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Vaginal Cancer

Cancer of the vagina is relatively rare, accounting for about 2% of gynaecological malignancies. There are two main types of vaginal cancer; squamous cell cancer and adenocarcinoma. Over four fifths of all vaginal cancers are squamous carcinoma, this is more common in women between the ages of 60 and 80. The other type of vaginal cancer; adenocarcinoma is usually found in young women under 30 years old.

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  • PubMed search for publications about Vaginal Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Vaginal Cancer
    MeSH term: Vaginal Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Wang R, Fan Q, Liu H, Su M
Isolated Vaginal Recurrence of Early-Stage Rectal Cancer Detected by 18F-FDG PET/CT.
Clin Nucl Med. 2019; 44(6):499-500 [PubMed] Related Publications
The relapses of rectal cancer are most frequently localized in the pelvis, liver, and pelvic and para-aortic lymph nodes and lungs, whereas the vagina is an unusual site. We present here a 60-year-old woman presenting with lower abdominal discomfort 23 months after radical resection of rectal adenocarcinoma. An isolated, solitary, hypermetabolic mass in the right part of the vagina was detected by F-FDG PET/CT. Ultimately, the vaginal neoplasm was proved to be adenocarcinoma of rectal origin based on its shared histologic features and compatible immunostaining profile.

Fu S, Fokom Domgue J, Chan W, et al.
Cervical, Vaginal, and Vulvar Cancer Costs Incurred by the Medicaid Program in Publicly Insured Patients in Texas.
J Low Genit Tract Dis. 2019; 23(2):102-109 [PubMed] Related Publications
OBJECTIVES: To determine from the perspective of the State of Texas, the direct medical care costs associated with cervical, vaginal, and vulvar cancers in Texas Medicaid enrollees.
MATERIALS AND METHODS: We conducted a case-control study and searched Texas Medicaid databases between 2008 and 2012 for eligible cancer patients. A comparison group was selected for each cancer site using a 2-step 1:1 propensity score matching method. Patients were followed for 2 years after cancer diagnosis to estimate monthly and yearly direct medical costs. For each cancer site, the differential cost between patients and the matched comparison individuals was the estimated cost associated with cancer.
RESULTS: The study included 583 cervical, 62 vaginal, and 137 vulvar cancer patients and equal numbers of cancer-free comparison individuals. Among the cases, 322 cervical cancer patients, 46 vaginal cancer patients, and 102 vulvar cancer patients were Medicaid-Medicare dual eligible enrollees. For Medicaid-only enrollees, the adjusted first- and second-year mean total differential costs were US $19,859 and $3,110 for cervical cancer, US $19,627 and $4,582 for vaginal cancer, and US $7,631 and $777 for vulvar cancer patients, respectively. For Medicaid-Medicare dual eligible enrollees, adjusted first- and second-year mean total differential costs incurred by Medicaid were US $2,565 and $792 for cervical cancer, US $1,293 and $181 for vaginal cancer, and US $1,774 and $1,049 for vulvar cancer patients, respectively.
CONCLUSIONS: The direct medical costs associated with cervical, vaginal, and vulvar cancers in Texas Medicaid were substantial in the first 2 years after cancer diagnosis, but dual eligibility for Medicare coverage attenuated Medicaid costs.

Göbel J, Košťál M, Hensel G, Hátlová J
Primary malignant melanoma of the vagina, case report and review of the literature.
Ceska Gynekol. Winter 2018; 83(3):201-199 [PubMed] Related Publications
OBJECTIVE: Presentation of primary malignant melanoma of the vagina. Summary of clinical findings and management.
DESIGN: Case report.
SETTING: Nemocnice Pardubického kraje a.s., Porodnicko-gynekologická klinika, Pardubice.
OBSERVATION: We report a case of primary malignat melanoma in a 44 year old woman, with symptoms of abnormal vaginal bleeding and painful intercourse.
CONCLUSION: Primary malignant melanoma of the vagina is rare disease. Goal of therapy is complete removal of primary tumor.

