Histopathological variants of head and neck squamous cell carcinomas: A multicenter study in Latin America

Histopathological variants of head and neck squamous cell carcinoma (HNSCC) are uncommon and account for approximately 5-15 % of all HNSCC cases. Owing to their heterogeneous clinicopathological characteristics, a correct diagnosis can be challenging. We aimed to analyze the clinicopathological, histochemical (HC), immunohistochemical (IHC), and in situ hybridization (ISH) findings of HNSCC variants in a Latin American population. In total, 1415 HNSCCs were retrospectively evaluated in accordance with the 2023 World Health Organization criteria. Sixty-six (4.6 %) HNSCC variants were identified, including verrucous carcinoma (VC, n = 21), basaloid SCC (BSCC, n = 13), spindle cell SCC (SCSCC, n = 8), adenosquamous carcinoma (ASC, n = 6), clear cell SCC (CCSCC, n = 4), cuniculatum carcinoma (CC, n = 4), lymphoepithelial carcinoma (LC, n = 3), papillary SCC (PSCC, n = 2), acantholytic SCC (ASCC, n = 2), pigmented SCC (PigSCC, n = 2), and carcinoma with rhabdoid phenotype (CRP, n = 1). Histomorphology, supported by IHC (mainly p53 and Ki-67), allows the diagnosis of most cases of VC, CC, PSCC, ASCC, and PigSCC. Mutant-type p53 pattern is common in BSCCs. SCSCC diagnosis requires IHC to highlight the epithelial phenotype in most cases, almost all of which exhibit a mutant-type p53 pattern. Human papillomavirus-associated BSCC and SCSCC are rare. HC analysis supported by IHC is relevant for most ASC and CCSCC diagnoses. Owing to the inflammatory component, IHC may be crucial for highlighting LC cells, with potential Epstein-Barr virus infection. CRP diagnosis relies on IHC and ISH findings in strict clinical correlation. Therefore, detailed clinicopathological characterization of HNSCC variants is fundamental because it provides valuable data with diagnostic, therapeutic, and prognostic impacts.