Metastatic Malignant Melanoma

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Image Description

Metastatic malignant melanoma in liver is rare but should be included in the differential diagnosis of any liver malignancy that appears to be metastatic (Note: secondary liver tumors are far more common than primary hepatic neoplasms). Ocular (uveal) melanomas have a biologic tendency to metastasize to the liver.

Liver metastases may appear several years after resection of the primary tumor. FNA smears will show pleomorphic cells with intranuclear inclusions, prominent nucleoli, and cytoplasmic melanin (absent in amelanotic melanomas). Immunohistochemistry is sensitive and specific for the diagnosis of metastatic melanoma. Useful markers include HMB-45, S-100 protein, MART-1, and tyrosinase.

Treatment: Due to the diffuse, miliary involvement of the liver, surgical therapy is usually not an option. However, since liver is often the sole metastatic site in 70% to 90% of cases, transarterial approaches have been utilized, including hepatic artery infusion chemotherapy, transarterial chemoembolization, and selective internal radiation therapy. About 50% of patients show tumor regression or disease stabilization.

The photograph shows metastatic melanoma in liver in a young female patient. Some nodules are amelanotic and others are heavily pigmented. Image copyright: pathorama.ch.

About the Disease

Metastasis is the most common malignancy in non-cirrhotic livers in the Western countries. About 40%-50% of patients dying from cancer have liver metastases. Liver is highly susceptible due to dual blood supply (hepatic and portal) and fenestrations in sinusoidal epithelium which allow tumor cells to escape into the parenchyma. Primary sites in adults: pancreas, stomach, colon, lung, breast, kidney, malignant melanomas, and soft tissue sarcomas. Malignancies of gall bladder, extrahepatic bile ducts, stomach, and pancreas can spread to liver by direct extension. Primary sites in children: neuroblastoma, Wilms tumor, and rhabdomyosarcoma. Presentation ranges from no symptoms to fulminant hepatic failure. Patients may develop malaise, anorexia, weight loss, abdominal pain, and obstructive jaundice. Diagnosis can be accurately made in most cases by CT- or ultrasound guided-FNA and needle core biopsies. Metastases form multiple, discrete expansive masses or ill-defined infiltrative areas. Larger nodules undergo necrosis and fibrosis producing umbilication. Liver may be greatly enlarged with an irregular surface. Malignancies of breast, stomach, lung, pancreas, and lymphomas may produce miliary involvement. Metastases are quite rare in cirrhotic livers. Microscopic features are those of the primary tumor. Metastatic adenocarcinomas may invade bile ducts and show intrabiliary growth mimicking cholangiocarcinoma. Prognosis is poor in most cases (with some exceptions). Most patients die within 1 year of presentation. Resection of isolated liver metastases from colo-rectal cancers can produce long-term disease-free survival or even cure in some cases. Patients with liver metastases from neuroendocrine tumors and Carcinoid syndrome get dramatic relief from symptoms after resection of metastatic foci. References: 1. Iacobuzio-Donahue, C. A. & Montgomery E. (2012). Gastrointestinal and Liver Pathology - 2nd Edition. Philadelphia, PA. Elsevier Saunders. 2. Feldman, M., Friedman, L. S., & Brandt, L. J. (2016). Sleisenger & Fordtran's Gastrointestinal & Liver Disease - 10th Edition. Philadelphia, PA. Elsevier Saunders. 3. Goldblum, J. R. et al (2018). Rosai and Ackerman's Surgical Pathology - 11th Edition. Philadelphia, PA. Elsevier.4. DeVita, V. T., Lawrence, T. S., & Rosenberg, S. A. (2019). Cancer - Principles & Practice of Oncology - 11th Edition. Wolters Kluwer.

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