|Ahead of print publication
A rare synchronous presentation of primary malignant melanoma in cervix and vagina
Usha K N. Pai1, Sreekumar Pillai2, NR Arunkumar3
1 Department of Pathology, Jubilee Mission Medical College and Research Institute, Kerala, India
2 Department of Surgical Oncology, Jubilee Mission Medical College and Research Institute, Kerala, India
3 Department of Surgery, Thrissur District Co-Operative Hospital, Kerala, India
|Date of Submission||06-Aug-2021|
|Date of Acceptance||21-Sep-2021|
|Date of Web Publication||27-Apr-2022|
Usha K N. Pai,
Department of Pathology, Jubilee Mission Medical College and Research Institute, Thrissur - 680 005, Kerala
Source of Support: None, Conflict of Interest: None
Malignant melanoma, primarily a cutaneous malignancy, can also involve mucosal surfaces and constitutes 2% to 7% of all gynecological malignancies. Primary melanoma of the uterine cervix is an uncommon tumor and has poor prognosis. In the female genital tract, the synchronous occurrence of primary malignant melanoma in the cervix and vagina is rare. We report a case of a 48-year-old female patient who presented with a blackish vaginal mass and associated growth in the cervix. Biopsy from the vaginal mass was reported as malignant melanoma. Following this, she underwent radical surgery and adjuvant radiotherapy. After 12 months, the patient is doing well.
Keywords: Cervix, primary malignant melanoma, vagina
| > Introduction|| |
Malignant melanoma, primarily a skin cancer, rarely involves mucosal surfaces such as the oral cavity, conjunctiva, urinary bladder, esophagus, female genital tract, and anorectum. Of the mucosal melanomas, the female genital tract constitutes 18%, as stated in the National Cancer Data Base report on cutaneous and noncutaneous melanoma. The vulva and vagina are usual sites affected in gynecologic melanoma. Primary uterine cervical melanoma is uncommon, and so far, literature shows only around 100 cases. The synchronous occurrence of primary melanoma at sites such as the cervix and vagina is even rarer. Female genital tract melanoma is generally seen in postmenopausal women with varying symptoms such as vaginal bleeding, mass, or discharge. It is usually diagnosed at an advanced stage and therefore bears an unfavorable prognosis.
Migration of melanocytes from the neural crest or presence of melanocytes in the endocervical epithelium is postulated as the mechanism of origin of melanoma in the cervix. Its probable Schwann cell origin was reported first by Cid. Macroscopically, melanoma may present as a brownish-black exophytic, polypoidal, or ulcerated mass in the cervix. Amelanotic tumor, which lacks melanin pigment, can pose a diagnostic challenge. Histopathological evaluation supported by immunohistochemical tests will confirm the diagnosis. Unlike the cutaneous melanomas, there are no approved staging protocols for cervical melanoma in the American Joint Committee on Cancer (AJCC). Hence, the cervical cancer staging system of the International Federation of Gynecology and Obstetrics (FIGO) 2018 is adopted.
Similarly, FIGO 2009 cancer staging may be more pertinent for vaginal melanoma, although AJCC staging becomes more relevant for prognostication. Due to limited data available for cervical melanoma, there is no standard therapeutic protocol to date.
| > Case Report|| |
A 48-year-old para two woman presented with mass per vaginam of 1-year duration. Local examination revealed a pedunculated blackish suburethral nontender lesion in the anterior vaginal wall and blackish growth in the cervix. Biopsy from the vaginal lesion was reported as malignant melanoma. Preoperative magnetic resonance imaging (MRI) scan detected a growth in the cervix and posterior fornix [Figure 1]a and [Figure 1]b. Screening MRI did not reveal any other lesions. Subsequently, she underwent radical Wertheim's hysterectomy with bilateral pelvic lymph node dissection.
