NUT Is a Specific Immunohistochemical Marker for the Diagnosis of YAP1-NUTM1-rearranged Cutaneous Poroid Neoplasms

Nicolas Macagno (1, 2) , Thibault Kervarrec (3) , Pierre Sohier (4) , Brigitte Poirot (5) , Aurélie Haffner (6) , Agnès Carlotti (4) , Brigitte Balme (7) , Christine Castillo (8) , Marie-Laure Jullie (9) , Amélie Osio (5) , Jacqueline Lehmann-Che (10) , Eric Frouin (11) , Maxime Battistella (12)

1 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
2 ACPNP - Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM]
3 CHU Trousseau [Tours]
4 Hôpital Cochin [AP-HP]
5 INSERM - Institut National de la Santé et de la Recherche Médicale
6 TIMONE - Hôpital de la Timone [CHU - APHM]
7 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
8 Centre Léon Bérard [Lyon]
9 CHU Bordeaux
10 UFR Médecine UPCité - UFR Médecine [Santé] - Université Paris Cité
11 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
12 AP-HP - Hopital Saint-Louis [AP-HP]

YAP1-NUTM1 fusion transcripts have been recently reported in poroma and porocarcinoma. NUTM1 translocation can be screened by nuclear protein in testis (NUT) immunohistochemistry in various malignancies, but its diagnostic performance has not been thoroughly validated on a large cohort of cutaneous epithelial neoplasms. We have evaluated NUT immunohistochemical expression in a large cohort encompassing 835 cases of various cutaneous epidermal or adnexal epithelial neoplasms. NUT expression was specific to eccrine poromas and porocarcinoma, with 32% of cases showing NUT expression. All other cutaneous tumors tested lacked NUT expression, including mimickers such as seborrheic keratosis, Bowen disease, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, nodular hidradenoma, and all other adnexal tumors tested. Remarkably, NUT expression was more frequent in a distinct morphologic subgroup. Indeed, 93% of poroid hidradenoma (dermal/subcutaneous nodular poroma, 13/14) and 80% of poroid hidradenocarcinoma cases (malignant poroid hidradenoma, 4/5) showed NUT expression, in contrast to 17% and 11% of classic poroma (4/23) and porocarcinoma cases (4/35), respectively. RNA sequencing of 12 NUT-positive neoplasms further confirmed the presence of a YAP1-NUTM1 fusion transcript in all cases, and also an EMC7-NUTM1 gene fusion in a single case. In the setting of a cutaneous adnexal neoplasm, nuclear expression of NUT accurately and specifically diagnosed a specific subgroup of benign and malignant poroid tumors, all associated with a NUTM1 fusion, which frequently harbored a poroid hidradenoma morphology.

Domaines: Sciences du Vivant [q-bio]; Génétique; Cancer; Médecine humaine et pathologie

Nicolas Macagno, Thibault Kervarrec, Pierre Sohier, Brigitte Poirot, Aurélie Haffner, et al.. NUT Is a Specific Immunohistochemical Marker for the Diagnosis of YAP1-NUTM1-rearranged Cutaneous Poroid Neoplasms. American Journal of Surgical Pathology, 2021, 45 (9), pp.1221-1227. ⟨10.1097/PAS.0000000000001693⟩. ⟨hal-03210178⟩