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Hong R, Wang H, Lin Y, Yin X, Fang J, Pang J, Chen L, Wu H, Liang Z. The clinicopathological and molecular features of primary high-grade neuroendocrine tumour in the breast. Histopathology 2025; 86:900-915. [PMID: 39688109 DOI: 10.1111/his.15398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 09/17/2024] [Accepted: 11/30/2024] [Indexed: 12/18/2024]
Abstract
AIMS Nottingham grade for breast cancers, rather than gastro-entero-pancreatic (GEP) grade for neuroendocrine tumours (NETs), is currently applied to primary breast NETs, which need further clarification. High-grade NETs in breast also remain poorly recognised. METHODS AND RESULTS Among 595 breast carcinomas with diffuse synaptophysin (Syn) or chromogranin A (CgA) immunostaining (≥ 90%), 197 eligible cases were selected, including 69 NETs, 123 invasive breast carcinomas of no special type (IBC-NSTs) and five neuroendocrine carcinomas (NECs). The prognostic significance of these two grading systems in breast NETs was assessed. Furthermore, the clinicopathological features were compared in Nottingham G3 cases among three entities. Targeted sequencing and immunostaining (INSM1/p53/Rb/p16) were also performed in all Nottingham G3 NETs, NECs and 10 Nottingham G3 IBC-NSTs. All Nottingham G3 NETs (9 of 69, 13.0%) fell into GEP G3 cases (20 of 69, 29.0%). Nottingham grade provided better prognostic discrimination between G1/G2 and G3 NETs than GEP grade. Among Nottingham G3 cases, there was a trend towards reduced progression-free survival (PFS) in NETs compared with IBC-NSTs (P = 0.057), and the former were more often immunoreactive for INSM1 (44.4 versus 0%, P = 0.033). Nottingham G3 NETs were all of luminal-like phenotype (P < 0.001) and exhibited less aberrant p53 patterns (11.1 versus 80.0%, P = 0.023) as well as more favourable PFS (P = 0.012) and disease-specific survival (P = 0.002) than NECs. Rb loss (4 of 5, 80%), p16 overexpression (5 of 5, 100%) and RB1 mutation (2 of 5, 40%) were observed exclusively in NECs. Based on expression data, epithelial-mesenchymal transition and KRAS signalling pathways were significantly up-regulated in Nottingham G3 NETs (P < 0.05). CONCLUSIONS Nottingham grade, rather than GEP grade, holds important prognostic significance in primary breast NETs. Nottingham G3 NETs represent a small proportion of breast NETs, and may demonstrate distinct clinicopathological and molecular features from other high-grade breast carcinomas with diffuse neuroendocrine markers expression.
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Affiliation(s)
- Ruping Hong
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Hao Wang
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yan Lin
- Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xianglin Yin
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jiuyuan Fang
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Junyi Pang
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Longyun Chen
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Huanwen Wu
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Zhiyong Liang
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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Hickey K, Yaremko H, Orr C, Pace D. Neuroendocrine Breast Cancer-Associated Ectopic Adrenocorticotropic Hormone Syndrome Requiring Bilateral Adrenalectomy. Curr Oncol 2025; 32:205. [PMID: 40277762 PMCID: PMC12026433 DOI: 10.3390/curroncol32040205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/16/2025] [Accepted: 03/24/2025] [Indexed: 04/26/2025] Open
Abstract
Ectopic adrenocorticotropic hormone syndrome (EAS) occurs when a tumor develops neuroendocrine differentiation with the secretion of ACTH resulting in hypercortisolism and possibly Cushing's syndrome (CS). Only 5-10% of CS cases are attributed to EAS; of these, breast tumors comprise less than 1%. Two known variants of breast neuroendocrine tumors include neuroendocrine-differentiated carcinoma and ductal carcinoma with neuroendocrine features. Currently, guidelines for treatment are limited and EAS is associated with significant morbidity and mortality. A 39-year-old female presented with a rapidly enlarging breast mass. Biopsy demonstrated invasive poorly differentiated breast carcinoma with high-grade neuroendocrine features and necrosis. Staging at diagnosis confirmed metastatic disease of the liver and bone. First-line chemotherapy (Cisplatin/Etoposide/Durvalumab) was initiated with evidence of disease progression after four cycles. Given a poor response to therapy, a simple mastectomy was performed for local control and complete pathologic analysis, demonstrating high-grade neuroendocrine carcinoma with large-cell features. Second-line therapy (Adriamycin/Cyclophosphamide) was initiated for three cycles after which the patient required admission for severe and refractory hypokalemia. Workup confirmed elevated ACTH consistent with paraneoplastic EAS and further evidence of disease progression. Third-line therapy (Nab-Paclitaxel) was initiated, and genetic testing was completed, confirming the PIK3 mutation, for which access to Alpelisib therapy was requested. Given symptoms of progressive severe CS with significant liver disease limiting medical therapies, the patient underwent urgent bilateral laparoscopic adrenalectomy after which she was able to be discharged home while awaiting additional systemic therapy. EAS resulting in CS secondary to breast neuroendocrine carcinoma is a rare and challenging diagnosis. Further research is needed to inform treatment guidelines to improve outcomes. While patient survival is dependent upon the underlying disease process, laparoscopic bilateral adrenalectomy is an accepted, definitive treatment option.
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Affiliation(s)
- Kala Hickey
- Department of General Surgery, Faculty of Medicine, Memorial University, St. John’s, NL A1B 3V6, Canada
| | - Hannah Yaremko
- Faculty of Medicine, Memorial University, St. John’s, NL A1B 3V6, Canada
| | - Christine Orr
- Department of Medicine, Faculty of Medicine, Memorial University, St. John’s, NL A1B 3V6, Canada
| | - David Pace
- Department of General Surgery, Faculty of Medicine, Memorial University, St. John’s, NL A1B 3V6, Canada
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Sağdıç MF, Özaslan C. Rare Histological Types of Breast Cancer: A Single-Center Experience. Breast J 2025; 2025:1179914. [PMID: 40224949 PMCID: PMC11991780 DOI: 10.1155/tbj/1179914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 02/21/2025] [Indexed: 04/15/2025]
Abstract
Background: Breast carcinoma is divided into at least 21 separate histologies, according to the 2019 World Health Organization (WHO) classification. The present study is dedicated to a 5% or rarer group of all breast cancer cases. Method: In this study, we retrospectively considered the data of 4550 patients operated on for breast carcinoma at the Ankara Oncology Training and Research Hospital of the University of Health Sciences between January 2018 and February 2024. Of those cases, 401 were discovered to have rare breast cancer types. We also explored the cases by clinicopathological features, overall survival (OS), and disease-free survival (DFS). Results: Our findings revealed a total of 10 rare breast cancer types in patients explored: mucinous carcinoma, micropapillary carcinoma, papillary group carcinomas, metaplastic carcinoma, neuroendocrine carcinoma, tubular carcinoma, cribriform carcinoma, apocrine carcinoma, acinic cell carcinoma, and secretory carcinoma. While mucinous, tubular, cribriform, papillary group carcinomas, micropapillary, and secretory carcinomas are described as types associated with good prognosis, metaplastic, neuroendocrine, apocrine, and carcinomas are described as types associated with relatively poor prognosis. Conclusion: Scrutinizing the clinicopathological features of rare breast cancer types altogether may be the distinct contribution of this paper to the relevant literature and future research.
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Affiliation(s)
| | - Cihangir Özaslan
- Department of Surgical Oncology, University of Health Sciences Ankara Oncology Training and Research Hospital, Ankara, Turkey
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Di Rito A, Grillo A, Carbonara R. Therapeutic Management in Elderly Male Breast Cancer Patients: A Scoping Review. Curr Oncol Rep 2025; 27:120-134. [PMID: 39826033 DOI: 10.1007/s11912-024-01629-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/20/2025]
Abstract
PURPOSE OF REVIEW Male breast cancer (MBC) is a rare entity which often arises in elderly people. Aim of this review is to evaluate the principal issues related to MBC in elderly, because the therapeutic management of disease is not only related to the biological behavior of the tumor, but also to the comorbidities and frailty of older population. A scoping literature review was performed on Pubmed and Cochrane Database using the following keywords: therapeutic management/ male/ breast cancer/ elderly patients. Papers published before 2000, not edited in English or French language, or not related to the main topic, were excluded. Only articles related to therapeutic issues in MBC and including more than 10 elderly (≥ 65 years) patients were selected for the qualitative outcome analysis. RECENT FINDINGS 36 papers regarding surgery, radiotherapy, systemic therapy, racial disparities and therapeutic management in retrospective series of MBC in elderly were examined in details. MBC has a different biological behavior and a poorer prognosis than female, especially in cases with positive nodes at diagnosis. Elderly MBC patients have often larger tumors in more advanced stages at the time of diagnosis compared with younger patients. In spite of the advanced tumors at presentation, older patients present often cancers with more favorable biological characteristics, but they receive less guideline-concordant curative treatments (as adequate lymph node staging or adjuvant radiation therapy) compared to women. Moreover, racial differences in treatment of older MBC were observed. Therapeutic management of MBC in elderly patients is a subject rarely addressed in literature. Our review highlighted differences in the treatment and in guidelines-concordance for elderly MBC patients. Adequate geriatric assessment and use of therapeutic schemes adapted to age and comorbidities can avoid under/overtreatment, contributing to a better standard of care in this frail population.
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Affiliation(s)
- Alessia Di Rito
- Radiotherapy Unit, Hospital Mons. A.R. Dimiccoli, Barletta, Italy.
| | - Antonietta Grillo
- Radiotherapy Unit, Azienda Ospedaliero Universitaria Policlinico Di Bari, Bari, Italy
| | - Roberta Carbonara
- Radiation Oncology Department, General Regional Hospital "F.Miulli", Acquaviva Delle Fonti, Bari, Italy
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5
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Ju H, Liu M. Primary neuroendocrine tumor of the breast: A case report. Oncol Lett 2025; 29:79. [PMID: 39655273 PMCID: PMC11626422 DOI: 10.3892/ol.2024.14825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 10/18/2024] [Indexed: 12/12/2024] Open
Abstract
Primary neuroendocrine neoplasm of the breast (PNENB) is a rare subtype of breast cancer, accounting for <1% of all breast tumors. The morphological features of PNENB are similar to those of neuroendocrine tumors originating in the lungs or gastrointestinal system, with tumor cells exhibiting the strong expression of neuroendocrine markers, including chromogranin A and synaptophysin. Since this type of cancer was first reported, the definition, classification and diagnostic criteria of PNENB have evolved and changed. However, accurate diagnostic criteria and standard treatment guidelines are lacking. The present report describes a specific case of PNENB, which was consistent with the morphological and molecular features of other cases in most previous studies. In addition, the current body of literature on PNENB, including its development, diagnosis, molecular features, treatment and prognosis is reviewed.
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Affiliation(s)
- Husileng Ju
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010059, P.R. China
| | - Ming Liu
- Department of Thyroid and Breast Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010059, P.R. China
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Jeon Y, Kim JY, Ahn JS, Im YH, Choi K, Jeong SY, Jung Y, Jang J, Choi DH, Hong J, Kim HJ, Cho SY, Park YH. Breast cancers with neuroendocrine differentiation: Retrospective case studies series from a single institution based on the 2019 WHO classification. Cancer Treat Res Commun 2024; 42:100857. [PMID: 39719737 DOI: 10.1016/j.ctarc.2024.100857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 11/20/2024] [Accepted: 12/04/2024] [Indexed: 12/26/2024]
Abstract
BACKGROUND The World Health Organization's fifth edition of tumor series classification was published in 2019 and adopted the term 'Neuroendocrine neoplasm (NEN)' to encompass all tumor classes with predominant neuroendocrine differentiation (NED). Based on the updated classification of the NEN, we conducted a case series using the Clinical Data Warehouse platform of SMC. METHODS In this retrospective study, breast NENs and invasive breast carcinomas no special type (IBCNST) with NED, were defined as 'NENS'. Based on pathology slide findings, a pathologist reclassified the diagnoses. Clinical presentation, tumor characteristics, and clinical outcomes of breast 'NENS' were reviewed retrospectively. RESULTS A total of 34,370 patients were diagnosed with breast cancer from 1995 to 2022 in SMC, and 14 (0.04 %) patients were diagnosed with breast 'NENS': eight NECs, three NETs, and three IBCNST with NED. The patients' median age was 48.5 years. All patients were treated with curative intent surgery; five patients received neoadjuvant chemotherapy, twelve patients received radiotherapy, six patients received adjuvant chemotherapy, and eight patients received hormone therapy. The median follow-up period for the eight patients with breast NEC was 20.4 months. The median disease-free and overall survival were 14.2 months and 23.6 months, respectively. Patients with NET or IBCNST with NED (n = 6) had an overall favorable outcome, with no deaths, with only one case of disease recurrence. CONCLUSION The incidence of primary breast NENS' was very low (0.04 %) in this single-center study. Among them, primary breast NEC was associated with poor overall survival. Novel treatments are thus required to improve the prognosis of primary breast NEC.
