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Adenoid cystic carcinoma (ACC) is a rare neoplasm most frequently observed in the salivary glands, that can occur in other organs, including the vulva and vagina. Oncogenic mechanisms involving MYB, NFIB , and MYB-NFIB rearrangements have been described, but evidence in the vulva and vagina remains scarce. Our aim is to report the clinicopathologic features, immunohistochemical, and molecular findings in a series of vulvar and vaginal ACCs. Five cases were included. Medical records and slides were reviewed. Formalin-fixed paraffin-embedded material was available in 4 cases, where additional immunohistochemical and molecular studies were carried out. Fluorescence in situ hybridization using MYB, MYBL1 , and NFIB bacterial artificial chromosome-clones break-apart and MYB::NFIB BAC-clones fusion probes was performed. The patients' mean age at diagnosis was 52 years. Tumor size ranged from 0.5 to 5 cm. Microscopic examination revealed tubular, cribriform, and solid patterns. Perineural invasion was seen in 4 cases. Patients were treated with surgery, some with adjuvant radiation therapy. During follow-up (mean: 11 yr), 4 patients developed local recurrences. Recently, one of these patients developed pulmonary disease. Cam 5.2, CK5/6, CD117, and DOG-1 were positive in all 4 cases and S100 and calponin were positive in 3 cases. MYB rearrangement was present in 3 cases, including one with concurrent MYB amplification. There were no MYBL1 or NFIB rearrangements and no MYB :: NFIB fusions. Our findings corroborate that the histologic, immunohistochemical, and oncogenic background is similar between ACCs of the lower female genital tract and ACCs elsewhere, although the canonical MYB::NFIB fusion seems to be a less common finding in this location., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities. PReferentially expressed Antigen in MElanoma (PRAME) is a melanoma-associated protein, and immunohistochemistry (IHC) for PRAME distinguishes cutaneous, oral mucosal, and retinal melanoma from atypical nevi. Given the biological differences between VVM and cutaneous melanoma, the utility of PRAME IHC for the diagnosis of VVM is unknown. We accrued a cohort of 20 VVM and 21 benign vulvar melanocytic nevi. We found that nuclear PRAME IHC staining with 4+ intensity was present in 85% of the VVM and 0% of the nevi. With the assistance of PRAME IHC, we found evidence of close or positive margin involvement in 3 of 10 cases where margins were originally diagnosed as negative for melanoma in situ. Our study is the first to assess PRAME IHC in a cohort of VVM cases and provides confidence for using PRAME IHC to assist with diagnosis and margin assessment in this rare disease., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

Introduction: Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer., Material and Methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival., Results: We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%-100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival., Conclusions: This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Human papillomavirus (HPV) infection is necessary but insufficient for progression of epithelial cells from dysplasia to carcinoma-in situ (CIS) to invasive cancer. The combination of mutant cellular and viral oncogenes that regulate progression of cervical cancer (CC) remains unclear. Using combinations of HPV16 E6/E7 (E+), mutant Kras (mKras) (K+) and/or loss of Pten (P-/-), we generated autochthonous models of CC without exogenous estrogen, carcinogen or promoters. Furthermore, intravaginal instillation of adenoCre virus enabled focal activation of the oncogenes/inactivation of the tumor suppressor gene. In P+/+ mice, E6/E7 alone (P+/+E+K-) failed to cause premalignant changes, while mKras alone (P+/+E-K+) caused persistent mucosal abnormalities in about one-third of mice, but no cancers. To develop cancer, P+/+ mice needed both E6/E7 and mKras expression. Longitudinal endoscopies of P+/+E+K+ mice predicted carcinoma development by detection of mucosal lesions, found on an average of 23 weeks prior to death, unlike longitudinal quantitative PCRs of vaginal lavage samples from the same mice. Endoscopy revealed that individual mice differed widely in the time required for mucosal lesions to appear after adenoCre and in the time required for these lesions to progress to cancer. These cancers developed in the transition zone that extends, unlike in women, from the murine cervix to the distal vagina. The P-/-E+K+ genotype led to precipitous cancer development within a few weeks and E6/E7-independent cancer development occurred in the P-/-E-K+ genotype. In the P-/-E+K- genotype, mice only developed CIS. Thus, distinct combinations of viral and cellular oncogenes are involved in distinct steps in cervical carcinogenesis., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

To evaluate the correlation between p16 expression and clinical outcomes in patients with primary vaginal cancer treated with definitive radiotherapy. P16 immunohistochemical was performed on 25 patient samples and recorded from pathology reports in 7 patients. P53 immunohistochemical was performed on 3 p16-negative samples. Baseline characteristics were compared using the Fisher exact test. Outcomes were compared using log-rank tests, and cox proportional hazards models. Survival and recurrence analysis was performed with the Kaplan-Meier method and cumulative incidence estimates. P16 expression was positive in 29 patients and negative in 3 patients. Two of the p16-negative tumors showed positive expression of p53. The median overall survival, progression-free survival and 2-yr cumulative incidence of recurrence were 66 mo [95% confidence interval (CI), 31-96], 34 mo (95% CI, 21-86), and 19% (95% CI, 7%-34%), respectively. P16-positive tumors had higher median overall survival and progression-free survival compared with p16-negative tumors (82 vs. 31 mo, P=0.02 and 35 vs 16 mo, P=0.04, respectively). The 2-yr cumulative incidence of recurrence was 14% for p16-positive tumors compared with 67% for p16-negative tumors (P=0.07). On univariable analysis, p16-negative status, age older than 65, and advanced stage were associated with inferior overall survival. P16 negativity is an independent predictor of inferior overall survival. P16-positive vaginal cancers have a better prognosis and decreased incidence of recurrence compared with p16-negative tumors. These prognostic findings associated with p16-negative vaginal cancers will need to be confirmed in larger patient cohorts.

