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A series of 48 excised thin (≤5 mm in tumor thickness) invasive squamous cell carcinomas (SCCs) of the vulva in 44 patients were studied to determine the interrelationships of tumor type with type of adjacent vulvar intraepithelial neoplasia (VIN) and lichen sclerosus. The SCCs were of conventional keratinizing type in 38 tumors (79%), warty type in 6 (13%), and basaloid type in 4 (8%). VIN adjacent to SCC was found in 37 (77%) of the tumors. Of these, 19 were classic VIN (51%) and 18 were simplex (differentiated) VIN (49%). All 10 warty and basaloid SCCs had adjacent classic VIN. Of the 38 keratinizing SCCs, 27 (71%) had adjacent VIN, consisting of simplex VIN in 67% and classic VIN in 33%. The median age of the patients with classic VIN, simplex VIN, and no VIN were 62, 78, and 75 years, respectively. In the overall statistical analysis, the differences between the VIN types and the types of SCC were highly significant. In pairwise comparisons, significant differences in SCC type were found when the classic VIN group was compared with the simplex VIN group and when the classic VIN group was compared with the no VIN group. In contrast, no difference was found when the simplex VIN group was compared with the no VIN group. Lichen sclerosus (LS) was present in 14 of the 44 patients (32%). All SCCs in patients with LS were of keratinizing type. Of the 30 patients without LS, the SCCs were of the keratinizing type in 20 patients (67%), the warty type in 6 patients (20%), and the basaloid type in 4 patients (13%). Only 1 of the 19 (5%) patients with classic VIN had LS compared with 9 (56%) of the 16 patients with simplex VIN and 4 (44%) of 9 patients with no adjacent VIN. Atypical LS occurred in 8 of 14 patients with LS (57%); 4 of these (50%) also had simplex VIN and none had classic VIN. Significant differences in the overall comparison were found when comparing the percentage of keratinizing SCC and percentage of LS between the groups with classic VIN, simplex VIN, and no VIN. Pairwise comparisons revealed the similarity of features between the simplex VIN group and the no VIN group, and the distinction of both of these groups from the classic VIN group. Both the simplex VIN group and the no VIN group have a significantly greater association with keratinizing SCC and LS (including atypical LS) than does the classic VIN group. Strong staining for p53 with a high labeling index was commonly found in atypical LS and simplex VIN and may be of value in confirmation of these lesions. These findings support the theory that simplex VIN is the most likely precursor of conventional keratinizing SCC, the most common type of vulvar invasive carcinoma. Atypical LS may be closely related to simplex VIN.