[Malignant mesothelioma of the vaginal testis: diagnostic and therapeutic considerations]. / Le mésothéliome malin de la vaginale testiculaire : aspects diagnostiques et thérapeutiques.

Mesothelioma of the testicular vagina is a rare malignant tumour, most often discovered by chance. The rarity of this type of tumour has not led to the development of specific guidelines. Median survival is estimated at 30 months. The lack of data and official recommendations makes surgical and medical management and follow-up difficult. Men who have not undergone radical orchiectomy die very rapidly after diagnosis. The remission rate at 1 year post-orchidectomy is 47 %, the recurrence rate at 1 year is 53 % and 92 % of relapses occur within 5 years post-operatively. The treatment option of hemiscrotectomy in the first instance has rarely been used; a second-look resection with negative margins may be proposed. The usefulness of adjuvant chemotherapy and/or radiotherapy has not been clearly demonstrated. Local recurrence is accompanied by metastasis in 85 % of cases. In the case of metastatic cancer (15 %), the retro-peritoneal, inguinal and iliac lymph nodes may be invaded. Follow-up by injected thoraco-abdomino-pelvic CT scan is recommended every 3 months for 2 years, then once a year for 3 years, for a total of 5 years of close follow-up. The long-term recurrence rate is 3 %.

Le mésothéliome de la vaginale testiculaire est une tumeur maligne rare et souvent de découverte fortuite. Sa rareté d'apparition n'a pas permis de développer des recommandations spécifiques. La survie médiane est estimée à 30 mois. Le manque de recommandations officielles rend sa prise en charge chirurgicale, médicale et son suivi difficiles. Les hommes n'ayant pas bénéficié d'orchidectomie radicale décèdent très rapidement après le diagnostic. Le taux de rémission à 1 an post-orchidectomie est de 47 %, le taux de récurrence à 1 an est de 53 % et 92 % des rechutes se font endéans les 5 ans post-opératoires. L'option thérapeutique par hémi-scrotectomie en première intention a rarement été pratiquée, une résection de «second look¼ en marges saines peut être proposée. L'utilité d'une chimiothérapie et/ou d'une radiothérapie adjuvante n'a pas été clairement démontrée. Une rechute locale est accompagnée de métastases dans 85 % des cas. En cas de cancer d'emblée métastatique (15 %), les relais ganglionnaires rétro-péritonéaux, inguinaux et iliaques peuvent être envahis. Un suivi par scanner thoraco-abdomino-pelvien injecté est recommandé tous les 3 mois pendant 2 ans, puis 1 fois par an pendant 3 ans pour un total de 5 ans. Le taux de récidive au long cours est de 3 %.

Risk factors for vaginal squamous intra-epithelial lesions in women with high-grade cervical lesions.

OBJECTIVE: To investigate the high-risk factors associated with concurrent cervical intra-epithelial neoplasia (CIN) and vaginal intra-epithelial neoplasia (VaIN) in patients with high-grade lesions. METHODS: This retrospective study at the Obstetrics and Gynecology Hospital of Fudan University included patients diagnosed with concurrent CIN2/3 and VaIN2/3 (concurrent group) over the period from January 1, 2019, to December 31, 2019. Patients with only CIN2/3 during the corresponding period were selected chronologically on a 1:2 basis (CIN group). Demographic data, human papillomavirus (HPV) infection rates, genotypes, and cytology results were compared between the groups. RESULTS: A total of 128 patients were included. The median age in the concurrent group was 50 years (range 20-79), which was significantly higher than the median age of 38 (range 23-72) in the CIN group (p<0.001). The cytological sensitivity for identifying high-grade lesions was markedly higher in the concurrent group at 83.1% (103 out of 124) compared with 68.4% (175 out of 256) in the CIN-only group (p=0.002). The prevalence of HPV 16 was 62.8% in the concurrent group, significantly higher than 51.6% in the CIN group (p=0.04). CONCLUSIONS: The risk of concurrent VaIN2/3 increases with age among women with CIN2/3. Cytology screening is effective for detecting concurrent VaIN2/3, with a sensitivity of 83.1%.

Radiological features of multifocal embryonal rhabdomyosarcoma affecting the vagina and the urinary bladder in a pediatric patient.