We estimated the overall and type-specific prevalence of human papillomavirus (HPV) and p16 overexpression in vaginal cancer and vaginal intraepithelial neoplasia (VaIN). We conducted a systematic search of PubMed, Embase and Cochrane Library to identify studies published between 1986 and 2017 using PCR-based or Hybrid Capture 2 tests to evaluate the presence of HPV DNA and/or using any method to detect p16 overexpression in VaIN, vaginal squamous cell carcinoma (VaSCC), or other types of vaginal cancer. Applying a random effects model, we estimated the pooled prevalence of HPV and p16 overexpression along with 95% confidence intervals (CIs). The I 2 statistic was used to assess heterogeneity. We included 26 studies, reporting HPV prevalence and six studies evaluating p16 overexpression. The pooled HPV prevalences in VaSCC (n = 593) and VaIN (n = 1,374) were 66.7% (95% CI = 54.7-77.8) and 85.2% (95% CI = 78.2-91.0), respectively. Substantial inter-study heterogeneity was observed, and analyses stratified on geographic region, type of tissue, HPV detection method or PCR primer type did not fully explain the observed heterogeneity. The most predominant HPV type among the HPV positive VaSCC and VaIN cases was HPV16, followed by HPV33, and HPV45 (in VaIN) and HPV18, and HPV33 (in VaSCC). In pooled analyses, 89.9% (95% CI = 81.7-94.6) of HPV positive and 38.9% (95% CI = 0.9-90.0) of HPV negative vaginal cancers were positive for p16 overexpression. Our findings suggest that vaccination against HPV might prevent a substantial proportion of vaginal neoplasia and highlight the need for further studies of the possible clinical value of p16 testing in these patients., (© 2018 UICC.)

The incidence of cervical adenocarcinoma, both absolute and relative to squamous cell carcinoma, is increasing. Most cervical adenocarcinomas are human papillomavirus associated, although non-human papillomavirus-associated neoplasms exist; the latter include gastric-type adenocarcinoma (GAS) and clear cell carcinoma (CCC). Histologically, these 2 tumors may superficially resemble one other and although morphologic evaluation usually permits a correct diagnosis, immunohistochemistry may be required to resolve diagnostic uncertainty, especially in a small biopsy specimen. Markers of CCC include hepatocyte nuclear factor 1 beta (HNF1β) and Napsin A. In order to explore the utility of these markers in distinguishing between GAS and CCC, we stained 24 cases of GAS (19 cervical, 5 vaginal), 3 of cervical gastric-type adenocarcinoma in situ (gAIS) and 14 CCCs (13 cervical, 1 vaginal) with these antibodies. We found HNF1β expression in 21 of 23 cases of GAS (91.3%; there was no material available for staining in 1 case), 3/3 cases of gAIS (100%) and 10 of 14 (71.4%) CCCs. Napsin A was expressed in 4 of 24 (16.7%) cases of GAS, 0 of 3 (0%) gAIS, and 11 of 14 (78.6%) CCC. On the basis of these findings, Napsin A is of value in resolving diagnostic confusion between GAS and CCC, whereas HNF1β lacks specificity and its use in this setting is discouraged.

This is a case of a 62-year-old woman with a remote history of acinic cell carcinoma of the parotid gland, who presented with a palpable vaginal mass, anterior vaginal wall prolapse, and stress urinary incontinence. A 2 cm firm mobile mass on the anterior vaginal wall was found on clinical examination. A computed tomographic scan revealed a mass between the vaginal vault and bladder that was eventually surgically excised. The histology, supported by the immunohistochemistry, revealed metastatic acinic cell carcinoma to the vagina after 37 years of her initial diagnosis. This is the first reported case in the literature to occur in the vagina.

Lymphoepithelioma-like carcinoma (LELC) is an uncommon variant of squamous cell carcinoma, which is histologically identical to lymphoepithelial carcinoma of the nasopharynx. LELCs have been reported at a variety of sites, including the stomach, salivary gland, thymus, cervix, endometrium, breast, skin, bladder, and lung. We report 2 LELCs of the vagina and 1 of the anal canal, the first report of LELC at the latter site. All 3 neoplasms were diffusely positive with p16 (block-type immunoreactivity) and the anal canal lesion contained high-risk human papillomavirus type 16; the 2 vaginal neoplasms underwent human papillomavirus testing but were unsuitable for analysis. All cases were Epstein-Barr virus negative. In reporting these cases, we highlight the potential for misdiagnosis and suggest an association with human papillomavirus infection similar to LELCs in the uterine cervix.

Vaginal cancer is rare and largely unexplored. We found here that kallikrein-related peptidase 5 (KLK5) is coordinately expressed along with other KLKs in all stratified epithelia, including vagina, pointing to potential role(s) in differentiation. Further, we propose that KLK5 could be implicated in vaginal cancer development based on the fact that Klk5-/- mice are prone to develop vaginal tumors when exposed to 7,12-dimethylbenz[a]anthracene. Nf-κb activation is markedly enhanced in Klk5-/-, leading to increased resistance to apoptosis of mutated vaginal cells. This explains the higher tumor numbers observed in Klk5-/- compared to wildtype. Thus, KLK5 may represent a putative suppressor of vaginal cancer.

We reported a case of giant solitary fibrous tumor of vagina and reviewed literature. The clinical features, diagnosis, and treatment schemes for the disease were summarized to improve the understanding of the disease. An elder female patient came to the Third Xiangya Hospital, Central South University, because of abdominal distention and pain for 5 days after menopause for 9 years. The patient was diagnosed as a solitary fibrous tumor of vagina by pathology and immunohistochemistry after complete resection. The tumor size of the patient was the largest according to reported literature, and the tumor recurred 10 months after surgery. The strong positive expression of CD34 and high Ki-67 proliferation index in tumor immunohistochemistry indicate that the prognosis of patients will be poor.

Primary vaginal melanoma is a rare mucosal neoplasm, which is more aggressive than cutaneous melanoma. Information regarding its morphologic patterns is limited. In particular, the rhabdoid phenotype, mostly observed in metastatic or recurrent cutaneous melanomas, has yet to be reported at this anatomic location. Hence, a potential diagnostic difficulty may arise because of the inability to recognize this unusual histologic variant and its immunohistochemical aberrance. In this report, we describe the case of a primary vaginal melanoma in a 62-year-old woman, who exhibited both rhabdoid and small blue round cell morphologies, absence of S100 protein, and aberrant expression of desmin, CD56, and FLI-1. This report can facilitate the task of expanding the morphologic spectrum of vaginal melanoma, and prevent misdiagnosis and inadequate medical treatment.

Background: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients., Methods: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses., Results: The majority of PVC patients (72%) had >50% LRIG1- and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival., Conclusion: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified.

