摘要目的 分析乳腺恶性叶状肿瘤(phyllodes tumors,PT)的病理组织学、免疫表型和DNA倍体情况,并将其与临床治疗和预后相关联,探讨恶性PT的诊断和鉴别诊断要点及预后相关因素.方法 收集1999至2013年10例乳腺恶性PT的临床病理资料,采用免疫组织化学EnVision法进行CK5/6、广谱细胞角蛋白、34βE12及p63等染色以除外化生性癌,明确恶性PT诊断,检测Ki-67、CD34、平滑肌肌动蛋白(SMA)、结蛋白、p53、p16、bcl-2、CD117、雌激素受体(ER)-α和孕激素受体(PR)在间叶性肿瘤细胞中的表达情况,流式细胞术检测10例石蜡包埋组织的肿瘤DNA倍体,将常规形态学特点、免疫表型以及倍体分析结果与随访结果进行关联分析.结果 患者中位发病年龄为46.5岁,肿瘤大小平均7.4 cm(2.0 ～25.0 cm).随访时间为22 ～ 125个月.局部复发3/8例,平均复发时间24个月；远处转移3/8例,均死于该病.组织学上肿瘤异质性明显,间叶性肿瘤细胞弥漫结节状增生、叶状增生和导管周围增生并存,多数病例呈梭形细胞肉瘤样分化.间叶性肿瘤细胞Ki-67阳性指数平均值为11.4％.CD34、SMA、p53、p16、bcl-2在间叶性肿瘤细胞中的阳性表达比例分别为3/10、9/10、6/10、8/10、4/10.CD117、ER-α和PR阴性.2/9例为三倍体.结论 恶性PT的诊断要注意其生长方式的多样性和组织形态的异质性.免疫组织化学Ki-67高表达、CD34表达下降可作为诊断恶性PT的重要辅助指标,对其预后判断也有一定意义.以弥漫间质增生为主、有异源性分化、Ki-67阳性指数≥20.0％和异倍体的恶性PT尤其要警惕转移的可能性.

abstractsObjective To study the clinicopathologic features of malignant phyllodes tumors (PT)by histopathologic analyses,immunohistochemical profiling and DNA content assay,and evaluation of the clinical outcome.Methods Ten patients with malignant PT from 1999 to 2013 who were treated by surgery were enrolled in this study.The morphologic characteristics were studied under light microscope,standard two-step EnVision method of immunohistochemical staining was used to assess the expression of CK5/6,CKpan,34β3E12,desmin,p63,ER-α,PR,Ki-67,CD34,SMA,p53,p16,bcl-2 and CD117 in the tumors.The corresponding paraffin blocks were also used for flow cytometric DNA content assay.These data were correlated with the follow-up results.Results The median age of onset was 46.5 years old.The mean tumor size was 7.4 cm (2.0-25.0 cm).At the end of the follow-up period (22 to 125 months),there were tumor recurrences in 3/8 patients and the median time of recurrence was 24 months.Metastasis occurred in 3/8 patients who all died of the tumors.PT had heterogeneous histology,with stromal overgrowth with leaf-like projections,periductal stromal overgrowth,and most commonly,diffuse stromal overgrowth with sarcomatous differentiation.The mean positive index of Ki-67 was 11.4％.The stromal tumor cells were positive for CD34,SMA,p53,p16,and bcl-2 in 3/10,9/10,6/10,8/10,and 4/10 cases,respectively.CD117,ER-α and PR were negative.Interpretable DNA histograms were obtained in nine cases with triploidy in two cases.Conclusions The diagnosis of malignant PT should be considered based on the diversity of growth patterns and heterogeneous histology.Ki-67 and CD34 are valuable diagnostic and prognostic factors in patients with malignant PT.Tumors with diffuse stromal overgrowth,heterologous elements,Ki-67 ≥20％ or aneuploidy are more likely to metastasize.