Bogani G, Ditto A, Ferla S, et al.
Treatment modalities for recurrent high-grade vaginal intraepithelial neoplasia.
J Gynecol Oncol. 2019; 30(2):e20 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: We have investigated outcomes of women presenting with recurrent high-grade vaginal intra-epithelial neoplasia.
METHODS: Data of consecutive women diagnosed with recurrent high-grade vaginal intra-epithelial neoplasia after primary treatment(s) were retrieved. Risk of developing new recurrence over the time was assessed using Kaplan-Meier and Cox models.
RESULTS: Data of 117 women were available for the analysis. At primary diagnosis, 41 (35%), 4 (3.4%) and 72 (61.6%) patients had had laser, pure surgical and medical treatments, respectively. Secondary treatments included: laser ablation and medical treatment in 95 (81.2%) and 22 (18.8%) cases, respectively. After a mean (standard deviation) follow-up of 72.3 (±39.5) months, 37 (31.6%) out of the entire cohort of 117 patients developed a second recurrence. Median time to recurrence was 20 (range,5-42) months. Patients with recurrent high-grade vaginal intra-epithelial neoplasia undergoing medical treatments were at higher risk of developing a second recurrence in comparison to women having laser treatment (p=0.013, log-rank test). After we corrected our results for type of treatment used for recurrent disease, we observed that the execution of primary laser treatment was independently associated with a lower risk of developing new recurrences (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.21-0.99; p=0.050). The other variable that is independently associated with a new recurrence is the persistent infection from HPV16 or 18 (HR=3.87; 95% CI=1.15-13.0; p=0.028).
CONCLUSION: Patients with recurrent high-grade vaginal intra-epithelial neoplasia are at high risk of developing new recurrences. Our data underline that the choice of primary treatment might have an impact of further outcomes.

Fu Z, Chen X, Yang X, Li Q
Diagnosis of Primary Clear Cell Carcinoma of the Vagina by 18F-FDG PET/CT.
Clin Nucl Med. 2019; 44(4):332-333 [PubMed] Related Publications
A 41-year-old woman presented with irregular vaginal bleeding, and a vaginal tumor was found and proved to be a clear cell carcinoma by biopsy. An F-FDG PET/CT was performed to exclude its metastatic possibility, which showed the vaginal tumor was the only lesion with F-FDG avidity. The vaginectomy and hysterectomy were performed to resect the lesion, and primary clear cell carcinoma of the vagina was finally diagnosed.

Ong KJ, Checchi M, Burns L, et al.
Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates.
Sex Transm Infect. 2019; 95(1):28-35 [PubMed] Related Publications
BACKGROUND: Many economic evaluations of human papillomavirus vaccination should ideally consider multiple disease outcomes, including anogenital warts, respiratory papillomatosis and non-cervical cancers (eg, anal, oropharyngeal, penile, vulvar and vaginal cancers). However, published economic evaluations largely relied on estimates from single studies or informal rapid literature reviews.
METHODS: We conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider's perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$.
RESULTS: Sixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124-US$883 (anogenital warts), US$6912-US$52 579 (head and neck cancers), US$12 936-US$51 571 (anal cancer), US$17 524-34 258 (vaginal cancer), US$14 686-US$28 502 (vulvar cancer) and US$9975-US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer).
CONCLUSIONS: Differences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.

Bryan S, Barbara C, Thomas J, Olaitan A
HPV vaccine in the treatment of usual type vulval and vaginal intraepithelial neoplasia: a systematic review.
BMC Womens Health. 2019; 19(1):3 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: HPV DNA is found in almost 80% of VIN/VaIN. Current management is inadequate, with high recurrence rates. Our objective was to review the literature regarding the role of HPV vaccine in secondary prevention and treatment of VIN/VaIN.
METHODS: Database searches included Ovid Medline, Embase, Web of Science, The Cochrane Library and Clinicaltrials.gov . Search terms included HPV vaccine AND therapeutic vaccine* AND VIN OR VAIN, published in English with no defined date limit. Searches were carried out with a UCL librarian in March 2018. We included any type of study design using any form of HPV vaccine in the treatment of women with a histologically confirmed diagnosis of VIN/VaIN. We excluded studies of other lower genital tract disease, vulval/vaginal carcinoma and prophylactic use of vaccines. The outcome measures were lesion response to vaccination, symptom improvement, immune response and HPV clearance.
RESULTS: We identified 93 articles, 7 studies met our inclusion criteria; these were uncontrolled case series. There were no RCTs or systematic reviews identified. Reduction in lesion size was reported by all 7 studies, symptom relief by 5, HPV clearance by 6, histological regression by 5, and immune response by 6.
CONCLUSIONS: This review finds the evidence relating to the use of HPV vaccine in the treatment of women with VIN/VaIN is of very low quality and insufficient to guide practice. Further longitudinal studies are needed to assess its use in prevention of progression to cancer.

