通过家族性肝腺瘤病（FHA）患者家系图及家系成员基因突变分析，探讨FHA发病机制和临床诊治特点。

回顾性分析2016年3月在中山大学肿瘤防治中心接受诊治的1例FHA患者。患者女，24岁。增强MRI示肝右叶占位，边界清晰，信号不均匀，大小14.9 cm×9.9 cm ×13.2 cm，伴有肝硬化背景，肝内弥漫多发肝硬化结节，S5/6见可疑癌变结节。2016年8月复查发现异常凝血酶原（PIVKA-Ⅱ）升高（307 mAU/ml）。超声引导下穿刺活检证实S8镜下坏死及增生组织，S6病灶肝细胞增生伴异型性，部分细胞脂肪变性，结合免疫组化诊断为肝细胞腺瘤（HCA）。未见恶性肿瘤证据，因HCA病灶范围较大且多发，无手术指征，建议密切随访观察。其家族中有多例确诊和疑似HCA病例。对其肿瘤组织及家族多位成员的血液样本进行了全外显子组测序。

该患者家族三代人中5人有肝病病史，其中4人明确有肝肿物（2人经影像和病理明确为HCA，另外2人肝脏肿物性质不明，影像学考虑为血管瘤或HCA），均为女性，无乙肝病史，AFP未见异常，无避孕药物或激素类药物服用史。全外显子组测序共筛选出2 522个候选变异位点。进一步去除488个常见变异和10个疑似假阳性位点后，最终得到一系列罕见变异位点，这些变异位点主要集中在外显子区域，但未发现与已知的HCA相关的基因变异。

FHA具有家族遗传易感性的特点，临床上治疗复杂。研究发现罕见变异位点，FHA发病可能与基因突变有关。

To explore the pathogenesis, clinical diagnosis and treatment characteristics of FHA through analyzing the pedigree of FHA and gene mutation of family members.

Clinical data of 1 FHA patient admitted to Sun Yat-sen University Cancer Center in March 2016 were retrospectively analyzed. In this 24-year-old female patient, gadoxetate disodium-enhanced MRI showed a space-occupying lesion in the right lobe of the liver with clear margin and uneven signal, 14.9 cm×9.9 cm×13.2 cm in size, complicated by liver cirrhosis and multiple diffuse liver cirrhosis nodules, and suspicious cancerous nodules were seen in liver segment 5/6 (S5/6). In August, 2016, abnormal elevation of prothrombin (PIVKA-Ⅱ) was detected (307 mAU/ml). Ultrasound-guided puncture biopsy confirmed necrotic and hyperplastic tissues in S8, and hepatocellular hyperplasia with atypia and fatty degeneration of partial cells in S6. Immunohistochemistry was combined to make the diagnosis of hepatocellular adenoma (HCA). No evidence of malignant tumor was found. Considering the large range and multiple lesions of HCA, and no surgical indication, intimate follow-up was recommended. In her family, multiple members were confirmed and suspected with HCA. Whole-exome sequencing was performed in the tumor tissues and blood samples from multiple family members.

Five family members of three generations had a history of liver disease, and 4 of them were diagnosed with liver tumors (2 diagnosed with HCA by imaging and pathological examinations, and the other 2 patients were diagnosed with hemangioma or HCA by imaging examination). All these 4 patients diagnosed with liver tumors were female, and they had no history of hepatitis B, normal AFP level, and no history of taking contraceptives or hormones. A total of 2522 candidate mutation loci were screened by whole-exome sequencing. After eliminating 488 common mutation loci and 10 suspected false-positive loci, a series of rare mutation loci were finally obtained, mainly distributed in the exon region. However, no gene mutation related to HCA was found.

FHA is characterized with familial genetic susceptibility, and clinical treatment of FHA is complicated. In this study, rare mutation loci are identified, suggesting the pathogenesis of FHA may be associated with gene mutation.