Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases DOI Creative Commons
Mélanie Legrand, Baptiste Louveau, Nicolas Macagno

et al.

Histopathology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Aims Sebaceous neoplasms constitute a group of adnexal tumours, including sebaceous adenoma, sebaceoma and carcinoma. Although mismatch repair deficiency may be observed, the nature genetic alterations contributing to development most these tumours is still unknown. In present study, we describe clinical, microscopic, molecular features eight sebaceomas with GRHL gene rearrangement. Methods results Among sebaceomas, four occurred in women men; median age was 63 years (range = 29–89). The were located head neck area all cases. Microscopic examination revealed well‐demarcated lesion dermis focal extension into subcutaneous tissue (three cases). displayed macronodular (eight cases), cribriform (seven cases) organoid (six growth patterns, occurring combination. mainly composed immature basophilic cells associated scattered mature sebocytes. Numerous small infundibular cysts seven Mitotic activity low (none/one mitoses/mm 2 ). Immunohistochemistry showed positivity for androgen receptor p63. Preserved expression MLH1, PMS2, MSH2 MSH6 observed RNA‐sequencing RCOR1 :: GRHL2 BCL6::GRHL1 (two BCOR (one case), GRHL1 case) TLE1::GRHL1 fusion transcript. Methylation analysis demonstrated that ‐fused form an independent cluster highlight proximity such poromas folliculo‐sebaceous differentiation. Conclusions conclusion, report recurrent fusions genes distinctive subset harbouring infundibulocystic differentiation, frequent pattern lack deficiency.

Language: Английский

Gene fusions in poroma, porocarcinoma and related adnexal skin tumours: An update DOI Creative Commons
Thibault Kervarrec, Daniel Pissaloux, Franck Tirode

et al.

Histopathology, Journal Year: 2023, Volume and Issue: 84(2), P. 266 - 278

Published: Aug. 23, 2023

Poroma is a benign sweat gland tumour showing morphological features recapitulating the superficial portion of eccrine coil. A subset poromas may transform into porocarcinoma, its malignant counterpart. and porocarcinoma are characterised by recurrent gene fusions involving YAP1 , transcriptional co‐activator, which controlled Hippo signalling pathway. The fusion genes frequently involve MAML2 NUTM1 also rearranged in other cutaneous extracutaneous neoplasms. We aimed to review clinical, molecular this category adnexal neoplasms with special focus upon emerging differential diagnoses, discuss how their systematic characterisation contribute standardisation diagnosis, more accurate classification and, ultimately, refinement prognosis therapeutic modalities.

Language: Английский

Citations

19
Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases DOI Creative Commons
Thibault Kervarrec,

Danna Westphal,

Daniel Pissaloux

et al.

Histopathology, Journal Year: 2024, Volume and Issue: 85(4), P. 566 - 578

Published: May 24, 2024

Aims Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of duct and may arise from transformation preexisting benign poroma. In 2019, Sekine et al. demonstrated presence YAP1::MAML2 YAP1::NUTM1 fusions in most poromas porocarcinomas. Recently, our group identified PAK2‐ subset poromas. Herein we report series 12 porocarcinoma cases harbouring PAK1/2/3 fusions. Methods Results Five patients were male median age was 79 years (ranges: 59–95). Tumours located on trunk ( n = 7), thigh 3), neck 1), or groin area 1). Four developed distant metastases. Microscopically, seven harboured poroma component invasive part. Ductal formations observed all, while infundibular/horn cysts cells with vacuolated cytoplasm detected six tumours, respectively. three cases, consisted proliferation elongated cells, some which formed pseudovascular spaces, whereas others predominant solid trabecular growth pattern. Immunohistochemical staining for CEA EMA confirmed ducts. Focal androgen receptor expression specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 2), ZDHHC5::PAK1 DLG1::PAK2 , CTDSP1::PAK1 CTNND1::PAK1 SSR1::PAK3 CTNNA1::PAK2 RNF13::PAK2 ROBO1::PAK2, CD47::PAK2 . Activating mutation HRAS (G13V, 3, G13R, 1, Q61L, 2) present cases. Conclusion Our study suggests that oncogenic driver porocarcinomas lacking YAP1 rearrangement.

