Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma

Abstract

Inflammatory hepatocellular adenoma can show overlapping histological features with focal nodular hyperplasia, including inflammation, fibrous stroma, and ductular reaction. Expression of serum amyloidassociated protein in inflammatory hepatocellular adenoma and map-like pattern of glutamine synthetase in focal nodular hyperplasia can be helpful in this distinction, but the pitfalls and limitations of these markers have not been established. Morphology and immunohistochemistry were analyzed in 54 inflammatory hepatocellular adenomas, 40 focal nodular hyperplasia, and 3 indeterminate lesions. Morphological analysis demonstrated that nodularity, fibrous stroma, dystrophic blood vessels, and ductular reaction were more common in focal nodular hyperplasia, while telangiectasia, hemorrhage, and steatosis were more common in inflammatory hepatocellular adenoma, but there was frequent overlap of morphological features. 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. Positive staining for serum amyloid-associated protein was seen in the majority of inflammatory hepatocellular adenomas (92.6%) and in the minority of focal nodular hyperplasia (17.5%). The glutamine synthetase staining pattern was map-like in 90% of focal nodular hyperplasia cases, with the remaining 10% of cases showing pseudo map-like staining. Three cases were labeled as indeterminate and showed focal nodular hyperplasia-like morphology but lacked map-like glutamine synthetase staining pattern; these cases demonstrated a patchy pseudo map-like glutamine synthetase pattern along with the expression of serum amyloid-associated protein. Our results highlight the diagnostic errors that can be caused by variant patterns of staining with glutamine synthetase and serum amyloid-associated protein in inflammatory hepatocellular adenoma and focal nodular hyperplasia.

Calcified Telangiectatic Hyperplastic Nodule Associated With Vascular Malformation in a Child: A Case Report

“…Endothelial cells are Calcified Telangiectatic Hyperplastic Nodule Associated With Vascular Malformation  usually negative for CD34 in normal liver sinusoids but they can become positive in vascular flow alterations and neoplasms [14] like it appeared in our case. On the other hand, GS staining pattern in FNH is described as "map-like" because large groups of hepatocytes around the hepatic veins express GS, while GS patterns in HA are highly variable and range from negative to either uniform around the central venules or patchy at the periphery [10,15]. In our patient, the lesion was GS negative, thus excluding FNH and pointing to a possible HA pattern.…”

Immunohistochemical pitfalls in the diagnosis of hepatocellular adenomas and focal nodular hyperplasia: accurate understanding of diverse staining patterns is essential for diagnosis and risk assessment

“…The 50% cutoff was chosen on the basis of the results of the study by Bioulac-Sage et al 3 They had described homogeneous and heterogeneous patterns of glutamine synthetase staining within this group, but did not provide the number of cases for each category. In our study, 2 we also observed homogenous and heterogeneous patterns within the diffuse glutamine synthetase staining group and described them as diffuse-strong and diffuse-intermediate staining, respectively; in addition, we also provided number of cases showing these two patterns within the diffuse category.…”

“…2 This group has done seminal work regarding the immunohistochemical and molecular features of hepatocellular adenoma and focal nodular hyperplasia. We agree with their previously published data, but it appears that some of our immunohistochemical data has not been clearly represented in their commentary.…”

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

“…Strong GS expression in the cytoplasm of hepatocytes, with positive cells forming large sheets arranged in an anastomosed geographic or ''maplike'' pattern, is essentially diagnostic of focal nodular hyperplasia (FNH). 126,127 Glutamine synthetase is usually not expressed in hepatocytes around fibrous scars containing arteries and bile ductules. This unique ''maplike'' pattern is seen in virtually all FNH cases, including those that are morphologically uncharacteristic (Figure 6, A).…”