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Affiliation(s)
- Youngkyung Jeon
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Medical Oncology and Hematology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea
| | - Ji-Yeon Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jin Seok Ahn
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young-Hyuck Im
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyuehee Choi
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sun Young Jeong
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yeji Jung
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jaeyeon Jang
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dae-Ho Choi
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joohyun Hong
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyo Jung Kim
- Department of Digital Health, Samsung Advanced Institute for Health Science & Technology, Sungkyunkwan University, Seoul, Republic of Korea; Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Soo Youn Cho
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yeon Hee Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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7
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Song B, Singh H. Rare Breast Cancers Review. Healthcare (Basel) 2024; 12:2483. [PMID: 39685105 DOI: 10.3390/healthcare12232483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/24/2024] [Accepted: 11/17/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES Breast cancer is one of the most common malignancies in women, with rare subtypes presenting unique clinical challenges. This review provides a comprehensive analysis of rare breast cancers, including both epithelial and non-epithelial subtypes, and explores their epidemiology, pathology, prognosis, and treatment approaches. METHODS A systematic review was conducted focusing on recent advancements in the treatment of rare breast cancer subtypes. Articles were selected based on criteria emphasizing studies from the past five years, with older foundational studies included where necessary. The analysis incorporated molecular profiling, clinical trials, and advancements in targeted and immunotherapies, where possible. RESULTS Rare epithelial subtypes, such as tubular, mucinous, and medullary carcinomas, demonstrate distinct clinical and pathological features, with generally favorable prognoses compared to invasive ductal carcinoma (IDC). Non-epithelial cancers, including sarcomas and primary breast lymphomas, require individualized treatment due to aggressive behavior and poor prognosis in certain cases. Recent advancements in targeted therapies (e.g., HER2 inhibitors, PI3K inhibitors, and PARP inhibitors) and immunotherapies (e.g., PD-1 inhibitors) have shown promise in improving outcomes for specific molecularly characterized subtypes. CONCLUSIONS While the management of common breast cancers has become increasingly sophisticated, rare subtypes continue to pose challenges due to limited research and small patient populations. Advances in molecular profiling and next-generation sequencing are pivotal in identifying actionable mutations and expanding personalized treatment options. Future research should focus on clinical trials and collaborative efforts to refine treatment strategies and improve outcomes for these rare subtypes.
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Affiliation(s)
- Bowen Song
- Department of Diagnostic and Interventional Imaging, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Harnoor Singh
- Department of Diagnostic and Interventional Imaging, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
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8
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Cuevas A, Khattak F. Primary Neuroendocrine Tumor of the Breast: A Case Report and Review of Current Guidelines. Cureus 2024; 16:e73151. [PMID: 39651006 PMCID: PMC11623784 DOI: 10.7759/cureus.73151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2024] [Indexed: 12/11/2024] Open
Abstract
Primary neuroendocrine tumor of the breast is a rare subtype of breast carcinoma that most commonly affects postmenopausal women in their sixth or seventh decade of life. We report a case of a 52-year-old female who presented to our clinic with concerns about a self-palpable mass involving her left breast that had not been detected on a routine mammogram five months prior. Upon clinical exam and diagnostic workup comprising imaging, a tissue biopsy, and immunostaining, she was found to have primary high-grade neuroendocrine carcinoma of the breast with necrosis. Subsequently, management of her case involved a first-line systemic chemotherapy regimen, including carboplatin with etoposide and atezolizumab. Less than two months after beginning therapy, she had undergone three cycles but did not show any significant clinical response, requiring further workup. This case demonstrates the challenges faced with treating such a rare subtype of breast carcinoma and the necessity of documenting other similar cases for improved understanding and patient outcomes.
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Affiliation(s)
- Abigail Cuevas
- College of Medicine, University of Illinois at Chicago, Rockford, USA
| | - Fauzia Khattak
- Medical Oncology, UW (University of Wisconsin) Health, Rockford, USA
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9
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Zhang B, Huang F, Guo S, Wu D, Xiao X, Zhang T. Primary Large-Cell Neuroendocrine Carcinoma of the Breast. Diagnostics (Basel) 2024; 14:2347. [PMID: 39518315 PMCID: PMC11544942 DOI: 10.3390/diagnostics14212347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 09/30/2024] [Accepted: 10/11/2024] [Indexed: 11/16/2024] Open
Abstract
Breast neuroendocrine carcinoma (NECB) is a rare type of breast tumor. Large-cell neuroendocrine carcinomas of the breast (LCNECB) are a special and rare histological subtype of NECB. Here, we present a case of a 59-year-old woman who was diagnosed with an LCNECB. A mass in the upper outer quadrant of the right breast was revealed via imaging. A histological examination showed the tumor cells were composed of clusters of large cells with obvious atypia that were polygonal or irregularly shaped. The patient underwent a right-breast-conserving radical surgery and sentinel lymph node biopsy (SLB). A histopathological examination revealed that the tumor of the right breast was 2.5 × 2 cm in size with vascular invasion, and the sentinel lymph node was negative. The immunohistochemical results showed that the tumor cells were diffuse and positive for chromogranin A (CgA), synaptophysin (Syn), and INSM1. The patient successfully completed chemotherapy and radiotherapy and is currently undergoing endocrine therapy.
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Affiliation(s)
- Bicheng Zhang
- Department of Radiation Oncology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China; (B.Z.)
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Fengbo Huang
- Department of Pathology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China
| | - Siyu Guo
- Department of Radiation Oncology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China; (B.Z.)
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Dang Wu
- Department of Radiation Oncology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China; (B.Z.)
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Xiaofang Xiao
- Department of Medical Oncology, The Fourth Affiliated Hospital of Zhejiang University, School of Medicine, Yiwu 322000, China;
| | - Ting Zhang
- Department of Radiation Oncology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China; (B.Z.)
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
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10
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Usul G, Kelten Talu EC, Yılmaz İ, Issın GN, Bektaş S, Can Trabulus D. The Association of Neuroendocrine Differentiation with MicroRNA 21 and MicroRNA let7f Expression and the Clinicopathological Parameters in Primary Invasive Breast Carcinomas with Neuroendocrine Features. Diagnostics (Basel) 2024; 14:2211. [PMID: 39410615 PMCID: PMC11475674 DOI: 10.3390/diagnostics14192211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/26/2024] [Accepted: 09/30/2024] [Indexed: 10/20/2024] Open
Abstract
MiRNAs have been reported as biomarkers with diagnostic, prognostic, and predictive value for many different diseases. Therapeutic agents targeting some miRNAs are currently being developed. We aimed to compare BC-NEFs (carcinoma of the breast with neuroendocrine features) with IDC (invasive ductal carcinoma) cases without neuroendocrine features in terms of the level of miRNA expression known to show the oncogenic (miR-21) and tumor-suppressor effects (miR-let7f) and the clinicopathological features. A total of 29 patients with a diagnosis of BC-NEFs (15 cases with neuroendocrine differentiation >50% of the whole section of tumor and 14 cases with neuroendocrine differentiation 10-50% of the tumor) and 30 patients with a diagnosis of IDC (no neuroendocrine differentiation) were retrospectively re-evaluated. Expression levels of miR-21 and miR-let7f were determined by the qRT-PCR method in paraffin tissue blocks. MiR-21 expression was significantly higher in the IDC group than in the group with BC-NEFs. miR-let7f expression was significantly lower in the group with BC-NEFs compared to the IDC group. A high expression level of miR-21 was found to be associated with progesterone receptor (PR) negativity. Our findings show that the presence of NEFs in breast carcinomas makes a significant difference in the expression levels of the investigated oncogenic (miR-21) and tumor-suppressor (miR-let7f) miRNAs. These findings suggest that miRNAs may be a potential biomarker in BC-NEFs and would benefit from targeted therapy.
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Affiliation(s)
- Gamze Usul
- Department of Pathology, Istanbul Training and Research Hospital, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul 34098, Türkiye
| | - Esra Canan Kelten Talu
- Department of Pathology, Istanbul Training and Research Hospital, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul 34098, Türkiye
- Department of Molecular Pathology, Faculty of Medicine, Institute of Health Sciences, Dokuz Eylul University, İzmir 35410, Türkiye
| | - İsmail Yılmaz
- Department of Pathology, Sultan Abdülhamid Han Training and Research Hospital, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul 34668, Türkiye
| | - Gizem Narlı Issın
- Mengücek Gazi Education and Research Hospital, Faculty of Medicine, Binali Yıldırım University, Erzincan 24180, Türkiye
| | - Sibel Bektaş
- Department of Pathology, Gaziosmanpaşa Training and Research Hospital, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul 34255, Türkiye
| | - Didem Can Trabulus
- Department of General Surgery, Istanbul Training and Research Hospital, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul 34098, Türkiye
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11
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Mohamedali R, Nishith N, Raj R, Ahuja N, Sharma A, Somal PK, Pawar RN, Sancheti S. Unveiling Rare Breast Neoplasms: Diagnostic Challenges and Insights. Discoveries (Craiova) 2024; 12:e200. [PMID: 40093349 PMCID: PMC11910015 DOI: 10.15190/d.2024.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/30/2024] [Accepted: 12/30/2024] [Indexed: 03/19/2025] Open
Abstract
Breast neoplasm encompasses a diversified range of different diseases characterized by unique biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. The histological variability has profound prognostic implications, thus playing a pivotal role in diagnosing breast neoplasm. Special histologies can occur rarely, and most information on outcomes and treatments is mainly derived from small series and case reports. Thus, reporting such unusual occurrences is of utmost importance. This is a retrospective study of four years in which 11 cases of breast neoplasm diagnosed on histopathology were assessed. The clinical details were acquired from an electronic search. The hematoxylin and eosin and immunohistochemistry slides were retrieved from the archives to review the histopathological features. The patient's age ranged from 32 to 72 years (median: 51 years). Eleven unusual cases of breast neoplasms were diagnosed and categorized according to the latest World Health Organisation (WHO) classification. These cases include rare and salivary gland type tumors (2 cases), neuroendocrine neoplasms (1 case), hamartomas of the breast (2 cases), fibroblastic and myofibroblastic tumors of the breast (1 case), peripheral nerve sheath tumor (1 case) and hematolymphoid tumors of the breast (4 cases). The management of unusual breast cancer histotypes represents a real challenge in daily clinical practice. Our data suggest that these variants are distinct clinicopathological entities with unique hormonal receptor statuses. The occurrence of such entities is rare, and they demonstrate different clinical behaviors and responses to treatment, suggesting that a few genomic-specific events might also drive them. Therefore, it is important to indulge in future research on such rare breast neoplasms.
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Affiliation(s)
- Rasheeda Mohamedali
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
| | - Nilay Nishith
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
| | - Rahul Raj
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
| | - Nishtha Ahuja
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
| | - Aishwarya Sharma
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
| | - Puneet Kaur Somal
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
| | - Ravikiran N Pawar
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
| | - Sankalp Sancheti
- Department of Pathology, Homi Bhabha Cancer Hospital and Research Centre, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), New Chandigarh, Punjab, India
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12
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Vegni F, De Stefano IS, Policardo F, Tralongo P, Feraco A, Carlino A, Ferraro G, Zhang Q, Scaglione G, D'Alessandris N, Navarra E, Zannoni G, Santoro A, Mule A, Rossi ED. Neuroendocrine neoplasms of the breast: a review of literature. Virchows Arch 2024; 485:197-212. [PMID: 38980337 PMCID: PMC11329594 DOI: 10.1007/s00428-024-03856-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 06/14/2024] [Accepted: 06/18/2024] [Indexed: 07/10/2024]
Abstract
Primary neuroendocrine neoplasms (NENs) of the breast are characterized by neuroendocrine architectural and cytological features, which must be supported by immunohistochemical positivity for neuroendocrine markers (such as Chromogranin and Synaptophysin). According to the literature, making a diagnosis of primary neuroendocrine breast cancer always needs to rule out a possible primary neuroendocrine neoplasm from another site. Currently, the latest 2022 version of the WHO of endocrine and neuroendocrine neoplasms has classified breast NENs as well-differentiated neuroendocrine tumours (NETs) and aggressive neuroendocrine carcinomas (NECs), differentiating them from invasive breast cancers of no special type (IBCs-NST). with neuroendocrine features. The current review article describes six cases from our series and a comprehensive review of the literature in the field of NENs of the breast.
