发生β-catenin基因突变的侵袭性纤维瘤病的临床病理特征

Clinicopathological features of invasive fibromatosis with β-catenin gene mutation

目的探讨发生β-catenin基因突变的侵袭性纤维瘤病(AF)的临床病理特征。方法收集2015年1月至2018年12月于郑州大学第一附属医院确诊的23例发生β-catenin基因突变的AF患者的临床资料。所有患者均接受外科手术治疗。分析其病理学特点,采用免疫组织化学EnVision法检测相关标志物,采用聚合酶链反应-变性高效液相色谱技术-Sanger测序法检测患者β-catenin基因突变位点。结果 23例患者中女17例(73.9%),男6例(26.1%),中位年龄26岁。病变发生于腹壁、腹壁外(肩部、胸背、大腿、臀部)、腹腔内(盆腔)的各有5、17、1例,分别占21.7%、73.9%、4.3%。肿物直径为3.0~18.0 cm。肿物多局限于肌肉、腱膜、筋膜,切面呈灰白色,质韧硬,无包膜,与周围组织分界不清,镜下表现为形态温和一致的成纤维细胞,间以多少不等的胶原纤维,形成平行的宽束状或不典型的车辐状结构;梭形细胞核肥胖或细长,胞质界限不清,偶见核分裂。β-catenin蛋白阳性表达率和阴性表达率分别为73.9%(17/23)、26.1%(6/23)。23例患者β-catenin基因突变均位于第三外显子,突变位点为T41A、S45F、S45P的分别有12、8、3例,分别占52.2%、34.8%、13.0%。结论组织病理学、免疫组织学标记有助于AF的诊断和鉴别诊断,分子病理检测到β-catenin基因突变为诊断AF的有力证据。不同β-catenin基因突变位点的AF患者的预后也不同。

Objective To investigate the clinicopathological features of invasive fibromatosis with β-catenin gene mutation.Methods The clinical data of 23 cases of AF with β-catenin gene mutation diagnosed in the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2018 were collected. All patients received surgical treatment. The pathological characteristics were analyzed. Immunohistochemical EnVision method was used to detect relevant markers. Detection of β-catenin gene mutations in 23 patients by polymerase chain reaction-denaturing high performance liquid chromatography with Sanger sequencing site.Results Of the 23 patients, 17 cases were female(73.9%), 6 cases were male(26.1%). The median age was 26 years old. The site of the lesion was 5 cases with abdominal wall occupying position and 17 cases with extraabdominal wall(shoulder, chest back, thigh, hip) and 1 case of intraperitoneal(pelvic mass) occupying space, accounting for 21.7%, 73.9% and 4.3% respectively. The diameter of the tumor was from 3.0 to 18.0 cm. The mass was limited to muscle, aponeurosis or fascia. The section was grayish white, tough and hard, without capsule, and could not be separated from the surrounding tissue. Microscopic appearance of mild and consistent fibroblasts with varying amounts of collagen fibers to form parallel broad bundles or atypical spokes fusiform structure. Spindle nuclei were obese or slender, cytoplasmic boundaries unclear, occasionally mitotic. The positive and negative expression rates of β-catenin protein were 73.9%(17/23) and 26.1%(6/23), respectively. The mutations of β-catenin gene in 23 patients were all located in exon 3. The mutation sites of T41 A, S45 F and S45 P were 12, 8 and 3 cases respectively, accounting for 52.2%, 34.8% and 13.0% respectively.Conclusion Histopathological and immunohistochemical markers are helpful for the diagnosis and differential diagnosis of AF, and the mutation of β-catenin gene detected by molecular pathology is strong evidence for the diagnosis of AF. The prognosis of AF patients with different β-catenin gene mutation sites is also different.