Background: Enteric-type glandular lesions are extremely rare in the vagina. Their histological origin remains a matter of speculation at present., Method: We review two rectal mucosal prolapse-like polyps and one intestinal-type adenosis in the vagina., Results: Case 1, a 64-year-old woman, presented with a vaginal polypoid lesion with a size of 4 × 3 × 3 cm. Case 2, an 8-year-old girl, had a 1.5 × 1.5 × 0.8-cm pedunculated polyp in the vaginal navicular fossa and a clinically suspected rectovaginal fistula. Case 1 and 3 had an obsolete severe perineal laceration. On histopathological examination, cases 1 and 2 resembled rectal mucosal prolapse or inflammatory cloacogenic polyp (rectal mucosal prolapse-like polyp). Case 3 had an incidental intestinal-type adenosis in the removed vaginal wall. Immunohistochemistry confirmed the intestinal differentiation in all 3 lesions by showing diffuse CDX2-positive, CK20-positive, and scattered chromogranin A-positive neuroendocrinal cells in the lower compartment of the crypt., Conclusions: In summary, we report herein three unusual cases of benign intestinal-type glandular lesions in the vagina including two rectal mucosal prolapse-like polyps and one case of intestinal-type adenosis, and discuss possibilities for their histogenetic basis.

Objectives: Primary mucinous vaginal adenocarcinoma of intestinal type is an extremely rare malignancy of uncertain histogenesis, which makes for a diagnostic challenge. We report a case and describe the histopathologic features and the unusual immunoprofile of this rare entity., Methods: We report a case of vaginal mucinous adenocarcinoma of intestinal type in a diethylstilbestrol-exposed woman in which intestinal metaplasia of the Skene duct was found at the time of recurrence., Results: As the histogenesis of primary vaginal intestinaltype adenocarcinomas remains uncertain, the finding of Skene duct metaplasia in association with invasive adenocarcinoma lends support to the origin of vaginal mucinous adenocarcinomas of intestinal type to be metaplasia, at least in some cases. Such an origin accounts for the unusual immunohistochemical profile, which raises concern for a metastatic adenocarcinoma of gastrointestinal origin., Conclusions: Recognition of this rare entity is important, particularly to avoid the pitfall of misdiagnosing metastatic disease., (Copyright© by the American Society for Clinical Pathology.)

Objective: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact., Methods: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing., Results: Vaginal tumors were found to have a higher viral load (p = 0.024) compared to vulvar tumors but a high copy number (> median value, 15,000) as well as high methylation (>50%) was significantly (p = 0.010 and p = 0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150,000 copies not highly methylated (n = 25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n = 6, 11.1%); (3) tumors with viral DNA fully integrated (n = 11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium- or unmethylated (<50%) and having a high viral load (> total mean value 150,000; n = 12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed., Conclusion: HPV16- related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16- related parameters were found to be of clinical importance in the vulvar series only.

Objectives: Survival as it relates to p16 overexpression and MIB-1 (Ki-67) proliferation in primary squamous cell vaginal carcinoma was studied., Methods: Retrospective chart review from 1997 to 2006 revealed 43 patients who were treated for primary vaginal cancer at Emory University hospitals. Tissue was evaluated by immunohistochemical staining for the presence of p16 and MIB-1 markers, and survival data were examined., Results: Patients who had primary squamous cell vaginal cancers (n = 31) with a positive diffuse staining of p16 had significantly (P = .003) improved survival (~49.5 months) compared with p16-negative patients (~25.3 months). Stage-specific analysis with 30 additional reported cases showed a significant survival benefit for p16-positive vaginal cancers compared with p16-negative cancers for stages I and II (P = .017; hazard ratio [HR] 0.400; 95% confidence interval [CI], 0.189-0.850) and stages III and IV (P = .001; HR, 0.176; 95% CI, 0.066-0.479). No difference was observed in survival for MIB-1-positive tumors (P = .984; HR, 1.008; 95% CI, 0.483-2.104)., Conclusions: The p16 marker has a significant prognostic impact in primary squamous cell vaginal cancers across all tumor stages., (Copyright© by the American Society for Clinical Pathology.)

Angiomyofibroblastoma (AMFB) is a benign tumor that belongs to the category of the "stromal tumors of the lower female genital tract," together with cellular angiofibroma and myofibroblastoma. Previous studies have shown overlapping morphologic and immunohistochemical features between these tumors and spindle cell lipoma, mammary-type myofibroblastoma, and vulvovaginal cellular angiofibroma and myofibroblastoma. In addition, typical loss of genetic material from the 13q14 region has been documented in all the above-mentioned tumors, suggesting that they are histogenetically related. We report the clinicopathologic features of 11 new cases of vulvovaginal AMFBs. Histologically, the basic common theme was a proliferation of bland-looking spindle to round-to-epithelioid cells set in an edematous to fibrous stroma, frequently arranged around thin-walled blood vessels. Two cases were composed of a prominent mature fatty component closely admixed with typical areas of AMFB, and thus, they were designated as "lipomatous AMFBs." Notably, 1 case was closely reminiscent of Sertoli cell tumor, sclerosing type, because of its predominant cord-like arrangement. Immunohistochemically, all tumors were diffusely positive for vimentin, whereas desmin and α-smooth muscle actin were expressed in a minority of cases, suggesting a fibroblastic rather than myofibroblastic differentiation. Most cases of AMFBs coexpressed Bcl-2 protein and CD99. Interestingly, all 5 cases of AMFB with evaluable signals failed to show monoallelic loss of FOXO1 loci (13q14) by fluorescence in situ hybridization. These cytogenetic findings suggest that vulvovaginal AMFB is not genetically related to cellular angiofibroma and myofibroblastoma of the lower female genital tract., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Primary intestinal-type glandular lesions of the vagina are rare. We report a series of 14 lesions, including 1 intestinal-type polyp without neoplastic features, 3 adenomas (2 with high-grade dysplasia), and 10 adenocarcinomas. Patients ranged in age from 20 to 86 years (mean 60 y) and presented with vaginal bleeding or a mass. No history of diethylstilbestrol exposure, adenosis, or endometriosis was elicited in any patient. The lesions were mostly polypoid, small (0.8 to 2.0 cm), and located in the posterior (6 cases) and lower (7 cases) vagina. One carcinoma metastasized to a para-aortic lymph node; the others were confined to the vagina. The neoplasms exhibited histologic features identical to those seen in primary large intestinal tumors, including variable numbers of goblet cells and in 1 case neuroendocrine cells. Five of the adenocarcinomas contained areas consistent with a precursor adenoma. In 3 cases, a benign urothelium-lined duct was adjacent to the lesion, and in 2 patients benign intestinal-type epithelium was present; no other potential benign precursor lesions were seen. Immunohistochemical analysis was performed on 6 cases; the tumors were positive for CDX-2 (6/6), CK20 (5/6), CEA (5/5), CK7 (4/6), and CA-125 (2/4) and were negative for ER (0/6) and p16 (0/2). Clinical outcome data were available in 3 patients with adenocarcinomas; 1 died of disease in <1 year, and 2 were alive with no evidence of disease at 2 and 7 years. The pertinent literature is reviewed, and the potential origin and differential diagnosis of these lesions are discussed.