|Figure 1: (a and b) High signal intensity lesion in the cervix in MRI-T1WI axial and T2WI sagittal images, respectively|
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Gross examination revealed a polypoidal blackish mass measuring 2.5 cm × 2 cm × 2 cm involving the external os and the endocervical canal and a blackish lesion measuring 1.6 cm × 0.3 cm × 0.3 cm in the upper two-thirds of the vagina. Myometrium showed an intramural fibroid. Bilateral parametria were free from the tumor [Figure 2]a and [Figure 2]b. On histology, cervical and vaginal lesions showed a tumor composed of epithelioid-type cells with pleomorphic vesicular nuclei and prominent nucleoli. The brownish-black granular pigment was present in many tumor cells, and mitoses were seen. Junctional activity identified in both the cervical and vaginal squamous epithelium indicated two primary lesions. Multiple bilateral pelvic lymph nodes were free from metastases. Immunohistochemical stains for vimentin, HMB45, and S100 protein on both cervical and vaginal lesions established the diagnosis of malignant melanoma [Figure 3] and [Figure 4]. Hence, the final diagnosis of primary malignant melanoma concurrently occurring in the cervix (FIGO Stage IB2) and vagina (AJCC-pT3a pN0) was inferred. The patient underwent radiotherapy (22 doses of teletherapy and 2 doses of brachytherapy). After 12 months of follow-up, the patient is doing well.
|Figure 2: (a and b) Gross specimen showing blackish tumor in the cervix and vagina|
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|Figure 3: Photomicrographs of the cervix, magnification × 100. (a) Hematoxylin and eosin-melanoma cells with junctional activity, (b) Vimentin, (c) HMB45, (d) S100|
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|Figure 4: Photomicrographs of the vagina, magnification × 100. (a) Hematoxylin and eosin-melanoma cells with junctional activity, (b) Vimentin, (c) HMB45, (d) S100|
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| > Discussion|| |
Primary malignant melanoma of the female genital tract usually occurs in the postmenopausal age group presenting as vaginal discharge or bleeding per vagina or as vaginal mass. Vulva and vagina are the common sites of involvement. The uterine cervix is an uncommon location for melanoma. To the best of our knowledge, there is no report of synchronous occurrence of primary melanoma in the cervix and vagina in the literature. Metastasis to the cervix from other primary sites such as skin, oral cavity, esophagus, conjunctiva, urinary bladder, or anorectum needs exclusion. As stated by Norms and Taylor, the requisite criteria for the diagnosis of cervical melanoma are (1) the presence of melanocytes in the normal cervical epithelium, (2) the absence of melanoma in the other sites of the body, (3) evidence of junctional activity in the cervix, and (4) metastasis of melanoma according to the pattern of cervical carcinoma. Cervical melanoma presents as an ulcerated or polypoidal brownish-black pigmented mass in most cases. Microscopy shows either epithelioid type cells, spindle cells, or both types of cells with pleomorphic nuclei, conspicuous nucleoli, with or without associated brownish-black melanin pigment in the cytoplasm. The presence of junctional activity in the overlying epithelium is a necessary criterion and confirms the diagnosis of two separate primary lesions, as seen in this case [Figure 3] and [Figure 4]. Immunohistochemical stains using vimentin, HMB45, S100, and melan-A will confirm the diagnosis. The prognosis is poor because it spreads through hematogenous or lymphatic routes to regional lymph nodes and adjacent and distant organs.
Regarding the tumor staging for cervical melanoma, FIGO staging is widely accepted due to its better correlation with the patient outcome. For vaginal melanoma, AJCC staging is more appropriate. The standard therapeutic approach for cervical melanoma is Wertheim's hysterectomy with bilateral pelvic lymph node dissection. In the vagina, wide local excision is recommended with at least 2-cm tumor-free margin, whenever achievable. Adjuvant therapy, like radiation, is applicable for an advanced-stage tumor or as a palliative measure.
Carbon ion radiotherapy may be used as a substitute for conventional radiotherapy. The effects of chemotherapeutic drugs in gynecological melanoma have not been rewarding. In the future, sufficient research on molecular pathways can unravel the efficacy of targeted therapy in mucosal melanoma. Angiolo Gadducci et al., in their analysis, have suggested a feasible treatment algorithm in the management of melanoma of the female genital tract, which may improve the results in days to come.
| > Conclusion|| |
Primary malignant melanoma occurring synchronously in the cervix and vagina has not been reported hitherto in English literature. Due to the advanced stage of melanoma at diagnosis and the unsatisfactory response to adjuvant therapy, the overall survival rate in cases of gynecological melanoma is poor. Radical surgery with or without adjuvant radiotherapy is the widely accepted mode of treatment.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We acknowledge Dr. Aneesh MK, Assistant Professor, Department of Radiology, Jubilee Mission Medical College and Research Institute, Thrissur, for contributing the MRI images of this article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]