Zhang LZ, Huang LY, Huang AL, et al.
Adenoid cystic carcinoma of the vagina: A case report.
Medicine (Baltimore). 2019; 98(1):e13852 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Squamous carcinoma is the most common malignancy of vagina. Adenoid cystic carcinoma (ACC) in the vagina is very rare.
PATIENT CONCERNS: In the present study, we present a 45-year-old woman with a palpable swelling in the vagina. The patient reported body paresthesia, chest congestion, expiratory dyspnea, and itching in the thigh root.
DIAGNOSIS: The ultrasound results revealed inhomogeneous echoes of the muscular layer in the middle and distal of the vagina, and probed a slightly richer blood flow signal. Then biopsy was performed. On microscopic examination, it was observed that tumor cells were arranged in a tubular or cribriform pattern, and exhibited a consistent size, small nuclei, and nuclear fission. The myoepithelium was lined around the glandular cavity, but the myoepithelium was tumorous. Immunohistochemistry was performed for further verification. Vimentin was positive in mesenchyme and CK-P was positive in epithelial cells. P63 and calponin were spotted, which were focal positive around the glandular cavity. Finally, the patient was diagnosed as ACC.
INTERVENTIONS: At last, the patient chose chemoradiotherapy, not surgical excision.
OUTCOMES: The patient is alive and well 13 months after the initial diagnosis.
LESSONS: ACC in the vagina is extremely rare. To our knowledge, this report is the first case of ACC arising from the vagina in English-language literature. Extensive surgical section of the tumour and chemoradiotherapy are recommended for therapy. Because of rarity, the prognosis of ACC in vagina is not known.

Ling DC, Vargo JA, Glaser SM, et al.
Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer.
Gynecol Oncol. 2019; 152(3):581-586 [PubMed] Related Publications
BACKGROUND: Limited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT.
METHODS: A retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to <75 Gy and <90 Gy, respectively. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities, defined according to CTCAE v4, were recorded.
RESULTS: Prior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6-75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3-81.8), 70.6 Gy (range: 32.0-80.5), and 52.7 Gy (range: 29.6-75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities.
CONCLUSION: Re-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation.

Broggi G, Piombino E, Magro G, Vecchio GM
Intestinal-type adenocarcinoma of the vagina: clinico-pathologic features of a common tumor with a rare localization.
Pathologica. 2018; 110(2):92-95 [PubMed] Related Publications
Intestinal-type adenocarcinoma is a rare primary vaginal carcinoma and considerably more uncommon than metastatic lesions which represent the most frequent malignancy at this anatomic site. Among all malignant tumors, colorectal, breast and female genital tract carcinomas have the tendency to metastasize to the vagina.
As morphologic and immunohistochemical features of intestinal-type adenocarcinoma occurring primarily in the vagina are not specific, clinical and radiologic information is crucial to exclude a metastatic lesion.
Herein we present a rare case of intestinal-type adenocarcinoma from a villous adenoma, presenting as a polypoid mass in the posterior wall of vaginal introitus of 51-year-old menopausal woman. To the best of our knowledge, only 19 cases of intestinal-type adenocarcinoma of the vagina have been reported in the English literature so far. Notably the origin from a previous villous adenoma has been well documented only in a few cases.

Tanwar RK, Saxena B, Ali S, Saxena S
Primary malignant melanoma of the vagina: Report of two rare cases.
J Cancer Res Ther. 2018 Oct-Dec; 14(6):1439-1441 [PubMed] Related Publications
We hereby present two rare cases of primary malignant melanoma of vagina in women aged 65 and 50 years, respectively. At the time of presentation, the disease in both cases was locally advanced and subsequently metastasized to distant organs.

Boggio F, Lopez G, Del Gobbo A, et al.
Amelanotic primary vaginal melanoma: A case report with cyto-histological correlations.
Diagn Cytopathol. 2019; 47(3):230-233 [PubMed] Related Publications
Vaginal mucosa represents a rare site for primary melanoma. These neoplasms more commonly occur in the postmenopausal period, usually presenting with vaginal discharge, bleeding, or palpable mass. We report a case of an 89-year-old woman presenting with vaginal bleeding and a non-pigmented lesion in the lower third of the vagina at the gynaecological examination. A PAP smear and tissue incisional biopsy were concurrently performed. The cytological sample showed a subpopulation of non-cohesive, atypical epithelioid cells suggestive for malignancy. The histological examination showed the same morphological characteristics in the neoplastic population widely underlying the vaginal epithelium, with scattered intraepithelial nests and single elements. In both samples, there was no evidence of melanin pigment within the malignant cells. Immunohistochemical analysis performed on the tissue biopsy demonstrated a strong and diffuse positivity for melanocytic markers (HMB-45, S-100, Melan-A), confirming the diagnosis of primary amelanotic vaginal melanoma.

