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.

Presence of tumor cells in the vagina during surgical treatment could be the source of vaginal recurrence in patients with endometrial carcinoma - A pilot prospective study.

BACKGROUND: The commonest site of recurrence in endometrial cancer (EC) is the vagina, with a rate of 16%. The aim of this study was to determine if vaginal recurrences in EC patients could develop due to contamination of the vagina with glandular tumor cells dropping off on polypoid, large size EC or tumors involving the endocervix, through manipulation of the uterus during surgery. METHODS: This pilot prospective study included 10 consecutive patients with EC, surgically treated with hysterectomy and additional lymphadenectomy according to stage. In every case, 2 proximal vaginal smears were collected before and during the hysterectomy procedure. All smears underwent Papanicolaou staining and the presence of atypical glandular cells in the smears was correlated with clinico-pathological parameters. RESULTS: Residual tumor was identified on the surgical specimen in the 10 cases; the tumor characteristics were large size (median 6 cm), polypoid type (80%), infiltrating the cervix (70%), and infiltrating more than half of the myometrium (60%). The smears obtained from the vagina showed that five cases (50%) presented tumor cells of glandular type in all smears (before and during the surgery), while in 3 cases (30%) the smears were negative for tumor cells preoperatively, but positive in the perioperative smears. CONCLUSIONS: Our results suggest that the vagina is most often contaminated preoperatively due to bleeding; however, the vaginal wound may also be contaminated perioperatively. We propose a change in the surgical procedure, which is easy to perform and inexpensive compared to postsurgical vaginal radiotherapy.

Risk of vaginal cancer among hysterectomised women with cervical intraepithelial neoplasia: a population-based national cohort study.

OBJECTIVE: To study the risk of vaginal cancer among hysterectomised women with and without cervical intraepithelial neoplasia (CIN). DESIGN: Population-based national cohort study. SETTING AND POPULATION: All Swedish women, 5 million in total, aged 20 and up, 1987-2011 using national registries. METHODS: The study cohort was subdivided into four exposure groups: hysterectomised with no previous history of CIN3 and without prevalent CIN at hysterectomy; hysterectomised with a history of CIN3/adenocarcinoma in situ (AIS); hysterectomised with prevalent CIN at hysterectomy; non-hysterectomised. MAIN OUTCOME MEASURE: Vaginal cancer. RESULTS: We identified 898 incident cases of vaginal cancer. Women with prevalent CIN at hysterectomy and those with a history of CIN3/AIS had incidence rates (IR) of vaginal cancer of 51.3 (95% CI 34.4-76.5) and 17.1 (95% CI 12.5-23.4) per 100 000, respectively. Age-adjusted IR-ratios (IRRs) compared with hysterectomised women with benign cervical history were 21.0 (95% CI 13.4-32.9) and 5.81 (95% CI 4.00-8.43), respectively. IR for non-hysterectomised women was 0.87 (95% CI 0.81-0.93) and IRR was 0.37 (95% CI 0.30-0.46). In hysterectomised women with prevalent CIN, the IR remained high after 15 years of follow up: 65.7 (95% CI 21.2-203.6). CONCLUSIONS: Our findings suggest that hysterectomised women with prevalent CIN at surgery should be offered surveillance. Hysterectomised women without the studied risk factors have a more than doubled risk of contracting vaginal cancer compared with non-hysterectomised women in the general population. Still, the incidence rate does not justify screening. TWEETABLE ABSTRACT: High risk of contracting vaginal cancer among hysterectomised women having prevalent CIN at surgery.

Anterior Pelvic Exenteration for Chemo-irradiated Non-diethylstilbestrol Exposed Clear Cell Vaginal Cancer.

