A serum amyloid A-positive hepatocellular neoplasm arising in alcoholic cirrhosis: a previously unrecognized type of inflammatory hepatocellular tumor

Abstract

Hepatocellular adenoma usually arises in the absence of significant fibrosis. Herein, we report seven patients with serum amyloid A-positive hepatocellular neoplasm, which shares features with inflammatory hepatocellular adenoma arising in alcoholic cirrhosis. Seven patients (two women and five men, age range 41-67 years) with hypervascular hepatocellular nodules associated with alcoholic cirrhosis were retrieved from our pathological files (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011). The hepatocellular nodules were multiple (43) in all patients and 17 nodules were histologically examined. We surveyed the immunoreactivity for serum amyloid A, glutamine synthetase, and glypican-3 in the hepatocellular nodules and control lesions, including 5 focal nodular hyperplasia, 18 dysplastic nodules, and 54 hepatocellular carcinomas in various background diseases. In all, 15 of 17 nodules showed strong and distinct immunoreactivity for serum amyloid A, sharing features with inflammatory hepatocellular adenoma. The serum amyloid A-positive hepatocellular neoplasms showed increased cellular density, inflammatory infiltrate, sinusoidal dilatation, and ductular reaction to various degrees. Although about a half of dysplastic nodules and hepatocellular carcinomas showed focal immunoreactivity for serum amyloid A, the extent of serum amyloid A expression was significantly higher in serum amyloid A-positive hepatocellular neoplasms, than in control nodules. The serum amyloid A-positive hepatocellular neoplasms did not show the overexpression of glutamine synthetase or immunoreactivity for glypican-3. In contrast, most hepatocellular carcinomas showed the overexpression of glutamine synthetase and immunoreactivity for glypican-3, irrespective of background diseases. In conclusion, this study highlights a characteristic group of hepatocellular neoplasms arising in alcoholic cirrhosis, which share features with inflammatory hepatocellular adenomas. These serum amyloid Apositive hepatocellular neoplasms may be a new type of inflammatory hepatocellular tumors in alcoholic patients.

Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis

“…These results suggest that immunophenotype alone is not a sufficient diagnostic criterion to identify an inflammatory adenoma developed in a cirrhotic liver. Cirrhotic nodules strongly expressing serum amyloid A have been formerly reported by Sasaki et al 11,12 in patients with alcoholic cirrhosis. Interestingly, these nodules also shared similar histological features with inflammatory adenoma but only two cases demonstrated a classical STAT3-activating mutation.…”

“…Authors suggested that these lesions might represent a new subtype of inflammatory hepatocellular tumors that may develop in the setting of alcoholic cirrhosis. 11,12 In the present study, we report a series of 10 hepatocellular neoplasms developed in three patients with cirrhosis that shared immunohistochemical and molecular features with inflammatory adenoma. In order to determine whether 'classical' cirrhotic nodules may also belong to this particular subset of lesions, we also further investigated a series of 32 macronodules developed on cirrhosis of various etiologies.…”

“…1,10 Recently, Sasaki et al 11,12 reported cases of benign hepatocellular nodules in patients with alcoholic cirrhosis that displayed serum amyloid A immunohistochemical expression and shared overlapping histological features with inflammatory adenoma. Moreover, an activating somatic STAT3 mutation was identified in 2 out of 17 cases.…”

Contrast-enhanced ultrasonographic findings of serum amyloid A-positive hepatocellular neoplasm: Does hepatocellular adenoma arise in cirrhotic liver?

“…Inflammatory HCA accounts for 45%-60% of all HCAs [1][2][3][4] , and has mutations of the IL6ST gene [12][13][14] . Alcohol intake and obesity are association with inflammatory HCA [9,[15][16][17] .…”

“…Recently, some reports about serum amyloid A (SAA) positive hepatocellular neoplasm were published. All nodules shared features with inflammatory HCA arising in alcoholic cirrhosis [9][10][11] . In this report, we describe contrast-enhanced ultrasonographic findings of SAA positive hepatocellular neoplasm which had features similar to inflammatory HCAs.…”