Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Virchows Arch. 2024 Apr;484(4):587-595. doi: 10.1007/s00428-023-03680-w. Epub 2023 Oct 23.
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by numerous colorectal adenomas. In addition, FAP patients may develop extraintestinal manifestations. Several cases of hepatocellular adenomas (HCA) detected accidentally in FAP patients have raised the so-far unsolved question of whether they represent a specific manifestation of FAP or a mere coincidence. To investigate the incidence of liver tumors in FAP patients, we analyzed our diagnostic database from 1991 to 2021. Among the 58 hepatic mass lesions identified, five HCAs occurring in three patients with FAP were identified, and comprehensive morphological, immunohistological, and molecular analysis employing targeted next-generation sequencing was conducted for characterization. The HCAs in this study showed no cytological or histological atypia. They displayed a diffuse, strong positivity for glutamine synthetase but no nuclear beta-catenin immunostaining. In two patients, the adenomas showed moderate immunoreactivity against serum amyloid A. Consistent with the diagnosis of FAP, molecular profiling revealed a pathogenic germline mutation of the APC gene in all analyzed adenomas as well as deleterious somatic second hits. All somatic mutations were localized between codons 1345 and 1577. No mutations were found in the catenin beta 1 gene. HCA in FAP patients can be a specific, although rare, neoplastic manifestation of this inborn disease and represents a distinct subgroup of HCAs. These benign tumors represent an important differential diagnosis for hepatic metastases in FAP patients and require adequate clinical and molecular (diagnostic) assessments for optimal patient guidance.
家族性腺瘤性息肉病（FAP）是一种常染色体显性遗传综合征，由腺瘤性结肠息肉病（APC）基因的种系突变引起，其特征是大肠内存在大量腺瘤。此外，FAP 患者可能会出现肠外表现。在 FAP 患者中偶然发现的一些肝细胞腺瘤（HCA）病例提出了一个迄今尚未解决的问题，即它们是否代表 FAP 的特定表现还是仅仅是巧合。为了研究 FAP 患者中肝肿瘤的发生率，我们分析了 1991 年至 2021 年的诊断数据库。在确定的 58 个肝肿块病变中，发现了 3 例 FAP 患者的 5 个 HCA，并对其进行了全面的形态学、免疫组织化学和采用靶向下一代测序的分子分析以进行特征描述。本研究中的 HCA 没有细胞学或组织学异型性。它们对谷氨酰胺合成酶呈弥漫性强阳性，但核β-连环蛋白免疫染色阴性。在 2 例患者中，腺瘤对血清淀粉样蛋白 A 呈中度免疫反应性。与 FAP 的诊断一致，分子分析显示所有分析的腺瘤中 APC 基因均存在致病性种系突变和有害的体细胞二次打击。所有体细胞突变均定位于密码子 1345 和 1577 之间。在连接蛋白β1 基因中未发现突变。FAP 患者中的 HCA 可能是这种先天性疾病的一种特定但罕见的肿瘤表现形式，代表了 HCA 的一个独特亚组。这些良性肿瘤是 FAP 患者肝转移的重要鉴别诊断，需要进行充分的临床和分子（诊断）评估，以实现最佳的患者指导。