Cong Q, Fu Z, Zhang D, Sui L
Importance of Colposcopy Impression in the Early Diagnosis of Posthysterectomy Vaginal Cancer.
J Low Genit Tract Dis. 2019; 23(1):13-17 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: The aim of the study was to investigate the value of cytology, high-risk human papillomavirus (hrHPV) status and colposcopy in the early diagnosis of vaginal cancer after hysterectomy.
MATERIALS AND METHODS: A retrospective study was performed in the Obstetrics and Gynecology Hospital of Fudan University. Posthysterectomy patients who were diagnosed with vaginal high-grade intraepithelial lesion (HSIL) by colposcopy-directed biopsy with colposcopy impression of extensive HSIL or suspicion of cancer and underwent upper or total vaginectomy from January 2009 to December 2017 were included.
RESULTS: Eighty-six posthysterectomy vaginal HSIL patients were included. Available abnormal cytology and positive hrHPV were observed in 90.7% (49/54) and 96.2% (51/53) of the patients, respectively. A total of 18.6% (16/86) of the patients were diagnosed with squamous cell cancer by vaginectomy, and the average interval between hysterectomy and vaginectomy was 3.5 years. Among them, 62.5% (10/16) cancers occurred after hysterectomy for cervical cancer, 31.2% (5/16) after hysterectomy for cervical precancer, and 6.3% (1/16) after hysterectomy for myoma. An indication for hysterectomy (cervical cancer vs HSIL, odds ratio = 7.2, 95% CI = 1.9-28.0, p = .004) and colposcopy impression of vaginal cancer (vaginal cancer vs HSIL, odds ratio = 5.9, 95% CI = 1.3-26.8, p = .021) were high-risk factors of cancer confirmed by vaginectomy in colposcopy-directed biopsy vaginal intraepithelial neoplasia 2/3 posthysterectomy in multiple logistic regression analysis.
CONCLUSIONS: Colposcopy is pivotal in the evaluation of abnormal cytology/hrHPV tests in follow-up of cervical cancer patients after hysterectomy and decision-making for vaginectomy in detecting early cancer.

Adams TS, Cuello MA
Cancer of the vagina.
Int J Gynaecol Obstet. 2018; 143 Suppl 2:14-21 [PubMed] Related Publications
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.

Wilkie GL, Taggart AA, Prensner JR, et al.
Burkitt Lymphoma Presenting as Menorrhagia and a Vaginal Mass in an Adolescent.
J Pediatr Adolesc Gynecol. 2019; 32(1):90-92 [PubMed] Related Publications
BACKGROUND: Menorrhagia is a common gynecologic complaint among adolescents, which rarely is secondary to malignancy. Burkitt lymphoma can mimic gynecologic malignancy, however it is rarely seen in adolescents. Burkitt lymphoma of the gynecologic tract requires early diagnosis and intervention for optimal outcomes.
CASE: We report a case of a 15-year-old adolescent who had multiple admissions for menorrhagia that was thought to be secondary to anovulatory bleeding until pelvic ultrasound revealed a large 8-cm vaginal/cervical mass. Histologic examination of the biopsy specimen revealed Burkitt lymphoma, which was treated with chemotherapy leading to resolution of her menorrhagia.
SUMMARY AND CONCLUSION: Burkitt lymphoma presenting as a vaginal/cervical mass is exceedingly rare, especially in the adolescent patient. Burkitt lymphoma is generally highly responsive to chemotherapy, and symptoms rapidly improve after initiation of treatment.

Bradbury M, Xercavins N, García-Jiménez Á, et al.
Vaginal Intraepithelial Neoplasia: Clinical Presentation, Management, and Outcomes in Relation to HIV Infection Status.
J Low Genit Tract Dis. 2019; 23(1):7-12 [PubMed] Related Publications
OBJECTIVES: The data available on vaginal intraepithelial neoplasia (VAIN) and infection by HIV are scarce. We therefore aimed to review the clinical presentation, management, and survival outcomes of VAIN in this group of women.
MATERIALS AND METHODS: This is an observational cohort study of women diagnosed with VAIN for a 23-year period. Clinical characteristics and outcomes were analyzed according to women's HIV infection status. Disease-free and progression-free survival were compared between groups.
RESULTS: Twenty-two of 87 women were HIV positive (25.3%) compared with the HIV-negative group, HIV-positive women were younger (median age = 39 vs 57 years, p < .001) and more frequently smokers (p < .001). They also presented with multifocal and multicentric disease more often (p = .004 and p = .033, respectively) in relation to infection by human papillomavirus. All HIV-positive women were receiving antiretroviral treatment. The median time from the diagnosis of HIV to the development of VAIN was 14 years (range = 1-22 years). There were no significant differences in survival outcomes between groups.
CONCLUSIONS: HIV-positive women are at an increased risk of developing VAIN and frequently present at a younger age with multifocal and multicentric disease. Vaginal intraepithelial neoplasia lesions can develop many years after the initial diagnosis of HIV infection reason why prolonged surveillance is essential to enable prompt diagnosis and treatment.

