Vulvar squamous cell carcinoma in young women: a clinicopathologic study of 21 cases

Abstract

Objectives: Invasive squamous cell carcinoma (ISCC) of the vulva occurs most often in older women and the clinical, pathological, and immunohistochemical features of vulvar ISCC in young women are poorly characterized. The aim of this study was to examine clinical and pathological features of ISCC presenting in women younger than 40 years of age.

Methods: Patients younger than 40 years of age who presented with vulvar ISCC were identified in the population-based tumor registry of the British Columbia Cancer Agency (BCCA) for the period 1970-1998. Clinical data and follow-up were obtained. The pathologic material was reviewed and morphologic features assessed. Immunohistochemical staining for MIB-1 and p53 proteins was done and the presence of human papillomavirus (HPV) DNA was assessed by microdissection/PCR.

Results: Twenty-one cases, accounting for 5% of all cases of vulvar ISCC encountered at BCCA during this period, were identified, with patient's ages ranging from 17 to 39 years (mean 33). The number of cases of vulvar ISCC in young women, as a percentage of all cases of vulvar ISCC, increased significantly over the study period. Lichen sclerosus was seen in 3 cases. Vulvar intraepithelial neoplasia (VIN) was present in 20 of 21 cases and was multifocal in 4 of them. VIN was subclassified as warty in 7 cases, mixed warty and basaloid in 6, basaloid in 4, and differentiated in 3. There was MIB-1 immunostaining throughout the full thickness of warty and basaloid VIN. Only basal cells stained for MIB-1 in differentiated VIN. Increased p53 expression was present in only 2 cases; both were differentiated-type VIN. HPV DNA was detected in 17 of 20 cases. The tumors were staged as follows: stage IA, 3 cases; stage IB, 13 cases; stage II, 3 cases; stage III, 2 cases. Depth of invasion ranged from <1 to 8.5 mm. The definitive surgical procedure was vulvectomy with lymph node dissection in 14 cases, wide local excision in 6, and excisional biopsy in 1. Clinical follow-up of 1 to 28 years (median, 5 years) showed that 5 patients had local recurrence and 2 died of disease. Of the 21 patients in this study, 1 had concurrent HIV infection and 1 patient with Crohn's disease was treated with corticosteroids; the remaining patients had no clinical evidence of depressed immune function.

Conclusions: The incidence of vulvar ISCC in young women has increased over time; this increase cannot be accounted for by ISCC in immunocompromised patients. The overall disease outcome was excellent, with 2 of 21 patients dead of disease. Most tumors were associated with HPV, but cases of ISCC in the absence of HPV, and associated with differentiated VIN, were encountered. p53 staining of the basal layer can aid in recognition of differentiated VIN while MIB-1 staining within the upper layers of the squamous epithelium is consistently present in warty and basaloid VIN, but not in differentiated VIN.