Skin-analogue primary poroid neoplasms of the head and neck with YAP1/WWTR1::MAML2/NUTM1 fusions: clinicopathologic and genetic spectrum of a novel tumor family delineated in a series of 10 cases.

Porocarcinoma is a rare type of aggressive skin adnexal carcinoma with terminal sweat duct differentiation, representing the malignant counterpart of the more common benign eccrine poroma. Diagnosis is based on distinctive morphology, supplemented by immunohistochemistry. While all tumors display a squamous immunophenotype, porocarcinomas only infrequently show frankly squamous cell cytology (squamous variant). Most poromas and porocarcinomas harbor YAP1::MAML2/NUTM1 or, rarely, WWTR1::NUTM1 fusions. We herein describe 10 extra-cutaneous primary (8 salivary, 1 mandibular, 1 nasopharyngeal) poroid neoplasms affecting 6 males and 4 females, aged 17 to 71 years (median, 49). The salivary cases originated in the parotid (n = 6; 1 within intraparotid lymph node), lower lip minor salivary glands (1), and palate (1). All, but one case, were treated by excision with or without lymph node dissection (two received adjuvant chemoradiation). Immune chemotherapy was given to the nasopharyngeal case. Histologically, five cases were frankly malignant (porocarcinoma-like), two infiltrating low-grade and three bland-looking (poroma-like). Three bland tumors were predominantly cystic. Regional lymph nodes were positive in three of three sampled cases. Limited follow-up was available for six patients (1-43 months; median, 6). Five patients were disease-free and one was alive with disease at 16 months. Targeted RNA sequencing revealed YAP1 fusions in nine cases (fused to MAML2 in four and to NUTM1 in five cases) and a WWTR1::NUTM1 fusion in one case. This series introduces skin-analogue poroid neoplasms as a distinct extra-cutaneous head and neck entity, originating mostly from major and minor salivary glands and recapitulating/spanning the spectrum of cutaneous poroid tumors with some cases showing bland poroma-like morphology, while others are high-grade porocarcinoma-like malignancies. This tumor type should be distinguished from the many primary and metastatic salivary neoplasms with squamous immunophenotype. In particular, the NUTM1-rearranged (NUTM1-immunopositive) cases should be distinguished from the more aggressive NUT carcinoma, as both share overlapping anatomic sites and squamous cell phenotype and express NUTM1. Moreover, MAML2-fused cases might be confused with variant or high-grade mucoepidermoid carcinomas, as they share squamous phenotype and MAML2 rearrangements. The biology of bland cases and their nosology (benign vs low-grade malignant) remain to be further characterized.