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Department of Diagnostic Genomics, Monash Health, Clayton, Vic, AustraliaSchool of Clinical Sciences, Faculty of Medicine, Nursing and Clinical Sciences, Monash University, Vic, Australia
Malignant melanomas usually arise from the skin, retina, uvea, and meninges along with the oral cavity, oesophagus and anorectal mucosa. They have been documented in the gastrointestinal tract, but most of these cases are metastases. Primary malignant melanoma of the biliary tract is an extremely rare pathological diagnosis. Although the first case was described as early as 1963, to date only 14 cases have been reported to the best of our knowledge.
The diagnosis is usually reached by a combination of morphology with immunohistochemistry, along with detailed clinical history and examination. It is also important to rule out gastrointestinal clear cell sarcoma (GI CCS), also called malignant gastrointestinal neuroectodermal tumour (malignant GNET). This tumour has a similar immunoprofile to malignant melanoma and hence the need for molecular testing to complete the diagnosis.
A 72-year-old male who was undergoing investigations for haematuria, was found to have an incidental distal common bile duct (CBD) mass. The computed tomography (CT) scan revealed marked intrahepatic and extrahepatic duct dilatation to the level of the ampulla where a polypoid soft tissue mass measuring 25 mm in maximum diameter was identified (Fig. 1). The portal vein and superior mesenteric veins were clear of the tumour and there were no metastases seen.
Fig. 1CT scan: 25 mm polypoid mass in the distal common bile duct.
The patient underwent a resection of the mass via a pancreaticoduodenectomy (Whipple's procedure). On macroscopic examination, a polypoid mass was identified, filling the distal CBD and measuring 25×20×15 mm. The cut surface of the mass was solid, white and fleshy. The mass was attached to the CBD and there was no extension into the pancreatic parenchyma.
This CBD mass was entirely sampled, and it revealed a well circumscribed spindle cell polypoid tumour, composed of cells arranged in sheets and fascicles. The mass appeared to arise from the mucosa of the distal common bile duct but did not have any intraepithelial melanocytic component. The tumour cells were predominantly spindle shaped with a moderate amount of pale eosinophilic cytoplasm and vesicular nucleus with 1–2 prominent nucleoli. Some of the cells had brownish pigment in their cytoplasm. There was brisk mitotic activity, and many apoptotic bodies were identified. There was no lymphovascular or perineural invasion. There was no dysplasia in the surrounding CBD lining. There was no nodal metastasis in any of the 14 lymph nodes identified. Immunohistochemical testing revealed the tumour cells to be positive for S100, SOX10, Melan-A and HMB45 (Fig. 2). They were negative for CK7, CK20, DOG1, CD117 (cKIT), synapophysin, chromogranin and CD56. The differential diagnoses at this stage were malignant melanoma and GI CCS given their similar immunoprofiles (as mentioned).
The diagnosis of GI CCS requires the presence of EWSR1 gene rearrangements. It was decided to perform an in-house 507-gene RNA fusion panel. The RNA extracted from the tumour had optimal RNA quality and quantity. The sequencing was performed, and the resulting output passed the requisite sequencing quality control parameters. However, this did not reveal either EWSR1-ATF1 or EWSR1-CREB1 fusions, thus excluding a diagnosis of GI CCS. A thorough clinical history and examination did not reveal a primary skin or ophthalmic melanoma. Thus, a final diagnosis of primary CBD melanoma was rendered.
As stated earlier, a vast majority of the melanomas identified in the gastrointestinal tract are in fact metastases from cutaneous sites. Melanoma of the common bile duct is exceedingly rare. Most of the reported cases have been in males in the age group 40–50 years, with the range being 26–67 years.
Our case would be the oldest patient reported to date. All cases reported had presented with jaundice as the primary presenting symptom; however, in our case the CBD mass was found incidentally while the patient was being worked up for haematuria.
Many cases with morphology and immunoprofile like that of melanoma are in fact GI CCS. These tumours have characteristic EWSR1 gene rearrangement, including EWSR1-ATF1 fusion and EWSR1-CREB1 fusion. EWSR1-ATF1 is the same fusion transcript that is identified in CCS of soft tissue. We did not identify any of these fusions in our case. GI CCS are commonly identified in the small intestine, colon and stomach and are most often seen in young adults, with a median age of 33 years.
Interestingly, the majority of documented primary biliary tract melanomas have presented as polypoid, solid, intraluminal masses rather than an infiltrating tumour.
Our case also presented with similar findings with the entire tumour in the form of a malignant polyp with no infiltrating component. In contrast, metastatic malignant melanomas usually present as multifocal flat lesions.
The presence of a junctional component in these tumours is debatable and our case did not have a demonstrable junctional component on entire tumour sampling.
The exact prognosis of these cases is currently not well known due to the small number documented. Our patient went on to be staged with positron emission tomography (PET) post-operatively once the diagnosis of primary CBD melanoma was made. Although this did not reveal any PET-avid metastatic disease, two sub-centimetre nodules in the chest were found to have had interval growth since pre-operative staging CT of the chest; therefore, it was felt that this reflected metastatic disease. He was commenced on adjuvant nivolumab for treatment, and a repeat CT 3 months later showed complete resolution of the nodules radiologically. The patient will remain on nivolumab for 12 months post-operatively and is otherwise clinically well and devoid of any symptoms now 7 months post-operatively. He will continue to have surveillance as per melanoma guidelines in the years to come.
Conflicts of interest and sources of funding
The authors state that there are no conflicts of interest to disclose.
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