CAJ | 학술논문

目的探讨乳腺神经内分泌癌(NEC)的病理形态学和亚型。方法收集22例乳腺NEC，进行组织形态学观察和免疫组织化学（MaxVision法）染色，抗体包括：突触素、嗜铬粒素A(CgA)、神经元特异性烯醇化酶(NSE)、CD56、雌激素受体(ER)、孕激素受体(PR)、HER2、表皮生长因子受体(EGFR)、CK5/6、CK14、p63、E-cadherin、p120、p53和Ki-67。对HER2蛋白表达2+的病例行HER2荧光原位杂交检测。乳腺NEC的判断标准：50％以上的肿瘤至少表达1种神经内分泌标志物，同时其他器官没有发现NEC。结果除1例男性外余均为女性，年龄在31 ～96岁（平均65.2岁）。病变发生在左乳15例(68.2％)，右乳7例(31.8％)。肿瘤大小0.5～5.5 cm(平均2.7 cm)。6例有腋窝淋巴结转移。组织学类型包括：实性黏附型9例、黏液型6例、实性乳头状型3例、小细胞型2例、大细胞型1例、腺泡型1例。各种标志物的免疫组织化学染色阳性比例：突触素为100％( 22/22)、NSE为12/13、CgA为54.5％ (12/22)、CD56为5/16、ER为90.5％ (19/21)、PR为81.0％( 17/21)，无一例HER2蛋白过表达(3+)，EGFR、CK5/6、CK14和p63均为阴性。所有E-cadherin和（或）p120标记的病例均显示细胞膜阳性(19/19)。p53阳性比例为6/17。Ki-67阳性指数＜3％者占9.5％(2/21)，3％～20％者占66.7％(14/21)，＞20％者占23.8％ (5/21)。2例HER2蛋白表达2+者，荧光原位杂交检测结果均无基因扩增。免疫分子分型绝大多数为腺腔A型，无HER2过表达型和基底细胞样型。结论乳腺NEC好发于老年人，发生在左侧乳腺者多于右侧，最常见的亚型是实性黏附型，其次为黏液型，免疫表型归属于浸润性导管癌的特殊类型。
목적 탐토유선신경내분비암(NEC)적병리형태학화아형。방법 수집22례유선NEC，진행조직형태학관찰화면역조직화학（MaxVision법）염색，항체포괄：돌촉소、기락립소A(CgA)、신경원특이성희순화매(NSE)、CD56、자격소수체(ER)、잉격소수체(PR)、HER2、표피생장인자수체(EGFR)、CK5/6、CK14、p63、E-cadherin、p120、p53화Ki-67。대HER2단백표체2+적병례행HER2형광원위잡교검측。유선NEC적판단표준：50％이상적종류지소표체1충신경내분비표지물，동시기타기관몰유발현NEC。결과 제1례남성외여균위녀성，년령재31 ～96세（평균65.2세）。병변발생재좌유15례(68.2％)，우유7례(31.8％)。종류대소0.5～5.5 cm(평균2.7 cm)。6례유액와림파결전이。조직학류형포괄：실성점부형9례、점액형6례、실성유두상형3례、소세포형2례、대세포형1례、선포형1례。각충표지물적면역조직화학염색양성비례：돌촉소위100％( 22/22)、NSE위12/13、CgA위54.5％ (12/22)、CD56위5/16、ER위90.5％ (19/21)、PR위81.0％( 17/21)，무일례HER2단백과표체(3+)，EGFR、CK5/6、CK14화p63균위음성。소유E-cadherin화（혹）p120표기적병례균현시세포막양성(19/19)。p53양성비례위6/17。Ki-67양성지수＜3％자점9.5％(2/21)，3％～20％자점66.7％(14/21)，＞20％자점23.8％ (5/21)。2례HER2단백표체2+자，형광원위잡교검측결과균무기인확증。면역분자분형절대다수위선강A형，무HER2과표체형화기저세포양형。결론 유선NEC호발우노년인，발생재좌측유선자다우우측，최상견적아형시실성점부형，기차위점액형，면역표형귀속우침윤성도관암적특수류형。
Objective To study the clinical features and histopathology of the neuroendocrine carcinoma (NEC) of the breast. Methods Twenty-two cases of NEC of the breast were analysed by morphology and immunohistochemistry using synaptophysin, chromogranin A, NSE, CD56, estrogen receptor (ER), progesterone receptor ( PR), HER2, EGFR, CK5/6, CK14, p63, E-cadherin, p120, p53 and Ki-67 staining. HER2 gene amplification was detected by fluorescence in situ hybridization (FISH) for cases with HER2 protein expression 2 +. The diagnosis of breast NEC relies on the expression of neuroendocrine markers expression in more than 50％ of tumor cells, and no evidence of neuroendocrine carcinoma in any other parts of the body at the same time. Results The patients aged from 31 to 96 years ( mean 65. 2years), and all were female but one. Amongst the 22 patients studied, the NECs were in the left breast in 15 cases (68. 2％ ) and in the right breast in seven cases (31.8％) ; the tumor size was 0. 5 to 5. 5 cm ( mean 2. 7 cm). Lymph node metastasis was found in six cases. Basing on the morphologic features, these 22 cases were categorized into six subtypes including nine cases of solid cohesive, six of mucinous, three of solid papillary, two of small cell, one of large cell and one of alveolar variants. Immunohistochemically, the expression rate of markers was 100％ (22/22) for synaptophysin, 12/13 for NSE, 54. 5％ ( 12/22 ) for chromogranin A, and 5/16 for CD56. Also, 90.5％ (19 of 21) of cases expressed ER, 81.0％ (17 of 21)of cases expressed PR, and none expressed EGFR, CK5/6, CK14 and p63. HER2 protein over-expression (3 + ) and gene amplification was not detected in any case. All cases (19/19) were positive for membrane staining for E-cadherin and p120. p53 expression was seen in 6 of 17 cases. Ki-67 labeling index was less than 3％ in 9. 5％ (2/21) of the cases, 3％ to 20％ in 66.7％ ( 14/21 ) of the cases and more than 20％ in 23. 8％ (5/21) of the cases. Both cases of HER2 (2 + ) did not show gene amplification by FISH. On the basis of immunophenotypes, most of the breast NECs were of the luminal molecular subtype, but not HER2-overexpression or basal-like subtypes. Conclusions NEC of breast more likely occurs in elderly patients and in the left breast than the right breast. The most common morphology is the solid cohesive subtype, followed by the mucinous variant.