Rhabdomyosarcomas are the most common soft-tissue sarcomas, found usually in the younger age group. Histologically, they are subdivided into embryonal, alveolar, pleomorphic and not otherwise specified. They have a heterogenous appearance on imaging with few additional characteristic features based on the subtype. Botryoid variant of embryonal rhabdomyosarcoma commonly involves the genitourinary and the biliary system. They can be multifocal. Most of these lesions have a heterogenous appearance on imaging with areas of necrosis and haemorrhage. On ultrasound, they are polypoidal with cystic areas and are vascular. The lesions are hyperintense on T2 sequences, isointense to the skeletal muscle on T1 sequences and show heterogenous enhancement. Surgery is the mainstay of treatment along with radiotherapy or chemotherapy depending on the site and the stage of the tumour. We report a case of botryoid variant of rhabdomyosarcoma involving the vagina and the urinary bladder.

Dose-response relationship between volume base dose and tumor local control in definitive radiotherapy for vaginal cancer.

OBJECTIVE: This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina. MATERIALS AND METHODS: We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion. RESULTS: A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 GyEQD2,10 (95% CI: 75.3-96.6 GyEQD2,10). CONCLUSIONS: A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.

HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion.

PURPOSE: We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL). METHODS: Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48-72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2. RESULTS: The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT. CONCLUSIONS: HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.

A paradigm shift in understanding vulvovaginal melanoma as a distinct tumor type compared with cutaneous melanoma.

OBJECTIVE: Our goal was to compare molecular and immune profiles of vulvovaginal melanoma (VVM) with cutaneous melanoma (CM) and explore the significance of immune checkpoint inhibitor (ICI) agents on survival. METHODS: Samples from VVM and CM tumors underwent comprehensive molecular and immune profiling. Treatment and survival data were extracted from insurance claims data and OS was calculated from time of ICI treatment to last contact. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons. RESULTS: Molecular analysis was performed on 142 VVM and 3823 CM tumors. VVM demonstrated significantly (q < 0·01) less frequent BRAF and more frequent KIT, ATRX, and SF3B1 mutations. Alterations in pathways involving DNA damage and mRNA splicing were more common in VVM, while alterations in cell cycle and chromatin remodeling were less common. Immunogenicity of VVM was lower than CM, with an absence of high TMB (0% vs 46.9%) and lower PD-L1 positivity (18·0% vs 29·5%). Median immune checkpoint gene expression was lower in VVM, as were cell fractions for type I macrophages and CD8+ T-cells(q < 0·01). Myeloid dendritic cells were increased in VVM(q < 0·01). Median OS was shorter for VVM than for CM patients treated with ICIs (17·6 versus 37·9 months, HR:1·65 (95% CI 1·02-2·67) p = 0·04). CONCLUSIONS: VVM has a distinct molecular and immune profile compared to CM, which may contribute to the worse survival in VVM compared to CM patients treated with ICI therapy. Though ICIs have been a mainstay of treatment in recent years, our findings suggest that new therapeutic strategies are needed.

Tumour necrosis is a valuable histopathological prognostic parameter in melanomas of the vulva and vagina.

Vulvar and vaginal melanomas (VVMs) are rare and aggressive malignancies with limited prognostic models available and there is no standard reporting protocol. VVMs were selected from six tertiary Canadian hospitals from 2000-2021, resected from patients aged ≥18 years, with 6 months or longer follow-up data, and confirmation of melanocytic differentiation by at least two immunohistochemical markers. Cases were reviewed by pathologists to identify histological biomarkers. Survival outcomes were tested with Kaplan-Meier log-rank, univariate Cox, and multivariate Cox regression. There were 79 VVMs with median follow-up at 26 months. Univariate analysis revealed that tumour necrosis, tumour ulceration, positive lymph nodes, and metastasis at diagnosis were significantly associated with disease-specific mortality, progression, and metastasis. Multivariate analysis identified tumour necrosis as an independent prognostic factor for disease-specific mortality (HR 4.803, 95% CI 1.954-11.803, p<0.001), progression (HR 2.676, 95% CI 1.403-5.102, p=0.003), and time-to-metastasis for non-metastatic patients at diagnosis (HR 3.761, 95%CI 1.678-8.431, p=0.001). Kaplan-Meier survival analyses demonstrated that tumour necrosis was a poor prognostic factor for disease-specific, progression-free, and metastasis-free survival (p<0.001 for all comparisons). Vaginal melanomas displayed decreased survival compared to vulvar or clitoral melanomas. This study identifies tumour necrosis as an independent prognostic factor for VVMs. Vaginal melanomas specifically showed worse survival outcomes compared to vulvar or clitoral melanomas, consistent with previously reported findings in the literature, emphasising the importance of differentiating between these primary tumour epicentres for prognostication and treatment planning in the care of genital melanoma patients.

Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report.

BACKGROUND: The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. CASE PRESENTATION: This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. CONCLUSIONS: When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.

Comprehensive evaluation of vaginal intraepithelial neoplasia development after hysterectomy: insights into diagnosis and treatment strategies.