Kondo E, Maki S, Nii M, et al.
Long-term survival of a patient with malignant transformation of extragonadal endometriosis treated solely with chemotherapy: A case report.
J Obstet Gynaecol Res. 2018; 44(12):2186-2189 [PubMed] Related Publications
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/m

Tranoulis A, Georgiou D, Laios A, et al.
5-Flouorouracil Is an Attractive Medical Treatment in Women With Vaginal Intraepithelial Neoplasia: A Meta-Analysis.
J Low Genit Tract Dis. 2018; 22(4):375-381 [PubMed] Related Publications
OBJECTIVE: In the absence of standard guidelines, the management of vaginal intraepithelial neoplasia (VaIN) remains a field of debate. The aim of this systematic review and meta-analysis was to ascertain the 5-flouorouracil (5-FU) effectiveness in this context.
MATERIALS AND METHODS: A literature search was conducted throughout the PubMed, EMBASE, SCOPUS, ClinicalTrials.gov, and Cochrane Databases for relevant studies. We computed the summary proportions of women treated for VaIN with 5-FU for the outcomes of complete response and recurrence by random-effects meta-analysis. We also performed a subgroup analysis by computing the summary proportions for complete response among women with high-grade VaIN, persistent disease, and recurrence respectively.
RESULTS: Fourteen observational studies reporting on 358 women included in the study. The study quality was moderate. The summary proportions of women who had complete response after the first 5-FU course were 82.18% (95% CI = 69.80%-88.82%). The summary proportions of women who recurred were 16.42% (95% CI = 7.39%-28.14%). The summary proportions of women with complete response in the high-grade VaIN, persistent disease, and recurrence subgroups were 77.53% (95% CI = 59.90%-91.15%), 53.92% (95% CI = 34.62%-72.61%), and 72.32% (95% CI = 48.12%-91.05%), respectively.
CONCLUSIONS: This is the first meta-analysis to date to provide a convincing overview of 5-FU efficacy on the VaIN treatment. Albeit a medium risk of bias warrants some caution with interpretation of the results, 5-FU can be an attractive alternative to surgery, especially among young women with multifocal and recurrent disease.

Matsuo K, Blake EA, Machida H, et al.
Incidences and risk factors of metachronous vulvar, vaginal, and anal cancers after cervical cancer diagnosis.
Gynecol Oncol. 2018; 150(3):501-508 [PubMed] Related Publications
OBJECTIVE: To examine incidences and risk factors for metachronous vulvar, vaginal, and anal malignancies after a cervical cancer diagnosis.
METHODS: This is a retrospective study examining data from the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Cumulative incidences of vulvar, vaginal, and anal cancers after the diagnosis of cervical cancer were assessed (n = 79,050). Multivariable analysis was performed to determine independent risk factors for these metachronous cancers.
RESULTS: Vaginal cancer (20-year cumulative incidence, 0.57%) was the most common type of metachronous malignancy, followed by vulvar cancer (0.33%), and anal cancer (0.16%, P < 0.001). Median time to diagnosis was 5.4 years for vaginal cancer, 6.5 years for vulvar cancer, and 13.5 years for anal cancer. On multivariable analysis, metachronous vulvar cancer was associated with older age (hazard ratio [HR] per year 1.04, 95% confidence interval [CI] 1.02-1.05, P < 0.001), squamous histology (HR 2.64, 95%CI 1.38-5.05, P = 0.003), and radiotherapy use (HR 2.52, 95%CI 1.66-3.84, P < 0.001); metachronous vaginal cancer was associated with older age (HR per year 1.03, 95%CI 1.02-1.04, P < 0.001) and Black race (HR 1.73, 95%CI 1.20-2.48, P = 0.003); and metachronous anal cancer was associated with older age (HR 1.03, 95%CI 1.01-1.05, P = 0.017). Overall survival of metachronous cancer was poor (5-year rates: 46.3% for vulvar, 43.0% for vaginal, and 47.5% for anal cancer, respectively).
CONCLUSION: Although rare, the rate of ano-genital cancers continues to increase over time after a cervical cancer diagnosis. Long-term follow-up and surveillance after cervical cancer treatment is therefore reasonable to detect these metachronous malignancies, particularly in those with risk factors.

