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1
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Laokulrath N, Gudi MA, Tan PH, Tan TYZ, Lim GH. Fibromatosis-Like Metaplastic Carcinoma of the Breast: A Challenging Diagnosis With Potential Pitfalls. Int J Surg Pathol 2024:10668969241300498. [PMID: 39692324 DOI: 10.1177/10668969241300498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
Fibromatosis-like metaplastic carcinoma (FLMC) is a rare subtype of metaplastic carcinoma of the breast. Diagnosing this entity poses significant challenges, particularly in core biopsies due to limited sampling and overlap with benign spindle cell lesions such as nodular fasciitis and fibromatosis. We present an example of FLMC in an asymptomatic middle-aged woman. As her breast imaging revealed an irregular lobulated mass, a core biopsy was performed which showed benign breast tissue with fibrosis. However, this was discordant with her imaging findings, hence a subsequent vacuum-assisted biopsy was done which revealed low-grade spindle cell proliferation, consistent with FLMC. This report emphasizes the necessity of a triple assessment and highlights the potential pitfalls in diagnosing FLMC, particularly the risk of misinterpretation due to its histological similarities with benign entities. Understanding these challenges will be crucial to avoid diagnostic delays of this rare breast cancer subtype.
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Affiliation(s)
- Natthawadee Laokulrath
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore
- Department of Pathology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Mihir Ananta Gudi
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore
| | - Puay Hoon Tan
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore
| | | | - Geok Hoon Lim
- Breast Department, KK Women's and Children's Hospital, Singapore
- Duke-NUS Medical School
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2
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Turashvili G. Nonneoplastic and neoplastic sclerosing lesions of the breast. Histopathology 2024; 85:383-396. [PMID: 38923027 DOI: 10.1111/his.15252] [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] [Indexed: 06/28/2024]
Abstract
Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.
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Affiliation(s)
- Gulisa Turashvili
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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3
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Varga Z, Maccio U. Molecular pathology in breast disease: diagnostic, prognostic, and therapeutic tools. Virchows Arch 2024; 484:247-261. [PMID: 38015260 PMCID: PMC10948467 DOI: 10.1007/s00428-023-03709-0] [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: 07/31/2023] [Revised: 11/08/2023] [Accepted: 11/14/2023] [Indexed: 11/29/2023]
Abstract
Molecular testing in breast cancer gained increasing attention and importance as specific molecular results can tailor not only oncological decisions on systemic adjuvant or neoadjuvant or in metastatic setting, but increasingly serve in diagnostic routine histopathological services to differentiate between morphologically overlapping or ambiguous histological pictures. Diagnostic tools involve in most cases a broad spectrum of immunohistochemical panels, followed by entity-specific in situ hybridization probes and in given cases NGS-based sequencing. Workflow of which methodology is applied and in which order depends on the specific entity resp. on the given differential diagnosis in question. Regarding prognostic/predictive molecular testing, the choice of assay and the workflow are based on clinical algorithms and on the evidence of targeted therapies following the molecular alterations. In this review paper, we aim to address the use of molecular technics in [1] the histological diagnostic setting (such as subtyping of invasive carcinomas/malignant spindle cell tumors and sarcomas and some B3 lesions) and [2] in the context of adjuvant or neoadjuvant or other clinical settings with special focus of targeted therapies.
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Affiliation(s)
- Zsuzsanna Varga
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland.
| | - Umberto Maccio
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland
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4
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Webersinke G, Burghofer J, Malli T, Rammer M, Jahn SW, Niendorf A, Tavassoli FA, Moinfar F. TERT Promoter Mutation c.-124C>T Commonly Occurs in Low-Grade Fibromatosis-like Metaplastic Breast Carcinoma. Arch Pathol Lab Med 2023; 147:1451-1457. [PMID: 36897999 DOI: 10.5858/arpa.2022-0159-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2022] [Indexed: 03/12/2023]
Abstract
CONTEXT.— Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences. OBJECTIVE.— To genetically characterize FLMC. DESIGN.— To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases. RESULTS.— All cases shared TERT alterations (6 patients with recurrent c.-124C>T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability, with only few copy number variations and a low tumor mutational burden. CONCLUSIONS— We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C>T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.
