Not infrequently, the pathologist receives biopsies from the vagi­nal vault. This usually implies that the patient had a (recent) hys­terectomy, and on follow-up a polypoid lesion is seen in the scar area of the vaginal apex. In most cases this is granulation tissue, histologi­cally characterized by heavily inflamed, richly vascularized loose con­nective tissue, which may or may not be covered by stratified squamous epithelium. The differential diagnosis includes a malignant tumor, especially (recurrent) endometrial or cervical carcinoma. Therefore it is important that the clinical information be provided if, when and why a hysterectomy was performed. Occasionally the tissue will turn out to be a prolapsed fallopian tube. The typical scenario for this is when a vaginal hysterectomy was performed, in which case the adnexa are often left behind. If a wound dehiscence at the vaginal apex occurs, the fimbriated end of the fallopian tube can prolapse into the vagina. This can lead to vaginal discharge and/or ascending infec­tions. Unlike granulation tissue or tumor, biopsy of the fallopian tube is painful, which may be the first clue to the nature of the lesion. Histologically, the tubal tissue can be very inflamed and vascularized, similar to granulation tissue. The finding of a tubal-type ciliated epithelium is diagnostic and should be searched for in any granulation tissue-like biopsy from the vaginal vault. Another entity seen in the vaginal vault is the rare postoperative spindle cell nodule. As the name implies, it develops within weeks to months after a surgical procedure. Histologically it is composed of fascicles of plump spindle cells with interspersed chronic inflammatory cells. Although mitotic figures may be numerous, cytologic features of this benign lesion are otherwise bland.

Human papilloma virus (HPV) plays an important role in both infec­tious and neoplastic lesions of the cervicovaginal mucosa. While the molecular pathogenetic mechanisms of HPV-associated tumorigenesis

Papillomaviruses are highly species- and site-specific, and there are more than 100 different identified human types. Separate types are defined as having a greater than 10% divergence in the DNA sequence of the L1, E6 and E7 genes. If the difference is less than 10% com­pared to an already known type, it is referred to as a variant or sub­type. About 40 HPV types target the skin and mucosae of the human anogenital region. Based on the frequency of their association with invasive carcinoma, they are classified into low risk (including HPV 6, 11, 40, 42, 43, 44, 54) and high risk (including 16, 18, 31, 33, 35, 39, 45, 51, 52, 58) types. Some of the abovementioned HPV E6/E7 functions are specific to high risk types, and/or the high risk type viral proteins have a higher affinity to their cellular target proteins than the low risk type proteins. This explains why HPV 16 is the most frequent type associated with invasive carcinoma, accounting for 54% of squa­mous cell carcinomas and over 40% of adenocarcinomas.

several times since. At present, the three-tiered Cervical Intraepithelial Neoplasia (CIN) system and the two-tiered Squamous Intraepithelial Lesion (SIL) system are most frequently used. In the CIN classification lesions are graded as mild, moderate and severe dysplasia (CIN 1, 2, and 3, respectively), based on the proportion of the full thickness of the squa­mous epithelium that is occupied by immature dysplastic cells: in CIN 1, dysplastic cells are confined to the lower third, in CIN 2, they extend into the middle third, and in CIN 3, they extend into the upper third of the epithelium. The term carcinoma in situ refers to those lesions within the CIN 3 category that show virtually no maturation at all. The analogous classification for Vaginal Intraepithelial Neoplasia is VAIN 1–3, respectively. The CIN nomenclature was introduced under the assumption that the different grades of CIN represent a continuum on a spectrum of the same disease process, invasive carcinoma being the end point. With improved understanding of the molecular pathogene­sis, including the facts outlined above, it is now thought that intraep­ithelial lesions can be divided into purely infectious lesions and those in which integration of the viral DNA into the host cell genome has led to transformation into a neoplastic lesion. Based on this biologic dichotomy, and in analogy with the Bethesda system used for cervical cytology reports, histopathologic findings have recently been classified as low grade (LG) versus high grade (HG) Squamous Intraepithelial Lesions (SIL). LG-SIL encompasses condylomas and CIN 1, whereas HG-SIL comprises CIN 2, CIN 3 and carcinoma in situ. (This is the classification commonly used in the USA; note that in many European countries, CIN 2 is classified as a low-grade lesion!). This two-tiered system is felt to better reflect the different biologic behavior of the lesions, and parallels clinical management: the vast majority of low grade lesions regresses spontaneously and does not need active treat­ment, while high grade lesions have a greater risk of progressing to inva­sive carcinoma and therefore are surgically removed.

exhibit the epidemiologic features of a sexually transmitted disease (STD). Early age at first vaginal intercourse, number of sexual part­ners, oral contraceptive use and a history of other STDs (herpes, chlamydia, syphilis) are risk factors for cervical carcinoma. HPV infec­tion is a necessary, but not sufficient, condition for developing almost all cervical carcinomas. Other, much less well understood factors must also play a role in carcinogenesis. Probably the most important of those is the immune system. It is known that precursor lesions have a much higher risk of progression, and can progress more rapidly under immunocompromised conditions, including HIV/AIDS, post­transplantation immunosuppression or chemotherapy. In addition, tobacco smoking is another independent risk factor for cervical squa­mous cell carcinoma (but not adenocarcinoma) and is associated with an increased prevalence of HPV infections.