乳腺肌纤维母细胞瘤九例临床病理学分析

Mammary myofibroblastoma：a clinicopathologic analysis of nine cases

目的探讨乳腺肌纤维母细胞瘤的临床病理特征、诊断及鉴别诊断要点。方法收集2006—2017年复旦大学附属肿瘤医院病理科诊断的乳腺肌纤维母细胞瘤9例患者资料及预后信息，分析其临床特点、组织病理学特征及免疫表型，其中1例荧光原位杂交（FISH）法行FOXO1单等位基因缺失检测。结果患者女性7例，男性2例；平均和中位年龄分别为54岁和50岁（年龄范围40～83岁）。发生于左乳和右乳各4例，1例位于左腋下副乳腺组织。临床上8例为自检发现肿块，其中3例伴疼痛。大体上均表现为境界清楚的结节（平均直径2.5 cm）。低倍镜下可见肿瘤与周围组织分界尚清，肿瘤内部无乳腺导管及小叶结构。其中7例为经典型，肿瘤由束状/交织状排列的梭形细胞间隔以数量不等的胶原组成，细胞形态温和，无核分裂象；1例为上皮样亚型，上皮样肿瘤细胞弥漫浸润或呈簇状分布；1例为梭形细胞与上皮样细胞混合型。3例中可见核深染的不典型细胞。免疫组织化学结果显示肿瘤细胞弥漫表达结蛋白（9/9）和CD34（6/9），并表达雌激素受体（7/7）、孕激素受体（6/6）和bcl-2（3/3）。平滑肌肌动蛋白（4/7）和Calponin（1/2）在部分病例中呈不同比例阳性，H-caldesmon（1/2）弱阳性，上皮标志物均阴性。Ki-67阳性指数均低于10%。FOXO1/13q14单等位基因缺失检测结果为阴性。9例随访时间12～78个月，均未复发。结论乳腺肌纤维母细胞瘤是一种罕见的良性间叶源性肿瘤。少数肿瘤可出现形态学变异，其中上皮样亚型乳腺肌纤维母细胞瘤可酷似浸润性小叶癌，在病理诊断尤其是空芯针穿刺活检或冷冻切片诊断中容易误诊。熟悉该肿瘤的临床病理特征对于准确诊断、合理治疗具有十分重要的意义。

ObjectiveTo study the clinicopathologic characteristics and differential diagnosis of mammary myofibroblastoma.MethodsNine cases of mammary myofibroblastoma diagnosed between 2006 and 2017 were collected from the Department of Pathology, Fudan University Shanghai Cancer Center. Clinical and histopathologic features of these nine cases were examined, immunohistochemical staining was performed, FISH analysis for the detection of FOXO1 gene was performed in one case, and follow-up data were also collected.ResultsThere were seven female and two male patients, with a mean age of 54 years, median age of 50 years （ranging from 40 to 83 years）. Four lesions each were located in the left and right breast, and one was in the left subaxillary accessory breast tissue. Clinically, 8 patients presented with a breast mass, 3 of which accompanied with pain. All of the tumors were well-demarcated grossly with a mean diameter of 2.5 cm. Microscopically, there were no entrapped ductal or lobular structures within the tumor. Seven tumors were classic type, which were composed of bland-looking spindle neoplastic cells without mitoses, arranging in intersecting fascicles, and interrupted by thick hyalinized collagen bundles. One case was of epithelioid variant, demonstrating epithelioid neoplastic cells diffusely arranged or in cluster. The other one case was mixed spindle and epithelioid-cell type. Atypical tumor cells were observed in 3 cases. Immunohistochemically, tumor cells were diffusely positive for desmin （9/9） and CD34 （6/9）, as well as ER （7/7）, PR （6/6） and bcl-2 （3/3）. SMA （4/7） and Calponin （1/2） were focally or partially positive in some cases. H-caldesmon （1/2） was weakly positive and epithelial markers were negative. Ki-67 proliferation index was low （〈10%）. There was no monoallelic loss of FOXO1/13q14 loci in the detected case according to FISH analysis. Follow-up data were available for all patients, and follow-up period ranged from 12 to 78 months. All patients remained well without recurrence.ConclusionsMammary myofibroblastoma is a rare benign mesenchymal tumor. In some circumstances, it may exhibit confusing morphologies, including some variants. The epithelioid variant of mammary myofibroblastoma might mimic invasive lobular carcinoma, leading to the diagnostic dilemmas and even misdiagnosis, especially in core needle biopsy specimen or frozen sections. Familiarity with the characteristics of this tumor is of great importance for accurate diagnosis and proper treatment.