[ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma: a clinicopathological analysis]

Objective: To investigate the clinicopathologic features, immunophenotype, molecular genetic changes of ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma (ETV6-RLGSNAC). Methods: Primary sinonasal epithelial malignant tumors were collected from January 2015 to January 2020 in the Department of Pathology, Eye, Ear, Nose and Throat Hospital affiliated to Fudan University. Through morphological observation, immunohistochemical detection and fluorescence in situ hybridization (FISH), ETV6-RLGSNAC was screened out for clinicopathological feature analysis, and relevant literatures were reviewed. Results: There were 550 cases of primary sinonasal epithelial malignant tumors, among which 82 cases were adenocarcinoma. There were 29 cases of low-grade non-intestinal adenocarcinoma, only 3 cases of ETV6-RLGSNAC were screened out. Of the 3 patients, 2 cases were male and 1 case was female, with a mean age of 54 years (range 37-64 years). The main clinical manifestations were nasal stenosis, nasal obstruction and epistaxis. A neoplasm with smooth surfaces was observed under nasal endoscopy. Imaging showed an expansive mass in the sinonasal area. Gross examination showed gray-yellow cut surface with firm texture and a maximum diameter of 2-3 cm. Microscopically, tumors were non-encapsulated and well-circumscribed with expansive growth pattern. The tumor cells were small and mild, cylindrical and cuboidal, and arranged in regular glandular and trabecular patterns. The cytoplasm was eosinophilic and the nuclei were basally located with inconspicuous nucleoli. By immunohistochemistry (IHC), CK7, SOX-10, DOG1 and vimentin were positive and S-100 expressed in small clusters of cells in all cases. GCDFP-15, CD56, CK20, mammaglobin, TTF-1, NR4A3 were all negative. The Ki-67 value-added index of all cases was low (<5%). ETV6 gene rearrangement was confirmed in all the cases by FISH, and two cases had NTRK3 gene rearrangement. All three patients underwent radical resection after diagnosis, and one also had adjuvant radiotherapy. All three patients were available with a follow-up time of 12-25 months, and all were recurrence free. Conclusions: ETV6-RLGSNAC is a rare low-grade and newly named non-intestinal adenocarcinoma. The histomorphology is similar to other low-grade nasal sinonasal adenocarcinomas and some salivary gland tumors. IHC and FISH are useful for the diagnosis and differential diagnosis.