Open Journal of Obstetrics and Gynecology, 2012, 2, 279-282 OJOG Published Online September 2012 (
Unusual primary location of the malignant melanoma, the
cervico-vaginal region: 3 cases and literature review*
El Fatemi Hinde1, Bennani Amal1, Saadi Hannane2, Bouchikhi Cherhazade2, Bannani Abdelaziz2,
Mellas Nawfel3, Mesbahi Omar3
1Department of P athology, Hassan II Teaching Hospital, Fez, Morocco
2Department of Gynecology, Hassan II Teaching Hospital, Fez, Morocco
3Department of O n cology, Hassan II Teaching Hospital, Fez, Morocco
Received 4 July 2012; revised 8 August 2012; accepted 20 August 2012
Introduction: Malignant melanoma (MM) represents
1% of all cancers and has an incidence of 3% - 7% in
the female genital tract, the majority of cases being
reported in the vulva. The cervico-vaginal region is
an unusual primary location of the malignant mela-
noma. Case report: The clinical and morphologic
findings of 3 MM patients with cervico-vaginal tu-
mours mimicking cervical polyp in third case. His-
tologically, the neoplasia was formed by nodules of
broad cytoplasmic cells with poorly defined borders
with pleomorphic nuclei with prominent nucleolar.
Tumor cells were positive for S-100 protein, Melan A,
HMB 45 and CD117. The authors discuss three cases
of cervico-vaginal melanoma and analyze clinical and
prognostic aspects of this disease. Conclusion: Pri-
mary MM of the cervix should be considered in the
differential diagnosis of cervical malignancies. Early
diagnosis is essential in order to warrant a better
prognosis, although there are no cases of cure de-
Keywords: Genital Tract; Malignant Melanoma; Cervix;
Vagina; Chemotherapy; CD117
Mucosal melanoma is a rare cancer that is clearly distinct
from its cutaneous counterpart in biology, clinical course,
and prognosis. Recent studies have shown important
differences in the frequencies of various genetic altera-
tions in different subtypes of melanoma. Activating mu-
tations in the c-KIT gene are detected in a significant
number of patients with mucosal melanoma [1]. The
prognosis currently tends to be very poor, with a 5-year
survival rates of 8.4%, regardless of treatment, which
usually involves primary surgery (conservative or radical)
and adjuvant radiotherapy or systemic chemotherapy
regimens [2,3]. The authors discuss three cases of gyne-
cological melanoma and analyze clinical and prognostic
aspects of this disease.
Cases 1 and 2: We describe two cases of 54-year-old and
60-year-old postmenopausal female patients with history
of 2 months of abnormal genital bleeding. On vaginal
examination there was a firm mass growth of size 3 cm
attached to the right lateral wall of o the upper-third of
the vagina. A biopsy of the vaginal tumor was taken,
which revealed melanoma. Radiological assessment was
performed. Abdominal and pelvic Ultrasound (US), CT
(Figure 1) and magnetic resonance (MRI) confirmed the
presence of invasive vaginal lesion of 5 cm located in the
right lateral wall without lymph node involvement or
distant metastasis.
Case 3: A female patient 43 years of age, with history
of 4 months of abnormal genital bleeding. A gynecologi-
cal examination showed a cervical polyp. The excision
Figure 1. Invasive vaginal lesion located in the lateral wall.
*We declare no conflicts of interest.
El F. Hinde et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 279-282
was performed which revealed melanoma. Magnetic re-
sonance (MRI) (Figure 2) showed cervical tissular mass
with infiltration of the anorectal wall without lymph
Microscopically, in the three cases, neoplasia was
formed by nodules of broad cytoplasmic cells with
poorly defined borders with pleomorphic nuclei with
prominent nucleolar. These areas displayed transition
with areas with fascicules of elongated cells of moderate
cytoplasm. Immunohistochemical stains were positive
for S-100 protein, Melan A (Figure 3), HMB 45 and
CD117 (Figure 4) in neoplastic cells. CKAE1/AE3 and
CEA were negative.
Surgery was not indicated given the advanced stage of
The first patient received chemotherapy with a poor
Figure 2. Cervical tissular mass with infiltration of the anorec-
tal wall.
Figure 3. Immunohistochemical stains positivity for Melan A
in neoplast ic cells.
