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Hepatocellular adenoma subtypes—Which is it?

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Karen Lusky

July 2017—Kisha Mitchell Richards, MBBS, a pathologist at Greenwich Hospital, Yale New Haven Health, Greenwich, Conn., recalls that when she was a resident, adenoma was just adenoma. “Nowadays it’s not quite where breast is, where it’s a two-page report, but there are now subtypes of hepatocellular adenomas,” she said in a CAP16 presentation on liver neoplasms. The subtypes are the HNF1 alpha or TCF1 inactivated adenoma, inflammatory adenoma, beta-catenin mutated adenoma, and the unclassified adenoma, which she notes is basically adenoma NOS (not otherwise specified).

The HNF1 alpha or TCF1 inactivated adenoma is frequently but not always steatotic. “So certainly if you have diffuse steatosis, you think of that subtype,” Dr. Richards said. “It’s commonly associated clinically with young women with or without diabetes. The immunostain used for that is a liver fatty-acid-binding protein, and you usually have a loss of expression in those.”

If you see an adenoma and wonder if it’s focal nodular hyperplasia, she said, it could be an inflammatory adenoma. “The adenoma looks inflammatory and there’s often sinusoidal dilatation.” Focal nodular hyperplasia can look inflammatory, she told CAP TODAY in an interview. “That’s why it can be confused with the inflammatory adenoma. Often an FNH has inflammatory cells.”

Dr. Richards cautioned that some of the inflammatory adenomas have the beta-catenin mutation and are at risk for progressing to hepatocellular carcinoma. The stains that tend to be used for the inflammatory adenoma are serum amyloid A and C-reactive protein, she said, adding that she usually uses the former. (The amyloid stain may also be positive in an inflamed liver.)

“If [the lesion] is benign appearing, you see some fibrous bands and central scar, ductular proliferation and inflammation, and you think it’s an FNH, use glutamine synthetase and amyloid A, depending on the setting, to help distinguish the inflammatory type [of adenoma] versus an FNH,” Dr. Richards advised.

Glutamine synthetase is useful in FNH, she says, because it has a different pattern of staining in FNH, “a geographic pattern of staining.” However, “you can also have what is called pseudo map-like positivity,” she cautioned. She discussed a study by Nancy Joseph, MD, PhD, and Sanjay Kakar, MD, of the Department of Anatomic Pathology, University of California, San Francisco, and colleagues that addresses that subject (Joseph NM, et al. Mod Pathol. 2014;27[1]:62–72). In their article, the authors wrote, “The majority of inflammatory hepatocellular adenomas demonstrated perivascular and/or patchy glutamine synthetase staining (73.6%), while the remaining cases had diffuse (7.5%), negative (3.8%), or patchy pattern of staining (15%) that showed subtle differences from the classic map-like staining pattern and was designated as pseudo map-like staining.” The “pattern was observed focally at the periphery of the lesion,” they noted.

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