Murofushi KN, Kitamura N, Yoshioka Y, et al.
A Clinical Evaluation of American Brachytherapy Society Consensus Guideline for Bulky Vaginal Mass in Gynecological Cancer.
Int J Gynecol Cancer. 2018; 28(7):1438-1445 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: American Brachytherapy Society (ABS)-recommended interstitial brachytherapy (IBT) should be considered for bulky vaginal tumor thicker than 5 mm. The aim of this study was to evaluate the ABS consensus guideline for patients with severe vaginal invasion based on our long-term follow-up results.
METHODS/MATERIALS: The study included 7 patients with vaginal cancer and 14 patients with cervical cancer invading to the lower vagina. Based on prebrachytherapy magnetic resonance imaging findings, patients received intracavitary brachytherapy (ICT) for vaginal tumors 5 mm or less or IBT for vaginal tumors less than 5 mm. Nine patients received ICT and the remaining 12 patients received IBT. For dosimetric comparison, an experimental recalculation as the virtual IBT for patients actually treated by ICT, and vice versa, was performed.
RESULTS: The 5-year local control rate for all tumors was 89.4%. No differences in local control between ICT- and IBT-treated groups were observed (P = 0.21). One patient experienced a grade 3 rectal complication. There were no significant differences in the CTV D90 and rectum D2cc between the 2 groups (P = 0.13 and 0.39, respectively). In the dosimetric study of ICT-treated patients, neither the actual ICT plans nor the experimental IBT plans exceeded the limited dose for organs at risk, which were recommended in the guideline published from the ABS. In the IBT-treated patients, D2cc for bladder and rectum of the experimental ICT plans was significantly higher than for the actual IBT plans (P < 0.001 and <0.001, respectively), and 11 experimental ICT plans (92%) exceeded the limited dose for bladder and/or rectum D2cc.
CONCLUSIONS: Tumor control and toxicity after selected brachytherapy according to vaginal tumor thickness were satisfactory; IBT instead of ICT is recommended for patients with vaginal tumor thickness greater than 5 mm to maintain bladder and/or rectum D2cc.

Shoeir S, Balachandran AA, Wang J, Sultan AH
Mesonephric adenocarcinoma of the vagina masquerading as a suburethral cyst.
BMJ Case Rep. 2018; 2018 [PubMed] Related Publications
Mesonephric adenocarcinoma (MA) of the vagina is an extremely rare tumour of the female genital tract. There are currently 22 reported cases in the published literature. Consequently, its pathophysiology and disease progression remain poorly understood.A 63-year-old woman presented with a history of a swelling in her vagina. Two-dimensional pelvic floor ultrasound and MRI demonstrated a multiloculated cyst with no malignant features. Initial workup provided a working diagnosis of a suburethral cyst. The diagnosis of MA was made on histology after excision of the cyst. Subsequent postoperative investigation showed no spread of the disease. The patient completed a course of prophylactic brachytherapy to prevent the possibility of any recurrence of disease. Due to its rarity, it remains difficult to diagnose MA of the vagina even on histological analysis. We would therefore recommend a low threshold to excise or perform tissue biopsy of unspecified vaginal masses.

Haykal T, Pandit T, Bachuwa G, Danish R
Stage 1 small cell cancer of the vagina.
BMJ Case Rep. 2018; 2018 [PubMed] Related Publications
This is the case of a 56-year-old white woman with a medical history significant for chronic obstructive pulmonary disease, migraine, hypertension, tobacco abuse and hypercholesterolaemia. Her surgical history is significant for total hysterectomy and bilateral salpingo-oophorectomy for diffuse endometriosis. The patient presented with a vaginal lesion. The biopsy was positive for primary vaginal small cell carcinoma and human papilloma virus (HPV). Initial staging positron emission tomography (PET) scan confirmed stage 1 disease. The patient was started on chemotherapy with cisplatin and etoposide for four cycles, followed by concurrent chemotherapy with cisplatin/taxol and radiation therapy.

