Lu Ye, Kong Xiangyi, Zhang Wenxiang, Wang Xiangyu, Pei Shengbin, Fang Yi, Gao Jidong, Wang Jing
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Breast. 2025 May 14;82:104501. doi: 10.1016/j.breast.2025.104501.
Tall Cell Carcinoma with Reversed Polarity (TCCRP) is a rare and distinct subtype of invasive breast carcinoma, first described in 2003. It is histologically characterized by tall columnar epithelial cells with reversed nuclear polarity and shares morphological features with papillary thyroid carcinoma (PTC). However, its unique molecular signature, including IDH2 and PIK3CA mutations, differentiates it from other breast cancer subtypes. A retrospective systematic study of 91 published cases of TCCRP was conducted, including two cases from our institution. Clinical, pathological, molecular, and treatment-related data were collected and analyzed. Descriptive statistics and Kaplan-Meier survival analysis were employed to evaluate disease-free survival (DFS) and overall survival (OS). Subgroup analyses explored associations between clinical features, molecular markers, and outcomes. The median age at diagnosis was 64 years, with a predominance of small tumors (mean size: 10.4 mm, T1 stage). Histologically, hallmark features included reversed nuclear polarity (100 %), nuclear grooves, and intranuclear pseudoinclusions. Immunohistochemical analysis confirmed a triple-negative profile (ER-/PR-/HER2-) in most cases, with consistent breast-specific marker expression (GATA3, CK7). Molecular testing revealed frequent IDH2 R172 (84.6 %) and PIK3CA (72.5 %) mutations. Surgical management, predominantly breast-conserving surgery (BCS), was the primary treatment, with adjuvant therapies rarely utilized. At a median follow-up of 35.8 months, recurrence occurred in only 2.2 % of cases, and the overall survival rate was 100 %. TCCRP is a rare, low-grade breast cancer subtype with a favorable prognosis and low recurrence risk based on currently available data, but longer follow-up studies are needed to confirm this observation. Its distinct histological and molecular features enable accurate diagnosis and differentiation from other breast cancers and metastatic thyroid carcinoma. Given its indolent nature, conservative treatment strategies, including BCS, are effective, and adjuvant therapies can be minimized. Future research should explore targeted therapies for IDH2 and PIK3CA mutations to expand treatment options for this unique subtype.
高细胞性极性反转癌（TCCRP）是浸润性乳腺癌中一种罕见且独特的亚型，于2003年首次被描述。其组织学特征为高柱状上皮细胞且核极性反转，与甲状腺乳头状癌（PTC）具有共同的形态学特征。然而，其独特的分子特征，包括异柠檬酸脱氢酶2（IDH2）和磷脂酰肌醇-3激酶催化亚基α（PIK3CA）突变，使其与其他乳腺癌亚型区分开来。对已发表的91例TCCRP病例进行了回顾性系统研究，其中包括我们机构的2例病例。收集并分析了临床、病理、分子及治疗相关数据。采用描述性统计和Kaplan-Meier生存分析来评估无病生存期（DFS）和总生存期（OS）。亚组分析探讨了临床特征、分子标志物与预后之间的关联。诊断时的中位年龄为64岁，以小肿瘤为主（平均大小：10.4毫米，T1期）。组织学上，标志性特征包括核极性反转（100%）、核沟和核内假包涵体。免疫组化分析证实大多数病例为三阴性表型（雌激素受体阴性/孕激素受体阴性/人表皮生长因子受体2阴性），乳腺特异性标志物表达一致（GATA3、细胞角蛋白7）。分子检测显示IDH2 R172突变（84.6%）和PIK3CA突变（72.5%）较为常见。手术治疗，主要是保乳手术（BCS），是主要治疗方式，很少使用辅助治疗。中位随访35.8个月时，仅2.2%的病例出现复发，总生存率为100%。基于现有数据，TCCRP是一种罕见的低级别乳腺癌亚型，预后良好且复发风险低，但需要更长时间的随访研究来证实这一观察结果。其独特的组织学和分子特征有助于准确诊断并与其他乳腺癌及甲状腺转移癌相鉴别。鉴于其惰性本质，包括BCS在内的保守治疗策略是有效的，且可尽量减少辅助治疗。未来的研究应探索针对IDH2和PIK3CA突变的靶向治疗，以扩展针对这种独特亚型乳腺癌的治疗选择。
