Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directions

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 carcin...

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Main Authors: Ye Lu, Xiangyi Kong, Wenxiang Zhang, Xiangyu Wang, Shengbin Pei, Yi Fang, Jidong Gao, Jing Wang
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Breast
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Online Access:http://www.sciencedirect.com/science/article/pii/S0960977625005181
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author Ye Lu
Xiangyi Kong
Wenxiang Zhang
Xiangyu Wang
Shengbin Pei
Yi Fang
Jidong Gao
Jing Wang
author_facet Ye Lu
Xiangyi Kong
Wenxiang Zhang
Xiangyu Wang
Shengbin Pei
Yi Fang
Jidong Gao
Jing Wang
author_sort Ye Lu
collection DOAJ
description 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.
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spelling doaj-art-d96ae81b96db4f6eb47b4d0c9bcf1e1c2025-07-17T04:43:53ZengElsevierBreast1532-30802025-08-0182104501Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directionsYe Lu0Xiangyi Kong1Wenxiang Zhang2Xiangyu Wang3Shengbin Pei4Yi Fang5Jidong Gao6Jing Wang7Department 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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; Corresponding author. 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; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China; Corresponding author. Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, 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; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S0960977625005181Tall Cell Carcinoma with Reversed PolarityTriple-negative breast cancerClinicopathological featuresSurvival outcomesTreatment strategy
spellingShingle Ye Lu
Xiangyi Kong
Wenxiang Zhang
Xiangyu Wang
Shengbin Pei
Yi Fang
Jidong Gao
Jing Wang
Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directions
Breast
Tall Cell Carcinoma with Reversed Polarity
Triple-negative breast cancer
Clinicopathological features
Survival outcomes
Treatment strategy
title Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directions
title_full Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directions
title_fullStr Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directions
title_full_unstemmed Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directions
title_short Tall Cell Carcinoma with Reversed Polarity of the breast: Clinicopathological insights, molecular profile, and future therapeutic directions
title_sort tall cell carcinoma with reversed polarity of the breast clinicopathological insights molecular profile and future therapeutic directions
topic Tall Cell Carcinoma with Reversed Polarity
Triple-negative breast cancer
Clinicopathological features
Survival outcomes
Treatment strategy
url http://www.sciencedirect.com/science/article/pii/S0960977625005181
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