Next Article in Journal
Single-Arm, Prospective, Interventional Study of Helicobacter pylori Eradication Rescue Therapy with Rifabutin, Metronidazole, and Vonoprazan
Next Article in Special Issue
How to Avoid Becoming a Risk Factor of Fecal Incontinence Due to OASIS—A Narrative Review
Previous Article in Journal
Venous and Arterial Thromboembolism in Lung Cancer Patients: A Retrospective Analysis
Previous Article in Special Issue
Sonography as a Diagnostic Tool in Midurethral Sling Complications: A Narrative Review
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Survival and Treatment Modalities in Primary Vaginal Melanoma—Case Report and a Narrative Review

1
Clinical Department of Gynecology and Obstetrics, City Hospital, 35-241 Rzeszów, Poland
2
Medical University of Gdańsk, 17 Smoluchowskiego St., 80-241 Gdańsk, Poland
3
Pathology Department, Clinical Provincial Hospital no 2, 35-241 Rzeszów, Poland
4
Department of Gynecology and Obstetrics, Medical University of Gdańsk, 17 Smoluchowskiego St., 80-241 Gdańsk, Poland
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2024, 13(13), 3771; https://doi.org/10.3390/jcm13133771
Submission received: 1 May 2024 / Revised: 3 June 2024 / Accepted: 13 June 2024 / Published: 27 June 2024
(This article belongs to the Special Issue Prevention and Treatment for Pelvic and Relative Diseases)

Abstract

:
Background/Objectives: Primary vaginal melanoma (PVM) is a rare cancer representing five percent of vaginal cancers and less than one percent of all female vaginal melanomas, with an incidence rate of 0.46 per million women per year. The aim of this study was to present a case of combined therapy and conservative surgical treatment in a young patient with PVM and to perform a systematic review of the same subject. Methods: We performed a narrative review of the literature and presented a case report. Results: The review yielded a total of 43 articles. We presented treatment modalities and survival outcomes. The presented case involved a combination of surgical treatment with adjuvant therapy comprising nivolumab and ipilimumab. Conclusions: PVM is a disease with a poor prognosis; however, new treatment options are promising and have a great chance of significantly improving survival. The combination of the wide local excision of the primary lesion followed by adjuvant therapies results in the best outcomes in the treatment of PVM. Future clinical studies are warranted to provide new evidence for the treatment outcomes of nonsurgical, metastatic PVM and the adjuvant treatment of PVM.

1. Introduction

Primary vaginal melanoma (PVM) is a rare cancer representing five percent of vaginal cancers and less than one percent of all female vaginal melanomas, with an incidence rate of 0.46 per million women per year [1]. The average age of incidence is 68 years, with a predominance in the white population. It mostly occurs in postmenopausal women, and its etiology is unclear [2]. Patients are usually referred with primary, postmenopausal vaginal bleeding, pain, palpable mass, abnormal vaginal secretion, vaginal lumps, difficulty in sexual intercourse, and itching [2,3]. The lesion is usually found in the lower one-third of the anterior wall of the vagina. Metastases appear rapidly (average 10 months), mainly to the lungs (75%) and liver (43.8%). The five-year survival rate is estimated to be 15% (5–25%) [4,5]. Currently, no standards of effective treatment for patients with PVM have been defined. The most common treatment is surgical excision followed by an adjuvant radiotherapy, chemotherapy, immunotherapy, or mixed targeted therapy [3]. Surgical treatment includes wide local excision or radical excision with the aim of achieving a negative margin. Performing an extended abdominal surgery with lymphadenectomy is controversial and its benefit is doubted. Few adjuvant chemotherapy regimens have been proved beneficial alone or in combination in clinical trials. One of the recent promising results reported is treatment with interferon alpha, which has become a standard of care for some groups of patients [6]. Numerous novel methods of treatment are being tested in clinical trials. The aim of this study is to present a case of the application of a combined therapy and conservative surgical treatment in a young patient with PVM, and to perform a systematic review of the surgical and adjuvant strategies for PVM treatment and survival.

2. Materials and Methods

2.1. Search Strategy

This systematic review was performed according to the PRISMA 2020 (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines [7]. The research questions are presented in the Patients, Interventions, Comparison, Outcome, and Study Design (PICOS) criteria in Table 1. We searched MEDLINE via the PubMed and Web of Science databases. Additionally, Cochrane Reviews were checked for applicable studies. We used the following keywords: melanoma, skin cancer, skin carcinoma, mucosal cancer, mucosal carcinoma, vagina, and primary. The search terms were combined using the Boolean operators ‘AND’ and ‘OR’. No filters were used. The full search strategy for MEDLINE via PubMed was as follows: ((melan*) OR (skin cancer) OR (skin carcinoma)) AND (vagi*) AND (prima*). The full search strategy for the Web of Science was as follows: ((ALL = (vagi*)) AND ALL = (prima*)) AND ALL = (melan*). The citations were synthesized using EndNote 21. Duplicates were removed using EndNote 21. The references of systematic reviews of similar subjects were scanned and analyzed for relevant studies that were not found in our search. The study was not registered in publicly accessible database.
On 22 March 2024, the MEDLINE via PubMed and Web of Science databases were searched. The initial search yielded 1049 results. No relevant articles were found in the Cochrane Library. A total of 178 duplicates were identified by EndNote and removed. A total of 74 articles were chosen for full-text screening. Of these, 30 reports were excluded for not being compliant with the systematic review’s PICOS criteria. No studies were found or assessed for eligibility by reference analysis. A total of 46 reports met the inclusion criteria, including 24 case reports [2,6,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29] and 19 cohort studies [1,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47] (Figure 1).

2.2. Study Selection

The inclusion criteria were as follows: age > 18 years, histopathological diagnosis of primary vaginal melanoma, treatment modality, and survival.
The exclusion criteria were as follows: study outcomes not reported in English, not a full-text article type (conference meeting abstracts, posters, abstracts only, or no full-text available), disease other than primary vaginal melanoma reported in the study, and no survival outcomes. The selection process included reading titles and abstracts, reading full texts, and extracting data by two independent reviewers (P.T. and M.Ł.), with disagreements resolved by a third reviewer (P.G.).