Background: This study aimed to determine human papillomavirus (HPV) status and to investigate p16(INK4A) and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV)., Methods: The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (2 years) and long-term (8 years) PCV survivors. p16(INK4A) and Ki-67 expression was evaluated by immunohistochemistry., Results: Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16(INK4A) expression was significantly correlated with low histopathological grade (P=0.004), HPV positivity (P=0.032), and long-term survival (P=0.045). High Ki-67 expression was negatively correlated with histopathological grade (P<0.001) and tumour size (P=0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival., Conclusion: High p16(INK4A) expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16(INK4A) and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16(INK4A) expression as a marker for HPV positivity, but this has to be further elucidated.

Background: The role of p16INK4A expression in uterine cervix cancer is well established. In the remaining female lower genital tract cancers, the importance of p16INK4A up-regulation is less clear. In our study, we analyzed the role of p16INK4A expression and HPV infection in carcinomas of the vulva and the vagina in Tunisian women., Materials and Methods: We conducted a retrospective study of 30 carcinomas including 15 vulvar squamous cell carcinomas (SCCs) and 15 vaginal SCCs. Immunohistochemistry was used to determine p16INK4A expression. HPV detection and typing was by in situ hybridization., Results: p16INK4A expression was detected in 86.7% of vaginal SCCs with a strong and diffuse immunostaining in 60% of cases, and also in 73.3% of vulvar SCCs with focal immunoreactivity in 53.3% The association between p16INK4A expression and HPV infection was significant in vaginal SCCs (p=0.001) but not vulvar SCCs (p>0.05)., Conclusions: p16INK4A expression could be used as a useful marker for HPV positivity in vaginal SCCs similar to that described in uterine cervix cancers. However, our data support the presence of 2 different mechanisms for p16INK4A expression in HPV-related and HPV-unrelated vulvar carcinomas.

Aims: Myogenin (myf4) is a nuclear transcription factor that is considered to be a sensitive and highly specific marker for skeletal muscle differentiation. Following the identification of focal strong nuclear staining with myogenin in two fibroepithelial polyps of the lower female genital tract (the index cases), we stained a series of vulvovaginal spindle cell lesions with this marker in order to investigate how widespread myogenin staining is in these lesions., Methods and Results: Fibroepithelial polyps (n = 13), other vulvovaginal mesenchymal lesions (n = 21) and vulval or vaginal spindle cell squamous carcinomas (n = 4) were stained for myogenin. Apart from the index cases, all of the other cases were negative, except for one vaginal spindle cell squamous carcinoma, which showed focal weak nuclear immunoreactivity. Ten of 12 embryonal rhabdomyosarcomas of the lower female genital tract were myogenin-positive, as was a single vaginal rhabdomyoma., Conclusions: Our study illustrates that focal myogenin immunoreactivity occurs uncommonly in fibroepithelial polyps of the lower female genital tract. This may result in diagnostic confusion and misdiagnosis as a skeletal muscle neoplasm, especially the sarcoma botryoides variant of embryonal rhabdomyosarcoma., (© 2013 John Wiley & Sons Ltd.)

Objective: This study aimed to analyze the prognostic value of DNA content and biological markers for cell cycle regulation and invasion in primary carcinoma of the vagina (PCV)., Material and Methods: Seventy-two consecutive patients with PCV, categorized as short-term (≤ 2 years) and long-term (≥ 8 years) survivors, were evaluated for DNA content by image cytometry, and for expression of p53, p21, cyclin A, Ki67, E-cadherin, and laminin-5γ2 chain by immunohistochemistry. The relationship between these biological markers and histopathological and clinical parameters was assessed., Results: All PCV showed aneuploid DNA content. Most of the PCV patients showed no overexpression of p53 and high expression of p21, cyclin A, and Ki67. Loss or underexpression of E-cadherin was found in 94% (68/72) of PCV patients, and all patients showed immunopositivity for the laminin-5γ2 chain. Tumors with a vaginal longitudinal location in the lower third or in the entire vagina more often had overexpression of p53, high expression of Ki67 (P = 0.044), and underexpression of E-cadherin (P = 0.038), than tumors confined only to the upper third. Overexpression of p53 was significantly associated with short-term survival in the univariate analysis, but not in the multivariate analysis adjusted for age at diagnosis and tumor size., Conclusions: The expression level of some markers was related to tumor location, which might be indicative of different genesis. Overexpression of p53 was associated with short-term survival, but the only independent predictors of survival were age at diagnosis and tumor size.

Vaginal villous or tubulovillous adenomas (TVA) are uncommon tumors histologically similar to their intestinal counterparts. After reviewing the literature, we report the eighth case of TVA, which presented as a polypoid tumor in the vagina, at suburethral level, in a 19-yr-old woman with Arnold-Chiari type II malformation and a myelomeningocele at birth. The tumor consisted of long villi lined by columnar cells with brush borders, pseudostratified nuclei, and foci of high-grade atypia. Immunohistochemistry was positive for cytokeratin 7, estrogen and progesterone receptors, CA19.9, p16, p53, and Ki-67 (53%), with a normal membranous pattern for β-catenin, but negative for cytokeratin 20, CDX2, carcinoembryonic antigen, chromogranin A, and synaptophysin. Neither human papillomavirus nor mutations in the K-RAS, BRAF, or LKB1/STK11 genes were detected. Although a rare neoplasm, awareness of this tumor is important as it must be distinguished from colonic adenocarcinoma or other malignant or benign conditions. The existence of 2 previously reported malignant cases merging with TVAs, and the presence of foci of high-grade dysplasia (p53-positive) in the present case, support TVA as a premalignant lesion.