Gebhardt BJ, Vargo JA, Kim H, et al.
Image-based multichannel vaginal cylinder brachytherapy for the definitive treatment of gynecologic malignancies in the vagina.
Gynecol Oncol. 2018; 150(2):293-299 [PubMed] Related Publications
PURPOSE: Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC.
METHODS AND MATERIALS: Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70-80 Gy.
RESULTS: The median high-risk clinical target volume was 24.4 cm
CONCLUSIONS: Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

Talia KL, Wong RW, McCluggage WG
Expression of Markers of Müllerian Clear Cell Carcinoma in Primary Cervical and Vaginal Gastric-type Adenocarcinomas.
Int J Gynecol Pathol. 2019; 38(3):276-282 [PubMed] Related Publications
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.

Morganstern BA, Scaccia S, Wu W, et al.
Synchronous, but separate, bladder and vaginal rhabdomyosarcoma: a novel genetic case report.
Can J Urol. 2018; 25(3):9357-9359 [PubMed] Related Publications
Embryonal rhabdomyosarcoma is a rare cancer that often requires multimodality therapy to treat; however, these therapies can cause changes in the biology of the tumor. Several reports have documented pathologic changes but only recently have genetic changes been mapped. We present case of two separate synchronous primary rhabdomyosarcomas in a 17-month-old patient and discuss the pathophysiology and genetic changes that occur with treatment. We hypothesize that a genetic field defect arising in development of the urogenital sinus caused the tumors, but that treatment modalities may have caused genetic alterations changing clinical behavior of the tumors and responses to treatment.

Inoue K, Tsubamoto H, Isono-Nakata R, et al.
Itraconazole treatment of primary malignant melanoma of the vagina evaluated using positron emission tomography and tissue cDNA microarray: a case report.
BMC Cancer. 2018; 18(1):630 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary malignant melanoma of the vagina is extremely rare, with a poorer prognosis than cutaneous malignant melanoma. Previous studies have explored the repurposing of itraconazole, a common oral anti-fungal agent, for the treatment of various cancers. Here, we describe a patient with metastatic, unresectable vaginal malignant melanoma treated with 200 mg oral itraconazole twice a day in a clinical window-of-opportunity trial.
CASE PRESENTATION: A 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and
CONCLUSION: The findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.

Minard-Colin V, Walterhouse D, Bisogno G, et al.
Localized vaginal/uterine rhabdomyosarcoma-results of a pooled analysis from four international cooperative groups.
Pediatr Blood Cancer. 2018; 65(9):e27096 [PubMed] Related Publications
BACKGROUND: Vaginal/uterine rhabdomyosarcoma (VU RMS) is one of the most favorable RMS sites. To determine the optimal therapy, the experience of four cooperative groups (Children's Oncology Group [COG], International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Group [MMT], Italian Cooperative Soft Tissue Sarcoma Group [ICG], and European pediatric Soft tissue sarcoma Study Group [EpSSG]) was analyzed.
PROCEDURE: From 1981 to 2009, 237 patients were identified. Median age (years) at diagnosis differed by tumor location; it was 1.9 for vagina (n = 160), 2.7 for uterus corpus (n = 26), and 13.5 for uterus cervix (n = 51). Twenty-eight percent of patients received radiation therapy (RT) as part of primary therapy (23% COG, 27% MMT, 46% ICG, and 42% EpSSG), with significant differences in the use of brachytherapy between the cooperative groups (23% COG, 76% MMT, 64% ICG, and 88% EpSSG).
RESULTS: Ten-year event-free (EFS) and overall survival (OS) were 74% (95% CI, 67-79%) and 92% (95% CI, 88-96%), respectively. In univariate analysis, OS was inferior for patients with uterine RMS and for those with regional lymph node involvement. Although EFS was slightly lower in patients without initial RT (71% without RT vs. 81% with RT; P = 0.08), there was no difference in OS (94% without RT vs. 89% with RT; P = 0.18). Local control using brachytherapy was excellent (93%). Fifty-one (51.5%) of the 99 survivors with known primary therapy and treatment for relapse were cured with chemotherapy with or without conservative surgery.
CONCLUSIONS: About half of all patients with VU RMS can be cured without systematic RT or radical surgery. When RT is indicated, modalities that limit sequelae should be considered, such as brachytherapy.

Mori Y, Kinoshita S, Kanamori T, et al.
The Successful Treatment of Metastatic Extraosseous Ewing Sarcoma with Pazopanib.
Intern Med. 2018; 57(18):2753-2757 [PubMed] Free Access to Full Article Related Publications
The clinical efficacy and outcomes of pazopanib treatment for metastatic extraosseous Ewing sarcoma remain unclear. We herein report a case of heavily pre-treated metastatic extraosseous Ewing sarcoma in which pazopanib treatment achieved a significant improvement. A 17-year-old girl was referred to our hospital due to metastatic extraosseous Ewing sarcoma. The initial cytotoxic chemotherapy was temporarily effective, however, her disease eventually progressed, and she was subsequently treated with pazopanib. The recurrent tumor showed a marked response to pazopanib therapy; the therapeutic effect has lasted for more than 26 months. The present case suggests that pazopanib may be a therapeutic option for extraosseous Ewing sarcoma.