2.3. Data Extraction

Two independent authors collected relevant data from the literature into spreadsheets for each included study, including the first author, year published, design, number of patients, age, depth of invasion, size, clinical stage at referral, treatment modality, radicality of surgery, number of adjuvant therapies and their modalities, recurrence rate, overall survival, and follow-up outcomes.

2.4. Risk of Bias and Literature Quality Evaluation

The quality of the included cohort studies was assessed by two independent researchers using the Newcastle–Ottawa scale [48], and disagreements were resolved by consulting a third researcher. The studies were assessed for selection (up to four stars), comparability (up to two stars), and exposure (up to four stars). The summary plots were created using the robvis tool [49].

3. Results

3.1. Case Report

A 29-year-old woman was referred to the hospital because of a suspected cervical polyp. The woman reported vaginal spotting and abdominal pain that had occurred for one month.
The examination carried out with the specula revealed a lofty pigmented lesion located in one-third of the proximal left vaginal sidewall, measuring two to three centimeters, with bleeding to the touch. The lesion was completely removed. Histopathological examination revealed malignant melanoma (nodular type) infiltrating the mucous membrane and deeper tissues. The lesion was removed without any margin of healthy tissue, with Breslow 15 mm and a Clark V level. Immunohistochemical staining for vimentin and melan A was positive. No metastatic foci were found in the imaging screening. The patient was referred to a reference center. After further imaging, metastases to the periaortic lymph nodes were found. No V600 BRAF mutation was detected by molecular examination. The patient was offered systemic treatment with possible future surgery in case of a reaction to the treatment. Due to the advanced stage of the neoplastic process, nivolumab and ipilimumab were included in the treatment. Imaging of the whole body three months after the end of treatment revealed numerous metastases in the uterus, brain, lungs, and liver. Palliative radiotherapy and chemotherapy were offered; however, no regression of the disease was achieved. One year after the diagnosis was made, the patient died of the disease.

3.2. Systematic Review

The cohort studies included were published between 1989 and 2023. A total of five case series and 14 retrospective studies were analyzed. The mean age ranged from 49 to 81.25 years. The primary treatment in most patients was surgery, which varied between wide local excision and extended surgery. The latter included vaginectomy with hysterectomy and bilateral salpingo-oophorectomy, with some cases extending to the pelvic exenteration. In two studies, external radiation was the first-line treatment. Surgical procedures were followed by systemic treatment in most cases. Adjuvant therapy was predominantly administered to patients undergoing local treatment. Among the adjuvant therapies, external radiotherapy was the most used. Doses of radiotherapy ranged from 45 Gy to 60 Gy, often delivered in fractions of 1.8 Gy to 2 Gy per session. Interferon alpha-2b was administered in 10 patients, but specific doses were not detailed. Chemotherapeutic agents were used in six patients and included dacarbazine (no dose specified) and temozolomide (administered in combination with radiotherapy). A total of 52 patients were treated with combined chemotherapy, interferon alpha-2b, or immunotherapy. There were no doses and schemes of immunotherapy specified. The recurrence rate varied significantly from 12.5% to 100%, although the size and heterogeneity of the groups were influential factors. Overall survival (OS) differed significantly between study groups and is not precisely estimable due to the use of median and mean values or the absence of reported data. Of the 828 patients across the studies, 514 patients have died of disease. Survival across the studies ranged from 2 months to 2325 months. Patients were recorded as deceased due to the poor prognosis of vaginal melanoma. Only four patients were reported to have no evidence of disease.
A summary of the cohort studies’ designs, cohort characteristics, interventions, and treatment outcomes are presented in Table 2.
The case reports included were published between 1989 and 2023. The ages ranged from 31 to 80 years, with a mean of 58 years. The depth of tumor invasion varied from 2 mm to 13 mm. The primary treatment for all patients was surgery; 12 patients underwent radical procedures (total vaginectomy and/or hysterectomy with or without abdominal exenteration), 7 patients underwent limited surgery (including wide local excision), and 3 patients underwent partial vaginectomy. In one instance, due to the advanced stage of the disease, the operation involved laparoscopic pelvic lymph node biopsy alone. One patient was lost to follow-up immediately after receiving the pathological examination results, resulting in no medical intervention being administered. Adjuvant therapy was administered in most patients and included external radiotherapy, brachytherapy, immunotherapy, and chemotherapy. Six patients underwent chemotherapy, eight patients underwent immunotherapy, and eight patients underwent radiotherapy (brachytherapy or external radiotherapy). Specific chemotherapy agents were not reported, with mentions of “chemotherapy” or “palliative chemotherapy”. Eight patients underwent radiotherapy, and one of them underwent brachytherapy. In some cases, adjuvant treatment modalities were combined. In eight patients, adjuvant therapy was not applied. The therapeutic success was gauged by the occurrence of recurrence, which was observed in nine patients. OS was only reported in four patients because the patients died before the follow-up visit. Twelve patients were alive and had no signs of disease during the last follow-up visit, four were lost to follow-up, four died from disease, and four were alive but had disease.
A summary of the patients included in the case reports, interventions, and treatment outcomes is presented in Table 3.
The summary plot of the risk of bias assessment is presented in Figure 2. The studies were classified as having a moderate or high risk of bias due to concerns about comparability, possible selection bias that primarily arises from the rarity of the disease, and the selection of the study group (e.g., only patients with first-stage disease).

