Primary Malignant Melanoma of the Cervix with Rapidly Progressing Metastases

Introduction: Mucosal melanomas only account for 0.03% of newly diagnosed cancer cases. Female genital tract melanomas account for only 3% of all melanomas, with melanoma of the cervix accounting for less than 3% of all female genital tract melanomas. It is difficult to understand how mucosal melanomas arise as the pathogenesis is still unknown. The incidence of cutaneous melanoma has greatly increased over the years whereas the incidence of mucosal melanomas has stayed relatively steady. Given the rarity of melanoma of the cervix, a standard of care treatment has not been established. Based on the limited cases that have previously been treated, the first option is surgery for early stage melanomas with adjuvant radiation therapy indicated in some cases. The use of systemic chemotherapy is still controversial as it has not been shown to prevent metastases. Case Report: A 66-year-old postmenopausal female presented with heavy vaginal bleeding. A transvaginal ultrasound showed a complex cystic structure in the cervix and she was referred to gynecologic oncology. She was up to date on her pap smears, and they have always been normal. Patient was found to have a fungating 4 x 5 cm mass in the upper vagina and pathology demonstrated poorly differentiated malignant neoplasm. The patient was diagnosed with FIGO Stage IIA2 cervical cancer. Patient’s initial PET/CT demonstrated hypermetabolic area in the cervix consistent with known cervical carcinoma with no other uptake in the uterus. Weekly chemosensitization with cisplatin and external beam radiation was initiated. On clinical examination after treatment by the gynecologic oncologist, visible disease was seen confined to the cervix. An MRI of the pelvis showed response with the suspected tumor limited to the cervical stroma in the anterior and lateral portion of the cervix with no definitive parametrial tumor and no evidence of nodal metastasis. Second opinion from pathology review was received and results showed poorly differentiated malignant neoplasm immunohistochemically consistent with “melanoma”. After 25 fractions of daily radiotherapy with weekly cisplatin, patient underwent exploratory laparotomy for radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling. Final pathology of the uterus and cervix showed invasive poorly differentiated melanoma with deepest invasion of melanoma measuring 8mm and negative surgical margins. All lymph nodes removed during surgery were negative for malignancy. Adjuvant Pembrolizumab was started at this time. Two months postoperatively, the patient underwent CT surveillance again due to new onset chest wall and axillary nodules varying in size from 2-4 cm. Right chest wall axilla biopsy pathology was consistent with melanoma. At this time Pembrolizumab was discontinued and the patient was transitioned to Nivolumab and Ipilimumab 19 days after discontinuing Pembrolizumab. Four months postoperatively, additional CT scans were performed showing widespread metastatic disease in the lungs, chest wall, liver, peritoneum, retroperitoneum and left eye. Patient underwent left frontal craniotomy with tumor resection, and pathology was consistent with metastatic melanoma. Subsequent to craniotomy, the patient underwent three treatments with stereotactic radiosurgery. Despite treatment, six months postoperatively, the patient’s symptoms continued to progress with slurred speech, generalized weakness and abdominal pain. Ultimately, the patient passed away nine months after the diagnosis and four months after a combination of external beam radiotherapy, surgery, and vaginal brachytherapy. Discussion: Melanoma of the cervix is a rare type of cervical cancer with poor prognosis. Globally, 5-year survival is 18.8% for stage I, 11.1% for stage II, and 0% for stages III–IV. It has been shown that median overall survival time decreases with increasing FIGO stage. Risk factors have not been identified for gynecologic melanomas or most other mucosal melanomas. Pembrolizumab is most effective for cutaneous melanomas, however, has been shown to prolong progression free survival in mucosal melanomas. The median overall survival is significantly shorter for patients with mucosal melanoma (11.3 months) as compared to patients with a cutaneous primary (23.5 months). Primary malignant melanoma of the cervix (PMMC) remains a rare tumor and the prognosis is generally poor. Radical hysterectomy, chemoradiation, and immunotherapy have all been utilized in the treatment of PMMC. Further investigation of primary melanoma of the cervix is necessary to formulate a standard of care treatment.