Liver Metastases : Diagnosis

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Diagnostic Work-up of Liver Metastases: A tissue diagnosis has to be established before therapy can be initiated. This is accomplished by FNA and needle core biopsies (NCB) obtained via transabdominal ultrasound, endoscopic ultrasound, or CT-guided procedures. The choice of procedure depends upon the size and location of the lesion, the suspected diagnosis, the risk of complications, and the experience of the radiologist performing the procedure.

In addition to an adequate FNA sample, a well-prepared cellblock and/or needle core biopsy is essential to provide material for immunohistochemical studies. This allows the pathologist to establish the diagnosis of malignancy, distinguish metastases from primary hepatocellular carcinoma or cholangiocarcinoma, and determine the site of primary tumor. Accurate diagnosis depends upon correct interpretation of FNA/NCB findings in the light of history of previous cancer, radiologic findings and serum tumor marker levels (where applicable).

Once the diagnosis of malignancy is confirmed, the first step is to recognize the general tumor type, i.e. whether is a carcinoma, sarcoma, lymphoma, or melanoma, followed by distinction between primary vs. metastases. A basic panel consisting of epithelial markers (pankeratin AE1/AE3, CAM5.2), mesenchymal marker (vimentin), lymphoid marker (CD45), and melanocytic marker (S-100 protein) can help narrow down differential diagnosis. Additional more specific immunohistochemical stains can be performed based on the initial results.

Microscopic Features: The microscopic features of liver metastases, including the extent of stromal reaction, mirror those of the primary tumor. There is usually clear demarcation between the metastatic deposit and the surrounding liver parenchyma. Invasion of portal and hepatic veins is seen less frequently than with hepatocellular carcinoma. Metastatic adenocarcinomas may invade bile ducts and show intrabiliary growth pattern mimicking cholangiocarcinoma.

This photomicrograph of a CT-guided needle core biopsy of a liver mass shows metastatic neuroendocrine carcinoma. The primary site was pancreas.

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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