4. Discussion

This case is an illustration of the rapid and aggressive course of vaginal melanoma. PVM is a rare disease with no standardized treatment; therefore, the management of each patient with PVM is highly personalized and dependent on the stage of the disease. PVM diagnosis is often made in the late stage of the disease, with over 50% of patients having nodal involvement at the diagnosis [50,51]. Despite early diagnosis and aggressive treatment, the prognosis is poor. There is no optimal, efficient method for treating this type of cancer thus far. Currently, the basic method of treatment for vaginal melanoma is total surgical resection with a wide margin of healthy tissues [52]. Surgical resection is the only treatment modality for this disease for which there is evidence of complete cure. Surgery is the primary treatment modality in the absence of metastatic disease. Some authors have proposed extending the surgical procedure with the removal of regional lymph nodes by marking them with a sentinel node; however, this approach was proven not to be associated with improved survival [53,54]. In surgical resection, an 8 to 20 mm free margin should be obtained [46]. In some cases, that may be difficult due to a lesion location, and therefore the surgery can be extended. Although a meta-analysis was not performed due to the high heterogeneity of the results, we believe that our systematic review provides systematic evidence to the field in terms of (a) the range of surgeries that need to be performed and (b) the importance of adjuvant therapy that follows surgical treatment. The results of the present review show that wide local excision of the primary lesion followed by adjuvant therapies provides the greatest likelihood of a favorable disease course, although the prognosis remains poor. The results of the performed review suggest that performing extended surgeries with lymph node resection does not result in better overall survival. In our opinion, the greatest improvement to be made in PVM is in adjuvant therapies with a special focus on immunotherapy.
To date, limited studies have been carried out to assess adjuvant treatment after surgery. The use of radiotherapy as an adjuvant treatment may result in better local control of the disease; however, there is little evidence to support this statement [55]. Radiotherapy was one of the most frequent adjuvant treatment modalities in the literature review; however, it is suggested that radiotherapy may be used as an alternative for patients unfit for more aggressive treatment or as a synergy for other treatment modalities [55]. Wang et al. stressed the importance of chemotherapy and immunotherapy in combination with surgical confluence as the main therapeutic method for improving patient prognosis [56]. The use of interferon alpha was noted to prolong survival and is a promising treatment option; however, there are no high-quality studies assessing the effectiveness of such treatment in mucosal melanoma [21]. Targeted therapies are proven to be effective in treating cutaneous melanomas and most commonly include BRAF kinase inhibitors, often in combination with an MEK inhibitor. Despite mucosal melanomas rarely presenting BRAF or MEK mutations, they should be tested for these mutations, as the BRAF and MEK inhibitors may be considered as a treatment option. Mucosal melanomas sometimes have an activating mutation in the KIT, and sometimes tyrosine kinase inhibitors (imatinib and dasatinib) may be considered as an option [57]. Monoclonal antibodies against programmed cell death 1 (nivolumab) and against cytotoxic T-lymphocyte antigen 4 (ipilimumab) are in routine use in some countries. In the present case report, due to the inoperability of the lesion, the rapid appearance of metastases, and the lack of previous treatment, the patient was offered immunotherapy consisting of a combination of nivolumab and ipilimumab. Nivolumab has been proven to be an effective treatment option for skin melanoma [58]; however, there is no evidence supporting its use for treating mucosal melanoma. In a study by Robert et al., patients treated with nivolumab exhibited a longer survival time and inhibition of disease progression than patients treated with dacarbazine [59]. The use of ipilimumab in the monotherapy of mucosal melanoma prolonged the survival period without disease progression [60,61]. In October 2015, the use of ipilimumab–nivolumab in a combination therapy regimen for nonsurgical or metastatic melanoma in patients without the BRAF V600 mutation was registered in the United States of America, and in January 2016, it was used for all previously untreated patients with advanced disease. Previous studies have shown that nivolumab and ipilimumab treatment regimens and nivolumab monotherapy are superior to ipilimumab monotherapy in terms of progression-free survival time without disease and the percentage of objective responses [62,63]. In May 2016, the use of a combination of nivolumab and ipilimumab was approved in the European Union for patients with nonsurgical or metastatic melanoma, regardless of the BRAF mutation status. It is the first and only approved combination of immunocompetent molecules in the European Union that is currently undergoing clinical trials (NCT02626962, NCT04655157, and NCT01844505). Currently, the combination of ipilimumab with nivolumab may improve the response rate, resulting in a median progression-free survival of 11.5 months (2.9 months of progression-free survival for ipilimumab alone or 6.9 months for nivolumab alone) in metastatic disease [62]. However, when it comes to combined immunotherapy, the high rates of grade three and grade four toxicity should be taken under consideration. The clinical decision making is also complicated, with a modest improvement in the 3-year survival of 58% for patients treated with nivolumab–ipilimumab compared with 52% for patients with nivolumab monotherapy [64].
The rarity of the disease ensures that large-scale trials are unlikely to be feasible. Surgical excision remains the first line of treatment. In metastatic disease, immunotherapy, sometimes combined with chemotherapy or radiotherapy, has the greatest chance of prolonging the survival with the disease. Clinical decision making should be highly personalized and optimized based on the tumor biology, toxicity of the treatment, and tumor response. Including patients with PVM in the ongoing trials for new lines of treatment allows us to bring new evidence to the field and to offer the potential for a better survival for these groups of patients.

5. Conclusions

PVM is a disease with a poor prognosis; however, new treatment options are promising and have a great chance of significantly improving survival. The combination of the wide local excision of the primary lesion followed by adjuvant therapies still results in the best outcomes in the treatment of PVM. Future clinical studies are warranted to provide new evidence for the treatment outcomes of nonsurgical, metastatic PVM and the adjuvant treatment of PVM.

Author Contributions

Conceptualization, P.G., M.H. and P.T.; methodology, M.H. and P.T.; formal analysis, P.G., M.H., M.Ł. and P.T.; investigation, M.H., M.Ł. and P.T.; data curation, M.H. and M.Ł.; writing—original draft preparation, P.T., M.Ł. and P.T.; writing—review and editing, P.T., P.G., M.Ś., P.Z. and M.Ż.; visualization, P.T.; supervision, P.T., M.Ś. and P.G.; funding acquisition, P.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were waived for this study due to being a systematic review and obtaining consent for the case presentation from the patient.

