Liver Metastases vs Primary Hepatocellular CA

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Image Description

LIVER METASTASES vs PRIMARY HEPATOCELLULAR CARCINOMA (HCC): Metastatic renal cell carcinoma and adrenocortical carcinoma can mimic primary HCC on cytology smears as well as needle core biopsy samples. Immunohistochemical stains help differentiate among these three entities.

Features favoring adrenocortical carcinoma: vimentin+, synaptophysin+, MART-1+, calretinin+, inhibin+, and cytokeratin+ (weak). Features favoring clear cell renal cell carcinoma: cytokeratin+, vimentin+, EMA+, RCC+, and CD10+. Papillary RCC and Chromophobe RCC do not express vimentin. Alpha-methyl CoA Racemase (AMACR) is expressed by papillary RCC. Chromophobe RCC is positive for colloidal iron (which is negative in both hepatocellular carcinoma and adrenocortical carcinoma). Primary HCC is favored by: positivity for low mol.wt. cytokeratins, HepPar+, CD10+ (canalicular pattern), and CEA+ (canalicular pattern).

METASTATIC ADENOCARCINOMAS VS HEPATOCELLULAR CARCINOMA: HCC can occasionally form acinar or glandular structures and mimic adenocarcinoma. Adenocarcinomas generally show mucin in the gland lumens or within individual cells. Special stains for mucin such as mucicarmine can establish a malignancy as an adenocarcinoma. Bile pigment, when present, is pathognomonic for HCC. Immunohistochemistry is extremely helpful in this situation. Results that favor adenocarcinomas: positivity for both low and high-molecular weight keratins, cytoplasmic expression of CEA, and positivity for MOC31. Features favoring HCC: expression of only low molecular weight keratins, canalicular staining pattern with CEA and CD10. AFP, when expressed, is specific for HCC. HepPar is a somewhat non-specific marker for HCC and is also expressed by adrenocortical carcinoma, yolk sac tumor, ovarian carcinoma, colonic carcinoma, lung carcinoma, and endocervical carcinoma.

Other rare liver metastases that may mimic primary HCC include: hepatoid yolk sac tumor, hepatoid gastric carcinoma, and oxyphilic follicular thyroid carcinoma.

About this image: Metastatic colo-rectal adenocarcinoma showing moderate-to-poorly differentiated glands infiltrating liver parenchyma accompanied by desmoplastic stroma.

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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