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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.

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