黏液性血管瘤样纤维组织细胞瘤临床病理和分子遗传学特征

Clinicopathologic and molecular characteristics of myxoid angiomatoid fibrous histiocytoma

目的探讨黏液性血管瘤样纤维组织细胞瘤(MAFH)的临床病理特征、免疫表型和分子遗传学特征及其诊断和鉴别诊断要点。方法收集2015年1月至2018年8月间就诊于浙江省人民医院的3例MAFH患者的临床资料,分析其临床和影像学特征、组织形态学、免疫表型、分子遗传学特征以及患者的预后。结果3例患者中,男1例,女2例;年龄分别为37岁、46岁和57岁。临床上均表现为缓慢增大的无痛性肿物,病史分别为2周、2个月和50年。3例患者的肿瘤均位于肢体或肢端的深部软组织内(右髋部、左前臂和左腕部各1例),2例术前影像学考虑为腱鞘囊肿或腱鞘巨细胞瘤。肿瘤直径3.0~7.5 cm,大体界限清楚,切面灰白、灰褐,有黏质感,2例可见不同程度的出血、囊性变。低倍镜下观察,3例均可见厚的纤维性假包膜伴包膜周围的淋巴浆细胞袖套,以多结节状或分叶状生长为主,2例可见明显的出血性囊腔形成。黏液性肿瘤区域分别占60.0%、80.0%和90.0%,瘤细胞卵圆形至星芒状,呈条索状、微囊状和网状分布于丰富的黏液性基质之中。3例均可见黏液性肿瘤成分过渡为局灶典型的非黏液性血管瘤样纤维组织细胞瘤(AFH)组织学形态。瘤细胞异型性轻微,核分裂象稀少(每50倍高倍视野1~2个),未见肿瘤性坏死,1例可见局灶明显的细胞质内空泡。免疫组化染色显示,2例局灶表达结蛋白,2例局灶表达上皮膜抗原,1例局灶表达CD99,Ki67阳性指数1%~5%。荧光原位杂交检测3例均存在EWSR1基因重排。1例术后随访15个月复发;1例第1次术后24个月复发,复发的肿瘤缓慢增大,120个月后第2次切除,再随访2个月未见复发和转移;1例术后32个月未见复发和转移。结论MAFH是一种罕见的AFH组织学亚型,生物学行为低度恶性,形态学上易于误诊。仔细观察寻找典型的AFH组织学特点、并辅以EWSR1基因的重排检测可助于MAFH的诊断和鉴别诊断。

Objective To investigate the molecular genetic and clinicopathologic characteristics,immunophenotypes,diagnostic and differential diagnostic features of myxoid angiomatoid fibrous histiocytoma(MAFH).Methods Three cases of MAFH were collected from the archives of Zhejiang Provincial People′s Hospital between January 2015 to August 2018.The clinical and radiologic features,histomorphology,immunohistochemistry,molecular genetics and prognosis were analyzed.Results Patients consisted of 2 women and 1 man aged 37 years,46 years,and 57 years,respectively.The clinical manifestations of 3 patients were presented as a painless,slowly-enlarged mass with a duration ranging of 2 weeks,2 months and 50 years.These tumors were located at the deep somatic soft tissue of extremities or limbs(right hip,left forearm,left wrist,respectively)and 2 were preoperatively considered as ganglion cyst or giant cell tumor of tendon sheath by imaging examinations.The diameter of circumscribed mass lesion was ranged from 3.0 to 7.5 cm,which exhibited a gray white to tan and gelatinous cut surface.Extensive hemorrhage and cystic changes were observed in 2 cases.Under low magnification,all tumors showed a dense fibrous pseudo-capsule with a peritumoral lymphoplasmacytic cuff and a multi-nodular growth pattern.Blood-filled cystic spaces were observed in 2 tumors.The myxoid stroma occupied 60.0%,80.0%and 90.0%area of the entire tumor,respectively.Within the myxoid areas,tumor cells were oval to stellate and arranged in cord-like,microcystic and reticular growth patterns.Transitions of myxoid tumor components to more solid areas with typical histology of angiomatoid fibrous histiocytoma(AFH)were observed at least focally in all the three cases.The tumor cells exhibited minimal atypia and scarce mitoses(1 to 2/50 HPF)without necrosis,and prominently focal intracytoplasmic vacuoles were identified in one case.The results of immunohistochemistry staining showed that,2/3 cases focally expressed desmin,2/3 focally expressed epithelial membrane antigen(EMA),and 1/3 focally expressed CD99.The positive index of Ki67 was approximately 1%to 5%.Fluorescence in situ hybridization analysis showed that EWSR1 gene rearrangement occurred in all of the three cases.During the period of follow-up,one case showed local recurrence at 15 months,one case showed postoperative recurrence at 24 months,and the recurrent tumor slowly grew for 120 months until the second resection,without recurrence at the following 2 months.The left case showed a disease-free survival at 32 months.Conclusions MAFH is a rare subtype of AFH with a low-grade behavior and may lead to diagnostic confusions.Carefully searching for the typical AFH histomorphology and combining with EWSR1 gene rearrangement test can help to distinguish MAFH from other mimickers.