Informed Consent Statement

Written informed consent has been obtained from the patient(s) to publish this paper.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Wohlmuth, C.; Wohlmuth-Wieser, I.; May, T.; Vicus, D.; Gien, L.T.; Laframboise, S. Malignant Melanoma of the Vulva and Vagina: A US Population-Based Study of 1863 Patients. Am. J. Clin. Dermatol. 2020, 21, 285–295. [Google Scholar] [CrossRef] [PubMed]
  2. Bai, S.; Wu, Q.; Song, L.; Wu, W. Treatment of primary vaginal malignant melanoma and review of previous literature: A case report. Medicine 2023, 102, e36128. [Google Scholar] [CrossRef] [PubMed]
  3. Dobrică, E.C.; Vâjâitu, C.; Condrat, C.E.; Crețoiu, D.; Popa, I.; Gaspar, B.S.; Suciu, N.; Crețoiu, S.M.; Varlas, V.N. Vulvar and Vaginal Melanomas-The Darker Shades of Gynecological Cancers. Biomedicines 2021, 9, 758. [Google Scholar] [CrossRef] [PubMed]
  4. Kirschner, A.N.; Kidd, E.A.; DeWees, T.; Perkins, S.M. Treatment Approach and Outcomes of Vaginal Melanoma. Int. J. Gynecol. Cancer 2013, 23, 1484–1489. [Google Scholar] [CrossRef] [PubMed]
  5. Vaysse, C.; Pautier, P.; Filleron, T.; Maisongrosse, V.; Rodier, J.F.; Lavoue, V.; Reyal, F.; Thomas, L.; de la Fouchardière, A.; Delannes, M. A large retrospective multicenter study of vaginal melanomas: Implications for new management. Melanoma Res. 2013, 23, 138–146. [Google Scholar] [CrossRef] [PubMed]
  6. Puri, S.; Asotra, S. Primary vaginal malignant melanoma: A rare entity with review of literature. J. Cancer Res. Ther. 2019, 15, 1392–1394. [Google Scholar] [CrossRef] [PubMed]
  7. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  8. Schwartz, J. Primary Malignant-Melanoma of the Vagina—Case Presentation with Electron-Microscopic Findings. J. Gynecol. Surg. 1989, 5, 109–115. [Google Scholar] [CrossRef]
  9. Moros, M.L.; Ferrer, F.P.; Mitchell, M.J.; Romeo, J.A.; Lacruz, R.L. Primary malignant melanoma of the vagina. Poor response to radical surgery and adjuvant therapy. Eur. J. Obstet. Gynecol. Reprod. Biol. 2004, 113, 248–250. [Google Scholar] [CrossRef]
  10. Gökaslan, H.; Sismanoglu, A.; Pekin, T.; Kaya, H.; Ceyhan, N. Primary malignant melanoma of the vagina:: A case report and review of the current treatment options. Eur. J. Obstet. Gynecol. Reprod. Biol. 2005, 121, 243–248. [Google Scholar] [CrossRef]
  11. Grenader, T.; Isacson, R.; Reinus, C.; Rosengarten, O.; Barenholz, O.; Hyman, J.; Gabizon, A.; Beller, U. Primary amelanotic melanoma of the vagina. Onkologie 2008, 31, 474–476. [Google Scholar] [CrossRef] [PubMed]
  12. Albareda, J.; Olier, C.; Alemany, I. Primary melanoma of the vagina. A clinical case. J. Turk. Ger. Gynecol. Assoc. 2011, 12, 50–52. [Google Scholar] [CrossRef]
  13. Kühn, F.; Dieterich, M.; Klar, E.; Gerber, B.; Prinz, C. Primary Malignant Vaginal Melanoma—Case Report and Review of the Literature. Geburtshilfe Frauenheilkd. 2012, 72, 740–743. [Google Scholar] [CrossRef] [PubMed]
  14. Androutsopoulos, G.; Terzakis, E.; Ioannidou, G.; Tsamandas, A.; Decavalas, G. Vaginal primary malignant melanoma: A rare and aggressive tumor. Case Rep. Obstet. Gynecol. 2013, 2013, 137908. [Google Scholar] [CrossRef] [PubMed]
  15. Chaudhuri, S.; Das, D.; Chowdhury, S.; Gupta, A.D. Primary malignant melanoma of the vagina: A case report and review of literature. South Asian J. Cancer 2013, 2, 4. [Google Scholar] [CrossRef] [PubMed]
  16. Chen, L.F.; Xiong, Y.; Wang, H.; Liang, L.Z.; Shang, H.L.; Yan, X.J. Malignant melanoma of the vagina: A case report and review of the literature. Oncol. Lett. 2014, 8, 1585–1588. [Google Scholar] [CrossRef] [PubMed]
  17. Rema, P.; Suchetha, S.; Ahmed, I. Primary Malignant Melanoma of Vagina Treated by Total Pelvic Exenteration. Indian J. Surg. 2016, 78, 65. [Google Scholar] [CrossRef] [PubMed]
  18. Chitrathara, K.; Subramanian, A.; Raj, S.; Sanam, P.; Kunheri, B. Primary Vaginal Malignant Melanoma with Urethral Involvement Managed by Bladder Preservation. Indian J. Gynecol. Oncol. 2017, 15, 3. [Google Scholar] [CrossRef]
  19. Kalampokas, E.; Kalampokas, T.; Damaskos, C. Primary Vaginal Melanoma, A Rare and Aggressive Entity. A Case Report and Review of the Literature. Vivo 2017, 31, 133–139. [Google Scholar] [CrossRef]
  20. Lee, C.K.; Lin, H.; Su, C.F.; Kok, V.C. Primary Vaginal Melanoma with Rhabdoid Features: A Case Report and Literature Review. Int. J. Gynecol. Pathol. 2017, 36, 499–504. [Google Scholar] [CrossRef]
  21. Rapi, V.; Dogan, A.; Schultheis, B.; Hartmann, F.; Rezniczek, G.A.; Tempfer, C.B. Melanoma of the Vagina: Case Report and Systematic Review of the Literature. Anticancer Res. 2017, 37, 6911–6920. [Google Scholar] [CrossRef]
