## 4 Discussions  
Given the low incidence and rarity of gynecological mucosal melanoma being reported, most of the data regarding patient care and treatment have been deduced from other studies that included cutaneous and mucosal melanomas of diverse origins. Primary surgical resection represents the first therapeutic option and the scope of this is to obtain negative margins [9; 10]. Different melanoma subtypes have distinct molecular lines. Mucosal, acral and chronic sun-induced damage (CSD)--associated melanomas have different characteristics of chromosomal damage in contrast with those appearing from skin without CSD [11; 12]. Regarding biological characteristics, MM and cutaneous melanoma (CM) are different. Thus, MMs have a significantly smaller percentage, less than 15% of BRAF gene mutations, than CM without chronic sun damage [1; 13; 14; 15]. Moreover, the increased BRAF gene mutation in MM damages gene regions other than codon 600 or is a non-activating mutation, so it is not expected to have an effect on target therapy [1; 14]. Moreover, gene copy numbers and structural changes, for example in KIT, are significantly more magnified in MM than in CM [1; 16; 17]. The treatment of MM involves a multidisciplinary team, as it is a multimodal therapy adapted to disease stage. In localized disease instances, surgery is the main treatment followed by adjuvant therapy in stage 3 of the disease; adjuvant radiotherapy is indicated in clinical positive lymph nodes. In metastatic disease, target treatment and immunotherapy are the principal approaches which can integrate radiotherapy and surgery in well selected cases [3; 18]. For vulvovaginal melanoma, surgery, if it is possible, is to be preferred as primary treatment, not requiring an exon literature procedure. Surgery has two important scopes: the treatment of the primary tumor and the assessment of lymph node regions. Surgical cytoreduction can be performed in individualized in well selected metastatic cases and is not a routine practice [6; 19]. For newly diagnosed vulvovaginal MM or for a relapsed disease, pelvic exoneration is not usually performed. Sentinel lymph node (SLN) mapping of the inguinal lymph nodes can be easily carried out by experienced surgeons, but strong recommendations regarding this technique in vaginal melanomas cannot be given [6; 20] and the appropriate approach of SLN-positive  
Figure 3: Aspects of radiotherapy plan highlighting the structures: (**a**) the description of field distribution; (**b**) the description of structures defined in planned treatment. cases and the role of additional inguino-femoral lymphadenectomy needs to be determined in further studies [6]. The therapeutic value of SLN biopsy is limited, being more important as a tool for diagnosis. SLN biopsy improved disease-free survival by 7% and 10% for patients with intermediary thickness (1.2-3.5 mm diameter) or thick (3.5 mm diameter) primary lesions [5]. The ongoing discussions over the importance of lymph node dissection will end when molecularly guided imaging or a new biological therapy becomes accessible intended to identify and treat metastatic disease [21]. Immunotherapy and target therapy has demonstrated strong efficacy in the treatment of CM [9]. It has been reported that novel immunotherapeutic and targeted agents increase survival in melanoma and should be considered in cases of vulvovaginal melanoma. The use of verumafenib in melanomas with a BRAFV600E mutation significantly increased progression-free survival (PFS) as opposed to dacarbazine in a phase III trial [22]. The median PFS was 5.3 months for veumafenib against 1.6 months for dacarbazine. BRAF inhibitor concurrent with MEK inhibitors is an elective procedure in the case of a BRAF V600-activating mutation [1]. If there is no mutation, anti-PD1 as unique therapy or combined therapy (nivolumab and ipilimumab) is recommendable [1, 23]. The efficacy of associating nivolumab with ipilimumab seemed to be greater than the single use of the agents and the activity was lower in MM than in CM [1, 16].