BACKGROUND/AIM: Clear cell vaginal adeno-carcinomas are rare tumors occurring in women which are usually treated by chemo radiotherapy with good outcomes. However, in certain cases, this treatment is not associated with complete response and a further surgery is needed. CASE REPORT: We present the case of a 38-year-old patient diagnosed with stage IVA clear cell vaginal cancer who had been previously submitted to radio chemotherapy and in whom the lesion persisted after the oncological treatment; therefore, the patient was proposed for surgery with curative intent. The tumor was resected by performing an anterior pelvic exenteration with good outcomes, the patient being discharged in the seventh postoperative day. At one-year follow-up the patient remains free of recurrent disease. CONCLUSION: Pelvic exenteration with curative intent might be the option of choice for persistent locally advanced clear cell vaginal cancer.

Malignant transformation of vaginal adenosis to clear cell carcinoma without prenatal diethylstilbestrol exposure: a case report and literature review.

BACKGROUND: We report an extremely rare case of vaginal clear cell carcinoma, which originated from the malignant transformation of vaginal adenosis without prenatal diethylstilbestrol (DES) exposure. CASE PRESENTATION: In this case, the patient was a Chinese woman with a history of two decades of intermittent vaginal pain, sexual intercourse pain and vaginal contact bleeding. On September 1, 2011, when the patient was 39 years old, a vaginal biopsy revealed vaginal adenosis. After intermittent drug and laser treatment, her symptoms did not improve. Four years later, on March 4, 2015, another vaginal biopsy for abnormal vaginal cytology revealed atypical vaginal adenosis. After treatment with sirolimus, her symptoms and abnormal vaginal cytology results persisted, and she underwent laparoscopic hysterectomy with bilateral salpingo-oophorectomy and excision of the vaginal lesions. One year after the hysterectomy, on August 15, 2017, the vaginal cytology results suggested atypical glandular cells, and a biopsy revealed vaginal clear cell carcinoma originating from the atypical vaginal adenosis. A wide local resection of the vaginal lesions was performed, followed by concurrent chemoradiotherapy. Regular follow-up over 16 months showed no evidence of the recurrence of vaginal adenosis or cancer. CONCLUSIONS: Based on the evolution of a series of pathological evidence, we report the fourth case in the world of vaginal clear cell carcinoma originating from vaginal adenosis without prenatal DES exposure. Wide local excision with radiotherapy provided at least 16 months of disease-free survival.

Estimates of the incidence of infection-related cancers in Italy and Italian regions in 2018.

INTRODUCTION: Chronic infections and infestations represent one of the leading causes of cancer. Eleven agents have been categorized by the International Agency for Research on Cancer (IARC) in Group 1, 3 in Group 2A and 4 in Group 2B. We previously estimated that the incidence of cancers associated with infectious agents accounted for the 8.5% of new cancer cases diagnosed in Italy in 2014. METHODS: In the present study we evaluated the incidence of cancer in Italy and in the 20 Italian regions in 2018, based on the data of Cancer Registries, and calculated the fraction attributable to infectious agents. RESULTS: Cancers of infectious origin contributed to the overall burden of cancer in Italy with more than 27,000 yearly cases, the 92% of which was attributable to Helicobacter pylori, human papillomaviruses, and hepatitis B and C viruses. With the exception of papillomavirus-related cancers, the incidence of cancers of infectious origin was higher in males (16,000 cases) than in females (11,000 cases). There were regional and geographical variations of cancers depending on the type of cancer and on the gender. Nevertheless, the overall figures were rather similar, the infection-related cancers accounting for the 7.2, 7.6, and 7.1% of all cancers in Northern, Central, and Southern Italy, respectively. CONCLUSIONS: The estimate of the incidence of cancers attributable to infectious agents in Italy in 2018 (7.3% of all cancer cases) is approximately half of the worldwide burden, which has been estimated by IARC to be the 15.4% of all cancer cases in 2012.

Cancer of the vagina.

