雄激素长期治疗再生障碍性贫血诱发肝细胞腺瘤的临床病理学观察

Clinical and pathological observation of hepatocyte adenoma induced by long-term treatment of aplastic anemia by androgens

目的探讨雄激素长期治疗再生障碍性贫血(aplastic anemia,AA)诱发肝细胞腺瘤(hepatic adenoma,HCA)的临床病理特点。方法收集解放军总医院第一医学中心病理科诊断HCA的病例126例,其中3例HCA有再生障碍性贫血并使用雄激素长期治疗的病史,回顾性总结分析其临床病理学特征、免疫组织化学染色结果、诊断及鉴别诊断等。结果 3例患者年龄13~21岁,其中男性2例,女性1例,均有雄激素治疗再生障碍性贫血的病史,无肝炎及肝硬化病史,肿瘤标志物甲胎蛋白(alpha fetoprotein,AFP)正常,除1例出现腹腔出血外,其余2例均为影像学发现肝占位。2例为左、右叶肝内多发肿瘤,1例为右侧肝脏单发肿瘤。病变区肝小叶结构不明显,未见汇管区及中央静脉。肿瘤细胞轻度异型,无脂肪变性,可见淤胆,肝板由1~2层肝细胞构成,部分排列成假腺样结构,肝血窦及薄壁血管丰富,可见髓外造血,病变内无炎细胞浸润。免疫组织化学标记CD34显示瘤组织内丰富的微血管,β-catenin显示瘤细胞斑片状核阳性,GS显示瘤细胞胞浆阳性,Ki67增殖指数低(<5%)。网织纤维染色显示细胞索排列紊乱,部分区域肝板增厚。所有病例均经外科手术切除肿瘤且停止使用雄激素治疗,随访3~24个月,尚未出现肿瘤复发。结论 HCA需与高分化肝细胞癌及肝细胞局灶性结节性增生等肝肿瘤鉴别。服用雄激素类的患者应接受超声和CT的监测,并对肿瘤标志物进行检测,以便早期发现和治疗HCA。

Objective To explore the clinicopathological characteristics of hepatocyte adenoma induced by aplastic anemia treated with androgens for a long time.Methods A total of 126 cases of HCA diagnosed by the pathology department of the first medical center of the PLA general hospital were collected,among which 3 cases had a history of aplastic anemia and were treated with androgens for a long time.Results The 3 patients were aged 13 ~ 21 years,with an average age of 18 years,including 2 males and 1 female,all of whom had history of aplastic anemia treated with androgen,and no history of hepatitis or cirrhosis. The tumor marker AFP was normal. Two patients had multiple hepatic tumors in the left and right lobes,and one had a single tumor in the right liver. The hepatic lobular structure in the lesion area was not obvious,and no portal area and central vein were found. The liver plate is composed of 1 ~ 2 layers of liver cells,some of which are arranged into pseudo adenoid structures. There are abundant hepatic sinusoids and parenchyma vessels,and extramedullary hematopoiesis is visible. There is no inflammatory cell infiltration in the lesion.Immunohistochemical marker CD34 showed abundant microvessels in tumor tissues,β-catenin showed positive patchy nuclei of tumor cells,GS showed positive cytoplasm of tumor cells,and Ki67 proliferation index was low( < 5%).The reticulated fiber staining revealed a disorganized arrangement of cell cords and thickened liver plates in some areas. All patients underwent surgical resection of the tumor and discontinued the use of androgen therapy. The 3 patients were followed up for 3 ~ 24 months without tumor recurrence.Conclusion HCA should be differentiated from liver tumors such as well-differentiated hepatocellular carcinoma and focal nodular hyperplasia of hepatocytes. The 3 cases in this paper belong to β-HCA and have the risk of malignant transformation.Patients taking androgens should be monitored with US and CT,and tumor markers tested for early detection and treatment of HCA.