【作者】 张莹；

【导师】 唐峰；

【作者基本信息】 复旦大学 ， 病理学， 2012， 硕士

【摘要】 背景：乳腺神经内分泌癌(Neuroendocrine carcinoma of the breast, NEC of the breast)是近几十年才被提出的一种罕见的乳腺恶性肿瘤,2003年WHO统一命名并指出其发病率约占到全部乳腺恶性肿瘤的2-5%。乳腺NEC是一类独立的疾病,其临床表现与浸润性导管癌(IDC,NOS)相似,但生物学行为及预后却可能有着很大差别。对乳腺NEC的临床病理特征与IDC,NOS进行比较,明确二者的生物学特征及预后的差别对临床有重要意义。与IDC,NOS有关的预后相关因素包括年龄大小、肿瘤直径大小、淋巴结有无转移、TNM分期、组织学类型和激素受体表达水平等,它们在预测复发风险方面具有重要作用。而在NEC中,这些因素是否与预后相关仍无定论。乳腺NEC的形态学表现具有高度异质性,可能有非NEC乳腺癌的形态学特征,而不同亚型的NEC的形态学特征也可以有非常大的差异。2003年世界卫生组织(WHO)肿瘤分类按照形态将其分为三个亚型：实性型(solid/carcinoid-like)、小细胞／雀麦细胞癌(small cell/oat cell)及大细胞型(large cell)。不同类型的乳腺NEC的预后情况差别较大,故明确其形态学分型有重要意义。方法：本研究搜集华山医院475例IDC,NOS患者和107例乳腺NEC患者的详细病史资料,进行临床评测、跟踪随访、形态学分型、免疫组化染色,对各临床病理因素在国内IDC,NOS患者和NEC患者中进行比较,讨论其在预后分析中的作用、并研究各亚型之间预后差别。结果：475例IDC,NOS患者均具有完善的临床及预后资料,随访时问2-149月(平均100个月),107例NEC患者均具有完善的临床及预后资料,随访时间1-137月(平均36个月)。两组患者在年龄(P<.0001)、月经情况(P<.0001)、肿瘤大小(P=.014)、淋巴结转移情况(P=.026)、核分裂卡(P=.036)、ER(P<.0001)、 PR(P<.0001)、HER2(P<.0001)等方面的差别有统计学意义,且NEC组患者预后比IDC,NOS组好,OS(P=.03,Log-rank=4.696)、LRFS (P=.043, Log-rank=4.098)。单因素分析结果显示,与NEC预后相关的因素为肿瘤大小(P=.003)、远处转移(P<.0001)、TNM分期(P<.0001)以及PR(P=.001)、Ki67表达情况(P=.009),其中除了PR与NEC良好预后相关,其他几项都是不良的预后因素。多因素分析远处转移是NEC的独立预后因素。我们对107例乳腺NEC进行形态学分型,分为实性粘附型(solid cohesive)、实性乳头型(solid papillary)、细胞黏液型(cellular mucinous)、腺泡型(alveolar)、小细胞／燕麦细胞癌(small cell/oat cell)、大细胞型(1arge cell)六型。Kaplan-Meier生存分析结果六型预后无明显差别(P=.819)。结论：乳腺NEC是一种独立的、罕见的乳腺恶性肿瘤。其与IDC,NOS在发病年龄、月经情况、肿瘤大小、淋巴结转移、核分裂相等临床病理特征方面有显著差别,OS和LRFS也明显高于IDC,NOS。肿瘤大小、远处转移、TNM分期、Ki67都是乳腺NEC的不良预后因素,而PR与良好的预后和较高OS相关。乳腺NEC的形态学分型可分为六型,我们研究结果显示它们的预后没有明显差别。更多还原

【Abstract】 Background:Neuroendocrine carcinoma of the breast (NEC of the breast) is a rare mammary carcinoma that has been reported since the past four decades. In2003the World Health Organization named it as NEC of the breast with an incidence rate of2-5%among all mammary malignancies. NEC of the breast is a distinct disease, with similar clinical features to Invasive ductal carcimoma, not otherwise specialized(IDC, NOS) but different biological features and outcome. It is clinically beneficial to compare the clinicopathologic features of NEC and IDC,NOS and to figure out those diffenences. Prognostic factors of IDC,NOS include age, tumor size, LN metastasis, TNM stage, histological type and hormone receptor expression, which are significant in predicting recurrence risk. Whether these factors still work in NEC of the breast is in debate. NEC of the breast is highly heterogeneous with morphological features characteristic of non-neuroendocrine carcinoma, and different subtypes of NEC can have various histological features. The2003WHO Tumour Series divided NEC of the breast as having three subtypes:solid/carcinoid-like, small cell/oat cell and large cell. With different morphological subtypes having quite different prognosis, it is important to distinguish between them.Methods:We conducted a comparative study on107NEC patients and475invasive ductal carcinoma, not otherwise specified(IDC, NOS) patients from the department of pathology Huashan Hospital, Fudan University, to determine the demographic, pathologic, and clinical features at presentation, along with patient outcomes and prognostic factors.Results:All475patients with IDC,NOS have complete clinical and prognostic data, with follow-up time from2to149months(median,100m). All107patients with NEC have complete clinical and prognostic data, with follow-up time from1to137months (median,36m). There are significant differences in age(P<.0001), menopausal status(P<.0001), tumor size(P=.014), LN metastasis(P=.026), mitotic figure(P=.036), ER(P<.0001), PR(P<.0001), HER2(P<.0001). Also, NEC patients have a significantly better prognosis than IDC,NOS patients with higher OS (P=.03, Log-rank=4.696) and LRFS (P=.043, Log-rank=4.098). Statistical analysis revealed that tumor size(P=.003), distant metastasis(P<.0001), TNM stage(P<.0001), Ki67(p=.009) are related to worse prognosis, while PR(P=.001) is a good prognostic factor. Multivariate analysis showed that distant metastasis is a dependant prognostic factor. Finally, we divided NEC of the breast to six morphological subtypes(solid cohesive, solid papillary, cellular mucinous, alveolar, small cell/oat cell, large cell). Kaplan-Meier survival analysis revealed no significant differences between them.Conclusions:NEC of the breast is a distinct and rare malignancy. Several clinicopathologic features including age, menopausal status, tumor size, LN metastasis, mitotic figure, ER, PR, HER2and OS, LRFS are significantly different with IDC,NOS. Prognostic factors of NEC are tumor size, distant metastasis, TNM stage, Ki67and PR. OS between six morphological subtypes are of no statistical significance.更多还原