Distinction of Hepatocellular Carcinoma From Benign Hepatic Mimickers Using Glypican-3 and CD34 Immunohistochemistry

Abstract

Distinguishing a well-differentiated hepatocellular carcinoma (HCC) from normal and cirrhotic liver tissue or benign liver nodules, such as hepatic adenoma (HA) and focal nodular hyperplasia (FNH), may be very difficult in some cases, particularly in small needle core biopsies. We studied the expression of Glypican-3 (GPC3) and CD34 in 107 cases of HCC, 19 cases of HA, and 16 cases of focal nodular hyperplasia (FNH). In addition, we studied GPC3 expression in 225 cases of nonhepatic human tumors with epithelial differentiation. Ninety-four of 107 cases (88%) of HCC showed focal or diffuse cytoplasmic GPC3 staining, whereas all HA and FNH cases were GPC3-negative, and only 7 of 225 cases (3%) of nonhepatic tumors with epithelial differentiation expressed GPC3. The sensitivity and specificity of GPC3 for HCC was 88% and 97%, respectively. There were three CD34 staining patterns observed in hepatic tissue: negative, incomplete positive, and complete positive. In negative staining pattern, only blood vessels in portal triads or rare sinusoidal spaces immediately adjacent to portal tracts were positive. The negative staining pattern was seen in normal or cirrhotic liver tissue only. The complete CD34 staining pattern showed virtually all sinusoidal spaces with CD34-positive staining throughout the lesion. The complete CD34 staining pattern was seen in virtually all cases of HCC and in only some cases of HA and FNH. The incomplete CD34 staining pattern was characterized by either CD34 positivity in virtually all sinusoidal spaces in some but not all nodules or CD34 positivity in the peripheral sinusoidal spaces adjacent to portal triads. The incomplete CD34 staining pattern was seen in rare cases of HCC and in most cases of HA and FNH. We conclude that GPC3 is a very specific marker not only for differentiating HCC from nonhepatic tumors with epithelial differentiation, but also for differentiating HCC from HA and FNH. GPC3 immunoreactivity, in combination with a complete CD34 immunostaining pattern, greatly facilitates the accuracy of distinguishing between malignant hepatic lesions and benign mimickers.

Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma

“…GPC3 is an oncofetal protein, which is expressed in 480% of hepatocellular carcinomas and has higher sensitivity than HepPar-1 and CEA for poorly differentiated hepatocellular carcinoma. [22][23][24][30][31][32][33][34][35][36][37][38] GPC3 is not a specific marker for hepatocellular differentiation and is expressed in a variety of other tumors, most of which do not share clinical or morphological resemblance to hepatocellular carcinoma. 39 Expression in cholangiocarcinoma has been described but is rare (o5% based on combined results of five studies including the present).…”

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

“…111 Malignant Hepatocellular Markers Glypican-3.-Glypican-3 (GPC3) is an oncofetal protein that can be detected in 70% to 80% of HCCs but not in benign hepatocellular lesions, such as hepatocellular adenoma. [112][113][114] Positive stains can be cytoplasmic, membranous, canal icular, and/or cytoplasmi c dotlike. Immunoreactivity is often heterogeneous within the tumor and is frequently focal/patchy and weak in well-differentiated HCC.…”

“…In contrast, a diffuse sinusoidal staining pattern is characteristic of HCC (Figure 8, B), seen in 95% of cases. 114,134 Hepatocellular adenomas predominantly show patchy sinusoidal staining (Figure 8, C), but diffuse staining can be seen in approximately 20% of cases. Patchy staining with periseptal accentuation is also common for FNH.…”

“…Among these, GPC3 appears to have been better investigated; it has never been found to be positive in adenomas. [112][113][114]151 HSP70 has also been reported to be negative in adenomas in 2 small series. 151,152 Despite their low sensitivity to detect HCC on core biopsies, both GPC3 and HSP70 appear to be useful in the distinction between HCC and hepatocellular adenoma, given their high specificity.…”

Microvascular density in prostate core biopsy: Prognostic predictors?

“…Značajno povišen indeks mikrovaskularne gustine u karcinomu prostate je zapažen i od strane drugih autora, koji pokazaju da je visok nivo vaskularne gustine u karcinomu prostate povezan sa lošim ishodom bolesti. 17,18 U našem radu je dokazano da je visok stepen indeksa mikrovaskularne gustine u analiziranim biopsijama karcinoma prostate značajno je veći u ispitanika čija je prosečna starost veća. Osim toga u ispitanika sa visokim indeksom mikrovaskularne gustine je zabeležen i značajno veći Gleason score u odnosu na ispitanike sa niskim indeksom mikrovaskularne gustine u tumorskom tkivu.…”