Sialic acid immunoglobulin-like lectin (Siglec)-6 is a transmembrane receptor that binds leptin. Leptin is an obesity-associated peptide hormone overexpressed in gestational trophoblastic disease (GTD). GTD encompasses several placental abnormalities that range from benign to malignant. Among GTD, molar placentas are characterized by excess proliferation, whereas gestational trophoblastic neoplasias (GTN) have characteristically aggressive invasion. We hypothesized that in GTD, Siglec-6 expression would increase with disease severity and that Siglec-6 and leptin would promote proliferation, inhibit apoptosis and/or promote invasion. Siglec-6 expression patterns were evaluated with particular attention to the diagnostic utility of Siglec-6 in GTD (controls: normal placentas (n=32), hydropic abortus placentas (n=7), non-GTD reproductive tract cancers (n=2); GTD: partial moles (PM; n=11), complete moles (n=24), GTN (n=6)). In normal placentas, Siglec-6 expression dramatically decreased after 8 weeks gestation. Complete molar placentas had significantly higher Siglec-6 expression than controls, but expression was not significantly different from PM. In GTN, Siglec-6 expression was low. These data suggest that Siglec-6 may have diagnostic utility for distinguishing complete moles from normal and hydropic abortus placentas. Functional studies in choriocarcinoma-derived BeWO cells demonstrated a complex interplay between Siglec-6 expression and leptin exposure. In cells lacking Siglec-6, leptin treatment promoted invasion, likely through interaction with LepR leptin receptor, without affecting proliferation or apoptosis. Siglec-6 expression promoted proliferation in a leptin-dependent manner, but protected cells from apoptosis and promoted invasion in a leptin-independent manner. We propose that Siglec-6 and leptin play a role in the aberrant properties characteristic of GTD, namely excess proliferation and invasion.

Objective: To study the clinicopathologic features of primitive neuroectodermal tumor (PNET) in female genital tract., Methods: Six cases of PNET arising in female genital tract were retrospectively reviewed. The clinicopathologic features, immunohistochemical findings and EWS gene translocation study results were analyzed., Results: The age of patients ranged from 10 to 27 years (mean = 20 years). The sites of involvement included ovary (1 case), uterus (1 case), vulva (2 cases) and vagina (2 cases). The greatest diameter of the tumor ranged from 2 to 10 cm (mean = 5.4 cm). The tumor had nodular appearance and showed grayish-pink fleshy cut surface, accompanied by foci of hemorrhage and necrosis. Histologically, the tumor was composed of malignant small round cells with indistinct cell borders, hyperchromatic nuclei, dense chromatin, tiny nucleoli and scanty cytoplasm. The tumor cells were arranged in sheets or lobules. Homer-Wright rosettes were identified in 1 case. Immunohistochemical study showed that the tumor cells were positive for CD99, FLI-1 and CD56 (6/6). Focal expression of vimentin (5/6), NSE (5/6), nestin (4/6), synaptophysin (4/6), S-100 protein (2/6) and chromogranin A (1/6) was also demonstrated. EWS gene translocation was detected in 5 cases studied. Follow-up information was available in 2 patients (7 and 17 months of follow up, respectively). One of them died of tumor metastasis 17 months after diagnosis. The other patient was still alive., Conclusions: PNET arising in female genital tract is rare. It mainly involves ovary, uterus, vulva and vagina. Immunohistochemical study using a panel of antibodies and fluorescence in-situ hybridization play an important role in definitive diagnosis of this rare malignancy.

Partial monosomy 13q, a chromosomal alteration originally reported in spindle cell lipoma, has also been documented in a few cases of mammary myofibroblastoma. Subsequently, a monoallelic loss of RB1 and FOXO1, located on 13q14, was identified in some cases of cellular angiofibroma, a benign stromal tumor of the lower female genital tract. This cytogenetic finding and the overlapping morphologic and immunohistochemical features shared by spindle cell lipoma, mammary myofibroblastoma, and cellular angiofibroma strongly suggest a histogenetic link among these tumors. Recently, we have emphasized morphologic and immunohistochemical similarities between mammary and vulvovaginal myofibroblastoma. The aim of the present study was to asses if these 2 tumors share the same chromosomal alteration. We studied the chromosome 13q14 region by fluorescence in situ hybridization analysis in a series of mammary and vaginal myofibroblastomas, with a readable signal in 7 of 13 mammary myofibroblastomas and 5 of 7 cases of vaginal myofibroblastomas. Despite histologic variation, most of the mammary (5/7) and vaginal (3/5) myofibroblastomas showed monoallelic deletion of FOXO1 in more than 22% of the cell populations. Our findings confirm that mammary myofibroblastoma is a tumor that exhibits chromosome abnormalities associated with the loss of the 13q14 region. In addition, we show for the first time that myofibroblastoma of the lower female genital tract also exhibits the same chromosomal abnormality, supporting the hypothesis that both tumors are in the spectrum of a single entity, likely arising from a common precursor cell., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Involvement of the female genital tract by myeloid sarcoma as the initial presentation is extremely uncommon, especially in the vagina. The lack of specific histologic features and the unusual location can be a diagnostic challenge to both the surgical pathologist and the clinician. The very few reported cases of myeloid sarcoma occurring in the vagina have been exclusively seen in adults. We report a 16-year-old girl who presented with a vaginal mass of 4 weeks duration. The initial clinical impression was a Bartholin cyst vs an abscess. However, because of persistence of the vaginal mass after a full course of antibiotic treatment, a biopsy was performed. Immunohistochemistry supported the diagnosis of myeloid sarcoma. Peripheral blood and bone marrow studies were normal. The patient received 4 cycles of chemotherapy and remained disease free 5 months from therapy completion. The clinical course, diagnostic workup, and differential diagnosis of our patient are discussed. Reported cases of myeloid sarcoma occurring in the vagina are reviewed and summarized., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The histological and immunohistochemical features of 13 cases of suspected vaginal fibroepithelial polyps are reported. The characteristic microscopical features of these lesions were an abundant oedematous or fibrous stroma containing spindle-shaped and stellate cells and the presence of variable inflammation and haemorrhage. There was often a superficial layer of compressed tissue, but the stroma in the peripheral areas of the masses was generally more loosely arranged than in central areas. The connective tissue cells expressed vimentin and desmin, but did not express smooth muscle actin or calponin. Individual cases had additional changes including granulomatous inflammation, epithelial dysplasia suggestive of papillomavirus infection and a lesion resembling phyllodes tumour in women., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The so-called mixed tumors occur in a variety of sites throughout the body. While most cases are encountered in the salivary glands, several cases have been described in the female genital tract. A variety of monikers have been applied to this lesion including "spindle cell epithelioma." As in other locations, the vaginal spindle cell epithelioma (VSE) consists of a proliferation of both epithelial and mesenchymal components. Based on our extensive review of the literature, we present the 53rd reported case of VSE. More significantly, we present the most up-to-date review of this lesion, including its immunohistochemical and electron microscopic features. We also review the theories pertaining to its histogenesis incorporating current embryologic data, which together suggest a Müllerian derivation., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

