94 HPV-Associated Adenosquamous Carcinoma of the Tonsil: A Diagnostic Pitfall in Small Biopsies

Introduction/Objective Accurate diagnosis of head and neck tumors is critical, particularly with HPV-associated variants. While HPV-related squamous cell carcinoma (SCC) is well-characterized, rarer subtypes like HPV-associated adenosquamous carcinoma (ASC) are less recognized and may present diagnostic challenges. Small biopsies risk sampling error, especially in tumors with mixed histology, leading to potential misclassification and inappropriate management. We present a case of an HPV-associated ASC of the tonsil initially misdiagnosed on biopsy, highlighting the importance of comprehensive evaluation. Methods/Case Report A 68-year-old male presented with a left tonsillar mass. Initial biopsy at an outside hospital revealed p16-positive nonkeratinizing SCC. While awaiting the report, a repeat biopsy was performed, demonstrating p16-associated adenocarcinoma, confirmed with HPV RNA in situ hybridization. Following surgical excision, final histology revealed HPV-associated adenosquamous carcinoma with intermixed glandular and squamous components, reconciling the discordant biopsies. Comprehensive tissue evaluation was crucial to reaching the final diagnosis. Results NA Conclusion This case underscores the diagnostic pitfalls in small biopsies of head and neck tumors, particularly when dealing with rare subtypes like HPV-associated ASC. Fragmented or non-representative sampling may yield misleading results, especially when distinct histologic components are spatially heterogeneous. This case highlights the importance of maintaining a broad differential and pursuing re-biopsy when initial findings are incongruent.