Objective: This study describes the characteristics of patients with primary malignant melanoma of the vagina and their treatment at National Institute of Cancer Research and Hospital in Dhaka, Bangladesh, from February 2013-January 2015. Materials/Methods: Eight patients with primary malignant melanoma of the vagina were identified. Medical records were reviewed for demographic information, treatment, and outcomes. This investigation was approved by the Ethics Committee of the National Institute of Cancer Research and Hospital. Results: The median age was 48 years (range: 35 - 65 years) and most patients were premenopausal. Seven of the eight patients presented with International Federation of Gynecology and Obstetrics (FIGO) stage II. The five patients had disease confined mainly to the upper and middle thirds of the vagina. One patient was diagnosed with stage IV disease. In two patients, cervical metastases were present. Almost all patients received radiotherapy. Two patients with stage II disease developed local recurrences within eighteen months. The one patient with stage IV disease died ten months after diagnosis. Conclusion: Primary malignant melanomas of the vagina are uncommon, highly aggressive tumors that are associated with poor overall survival. Surgery is the mainstay of treatment. Nearly 80% of vaginal melanomas will recur. Overall 5-year survival ranges from 5% to 25%. The size of the tumor (>than 3 cm) and the presence of lymphadenopathy at diagnosis worsen the overall survival.
Primary malignant melanoma of vagina (PMMV) is an extremely rare and highly aggressive tumor, with fewer than 500 cases reported worldwide [
The etiology of this rare malignancy is largely unknown. PMMV originates from the malignant transformation of melanocytes in the basal portion of vaginal mucosa. The somatic mutation profiles of mucosal melanomas show BRAF mutations, common in cutaneous melanomas, to be rare while c-KIT mutations representing mutations of a type III transmembrane receptor tyrosine kinase are more common [
There are no uniform treatment guidelines at present. While surgery is the primary treatment for vaginal melanoma, a combined modality approach with radiation and immunotherapy may improve survival [
We report the first case series of vaginal melanomas from Bangladesh.
PMMV are included in this study from the period January 2013 to January 2015 at National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh. This investigation was approved by the Ethics Committee of the National Institute of Cancer Research and Hospital. For this review of eight patients, there were no indeterminate results, missing data, and data outliers.
Clinical characteristics were recorded including age, menopausal status and presenting symptoms. Tumor factors included tumor size, location and International Federation of Gynecology & Obstetrics (FIGO) stage [
NICRH is a government supported 300-bed hospital, which treats an average of 1000 new gynecologic cancer patients per year. Eight patients diagnosed with PMMV were identified. Patient demographics, tumor characteristics and treatment information are described in
Age | Number of Patients |
---|---|
<45 | 6 |
>45 | 2 |
Menopausal Status | |
Premenopausal | 6 |
Postmenopausal | 2 |
Presenting Symptoms | |
Vaginal bleeding | 7 |
Vaginal mass | 2 |
Vaginal discharge | 3 |
FIGO Stage | |
I | -- |
II | 7 |
III | -- |
IV | 1 |
Tumor Size | |
<3 cm | 3 |
>3 cm | 5 |
Tumor Site | |
Upper and middle third of vagina | 5 |
Lower third of vagina | 3 |
Lesion Number | |
Multifocal | 4 |
Unifocal | 4 |
Pathology | |
Melanotic | 6 |
Amelanotic | 2 |
Lymph node Status | |
Positive | 1 |
Negative | 4 |
Unknown | 3 |
Surgical Intervention | Number of Patients |
---|---|
Wide local excision | 3 |
Radical hysterectomy Vaginectomy Inguinal Pelvic lymphadenectomy | 4 |
No surgery | 1 |
Radiation Therapy | |
Surgery with EBRT | 4 |
Surgery with EBRT and ICRT | 2 |
Surgery, chemotherapy and EBRT | 1 |
Chemotherapy | |
Chemotherapy, surgery, EBRT | 1 |
Chemotherapy with EBRT | 1 |
EBRT: external beam radiotherapy; ICRT: intracavitary radiotherapy.
and pelvic lymphadenectomy. Lymphedema developed in the four patients who underwent lymphadenectomy.