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Affiliation(s)
- Federica Vegni
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Ilenia Sara De Stefano
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Federica Policardo
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Pietro Tralongo
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Angela Feraco
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Angela Carlino
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Giulia Ferraro
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Qianqian Zhang
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Giulia Scaglione
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Nicoletta D'Alessandris
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Elena Navarra
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Gianfranco Zannoni
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Angela Santoro
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Antonino Mule
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Esther Diana Rossi
- Division of Anatomic Pathology and Histology-Fondazione, Policlinico Universitario "Agostino Gemelli"-IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.
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13
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Conti M, Morciano F, Amodeo S, Gori E, Romanucci G, Belli P, Tommasini O, Fornasa F, Rella R. Special Types of Breast Cancer: Clinical Behavior and Radiological Appearance. J Imaging 2024; 10:182. [PMID: 39194971 DOI: 10.3390/jimaging10080182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 07/21/2024] [Accepted: 07/23/2024] [Indexed: 08/29/2024] Open
Abstract
Breast cancer is a complex disease that includes entities with different characteristics, behaviors, and responses to treatment. Breast cancers are categorized into subgroups based on histological type and grade, and these subgroups affect clinical presentation and oncological outcomes. The subgroup of "special types" encompasses all those breast cancers with insufficient features to belong to the subgroup "invasive ductal carcinoma not otherwise specified". These cancers account for around 25% of all cases, some of them having a relatively good prognosis despite high histological grade. The purpose of this paper is to review and illustrate the radiological appearance of each special type, highlighting insights and pitfalls to guide breast radiologists in their routine work.
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Affiliation(s)
- Marco Conti
- UOC di Radiologia Toracica e Cardiovascolare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - Francesca Morciano
- Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
| | - Silvia Amodeo
- Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
| | - Elisabetta Gori
- Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
| | - Giovanna Romanucci
- UOSD Breast Unit ULSS9, Ospedale di Marzana, Piazzale Lambranzi 1, 37142 Verona, Italy
| | - Paolo Belli
- UOC di Radiologia Toracica e Cardiovascolare, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
- Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
| | - Oscar Tommasini
- UOC Diagnostica per Immagini, Dipartimento Emergenza e Accettazione, Ospedale G.B. Grassi, Via Gian Carlo Passeroni, 28, 00122 Rome, Italy
| | - Francesca Fornasa
- UOSD Breast Unit ULSS9, Ospedale di Marzana, Piazzale Lambranzi 1, 37142 Verona, Italy
| | - Rossella Rella
- UOC Diagnostica per Immagini, Dipartimento Emergenza e Accettazione, Ospedale G.B. Grassi, Via Gian Carlo Passeroni, 28, 00122 Rome, Italy
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14
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Peng L, Ma M, Zhao D, Zhao J, Sun Q, Mao F. Comparison of clinical characteristics and outcomes in primary neuroendocrine breast carcinoma versus invasive ductal carcinoma. Front Oncol 2024; 14:1291034. [PMID: 38800403 PMCID: PMC11116559 DOI: 10.3389/fonc.2024.1291034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 04/22/2024] [Indexed: 05/29/2024] Open
Abstract
Background Neuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion. Methods We conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis. Results A total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5 cm (36.5%) and >5 cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P<0.001) and HER2-negative (90.5% versus 76.4%, P=0.001) expression statuses among these patients. Of 121 primary NECB patients, 11 (9.1%) experienced relapses during the follow-up period. We found that tumor size was an independent risk factor for relapse. For hormone receptors on tumor cells, ER-positive breast cancer patients had significantly lower odds of relapse than receptor-negative patients. Conclusions Our data demonstrate no significant difference in mortality and relapse between the primary NECB and NST groups. The tumor size in the primary NECB group was significantly larger than that in the NST group. In addition, the absence of ER independently increased the relapse rate for breast carcinoma patients.
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Affiliation(s)
- Li Peng
- Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Mingwei Ma
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Dachun Zhao
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jialin Zhao
- Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Qiang Sun
- Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Feng Mao
- Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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Püsküllüoğlu M, Grela-Wojewoda A, Ambicka A, Pacholczak-Madej R, Pietruszka A, Mucha-Małecka A, Rudzińska A, Ziobro M, Ryś J, Mituś JW. Non-metastatic primary neuroendocrine neoplasms of the breast: a reference cancer center's experience of a heterogenous entity. Front Endocrinol (Lausanne) 2024; 15:1217495. [PMID: 38800480 PMCID: PMC11116701 DOI: 10.3389/fendo.2024.1217495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 04/16/2024] [Indexed: 05/29/2024] Open
Abstract
Background Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. Methods The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. Results We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Conclusion Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.
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Affiliation(s)
- Mirosława Püsküllüoğlu
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Aleksandra Grela-Wojewoda
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Aleksandra Ambicka
- Department of Tumour Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Renata Pacholczak-Madej
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
- Department of Anatomy, Jagiellonian University Medical College, Kraków, Poland
| | - Agnieszka Pietruszka
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Anna Mucha-Małecka
- Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków Branch, Kraków, Poland
| | - Agnieszka Rudzińska
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Marek Ziobro
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Janusz Ryś
- Department of Tumour Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
| | - Jerzy W. Mituś
- Department of Anatomy, Jagiellonian University Medical College, Kraków, Poland
- Department of Surgical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland
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16
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Mohamed A, Zeidalkilani J, Asa SL, Trybula M, Montero AJ. Management of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature. Oncol Rev 2024; 18:12114. [PMID: 38404967 PMCID: PMC10884130 DOI: 10.3389/or.2024.12114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 01/15/2024] [Indexed: 02/27/2024] Open
Abstract
Extra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare tumors that usually arise in the gastrointestinal and genitourinary tracts. Primary neuroendocrine carcinoma of the breast (NEBC) is extremely rare, representing less than 0.1% of all breast cancers and less than 1% of neuroendocrine neoplasms. Consequently, they can be misdiagnosed as other types of breast cancer, however, proper immunohistochemical (IHC) studies can assist with making the correct diagnosis. Management of NEBC can be challenging given the paucity of evidence-based literature and should not routinely follow the therapeutic guidelines of other breast cancers. In this article, we review the current literature regarding the management of NEBC.
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Affiliation(s)
- A. Mohamed
- Division of Hematology and Medical Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
| | - J. Zeidalkilani
- Department of Medicine, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
| | - S. L. Asa
- Department of Pathology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States
| | - M. Trybula
- Division of Hematology and Medical Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
| | - Alberto J. Montero
- Division of Hematology and Medical Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
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17
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Amsiguine N, Essaber H, Elbakkari A, Allioui S, Jerguigue H, Omor Y, Latib R. Neuroendocrine breast carcinoma: The importance of the correlation between histological and radiological findings. Radiol Case Rep 2024; 19:489-492. [PMID: 38046918 PMCID: PMC10692488 DOI: 10.1016/j.radcr.2023.10.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 10/12/2023] [Accepted: 10/19/2023] [Indexed: 12/05/2023] Open
Abstract
Neuroendocrine breast carcinoma (NEBC) is an uncommon and malignant breast lesion. The absence of proper testing for this type of breast cancer carcinoma exacerbates this paucity. Additionally, only scant evidence of these tumors is present because of the repeated revisions in their diagnostic criteria throughout time. This case report highlights the importance of the correlation between histological and radiological findings in the diagnosis and treatment of neuroendocrine breast cancer. We describe the clinical, radiological, and histological characteristics of a patient diagnosed with neuroendocrine carcinoma. The breast parenchyma was penetrated by a carcinomatous tumor growth that contained trabeculae and lobules, exhibiting mild cytonuclear atypia, and having a low mitotic index. This report emphasizes the value of a multidisciplinary strategy for precise diagnosis and treatment planning.
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Affiliation(s)
- Najwa Amsiguine
- Radiology Department, National Institute of Oncology, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
| | - Hatim Essaber
- Radiology Department, National Institute of Oncology, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
| | - Assaad Elbakkari
- Radiology Department, National Institute of Oncology, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
| | - Soukaina Allioui
- Radiology Department, National Institute of Oncology, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
| | - Hounaida Jerguigue
- Radiology Department, National Institute of Oncology, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
| | - Youssef Omor
- Radiology Department, National Institute of Oncology, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
| | - Rachida Latib
- Radiology Department, National Institute of Oncology, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
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18
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Xia C, Shen S, Pang J, Chen L, Yan J, Liang Z, Ren X. Expression of neuroendocrine markers predicts increased survival in triple-negative breast cancer patients. Front Endocrinol (Lausanne) 2023; 14:1205631. [PMID: 38125789 PMCID: PMC10731013 DOI: 10.3389/fendo.2023.1205631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 11/20/2023] [Indexed: 12/23/2023] Open
Abstract
Background The significance of neuroendocrine (NE) markers in triple-negative breast cancer (TNBC) patients has not been investigated. This study aims to clarify the incidence and prognostic significance of NE marker expression in TNBC, determine its association with other clinicopathological parameters, and further explore the pathological features and potential treatment options for TNBC patients expressing NE markers. Methods Clinicopathological data were collected from 396 TNBC patients undergoing radical breast cancer surgery at Peking Union Medical College Hospital from January 2002 to December 2014, with a final follow-up in July 2019. Immunohistochemistry (IHC) staining was performed for NE markers including chromogranin A (CgA) and synaptophysin (Syn). For TNBC patients with positive NE marker expression, IHC staining was then performed for alpha-thalassemia/mental retardation X-linked (ATRX), O(6)-methylguanine-methyltransferase (MGMT), somatostatin receptor 2 (SSTR2), and programmed death receptor-ligand 1 (PD-L1). The chi-square or Fisher exact test was used to evaluate the correlations between NE marker expression and other parameters. Survival curves were plotted using the Kaplan-Meier (K-M) method to assess the prognostic significance of NE markers in TNBC. Results NE marker-positive staining was observed in 7.6% (30/396) of all TNBC cases. Only 0.5% (2/396) cases had ≥ 90% neoplastic cells expressing NE markers. Positive NE marker expression was associated with negative basal-like marker expression. K-M survival analysis showed that the NE marker-positive TNBC patients had higher disease-free survival (DFS) rates than the NE marker-negative patients at the same stage. Among the 30 NE marker-positive TNBC cases, 13.3% and 26.7% showed negative IHC staining for ATRX and MGMT, respectively, while 13.3% had a 3+ score for SSTR2 IHC staining. For PD-L1 IHC staining, 13.3% of the 30 TNBC cases were higher than 10 scores in Combined Positive Score (CPS), and 10.0% were higher than 10% in Tumor Cell Proportion Score (TPS). Conclusion There was a small proportion of TNBC patients expressing NE markers. TNBC patients with positive NE marker expression had a better prognosis than the negative group at the same stage. TNBC cases with positive NE marker expression may potentially benefit from immunotherapy or somatostatin analogue treatment.
