Recurrent PAK2 rearrangements in poroma with folliculo‐sebaceous differentiation

Thibault Kervarrec (1, 2) , Daniel Pissaloux (3, 4) , Sandrine Paindavoine (3) , Franck Tirode (4) , Amélie Osio (5) , Samia Mourah (5) , Fanélie Jouenne (5) , Pierre Sohier (6, 7) , Eduardo Calonje (8) , Agnes Pekar (8) , Evelyn Vanesa Erazo Luna (8) , Keisuke Goto (9) , Flore Delalande (10) , Eric Frouin (11) , Nicolas Macagno (12) , Françoise Drouot (13) , Monique Faisan (14) , Bernard Cribier (15, 16) , Maxime Battistella (5, 17) , Arnaud de la Fouchardière (3)

1 Service de Pathologie [CHRU Tours]
2 UMR ISP - Infectiologie et Santé Publique
3 Centre Léon Bérard [Lyon]
4 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
5 AP-HP - Hopital Saint-Louis [AP-HP]
6 UFR Médecine UPCité - UFR Médecine [Santé] - Université Paris Cité
7 Hôpital Cochin [AP-HP]
8 St. John's Institute of Dermatology
9 Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital
10 CHRO - Centre Hospitalier Régional d'Orléans
11 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
12 TIMONE - Hôpital de la Timone [CHU - APHM]
13 Cypath [Dijon]
14 Cypath (Lyon)
15 HUS - Les Hôpitaux Universitaires de Strasbourg
16 Nouvel Hôpital Civil de Strasbourg
17 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie

Aims: Poroma is a benign adnexal neoplasm with differentiation towards the upper portion of the sweat gland apparatus. In 2019, Sekine et al. demonstrated recurrent YAP1::MAML2 and YAP1::NUTM1 fusion in poroma and porocarcinoma. Follicular, sebaceous and/or apocrine differentiation has been reported in rare cases of poroma and whether these tumours constitute a variant of poroma or represent a distinctive tumour is a matter to debate. Herein we describe the clinical, immunophenotypic, and molecular features of 13 cases of poroma with folliculo-sebaceous differentiation. Methods and results: Most of the tumours were located on the head and neck region (n = 7), and on the thigh (n = 3). All presented were adults with a slight male predilection. The median tumour size was 10 mm (range: 4-25). Microscopically, lesions displayed features of poroma with nodules of monotonous basophilic cells associated with a second population of larger eosinophilic cells. In all cases, ducts and scattered sebocytes were identified. Infundibular cysts were present in 10 cases. In two cases high mitotic activity was noted, and in three cases cytologic atypia and areas of necrosis were identified. Whole transcriptome RNA sequencing demonstrated in-frame fusion transcripts involving RNF13::PAK2 (n = 4), EPHB3::PAK2 (n = 2), DLG1::PAK2 (n = 2), LRIG1::PAK2 (n = 1), ATP1B3::PAK2 (n = 1), TM9SF4::PAK2 (n = 1), and CTNNA1::PAK2 (n = 1). Moreover, fluorescence in situ hybridisation (FISH) analysis revealed PAK2 rearrangement in an additional case. No YAP1::MAML2 or YAP1::NUTM1 fusion was detected. Conclusion: Recurrent fusions involving the PAK2 gene in all analysed poroma with folliculo-sebaceous differentiation in this study confirms that this neoplasm represents a separate tumour entity distinct from YAP1::MAML2 or YAP1::NUTM1 rearranged poromas.

Keywords: PAK2; apocrine poroma; folliculo-sebaceous differentiation; holocrine poroma; infundibular adenoma

Domains: Cellular Biology

Thibault Kervarrec, Daniel Pissaloux, Sandrine Paindavoine, Franck Tirode, Amélie Osio, et al.. Recurrent PAK2 rearrangements in poroma with folliculo‐sebaceous differentiation. Histopathology, 2023, 83 (2), pp.310 - 319. ⟨10.1111/his.14940⟩. ⟨hal-04169743⟩