Published online Jul 24, 2024. doi: 10.5306/wjco.v15.i7.953
Revised: May 8, 2024
Accepted: June 7, 2024
Published online: July 24, 2024
Processing time: 117 Days and 14.7 Hours
Primary malignant melanoma of the cervix (PMMC) is an extremely rare disease that originates from primary cervical malignant melanoma and frequently re
Here, we report a case of amelanotic PMMC, with a history of breast cancer and thyroid carcinoma. The patient was finally diagnosed by immunohistochemical staining and staged as IB2 based on the International Federation of Gynecology and Obstetrics with reference to National Comprehensive Cancer Network guide
The differential diagnosis process reenforced the notion that immunohistochemical staining is the most reliable approach for amelanotic PMMC diagnosis. Due to the lack of established therapeutic guidelines, empirical information from limited available studies does not provide the rationale for treatment-decision making. By integrating 'omics' technologies and patient-derived xenografts or mini-patient-derived xenograft models this will help to identify selective thera
Core Tip: We report a case of unsuspected amelanotic primary malignant melanoma of the cervix (PMMC) with a history of breast cancer. The patient underwent radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, and then received radiotherapy combined with immunotherapy. She has remained free of disease for more than 1 year. The successful management of this patient underscores the critical role of routine immunohistochemical staining during cervical cancer diagnosis to exclude unsuspected PMMC, and adjuvant immunotherapy may be an option for PMMC.
- Citation: Duan JL, Yang J, Zhang YL, Huang WT. Amelanotic primary cervical malignant melanoma: A case report and review of literature. World J Clin Oncol 2024; 15(7): 953-960
- URL: https://www.wjgnet.com/2218-4333/full/v15/i7/953.htm
- DOI: https://dx.doi.org/10.5306/wjco.v15.i7.953
Primary malignant melanoma of the cervix (PMMC) is extremely rare. Due to a lack of melanocytes in the cervix, PMMC represents a challenge in clinical diagnosis. Currently, there is no consensus or guidelines for the treatment and management of PMMC. In most cases, treatment follows the surgical criteria for cervical squamous cell carcinoma. PMMC can be managed postoperatively or preoperatively.
A 56-year-old woman presented to our hospital in December 2022 with one-day postmenopausal bleeding.
The surgery was planned by a multidisciplinary team and she underwent radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, and one lesion (2.8 cm × 1.5 cm × 1.3 cm) was observed in the lower end of the cervix and its section appeared white in color. Biopsies were further evaluated by pathological examination. The tumor had invaded into 1/2 layer of the cervical muscle wall, and the depth of tumor invasion in the cervix was approximately 6 mm. The endometrium, bilateral adnexa, lymph nodes, and vaginal stump were free of tumors.
Eighteen years ago, she was diagnosed with breast duct carcinoma, and she underwent radical left unilateral mastectomy and then right unilateral mastectomy in 2014. She additionally underwent thyroidectomy two years later due to thyroid carcinoma.
Eighteen years ago, she was diagnosed with breast duct carcinoma, and underwent radical left unilateral mastectomy and then right unilateral mastectomy in 2014. She additionally underwent thyroidectomy two years later due to thyroid carcinoma.
Slight bulging of the anterior vaginal wall and posterior vaginal fornix was observed.
Human papillomavirus screening was negative. Quantitative DNA ploidy analysis identified at least 3 heterotypic cells and the DNA index value was over 2.5. Unexpectedly, a routine serum chemistry panel and plasma tumor biomarker examination, including squamous cell carcinoma antigen, were all within normal limits.
Ultrasound findings revealed a hypoechoic area measuring approximately 14 mm × 15 mm × 12 mm with clear boun
The surgery was planned by a multidisciplinary team and the patient underwent radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy.
Considering the negative expression of pan-Keratin (AE1/AE3) and GATA3, as well the histological findings, this generally rules out the possibility that the tumor originated from primary breast cancer. Negative p40 and p16 reactivity in resected tumors on immunohistochemical (IHC) staining excluded the possibility of primary cervical cancer. Stepwise serial diagnostic IHC staining of biomarkers related to common cancers was performed. Surprisingly, the cells were strongly positive for MelanA, S-100, SOX-10 and HMB45, the biomarker for cervical melanoma (Figure 3). Due to the lack of melanin observed in the lesion, primary cervical malignant melanoma was not considered initially. The patient was finally diagnosed with primary cervical malignant melanoma.
Multiplex gene-panel testing indicated a genetic mutation of BRCA2 (exon11). She then received combination therapy consisting of the anti-PD1 antibody tislelizumab (200 mg, d1, q3w) and radiofrequency hyperthermia for 1.5 years.
The patient has undergone monthly follow-up visits. To date, she remains free of disease, without evidence of disease recurrence or metastasis for 1 year.
Primary cervical malignant melanoma represents an exceedingly uncommon tumor that can occur in the uterine cervix[1-4]. Since it was initially described as macroscopically "black cancer" of the cervix in 1889, only 149 cases have been reported to date[5]. The presence of melanin is one of the four criteria for the diagnosis of cervical melanoma[6]. Less than 20% of cases are, however, amelanotic and 3.5% cells in the cervical melanoma are melanin-containing cells compared with normal cervical epithelia[7,8]. Therefore, routine inclusion of IHC staining of combined S100 sensitivity, HBM45 specificity and MelanA staining is of great significance in facilitating the differential diagnosis of cervical malignancies without delays in situations where there is a lack of pigment. This is probably why IHC staining is more specific than Masson–Fontana staining[1,3]. Given that primary malignant melanoma frequently undergoes distant metastasis, excluding its origin from a primary cutaneous melanoma is a top priority for cervical melanoma diagnosis[9-12]. Both scanning and later positron emission tomography/computed tomography ruled out the presence of melanoma in other anatomic structures due to a distinct signal pattern from the paramagnetic properties of melanin[11,13]. This case was staged as IB2, without lymph node and distant metastasis, and she underwent regional lymph node dissection, although dissection of clinically negative regional lymph nodes is still controversial[14-18], indicating that a future study involving a larger sample size is necessary to determine the value of lymph node dissection in patients with PMMC.
Although melanoma is considered radio-resistant, the combination of ionizing radiation with hyperthermia provokes a systemic immune response and potentiates the efficacy of immunotherapy[19,20]. This case therefore received radiotherapy combined with immunotherapy, and the long-term effect is yet to be evaluated although she has been free of disease for 1 year. Notably, the combination of chemotherapy with either immunotherapy or radiotherapy has de
The differential diagnosis process reenforced the notion that immunohistochemical staining is the most reliable approach for amelanotic PMMC diagnosis. Due to the lack of established therapeutic guidelines, empirical information from limited previous studies does not provide the rationale for treatment-decision making. By integrating 'omics' technologies and PDXs or mini-PDX models this will help to identify selective therapeutic window(s) and screen the correct therapeutics for targeted therapies, immune checkpoint blockade or combination therapy strategies effectively and precisely that will ultimately improve patient survival.
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