On follow-up, two patients with stage II disease (one with positive lymph nodes and one with negative nodes) had recurrences in the pelvis. One patient, age 45 years, underwent a wide local excision followed by external and intracavitary radiation (
We report on eight cases of vaginal melanoma seen in a two-year period at NICRH in Bangladesh. Bangladesh, a country of 166 million people, does not have a uniform cancer reporting system [
There is a growing literature of single-institution case reports and case series for PMMV around the world. Reports representative of the international experience with PVVM from the last 20 years are summarized in
Reviews of the largest case-series help to give a general picture of patient characteristics, therapeutic interventions, and outcomes. Forty-four patients over a 9-year period seen at Fudan University in Shanghai were treated with excisional surgery. Progression-free survival was dependent on depth of invasion, lymph nodes sta-
Country | Year | Age | FIGO | Treatment | Follow-Up (Months) | Outcome |
---|---|---|---|---|---|---|
Japan [ | 2015 | 59 | II | RH, V, DTIC, IM | 5 | Lung metastases |
Bulgaria [ | 2014 | 71 | II | RH, V, LN IM, DTIC | 21 | Died 21 months |
China [ | 2014 | 35 | II | RH, LN, V | 6 | Pelvic recurrence; lost to follow-up |
Denmark [ | 2013 | 77 | II | exenteration | 7 | Recurrence at 7 months |
Morrocco [ | 2013 | 70 | IV | imatinib | 18 | regression |
India [ | 2013 | 60 | II | WLE, EBRT CT: TEM | 12 | Alive at one year |
Greece [ | 2013 | 80 | II | WLE, ICRT | 5 | Died lung metastases at one year* |
Germany [ | 2012 | 44 | III | exenteration | 4 | Died at 4 months |
India [ | 2012 | 66 | II | WLE,EBRT | 12 | Died with widespread recurrence |
China [ | 2011 | 54 | III | RH, V EBRT, IM, CT | 12 | Brain metastasis |
India [ | 2009 | 60 | II | WLE DTIC | 12 | Alive one year |
Turkey [ | 2009 | 51 | ! | V, LN DTIC, cispltin | 21 | Nodal metastases at 9 months Alive at 21 months |
Bangladesh [ | 2008 | 52 | I | WLE, EBRT | -- | Lost to follow-up |
Nepal [ | 2007 | 60 | II | WLE, EBRT | 6 | Recurrence 3 months Died at 6 months |
Germany [ | 2007 | 58 | I | WLE, EBRT | 6 | Metastasized at 6 months |
Spain [ | 2004 | 40 | I | RH, V, LN EBRT, IM | 8 | Recurred in liver and ascites at 7 months Died at 8 months |
South Africa [ | 2004 | 49 | II | WLE, IM DTIC & carboplatin | 24 | Alive at 2 years |
Israel [ | 2002 | 67 | II | WLE, EBRT ICRT | 11 | Alive at 11 months |
Italy [ | 1998 | 45 | IV | Exenteration DTIC fotemustine | 12 | Metastases at 4 months Alive at 12 months |
USA [ | 1998 | 55 | I | WLE, LN | 13 years | Alive at 13 years |
CT chemotherapy; DTIC dacarbazine chemotherapy; EBRT: external beam radiotherapy; ICRT: intracavitary radiotherapy; LN lymphadenectomy; RH radical hysterectomy; TEM: temozolamide chemotherapy; V vaginectomy; WLE: wide local excision; *personal communication with authors.