We report 2 cases of primary vaginal mucinous adenocarcinoma arising in adenosis in nondiethylstilbestrol-exposed women, 1 with uterus didelphys. Both tumors exhibited morphologic and immunohistochemical features (MUC6 and/or HIK 1083 positivity) identical to the recently described cervical gastric-type adenocarcinoma, a subtype of mucinous adenocarcinoma that is non-human papillomavirus related and possibly related to adenoma malignum. Both neoplasms were intensely p53 positive, suggesting that TP53 mutation may be implicated in their development. We believe that the vaginal tumors arose from adenosis through atypical adenosis, as benign and atypical glands were present at the periphery of the neoplasms. In reporting these cases, we discuss atypical adenosis and other types of non-diethylstilbestrol-associated vaginal adenocarcinomas. At least 9 other examples of primary vaginal, or more uncommonly cervical, adenocarcinomas arising in non-diethylstilbestrol-exposed women with congenital genitourinary malformations have been reported, suggesting a probable causal association between congenital malformation, vaginal adenosis, and vaginal adenocarcinoma.

We analyzed the clinicopathologic features of 10 cases of vulvovaginal myofibroblastoma to widen its morphological and immunohistochemical spectrum. Most tumors (8/10 cases) were located in the vagina. The patients' age ranged from 44 to 77 years, and tumor size ranged from 0.4 to 3 cm. Histologically, 5 tumors had the characteristics of vulvovaginal myofibroblastoma. In addition, we identified 3 cases composed of spindle-shaped cells arranged in short fascicles with intervening thick collagen bands, closely reminiscent of mammary myofibroblastoma. Notably, 1 case resembled Sertoli cell tumor, sclerosing type, because of its predominant cord-like arrangement. In another case, there were highly cellular areas composed of uniform-packed, rounded cells that, at low magnification, looked like a malignant "small round blue cell tumor." A variably thick band of native connective tissue separated tumors from the overlying squamous epithelium even if, in 3 cases, tumor cells extended up to the epithelium. In 7 cases, a variable number of vessels showed perivascular hyalinization. Only rare mitotic figures were identified. All tumors were diffusely positive for vimentin, desmin, and CD99. A variable staining intensity was observed for CD34, Bcl-2, B-cell lymphoma 2 (Bcl-2) CD10, estrogen receptor, and progesterone receptor in most cases, but none expressed α-smooth muscle actin. We emphasize that vulvovaginal myofibroblastoma encompasses a morphological spectrum wider than previously described. The overlapping morphological and immunohistochemical features of vulvovaginal and mammary myofibroblastomas led us to speculate that these are related entities with morphological variations on a common basic theme likely dependent on anatomical location., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: Endometrioid carcinoma of the endometrium (EEC) is treated with surgery and radiotherapy. Post-radiation recurrences are associated with increased risk of metastases. Comparison of the expression of genes important in the development and progression of EEC, and others involved in resistance to apoptosis and hypoxia and adaptation to radiation, was performed between post-radiation vaginal recurrences (PVRs) and primary EECs. We tried to reproduce the results by exposing an EEC cell line to hypoxia and radiation., Methods and Results: Immunohistochemistry and tissue microarrays were used to compare 24 PVRs with 82 primary EECs. PVRs exhibited increased expression of p53 (P < 0.0001), cytoplasmic FLICE-inhibitory protein (FLIP) (P < 0.0001), and Ki67 (P < 0.0001), and nuclear staining for FLIP, nuclear factor kappaB (NF-κB) family members (p50, P < 0.0001; c-Rel, P = 0.0077; RelB, P = 0.0157), and β-catenin (P = 0.0001). Differences regarding p50, hypoxia-inducible factor 1α (HIF-1α), and cytoplasmic FLIP were statistically significant when PVRs and primary EECs were matched for histological grade. Exposure of the EEC cell line to hypoxia induced nuclear expression of β-catenin, FLIP, and HIF-1α, as well as increased NF-κB activity. No changes in FLIP, HIF-1α or NF-κB were seen when cells were exposed to radiation. Nuclear expression of β-catenin was seen at 3 Gy, but not at 1 Gy., Conclusions: Genes involved in resistance to hypoxia are expressed in PVRs, and may play a role in the development of post-radiation recurrences., (© 2012 Blackwell Publishing Limited.)

Perivascular epithelioid cell tumors (PEComas), occasionally associated with the tuberous sclerosis complex, are characterized by varying amounts of spindle and epithelioid cells with clear to eosinophilic cytoplasm that display immunoreactivity for melanocytic markers, most frequently HMB-45. Perivascular epithelioid cell tumor of gynecologic origin is very rare, and there have been only a few reported cases. This study describes the clinical, histological, and immunohistochemical features and prognoses of three cases of gynecologic origin. Two of the three tumors were confined to the uterus and one to the vagina. None of the patients had tuberous sclerosis complex. Immunohistochemistry indicated that all three cases expressed at least one melanocytic marker, and HMB45 was a positive marker for all of them. These markers can be found in both epithelial cells and spindle cells. Except for MiTF, which was located in the nucleus, all the other antibodies were located in the cytoplasm. The three cases have been followed up for 26, 22, and three months, respectively, with disease-free survival in all cases. We conclude that PEComas of gynecologic origin have morphological and immunohistochemical features of the PEComa family, which are rare and should be included in the differential diagnosis with other tumors. Until more cases of this rare tumor are evaluated with longer follow-up, firm criteria for malignancy remain uncertain.

