bernard Lyon 1, Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France., Sohier P; CARADERM Network, Fédération de Recherche Clinique, Lille, France.; Department of Pathology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, AP-HP Centre-Université Paris Cité, Paris, France., Frouin E; CARADERM Network, Fédération de Recherche Clinique, Lille, France.; Department of Pathology, university Hospital of Nîmes, University of Nîmes, Nîmes, France., von Deimling A; Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University, Heidelberg, Germany.; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Goto K; Department of Pathology, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan.; Department of Diagnostic Pathology, Shizuoka Cancer Center Hospital, Sunto, Japan.; Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan.; Department of Dermatology, Hyogo Cancer Center, Akashi, Japan., Cribier B; CARADERM Network, Fédération de Recherche Clinique, Lille, France.; Dermatology Clinic, Hôpitaux Universitaires and Université de Strasbourg, Hôpital Civil, Strasbourg, France., Calonje E; Department of Dermatopathology, St John's Institute of Dermatology, St Thomas' Hospital, London, UK., Taibjee S; Dermatology Department, Dorset County Hospital NHS Foundation Trust, Dorchester, UK., Battistella M; CARADERM Network, Fédération de Recherche Clinique, Lille, France.; Department of Pathology, Saint-Louis University Hospital, Paris, France., Kervarrec T; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France.; CARADERM Network, Fédération de Recherche Clinique, Lille, France.; Biologie des infections à polyomavirus team, Université de Tours, Tours, France.
Jazyk: angličtina
Zdroj: Histopathology [Histopathology] 2024 Nov 20. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1111/his.15361
Abstrakt: Aims: Sebaceous neoplasms constitute a group of adnexal tumours, including sebaceous adenoma, sebaceoma and sebaceous carcinoma. Although mismatch repair deficiency may be observed, the nature of the genetic alterations contributing to the development of most of these tumours is still unknown. In the present study, we describe the clinical, microscopic, and molecular features of eight sebaceomas with GRHL gene rearrangement.
Methods and Results: Among these sebaceomas, four occurred in women and four in men; the median age was 63 years (range = 29-89). The tumours were located in the head and neck area in all cases. Microscopic examination revealed a well-demarcated lesion located in the dermis with focal extension into the subcutaneous tissue (three cases). The neoplasms displayed macronodular (eight cases), cribriform (seven cases) and organoid (six cases) growth patterns, occurring in combination. The tumours were mainly composed of immature basophilic cells associated with scattered mature sebocytes. Numerous small infundibular cysts were present in seven cases. Mitotic activity was low (none/one to four mitoses/mm 2 ). Immunohistochemistry showed positivity for androgen receptor and p63. Preserved expression of MLH1, PMS2, MSH2 and MSH6 was observed in all cases. RNA-sequencing revealed RCOR1::GRHL2 (three cases), BCL6::GRHL1 (two cases), a BCOR::GRHL2 (one case), RCOR1::GRHL1 (one case) and TLE1::GRHL1 (one case) fusion transcript. Methylation analysis demonstrated that GRHL-fused sebaceomas form an independent cluster and highlight the proximity of such tumours with poromas with folliculo-sebaceous differentiation.
Conclusions: In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.
(© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: