钙化性纤维性肿瘤的临床病理学研究及其组织学发生的再评价

Clinicopathologic features of calcifying fibrous tumor with reappraisal of its histogenesis

目的探讨钙化性纤维性肿瘤（CFT）的临床病理学特征及其组织学发生机制。方法对11例CFT的临床表现、组织学形态及免疫组织化学表型进行分析。结果11例CFT中男性5例，女性6例，年龄从25至52岁，平均38岁，位于盆腹腔6例、皮下软组织4例、阴囊内1例。临床上表现为缓慢增大的无痛性肿块，5例伴随其他病症或既往有炎性改变、外伤或手术史，4例病变为偶然发现，肿瘤多为单发，切除后未见复发。影像学显示病变为孤立性或多发性实性软组织肿块，境界清楚无包膜，实质内散在大小不等、数量不一的高密度钙化灶。大体上，肿瘤呈灰黄色，质硬，边清，圆形、卵圆形、分叶状或不规则形，最大径为0.5 ～20.0 cm，切面散在浅黄色斑点状钙化灶，切开时具有沙砾感。显微镜下显示肿瘤实质主要由玻璃样变的胶原纤维及厚壁血管构成，其中散在少量梭形细胞、单核炎性细胞、沙砾体及营养不良性钙化。此外，少数肿瘤边缘区局灶性中性粒细胞呈带状浸润，另见少量神经束及脂肪组织内陷。不同病例肿瘤实质外周区局灶性具有类似于孤立性纤维瘤、纤维瘤病、瘢痕疙瘩及炎性肌纤维母细胞瘤样形态学改变。沙砾体及营养不良性钙化分别形成于透明变性的血管及玻璃样变的胶原纤维。肿瘤组织内浸润的单核炎性细胞主要为淋巴浆细胞，局部区域可形成淋巴滤泡样结构。免疫组织化学染色显示所有受检的肿瘤组织内梭形细胞弥漫性表达波形蛋白，少数局灶性表达CD34、第八因子相关抗原及β-caltenin，其他标记为阴性。具有特征性的是，与炎性病变相比，CFT组织中浸润的浆细胞显著表达IgG及IgG4，且IgG4＋/IgG＋＞50％，IgG1及IgG3表达的细胞较少。结论CFT具有较为特征性的组织病理学表现，但其发病机制尚未明确。由于CFT与IgG4相关的硬化性疾病具有相似的组织学及免疫组织化学表型，因此，推测CFT可能为IgG4相关的硬化性疾病家族谱系中一种新的独立实体。该病变的发展呈良性经过，炎性改变及创伤可能为该病变的重要诱因，手术切除后罕见复发。

Objective To study the clinicopathologic features and histogenesis of calcifying fibrous tumor （CFT）. Methods The clinical manifestations, histopathologic characteristics and immunophenotype were analyzed in 11 cases of CFT. Results The male-to-female ratio was 5∶6, with a mean age of 38 years and age range of 25 to 52 years. The sites of involvement included abdominopelvic cavity （ n = 6）, soft tissue （n =4） and scrotum （n = 1 ）. Most patients presented with a gradually enlarging and painless mass.Nearly half of the cases were associated with other diseases or history of inflammation, trauma or surgical intervention. One third of the tumors represented incidental findings and showed no recurrence after resection. Imaging revealed a solitary solid soft tissue mass or multiple nodules with clear borders and associated high-density calcifications. Macroscopically, the tumors were well-circumscribed but non-encapsulated. They ranged from 0.5 to 20.0 cm in diameter and were tan-greyish, round to oval, lobulated or irregular and solid with rubbery consistency. The cut surface was whitish to tan-yellowish, gritty and showed scattered spotty yellowish discoloration corresponding to the foci of dystrophic calcifications.Histologically, CFT was composed of hyalinized fibrous tissue and thickened vessel walls with interspersed bland spindly fibroblastic cells, scattered psammomatous calcifications, dystrophic calcification and lymphoplasmacytic infiltration. In addition, focal cloak-like polymorph infiltration at the tumor periphery and entrapment of adipocytes and nerves were demonstrated in some cases. Foci resembling solitary fibrous tumor, fibromatosis, keloid or inflammatory myofibroblastic tumor were observed. Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin and focally positive for CD34, factor Ⅷ-related antigen and beta-catenin. The admixed plasma cells were notably IgG positive, with more than 50% being IgG4 positive. Conclusions CFT has characteristic histopathologic manifestations and shows morphologic and immunohistochemical overlaps with known IgG4-related sclerosing diseases. It is possible that CFT may represent another example of IgG4-related diseases. It often runs a benign clinical course, with rare recurrence after surgical resection. Previous inflammation and trauma may be the precipitating factors of CFT.