Immunohistochemical Profile of Polymorphous Adenocarcinoma of Minor Salivary Gland: A Systematic Review and Meta-Analysis

Polymorphous adenocarcinoma (PAC) is a rare variant of minor salivary gland tumors. Because of its architectural diversity, histological diagnosis of PAC can be difficult especially for small biopsies, and immunohistochemistry is of great help in differentiating it from its histologic mimics. The aim of this study is to conduct a systematic literature review to identify reliable immunohistochemical markers for PAC. We conducted an electronic literature search of the MEDLINE, ScienceDirect, SpringerLink, and Wiley Online Library databases, covering the literature published in the period between 1988 and 2021. The eligibility criteria included case reports and retrospective studies of PAC cases with details of immunohistochemical markers. Following the search and selection process, 32 studies with 409 cases were included in this systematic review. Overall, > 90% positivity was observed for pan-cytokeratin (CK) (97.3%), CK7 (96.8%), CK7/8 (97.4%), E-cadherin (90.0%), Vimentin (92.5%), S100 (97.0%), p63 (91.7%), and SOX10 (100%), while little to no positivity was observed for CK20 (0.0%), p40 (0.0%), and GFAP (5.0%). The average MIB-1 labeling index was 3.78%. The results of this systematic review indicate that CK7+/CK20−, p63+/p40−, S100+, Vimentin+, and GFAP– immunophenotype have diagnostic value for PAC. In addition, the use of S100, MSA, p40, and c-Kit provide additional layers of information helpful to differentiate PAC from adenoid cystic carcinoma, one of challenging differential diagnoses.