Diagnosis of a primary vaginal cancer is rare because most of these lesions will be metastatic from another primary site. Although cancer of the vagina is more common in postmenopausal women, an increase in young women being diagnosed with primary vaginal cancer has been reported, especially in countries with a high HIV prevalence. This will be associated with persistence of high-risk HPV infection. The emphasis should be on primary prevention with prophylactic HPV vaccination. Once there is a suspicion of a primary vaginal cancer, this should be confirmed histologically with biopsy. Staging has been done clinically, similar to cervical cancer; however, there is a role for imaging in assisting with staging as this is often a difficult assessment. Treatment should be individualized and depends on stage as well as histologic subtype. It is prudent to refer cases to centers of excellence with experience in dealing with this rare gynecological cancer.

Long-term survival of a patient with malignant transformation of extragonadal endometriosis treated solely with chemotherapy: A case report.

A 52-year-old woman presented to our hospital complaining of genital bleeding and was found to have a 50-mm vaginal tumor that involved the bladder, rectum, and small bowel and extended to the left pelvic side wall. Her history included a bilateral salpingo-oophorectomy and a total abdominal hysterectomy for fibroids and endometriosis. She had been prescribed estrogen replacement therapy (1.25 mg/day) following the second surgery and continued it for 8 years. The pathology of the vaginal biopsy showed endometrioid adenocarcinoma. Total pelvic exenteration was recommended for complete resection, but she chose chemotherapy (paclitaxel 175 mg/m2 and carboplatin AUC:6). Clinical complete remission was obtained for 11 years. She had a recurrence 11 years later. She was again found to have a 5-cm vaginal tumor. Surgical excision with upper vaginectomy was performed. The tumor was resected without invasion of the bladder, rectum and small bowel. Histologic examination of the specimen confirmed clear cell carcinoma with endometriosis. Chemotherapy may be the first-line treatment that can preclude aggressive surgery for malignant transformation of extragonadal endometriosis. However, combined chemotherapy and surgery is necessary for this disease.

Vaginal cuff recurrence after radical cystectomy: an under - studied site of bladder cancer relapse

ABSTRACT Introduction: Vaginal cuff recurrence of tumor following radical cystectomy is a rare site of disease recurrence, however it has never been specifically studied. The aim of the study is to evaluate incidence, risk factors, and long-term oncologic outcomes of vaginal cuff recur- rence in a cohort of female patients treated with radical cystectomy for invasive urothelial carcinoma of the bladder. Materials and Methods: From 1985 to 2012, a prospectively maintained institutional blad- der cancer registry was queried for vaginal cuff recurrence post radical cystectomy. Over- all mortality and cancer-specific mortality were reported using the Kaplan-Meier method for patients with vaginal cuff recurrence, recurrence at another local or distant site, and those without evidence of recurrence. Comparisons were performed using the log-rank test. Cox proportional hazards regression model was performed to assess predictors of vaginal cuff recurrence. Results: From 469 women treated with radical cystectomy for bladder cancer, 34 patients (7.3%) developed vaginal cuff recurrence, 130 patients (27.7%) had recurrence involving ei- ther a local or distant site, and 305 patients (65%) had no evidence of recurrence. The 5-year overall mortality-free survival rate was 32.4% for vaginal cuff recurrence, but 25.0% for other sites of recurrence. Cancer-specific mortality-free survival rate was 32.4% for vaginal cuff recurrence, and 30.3% for the other sites of recurrence. Multivariate Cox proportional hazards regression analysis demonstrated that the presence of tumor in posterior location at radical cystectomy (Hazard Ratio [HR], 0.353 [95% CI, 0.159-0.783]) and anterior vaginec- tomy, compared to no vaginectomy (HR, 2.595 [95% CI, 1.077-6.249]) were independently associated with vaginal cuff recurrence. Conclusion: Anterior vaginectomy, despite our best attempts, is perhaps not sufficient to prevent vaginal cuff recurrence. Therefore, follow-up evaluation is essential, and further studies are necessary to address the optimal approach for initial management. Patient Summary: Although vaginal cuff recurrence is an unusual site of recurrence, careful evaluation is needed before cystectomy and during follow-up to identify patients at risk.

