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Indiana Association 
of Pathologists, Inc.
Histology Laboratory, Indiana Medical History Museum 

Diagnosis and discussion: Hepatoid adenocarcinoma of lung

Hepatoid adenocarcinoma is a rare extrahepatic tumor with morphologic features similar to hepatocellular carcinoma. The most common site of origin for hepatoid adenocarcinoma is stomach. Other sites of origin are rare including ovary, lung, gallbladder, pancreas and uterus. There are only a few cases of hepatoid adenocarcinoma of lung that are reported in the literature. To the best of our knowledge, no previous fine needle aspiration of hepatoid adenocarcinoma of lung has been described before.

Ishikura et al proposed histologic criteria to diagnose hepatoid adenocarcinoma of lung based on his study of 5 cases; they defined hepatoid adenocarcinoma of lung as adenocarcinoma with typical acinar or papillary feature with a component that resembles hepatocellular carcinoma and produces AFP1. In 2014, Haninger and colleagues reviewed 16 articles available in the literature in addition to 5 more cases of their own2. AFP levels, provided in prior reports of hepatoid adenocarcinoma of lung only elevated in 12 of 16 cases. In Haninger’s series, 3 of 5 cases revealed pure hepatoid morphology without acinar or papillary components. They proposed a modification to the previous criteria: (1) the tumor can be pure hepatoid adenocarcinoma or have components of typical acinar or papillary adenocarcinoma, signet-ring cells or neuroendocrine carcinoma and (2) AFP expression is not required for diagnosis as long as other markers of hepatic differentiation are expressed.

Immunohistochemistry is useful to distinguish hepatoid adenocarcinoma of lung from hepatocellular carcinoma. CK5/6, CK7, CK19, CEA and MOC-31are usually positive in hepatoid adenocarcinoma of lung while they are typically negative in hepatocellular carcinoma. Low molecular weight cytokeratin, Hep Par 1, AFP and cytoplasmic TTF1 expression (not nuclear staining) can be expressed in both tumors. Glypican-3 and Arginase-1 are specific markers for hepatocellular carcinoma and they are usually negative for hepatoid adenocarcinoma.3

Hepatoid adenocarcinoma of lung is a rare tumor with male gender predilection and morphologic features similar to hepatocellular carcinoma. It can be diagnosed by fine needle aspiration biopsy. Distinguishing hepatoid adenocarcinoma of lung from metastatic hepatocellular carcinoma requires radiologic, morphologic and immunophenotypic correlation.

References:

1. Ishikura, H., et al., Hepatoid adenocarcinoma: a distinctive histological subtype of alpha-fetoprotein-producing lung carcinoma. Virchows Arch A Pathol Anat Histopathol, 1990. 417(1): p. 73-80.

2. Haninger, D.M., et al., Hepatoid adenocarcinoma of the lung: report of five cases and review of the literature. Mod Pathol, 2014. 27(4): p. 535-42.

3. Timek, D.T., et al., Arginase-1, HepPar-1, and Glypican-3 are the most effective panel of markers in distinguishing hepatocellular carcinoma from metastatic tumor on fine-needle aspiration specimens. Am J Clin Pathol, 2012. 138(2): p. 203-10.

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