Background: Vaginal metastasis from organs other than the uterus is rare. Generally, patients with vaginal metastasis from colorectal cancer have a dismal prognosis. Although biopsy is the best method to make the diagnosis, massive bleeding may occur. On the other hand, liquid-based cytology (LBC) has the utility to perform immunocytochemistry on additional unstained slides: we can make a diagnosis with several immunocytochemical findings., Case: A 67-year-old postmenopausal female presented to our hospital with vaginal bleeding. The patient had undergone colectomy because of her stage III sigmoid colon cancer 3 years earlier. The patient had also undergone hysterectomy for cervical cancer 30 years earlier. LBC from the vaginal stump revealed adenocarcinoma. Immunocytochemically, cancer cells were negative for cytokeratin 7 and positive for cytokeratin 20, which suggested metastasis from the sigmoid colon cancer; the diagnosis was made without a biopsy., Conclusion: When the patient has a metastatic lesion from colon adenocarcinoma, LBC with immunocytochemistry is useful in making a diagnosis., (Copyright © 2012 S. Karger AG, Basel.)

A case of unusual vaginal myofibroblastoma containing glands which expressed mammary and prostatic markers is described. The tumor occurred in 70-year-old woman in the proximal third of the vagina. It showed morphology and immunophenotype typical of so-called cervicovaginal myofibroblastoma. The peripheral zone of the lesion contained a few groups of glands suggesting vaginal adenosis or prostatic-type glands on initial examination. The glands showed a surprising simultaneous expression of mammary markers mammaglobin and GCDFP-15 and prostatic markers prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP). Immunostains for alpha-smooth muscle actin, p63 and CD10 highlighted the myoepithelial cell layer of the glands. The finding indicates that simultaneous use of both mammary and prostatic markers for examination of unusual glandular lesions in the vulvovaginal location can be helpful for an exact diagnosis, and can contribute to better understanding of prostatic and mammary differentiations in the female lower genital tract.

Objective: Less than 5% of women with cervical or vaginal biopsy proven high-grade squamous intraepithelial lesions (HG-SIL) show a negative Hybrid Capture 2 (HC2) result. We analyzed 1) human papillomavirus (HPV) genotypes by PCR in order to determine whether these cases represent infections by common or unusual types, and 2) the clinical, colposcopic and pathological differential characteristics of these patients., Methods: 646 women with a histological diagnosis of HG-SIL and a HC2 test collected within 6 months prior to the diagnosis were identified. Patients with a negative HC2 result were selected. HPV was typed in the biopsy specimen in all by PCR using SPF10 and GP5+/6+ primers, and p16(INK4a) immunostaining was performed. The clinical and colposcopy findings of these women were compared with a control group of HG-SIL with positive HC2 result., Results: 20 women (3.1%) with HG-SIL had a negative HC2. All biopsies were positive for p16(INK4). PCR analysis detected HPV types included in HC2 test in 55% of the cases, with an identical percentage of common viruses between women with relative light unit values above or below 0.40 (p=.361). False negative HC2 tests increased with age (p=.002) and were more frequent in patients with non satisfactory colposcopy or small sized lesions (p<.001)., Conclusion: A negative HC2 test is an infrequent event in women with HG-SIL. Common HPV types are identified in over half of the cases. Older women and patients with small lesions or non satisfactory colposcopy have a higher rate of HC2 negative results., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Blue nevi that arise from the Müllerian tract are rare melanocytic lesions. Several histopathologic variants of cellular blue nevi have been described. The angiomatoid variant is characterized by a vascular component, and is considered to be a rare variant. Few studies have explored the influence of pregnancy on melanocytic lesions., Case: A 29-year-old woman was presented with a pigmented vaginal lesion that increased gradually during pregnancy. A full term gynecologic examination showed a tumor mass protruding into the vaginal canal. The mass was resected during cesarean-section under the clinical impression of vaginal hemangioma., Result: Gross examination revealed a cystic mass measuring 6.0 × 4.3 × 3.5 cm, which was filled with dark friable material. Histologically, the mass showed a subepithelial cellular proliferation of heavily pigmented dendritic melanocytes with prominent vascular stroma. Cytologic pleomorphism, junctional activity, atypical mitosis, and necrosis were not found. The proliferation was immunoreactive for HMB-45, S-100 and melan-A, and non-immunoreactive for CD34, smooth muscle actin, and AE1/AE3. The MIB-1 proliferative index was less than 1%. The patient had a postoperative course without complication., Conclusions: Angiomatoid giant cellular blue nevus arising from the vagina during pregnancy is extremely rare. The low proliferative index and absence of cytologic pleomorphism, or necrosis, supports a benign biological behavior. Clinical follow-up showed no evidence of recurrence at one year after the resection of the mass.

Objective: Primary invasive squamous cell carcinoma of the vagina is a rare neoplasm. Investigations concerning the potential of new therapeutic targets are limited., Study Design: A total of 34 patients with primary invasive squamous cell carcinoma of the vagina was identified, who were treated at our institution between 1994 and 2008. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression was assessed using immunohistochemistry from paraffin-embedded tissue blocks., Results: EGFR was expressed in 33 of 34 (97.1%) and VEGF was expressed in 12 of 34 cases (35.3%). There was no statistically significant relationship between clinicopathologic parameters (clinical stage, grading, tumor size), patient survival, and EGFR and VEGF expression., Conclusion: VEGF was moderate and EGFR was frequently expressed in invasive squamous cell carcinoma of the vagina. In our sample size, immunohistochemical staining was not statistically significantly associated with prognosis., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Synovial sarcoma is a morphologically and genotypically distinctive soft tissue sarcoma with a strong predilection for young and middle aged adults and the deep soft tissues of the extremities. Rare cases of synovial sarcoma have been reported in a large variety of unusual sites, one of the least common being the female genital tract. We report 4 young women with synovial sarcoma involving the vulva (3 cases) and vagina (1 case). Two of the tumors were of the biphasic and 2 of the monophasic type; 3 of the tumors were poorly differentiated. The diagnosis in all the cases was supported by immunohistochemical findings and reverse transcription polymerase chain reaction and sequencing demonstration of SS18/SSX fusion transcripts. Two of the patients developed recurrent disease (1 dies of disease after 8 years) and 2 are currently disease-free.This study shows the importance of pathologists being aware of the rare occurrence of synovial sarcoma in the female genital tract, discusses the differential diagnosis with particular reference to this location, emphasizes the need for molecular genetic support in such cases, and reviews the sparse, earlier literature. Synovial sarcoma should be considered in the differential diagnosis of a vulvovaginal mesenchymal lesion, especially in a young female.

