Clinicopathological and Molecular Insights into Primary Retroperitoneal Squamous Cell Carcinoma: HPV Association and Discovery of Recurrent PIK3CA E545K Mutation

Abstract

Background/Aim: Primary retroperitoneal squamous cell carcinoma (PRSCC) is extremely rare, and its diagnosis and management are challenging. Previous reports have highlighted the potential role of human papillomavirus (HPV) in the pathogenesis of PRSCC. This study aimed to determine the clinicopathological and molecular characteristics of PRSCC. Patients and Methods: We searched PubMed for previously published PRSCC cases. Immunostaining, human papillomavirus (HPV) testing, and targeted DNA and RNA sequencing were performed. Results: A total of 25 cases of PRSCC were analyzed. The mean age was 54.3 years, with the majority being women. They presented with pain in the lower abdomen, pelvis, and lower extremities; deep vein thrombosis; urinary symptoms; hydronephrosis; and ureteral obstruction. Treatment modalities included chemotherapy, radiation therapy, and concurrent chemoradiotherapy, with varying outcomes. HPV DNA was detected in most cases, with tumors exhibiting diffuse p16 positivity. Additionally, two patients carried a hotspot E545K mutation in phosphatidylinositol-4,5-bis-phosphate 3-kinase catalytic subunit alpha (PIK3CA). Conclusion: This study provides insights into the clinico-pathological features of PRSCC and identified a novel recurrent PIK3CA mutation in HPV-associated PRSCCs. Our findings suggest the potential utility of next-generation sequencing for identifying therapeutic targets. Further studies are warranted to clarify whether PIK3CA E545K mutation has diagnostic and therapeutic potential in patients with PRSCC.