Wong RW, Moore M, Talia KL, et al.
Primary Vaginal Gastric-type Adenocarcinoma and Vaginal Adenosis Exhibiting Gastric Differentiation: Report of a Series With Detailed Immunohistochemical Analysis.
Am J Surg Pathol. 2018; 42(7):958-970 [PubMed] Related Publications
So-called gastric-type adenocarcinoma and related premalignant lesions have been characterized in the cervix, but similar lesions are not widely recognized in the vagina. We report a series of 11 vaginal glandular lesions exhibiting gastric differentiation, comprising 5 cases of adenocarcinoma and 6 of adenosis. All cases occurred in adults (aged 33 to 69) with no known history of diethylstilboestrol exposure. The vaginal adenocarcinomas exhibited morphologic features identical to gastric-type adenocarcinoma of the cervix, but 1 case additionally demonstrated basaloid and sarcomatoid components, which have not been previously reported in cervical gastric-type adenocarcinoma. Immunohistochemically, the adenocarcinomas were positive for MUC6 (4/5), PAX8 (3/5), CK7 (5/5), CK20 (1/5), CDX2 (5/5), CA19.9 (5/5), CEA (4/5), CA125 (5/5), and hepatocyte nuclear factor 1β (5/5). p16, estrogen receptor, and Napsin A were negative in all cases tested, whereas p53 exhibited mutation-type staining in 3/5 cases. In all 5 adenocarcinomas, a component of adenosis with benign or atypical nuclear features was identified; the adenosis displayed gastric morphology in 4 cases and tuboendometrial morphology in 1. The 6 cases of pure vaginal adenosis (without associated adenocarcinoma) all contained gastric-type mucinous glands together with tuboendometrial glands in 2 cases. There was focal intestinal differentiation with goblet cells in all 6 cases and neuroendocrine cells with eosinophilic granules in 3. Cytologic atypia was observed in 4/6 cases of pure vaginal adenosis. Immunohistochemically, the gastric-type adenosis (10 cases) was positive for MUC6 (10/10), estrogen receptor (5/10), PAX8 (8/10), CK7 (9/9), CK20 (2/9), CDX2 (5/9), CA19.9 (8/9), CEA (6/9), CA125 (6/9), hepatocyte nuclear factor 1β (10/10), and Napsin A (1/10). p53 exhibited wild-type immunoreactivity in all 10 cases, whereas p16 was negative in all cases tested. Scattered individual chromogranin-positive cells were present in all 5 cases of pure adenosis tested. Follow-up was available in 4 of the adenocarcinoma cases, with 3 patients dead of disease within 1 to 3 years and 1 patient alive with disease at 1 year. The morphologic and immunohistochemical findings in our study suggest a close relationship between vaginal gastric-type adenocarcinoma and adenosis exhibiting gastric differentiation. This probably represents a distinct pathway of vaginal gastric-type carcinogenesis analogous to that occurring in the cervix. We propose that gastric-type adenocarcinoma be recognized as a distinct histologic subtype of vaginal adenocarcinoma while vaginal adenosis of gastric-type represents a novel subtype of adenosis that requires further study to clarify its biological potential.

Johnson MT, Smith KC, Tsai LL
Vaginal spindle cell epithelioma: A first complete MRI and histopathologic description.
Clin Imaging. 2018 Jul - Aug; 50:181-184 [PubMed] Related Publications
Spindle cell epithelioma of the vagina is a benign entity with fewer than sixty cases described in the literature, and only two with limited imaging findings, since the early 1950s. Early pathology literature suggested the lesions were mixed tumors of myoepithelial origin, but subsequent studies have found relatively few immunohistochemical characteristics in common with other mixed cell tumors. More recently, Mullerian, urogenital sinus epithelial, and pluripotential cell origins have been proposed. Given lesion rarity and a typical lack of imaging before excision, the imaging appearance of vaginal spindle cell epitheliomas has not been fully described in the radiology literature, and without comprehensive pathology correlation. The authors describe a case of spindle cell epithelioma in a 54-year-old woman which was incidentally discovered on MRI performed for uterine fibroid embolization planning. Pathology and immunohistochemistry confirmed the diagnosis.

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