  22. Ahn, H.Y.; Park, J.W.; Kim, J.S. Primary malignant melanoma of the vagina in a postmenopausal woman. Australas. Med. J. 2018, 11, 87–90. [Google Scholar] [CrossRef]
  23. Zabroug, S.; Lalya, I.; Nimubona, D.; Bouzid, N.; El Omrani, A.; Khouchani, M. Primary Mucosal Melanoma of the Vagina: About a Case Treated by External Beam Radiotherapy and High-Dose-Rate Brachytherapy. Indian J. Gynecol. Oncol. 2018, 16, 28. [Google Scholar] [CrossRef]
  24. Paravathaneni, M.; Edlukudige Keshava, V.; Baralo, B.; Thirumaran, R. Primary Vaginal Malignant Melanoma: A Case Report and Review of Literature. Cureus 2020, 12, e10536. [Google Scholar] [CrossRef]
  25. Tokumitsu, R.; Hirakawa, T.; Yano, M.; Kirakosyan, E.; Sato, S.; Nasu, K.; Narahara, H. A Case of Vaginal Malignant Melanoma Completely Resected by Radical Surgery. Am. J. Case Rep. 2020, 21, e927462-1–e927462-5. [Google Scholar] [CrossRef] [PubMed]
  26. Guo, N.; Zhang, J.W. Primary vaginal malignant melanoma A rare case report of successful treatment with nivolumab. Medicine 2021, 100, e25691. [Google Scholar] [CrossRef]
  27. Yin, P.; Ma, X.L.; Zhang, Y.F.; Song, Y.; Wang, Y.T.; Lu, Z. Primary vaginal malignant melanoma successfully treated with combination therapy: A case report. Oncol. Lett. 2022, 24, 430. [Google Scholar] [CrossRef] [PubMed]
  28. Sticca, G.; Misheva, B.; Sebajang, H.; Samouelian, V.; Jamal, R. Primary malignant melanoma of the vagina: A case report. Gynecol. Oncol. Rep. 2023, 49, 101266. [Google Scholar] [CrossRef]
  29. Van Trappen, P.; Lebbe, I.; De Cuypere, E.; Claes, N. Case report: A robotic-vaginal approach for total vaginectomy and hysterectomy with pelvic sentinel lymph node dissection in primary vaginal melanoma: A 10-step technique and literature review. Front. Surg. 2023, 10, 1189196. [Google Scholar] [CrossRef]
  30. Levitan, Z.; Gordon, A.N.; Kaplan, A.L.; Kaufman, R.H. Primary malignant melanoma of the vagina: Report of four cases and review of the literature. Gynecol. Oncol. 1989, 33, 85–90. [Google Scholar] [CrossRef]
  31. Borazjani, G.; Prem, K.A.; Okagaki, T.; Twiggs, L.B.; Adcock, L.L. Primary malignant melanoma of the vagina: A clinicopathological analysis of 10 cases. Gynecol. Oncol. 1990, 37, 264–267. [Google Scholar] [CrossRef] [PubMed]
  32. Khoo, U.S.; Collins, R.J.; Ngan, H.Y. Malignant melanoma of the female genital tract. A report of nine cases in the Chinese of Hong Kong. Pathology 1991, 23, 312–317. [Google Scholar] [CrossRef] [PubMed]
  33. Van Nostrand, K.M.; Lucci, J.A., 3rd; Schell, M.; Berman, M.L.; Manetta, A.; DiSaia, P.J. Primary vaginal melanoma: Improved survival with radical pelvic surgery. Gynecol. Oncol. 1994, 55, 234–237. [Google Scholar] [CrossRef]
  34. Irvin, W.P.; Bliss, S.A.; Rice, L.W.; Taylor, P.T.; Andersen, W.A. Malignant melanoma of the vagina and locoregional control: Radical surgery revisited. Gynecol. Oncol. 1998, 71, 476–480. [Google Scholar] [CrossRef]
  35. Gupta, D.; Malpica, A.; Deavers, M.T.; Silva, E.G. Vaginal melanoma—A clinicopathologic and immunohistochemical study of 26 cases. Am. J. Surg. Pathol. 2002, 26, 1450–1457. [Google Scholar] [CrossRef]
  36. Gupta, D.; Neto, A.G.; Deavers, M.T.; Silva, E.G.; Malpica, A. Metastatic melanoma to the vagina: Clinicopathologic and immunohistochemical study of three cases and literature review. Int. J. Gynecol. Pathol. 2003, 22, 136–140. [Google Scholar] [CrossRef] [PubMed]
  37. Miner, T.J.; Delgado, R.; Zeisler, J.; Busam, K.; Alektiar, K.; Barakat, R.; Poynor, E. Primary vaginal melanoma: A critical analysis of therapy. Ann. Surg. Oncol. 2004, 11, 34–39. [Google Scholar] [CrossRef]
  38. Frumovitz, M.; Etchepareborda, M.; Sun, C.C.; Soliman, P.T.; Eifel, P.J.; Levenback, C.F.; Ramirez, P.T. Primary Malignant Melanoma of the Vagina. Obstet. Gynecol. 2010, 116, 1358–1365. [Google Scholar] [CrossRef]
  39. Huang, Q.D.; Huang, H.; Wan, T.; Deng, T.; Liu, J.H. Clinical outcome of 31 patients with primary malignant melanoma of the vagina. J. Gynecol. Oncol. 2013, 24, 330–335. [Google Scholar] [CrossRef]
  40. Xia, L.F.; Han, D.; Yang, W.T.; Li, J.; Chuang, L.; Wu, X.H. Primary Malignant Melanoma of the Vagina A Retrospective Clinicopathologic Study of 44 Cases. Int. J. Gynecol. Cancer 2014, 24, 149–155. [Google Scholar] [CrossRef]
  41. Tasaka, R.; Fukuda, T.; Wada, T.; Kawanishi, M.; Imai, K.; Kasai, M.; Hashiguchi, Y.; Ichimura, T.; Yasui, T.; Sumi, T. A retrospective clinical analysis of 5 cases of vaginal melanoma. Mol. Clin. Oncol. 2017, 6, 373–376. [Google Scholar] [CrossRef] [PubMed]
