Vulvar Squamous Cell Carcinoma With Sarcomatoid Features are HPV-independent Lesions: A Subset are Also Associated With TP 53-independent Lesions and Radiation Therapy.

Abstract

Vulvar squamous cell carcinoma of the vulva (VSCC) with sarcomatoid features is a rare variant characterized by spindle-cell morphology and occasional heterologous elements. They are difficult to evaluate due to rarity and lack unified nomenclature and histopathologic criteria. Eight cases of sarcomatoid VSCC were retrieved from archival electronic medical records from 2013 to 2021. Patients often presented at a mean age of 78-yr-old at stage FIGO (2018) III or above. The mean greatest diameter was 4.5 cm and mean depth of invasion was 11.5 mm. Spindle cells exhibited fascicular, nested, and cord-like growth patterns, though a haphazard arrangement or a mix of patterns was frequently observed. The sarcomatoid component frequently arose in the context of prior conventional VSCC treated with radiation therapy (n=6, 75% and chemotherapy (n=5, 63%) with latency periods of 5.2 and 5.4 yr, respectively. Associated lesions included differentiated vulvar intraepithelial neoplasia (n=4, 50%), lichen sclerosus (n=5, 63%), and vulvar acanthosis with altered differentiation (n=1, 13%). Immunohistochemistry showed that VSCC with sarcomatoid features aberrantly expressed p53 (n=4, 60%) through diffuse overexpression or null-type patterns. P16 was invariably negative in all cases. These findings suggest that VSCC with sarcomatoid features does not arise from the HPV-related carcinogenic pathway, and that a subset may also arise from the TP53-independent pathway. Recognizing sarcomatoid morphology in VSCC is important since it may confer an elevated risk of nodal metastasis and poorer survival. Larger studies are required to assess the etiology and prognostic implications of VSCC with sarcomatoid features.