Aim: To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance., Methods and Results: All cases of SCCVa diagnosed over a 15-year period from two hospitals in Barcelona, Spain (n=32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed <5 years before were excluded. HPV was detected and typed by polymerase chain reaction (PCR) using SPF10 primers. Immunohistochemistry was performed for p16 and p53. HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV-positive tumours were associated frequently with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% versus 0%; P=0.01). HPV-positive tumours were more frequently of non-keratinizing, basaloid or warty type than HPV-negative neoplasms (84% versus 14.3%; P<0.001), and showed diffuse positive immunoreactivity for p16(INK4a) (96%, versus 14.3%; P<0.001). The sensitivity and specificity of p16 to identify HPV-positive tumours were 96% and 85.7%, respectively., Conclusions: A high number of SCCVs are related to HPV infection and may be identified by immunohistochemistry for p16. HPV-positive tumours tend to affect women with history of cervical neoplasia., (© 2010 Blackwell Publishing Limited.)

Tubulo-squamous polyp of the vagina is a recently described histopathologic entity. This case report describes an as yet unreported morphologic feature of sebaceous glands in an example of this lesion. Further knowledge of the morphologic spectrum of this lesion should be of aid to histopathologists in its recognition. A brief review of currently available literature on this topic is also given.

Aggressive angiomyxoma is a rare mesenchymal neoplasm, which almost always occurs in the vulvovaginal region and which exhibits a marked tendency for local recurrence after excision. A wide range of other mesenchymal lesions occur in this region, which potentially mimic aggressive angiomyxoma to a variable extent. Because rearrangement of the HMGA2 gene has been shown in a significant percentage of aggressive angiomyxomas, we examined the expression of HMGA2 protein in this neoplasm and in a large number of other mesenchymal lesions occurring at this site, including many which were referred with a possible diagnosis of aggressive angiomyxoma. There was positive staining of tumor cell nuclei, mostly with a diffuse distribution, in all but 2 aggressive angiomyxomas (n=12). Blood vessel endothelial cells within the neoplasms, entrapped tissues, and surrounding normal tissues were negative. Ten of 23 leiomyomas were positive, as were occasional other neoplasms. Based on our study, we conclude that HMGA2 is positive in most aggressive angiomyxomas and is useful in diagnosis as most mesenchymal lesions which closely mimic this are negative. However, caution should be exercised as some other vulvovaginal mesenchymal lesions, especially, but not exclusively leiomyomas can be HMGA2-positive. As well as being of value in primary diagnosis, HMGA2 is useful in evaluating margins and in reexcision specimens of aggressive angiomyxoma in identifying foci of residual or recurrent tumor.

The investigators report a series of prostatic-type lesions occurring in the lower female genital tract. The cases included a 4.5-cm mass representing hyperplasia of the glandular and stromal tissue of paraurethral Skene gland, a small ectopic prostatic lesion in the vulva, and 4 tubulosquamous vaginal polyps. All lesions were immunopositive for prostate-specific antigen and/or prostatic acid phosphatase. A brief discussion of the earlier published material is included.

We report 4 myoepitheial neoplasms involving the vulva (2 cases) or vagina (2 cases) in patients aged 40 to 45. Two tumors were composed entirely of ovoid or spindle-shaped cells, one entirely of epithelioid cells, and in the other, there was a mixture of spindled and epithelioid cells. Small foci of ductal differentiation with squamous metaplasia were present in one case and a minor stromal component, which varied from myxoid to hyalinized, in all cases. In all cases, the tumor cells were positive for epithelial markers (cytokeratins and/or epithelial membrane antigen) and the myoid markers alpha smooth muscle actin and calponin. Desmin was positive in 3 cases. S100 and p63 were positive in 1 of the 4 neoplasms. On the basis of the nuclear features and degree of mitotic activity, 2 neoplasms were classified as benign myoepitheliomas and 2 as myoepithelial carcinomas. Judging by the paucity of cases in the literature, myoepithelial neoplasms appear extremely rare in the vulvovaginal region with only 3 previous case reports of primary vulval tumors. As far as we are aware, this is the first description of a primary vaginal myoepithelial neoplasm. At these sites, myoepithelial tumors are liable to be misdiagnosed as a variety of other neoplasms because the pathologist may not think of the diagnosis. In reporting these cases, we discuss the criteria for diagnosis and the differential diagnosis.

Tubulo-squamous polyp is a recently described and apparently benign lesion that most frequently involves the upper vagina of postmenopausal patients. Histologically, it is characterized by the presence of cysts, squamous epithelial nests, and small tubular structures that are surrounded by a hypocellular fibrous stroma. Some lesions show focal immunoreactivity for prostatic acid phosphatise and/or prostate-specific antigen raising the possibility of derivation from Skene's glands. In this report, an additional case of tubulo-squamous polyp is presented in which there was prominent basaloid epithelial differentiation, mainly in the form of elongated cords of cells around the peripheral and deep aspect of the lesion. This feature has not been recorded previously in tubulo-squamous polyp and potentially could create diagnostic difficulty with other lesions such as basal cell/adenoid basal carcinoma or small-cell neuroendocrine carcinoma.

We report a case in which a vaginal adenocarcinoma was discovered in a 67-year-old woman 16 years after hysterectomy for cervical adenocarcinoma in situ. Both the vaginal and cervical lesions exhibited morphologic and immunohistochemical (CDX2-positive) features of intestinal differentiation. Linear array human papillomavirus genotyping demonstrated the vaginal adenocarcinoma to contain human papillomavirus 45. We believe the vaginal adenocarcinoma to be related to the cervical adenocarcinoma in situ and to represent recurrence of this. This is an extremely rare phenomenon with, as far as we are aware, only one previous report in the literature.