Metastatic Neuroendocrine Tumor

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Image Description

Primary neuroendocrine neoplasms (NENs) of the liver are extremely rare and much less common than liver metastases from NENs arising elsewhere in the gastrointestinal tract, pancreas, lung, or other sites. Therefore, before a NEN is accepted as a liver primary, the possibility of metastases must be excluded. The route of spread of NENs of gastrointestinal tract and pancreas to the liver is via portal circulation.

The spectrum of metastatic neuroendocrine tumors in the liver is wide. It includes well-differentiated tumors (carcinoids) as well as small cell carcinomas. The well-differentiated tumors have a monomorphic appearance, minimal mitotic activity, and no necrosis on needle core biopsies. The smears are quite cellular with a monomorphic, often plasmacytoid appearance. Both smears as well as core biopsy samples show characteristic salt and pepper chromatin.

High-grade tumors, such as small cell carcinomas from the lung, show nuclear molding, necrosis, increased mitotic activity, and finely stippled chromatin. Immunohistochemical panel consisting of synaptophysin, chromogranin, and CD56 is useful in confirming the diagnosis.

Hepatic metastases from NENs are indolent and often highly symptomatic (Carcinoid syndrome). Complete resection often cannot be performed due to diffuse and multifocal involvement of the liver. Subtotal resection (debulking) is still recommended and can produce dramatic relief from symptoms of hormonal overproduction.

The photograph shows extensive liver metastases from neuroendocrine carcinoma of pancreas. The patient developed hepatic encephalopathy and acute renal failure. 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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