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Affiliation(s)
- Chuan Xia
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
| | - Songjie Shen
- Department of Breast Surgery, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
| | - Junyi Pang
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
| | - Longyun Chen
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
| | - Jie Yan
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
| | - Zhiyong Liang
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
| | - Xinyu Ren
- Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
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19
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Yang L, Lin H, Shen Y, Roy M, Albarracin C, Ding Q, Huo L, Chen H, Wei B, Bu H, Bedrosian I, Wu Y. Clinical outcome and therapeutic impact on neuroendocrine neoplasms of the breast: a national cancer database study. Breast Cancer Res Treat 2023; 202:23-32. [PMID: 37566192 PMCID: PMC12045006 DOI: 10.1007/s10549-023-07052-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 07/13/2023] [Indexed: 08/12/2023]
Abstract
PURPOSE Neuroendocrine neoplasms (NENs) of the breast are rare and not well-studied. NEN are subcategorized as well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC). The objectives of the current study were to review the clinicopathologic features of NENs, therapeutic efficacy of current systemic therapy and clinical outcomes of NEN of the breast. METHODS Between 2004 and 2015, 420 NET, 205 NEC, 146 Adenocarcinoma with NE differentiation (ACNED) and 1,479,520 of invasive carcinoma, not otherwise specified (IC-NOS) of the breast were identified in the National Caner Database. Overall survival was compared among groups using Kaplan-Meier method and Log-rank test. Multivariate analyses were performed to identify prognostic factors. RESULTS After adjusting for other prognostic factors, both NET and NEC of the breast showed significantly worse OS than IC-NOS (HR (95% CI) = 1.41 (1.17, 1.72), p = 0.005 and HR (95% CI) = 2.11 (1.67, 2.67), p < 0.001, respectively). Both NET and NEC benefited from endocrine therapy if the tumors were hormonal receptor positive (median OS for treated with vs without: 125 vs 57 months in NET, not reached vs 29 months in NEC). NEC also benefited from chemotherapy (median OS for treated with vs without: 42 vs 34 months), but not NET. CONCLUSION NEN is a unique pathologic and clinical entity, which has worse clinical outcome compared to IC-NOS of the breast. Current therapeutics used in the treatment of IC-NOS improve, but do not fully mitigate, the poorer prognosis of NEN patients. More effective therapy for patients with this unique tumor type are needed.
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Affiliation(s)
- Libo Yang
- Departments of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Heather Lin
- Departments of Biostatistics, Unit 1411, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Yu Shen
- Departments of Biostatistics, Unit 1411, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Madhuchhanda Roy
- Departments of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
- Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA
| | - Constance Albarracin
- Departments of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Qingqing Ding
- Departments of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Lei Huo
- Departments of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Hui Chen
- Departments of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Bing Wei
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Bu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Isabelle Bedrosian
- Departments of Breast Surgical Oncology, Unit 1434, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Yun Wu
- Departments of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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20
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Xia L, Lai J, Liu X, Kong F, Qiu S, Hu H, Zhu S, Cao J. Epidemiological and survival outcomes of neuroendocrine carcinoma of the breast: a SEER data analysis. Transl Cancer Res 2023; 12:1951-1962. [PMID: 37701099 PMCID: PMC10493786 DOI: 10.21037/tcr-23-368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 08/01/2023] [Indexed: 09/14/2023]
Abstract
BACKGROUND Neuroendocrine carcinoma of the breast (NECB) is a rare subtype of breast cancer, comprising only 0.1% to 5% of all breast cancer cases. Despite its rarity, it is important to gain a better understanding of the epidemiological, clinical, and prognostic features of NECB. The purpose of the study was to obtain population-based evaluations of the epidemiological and survival outcomes of NECB. METHODS The data of patients with neuroendocrine carcinoma diagnosed and enrolled between 2000 and 2017 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive statistical analyses were used to assess the distribution and tumor-related characteristics of these patients. Kaplan-Meier curves and univariate and multivariate Cox proportional risk models were used to analyze variables that might be associated with prognosis. RESULTS This study included 7,856 patients with neuroendocrine carcinoma. The median age of the patients was 64 years, and most of them were female, White, and diagnosed at ≥60 years old. The most common pathological type was neoplasm. Survival analysis indicated that there were significant differences in age, marital status, registration location, American Joint Committee on Cancer (AJCC) stage, breast subtype, surgery of primary tumor, and no cancer cause surgery patients with NECB. The results also indicated that treatment with surgery, including surgery of primary tumor, surgery combined with radiation, and no cancer cause surgery, were all effective in improving the prognosis compared with not providing surgical treatment. CONCLUSIONS In conclusion, NECB is a very rare lesion for which age, marital status, registration location, and surgery, AJCC stage, breast subtype were found to be independent prognostic factors.
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Affiliation(s)
- Longjie Xia
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People’s Hospital, Guangzhou, China
| | - Jianqin Lai
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People’s Hospital, Guangzhou, China
| | - Xiangxia Liu
- Department of Plastic Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Fanbiao Kong
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of Colorectal and Anal Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
- Institute of Minimally Invasive Technology and Applications Guangxi Academy of Medical Science, Nanning, China
| | - Shenghui Qiu
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People’s Hospital, Guangzhou, China
| | - Huiqiong Hu
- Department of General Surgery, Guangzhou First People’s Hospital, Guangzhou, China
| | - Shaoliang Zhu
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, Nanning, China
| | - Jie Cao
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of General Surgery, Guangzhou First People’s Hospital, Guangzhou, China
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21
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Rechsteiner A, Dietrich D, Varga Z. Prognostic relevance of mixed histological subtypes in invasive breast carcinoma: a retrospective analysis. J Cancer Res Clin Oncol 2023; 149:4967-4978. [PMID: 36310301 PMCID: PMC10349769 DOI: 10.1007/s00432-022-04443-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 10/19/2022] [Indexed: 11/06/2022]
Abstract
PURPOSE The prognostic and therapeutic power of special histological subtypes in breast cancer in pure form or in combination with other histological subtypes is still not established, and diagnostic guidelines are cautious regarding prognostic power based on the histological subtype alone. Therapy decisions are guided in most cases independently of the histological subtype and are directed by biomarkers and tumor stage. In this study, we analyzed a comprehensive large retrospective breast cancer cohort with a special focus on histological subtype (other than ductal non-special type or lobular carcinoma) and correlated pure or mixed histological forms with pathological tumor stage and overall disease-free survival. MATERIALS AND METHODS A total of 827 breast cancer cases with pure or mixed special histological types were retrospectively analyzed. Survival information was available in 645 of 827 cases. RESULTS A total of 293 cases had pure forms, and 534 cases had mixed histological subtypes. The most common pure special types were mucinous (23.9%), micropapillary (21.2%), high-grade metaplastic (13%), male breast cancer (8.2%), cribriform (6.8%), metastases (6.1%), apocrine and papillary (each 5.46%), NST with medullary and clear cell pattern (up to 3.4%) and high-grade neuroendocrine carcinomas (2.7%). Mixed forms were most frequently encountered in NST carcinomas with micropapillary components (41.8%), followed by mucinous (9.93%) and cribriform (6.74%) mixed patterns. In univariate analysis, no pure form had prognostic relevance compared with any mixed form with the basic pure element. Pooling pure histological subtypes with tumor stage and age in a linear random-effects model, the cribriform subtype had the most favorable prognosis, while male breast cancer showed the poorest outcome (p < 0.001). All other frequent pure forms had intermediate prognostic power (p < 0.001). CONCLUSION Our results show that the analyzed special histological breast cancer subtypes (other than ductal and lobular carcinomas) do not carry prognostic information alone, either in pure form or in any combination with other subtypes. Prognostic groups including special subtypes, however, can strongly stratify breast cancer if tumor stage, age and biomarkers are included in the prognostic measurements.
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Affiliation(s)
- Anna Rechsteiner
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland
| | | | - Zsuzsanna Varga
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland.
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22
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Jiang Y, Gao Z, Wang Y, Xu W. Primary Breast Small Cell Carcinoma With Merkel Cell Features: A Case Report and Literature Review. J Breast Cancer 2023; 26:26.e24. [PMID: 37272249 DOI: 10.4048/jbc.2023.26.e24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 04/17/2023] [Accepted: 04/30/2023] [Indexed: 06/06/2023] Open
Abstract
Neuroendocrine carcinoma of the breast is a rare malignant tumor which, with the features of Merkel cells is even rarer. Herein, we report a case of small cell carcinoma with Merkel cell features in a 52-year-old female. Microscopically, the tumor was characterized by diffuse and consistent small round cells that were de-adherent. The tumor cells had round or oval nuclei with delicate chromatin and small nucleoli, the cytoplasm was sparse and eosinophilic. Additionally, the tumor was accompanied by high-grade ductal carcinoma in situ. Immunohistochemical staining showed that infiltrating tumor cells were positive for neuroendocrine markers, and punctately positive for CK20. The patient underwent modified radical mastectomy, axillary lymph node dissection, and postoperative adjuvant chemotherapy. No recurrence or metastasis was observed during follow-up period. Primary breast small cell carcinoma with Merkel cell features is rare and easily misdiagnosed as Merkel cell carcinoma. Early diagnosis and treatment may improve patient prognosis.
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Affiliation(s)
- Ya Jiang
- Department of Pathology, 920th Hospital of Joint Logistics Support Force of PLA, Kunming, China
| | - Ziran Gao
- Department of Pathology, 920th Hospital of Joint Logistics Support Force of PLA, Kunming, China
| | - Yuanyuan Wang
- Department of Pathology, 920th Hospital of Joint Logistics Support Force of PLA, Kunming, China.
| | - Wenmang Xu
- Department of Pathology, 920th Hospital of Joint Logistics Support Force of PLA, Kunming, China.
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23
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Qiu Y, Dai Y, Zhu L, Hao X, Zhang L, Bao B, Chen Y, Wang J. Clinicopathological Characteristics and Prognostic Profiles of Breast Carcinoma with Neuroendocrine Features. Life (Basel) 2023; 13:life13020532. [PMID: 36836889 PMCID: PMC9967167 DOI: 10.3390/life13020532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/11/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
BACKGROUND Breast carcinoma with neuroendocrine features includes neuroendocrine neoplasm of the breast and invasive breast cancer with neuroendocrine differentiation. This study aimed to investigate the clinicopathological features and prognosis of this disease according to the fifth edition of the World Health Organization classification of breast tumors. MATERIALS AND METHODS A total of 87 patients with breast carcinoma with neuroendocrine features treated in the First Medical Center, Chinese PLA General Hospital from January 2001 to January 2022 were retrospectively enrolled in this study. RESULTS More than half of the patients were postmenopausal patients, especially those with neuroendocrine neoplasm (62.96%). There were more patients with human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, and most of them were Luminal B type (71.26%). The multivariate analysis showed that diabetes and stage IV disease were related to the progression-free survival of breast carcinoma with neuroendocrine features patients (p = 0.004 and p < 0.001, respectively). CONCLUSION Breast carcinoma with neuroendocrine features tended to be human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, most of them were Luminal B type, and the related factors of progression-free survival were diabetes and stage IV disease.
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Affiliation(s)
- Yue Qiu
- Graduate School, Chinese PLA Medical School, Beijing 100853, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Yongjing Dai
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Li Zhu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Xiaopeng Hao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Liping Zhang
- Graduate School, Inner Mongolia Medical University, Hohhot 010110, China
| | - Baoshi Bao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Yuhui Chen
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
- Correspondence: (Y.C.); (J.W.)
| | - Jiandong Wang
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
- Correspondence: (Y.C.); (J.W.)
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24
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El Arab KF, Bourhafour M, Elqasseh R, Khoaja A, Bouchbika Z, Benchakroun N, Jouhadi H, Tawfiq N, Ennachit M, Elkarroumi M, Benider A, Sahraoui S. Primary neuroendocrine tumors of the breast: About a case and of the review of the literature. Int J Surg Case Rep 2022; 99:107642. [PMID: 36122420 PMCID: PMC9568780 DOI: 10.1016/j.ijscr.2022.107642] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 09/08/2022] [Accepted: 09/09/2022] [Indexed: 11/30/2022] Open
Abstract
primary neuroendocrine carcinomas of the breast represent a minority and are currently included in the latest WHO classification of breast tumors. Their morphological and immunohistochemical features (chromogranin and synaptophysin expression) allow the retain the diagnosis. we report a case of primary neuroendocrine carcinoma of the breast in 50 years old Moroccan women who presented nodule 4,2 cm palpable and mobile of the left breast. Lumpectomy axillary lymph node resection was performed. a histopathological examination disclosed the diagnosis of primary breast neuroendocrine tumors with negative surgical margins and positive lymph nodes (13 N+/19 N). The tumor cells were positive for neuroendocrine markers, a highKi67 proliferation index and the membrane expression of the invasive tumor cells to the anti-HER2 antibody was 2, a FISH done which was equivocal. Our patient received 6 courses of chemotherapythen radiotherapy; currently she received adjuvant hormonal treatment with Tamoxifene.