  42. Sinasac, S.E.; Petrella, T.M.; Rouzbahman, M.; Sade, S.; Ghazarian, D.; Vicus, D. Melanoma of the Vulva and Vagina: Surgical Management and Outcomes Based on a Clinicopathologic Review of 68 Cases. J. Obstet. Gynaecol. Can. 2019, 41, 762–771. [Google Scholar] [CrossRef] [PubMed]
  43. Shakeel, O.; Ullah, F.; Khalid, N.; Ali, S.I.; Batool, S.; Amjad, A.; Anwer, A.W.; Ali, H.; Zafar, H.; Syed, A.A. Malignant Melanoma of the Female Genital Tract: Experience of an Oncology Center in Pakistan. Cureus J. Med. Sci. 2020, 12, e8484. [Google Scholar] [CrossRef] [PubMed]
  44. Khayyat, A.; Pour, M.A.E.; Mousavi, S.; Khalili-Toosi, A.R.; Amin, A. Primary Malignant Melanoma of the Genitourinary System: A Systemic Review and Report of Eight Cases. Cureus J. Med. Sci. 2022, 14, e30444. [Google Scholar] [CrossRef]
  45. Tian, H.; Wang, X.; Lian, B.; Si, L.; Gao, M.; Zheng, H.; Chi, Z.H.; Kong, Y.; Mao, L.L.; Bai, X.; et al. Surgical Outcomes of Vaginal or Cervical Melanoma. Front. Surg. 2022, 8, 771160. [Google Scholar] [CrossRef] [PubMed]
  46. Yazdanfard, N.W.; Mikkelsen, L.H.; Behrendt, N.; Fuglsang, K.; Blaakær, J.; Hölmich, L.R.; Froding, L.P.; Munch-Petersen, H.F.; Heegaard, S. Vaginal melanoma in Denmark from 1980 to 2018: A population-based study based on genetic profile and survival. Gynecol. Oncol. 2022, 165, 53–59. [Google Scholar] [CrossRef] [PubMed]
  47. Ishiguro, A.; Ogata, D.; Okuma, K.; Kashihara, T.; Murakami, N.; Hiki, K.; Yamakawa, K.; Jinnai, S.; Takahashi, A.; Namikawa, K.; et al. Malignant melanoma treatment using brachytherapy: Two case reports and 15 case series. J. Dermatol. 2023, 50, 94–97. [Google Scholar] [CrossRef] [PubMed]
  48. Wells, G.A.; Wells, G.; Shea, B.; Shea, B.; O’Connell, D.; Peterson, J.; Welch; Losos, M.; Tugwell, P.; Ga, S.W.; et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. 2014. Available online: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed on 20 April 2024).
  49. McGuinness, L.A.; Higgins, J.P.T. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res. Synth. Methods 2020, 12, 55–61. [Google Scholar] [CrossRef] [PubMed]
  50. DiMarco, D.S.; DiMarco, C.S.; Zincke, H.; Webb, M.J.; Keeney, G.L.; Bass, S.; Lightner, D.J. Outcome of surgical treatment for primary malignant melanoma of the female urethra. J. Urol. 2004, 171, 765–767. [Google Scholar] [CrossRef]
  51. Cobellis, L.; Calabrese, E.; Stefanon, B.; Raspagliesi, F. Malignant melanoma of the vagina. A report of 15 cases. Eur. J. Gynaecol. Oncol. 2000, 21, 295–297. [Google Scholar]
  52. Seetharamu, N.; Ott, P.A.; Pavlick, A.C. Mucosal melanomas: A case-based review of the literature. Oncologist 2010, 15, 772–781. [Google Scholar] [CrossRef] [PubMed]
  53. Jaramillo, B.A.; Ganjei, P.; Averette, H.E.; Sevin, B.U.; Lovecchio, J.L. Malignant melanoma of the vulva. Obstet. Gynecol. 1985, 66, 398–401. [Google Scholar] [PubMed]
  54. Trimble, E.L.; Lewis, J.L., Jr.; Williams, L.L.; Curtin, J.P.; Chapman, D.; Woodruff, J.M.; Rubin, S.C.; Hoskins, W.J. Management of vulvar melanoma. Gynecol. Oncol. 1992, 45, 254–258. [Google Scholar] [CrossRef] [PubMed]
  55. Cuccia, F.; D’Alessandro, S.; Blasi, L.; Chiantera, V.; Ferrera, G. The Role of Radiotherapy in the Management of Vaginal Melanoma: A Literature Review with a Focus on the Potential Synergistic Role of Immunotherapy. J. Pers. Med. 2023, 13, 1142. [Google Scholar] [CrossRef] [PubMed]
  56. Wang, Y.; Chang, W.; Pu, D. Clinical analysis of 15 patients with primary malignant melanoma in the genital tract. Zhonghua Fu Chan Ke Za Zhi 1997, 32, 226–228. [Google Scholar] [PubMed]
  57. Hodi, F.S.; Corless, C.L.; Giobbie-Hurder, A.; Fletcher, J.A.; Zhu, M.; Marino-Enriquez, A.; Friedlander, P.; Gonzalez, R.; Weber, J.S.; Gajewski, T.F.; et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J. Clin. Oncol. 2013, 31, 3182–3190. [Google Scholar] [CrossRef] [PubMed]
  58. Topalian, S.L.; Sznol, M.; McDermott, D.F.; Kluger, H.M.; Carvajal, R.D.; Sharfman, W.H.; Brahmer, J.R.; Lawrence, D.P.; Atkins, M.B.; Powderly, J.D.; et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 2014, 32, 1020–1030. [Google Scholar] [CrossRef] [PubMed]
  59. Robert, C.; Long, G.V.; Brady, B.; Dutriaux, C.; Maio, M.; Mortier, L.; Hassel, J.C.; Rutkowski, P.; McNeil, C.; Kalinka-Warzocha, E.; et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 2015, 372, 320–330. [Google Scholar] [CrossRef] [PubMed]
  60. Postow, M.A.; Luke, J.J.; Bluth, M.J.; Ramaiya, N.; Panageas, K.S.; Lawrence, D.P.; Ibrahim, N.; Flaherty, K.T.; Sullivan, R.J.; Ott, P.A.; et al. Ipilimumab for patients with advanced mucosal melanoma. Oncologist 2013, 18, 726–732. [Google Scholar] [CrossRef]
