Immunohistochemical and genetic analysis of respiratory epithelial Adenomatoid Hamartomas and Seromucinous Hamartomas: are they precursor lesions to Sinonasal low-grade Tubulopapillary adenocarcinomas?

Abstract

Respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH) are rare tumor-like lesions of the nasal cavity, paranasal sinuses, and nasopharynx. The pathogenesis of REAH/SH is still unclear. Neoplastic proliferation, chronic mechanical irritation, inflammation, or possible embryological tissue misplacement are speculated as possible mechanisms of their development. Low-grade tubulopapillary adenocarcinoma (LGTA) is a rare variant of non-salivary, non-intestinal type sinonasal adenocarcinoma. The aim of this study was to evaluate the immunohistochemical and genetic profiles of 10 cases of REAH/SH, with serous, mucinous and respiratory components evaluated separately, and to compare these findings with the features of 9 cases of LGTA. All cases of REAH/SH and LGTA were analyzed immunohistochemically with a cocktail of mucin antigens (MUC1, MUC2, MUC4, MUC5AC, MUC6), and with epithelial (CK7, CK20, CDX2, SATB2), and myoepithelial markers (S100 protein, p63, SOX10). The next-generation sequencing (NGS) assay was performed using FusionPlex Solid Tumor Kit (ArcherDx) in 10 cases of REAH/SH and the EGFR-ZNF267 gene fusion was detected in one of them. Two female REAH/SH cases were assessed for the presence of clonality. Using the HUMARA assay, one case was proved to be clonal. The serous component of REAH/SH was positive for CK7/MUC1 and SOX10 similarly to LGTA. Though REAH/SH and LGTA are histopathologically and clinically separate entities, the overlap in their morphological and immunohistochemical profiles, suggests that REAH/SH might be a precursor lesion of LGTA.