Case report
In late October 2024, a 44-year-old male with no significant past medical history and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 presented to King's College Hospital with obstructive jaundice. Computed tomography (CT) revealed a 3.5-cm soft tissue mass within the mid common bile duct (CBD), causing upstream biliary dilatation (Figs. 1 and 2). Liver function tests demonstrated cholestatic derangement, with total bilirubin 153 µmol/l, alanine transferase 638 IU/l, alkaline phosphatase (ALP) 721 IU/l, and gamma-glutamyl transferase (GGT) 832 IU/l. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated an intraductal mass extending 2 cm into the lower common hepatic duct and involving the cystic duct orifice. A sphincterotomy with plastic biliary stent placement relieved obstruction, resulting in bilirubin normalization to 20 µmol/l within one week. Brush cytology obtained during ERCP was non-diagnostic.
Staging investigations did not reveal any evidence of metastatic disease, thus the patient was counselled for pancreaticoduodenectomy, with intraoperative frozen section of the upper bile duct margin planned to determine the need for additional hepatic resection if positive for malignancy.
At laparotomy, frozen section analysis of the upper CBD margin was negative for malignancy. As the lower CBD was involved by tumour, a pylorus-preserving pancreaticoduodenectomy was performed. The pancreas was soft with a non-dilated duct, and a modified invagination technique was used for the pancreatico-jejunostomy. The patient's initial recovery was uneventful, and he was discharged on postoperative day 8 with no evidence of pancreatic fistula. One week later, however, he was readmitted with abdominal bleeding secondary to a gastroduodenal artery pseudoaneurysm. This was successfully managed with embolization and hepatic artery stent placement under angiographic guidance, after which he made a full recovery.
Histopathological examination revealed the CBD lesion to be malignant melanoma. Gross examination of the specimen demonstrated an intraductal polypoid tumour almost completely obliterating the mid CBD and cystic duct, with a dark brown to black solid cut surface containing whitish areas (Fig. 3A). Microscopically, the tumour was composed of epithelioid malignant cells arranged in solid nests and trabeculae, with moderately pleomorphic nuclei and lightly pigmented cytoplasm. Mitotic figures were scattered, and melanin pigment was observed within neoplastic cells and infiltrating macrophages. The stroma was moderately infiltrated by lymphocytes (Fig. 3B). Immunohistochemistry demonstrated diffuse positivity for melanocytic markers (HMB-45, Melan-A, SOX10) and BRAF V600E, while epithelial markers (AE1/AE3, MNF116, CK7) were negative (Fig. 3C-F). The tumour was predominantly intraductal with only focal invasion of the superficial duct wall. A definitive junctional component at the mucosal-submucosal interface was not identified. S-100 immunohistochemistry was not performed, as the diagnosis was supported by diffuse positivity for specific melanocytic markers including HMB-45, Melan-A, and SOX10. All resection margins and regional lymph nodes were free of tumour.
The patient reported a history of nevus excision six years prior, histologically confirmed as a dysplastic nevus without features of melanoma; this lesion was re-examined and again confirmed to be benign. A family history revealed melanoma in a second-degree relative (a cousin), with no additional family history of melanoma or other malignancies. Comprehensive dermatological assessment and full-body skin mapping did not identify any suspicious cutaneous, mucosal, or ocular lesions.
Following multidisciplinary discussion, the patient commenced adjuvant immunotherapy with nivolumab at a standard dose of 480 mg administered intravenously every 4 weeks, for a planned duration of 12 months. This approach was considered appropriate in the context of a BRAF V600E-mutant melanoma, with scheduled interval imaging for surveillance. At the time of last follow-up, the patient remains disease-free 12 months after surgery.
Discussion
Painless obstructive jaundice is the most common presentation of pancreatobiliary malignancy. Cholangiocarcinoma typically affects patients in the sixth decade of life, and cases occurring under the age of 50 remain understudied (10). Distal cholangiocarcinoma accounts for 20–30% of all cases (11).
Malignant melanoma has the potential to metastasize to virtually any organ (12). Abdominal involvement is reported in up to 60% of cases with metastatic melanoma (1). The biliary tract is affected in 4–20% of cases, most frequently at the level of the gallbladder (9,13). Cetiner et al (12) reported fewer than 20 cases of metastatic melanoma involving the common bile duct (CBD), and to date, no systematic review has been performed.
The clinical spectrum of metastatic disease varies from widespread dissemination with poor prognosis and no curative options (13) to isolated lesions amenable to surgical resection, such as gallbladder metastasis, where cholecystectomy may provide limited disease-free survival (13). Historically, the prognosis of metastatic melanoma was dismal, with 2-year survival rates <2% reported three decades ago (14). However, more recent series demonstrate that resection of isolated intra-abdominal metastatic deposits can yield 5-year survival rates of 12–25% in selected cases (14–16). Complete resection appears to be critical for long-term survival. Wood et al (17) reported a 24% 5-year survival among patients undergoing resection of solid organ metastases (adrenalectomy, splenectomy, hepatectomy, pancreatectomy), whereas no long-term survivors were observed following incomplete resection.
Primary melanoma of the CBD is exceedingly rare, and its pathological diagnosis remains controversial due to the absence of specific immunohistochemical features (13). Ricci et al (18) proposed diagnostic criteria for primary gallbladder melanoma, which have also been applied to CBD melanoma: absence of prior melanoma, exclusion of other primary sites, solitary polypoid lesion, and presence of a junctional component. Wagner et al (19) subsequently emphasized the histological finding of junctional melanocytes at the mucosal-submucosal interface, confirmed by S-100 immunoreactivity, as the strongest criterion for primary CBD melanoma. However, this feature has not been consistently reported by other authors (6–8).
In the present case, the diagnostic criteria proposed by Ricci et al (18) are largely fulfilled, including the absence of a prior melanoma, exclusion of alternative primary sites after comprehensive dermatological and systemic assessment, and the presence of a solitary intraductal polypoid lesion. Although a definitive junctional component, as emphasised by Wagner et al (19), was not identified, this feature has not been consistently demonstrated in previously reported cases of primary CBD melanoma. Given the predominantly intraductal growth pattern with only focal superficial invasion and the absence of metastatic disease, a primary biliary origin remains the most plausible diagnosis.
Moreover, although S-100 immunoreactivity and a junctional component have been proposed as diagnostic criteria, these features are not consistently reported in published cases of primary CBD melanoma, and their absence does not preclude the diagnosis when supported by morphology, specific melanocytic markers, and exclusion of alternative primary sites.
To date, only 13 cases of primary CBD melanoma have been described (6–9), with most diagnoses based on exclusion after extensive negative systemic work-up. In both primary and metastatic cases, upfront surgical resection remains the mainstay of treatment (6,17).
Applying the criteria from previous reports, the present case represents the 14th description of primary malignant melanoma of the CBD. While histological confirmation remains debated, the absence of cutaneous, mucosal, or ocular melanoma and the solitary intraductal lesion strongly support this diagnosis.
The identification of a BRAF V600E mutation in the present case is clinically significant and has important therapeutic implications. BRAF mutations are present in approximately 40–50% of cutaneous melanomas and have been associated with responsiveness to targeted therapy using BRAF inhibitors (20,21). Although data on molecular profiling in primary biliary melanoma are extremely limited, the presence of a BRAF V600E mutation provides a rationale for considering targeted therapy in the event of disease recurrence or metastatic progression. This molecular finding further distinguishes the present case from many previously reported cases and highlights the importance of comprehensive immunohistochemical and molecular assessment in rare melanocytic tumours of the biliary tract (20,21).
Although the prognosis of both primary and metastatic biliary melanoma has historically been poor, the present case may represent a more favourable biological and clinical scenario. Young age at presentation, complete (R0) surgical resection, and access to contemporary adjuvant immunotherapy are factors that have been associated with improved outcomes in melanoma more broadly. Nevertheless, given the rarity of primary CBD melanoma and the relatively short duration of follow-up in this case, which represents a limitation of this report, any prognostic inference must be made with caution, and longer-term surveillance remains essential to better define oncological outcomes.
This case underscores the importance of careful evaluation of patient demographics and history, particularly in younger individuals presenting with obstructive jaundice. Although preoperative differentiation from cholangiocarcinoma is difficult, clinicians must be aware of this rare entity. A diagnosis of melanoma after curative-intent pancreaticoduodenectomy represents a major shift in prognosis and postoperative management, with implications for patients, families, and the multidisciplinary team.
In conclusion, metastatic involvement of the biliary tree occurs in 4–20% of cases of metastatic melanoma. Primary CBD melanoma is exceedingly rare, with only 13 cases previously described. Both entities are associated with poor prognosis, with 5-year survival not exceeding 25% even in resected cases. Nevertheless, complete resection remains the standard of care, offering the best chance for long-term survival.
A comprehensive evaluation of patient history, prior skin lesions, and family history is essential when assessing younger patients with obstructive jaundice. While rare, the possibility of primary or metastatic melanoma should be considered, as unexpected histological findings following major hepatopancreatobiliary surgery can profoundly alter the oncological pathway.