  61. Del Vecchio, M.; Di Guardo, L.; Ascierto, P.A.; Grimaldi, A.M.; Sileni, V.C.; Pigozzo, J.; Ferraresi, V.; Nuzzo, C.; Rinaldi, G.; Testori, A.; et al. Efficacy and safety of ipilimumab 3mg/kg in patients with pretreated, metastatic, mucosal melanoma. Eur. J. Cancer 2014, 50, 121–127. [Google Scholar] [CrossRef]
  62. Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N. Engl. J. Med. 2015, 373, 23–34. [Google Scholar] [CrossRef] [PubMed]
  63. Hodi, F.S.; Chesney, J.; Pavlick, A.C.; Robert, C.; Grossmann, K.F.; McDermott, D.F.; Linette, G.P.; Meyer, N.; Giguere, J.K.; Agarwala, S.S.; et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016, 17, 1558–1568. [Google Scholar] [CrossRef] [PubMed]
  64. Wolchok, J.D.; Chiarion-Sileni, V.; Gonzalez, R.; Rutkowski, P.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Wagstaff, J.; Schadendorf, D.; Ferrucci, P.F.; et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N. Engl. J. Med. 2017, 377, 1345–1356. [Google Scholar] [CrossRef] [PubMed]
Figure 1. PRISMA flow chart of the literature search and article selection.
Figure 1. PRISMA flow chart of the literature search and article selection.
Jcm 13 03771 g001
Figure 2. Summary plot of risk of bias assessment using the Newcastle–Ottawa scale.
Figure 2. Summary plot of risk of bias assessment using the Newcastle–Ottawa scale.
Jcm 13 03771 g002
Table 1. PICOS criteria used in the study.
Table 1. PICOS criteria used in the study.
PatientsPatients with histopathological confirmation of PVM 1.
InterventionsTreatment with intention to treat regardless of its type.
ComparisonOther modality of treatment or no treatment.
OutcomeOverall survival, recurrence-free survival, follow-up outcomes.
Study DesignAny study design.
1 Primary vaginal melanoma.
Table 2. Summary of study designs, cohort characteristics, interventions, and treatment outcomes.
Table 2. Summary of study designs, cohort characteristics, interventions, and treatment outcomes.
First AuthorYear
Published
DesignNumber of
Patients
Age (Years)Primary Treatment (Number)Adjuvant TherapyRecurrence Rate (%)
OS (Months)
Follow-Up
Levitan Z et al.1989Case
series
468.25 (mean)WLE (3), none (1)ER (1)2 (50.0%)
103 mo, 2 mo, 5 mo, NR (1)
3 DOD
Borazjani G et al.1990Retrospective1069.5 (mean)Anterior exenteration (2), radical vulvectomy and partial vaginectomy (1), TAH-BSO (1), WLE (1), none (5)ChTx (3),
ER (7)
NR
14.9 mo
8 DOD, 1 NED, 1 DOC
Khoo U S et al.1991Retrospective464.5 (mean)WLE (3),
ER (1)
ER (3),
ChTx (1)
2 (50%)
16 mo., 2 mo., NR (2)
2 DOD, 2 NED
Van Nostrand K. M. et al.1994Case
series
864 (mean)WLE (4),
brachytherapy (2), total pelvic exenteration (1)
ER (2),
none (5)
1 (12.5%)
10 mo (mean WLE), 44 mo (mean ES), 23.25 (mean all)
7 DOD, 1 NED
Irvin W et al.1998Retrospective767.71 (mean)WLE (4), brachytherapy (2), none (1)ER (2),
none (5)
6 (85.7%)
21.3 mo
6 DOD, 1 DOC
Gupta D et al.2002Retrospective2660 (mean)WLE (10), anterior exenteration (7), hysterectomy with vaginectomy (3), vaginectomy (1), ER (2), ER + ChTx (1), NR (2)ER (7),
ChTx (3),
ER + ChTx (7)
5 (19.2%)
18.4 mo
15 DOD
Gupta D et al.2003Case series349 (mean)WLE (1), ER (2)ChTx (1)1 (33.3%)
48 mo, 3 mo, 14 mo
1 DOD
Miner TJ et al.2003Retrospective3562 (median)WLE (10), vaginectomy (2), ER (11), TAH-BSO (10), exenteration (2)ER (16), interferon a-2b (7), vaccine (7)18 (51.4%)
NR
NR
Frumovitz M et al.2010Retrospective3760.6 (median)WLE (28), pelvic exenteration (4), ER, ChTx or mixed (5)ER (20)33 (89.2%)
19.1 mo
2 DOD, 1 DOC, 34 NR
Huang Q et al.2013Retrospective3158.0 (median)ES (11), WLE (11), ChTx (7), none (2)Immunotherapy (19)11 (35.5%)
20.1 mo
23 DOD
Xia L et al.2013Retrospective4456.7 (median)WLE (21), RE (20), ChTx (3)ER, ChTx (24)30 (68.2%)
39.5 mo
21 DOD
Tasaka R et al.2016Retrospective578.0 (median)WLE (5)Interferon-B (3), DAVFeron therapy (1)5 (100.0%)
13.8 mo
4 DOD
Sinasac S et al.2019Retrospective1867.0 (mean)WLE (10), no surgery performed (3), NR (5)IFN-α (2)14 (77.8%)
10.5 mo
11 DOD
Shakeel O et al.2020Retrospective953.1 (mean)WLE (4), TAH-BSO (2), none (3)ER (8),
ER + ChTx (1)
5 (55.6%)
25 mo
13 DOD
Wohlmuth C et al.2020Retrospective46369.5 (mean)WLE (109), RE (77), DS (3) NS (41), no surgery performed (218) NR (15)0NR
16 mo
320 DOD, 143 NR
Khayyat A et al.2022Case series481.25 (mean)Palliative ER (2), ER (1), ChTx (1)0
4 (100.0%)
NR
3 DOD, 1 NR
Tian H et al.2022Retrospective62NRNonradical resection (29), radical resection (33)ChTx, interferon-α2β, immunotherapy (49)64
39.5 mo (mean ES), 25.4 mo (mean WLE)