Genital diseases in the mature woman.

Vulvovaginal conditions are common in mature women. This reflects age-related changes in immunity and skin barrier function of vulvovaginal tissues. Vaginal atrophy is commonly complicated by dryness and inflammation, which makes postmenopausal atrophic vaginitis a virtually ubiquitous condition. The differential of vaginitis includes inflammatory, infectious, and malignant diseases, plus drug hypersensitivity. Atrophic vaginitis is treated with estrogen replacement therapy. Vulvovaginal malignant melanoma occurs predominantly in postmenopausal women and carries a poor prognosis. Similarly, the incidence of vulvovaginal malignancies, such as squamous cell carcinoma and extramammary Paget disease, rises exponentially after 65 years of age. Early diagnosis of these malignancies is of utmost importance. Lichen sclerosus et atrophicus and vulvovaginal candidosis are among the most common postmenopausal vulvovaginal conditions. Lichen sclerosus et atrophicus is associated with significant morbidity, and its management can be challenging. The incidence of vulvovaginal candidosis increases in patients on estrogen replacement therapy.

Ten Years of Human Papillomavirus Vaccination in the United States.

Since human papillomavirus (HPV) vaccine was first introduced for females in the United States in 2006, vaccination policy has evolved as additional HPV vaccines were licensed and new data became available. The United States adopted a gender neutral routine HPV immunization policy in 2011, the first country to do so. Vaccination coverage is increasing, although it remains lower than for other vaccines recommended for adolescents. There are various reasons for low coverage, and efforts are ongoing to increase vaccine uptake. The safety profile of HPV vaccine has been well established from 10 years of postlicensure monitoring. Despite low coverage, the early effects of the HPV vaccination program have exceeded expectations.

Endometriosis presenting as a vaginal mass.

A 43-year-old woman with an anterior vaginal wall mass was referred to gynaecology outpatient for diagnosis and management. Clinical assessment was indicative of a urethral diverticulum, however MRI and ultrasound imaging suggested a Gartner's duct cyst. Following excision of the lesion, histology revealed evidence of an endometriotic cyst. The patient had no other symptoms of endometriosis and remained asymptomatic 3 months following excision. This case highlights the widespread locations in which endometrial tissue can be found, and therefore the range of symptomatology. This in turn lends itself to diagnostic difficulty without histological confirmation.

Vaginal cuff recurrence after radical cystectomy: an under - studied site of bladder cancer relapse.

INTRODUCTION: Vaginal cuff recurrence of tumor following radical cystectomy is a rare site of disease recurrence, however it has never been specifically studied. The aim of the study is to evaluate incidence, risk factors, and long-term oncologic outcomes of vaginal cuff recurrence in a cohort of female patients treated with radical cystectomy for invasive urothelial carcinoma of the bladder. MATERIALS AND METHODS: From 1985 to 2012, a prospectively maintained institutional bladder cancer registry was queried for vaginal cuff recurrence post radical cystectomy. Overall mortality and cancer-specific mortality were reported using the Kaplan-Meier method for patients with vaginal cuff recurrence, recurrence at another local or distant site, and those without evidence of recurrence. Comparisons were performed using the log-rank test. Cox proportional hazards regression model was performed to assess predictors of vaginal cuff recurrence. RESULTS: From 469 women treated with radical cystectomy for bladder cancer, 34 patients (7.3%) developed vaginal cuff recurrence, 130 patients (27.7%) had recurrence involving either a local or distant site, and 305 patients (65%) had no evidence of recurrence. The 5-year overall mortality-free survival rate was 32.4% for vaginal cuff recurrence, but 25.0% for other sites of recurrence. Cancer-specific mortality-free survival rate was 32.4% for vaginal cuff recurrence, and 30.3% for the other sites of recurrence. Multivariate Cox proportional hazards regression analysis demonstrated that the presence of tumor in posterior location at radical cystectomy (Hazard Ratio [HR], 0.353 [95% CI, 0.159-0.783]) and anterior vaginectomy, compared to no vaginectomy (HR, 2.595 [95% CI, 1.077-6.249]) were independently associated with vaginal cuff recurrence. CONCLUSION: Anterior vaginectomy, despite our best attempts, is perhaps not sufficient to prevent vaginal cuff recurrence. Therefore, follow-up evaluation is essential, and further studies are necessary to address the optimal approach for initial management. Patient Summary: Although vaginal cuff recurrence is an unusual site of recurrence, careful evaluation is needed before cystectomy and during follow-up to identify patients at risk.

