乳腺原发神经内分泌肿瘤18例临床病理特征

Neuroendocrine neoplasms of the breast:a clinicopathologic study of 18 cases

目的探讨乳腺原发神经内分泌肿瘤(neuroendocrine neoplasm of breast,BNEN)的临床病理学特征、免疫表型、鉴别诊断及预后。方法收集18例BNEN患者的临床病理资料,分别行HE、免疫组化Ventana uhraView两步法及FISH检测,并复习相关文献。结果18例BNEN患者均为女性,中位年龄53.3岁。临床表现多为孤立性乳房包块,肿瘤平均最大径2.8 cm(范围1.2~7.8 cm)。其中神经内分泌瘤(neuroendocrine tumor,NET)11例,神经内分泌癌(neuroendocrine carcinoma,NEC)4例,混合性神经内分泌肿瘤(neuroendocrine neoplasm,NEN)3例。BNEN生长方式多样,以富含细胞的实性结节、间质为纤细的纤维血管最为多见(13/18),也可见腺泡样、小梁状、菊形团及实性乳头状结构。8例肿瘤在周围乳腺组织内见导管原位癌。免疫表型:Syn(15/18,83.3%)、CgA(13/18,72.2%)均阳性,INSM1(3/5,60%)部分细胞核阳性。分子分型以Luminal B型最常见(11/18,61.1%)。66.7%(10/15)患者出现同侧腋窝淋巴结转移。15例患者平均随访45.3个月(范围2~85个月),其中1例患者于术后3个月复发,5例患者于术后8~77个月出现远处转移,除1例死于其他病因外,余14例均存活。结论BNEN临床罕见且具有异质性,易复发及转移,诊断主要依赖形态学及神经内分泌标志物进行鉴别。

Purpose To investigate the clinicopathological features,immunophenotype,differential diagnosis and prognosis of primary neuroendocrine neoplasms of the breast(BNEN).Methods The clinicopathological data of 18 patients with BNEN were collected.HE stain,immunohistochemical Ventana uhraView two-step method and FISH detection were performed respectively.And relevant literature was reviewed.Results All 18 patients were female with a median age of 53.3 years.The clinical features of most patients were a solitary breast mass.The tumors size ranged from 1.2 to 7.8 cm(mean,2.8 cm).11 cases were diagnosed as neuroendocrine tumor(NET),four cases were neuroendocrine carcinoma(NEC),and 3 cases were mixed NEN.The growth pattern of BNEN was diverse.Thirteen out of 18 cases showed densely cellular solid nests,separated by delicate fibrovascular stroma,other growth patterns including alveolar-like,trabecular,rosette,and solid papillary patterns were noted.Eight cases showed ductal carcinoma in situ within the surrounding breast tissue.Immunohistochemically,the positivity rates of Syn and CgA in BNEN were 83.3%(15/18)and 72.2%(13/18),respectively.INSM1 was positive in some tumors(3/5,60%).For BNEN,the common molecular typing was Luminal B(11/18,61.1%).Ipsilateral axillary lymph node metastasis rates were 66.7%(10/15).Fifteen patients were followed-up for a mean period 45.3 months(range,2-85 months).One patient experienced recurrence 3 months after surgery,and 5 patients developed distant metastasis 8-77 months of follow-up.All 14 patients were alive except one who died of other disease.Conclusion BNEN is a group of relatively rare,heterogeneous and aggressive neoplasms,which has a higher local recurrence rate and distant metastasis,and its diagnosis and assessment are based on morphological and the expression pattern of neuroendocrine markers.