38 DOD or lost to FU
Yazdanfard N et al.2022Retrospective5273 (mean)WLE (34) ES (4) ER (3), ER +IT (3), ER + ChTx (1), NR (7)ER (3), ER + immunotherapy (3), ER + electrochemotherapy (1)33 (63.5%)
17.5 mo (median)
NR
Ishiguro A et al.2023Case series667.5 (mean)Brachytherapy (5), WLE (1)ER (5), ER + immunotherapy (1)4 (66.7%)
NR
NR
Abbreviations: WLE—wide local excision, ER—external radiotherapy, mo—month, DOD—dead of disease, TAH-BSO—total abdominal hysterectomy with bilateral salpingo-oophorectomy, ChTx—chemotherapy, NR—not reported, NED—no evidence of disease, DOC—dead of other causes, NR—not reported, RE—radical excision, FU—follow-up, DS—debulking surgery, NS—not specified.
Table 3. Summary of patients in case reports, interventions, and treatment outcomes.
Table 3. Summary of patients in case reports, interventions, and treatment outcomes.
First AuthorYear
Published
Age
(Years)
Depth of Invasion (mm)Primary
Treatment
Adjuvant TherapyRecurrence (Yes/No)
OS (Months)
Follow-Up
Schwartz J et al.198979NRLocal excisionChTxyes
37 months
DOD
Moros M L et al.20044013 mmRadical hysterectomy and total vaginectomyImmunotherapy, ERyes
14 weeks
DOD
Gökaslan H et al.2005562 mmWide local excisionChTx, immunotherapyyes
16 months
DOD
Grenader T et al.200831NRPosterior pelvic exenterationChTxNR
NR
Lost to FU
Albareda J et al.2011639 mmLocal excisionImmunotherapy, palliative ChTxyes
NR
Alive but with disease at 1-year FU
Kühn F et al.201244>3 mmMultivisceral resectionChTx, immunotherapyyes
4 months
DOD
Androutsopoulos G et al.2013805 mmWide local excisionNone specifiedno
NR
Alive at 5 months FU
Chaudhuri S et al.201360NRWide local excisionER, ChTxno
NR
Alive at 1-year FU
Chen L F et al.201435NRRadical surgeryRadiotherapy and immunotherapyyes
NR
Lost to FU
Rema P et al.2016NRNRTotal pelvic exenterationERno
NR
Alive at 1-year FU
Chitrathara K et al.20173810 mmTotal vaginectomy and urethrectomyERno
NR
Alive at 14 months FU
Kalampokas E et al.2017754.85 mmPartial vaginectomy and lymphadenectomyNoneno
NR
Alive at 1-year FU
Lee C K et al.201762NRWide local excisionNoneno
NR
Alive at 6 months FU
Rapi V et al.201772NRWide local excision and lymphadenectomyNoneno
NR
Alive at 5 months FU
Ahn, H Y et al.201880NRWide local excision and lymphadenectomyNoneno
NR
Alive at 8 months FU
Zabroug S et al.2018314 mmPartial colpectomy and lymphadenectomyER, brachytherapyno
NR
Alive at 1-year FU
Puri S et al.201965NRBiopsyERno
NR
Alive at 6 months FU
Paravathaneni M et al.202056NRSurgical excisionNoneNR
NR
Lost to FU
Tokumitsu R et al.2020562.5 mmTotal vaginectomy, lymphadenectomy, modified radical hysterectomy, bilateral salpingo-oophorectomyNoneno
NR
Alive at 15 months FU
Guo N et al.202158NRLocal excision, lymph node dissectionImmunotherapyno
NR
Alive at 6 months FU
Yin P et al.202255NRRadical vaginectomy and bilateral salpingo-oophorectomyImmunotherapy, ERyes
NR
Alive at 1-year FU
Bai S et al.20235613 mmWide local excision and sentinel node biopsyChTxno
NR
Alive at last FU
Sticca G et al.20236811.3 mmPosterior exenterationNoneyes
NR
Lost to FU
Van Trappen P et al.2023738 mmRobotic total vaginectomy and hysterectomy with lymphadenectomyNoneno
NR
Alive at 4 months after surgery
Abbreviations: NR—not reported, ChTx—chemotherapy, DOD—dead of disease, ER—external radiation, FU—follow-up, OS—overall survival.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Guzik, P.; Łukasiewicz, M.; Harpula, M.; Zając, P.; Żmuda, M.; Śniadecki, M.; Topolewski, P. Survival and Treatment Modalities in Primary Vaginal Melanoma—Case Report and a Narrative Review. J. Clin. Med. 2024, 13, 3771. https://doi.org/10.3390/jcm13133771

AMA Style

Guzik P, Łukasiewicz M, Harpula M, Zając P, Żmuda M, Śniadecki M, Topolewski P. Survival and Treatment Modalities in Primary Vaginal Melanoma—Case Report and a Narrative Review. Journal of Clinical Medicine. 2024; 13(13):3771. https://doi.org/10.3390/jcm13133771

Chicago/Turabian Style

Guzik, Paweł, Martyna Łukasiewicz, Magdalena Harpula, Paweł Zając, Marcin Żmuda, Marcin Śniadecki, and Paweł Topolewski. 2024. "Survival and Treatment Modalities in Primary Vaginal Melanoma—Case Report and a Narrative Review" Journal of Clinical Medicine 13, no. 13: 3771. https://doi.org/10.3390/jcm13133771

APA Style

Guzik, P., Łukasiewicz, M., Harpula, M., Zając, P., Żmuda, M., Śniadecki, M., & Topolewski, P. (2024). Survival and Treatment Modalities in Primary Vaginal Melanoma—Case Report and a Narrative Review. Journal of Clinical Medicine, 13(13), 3771. https://doi.org/10.3390/jcm13133771

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop