외음부의 편평세포암과 전암성 병변의 조직학적, 면역화학적 특성 분석

Abstract

Backgrounds. Vulvar squamous cell carcinoma (VSCC) develops from two main subtypes of precancerous lesions, namely usual-type vulvar intraepithelial neoplasia (uVIN), which is associated with human papilloma virus (HPV), and differentiated-type VIN (dVIN), which is HPV-independent. dVIN has a higher rate of recurrence and progression to VSCC than uVIN. It is difficult to make a correct diagnosis of dVIN because the histologic differences between dVIN and normal vulvar epithelium are subtle. Materials and Methods. To further define the diagnostic characteristics of the two types of precancerous vulvar lesions, especially dVIN, the histopathologic features and immunohistochemical profiles of 36 lesions were studied. Results. In most cases, epithelium adjacent to VSCCs showed the histologic characteristics of either uVIN (20 cases, 56%) or dVIN (11 cases, 31%); however, five cases (14%) had indeterminate histopathology. Nineteen cases (53%) showed block-type immunoreactivity for p16INK4 with wild-type p53 expression (probably HPV-related), 13 (36%) showed p16INK4 negativity with abnormal p53 expression (HPV-independent), and the remaining four showed negativity (n=3, 11%) or positivity (n=1, 3%) for both markers. All p16INK4 block-positive cases were uVINs (n=19) histologically, while p16INK4-negative cases were either dVIN or indeterminate. All five indeterminate cases showed abnormal p53 expression, and three of them had cytologic atypia extending up to the midportion of the epidermis. These results suggest that the HPV-independent subtype may have a wider extent of cytologic atypia than previously described. Histologic dVIN (11 cases) showed p53 overexpression in 7 cases (58%), no expression in one case (8%), with the remaining three cases being p16INK4-negative/p53-wild-type. These results suggest that dVIN may have a pathogenic mechanism other than abnormal p53. Of 13 cases showing abnormal p53 expression, two (17%) did not show any appreciable level of cytologic atypia in the basal layer, indicating that p53 mutation may not be predicted by histologic features alone. Conclusions. A correlation between histopathologic features and immunohistochemical findings was observed in only 75% of VINs. Therefore, immunohistochemical staining for p53 and p16INK4 is required for the correct diagnosis and subtyping of VINs. Keywords: vulva, vulvar intraepithelial neoplasia, squamous cell carcinoma, p16INK4, p53