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Affiliation(s)
- K Fares El Arab
- Department of Medical Oncology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco.
| | - M Bourhafour
- Department of Medical Oncology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - R Elqasseh
- Department of Obstetrics And Gynecology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - A Khoaja
- Department of Anathomopathology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, university Hassan II, Casablanca, Morocco
| | - Z Bouchbika
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - N Benchakroun
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - H Jouhadi
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - N Tawfiq
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - M Ennachit
- Department of Obstetrics And Gynecology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - M Elkarroumi
- Department of Obstetrics And Gynecology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - Abdellatif Benider
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
| | - S Sahraoui
- Department of Radiotherapy, Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Casablanca, Morocco
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25
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Martinez EO, Jorns JM, Kong AL, Kijak J, Lee WY, Huang CC, Cortina CS. Primary Breast Neuroendocrine Tumors: An Analysis of the National Cancer Database. Ann Surg Oncol 2022; 29:6339-6346. [PMID: 35789311 PMCID: PMC9464685 DOI: 10.1245/s10434-022-12123-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 04/27/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND Primary breast neuroendocrine tumors (BNETs) represent < 1% of breast cancers. Diagnosing BNETs can be challenging, and a limited amount of cohort data currently exists in literature. We aimed to describe primary BNET characteristics, treatment modalities, and survival outcomes through the National Cancer Database (NCDB). METHODS A retrospective cohort analysis was performed using the NCDB from 2004 to 2017. BNET cases were compared with patients with invasive ductal carcinoma (IDC). A matched IDC cohort was created by matching patient age, race, and disease stage. Kaplan-Meier analysis was performed, and hazard ratios (HR) were calculated through the bootstrap sampling method. RESULTS A total of 1389 BNET and 1,967,401 IDC cases were identified. When compared with IDC patients, BNET patients were older, had more comorbidities, and were more often male (p < 0.01). BNETs were larger, higher grade, and more frequently hormone receptor negative (p < 0.01). While BNET patients were treated with surgery and radiotherapy (p < 0.01) less often compared with IDC patients, they presented at later disease stage (p < 0.001) and received systemic treatment more frequently (53.5% vs. 40%, p < 0.01). Patients with BNET had increased mortality compared with the matched IDC cohort: stage 1 HR 1.8, stage 2 HR 2.0, stage 3 HR 1.8, and stage 4 HR 1.5 (p < 0.001 for all). CONCLUSION Patients with BNET tend to present at higher clinical stages, are more frequently hormone receptor negative, and have inferior overall survival compared with patients with IDC. Further treatment strategies and studies are needed to elucidate optimal therapies to maximize patient outcomes.
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Affiliation(s)
- Enrique O Martinez
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Julie M Jorns
- Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Amanda L Kong
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
- MCW Cancer Center, Milwaukee, WI, USA
| | - Julie Kijak
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Wen-Yao Lee
- Chang Gung University, Taoyuan City, Taiwan
- Zilber School of Public Health, University of Wisconsin at Milwaukee, Milwaukee, WI, USA
| | - Chiang-Ching Huang
- Zilber School of Public Health, University of Wisconsin at Milwaukee, Milwaukee, WI, USA
| | - Chandler S Cortina
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
- MCW Cancer Center, Milwaukee, WI, USA.
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26
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Karihtala P, Porvari K, Roininen N, Voutilainen S, Mattson J, Heikkilä P, Haapasaari KM, Selander K. Comparison of the mutational profiles of neuroendocrine breast tumours, invasive ductal carcinomas and pancreatic neuroendocrine carcinomas. Oncogenesis 2022; 11:53. [PMID: 36085291 PMCID: PMC9463436 DOI: 10.1038/s41389-022-00427-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 08/12/2022] [Accepted: 08/19/2022] [Indexed: 11/09/2022] Open
Abstract
The pathophysiology and the optimal treatment of breast neuroendocrine tumours (NETs) are unknown. We compared the mutational profiles of breast NETs (n = 53) with those of 724 publicly available invasive ductal carcinoma (IDC) and 98 pancreatic NET (PNET) cases. The only significantly different pathogenetic or unknown variant rate between breast NETs and IDCs was detected in the TP53 (11.3% in breast NETs and 41% in IDCs, adjusted p value 0.027) and ADCK2 (9.4% in breast NETs vs. 0.28% in IDCs, adjusted p value 0.045) genes. Between breast NETs and PNETs, different pathogenetic or unknown variant frequencies were detected in 30 genes. For example, MEN1 was mutated in only 6% of breast NETs and 37% in PNETs (adjusted p value 0.00050), and GATA3 pathogenetic or unknown variants were only found in 17.0% of breast NETs and 0% in PNETs (adjusted p value 0.0010). The most commonly affected oncogenic pathways in the breast NET cases were PI3K/Akt/mTOR, NOTCH and RTK-RAS pathways. Breast NETs had typically clock-like mutational signatures and signatures associated with defective DNA mismatch repair in their mutational landscape. Our results suggest that the breast NET mutational profile more closely resembles that of IDCs than that of PNETs. These results also revealed several potentially druggable targets, such as MMRd, in breast NETs. In conclusion, breast NETs are indeed a separate breast cancer entity, but their optimal treatment remains to be elucidated.
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Affiliation(s)
- Peeter Karihtala
- Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland.
| | - Katja Porvari
- Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Nelli Roininen
- Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Sari Voutilainen
- Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
| | - Johanna Mattson
- Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
| | - Päivi Heikkilä
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Kirsi-Maria Haapasaari
- Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Katri Selander
- Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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27
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Zhong E, Pareja F, Hanna MG, Jungbluth AA, Rekhtman N, Brogi E. Expression of novel neuroendocrine markers in breast carcinomas: a study of INSM1, ASCL1, and POU2F3. Hum Pathol 2022; 127:102-111. [PMID: 35690220 PMCID: PMC10227884 DOI: 10.1016/j.humpath.2022.06.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 11/29/2022]
Abstract
INSM1, ASCL1, and POU2F3 are novel transcription factors involved in neuroendocrine (NE) differentiation of neoplasms in several organs, but data on their expression in breast carcinomas (BCs) are limited. We retrospectively evaluated the expression of these markers in a series of 97 BCs (58 with NE morphology and 39 with otherwise uncommon morphology) tested prospectively using immunohistochemistry (IHC). Nuclear staining in >50% of the cells was used as the positive cut-off. Thirty-two of the 97 BCs (33%) were INSM1-positive. INSM1-positivity correlated significantly with histologic type and presence of stromal mucin. INSM1 also correlated with synaptophysin and chromogranin, established markers of NE differentiation (P < .0001 and P = .0023, respectively). In BC with NE morphology, the expression of INSM1 supported NE differentiation, and INSM1 was more specific than synaptophysin and more sensitive and specific than chromogranin. INSM1 was the most expressed NE marker in 17 BCs. INSM1-positive BCs included 56% of solid papillary BCs, 88% of BCs with solid papillary features, and 75% of high-grade NE carcinomas. Of 35 BCs tested for POU2F3 and ASCL1, only 1 and 4 cases were positive, respectively. Our results show that INSM1 is a sensitive marker of NE differentiation in BC and should be included with synaptophysin and chromogranin in the IHC panel used to evaluate NE differentiation in BC with NE morphology. ASCL1 and POU2F3 are uncommon in BC and their routine assessment is not warranted.
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Affiliation(s)
- Elaine Zhong
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA
| | - Fresia Pareja
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA
| | - Matthew G Hanna
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA
| | - Achim A Jungbluth
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA
| | - Natasha Rekhtman
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA
| | - Edi Brogi
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, 10065 USA.
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28
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Yuan M, Chen D, Sun H, Wang X, Wan D. Primary neuroendocrine carcinoma of the breast with leptomeninges metastasis: A case report and literature review. J Int Med Res 2022; 50:3000605221118505. [PMID: 36069002 PMCID: PMC9459456 DOI: 10.1177/03000605221118505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Primary neuroendocrine carcinoma of the breast (NECB) is a rare tumour with an incident rate of 0.3-0.5%. The most common metastatic sites of NECB are liver, bones, lung, pancreas, soft tissues and brain, while leptomeninges metastasis (LM) is reported rarely. This current case report describes a 50-year-old female patient with NECB and LM whose overall survival was 2 months. The report also presents the current literature regarding the knowledge of this unusual tumour and metastatic type. The current patient was diagnosed with NECB with right cerebellar metastasis, followed by LM. She underwent modified radical mastectomy of the left breast, left whole breast radiation therapy and incomplete adjuvant chemotherapy until the metastasis occurred. Whole-brain radiation therapy and a first-line salvage regimen of etoposide and cis-platinum were then undertaken. The patient died 2 months after their LM diagnosis. Primary NECB with LM is sporadic, devoid of effective treatment and associated with a poor prognosis. Consequently, it is vitally important to identify LM in order to achieve longer patient survival.
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Affiliation(s)
- Mengqi Yuan
- Department of Oncology, China-Japan Friendship Hospital, Beijing, China.,Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Dongmei Chen
- Department of Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Hongliang Sun
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
| | - Xiuhong Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Donggui Wan
- Department of Oncology, China-Japan Friendship Hospital, Beijing, China
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29
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Chen YQ, Xu XF, Xu JW, Di TY, Wang XL, Huo LQ, Wang L, Gu J, Zhou GH. A high-quality model for predicting the prognosis of breast neuroendocrine carcinoma to help clinicians decide on appropriate treatment methods: A population-based analysis. Transl Oncol 2022; 22:101467. [PMID: 35700595 PMCID: PMC9198476 DOI: 10.1016/j.tranon.2022.101467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/30/2022] [Accepted: 06/05/2022] [Indexed: 12/01/2022] Open
Abstract
The incidence of breast neuroendocrine carcinoma (NEC) was approximately 1.96–2.37%. Breast NEC had poor prognosis than breast invasive ductal carcinoma (IDC). Patients with breast NEC may benefit from surgery plus chemotherapy. Efficient models were constructed to guide the treatment of breast NEC. Background Breast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments. Patients and methods A total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram. Results Nomograms were constructed for the breast NEC and breast IDC groups after PSM. The C–index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818–0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone. Conclusions We established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC.
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Affiliation(s)
- Yu-Qiu Chen
- Department of Clinical Pharmacy, Affiliated Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210002, China; Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Xiao-Fan Xu
- Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Jia-Wei Xu
- Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Tian-Yu Di
- Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Xu-Lin Wang
- Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Li-Qun Huo
- Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Lu Wang
- Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
| | - Jun Gu
- Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
| | - Guo-Hua Zhou
- Department of Clinical Pharmacy, Affiliated Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210002, China; Department of Clinical Pharmacy, Affiliated Jinling Hospital, School of Pharmacy, Southern Medical University, Guangzhou 510515, China.
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A Real-World, Population-Based Study for the Incidence and Outcomes of Neuroendocrine Neoplasms of Nondigestive, Nonpulmonary Primary. Pancreas 2022; 51:769-773. [PMID: 36395402 DOI: 10.1097/mpa.0000000000002108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVES The aim of this study was to assess incidence and outcomes of neuroendocrine neoplasms (NENs) arising from primary sites other than digestive organs, lung, or thymic gland. METHODS Surveillance, Epidemiology, and End Results database (1975-2016) was accessed, and cases of NENs arising from primary sites other than digestive organs, lung, or thymic gland were reviewed. Overall and cancer-specific survival outcomes for NENs arising from different organs compared with small intestinal NENs were evaluated. RESULTS A total of 4405 patients were included in the study. Compared with small intestinal NENs, some NENs arising from uncommon sites in the current study have worse cancer-specific survival (hazard ratio [HR] for genitourinary vs small intestinal NENs, 1.80; 95% confidence interval [CI], 1.44-2.25; HR for gynecological vs small intestinal NENs, 1.88; 95% CI, 1.52-2.33). When the analysis was limited for patients with distant stage only, small intestinal NENs have better outcomes compared with genitourinary and gynecological NENs (HR for genitourinary NENs with distant stage vs small intestinal NENs with distant stage, 1.38; 95% CI, 1.01-1.88; HR for gynecological NENs with distant stage vs small intestinal NENs with distant stage, 2.02; 95% CI, 1.54-2.66). CONCLUSIONS Compared with small intestinal NENs, NENs arising from uncommon sites (such as genitourinary, gynecological) have worse survival outcomes.
