Adenocarcinoma polimorfo de glândula salivar: caracterização histopatológica com investigação do gene PRKD1 e proteínas relacionadas à via de sinalização Hedgehog

Abstract

Polymorphous adenocarcinoma (PAC) is a rare malignant epithelial neoplasm that principally affects the minor salivary glands. It typically shows indolent growth, a generally favorable prognosis, and broad morphological heterogeneity, factors that often complicate its differential diagnosis from other salivary gland tumors. This thesis aimed to investigate the clinical, histopathological, immunohistochemical, and molecular aspects of PAC. A total of 18 cases were analyzed for clinical and histopathological evaluation, of which 15 were also subjected to molecular analysis of the PRKD1 gene and the expression of proteins in the Hedgehog (HH) signaling pathway. The lesions predominated in women (76.5%), with a mean age of 59.6 years, and the palate was the most frequently affected site (55.6%). Histologically, architectural diversity was observed with the coexistence of different growth patterns, particularly lobular, tubular, and cribriform. The cribriform subtype was associated with a higher frequency of invasion, including perineural invasion and infiltration of mucous acini. Among the 15 cases initially included in the PRKD1 gene analysis, eight met the quality requirements for PCR amplification and sequencing. The PRKD1 c.2130A>C/T (p.p.Glu710Asp) hotspot mutation was identified in four of them (50%). A novel variant at codon 704 (p.H704Y) was also detected in a case that simultaneously carried the p.Glu710Asp mutation. Immunohistochemistry consistently demonstrated expression of HH pathway proteins, suggesting their involvement in PAC tumor morphogenesis. A significant positive correlation was observed between PRKD1 expression and the HH components IHH, SMO, and GLI-1, indicating a possible interaction independent of SHH activation. Taken together, these findings reinforce the morphological complexity of PAC, confirm PRKD1 p.Glu710Asp as a relevant diagnostic marker, and demonstrate the involvement of the HH signaling pathway in tumor morphogenesis. By deepening the understanding of PAC biology, this study opens new avenues for the diagnosis and management of this rare neoplasm.