Sarcomatoid Squamous Cell Carcinoma of the Vulva Presenting with p53-Mutated Differentiated Vulvar Intraepithelial Carcinoma

Summary: Vulvar squamous cell carcinoma (SCC) and its precursors are classified as HPV-dependent or independent. Sarcomatoid carcinoma is a rare, poorly differentiated variant showing overlap with many other tumors; often a diagnosis of exclusion requiring immunohistochemical (IHC) confirmation. Differentiated vulvar intraepithelial neoplasia (DVIN) is a p53-mutated precursor lesion frequently associated with lichen sclerosus and known to show an aggressive clinical course. Herein is a case of DVIN associated with sarcomatoid SCC. Mapping biopsies of a vulvar lesion in a 62-year-old female demonstrated invasive poorly differentiated spindled-to-epithelioid cells with pleomorphism and macronuclei. An in-situ lesion was noted with basilar atypia, acanthosis, lack of granular layer, and intercellular bridges. The invasive component showed focal positivity for p63, Cam 5.2, CK5/6 and diffuse nuclear (mutational) positivity for p53, and was negative for S100, SOX10, desmin, and CD34. The in-situ component showed basilar (mutational) expression of p53. HPV high-risk in situ hybridization and p16 showed no significant staining in both components. This case demonstrates the challenges in evaluating poorly differentiated malignancies of the vulva, as the diagnostic precursor lesion was very focal. A thorough panel of IHC is necessary as well as careful correlation with clinical and microscopic findings.