Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Thibault Kervarrec - , Centre Hospitalier Régional Universitaire de Tours, Université de Tours, CARADERM Network (Autor:in)
  • Danna Westphal - , Deutsches Krebsforschungszentrum, DKFZ Standort Dresden, Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Daniel Pissaloux - , Centre Léon Bérard, Universite Claude Bernard Lyon 1 (Autor:in)
  • Mélanie Legrand - , Centre Hospitalier Régional Universitaire de Tours (Autor:in)
  • Franck Tirode - , Centre Léon Bérard, Universite Claude Bernard Lyon 1 (Autor:in)
  • Anne Neuhart - , Centre Léon Bérard, Universite Claude Bernard Lyon 1 (Autor:in)
  • Francoise Drouot - , CARADERM Network, Cypath (Autor:in)
  • Jürgen C. Becker - , Universität Duisburg-Essen, Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Nicolas Macagno - , CARADERM Network, Assistance publique - Hôpitaux de Marseille (Autor:in)
  • Alice Seris - , CARADERM Network, Centre Hospitalier de Pau (Autor:in)
  • Thomas Jouary - , CARADERM Network, Centre Hospitalier de Pau (Autor:in)
  • Fanny Beltzung - , Hôpital Haut-leveque (Autor:in)
  • Marie Laure Jullie - , CARADERM Network, Hôpital Haut-leveque (Autor:in)
  • Paul W. Harms - , University of Michigan, Ann Arbor (Autor:in)
  • Bernard Cribier - , Université de Strasbourg (Autor:in)
  • Samia Mourah - , Hôpital Saint-Louis AP-HP (Autor:in)
  • Fanélie Jouenne - , Hôpital Saint-Louis AP-HP (Autor:in)
  • Gaelle Fromont - , Centre Hospitalier Régional Universitaire de Tours (Autor:in)
  • Baptiste Louveau - , Hôpital Saint-Louis AP-HP (Autor:in)
  • Maxence Mancini - , Hôpital Saint-Louis AP-HP (Autor:in)
  • Dmitry V. Kazakov - , Pathologie Institut Enge (Autor:in)
  • Arnaud de la Fouchardière - , CARADERM Network, Nationales Zentrum für Tumorerkrankungen (NCT) Dresden, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Maxime Battistella - , CARADERM Network, Université Paris Cité (Autor:in)

Abstract

AIMS: Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions.

METHODS AND RESULTS: Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases.

CONCLUSION: Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.

Details

OriginalspracheEnglisch
Seiten (von - bis)566-578
Seitenumfang13
FachzeitschriftHistopathology
Jahrgang85
Ausgabenummer4
PublikationsstatusVeröffentlicht - Okt. 2024
Peer-Review-StatusJa

Externe IDs

Scopus 85193954277
ORCID /0000-0003-4340-0402/work/175220402

Schlagworte

Schlagwörter

  • Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Eccrine Porocarcinoma/pathology, Oncogene Proteins, Fusion/genetics, p21-Activated Kinases/genetics, Sweat Gland Neoplasms/pathology