Genetic, Immunohistochemical and mRNA In Situ Hybridization Profiling of Condyloma with Concurrent Squamous Cell Carcinoma and High-Grade Squamous Intraepithelial Lesion.

Condyloma acuminatum is a human papilloma virus (HPV)-associated papillary lesion of the lower anogenital tract. Although a majority are benign, rarely the coexistence of high-grade squamous intraepithelial lesion (HSIL) or invasive squamous cell carcinoma (SCC) with condyloma has been reported, which is important to recognize and diagnose. In this study, we examined the clinicopathologic, immunohistochemical (IHC), and HPV mRNA in situ hybridization (RISH) signal patterns of 63 condylomas, 35 condylomas with concurrent HSIL, 15 condylomas with concurrent SCC, 8 warty HSILs, and 17 warty SCCs. The genetic features of 10 condylomas with concurrent SCC and 14 warty SCCs were also examined. The search included cases in all sites of the lower anogenital tract. HPV-independent lesions were excluded. Our findings show that condylomas with concurrent HSIL or SCC often display different patterns of p16 immunohistochemical (IHC) staining and low-risk and high-risk (HR) HPV RISH-staining patterns depending on the area of the lesion evaluated. Our findings also support previous studies showing that condylomas can harbor both and low-risk and HR-HPV types either alone or in combination. HR-HPV RISH signal patterns were also more varied in condylomas with concurrent HSIL and SCC compared with warty HSIL or warty SCC. Follow-up data revealed that 38% of condylomas recurred and 26% progressed to HSIL. For condylomas with concurrent HSIL, 43% recurred and 9% progressed to SCC. Condylomas with concurrent SCC were associated with mutations in ASXL1, TERT, and CDKN2A/CDKN2B, whereas warty SCC was associated with mutations in PIK3CA, KMT2C, and FAT1.