Bioulac-Sage Paulette, Laumonier Hervé, Rullier Anne, Cubel Gaelle, Laurent Christophe, Zucman-Rossi Jessica, Balabaud Charles
Department of Pathology, Hôpital Pellegrin CHU Bordeaux, Bordeaux, France.
Liver Int. 2009 Mar;29(3):459-65. doi: 10.1111/j.1478-3231.2008.01849.x. Epub 2008 Sep 18.
Glutamine synthetase (GS) is a useful marker in tumour liver pathology, including hepatocellular adenomas and nodules in cirrhosis. We investigated the use of GS as a marker in various clinical situations, in which FNH diagnosis had been firmly established to determine its contribution to diagnosis.
Seventy-nine cases of resected FNH, all on normal (or occasionally steatotic) livers, were retrieved from our collection. The control group was composed of hepatocellular adenomas and well-differentiated hepatocellular carcinoma. The following stains: H&E, Masson's trichrome, Gordon-Sweet, PAS, perls and immunostains: CK7 and 19, and GS were carried out. FNH was diagnosed based on traditional pathological techniques. In case of uncertainty, particularly with hepatocellular adenoma, additional immunostainings including liver fatty acid-binding protein, serum amyloid A and beta-catenin were performed.
Glutamine synthetase immunostaining was similar in all FNH cases. Positive GS staining of hepatocytic cytoplasms formed large areas, anastomosed in a 'map-like' pattern, often surrounding hepatic veins, whereas GS was not expressed in hepatocytes close to fibrotic bands containing arteries and ductules. In comparison, hepatocellular adenoma staining was completely different, even in cases of fibrotic bands due to tumour remodelling related to necrosis or haemorrhage. In hepatocellular adenomas or well-differentiated hepatocellular carcinoma presenting beta-catenin mutation, GS was positive but with a completely different pattern that appeared diffuse and not 'map-like'.
Regardless of the FNH size or steatotic content, GS produced a similar and characteristic pattern and consequently represents a good marker for easily identifying resected FNH from other hepatocellular nodules.
谷氨酰胺合成酶（GS）是肿瘤性肝病的一种有用标志物，包括肝细胞腺瘤和肝硬化结节。我们研究了GS作为一种标志物在各种临床情况下的应用，其中肝局灶性结节性增生（FNH）的诊断已明确确立，以确定其对诊断的贡献。
从我们的病例收集中检索出79例切除的FNH病例，所有病例肝脏均正常（或偶尔有脂肪变性）。对照组由肝细胞腺瘤和高分化肝细胞癌组成。进行以下染色：苏木精-伊红染色（H&E）、马松三色染色、戈登-斯威特染色、过碘酸雪夫染色（PAS）、普鲁士蓝染色以及免疫染色：细胞角蛋白7和19以及GS。FNH根据传统病理技术进行诊断。在存在不确定性的情况下，特别是与肝细胞腺瘤鉴别时，进行包括肝脂肪酸结合蛋白、血清淀粉样蛋白A和β-连环蛋白在内的额外免疫染色。
所有FNH病例中谷氨酰胺合成酶免疫染色相似。肝细胞胞质GS阳性染色形成大片区域，呈“地图样”吻合，常围绕肝静脉，而靠近含有动脉和小胆管的纤维化带的肝细胞中GS不表达。相比之下，肝细胞腺瘤染色完全不同，即使在因肿瘤重塑（与坏死或出血相关）导致纤维化带的病例中也是如此。在出现β-连环蛋白突变的肝细胞腺瘤或高分化肝细胞癌中，GS呈阳性，但模式完全不同，表现为弥漫性而非“地图样”。
无论FNH大小或脂肪变性程度如何，GS产生相似且特征性的模式，因此是从其他肝细胞结节中轻松识别切除的FNH的良好标志物。
