Squamous Cell Carcinomas comprise 67–80 % of vaginal cancers [30]. In contrast to cervical SCC, many vaginal SCCs are HPV negative. HPV has been found in 50–80 % of primary vaginal SCCs [31, 32]. Type 16 is the most common, exist in 33–56 % of cases [32]. HPV – related carcinomas are frequently nonkeratinizing and of basaloid or warty subtypes [32]. The presence of HPV does not associated with clinical stage, tumor size or tumor grade and overall prognosis did not differed significantly between the HPV positive and HPV negative groups [31]. Grade is not a significant predictor of prognosis [30, 31]. Low grade squamous intraepithelial lesion (LSIL) being equivalent to VAIN – 1 and high grade squamous intraepithelial lesion (HSIL) being equivalent to VAIN – 2 or VAIN – 3 (Bethesda System terminology) [4]. The development of untreated VAIN is not well understood, but with treated cases there is an approximately 5 % risk of progression to invasive SCC [30].

Glandular tumors are similar to Clear Cell Carcinoma (CCC) of the ovary or endometrium. Most cases have associated with vaginal adenosis [4]. Primary vaginal adenocarcinomas not associated with DES exposure have a much higher median age at presentation (54 years) than DES associated cases [33]. Prognosis is worse than other types of cancers, with 5–year survival rate of 34 % compared to 58 % for SCC and 93 % for DES associated Clear Cell Carcinoma [30, 33]. The second most common type is the primary vaginal adenocarcinoma (after CCC) [34]. The mean age was 60 years and have histologic characteristics typical of endometrial endometrioid adenocarcinomas. Primary vaginal mucinous adenocarcinoma like cervical mucinous adenocarcinoma has been reported following hysterectomy, probably arising from adenosis or endocervicosis [35]. Primary serous adenocarcinoma has been reported as a primary tumor in the vagina [36]. Very rare cases of primary vaginal adenocarcinoma of intestinal type have been reported [37]. Immunohistochemical, are positive for CDX-2 and Cytokeratin 20 and clinical, endoscopic, radiologic exclusion of origin from a colorectal primary is necessary for diagnosis [37]. Mesonephric adenocarcinoma, to occur from the remnants of the mesonephric ducts, is one of the rarest types. The mean age was 41 years and presentation often with multicystic vaginal mass [38].

Other epithelial tumors: Adenosquamous cancer are approximately 2 % of primary vaginal cancers [4]. These tumors are composed of a mix of glandular and squamous components, lack adenosis or endometriosis and may behave more aggressive biology. Adenoid cystic carcinoma are composed of nests of basaloid epithelial cells with cribriform architecture with hyaline stroma within the rounded spaces. Perineural invasion is commonly seen [39]. Primary vaginal Small Cell Carcinoma (Neuroendocrine) is very rare. Usually this tumors express a neuroendocrine markers such as synaptophysin. The mean age is 59 years and the usual presenting symptom is postmenopausal bleeding [40]. Prognosis is very poor in these types. Vaginal paraganglioma is another very rare epithelioid tumor [41].

Mixed epithelial and mesenchymal tumors. Carcinosarcoma/Malignant Mixed Müllerian tumor (MMMT) has been reported as a primary vaginal tumor [42]. The epithelial component is usually SCC.

Mesenchymal tumors. Sarcomas are 3 % of primary vaginal cancers. There are two main tumors representatives, rhabdomyosarcoma and leiomyosarcoma. The most important round cell mesenchymal tumor at this site is rhabdomyosarcoma or sarcoma botryoides and that is the most common sarcoma of childhood [43]. The median age at presentation is 2 years [44]. The ki-67 is high and mitotic figures are usually frequent [4, 30]. The highly cellular spindle cell mesenchymal tumors include leiomyosarcoma, gastrointestinal stromal tumor (GIST) , solitary fibrous tumor and Synovial Sarcoma. Leiomyosarcomas are the most common vaginal stromal tumors, may have a similar presentation compared to leiomyosarcoma and can widen rapidly during pregnancy [4]. Leiomyosarcomas are the most common vaginal sarcoma in adults and present common with vaginal bleeding in a patient above age of 40 [4, 30]. Angiomyofibroblastoma and myofibroblastoma are associated with mesenchymal tumors that may occur in the vulva or vagina and may be related to Tamoxifen treatment [45, 46]. Angiomyofibroblastoma is benign but must be distinguished from the aggressive angiomyxoma [45].

Miscellaneous tumors: Primary vaginal malignant melanomas are 3–8 % of primary vaginal cancers [4] with mean age at 61 years [47]. Clark’s level, assigned based on histologic levels in the skin , is not appropriate at this site, but depth of invasion (measured in mm) should be reported. The prognosis is worse than that of cutaneous melanoma, with 5–year survival rates of 5–20 % [4, 30]. The vagina is the primary site of rare pediatric extragonadal yolk sac tumors. These tumors may clinically present similar to rhabdomyosarcoma with a friable polypoid mass associated with vaginal bleeding in a child [48, 49]. The mean age of patients are 4 years or younger [30]. Serum α-fetoprotein elevation may be helpful in suspecting the diagnosis [49]. Correct diagnosis is critical as these tumors respond well to platinum – based chemotherapy and surgical treatment may not be necessary [48].

Hematolymphoid tumors: Primary non – Hodgkin’s lymphoma of the female genital tract is rare, less than 1 % of extranodal lymphomas. The mean age of patients are 52 years [50]. There are very rare reports of other tumors such plasmatocytoma and eosinophilic granuloma [4].