The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review.

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.

Cooperation of genes in HPV16 E6/E7-dependent cervicovaginal carcinogenesis trackable by endoscopy and independent of exogenous estrogens or carcinogens.

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.

Prognostic Significance of P16 Expression and P53 Expression in Primary Vaginal Cancer.

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.

Metastatic Acinic Cell Carcinoma to the Vagina: A First Reported Case.

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.

Expression of Markers of Müllerian Clear Cell Carcinoma in Primary Cervical and Vaginal Gastric-type Adenocarcinomas.

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 (HNF1ß) 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 HNF1ß 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 HNF1ß lacks specificity and its use in this setting is discouraged.

Human Papillomavirus (HPV)-associated Lymphoepithelioma-like Carcinoma of the Vagina and Anal Canal: A Rare Variant of Squamous Cell Carcinoma.

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.

Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina.

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 I2 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.

[Giant solitary fibrous tumor of vagina: A case report and literature review].

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.

KLK5, a novel potential suppressor of vaginal carcinogenesis.

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.

Primary Vaginal Melanoma With Rhabdoid Features: A Case Report and Literature Review.

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.

Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma.

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.

Benign intestinal glandular lesions in the vagina: a possible correlation with implantation.

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.

Primary vaginal mucinous adenocarcinoma of intestinal type, associated with intestinal metaplasia of Skene ducts in a diethylstilbestrol-exposed woman.

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.

Viral load, integration and methylation of E2BS3 and 4 in human papilloma virus (HPV) 16-positive vaginal and vulvar carcinomas.

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.

Improved survival in p16-positive vaginal cancers across all tumor stages but no correlation with MIB-1.

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.

Vulvovaginal angiomyofibroblastomas: morphologic, immunohistochemical, and fluorescence in situ hybridization analysis for deletion of 13q14 region.

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.

Primary intestinal-type glandular lesions of the vagina: clinical, pathologic, and immunohistochemical features of 14 cases ranging from benign polyp to adenoma to adenocarcinoma.

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.

Human papillomavirus, p16(INK4A), and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina.

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.

p16INK4A expression in squamous cell carcinomas of the vagina and the vulva in Tunisian women.

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.

Myogenin expression in vulvovaginal spindle cell lesions: analysis of a series of cases with an emphasis on diagnostic pitfalls.

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.