# Melanoma Metastases Arising at Unexpected Sites: Gallbladder and Uterus
## 4 Discussion
In our case, it would have been particularly interesting to test the primary cutaneous tumor for BRAF mutational status to investigate whether it shared the same _BRAFV600K_ (1799 GT\(>\)AA) mutation with the metastatic lesion, but the paraffin-embedded blocks were not retrievable because they belonged to another institution. Due to the rarity of the disease, no therapeutic guidelines have yet been standardized. The role of surgery in the treatment of gallbladder metastatic melanoma remains questionable, since the majority of patients have widespread metastatic disease at the time of the diagnosis [22]. Resection of the gallbladder could be a palliative procedure to prevent further dissemination, but the question arising at present is whether it is better to perform a laparoscopic cholecystectomy (LC) or an open surgical cholecystectomy. A recent paper encourages the open surgical approach rather than the laparoscopic one, due to possible local recurrence, and for the detection of other gastrointestinal metastases, fearing the perforation of the gallbladder and intra-abdominal bile leak [22]. The localization of metastatic malignant melanoma in gynecologic organs is exceedingly rare, with the ovaries being a relatively more frequent site. [29]. Some authors have suggested that uterine involvement can be secondary to local retrograde lymphatic spread from existing ovarian metastasis [30]. Pathological studies of the anatomical distribution of metastases within the uterus revealed that they are apparently almost always found in the myometrium (96.2%), whereas the endometrium is involved in approximately one-third of cases [31]. Primary melanoma of the uterine cervix and vagina is relatively more common, accounting for only 3-7% of all cases [32]. In all reported cases of uterine metastatic malignant melanoma, the main complaint is about abnormal uterine bleeding, both in menopausal and non-menopausal women [29; 30; 32; 33; 34; 35; 36; 37; 38; 39; 40]. The final diagnosis is often problematic, as the wide spectrum of histological appearances of metastatic melanoma, especially when presenting as unpigmented tumor cells, and due to the polypoid morphology often mimicking a primary endometrial lesion [32; 33; 34; 35; 36; 37; 38; 39; 40]. Metastatic melanoma of the endometrium generally shows a poor prognosis, with most women having extensive system metastatic disease at the time of diagnosis [32; 33; 34; 35; 36; 37; 38; 39; 40]. However, for those with metastatic melanoma confined to the uterine corpus and no evidence of other metastatic disease, the prognosis was considerably improved [32; 33; 34; 35; 36; 37; 38; 39]. [PERSON] et al. described a case with the same site of the primary tumor (heel) as in our case [29]. The diagnosis of acral melanoma for this patient was dated 6 years prior to the discovery of the metastasis, with optimal clinical surveillance following the excision. The main complaint was postmenopausal vaginal bleeding, and hysterectomy revealed a polypoid lesion with irregular color and appearance [29]. Acral melanoma is a rare (4-7%) melanoma subtype associated with a poor outcome, probably due to the delayed diagnosis and its more aggressive biological behavior. Other cases described in the literature reported previous diagnoses of cutaneous melanoma dated approximately 5-6 years before the discovery of the endometrial metastasis, emphasizing that a thorough anamnesis and clinical examination are crucial. Patients who had metastatic disease confined to the uterus and who underwent a total abdominal hysterectomy and bilateral salpingo-oophoreectomy had a significantly good prognosis [32; 33; 34; 35; 36; 37; 38; 39; 40]. It should be kept in mind that abnormal uterine bleeding may be the first sign of metastatic disease in a woman with a history of malignant disease, as in our case, since the endometrium localization is very rare and clinically evident, while the myometrium localization is more common but asymptomatic.