alpha-Fetoprotein-producing liver carcinomas of primary extrahepatic origin

alpha-Fetoprotein (AFP)-producing carcinomas, hepatoid or otherwise, are increasingly being recognized at extrahepatic sites. Some of them not only mimic hepatocellular carcinomas (HCCs) in having a proclivity for vascular permeation and distant metastases but also exhibit identical morphology and immunoreactivity for alpha-1-antitrypsin and HepPar1. beta-Human chorionic gonadotropin (hCG) is also detected. This would create diagnostic problems in hepatic fine needle aspiration biopsies (FNABs) from patients with elevated serum AFP. Apart from HCC, its variants and germ cell tumors, one must consider metastatic AFP-producing carcinomas.

A man with gastric adenocarcinoma had a liver mass. Hepatic FNAB revealed an AFP-producing adenocarcinoma. The gastric tumor was positive for AFP, polyclonal carcinoembryonic antigen, HepPar1, CK19, hCG and synaptophysin. A woman with endocervical adenocarcinoma had multiple liver nodules. FNAB revealed an AFP-producing, undifferentiated carcinoma. The cervix showed a large cell neuroendocrine carcinoma coexisting with an adenocarcinoma in situ. The large cells were positive for synaptophysin, AFP, hCG and AE1/3. The glands showed diffuse HepPar1 and focal synaptophysin expression.

A wide histologic spectrum of extrahepatic carcinomas can produce AFP and other peptide hormones. The true AFP status probably is not recognized at the first presentation. Such carcinomas, whether hepatoid or not, behave aggressively. Their recognition at the initial presentation is crucial to early and appropriate therapy. These entities add a new dimension to the challenges of FNAB diagnosis.