HPV-related multiphenotypic sinonasal carcinoma: Clinicopathologic and immunohistochemical characterization of 3 cases with comprehensive literature review and emphasis on differential diagnosis.

HPV-related multiphenotypic sinonasal carcinoma (HMSC) represents a rare malignancy exhibiting surface and salivary gland-derived properties, and a strong association with high-risk HPV. We present the clinicopathologic and immunohistochemical characteristics of 3 examples of HMSC involving the nasal cavity (M:F = 2:1, age median = 66 years; range = 51-75 years). Histopathologically, all 3 HMSCs exhibited infiltrative lobules and nests of basaloid cells with focal cribriform and microcystic configuration. Neoplastic cells featured high N:C ratio with round-to-ovoid, vesicular or angulated nuclei, scant cytoplasm, and numerous mitoses. Pleomorphism, comedonecrosis and focal squamous differentiation were noted. High-grade surface dysplasia was easily identified in one HMSC. Surrounding stroma varied from myxohyaline-to-densely fibrous. By immunohistochemistry, lesional cells were positive for epithelial markers as well as SMA, calponin, SOX10, and S100. All HMSCs showed strong, diffuse p16 staining and harbored high-risk HPV by DNA ISH. A total of 124 previously reported HMSC cases were identified (M:F = 1:1.26, mean age = 56.6 years; range = 28-90 years) with 83.7 % involving the nasal cavity with or without extension into adjacent anatomic structures. Approximately 60 % of HMSCs clinically presented as T1/T2 lesions with lymph node metastases identified in 15.3 % at diagnosis. HPV33 was detected in 75 % of HMSCs. Locoregional recurrences occurred in 38.7 % of cases but 85.3 % of patients were alive after a mean follow-up period of 29 months (range = 1-256). CONCLUSION: Diagnosis of HMSC may be challenging, particularly in small biopsy specimens, owing to its relative rarity and significant histopathologic and immunophenotypic similarities to other sinonasal malignancies. Despite its high-grade histomorphologic features, prognosis for HMSC is considered favorable.