Vaginal intraepithelial neoplasia (VaIN), a precancerous lesion associated with human papillomavirus (HPV), impacts women's health and quality of life. However, the natural progression of VaIN after hysterectomy remains uncertain, due to its low incidence. The existing literature predominantly consists of single-center retrospective studies lacking robust evidence-based medicine. The management of VaIN after hysterectomy is diverse and controversial, lacking a consensus on the optimal approach. Therefore, it is imperative to investigate the development of VaIN after hysterectomy, emphasizing the importance of accurate diagnosis and effective management strategies.

Aggressive angiomyxoma of female pelvis and perineum: Retrospective study of 17 cases.

OBJECTIVE: Aggressive angiomyxoma is an uncommon mesenchymal neoplasm characterized by a high recurrence rate, usually observed in the lower genital tract of women during their reproductive age. STUDY DESIGN: Seventeen cases of aggressive angiomyxoma confirmed by pathology from January 2007 to December 2021 in Beijing Chao-yang Hospital were included. We collected clinical data and summarized the clinical and immunohistochemical features. RESULTS: All seventeen included patients were females, aged between 23 and 57 years (mean, 37.7 years; median, 42 years). Fourteen patients were newly diagnosed and three were recurrent. The tumors were located in vulva (58.8 %), vagina (23.5 %), buttock (11.8 %), and cervix (5.9 %). The tumors size were 2 to 15 cm in greatest dimension (mean 8 ± 4.4 cm, median 6 cm). Follow-up data was available for nine patients, which ranged from 25 to 124 months (mean, 82 months; median, 80 months). At the end of follow-up, no other recurrence or metastasis was reported. Immunohistochemical analysis showed immunoreactive for estrogen (10/11) and progesterone (8/11) receptor, desmin (6/8), smooth muscle actin (4/10), and vimentin (4/4), S-100 (1/8) and CD34 (1/7). The Ki67 level was less than 5 % in five cases. CONCLUSIONS: AAM is a hormone-sensitive, distinct rare mesenchymal neoplasm with high incidence of local recurrence. Surgery is the preferred treatment, with complete resection being an essential prerequisite for minimizing the risk of recurrence.

Primary Vaginal Mucinous Adenocarcinoma of Intestinal Type-Clinical, Radiological and Morphological Aspects.

Background and Objectives: Neoplasms of the vagina are rare and account for 1-2% of all tumors of the female reproductive system. Primary neoplasms of the vagina are most often carcinomas originating from squamous or glandular epithelium. Of the primary glandular tumors, clear cell, endometrioid, and serous adenocarcinomas are the most common types, while mucinous and mesonephric types are very rare. Mucinous adenocarcinoma is histologically subclassified into endocervical and intestinal types. We add to the existing literature another case of an extremely rare gynecological neoplasm-primary vaginal mucinous adenocarcinoma (PVMAC) intestinal type associated with vaginal villous adenoma with high-grade dysplasia. We discuss the clinical, radiological and morphological features of this rare entity. Materials and Methods: We report a case of a 59-year-old woman with PVMAC intestinal type associated with vaginal villous adenoma with high-grade dysplasia. The patient was evaluated with a gynecological exam, and biopsy, curettage and tumor excision were performed. The positron emission tomography-computed tomography (PET/CT) scan, at the level of the pelvis, supported the primary location of the disease. Histological and immunohistochemical methods were applied. Results: The gynecological examination of the vagina revealed an exophytic polypoid mass with a diameter of 3 cm, located on the posterior wall, in the area of introitus vaginae. The PET/CT scan revealed a hypermetabolic malignant formation involving the vagina and anal canal, without evidence of pelvic and inguinal lymphadenopathy, and also, it excluded disease at sites other than the vagina. The histological and immunohistochemical investigations, as well as the clinical and radiological data, lent support to the diagnosis "primary vaginal mucinous adenocarcinoma intestinal type". Conclusions: PVMAC intestinal type is a rare gynecological pathology, which presents a serious challenge for oncogynecologists, radiologists and pathologists.

Cervical clear cell carcinoma: Case report and literature review.