Figure 4. Immunohistochemical stains positivity for CD117 in
neoplastic cells.
tolerance. Imatinib was ad ministered as second lin e with
evolution after three cure, then stabilization of the dis-
ease. She died after one year.
The other two patients received chemotherapy with
dacarbazine. They had their third course with good de-
velopment and good tolerance.
Malignant melanomas are generally found in areas of
skin exposed to the sun, but can also be present in non
exposed sites, such as genital tract and esophagus,
among others [4]. The first case of malignant melanoma
of the female genital tract (MMFG) was reported by
Hewitt in 1861 [5].
Cervical melanoma arises from melanocytic cells of
the cervix; in fact, the cervix epithelium is capable of
forming the complete spectrum of melanocytic lesions,
from benign lentigines to blue nevi to melanoma [6]. The
usual form of presentation of primary melanoma of the
cervix on physical examination is a polypoid exophytic
mass, red, brown, grey, black, or blue in color [7], or a
colorless in the case of amelanotic melanomas, which
constitute up to 55% of cases at this anatomic site [8],
presented with vaginal bleeding [4,7,9,10]. Age range
varies from 20 to 78 years [7], being more common be-
tween 60 and 70 years [9]. Due to that the cervix is an
unusual site for this type of neoplasm, the International
Federation of Gynecology and Obstetrics (FIGO) staging
system for cervical cancer is used [11], rather than the
Clark and Breslow scales, because the FIGO staging
system correlates better with the prognosis. Diagnosis of
primary melanoma of the cervix entertains a high prob-
ability of being confused with another entity, due to the
rarity of the disease [10]. Differential diagnosis between
a primary cervical melanoma and a metastatic tumor is
important because the latter can be part of a metastatic
Copyright © 2012 SciRes. OPEN ACCESS
El F. Hinde et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 279-282 281
disease spreading to the cervix [9]. At the present mo-
ment there is no standard treatment for this disease,
while there is no doubt that the surgical approach is the
most usual and radical hysterectomy with or without
pelvic lymphadenectomy and/or superior vaginectomy is
reported most frequently [4,9,12,13], some authors en-
tertain doubts concerning survival if pelvic lymphadec-
tomy is performed [12]. Although there is no enough
information about the real role of negative margins in
primary melanoma of the cervix, the primary surgery
should have the purpose of obtaining negative margins
[7]; some authors recommend 2-cm margins as minimum
[10,13]. The role of radiotherapy (RT) has not been well
established, but it has been demonstrated that RT reduces
the tumor size [4,9,11]. The use of adjuvant pelvic RT is
considered in the case of not obtaining a satisfactory sur-
gical resection margins, when the parametrium is in-
volved, or when lymph nodes are found to be involved
[7]. Despite the low level of radiosensitivity exhib ited by
melanoma, the use of external or intracavitary RT is
recommended after surgery, or palliatively when the tu-
mor is inoperable because of its own conditions or those
of the patient [4,6,7,9].
Primary vaginal melanoma is also a very rare gyneco-
logic malignancy and limited data are available on which
to base recommendations for the primary management of
patients. Our cases are middle-aged women with primary
malignant melanoma of the vagina, 5 cm in diameter and
localized in the right lateral wall with infiltration to the
anterior rectal wall and anal sphincter without identified
local spread and distant metastasis. There was clinical
impression of an infiltration to the anterior rectal wall
and anal sphincter without any clinically identified local
spread and distant metastasis. The aim should have been
to completely resect the tumor with tumor-free surgical
margins and evaluate the related lymph nodes for tumor
involvement in primary treatment. Miner et al. reported
improved outcomes with surgical removal of macro-
scopic disease whenever possible [14]. There are several
treatment options but none of them is proved to be stan-
dard approach. The spectrum of surgical therapy ranges
from conservative surgery such as wide excision of the
lesion or total vaginectomy to radical extirpation with en
bloc removal of involved pelvic organs [14].
