NUT Is a Specific Immunohistochemical Marker for the... : The American Journal of Surgical Pathology (original) (raw)

Original Articles

NUT Is a Specific Immunohistochemical Marker for the Diagnosis of _YAP1-NUTM1_-rearranged Cutaneous Poroid Neoplasms

Macagno, Nicolas MD, PhD*,†,‡; Kervarrec, Thibault MD, PhD*,§; Sohier, Pierre MD, PhD*,∥,¶; Poirot, Brigitte PharmD, PhD#,**; Haffner, Aurélie MD†; Carlotti, Agnès MD*,∥; Balme, Brigitte MD*,††; Castillo, Christine MD‡‡; Jullie, Marie-Laure MD*,§§; Osio, Amélie MD*,∥∥; Lehmann-Che, Jacqueline PharmD, PhD¶,#,**; Frouin, Eric MD*,¶¶,##; Battistella, Maxime MD, PhD*,¶,**,∥∥

*CARADERM, French Network of Rare Cutaneous Cancer

†Department of Pathology, Timone University Hospital

‡Aix Marseille University, INSERM, MMG, Marseille

§Department of Pathology, Trousseau University Hospital, Tours

∥Department of Pathology, Cochin Hospital, AP-HP Paris University Center

¶University of Paris

#Molecular Oncology Unit

∥∥Department of Pathology, Hospital Saint-Louis, AP-HP

**INSERM, U976 HIPI, Paris

††Department of Dermatology, Lyon-Sud Hospital

‡‡Department of Biopathology, Léon Bérard Centre, Cypath, Lyon

§§Department of Pathology, Bordeaux University Hospitals, Pessac

¶¶Department of Pathology, University Hospital of Poitiers

##LITEC EA 4331, B36, Poitiers, France

N.M., T.K., and P.S.: wrote the manuscript. B.P., J.L.-C., and M.B.: performed molecular studies. M.B.: supervised the project.

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Nicolas Macagno, MD, PhD, Department of Pathology, Timone University Hospital, Marseille 13385, France (e-mail: [email protected]).

Abstract

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.