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Bhardwaj N, Rohilla M, Srinivasan R. Neither Russell nor Magenta bodies: A cytological dilemma in Breast Fine Needle Aspiration Cytology. Cytopathology 2022; 33:650-653. [PMID: 35665550 DOI: 10.1111/cyt.13153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 05/19/2022] [Accepted: 05/25/2022] [Indexed: 12/01/2022]
Affiliation(s)
- Neha Bhardwaj
- Department of Cytology, Postgraduate Institute of Medical Education and Research, Chandigarh
| | - Manish Rohilla
- Department of Cytology, Postgraduate Institute of Medical Education and Research, Chandigarh
| | - Radhika Srinivasan
- Department of Cytology, Postgraduate Institute of Medical Education and Research, Chandigarh
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Schaffrin-Nabe D, Schuster S, Tannapfel A, Voigtmann R. Case Report: Extensive Tumor Profiling in Primary Neuroendocrine Breast Cancer Cases as a Role Model for Personalized Treatment in Rare and Aggressive Cancer Types. Front Med (Lausanne) 2022; 9:841441. [PMID: 35721079 PMCID: PMC9203716 DOI: 10.3389/fmed.2022.841441] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 04/25/2022] [Indexed: 12/17/2022] Open
Abstract
Neuroendocrine breast cancer (NEBC) is a rare entity accounting for <0.1% of all breast carcinomas and <0.1% of all neuroendocrine carcinomas. In most cases treatment strategies in NEBC are empirical in absence of prospective trial data on NEBC cohorts. Herein, we present two case reports diagnosed with anaplastic and small cell NEBC. After initial therapies failed, comprehensive tumor profiling was applied, leading to individualized treatment options for both patients. In both patients, targetable alterations of the PI3K/AKT/mTOR pathway were found, including a PIK3CA mutation itself and an STK11 mutation that negatively regulates the mTOR complex. The epicrisis of the two patients exemplifies how to manage rare and difficult to treat cancers and how new diagnostic tools contribute to medical management.
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Affiliation(s)
- Dörthe Schaffrin-Nabe
- Praxis für Hämatologie und Onkologie, Bochum, Germany
- *Correspondence: Dörthe Schaffrin-Nabe
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Sun H, Dai S, Xu J, Liu L, Yu J, Sun T. Primary Neuroendocrine Tumor of the Breast: Current Understanding and Future Perspectives. Front Oncol 2022; 12:848485. [PMID: 35692784 PMCID: PMC9174548 DOI: 10.3389/fonc.2022.848485] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 04/14/2022] [Indexed: 02/05/2023] Open
Abstract
Primary neuroendocrine carcinoma of the breast (NECB) is characterized with heterogeneity, rarity, and poor differentiation, which is probably an underestimated subtype of breast cancer, including small cell NECs and large cell NECs. The diagnostic criteria for NECB have been constantly updated as the disease changes and the understanding increases. According to the latest WHO Classification, primary neuroendocrine neoplasm (NEN) of the breast consists of well-differentiated neuroendocrine tumors (NET), extremely aggressive neuroendocrine carcinomas (NEC) as well as invasive breast cancers of no special type (IBCs-NST) with neuroendocrine differentiation. The accurate diagnosis of NECB remains a challenge for its low incidence, which needs multi-disciplinary methods. For the rarity of the disease, there is a lack of large samples and prospective clinical research. For these invasive tumors, there are no standardized therapeutic guidelines or norms, and the treatment often refers to nonspecific breast cancer. In addition, the prognosis of such patients remains unknown. In 2003, the World Health Organization (WHO) listed NECB as an independent entity for the first time, while few features of NECB were clarified. In this review, it presents the WHO Classification, clinicopathologic characteristics, diagnosis, treatment, and prognosis of these patients. In addition, it summarizes the latest studies on molecular features of NECB, aiming to provide new therapeutic perspectives for the disease.
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Affiliation(s)
- Hongna Sun
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Shuang Dai
- Department of Medical Oncology, Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Junnan Xu
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Linan Liu
- Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
| | - Jiaxing Yu
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Tao Sun
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
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Ma ST, Wang DY, Liu YB, Tan HJ, Ge YY, Chi Y, Zhang BL. Prognostic factors of primary neuroendocrine breast cancer: A population-based study. Cancer Med 2022; 11:2533-2540. [PMID: 35499193 PMCID: PMC9249978 DOI: 10.1002/cam4.4557] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 09/09/2021] [Accepted: 12/30/2021] [Indexed: 11/06/2022] Open
Abstract
Background Primary neuroendocrine breast carcinomas (NEBCs) are an extremely rare and underrecognized subtype of mammalian carcinoma. The prognostic factors for NEBCs remain controversial. Methods In this multicenter retrospective study, the prognostic factors for patients with primary NEBCs who underwent surgery and had a pathologically confirmed diagnosis of neuroendocrine carcinoma in China and the United States were examined. The endpoints were disease‐free survival (DFS) and overall survival (OS). Results A total of 51 Chinese patients and 98 US patients were included. In the Chinese cohort, tumor grade and Ki‐67 levels were prognostic factors for DFS in univariate analysis (hazard ratio [HR] = 5.11 [1.67–15.60], p = 0.004; HR = 57.70 [6.36–523.40], p < 0.001, respectively) and multivariate analysis (HR = 100.52 [1.33–7570.21], p = 0.037; HR = 31.47 [1.05–945.82], p = 0.047, respectively). In the US cohort, age was an important prognostic factor for OS in univariate analysis (HR = 1.09 [1.04–1.15], p = 0.001). The random effects model for the combined cohorts revealed age and positive expression of estrogen receptor (ER) as potential prognostic factors for OS (HR = 1.08 [1.01–1.14], p = 0.015; HR = 0.10 [0.02–0.44], p = 0.003, respectively). Conclusions Tumor grade and Ki‐67 levels are important prognostic factors for DFS of patients with primary NEBCs. Age and ER status are important prognostic factors for OS of patients with primary NEBCs.
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Affiliation(s)
- Shu-Tao Ma
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ding-Yuan Wang
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi-Bing Liu
- Third Clinical Medical College, Jilin University, Changchun, China
| | - Hui-Jing Tan
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue-Yue Ge
- Department of Geriatric Medicine, National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Chinese Academy of Medical Sciences, Beijing, China
| | - Yihebali Chi
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bai-Lin Zhang
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Stimes N, Stanbery L, Albrethsen M, Trivedi C, Hamouda D, Dworkin L, Nemunaitis J. Small-cell breast carcinoma with response to atezolizumab: a case report. Immunotherapy 2022; 14:669-674. [PMID: 35481350 DOI: 10.2217/imt-2021-0100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background: Small-cell carcinoma of the breast is a rare disease with little research outlining molecular targets or optimal therapeutic management. We summarize a young female patient with poorly differentiated high-grade carcinoma with neuroendocrine features/small-cell carcinoma. Case presentation: A 31-year-old female presented with a large left breast mass. Initial biopsy revealed small-cell, triple-negative breast carcinoma. Treatment consisted of cisplatin and etoposide but was poorly tolerated and discontinued after one cycle. Combination abraxane/atezolizumab resulted in transient partial response in tumor size with 7 months of progression-free stability. Worsening metastatic disease was found 8 months after initial biopsy on radiologic studies and the patient expired 10 months after initial biopsy. Conclusion: Transient benefit in response to combination abraxane/atezolizumab was demonstrated.
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Affiliation(s)
- Nicholas Stimes
- College of Medicine, University of Toledo Medical Center, Toledo, OH 43614, USA
| | | | | | | | - Danae Hamouda
- College of Medicine, University of Toledo Medical Center, Toledo, OH 43614, USA
| | - Lance Dworkin
- College of Medicine, University of Toledo Medical Center, Toledo, OH 43614, USA
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Chai Y, Liu M, Li Z, Chen Y, Qi F, Li Q, Xu B. Retrospective literature review of primary neuroendocrine neoplasms of the breast (BNEN) in 209 Chinese patients: Treatment and prognostic factor analysis. Breast 2022; 62:93-102. [PMID: 35134665 PMCID: PMC8844750 DOI: 10.1016/j.breast.2022.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/23/2022] [Accepted: 01/24/2022] [Indexed: 11/19/2022] Open
Abstract
Background The prognostic factors and optimal choice of treatment for primary neuroendocrine neoplasms of the breast (BNEN) remain to be defined. Methods Patients diagnosed with BNEN in China were retrospectively reviewed from the literature following the systematic search of China National Knowledge Infrastructure (CNKI), Chinese biomedical literature service system (sinomed), wanfang medical network, and Pubmed database. The clinical characteristics and different treatment modalities of patients with BNEN were evaluated. Results A total of 209 cases with BNEN were enrolled. There were 204 female and 5 male patients. The median age was 51 years old (range, 17–82). Out of 209 patients with BNEN, 208 (99.5%) patients were treated with surgery (SG), 44 patients (21.1%) had received radiotherapy (RT), 173 patients (82.8%) experienced chemotherapy (CT). A total of 158 patients with hormone receptor (HR) positive (87.8%, 158/180) were treated with endocrine treatment (ET). The median follow-up time was 52.4 months (range, 6–144). The 3-year overall survival (OS) rate and 3-year disease-free survival (DFS) rate for the whole group were 93.7% and 85.3%, respectively. In univariate analyses, Ki67 expression ≥20%, HR negative, neuroendocrine carcinomas (NECs) were associated with decreased OS and DFS (P < 0.05). Patients treated with anthracycline/taxane-containing CT regimens, or taxane-containing CT regimens had superior OS and DFS than patients without those (P < 0.05). Among 69 patients with stage I who received CT had no significant differences in OS or DFS compared to those without CT. Multivariate Cox regression analysis showed that gender, HR expression, pathologic subtype, and CT were independent prognostic factors for DFS but not OS (P > 0.05). Conclusions The best selection of patients to get the most benefit from different treatment modalities warrant further exploration. The clinicopathological parameters including gender, HR expression, ki67 expression, pathologic type, stage, tumor size, and lymph node status may serve as both indicators of diagnosis and prognosis, and guide treatment decisions for BNEN.
Surgery is a cornerstone of BNEN. ET may have a long-term superior effect on patients with HR-positive. Low-risk BNEN patients may be spared CT and managed with ET. Many clinicopathological parameters were very important for BNEN.
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Affiliation(s)
- Yue Chai
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Liu
- Department of Medical Oncology, The Second People's Hospital/ Tumor Hospital of Jilin City, Jilin, China
| | - Zhijun Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yujie Chen
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Fei Qi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Bejing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Qiao Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Binghe Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Rakha E, Tan PH. Head to head: Do neuroendocrine tumours in the breast truly exist? Histopathology 2022; 81:2-14. [PMID: 35133666 DOI: 10.1111/his.14627] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/02/2022] [Accepted: 02/05/2022] [Indexed: 11/30/2022]
Abstract
Breast cancer (BC) is a heterogeneous disease with a spectrum of morphological features. Concepts of histogenesis and differentiation in BC remain controversial. Recent evidence supports differentiation rather than histogenesis as the underlying mechanism for the myriad morphological appearances of BC. Prognosis and response to therapy are determined by a combination of factors including tumour grade, stage and receptor status whereas tumour histological types play an independent role in only limited examples. Neuroendocrine tumours (NETs) comprise one of the most debated entities in the breast since their first description. Apart from the rare small cell NE carcinoma (NEC) which has well-characterised features similar to their counterparts in other organs, the true existence, diagnostic criteria and clinical significance of NE neoplasms (NENs) in the breast are shrouded in controversy. At the core of this discussion is whether normal NE cells exist in the breast, and if breast NETs have distinct morphology and clinical behaviour. When NETs are encountered in the breast, metastatic origin has to be excluded. The more frequent situation in which NE differentiation is observed in breast cancers is in the context of recognisable, morphologically well described special type neoplasms like the hypercellular mucinous carcinoma and solid papillary carcinoma. In this review, arguments for and against maintaining the category of NENs in the breast are articulated in relation to existing literature on this group of unusual tumours.
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Affiliation(s)
- Emad Rakha
- University of Nottingham and Nottingham University Hospital NHS Trust, Department of Histopathology, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK
| | - Puay Hoon Tan
- Division of Pathology, Singapore General Hospital, Academia, 20 College Road, Singapore, 169856
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Krawczyk N, Röwer R, Anlauf M, Muntanjohl C, Baldus SE, Neumann M, Banys-Paluchowski M, Otten S, Luczak K, Ruckhäberle E, Mohrmann S, Hoffmann J, Kaleta T, Jaeger B, Esposito I, Fehm T. Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis. Geburtshilfe Frauenheilkd 2022; 82:68-84. [PMID: 35027862 PMCID: PMC8747900 DOI: 10.1055/a-1557-1280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction
Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation.
Patients
Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records.
Results
Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%.
Conclusions
Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases.