In gynecological melanoma, no chemotherapy regimes
have been reported that substantially may reduce the
possibility of recurrence. Dacarbazine is utilized in ad-
vanced disease, as the case for our patients, and it has
been observed that up to 20% of patients may have re-
sponse [7,13]. It has been proposed that the combination
of cisplatin, bleomycin, and vinblastine can provoke a
better response than the use of solely dacarbazine [9],
while in other cases, the greater effectiveness of com-
bining dacarbazine with vincristine and carmustine has
been reported as well as immunotherapy utilizing local
BCG or the transfusion of activated lymphocytes [6].
Average survival reported in the world literature of
these patients ranges from 6 months to 14 years. The
majority of them report that they succumb to the disease
in the first 3 years after diagnosis [4]. Five-year survival
after radical hysterectomy as only treatment is very low:
less than 40% in stage I and 14% in stage II [9,15].
There are no standard guidelines for adequate staging
workup in mucosal melanoma. A thorough history and
physical examination are extremely important and many
experts recommend serum lactate dehydrogenase as well
as axial imaging of brain, chest, abdomen, and pelvis
and/or positron emission tomography (PET) scans to
evaluate the stage and extent of disease at diagnosis. The
staging system for mucosal melanoma has also not been
well established. Because of the advanced presentation
of most cases, Breslow depth alone seems to be of little
use in staging of the majority of primary mucosal mela-
nomas. Hence, oncologists use different systems to stage
mucosal melanoma. Although some clinicians prefer a
simple and practical staging system in which stage I is
localized, stage II is regional (lymph node involvement),
and stage III is distant disease, most use the American
Joint Committee on Cancer (AJCC) staging system, re-
ferring to distant metastatic disease as stage IV. Estab-
lishment of an effective staging systembased on prognos-
tic factors unique to mucosal melanoma would be bene-
ficial [1].
In 2006 shed light on c-KIT genetic alterations in me-
lanoma. That study showed that c-KIT amplification/
mutation occurred in 39% of mucosal melanomas, but
none of non-chronic sun damage cutaneous melanoma
cases. Mucosal melanoma has been shown to exhibit
amplifications or increased copy numbers of the 4q12
locus by comparative genomic hybridization. Mutations,
including the activating K462E mutations of the c-KIT
kinase domain, which are known to render sensitivity to
imatinib (a tyrosine kinase inhibitor) in gastrointestinal
stromal tumors, are also commonly seen in mucosal
melanoma. The prevalence of these mutations in mucosal
melanoma is 5% - 22% based on some studies [16-18],
which is much lower than what was originally expected.
Preclinical studies have shown sensitivity of c-KIT mu-
tant mucosal melanoma, providing a rationale for study-
ing imatinib in this melanoma type in clinical trials.
Marked tumor regression was reported in a patient with
metastatic mucosal melanoma who was treated with sin-
gle-agent imatinib [19]. This observation has been sub-
stantiated by several other anecdotal reports, demon-
strating objective responses in patients with advanced
mucosal and acral melanoma after imatinib monotherapy
[20,21]. A phase II trial investigating response to ima-
tinib in patients with unresectable melanoma harboring
Copyright © 2012 SciRes. OPEN ACCESS
El F. Hinde et al. / Open Journal of Obstetrics and Gynecology 2 (2012) 279-282
Copyright © 2012 SciRes.
somatic alterations of c-KIT is currently ongoing at six
institutions, including Memorial Sloan-Kettering Cancer
Primary malignant melanoma of female genital tract is
a rare disease with a poor prognosis, especially if it is not
detected in a timely fashion or if it is not treated correctly.
To date, no consensus has been established concerning
treatment of gynecologic primary Melanoma. But it is
recommended that this be surgical, procuring the estab-
lishment of 2-cm margins, accompanied by radio- or
[1] Seetharamu, N., Ott, P.A. and Pavlick, A.C. (2010) Mu-
cosal melanomas: A case-based review of the literature.
The Oncologist, 15, 772-781.
[2] Irvin Jr, W.P., Bliss, S.A., Rice, L.W., Taylor Jr, P.T. and
Andersen, W.A. (1998) Malignant melanoma of the va-
gina and locoregional control: Radical surgery revisited.
Gynecologic Oncology, 71, 476-480.
[3] Bonner, J.A., Perez-Ta mayo, C., Reid, G.C., Roberts, J.A.
and Morley, G.W. (1988) The management of vaginal
melanoma. Cancer, 62, 2066-2072.
