伴有细胞外黏液分泌的乳腺浸润性小叶癌的临床病理学特征

Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis

目的探讨伴有细胞外黏液分泌的乳腺浸润性小叶癌的临床病理学特征及预后。方法收集复旦大学附属肿瘤医院2009至2018年间诊断的7例伴有细胞外黏液分泌的浸润性小叶癌患者的临床病理资料,并对患者进行随访(随访时间39~123个月,中位时间55个月)。光镜下观察组织学形态及免疫组织化学染色结果,并对HER2免疫组织化学染色结果2+的病例行荧光原位杂交(FISH)检测。进一步分析患者生存情况,并对相关文献进行复习。结果7例患者均为女性,年龄43~73岁(中位年龄55岁),肿块最大径1~5 cm(中位最大径2 cm)。7例肿瘤样本组织学分级均为Ⅱ级,大部分区域呈现经典型浸润性小叶癌形态,局灶可见多少不等的细胞外黏液分泌区域;其中6例部分癌细胞可见胞质内黏液,胞核被挤于细胞一端,呈印戒样。2例患者伴有淋巴结转移,且分别在术后随访38个月和48个月时出现肝转移和骨转移,并分别于术后第48个月和第123个月死亡。其余5例患者,除1例失访外均无瘤生存。免疫组织化学染色显示,雌激素受体(ER)、孕激素受体(PR)阳性比例分别为7/7、6/7。7例中6例HER2免疫组织化学为0/1+,另1例HER2免疫组织化学为2+,FISH检测显示HER2扩增。HER2阳性比例为1/7。Ki-67阳性指数<5%~30%,其中Ki-67≤10%病例比例为5/7。按照2013版St. Gallen乳腺癌国际专家共识,7例患者分子分型均为腔面型,其中2例为腔面A型,5例为腔面B型。结论伴有细胞外黏液分泌的浸润性小叶癌多发生于50岁以上妇女,该组病例均为经典型浸润性小叶癌,组织学分级Ⅱ级,印戒样细胞多见。该组病例分子分型均为腔面型,以腔面B型多见。

Objective To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types;of those, two were luminal A and five were luminal B. Conclusions ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.