Premalignant lesions of the lower female genital tract: cervix, vagina and vulva

Premalignant lesions of the lower female genital tract encompassing the cervix, vagina and vulva are variably common and many, but by no means all, are related to infection by human papillomavirus (HPV). In this review, pathological aspects of the various premalignant lesions are discussed, mainly concentrating on new developments. The value of ancillary studies, mainly immunohistochemical, is discussed at the appropriate points. In the cervix, the terminology and morphological features of premalignant glandular lesions is covered, as is the distinction between adenocarcinoma in situ (AIS) and early invasive adenocarcinoma, which may be very problematic. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is emerging with lobular endocervical glandular hyperplasia (LEGH), including so-called atypical LEGH, representing a possible precursor of non HPV-related cervical adenocarcinomas exhibiting gastric differentiation; these include the cytologically bland adenoma malignum and the morphologically malignant gastric type adenocarcinoma. Stratified mucin producing intraepithelial lesion (SMILE) is a premalignant cervical lesion with morphological overlap between cervical intraepithelial neoplasia (CIN) and AIS and which is variably regarded as a form of reserve cell dysplasia or stratified AIS. It is now firmly established that there are two distinct types of vulval intraepithelial neoplasia (VIN) with a different pathogenesis, molecular events, morphological features and risk of progression to squamous carcinoma. These comprise a more common HPV-related usual type VIN (also referred to as classic, undifferentiated, basaloid, warty, Bowenoid type) and a more uncommon differentiated (simplex) type which is non-HPV related and which is sometimes associated with lichen sclerosus. The former has a relatively low risk of progression to HPV-related vulval squamous carcinoma and the latter a high risk of progression to non-HPV related vulval squamous carcinoma. Various aspects of vulval Paget's disease are also discussed.