[4] Siozos, C., Bhat, A., Lonsdale, R., Nieto, J.J. and Crocker,
S.G. (2005) Malignant melanoma of the uterine cervix.
Journal of Obstetrics and Gynaecology, 25, 826-827.
[5] Hewitt P. Sequel to a case of recurrent melanosis of both
groins and back: The disease reappearing in the brain,
heart, pancreas, liver and other organs. Lancet, 1861,
[6] Gupta, R., Singh, S. and Mandal, A.K. (2005) Primary
malignant melanoma of cervix—A case report. Indian
Journal of Cancer, 42, 201-204.
[7] Piura, B. (2008) Management of primary melanoma of
the female urogenital tract. The Lancet Oncology, 9, 973-
981. doi:10.1016/S1470-2045(08)70254-7
[8] Deshpande, A.H. and Munshi, M.M. (2001) Primary ma-
lignant melanoma of the uterine cervix: Report of a case
diagnosed by cervical scrape cytology and review of the
literature. Diagnostic Cytopathology, 25, 108-111.
[9] Baruah, J., Roy, K.K., Kumar, S. and Kumar, L. (2009) A
rare case of primary malignant melanoma of cervix. Ar-
chives of Gynecology and Obstetrics, 280, 453-456.
[10] An, J., Li, B., Wu, L., Lu, H. and Li, N. (2009) Primary
malignant amelanotic melanoma of the female genital
tract: Report of two cases and review of literature. Mela-
noma Research, 19, 267-270.
[11] Mousavi, A.S., Fakor, F., Nazari, Z., Ghae mmaghami, F.,
Hashemi, F.A. and Jamali, M. (2006) Primary malignant
melanoma of the uterine cervix: Case report and review
of the literature. Journal of Lower Genital Tract Disease,
10, 258-263. doi:10.1097/01.lgt.0000229564.11741.4e
[12] Wasef, W.R., Roberts, J.K. and Dixon, G.R. (1999) Pri-
mary malignant melanoma of the cervix uteri. Journal of
Obstetrics and Gynaecology, 19, 673-674.
[13] Cantuaria, G., Angioli, R., Nahmias, J., Estape, R. and
Penalver, M. (1999) Primarymalignant melanoma of the
uterine cervix: Case report and review of the literature.
Gynecologic Oncology, 75, 170-174.
[14] Miner, T.J., Delgado, R., Zeisler, J., et al. (2004) Primary
vaginal melanoma: A critical analysis of therapy. Annals
of Surgical Oncology, 11, 34-39.
[15] Clark, K.C., Butz, W.R. and Hapke, M.R. (1999) Primary
malignant melanoma of the uterine cervix: Case report
with world literature review. International Journal of Gy-
necological Pathology 18, 265-273.
[16] Curtin, J.A., Busam, K., Pinkel, D., et al. (2006) Somatic
activation of KIT in distinct subtypes of melanoma.
Journal of Clinical Oncology, 24, 4340-4346.
[17] Antonescu, C.R., Busam, K.J., Francone, T.D., et al.
(2007) L576P KIT mutation in anal melanomas correlates
with KIT protein expression and is sensitive to specific
kinase inhibition. International Journal of Cancer, 121,
257-264. doi:10.1002/ijc.22681
[18] Torres-Cabala, C.A., Wang, W.L., Trent, J., et al. (2009)
Correlation between KIT expression and KIT mutation in
melanoma: A study of 173 cases with emphasis on the
acral-lentiginous/mucosal type. Modern Pathology, 22,
1446-1456. doi:10.1038/modpathol.2009.116
[19] Hodi, F.S., Friedlander, P., Corless, C.L., et al. (2008)
Major response to imatinib mesylate in KIT-mutated
melanoma. Journal of Clinical Oncology, 26, 2046-2051.
[20] Lutzky, J., Bauer, J. and Bastian, B.C. (2008) Dose-de-
pendent, complete response to imatinib of a metastatic
mucosal mel anoma with a K642E KIT mutation. Pigment
Cell & Melanoma Research, 21, 492-493.
[21] Jiang, X., Zhou, J., Yuen, N.K., et al. (2008) Imatinib
targeting of KIT-mutant oncoprotein in melanoma. Clini-
cal Cancer Research, 14, 7726-7732.