Expanding the spectrum of low-grade sinonasal adenocarcinoma with biphasic seromucinous differentiation and activating HRAS/AKT1 mutations.

Hadnagy, Viktoria S; Körner, Meike; Rössle, Matthias; Dubach, Patrick; Pabst, Gunther; Kotulova, Alexandra; Weder, Stefan; Seifert, Robert; Rushing, Elisabeth J; Holzmann, David; Hüllner, Martin; Freiberger, Sandra N; Rupp, Niels J (2024). Expanding the spectrum of low-grade sinonasal adenocarcinoma with biphasic seromucinous differentiation and activating HRAS/AKT1 mutations. (In Press). Histopathology Wiley 10.1111/his.15251

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AIMS

Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and salivary-type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification.

METHODS AND RESULTS

Clinical, histological and molecular characterisation of four cases of biphasic, low-grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo-glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in-situ/precursor lesions adjacent to the tumour. Follow-up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years.

CONCLUSION

This study further corroborates a distinct biphasic low-grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial-myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC.

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