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Affiliation(s)
- Natalia Krawczyk
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Rowena Röwer
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Martin Anlauf
- Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Düsseldorf, Germany.,Institute of Pathology, Cytology and Molecular Pathology, St. Vincenz Hospital, Limburg, Germany
| | - Caja Muntanjohl
- Institute of Pathology, Cytology and Molecular Pathology, St. Vincenz Hospital, Limburg, Germany
| | - Stephan Ernst Baldus
- Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Düsseldorf, Germany.,Institute of Pathology, Cytology and Molecular Pathology, Bergisch Gladbach, Germany
| | - Monika Neumann
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Maggie Banys-Paluchowski
- Department of Obstetrics and Gynaecology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.,Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
| | - Sabine Otten
- Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Düsseldorf, Germany
| | - Katharina Luczak
- Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Düsseldorf, Germany
| | - Eugen Ruckhäberle
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Svjetlana Mohrmann
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Jürgen Hoffmann
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Thomas Kaleta
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Bernadette Jaeger
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
| | - Irene Esposito
- Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Düsseldorf, Germany
| | - Tanja Fehm
- Department of Obstetrics and Gynaecology, University of Düsseldorf, Düsseldorf, Germany
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Kayadibi Y, Erginoz E, Cavus GH, Kurt SA, Ozturk T, Velidedeoglu M. Primary neuroendocrine carcinomas of the breast and neuroendocrine differentiated breast cancers: Relationship between histopathological and radiological features. Eur J Radiol 2022; 147:110148. [PMID: 35007984 DOI: 10.1016/j.ejrad.2021.110148] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 11/16/2021] [Accepted: 12/30/2021] [Indexed: 11/30/2022]
Abstract
PURPOSE The aim of this study wasto investigate whole-breast imaging findings (mammography, ultrasonography (US), magnetic resonance imaging (MRI),clinical, and histopathological findings of primary neuroendocrine carcinomas of the breast (NEC) and neuroendocrine differentiated breast cancers (NEBC). METHODS Patients withadiagnosis of breast cancer with histopathological neuroendocrine features between the years 2010 and 2021 were retrospectively screened.The lesions were divided into two main groups depending on staining with neuroendocrine markers (synaptophysin and chromogranin A). Those showing focal staining were categorized as NEBC while those with diffuse staining as NEC.The mammography, US, and MRI of the lesionswere reviewed in consensus by two breast radiologists in order to assess imaging featuresretrospectively according to the Breast Imaging Reporting and Data System (BI-RADS) 5th lexicon.The findings were compared with breast cancers without neuroendocrine features (BC-WNE) which were randomly selected from the same database. RESULTS A total of 105 lesions [NEBC (n = 44), NEC(n = 11), BC-WNE (n = 50)] were evaluated.Patients with neuroendocrine tumors were older (p < 0.001) than those with BC-WNE. Compared with BC-WNE tumors, radiological findings typical of malignancy such as irregular shape [NEBC (7/20); NEC(3/7) vs BC-WNE (35/43); p < 0.001], spiculation [NEBC (2/20); NEC(0/7) vs BC-WNE (21/43); p < 0.001], architectural distortion [(NEBC (3/24); NEC(0/9) vs BC-WNE (31/50); p < 0.001)], calcification [(NEBC (6/24), NEC(0/9) vs BC-WNE (n = 27/50); p = 0.001)] on mamography, non-parallel orientation to skin [(NEBC (n = 17/29), NEC(n = 4/9), BC-WNE (n = 35/42); p = 0.008)], acoustic shadowing [(NEBC (n = 12/29), NEC(1/9), BC-WNE (n = 29/42); p = 0.009)], axillary lymphadenopathy [(NEBC(n = 3/30), NEC(n = 1/9), BC-WNE (21/50); p < 0.001)]on US were less common features of the neuroendocrine carcinomas of breast. Aside from shape features, there was no significant difference in contrast pattern (p = 0.866), kinetic curve (p = 0.454) and diffusion restriction (p = 0.242) on MRI. CONCLUSION Characteristic malignant imaging features, including irregular shape, spiculated margins, suspicious calcifications, and posterior acoustic shadowing, are uncommon in neuroendocrine carcinomas of breast. These carcinomas tend to show more benign imaging features when compared with BC-WNE.
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Affiliation(s)
- Yasemin Kayadibi
- Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty, Department of Radiology, Kocamustafapasa, Istanbul, Turkey.
| | - Ergin Erginoz
- Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty, Department of General Surgery, Kocamustafapasa, Istanbul, Turkey.
| | - Gokce Hande Cavus
- Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty, Department of Pathology, Kocamustafapasa, Istanbul, Turkey.
| | - Seda Aladag Kurt
- Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty, Department of Radiology, Kocamustafapasa, Istanbul, Turkey.
| | - Tulin Ozturk
- Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty, Department of Pathology, Kocamustafapasa, Istanbul, Turkey.
| | - Mehmet Velidedeoglu
- Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty, Department of General Surgery, Kocamustafapasa, Istanbul, Turkey.
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Zhu J, Wu G, Zhao Y, Yang B, Chen Q, Jiang J, Meng Y, Ji S, Gu K. Epidemiology, Treatment and Prognosis Analysis of Small Cell Breast Carcinoma: A Population-Based Study. Front Endocrinol (Lausanne) 2022; 13:802339. [PMID: 35444614 PMCID: PMC9013885 DOI: 10.3389/fendo.2022.802339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 03/02/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Primary small cell breast carcinoma (SCBC) is an uncommon malignancy with highly invasive behavior. The aim of this study was to find out more about the incidence, clinicopathologic characteristics and identify potential prognostic factors of SCBC. METHODS Data of patients with primary diagnosis of SCBC between 1975 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence after adjustment for age and percentage change per year in incidence were calculated. Disease-specific survival (DSS) and overall survival (OS) were analyzed among these SCBC patients identified from the SEER database. The whole cohorts were randomized into training and validation cohorts as ratio of 7: 3. Cox regression analysis was performed to determine predictors of survival with the training cohorts. Predictive models were constructed with training cohorts, and nomogram validation was performed using receiver operating characteristic curves, concordance indices and calibration curves in both training and validation cohorts. RESULTS 323 SCBC patients were enrolled finally during the research period. The overall incidence after adjustment for age between 1990 and 2018 was 0.14 per million per year, and the prevalence of the incidence has plateaued. Most of these tumors were poorly differentiated or undifferentiated. The most prevalent presenting stage was Stage II. Patients identified in this study were randomly divided into training (n = 226) and testing (n = 97) cohorts. Multivariate Cox proportional hazards model showed that chemotherapy, surgery and stage were important predictors of DSS and OS. CONCLUSION SCBC is considered an infrequent breast neoplasm with aggressive characteristics. Tumor stage is associated with poor prognosis. Combination of surgery and chemotherapy is the main treatment for SCBC.
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Affiliation(s)
- Jiahao Zhu
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Gang Wu
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Yutian Zhao
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Bo Yang
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Qingqing Chen
- Department of Radiotherapy and Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, China
| | - Jianwei Jiang
- Department of Breast Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, China
| | - You Meng
- Department of Breast Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, China
| | - Shengjun Ji
- Department of Radiotherapy and Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, China
- *Correspondence: Shengjun Ji, ; Ke Gu,
| | - Ke Gu
- Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, China
- *Correspondence: Shengjun Ji, ; Ke Gu,
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Ozaki Y, Miura S, Oki R, Morikawa T, Uchino K. Neuroendocrine Neoplasms of the Breast: The Latest WHO Classification and Review of the Literature. Cancers (Basel) 2021; 14:cancers14010196. [PMID: 35008357 PMCID: PMC8750232 DOI: 10.3390/cancers14010196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/28/2021] [Accepted: 12/28/2021] [Indexed: 11/23/2022] Open
Abstract
Simple Summary Breast tumors exhibiting neuroendocrine differentiation are a heterogeneous group of tumors that have been variously defined in previous World Health Organization (WHO) classifications. In the WHO Classification of Tumours, 5th edition, neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) of the breast, both of which are invasive cancers, are classified as neuroendocrine neoplasms (NENs) of the breast. However, the clinical significance of NE differentiation in breast cancers, especially in NETs of the breast, is not yet fully understood, and a large overlap appears to exist between breast cancers showing NE differentiation and invasive breast cancer of no special type (IBC-NST). While breast NECs show distinct clinical and morphological features, diagnosis of NETs based on the morphological characteristics alone can be challenging; one reason is that breast NETs do not necessarily have the same morphological characteristics as those of NENs arising in other organs. Thus, the heterogeneity of breast tumors with neuroendocrine differentiation and the changes in their classifications over the years have left many open issues that still need to be resolved. In this review, we shall summarize the history of breast “NENs,” including of mixed types of tumors and the characteristics of these tumors, and discuss their differences from NENs arising in other organs. Abstract Breast tumors with neuroendocrine (NE) differentiation comprise an uncommon and heterogeneous group of tumors, including invasive breast cancer of no special type (IBC-NST) with NE features, neuroendocrine tumors (NETs), and neuroendocrine carcinoma (NEC). The most recent World Health Organization (WHO) classification in 2019 defined neuroendocrine neoplasms (NENs) of the breast (Br-NENs) as tumors in which >90% of cells show histological evidence of NE differentiation, including NETs (low-grade tumors) and NEC (high-grade). Due to the low prevalence of these tumors and successive changes in their diagnostic criteria over the years, only limited evidence of these tumors exists, derived mainly from case reports and retrospective case series. Breast tumors with NE differentiation are usually treated like the more commonly occurring IBC-NSTs. Immunohistochemistry (IHC) of breast tumors with NE differentiation usually shows a hormone receptor (HR)-positive and human epidermal growth factor type 2 (HER2)-negative profile, so that hormonal therapy with cyclin-dependent kinase (CDK)4/6 inhibitors or other targeted agents would be reasonable treatment options. Herein, we present a review of the literature on breast tumors with NE differentiation as defined in the latest WHO 2019 classification, and discuss the clinical management of these tumors.
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Affiliation(s)
- Yukinori Ozaki
- Department of Medical Oncology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan; (R.O.); (K.U.)
- Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
- Correspondence: ; Tel.: +81-3-3520-0111
| | - Sakiko Miura
- Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan; (S.M.); (T.M.)
| | - Ryosuke Oki
- Department of Medical Oncology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan; (R.O.); (K.U.)
- Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Teppei Morikawa
- Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan; (S.M.); (T.M.)
| | - Keita Uchino
- Department of Medical Oncology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan; (R.O.); (K.U.)
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Wang X, Shi YF, Duan JH, Wang C, Tan HY. S-1 plus temozolomide as second-line treatment for neuroendocrine carcinoma of the breast: A case report. World J Clin Cases 2021; 9:7146-7153. [PMID: 34540971 PMCID: PMC8409205 DOI: 10.12998/wjcc.v9.i24.7146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/27/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine carcinoma of the breast (NECB) is a rare type of malignant tumor. Due to the rarity of NECB, the relevant literature mostly comprises case reports. Available data on treatment options for NECB are very limited. CASE SUMMARY A 62-year-old woman presented to our hospital in October 2016 for intermittent vomiting and diarrhea and masses in the liver found on abdominal computed tomography (CT) imaging. She was diagnosed in July 2012 with neuroendocrine carcinoma of the right breast in local hospital. The patient initially presented with a painful lesion of the right breast. She then undergone surgical resection and adjuvant chemotherapy with pirarubicin and paclitaxel for four cycles as well as endocrine therapy. She was regularly followed every 3 mo after surgery. Enhanced abdominal CT imaging at our hospital revealed multiple suspicious masses in the liver with the largest lesion measuring 8.4 cm × 6.3 cm. Chest CT revealed masses in the anterior chest wall and lung. Core needle biopsy of the lesion revealed liver metastases of NECB. A bone scan showed right second anterior rib metastases. Upper endoscopy and colonoscopy did not provide any evidence of another possible primary tumor. She stopped receiving endocrine therapy and then received etoposide and cisplatin (EP) chemotherapy as a first-line treatment regimen for six cycles at our hospital after liver, bone, and lung metastases. On October 2017, the chemotherapy regimen was changed to S-1 (40 mg twice daily, days 1-14) combined with temozolomide (200 mg once daily, days 10-14) (STEM) every 21 d as a second-line treatment regimen due to disease progression. Progression-free survival (PFS) and adverse effects after treatment were analyzed, and the efficacy of the STEM regimen was assessed using RECIST version 1.1. This patient achieved a partial response after using the STEM regimen, with a PFS of 23 mo. Adverse effects included only grade 1 digestive tract reactions with no need for a reduction in chemotherapy. CONCLUSION This case report suggests that the STEM regimen may be effective and well tolerated as the second-line treatment for advanced NECB. STEM is still highly effective in patients who show disease progression with the EP regimen. More evidence is needed to prove the validity of STEM.