Trends in Risks for Second Primary Cancers Associated With Index Human Papillomavirus-Associated Cancers.

Importance: In the last 4 decades, survival among patients with human papillomavirus (HPV)-associated cancers has improved, while the incidence of these cancers has increased among younger cohorts. Among survivors of HPV-associated cancers, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancers (HPV-SPCs). Objectives: To investigate the risk of HPV-SPCs among survivors of HPV-associated index cancers and to test the hypothesis that the HPV-SPC risk among these persons has increased over the last 4 decades. Design, Setting, and Participants: A retrospective cohort study of 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HPV-associated (cervical, vaginal, vulvar, oropharyngeal, anal, and penile) cancers diagnosed from January 1, 1973, through December 31, 2014. The dates of analysis were July 1, 2017, to January 31, 2018. Main Outcomes and Measures: The HPV-SPC risk was quantified by calculating standard incidence ratios (SIRs) and excess absolute risks (EARs) per 10 000 person-years at risk (PYR). The HPV-SPC risk by time was estimated using Poisson regression. Results: From 113 272 (73 085 female and 40 187 male) survivors of HPV-associated cancers, 1397 women and 1098 men developed HPV-SPCs. The SIRs for HPV-SPCs were 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men. The EARs were 18.2 per 10 000 PYR for women and 53.5 per 10 000 PYR for men. Among both women and men, those who had index oropharyngeal cancers had the highest HPV-SPC risk (SIR, 19.8 [95% CI, 18.4-21.4] and EAR, 80.6 per 10 000 PYR among women; SIR, 18.0 [95% CI, 16.9-19.1] and EAR, 61.5 per 10 000 PYR among men). Women who had index cervical cancers and men who had index anal cancers had the lowest HPV-SPC risk (SIR, 2.4 [95% CI, 2.2-2.7] and EAR, 4.5 per 10 000 PYR among women; SIR, 6.5 [95% CI, 4.7-8.8] and EAR, 18.5 per 10 000 PYR among men). Both women and men who had index HPV-associated cancers of any kind had a significantly higher risk of oropharyngeal HPV-SPCs. Over the last 4 decades, the risk of developing most types of HPV-SPCs after index cervical, vaginal, and vulvar cancers increased. Conclusions and Relevance: According to this study, the HPV-SPC risk among survivors of HPV-associated cancers is significant, implying that persistent HPV infection at multiple sites may be associated with HPV-SPCs. These findings have the potential to inform surveillance recommendations for survivors of HPV-associated cancers.

Microinvasive squamous carcinoma of neovagina created with peritoneal flap (Davidov): Case report and literature review.

Carcinoma of the vagina is a rare disease, and it is even more rare when it appears in a neovagina, having its incidence and optimum treatment constantly discussed. The aim of this article was to review the cases described in the currently available literature and describe the second documented case of carcinoma in a neovagina created with peritoneal flaps, and also list the possible pathways and risk factors for its development. The case we present is a 49-year-old female who after undergoing a laparoscopic colpectomy of the upper two-thirds of the vagina, with an immediate reconstruction with peritoneal flaps by laparoscopy, at a 4 months follow up presented a focal microinvasive squamous carcinoma in the vault of the neovagina. After reviewing the literature, we conclude that excisional treatment is the preferable option to avoid the progression to an invasive carcinoma. However, this case demonstrates the importance of the necessity to do regular cito-vulvovaginoscopic examinations after the complete surgical treatment because of the chance of persistent or recurrent lesions on the transplanted tissue.

Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study.

BACKGROUND: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal cancer following CIN2 or CIN3 diagnosis. METHODS: In a nationwide cohort study, we followed nearly 2.8 million women born in 1918-1990 who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. The cohort was linked to multiple nationwide registers to obtain information on cancer diagnoses and confounders. Follow-up started when the women reached 18 years, date of immigration, or January 1978, and continued until emigration, death, December 31, 2012, or the date of first diagnosis of anogenital or rectal cancer. RESULTS: Women with a history of CIN2 or CIN3 had higher risks for subsequent anal, vulvar, and vaginal cancer than women with no such history. The relative risks were higher for CIN3 than CIN2. No excess risk was found for rectal cancer. Analyses in which time since first CIN3 was taken into account showed increased relative risks for anal [HR = 4.8; 95% confidence interval (CI), 3.3-7.0], vulvar (HR = 3.2; 95% CI, 2.0-5.3), and vaginal (HR = 5.5; 95% CI, 2.4-12.3) cancers ≥25 years after CIN3 diagnosis. CONCLUSION: Women with a history of CIN2 or CIN3 have a long-term increased relative risk for developing anal, vulvar, and vaginal cancer due to an impaired ability to control a persistent HPV infection. IMPACT: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1090-7. ©2016 AACR.

RapidArc for centrally recurrent cervical cancer in the vaginal cuff following primary surgical therapy: a case report.

BACKGROUND: Pelvic recurrences of cervical cancer after primary surgical treatment can be potentially cured with radical hysterectomy or chemoradiation therapy. Combined radio-chemotherapy is believed to improve results compared to other option. Currently, RapidArc radiotherapy is considered an excellent technological advance that shows great potential for producing highly conformal doses to treatment volumes. CASE PRESENTATION: We present a case of a 67-year-old woman with history of early cervical cancer initially treated by radical laparoscopic hysterectomy. More than 5 years later, the patient presented with a central pelvic vaginal cuff recurrence that is histologically confirmed. Salvage radiotherapy using RapidArc with concurrent cisplatin-based chemotherapy was indicated. A high dose of 70 Gy was delivered to the gross recurrent disease with simultaneous integrated boost (SIB) to the subclinical disease and good sparing of organs at risk especially the rectum and sigmoid. CONCLUSIONS: This case clearly demonstrates a large benefit for salvage RapidArc radiotherapy to central pelvic recurrences of gynecological cancers with an excellent rate of local control and less rate of toxicity.

Primary vaginal endometrial stromal sarcoma associated with endometriosis: a case report with a review of the literature.

Extrauterine endometrial stromal sarcomas (ESSs) are quite rare tumors, and vagina is an unusual site for these tumors. This paper presents a very rare pathological entity of primary vaginal ESS. A 46-year-old woman with a complaint of postcoital vaginal bleeding, low abdominal pain, and constipation was admitted to the clinic. She had a mass of seven cm in size, located in the posterior fornix detected on physical examination. The preoperative biopsy showed ESS, surgical material, and evaluation of an endometrium confirmed the diagnosis of primary vaginal ESS. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial vaginectomy. The diagnosis of ESS performed by pathologic and immunohistochemical evaluation was: caldesmon (-), actin (-), desmin (-). CDIO (+), ER (+), PR (+), and vimentin (+). There was no ESS lesion in the endometrium. The patient was free of tumor for 22 months after the surgery without any additional therapy. In this study, the authors report the sixth case of primary vaginal ESS in the literature and aim to discuss diagnostic criteria and management protocols in the light of the literature.