RATIONALE: Clear cell carcinoma (CCC) is a highly invasive malignant tumor. CCCs of the female reproductive system occur mostly in the endometrium and ovaries and rarely in the cervix. So, it is difficult to diagnose cervical clear cell carcinoma (CCAC) on imaging. This report helps to further deepen our understanding of CCAC. PATIENT CONCERNS: A 39-year-old female patient presented with vaginal discharge with no obvious cause, elevated levels of carcinoembryonic antigen (CEA), CA125, CA153, and squamous cell carcinoma antigen (SCC), and underwent ultrasonography (US) CT and MRI examination in our hospital, which showed a mass in the cervix of the uterus, considered of cervical squamous carcinoma. DIAGNOSES: The cervix biopsy guided by vaginoscope biopsy and immunohistochemistry confirmed CCAC, combined Magnetic Resonance Imaging examination, CCAC with pelvic lymph node metastasis was considered. INTERVENTIONS AND OUTCOMES: The patient refused further treatment and was discharged from hospital. LESSONS: CCAC exhibited no specific symptoms, and is slightly different from cervical squamous carcinoma in image features, mainly relying on immunohistochemistry for diagnosis. The reported case raised awareness of CCAC.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes.

OBJECTIVE: Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. METHODS: Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. RESULTS: 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/ß10, to the high risk clinical target volume, and 60 Gy EQD2α/ß10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. CONCLUSIONS: In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Usage of nivolumab and ipilimumab for recurrent or advanced malignant vaginal melanoma: a two-case series.

Immune checkpoint inhibitors help treat malignant melanoma, but show limited use in treating malignant vaginal melanoma, an aggressive, rare gynecological malignancy. We identified two patients treated with ipilimumab and nivolumab for vaginal melanoma; both were immunonegative for programmed cell death-ligand 1 and wild-type BRAF. Case 1, a 56-year-old female who underwent radical surgery for stage 1 malignant vaginal melanoma, experienced recurrence 15 months postoperatively. She briefly responded to ipilimumab and nivolumab combination therapy before showing disease progression. Tumor shrinkage occurred with nivolumab and local radiotherapy and, 45 months postoperatively, she survives with the melanoma. Case 2, a 50-year-old female, presented with a 4-cm blackish polypoid vaginal tumor with metastatic pelvic lymph nodes. She received ipilimumab and nivolumab combination therapy for stage III unresectable malignant vaginal melanoma. The vaginal tumor shrank after the third course of treatment, and the lymphadenopathy disappeared. The patient underwent radical surgery and is currently disease-free, using nivolumab for maintenance therapy. Both patients had immune-related adverse events coinciding with periods of high therapeutic efficacy of immune checkpoint inhibitors. Neoadjuvant therapy with immune checkpoint inhibitors and radiotherapy for immune checkpoint inhibitor resensitization may effectively treat advanced or recurrent vaginal melanoma.

Neovagina creation methods in Müllerian anomalies and risk of malignancy: insights from a systematic review.

PURPOSE: This systematic review aims to provide a data synthesis about the risk of neovaginal cancer in women with Müllerian anomalies and to investigate the association between the adopted reconstructive technique and the cancer histotype. METHODS: PubMed, MEDLINE, Embase, Scopus, ClinicalTrials.gov and Web of Science databases were searched from inception to March 1st, 2023. Studies were included if: (1) only women affected by Müllerian malformations were included, (2) the congenital defect and the vaginoplasty technique were clearly reported, (3) the type of malignancy was specified. RESULTS: Literature search yielded 18 cases of squamous cell carcinoma and two cases of vaginal intraepithelial neoplasia 3 (VAIN 3). Of these, 3 had been operated on according to the Wharton technique, 8 according to the McIndoe technique, 3 with a split-skin graft vaginoplasty, 2 according to the Davydov technique, 2 with a simple cleavage technique, 1 according to the Vecchietti technique and 1 with a bladder flap vaginoplasty. A total of 17 cases of adenocarcinoma and 1 case of high-grade polypoid dysplasia were also described. Of these, 15 had undergone intestinal vaginoplasty, 1 had been operated on according to the McIndoe technique and 1 had undergone non-surgical vaginoplasty. Finally, 1 case of verrucous carcinoma in a woman who had undergone a split-skin graft vaginoplasty, was reported. CONCLUSION: Although rare, neovaginal carcinoma is a definite risk after vaginal reconstruction, regardless of the adopted technique. Gynaecologic visits including the speculum examination, the HPV DNA and/or the Pap smear tests should be scheduled on an annual basis.

Mullerian Polyp of the Vagina: Report of Three Cases of a Previously Undescribed Lesion With Discussion of the Differential Diagnosis.

Benign and malignant neoplasms of the vagina are rare. We report 3 primary vaginal polypoid lesions involving the upper or mid-vagina in patients aged 40, 60, and 67 years. The lesions bore a striking morphologic resemblance to benign endocervical or endometrial polyps and we suggest the designation Mullerian polyp of the vagina. As far as we are aware, similar cases have not been reported previously in the literature. Follow-up ranging from 6 to 21 months has been uneventful. In reporting these cases, we discuss the possible origin and differential diagnosis and review vaginal lesions with a benign glandular component.