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Affiliation(s)
- Xin Wang
- Beijing University of Chinese Medicine; Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yan-Fen Shi
- Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jiang-Hui Duan
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Chao Wang
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Huang-Ying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
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Masab M, Gross A, Flanagan M, Goldberg R, Malla M. Neuroendocrine Neoplasm of the Breast Presenting as a Liver Metastasis: A Rare Diagnostic Challenge. Cureus 2021; 13:e16860. [PMID: 34513437 PMCID: PMC8413109 DOI: 10.7759/cureus.16860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2021] [Indexed: 11/05/2022] Open
Abstract
We present a case of a 58-year-old female who presented initially to an outside institution with abdominal pain and was diagnosed on liver biopsy with a well-differentiated neuroendocrine tumor of an unknown primary source. She was referred to our academic institution for a second opinion after disease progression on the initial chemotherapy regimen. Through additional evaluation, diagnostics, and multi-disciplinary tumor board discussion she was diagnosed with metastases from a well-differentiated neuroendocrine neoplasm of the breast (NENB). Consequently, her treatment plan was modified leading to significant clinical and radiological improvement.
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Affiliation(s)
- Muhammad Masab
- Hematology and Medical Oncology, West Virginia University, Morgantown, USA
| | - Alexander Gross
- Pathology and Laboratory Medicine, West Virginia University, Morgantown, USA
| | - Melina Flanagan
- Pathology and Laboratory Medicine, West Virginia University, Morgantown, USA
| | - Richard Goldberg
- Hematology and Medical Oncology, West Virginia University, Morgantown, USA
| | - Midhun Malla
- Hematology and Medical Oncology, West Virginia University, Morgantown, USA
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Loap P, Laki F, Beuzeboc P, Fourquet A, Kirova YM. Five-year outcomes in patients treated with surgery and radiotherapy for primary neuroendocrine neoplasm of the breast. Breast J 2021; 27:776-780. [PMID: 34196070 DOI: 10.1111/tbj.14264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/03/2021] [Accepted: 06/04/2021] [Indexed: 12/01/2022]
Affiliation(s)
- Pierre Loap
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Fatima Laki
- Department of Surgery, Institut Curie, Paris, France
| | | | - Alain Fourquet
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Youlia M Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
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45
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Atchison L, Hardy T, Mancl T, Quaranta BP, Madan A. Locally Advanced Primary Small Cell Carcinoma of the Breast: A Case Report and Review of Current Evidence. Case Rep Oncol 2021; 14:761-766. [PMID: 34177527 PMCID: PMC8215941 DOI: 10.1159/000515505] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 02/25/2021] [Indexed: 12/22/2022] Open
Abstract
Small-cell breast carcinoma (SCBC) is a very rare type of aggressive breast cancer constituting less than 1% of all breast cancers. The WHO classification categorizes this tumor as small-cell neuroendocrine carcinoma, and its prognosis is usually worse as compared to invasive breast cancers. We report a 64-year-old Caucasian female who presented with a large fungating left breast mass. Biopsy of the mass revealed small-cell carcinoma of the breast, negative for all 3 receptors (estrogen, progesterone, and Her2/neu). Imaging studies were negative for distant metastasis. She was subsequently treated after multidisciplinary discussion utilizing neoadjuvant chemotherapy with platinum agents and etoposide, modified radical mastectomy with axillary lymph node dissection, and adjuvant radiation therapy. Since she has triple-negative small-cell breast cancer, she will be followed with active surveillance without hormonal therapy. With less than 100 cases reported and in the absence of evidence-based standard treatment guidelines, we have reviewed various case series reported in the literature. We further discuss various chemotherapy regimens used previously, adverse prognostic factors of breast neuroendocrine tumors, common receptor status, and genetic mutations found in SCBC.
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Affiliation(s)
- Linsey Atchison
- Department of Internal Medicine Residency, SOVAH, Danville, Virginia, USA
| | - Thomas Hardy
- Department of Pathology, SOVAH, Danville, Virginia, USA
| | - Tara Mancl
- Department of General Surgery, SOVAH, Danville, Virginia, USA
| | | | - Ankit Madan
- Department of Internal Medicine, Medical Oncology, SOVAH, Danville, Virginia, USA
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46
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Breast cancer with neuroendocrine differentiation: an update based on the latest WHO classification. Mod Pathol 2021; 34:1062-1073. [PMID: 33531618 DOI: 10.1038/s41379-021-00736-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 12/17/2020] [Accepted: 12/17/2020] [Indexed: 02/08/2023]
Abstract
Breast cancers with neuroendocrine (NE) differentiation are very heterogeneous, comprising broadly cancers that are morphologically similar to NE tumors (NET) of other anatomic sites, infiltrating breast carcinomas, no special type (IBC-NST) and other special subtypes with NE morphology and/or NE markers expression. Depending on the classification schemes, they are variably included into "NE breast cancers". The latest WHO classification harmonized NE breast cancers with NE neoplasms (NEN) of other organ systems, defined NEN into well-differentiated NET (low Nottingham grade) and poorly-differentiated NE carcinoma (NEC) (high Nottingham grade). Other IBC with NE differentiation are diagnosed based on solely the non-NEN component. Due to the changes in diagnostic criteria, variable results were obtained in the previous studies on NE breast cancers. Hence, the clinical value of NE differentiation in breast cancers is not well investigated and understood. In this review, the current understanding in the pathogenesis, clinical, prognostic, immunhistochemical, and molecular features of "NE breast cancers" is summarized. Controversial issues in their diagnosis and classification are also discussed.
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Abstract
PURPOSE OF REVIEW Breast cancer is a collection of diseases including the more common invasive ductal and lobular carcinomas and rarer subtypes of breast cancer. This review summarizes the features of rare breast cancers. RECENT FINDINGS Each of the rare tumors has defined pathological and clinical features that impact treatment recommendations. In this review, we summarize these for each rare type of breast cancer and where available we include molecular features of each tumor. Rare subtypes of breast cancer each have unique features. In many cases, data is limited for the optimal treatment approaches.
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Affiliation(s)
- Sarah Jenkins
- Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
- Medical Oncology Service, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
| | - Megan E Kachur
- Pathology Department, Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA
| | - Kamil Rechache
- Medical Oncology Service, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
| | - Justin M Wells
- Pathology Department, Walter Reed National Military Medical Center, Bethesda, MD, 20889, USA.
| | - Stanley Lipkowitz
- Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
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Yang L, Roy M, Lin H, Shen Y, Albarracin C, Huo L, Chen H, Wei B, Bedrosian I, Bu H, Wu Y. Validation of prognostic significance of the proposed uniform classification framework in neuroendocrine neoplasms of the breast. Breast Cancer Res Treat 2021; 186:403-415. [PMID: 33528758 DOI: 10.1007/s10549-021-06099-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 01/06/2021] [Indexed: 02/05/2023]
Abstract
PURPOSE A uniform classification framework for neuroendocrine neoplasms (NENs) in all the organ systems has been recently proposed by an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert panel. Based on the new classification system, the NENs of the breast are divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). This study is aimed to analysis the prognostic differences between NENs and invasive ductal carcinomas of no special type (IDCs-NST). METHODS The surveillance, epidemiology, and end results (SEER) database released on November 2018 was used for this study. Between 2003 and 2016, 361 NENs (NET = 239, NEC = 122) of the breast and 491,908 of IDCs-NST were identified. Survival analysis was performed for disease-specific survival (DSS) and overall survival (OS). RESULTS The 5-year DSS of NET, NEC, and IDC-NST was 63.39%, 46.00%, and 89.17%, respectively. And the 5-year OS of NET, NEC, and IDC-NST was 55.66%, 38.87%, and 83.17%, respectively. Within the same clinical stage or grade, NETs and NECs of the breast had worse DSS and OS than corresponding stage or grade IDCs-NST (all P < 0.050). In univariate and multivariate survival analysis, NENs of the breast had significantly worse DSS and OS than IDCs-NST (P < 0.001). CONCLUSION The universal classification framework for NEN allowed us to further refine the breast carcinoma with neuroendocrine differentiation as a unique pathologic and clinical entity, which has worse clinical outcome compared to IDC-NST.
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Affiliation(s)
- Libo Yang
- Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Madhuchhanda Roy
- Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Heather Lin
- Departments of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yu Shen
- Departments of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Constance Albarracin
- Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lei Huo
- Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hui Chen
- Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bing Wei
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Isabelle Bedrosian
- Departments of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hong Bu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Yun Wu
- Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Gallo M, Campione S, Di Vito V, Fortunati N, Lo Calzo F, Messina E, Ruggeri RM, Faggiano A, Colao AAL. Primary Neuroendocrine Neoplasms of the Breast: Still Open Issues. Front Endocrinol (Lausanne) 2021; 11:610230. [PMID: 33584543 PMCID: PMC7874233 DOI: 10.3389/fendo.2020.610230] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 12/08/2020] [Indexed: 11/13/2022] Open
Abstract
Neuroendocrine breast tumors represent a rare subtype of breast cancer, accounting for less than 1% of all neuroendocrine neoplasms. Starting from their pathology definition, and going through their prevalence, prognosis and treatment, our knowledge is still really uncertain. In the present short review of the medical literature on this topic, we have evaluated in details their epidemiology, risk factors, pathogenesis, pathology, clinical presentation, radiographic aspects, prognosis, and therapy. We have thus been able to identify a number of open issues regarding primary neuroendocrine neoplasms of the breast that need to be clarified. Our ultimate aim was actually to try to understand whether neuroendocrine neoplasms of the breast can be considered a definite clinical entity and if neuroendocrine differentiation of breast tumors has a really clinical relevance.
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Affiliation(s)
- Marco Gallo
- Oncological Endocrinology Unit, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Turin, Italy
- Endocrinology and Metabolic Diseases Unit, AO SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | | | - Valentina Di Vito
- Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Nicoletta Fortunati
- Oncological Endocrinology Unit, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Turin, Italy
| | - Fabio Lo Calzo
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University “Federico II”, Naples, Italy
| | - Erika Messina
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | | | - Antongiulio Faggiano
- Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, Rome, Italy
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Nakagaki KYR, Nunes MM, Garcia APV, De Brot M, Cassali GD. Neuroendocrine Carcinomas of the Canine Mammary Gland: Histopathological and Immunohistochemical Characteristics. Front Vet Sci 2021; 7:621714. [PMID: 33469557 PMCID: PMC7813755 DOI: 10.3389/fvets.2020.621714] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 12/07/2020] [Indexed: 11/26/2022] Open
Abstract
Invasive mammary carcinomas with neuroendocrine differentiation are rare in women and were reported only once in female dogs. For the present study, ten cases of solid mammary carcinoma positive for chromogramin A in immunohistochemistry were selected. Histopathological characteristics of these tumors were described and immunohistochemical evaluation was performed with chromogranin A, synaptophysin, CD56, NSE, PGP 9.5, pancitokeratin, Ki67, estrogen receptor (ER), and progesterone receptor (PR). The average animal age was 13.2 years old and the average tumor size was 4.8 cm. In total, 70% of the neoplasms were classified as grade III and 30% as grade II by the Nottingham histological grade system. High mitotic index was observed with a mean of 27.5 mitoses in 10 high magnification fields. Only one case showed typical carcinoid tumor characteristics. In addition, vascular invasion was shown in 3 tumors. All carcinomas were positive for chromogran A, while only two cases were reactive to synaptophysin. For PGP 9.2, NSE and CD56, we observed positivity of 100, 90, and 70%, respectively, in the samples, being that no tumor was positive for all the neuroendocrine markers. All neoplasms showed ER and PR in at least 10% of neoplastic cells, while Ki67 varied from 29 to 95%, with mean mitotic index of 67%. Four of the ten animals died within 1 year of the tumor diagnosis. Neuroendocrine neoplasms occur in the canine mammary gland and are propably underdiagnosed. This is due to their non-specific morphological characteristics and the low use of neuroendocrine immunohistochemistric markers the diagnostic routine. More studies are necessary to determine the prognosis of this new histological type.
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Affiliation(s)
- Karen Yumi Ribeiro Nakagaki
- Laboratory of Comparative Pathology, Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Maíra Meira Nunes
- Laboratory of Comparative Pathology, Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Ana Paula Vargas Garcia
- Laboratory of Comparative Pathology, Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Marina De Brot
- Department of Anatomic Pathology, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Geovanni Dantas Cassali
- Laboratory of Comparative Pathology, Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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