Language: Английский

Citations

8
Gene Fusion-Driven Cutaneous Adnexal Neoplasms: An Updated Review Emphasizing Molecular Characteristics DOI
Gerardo Cazzato, Maged Daruish, Francesco Fortarezza

et al.

American Journal of Dermatopathology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract: Gene rearrangements or fusions have emerged as critical oncogenic drivers in various cutaneous adnexal neoplasms. This review offers a comprehensive overview of both established and recently identified molecular alterations, with specific focus on gene fusions. Key alterations discussed include YAP1 rearrangements, CRTC1::MAML2 fusions, BRD3 MYB::NFIB ETV6::NTRK3 PLAG1 alongside rarer fusion transcripts, such MEF2C::SS18 , FOXK1::GRHL1/2 GPS2::GRHL RARA::NPEPPS . The article highlights the significance these genetic changes tumor biology their potential therapeutic implications for locally advanced metastatic skin tumors. It also addresses diagnostic challenges distinctions, providing updated insights into tumors driven by

Language: Английский

Citations

0
YAP1‐NUTM1 fusions are infrequent in porocarcinomas arising in a cohort including immunocompromised patients DOI
Mark D. Eisner, R.T. Winn,

T. Oliphant

et al.

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

Citations

0
Histologic and Genetic Features of 51 Melanocytic Neoplasms With Protein Kinase C Fusion Genes DOI
Arnaud de la Fouchardière, Daniel Pissaloux,

Aurélie Houlier

et al.

Modern Pathology, Journal Year: 2023, Volume and Issue: 36(11), P. 100286 - 100286

Published: July 19, 2023

Language: Английский

Citations

9
Tumeurs annexielles cutanées : mise au point et synthèse des gènes de fusion à connaître pour le diagnostic DOI
Thibault Kervarrec, Maxime Battistella, Nicolas Macagno

et al.

Annales de Pathologie, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Citations

1
YAP1::NR4A3 and YAP1::NCOA2 fusions in poroma: expanding the spectrum of molecular alterations in poroid tumors DOI
Léo‐Paul Secco, Louis Libbrecht,

Michiel Bonny

et al.

Virchows Archiv, Journal Year: 2024, Volume and Issue: 485(4), P. 749 - 753

Published: Aug. 23, 2024

Language: Английский

Citations

1
Nuclear pseudoinclusions as a clue for NUTM1‐rearranged poroid tumours recognition DOI
Antoine Taillandier, Mélanie Legrand,

Adrien Pétereau

et al.

Histopathology, Journal Year: 2024, Volume and Issue: 85(2), P. 362 - 365

Published: May 7, 2024

Language: Английский

Citations

0
Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases DOI Creative Commons
Mélanie Legrand, Baptiste Louveau, Nicolas Macagno

et al.

Histopathology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Aims Sebaceous neoplasms constitute a group of adnexal tumours, including sebaceous adenoma, sebaceoma and carcinoma. Although mismatch repair deficiency may be observed, the nature genetic alterations contributing to development most these tumours is still unknown. In present study, we describe clinical, microscopic, molecular features eight sebaceomas with GRHL gene rearrangement. Methods results Among sebaceomas, four occurred in women men; median age was 63 years (range = 29–89). The were located head neck area all cases. Microscopic examination revealed well‐demarcated lesion dermis focal extension into subcutaneous tissue (three cases). displayed macronodular (eight cases), cribriform (seven cases) organoid (six growth patterns, occurring combination. mainly composed immature basophilic cells associated scattered mature sebocytes. Numerous small infundibular cysts seven Mitotic activity low (none/one mitoses/mm 2 ). Immunohistochemistry showed positivity for androgen receptor p63. Preserved expression MLH1, PMS2, MSH2 MSH6 observed RNA‐sequencing RCOR1 :: GRHL2 BCL6::GRHL1 (two BCOR (one case), GRHL1 case) TLE1::GRHL1 fusion transcript. Methylation analysis demonstrated that ‐fused form an independent cluster highlight proximity such poromas folliculo‐sebaceous differentiation. Conclusions conclusion, report recurrent fusions genes distinctive subset harbouring infundibulocystic differentiation, frequent pattern lack deficiency.

Language: Английский

Citations

0