Country | Dates of Care | # of Patients | Treatment | Recurrence and Survival |
---|---|---|---|---|
Bangladesh | 2013-2015 | 8 | 4 RH V LN 3 WLE | 43% recurrence; 14% died in two years |
China [ | 2002-2011 | 44 | 21 WLE 20 RH V 5 EBRT,30 IM, 11 CT | 68.2% recurred; 47.7% died 5 lived longer than 5 years |
France [ | 2000-2010 | 6 | WLE | Median progression free survival 10.5 months |
USA [ | 1993-2012 | 14 | 5 WLE 3 WLE, LN 3 radical excision 3 exenteration 2 preop CT, 1 EBRT | Recurrence in 10 of 14 patients Median time to recurrence 6 months Median overall survival 2.1 years |
France [ | 1990-2007 | 46 | 4 exenteration 19 WLE 7 V 9 RH V LN 5 EBRT, 6 ICRT 6 CT, 4 IM | Median relapse free survival 10.9 months Median overall survival 28.4 months |
USA [ | 1980-2009 | 37 | 28 WLE 5 exenteration 5 EBRT, CT | Progression-free survival: 11.4 months, Overall survival: 19 months. |
---|---|---|---|---|
USA [ | 1970-2009 | 15 | WLE, EBRT, CT, IM | 2/15 alive over 8 years follow-up |
China [ | 1970-2005 | 31 | 15 Surgery & IM 7 surgery 4 CT & IM 3 CT 2 no treatment | 35.5% recurrence; 32.3% 5 year survival |
USA [ | 1976-1986 | 5 | 5 WLE 3 CT, IM | Time to recurrence 7 months; mean survival 31 months |
USA [ | 1970-2002 | 26 | 7 exenteration 10 WLE 3 RH V; 1 V 3 EBRT only | Fifteen patients died of the disease (3 - 83 months) Four patients no evidence of disease (5 - 24 months) Four patients alive with disease (6 - 276 months) |
USA [ | 1977-2001 | 35 | 10 WLE 2 V 10 RH V 2 exenteration 11 EBRT, 26 IM or CT | Median survival 20 months Surgical therapy: median survival 25 months Radiation therapy: median survival 13 months |
United Kingdom [ | 1975-2000 | 9 | 2 EBRT 1 RH,V 6 WLE | Median survival 24 months (range 4 to 60 months) |
China [ | 1979-1997 | 9 | 9 surgery, CT, IM | 20% 5-year survival; one long term survivor at 19 years |
USA [ | 1990 | 10 | 10 surgery, EBRT, CT | Mean time to recurrence: 8 months Mean survival: 15 months |
Austria [ | 1982-1996 | 14 | 7 biopsy 5 WLE 1 RH V 1 exenteration | Mean survival 10 months (range 1 - 153) 21% 5-year survival |
USA [ | 1966-1996 | 7 | 2 WLE 2 WLE, EBRT 2 ICRT 1 exenteration | Median time to death 20 months (2 ot 48 months) All Dead of disease |
USA [ | 1982-1996 | 13 | 5 V 9 WLE | 64% Estimated 5-year survival |
USA [ | 1972-1992 | 8 | 4 conservative: WLE, CT, EBRT 4 Radical: exent, RH | 4 patients radical surgery: 75% 2-year survival 4 patients conservative surgery: 0% 2-year survival |
Italy [ | 1969-1993 | 20 | 15 WLE | 15 evaluable patients; 2 died postoperatively All patients died of disease; median survival 19 months |
USA [ | 1986-1992 | 4 | 4 exenteration | All underwent pelvic exenteration; One post operative death Three patients alive at 31-to 97 months |
Hong Kong [ | 1978-1990 | 10 | 1 exenteration, CT 2 RH V 3 WLE 3EBRT ± CT | Five patients died 2 - 22 months Five patients median survival 18 months |
USA [ | 1936-1988 | 15 | 3 WLE 2 RH V 5 V, vulvectomy 3 exenteration 2 EBRT | 17.4% 5-year survival Two patients survival more than 5 years |
Spain [ | 1984, 1986 | 2 | 1 RH V 1 EBRT | Died at 4 and 6 months |
Sweden [ | 1960-1984 | 26 | Not stated | 13% 5-year survival |
USA [ | 1935-1976 | 19 | 7 RH V 8 WLE, EBRT 4 EBRT, ICRT | 21% 5-year survival One long-term survivor at 14 years |
CT chemotherapy; EBRT: external beam radiotherapy; ICRT: intracavitary radiotherapy; IM: immunotherapy; LN lymphadenectomy; RH radical hysterectomy; V vaginectomy; WLE: wide local excision.
tus and the addition of postoperative radiotherapy [
One retrospective, multi-institution study collected information on 54 patients with PMMV from 12 institutions over a 17-year period [
Overall, prognostic factors include tumor size, depth of invasion, mitotic counts, and lymph node involvement [
In South Asia, there have been several case reports of PMMV [
Existing literature has detailed the treatment options of surgical excision, and radiation [
Radiation therapy has been routinely used as adjuvant therapy although there are no large series comparing surgery alone to surgery with radiation. A recent study of carbon ion radiotherapy for 23 patients with genital mucosal melanoma showed a recurrence rate of 61% with a median follow-up of 17 months and a 53% three- year survival rate [
Since the first report of vaginal melanoma in 1887, there has been a slow accrual of case studies and case reports over the past 128 years [
The authors have no disclosures
Shahana Pervin,Farzana Islam,Annekathryn Goodman,1 1, (2016) Primary Malignant Melanoma of the Vagina in Bangladesh: Report of a Case Series and Review of the Literature. Open Journal of Obstetrics and Gynecology,06,313-324. doi: 10.4236/ojog.2016.65040