Primary Malignant Melanoma of the Genitourinary System: A Systemic Review and Report of Eight Cases

Abstract

Malignant melanoma (MM) of mucosal membranes (excluding anus and head-neck) is a rare but aggressive disease with poor outcomes. The knowledge of this tumor's development, etiology, and management is scarce, mainly due to the low case numbers. We presented eight cases and performed a comprehensive literature review on mucosal MM (between 1970 and 2020). We identified 47 manuscripts on 55 patients with primary mucosal MM (limited to urothelium and vagina) and reviewed demographics, tumor specifications (morphology, stage, etc.), management, and survival. We identified 10 manuscripts discussing treatment in 1595 mucosal and non-mucosal MM and extracted the data regarding the non-surgical treatment modalities of mucosal MM patients.In 63 cases, 48 tumors primarily occurred in the urothelium (urethra: 47, bladder: 1) and 15 in the vagina. Molecular studies in a subset of cases revealed alterations in c-KIT, NRAS, BRAF (non-V600E and V600E), TP53, and NF1. Fifty-three patients underwent surgery (with additional chemotherapy, immunotherapy, and radiotherapy in 19, eight, and eight patients, respectively). The outcome was available in 52 cases, showing 21 deaths, 10 without recurrence, two alive with disease, and five lost to follow-up. Shared genetic signatures in mucosal and skin MM suggest a similar development mechanism; however, unlike skin MM, there are less BRAF mutations and more PI3K/AKT/mTOR pathway alterations in mucosal MM. Prolonged chemotherapy (i.e., methotrexate) and immune-modulating agents (i.e., natalizumab) may be risk factors. The stage at diagnosis and proper surgical extirpation are keys to the prognosis and survival of patients.

Primary Malignant Melanoma of the Genitourinary Tract: Case Series of a Rare Form of Primary Mucosal Melanoma

“…Adjuvant therapy is often required [ 13 ]. Pelvic exenteration may be beneficial for vaginal melanoma and female urethral melanoma with a thickness of more than 3 mm [ 14 ].…”

Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway

“…In particular, gynecologic tract melanoma has a poor prognosis, with a 5-year survival rate lower than 25%. Because of the low survival rate and the lack of a standard treatment approach related to gynecologic tract melanoma [1][2][3], elucidation of the mechanisms underlying melanoma progression is crucial for achieving advancements in relevant gynecological surgery and treatment. Studies have indicated that extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase/protein kinase B (AKT) pathways play major roles in the progression of melanoma [4][5][6].…”

A Case Report of Primary Melanoma of the Urethra

“…The most common regions impacted in the genitourinary tract by malignant melanoma are the urethral meatus and distal urethra, although less commonly the bladder and ureter can be affected as well [2][3][4]. Unlike cutaneous melanoma, there is a lower incidence of BRAF mutations in mucosal melanomas; PI3K/Ak strain transforming (Akt)/mammalian target of rapamycin (mTOR) pathway alterations and c-kit mutations are more commonly observed in this group of neoplasms [5]. Poor outcomes for patients are typically due to the invasive nature and late diagnosis of the condition; the estimated three-year survival rate upon diagnosis is under 5% [1].…”