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Affiliation(s)
- Gerald Webersinke
- From the Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz/Hospital of the Sisters of Charity, Linz, Austria (Webersinke, Burghofer, Malli, Rammer)
| | - Jonathan Burghofer
- From the Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz/Hospital of the Sisters of Charity, Linz, Austria (Webersinke, Burghofer, Malli, Rammer)
| | - Theodora Malli
- From the Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz/Hospital of the Sisters of Charity, Linz, Austria (Webersinke, Burghofer, Malli, Rammer)
| | - Melanie Rammer
- From the Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz/Hospital of the Sisters of Charity, Linz, Austria (Webersinke, Burghofer, Malli, Rammer)
| | - Stephan Wenzel Jahn
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria (Jahn, Moinfar)
| | - Axel Niendorf
- Department of Pathology and Molecular Diagnostic, Hamburg-West, Hamburg, Germany (Niendorf)
| | - Fattaneh A Tavassoli
- Department of Pathology, Yale University School of Medicine, New Haven Connecticut (Tavassoli)
| | - Farid Moinfar
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria (Jahn, Moinfar)
- Department of Pathology and Molecular Pathology, Vinzenz Pathologieverbund Linz, Austria (Moinfar)
- The Vincent Academy of Pathology, Linz, Austria (Moinfar)
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5
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Bao WY, Zhou JH, Luo Y, Lu Y. Fibromatosis-like metaplastic carcinoma of the breast: Two case reports. World J Clin Cases 2023; 11:4384-4391. [PMID: 37449215 PMCID: PMC10336999 DOI: 10.12998/wjcc.v11.i18.4384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/18/2023] [Accepted: 05/12/2023] [Indexed: 06/26/2023] Open
Abstract
BACKGROUND Fibromatosis-like metaplastic carcinoma is classified as a rare type of metaplastic carcinoma of the breast by the 2012 WHO pathological and genetic classification criteria for breast tumors, which takes hyperplastic spindle cells as the main component and is often misdiagnosed as benign stromal proliferative lesions or benign mesenchymal tumors of the breast because of its mild morphology. Here, we collected the clinical data of 2 cases of fibromatosis-like metaplastic carcinoma of the breast and performed pathomorphological observation and immunohistochemical staining of the surgically resected specimens. According to the clinical features, imaging features, immunophenotype, diagnosis and differential diagnosis of 2 cases of fibromatosis-like metaplastic carcinoma of the breast, it was further differentiated.
CASE SUMMARY Case 1: A 56-year-old postmenopausal female was admitted due to "right breast mass for over 1 year and local ulceration for over 1 mo". Physical examination showed a mass with a diameter of 4.5 cm × 5.5 cm palpable at 2.5 cm from the nipple at 1 o'clock in the right breast. The skin on the surface of the mass ruptured about 3 cm, with a small amount of exudation and bleeding, less clear boundary, hard texture, fair activity, without obvious tenderness. No obvious abnormality was palpable in the left breast. No enlarged lymph nodes were palpable in the bilateral axillae and bilateral supraclavicular region. After removing the mass tissue, it was promptly sent to the pathology department for examination. Case 2: Female, 52-years-old, premenopausal, admitted due to "right breast mass for more than 3 mo". Physical examination showed a 4.0 cm × 4.0 cm diameter mass palpable at 2.0 cm of the nipple in the lower outer 7 o'clock direction of the right breast, with less clear boundary, hard texture, fair activity, no significant tenderness, no palpable significant abnormalities in the left breast, and no palpable enlarged lymph nodes in the bilateral axillae and bilateral supraclavicular region. The mass was resected and sent for pathological examination. Postoperative pathological examination revealed fibromatosis-like metaplastic carcinoma of the breast in both patient 1 and patient 2. No systemic therapy and local radiotherapy were performed after surgery, and no tumor recurrence or metastasis was observed.
CONCLUSION Fibromatosis-like metaplastic carcinoma of the breast is a rare subtype of metaplastic carcinoma that is often misdiagnosed, and the diagnosis relies on medical history collection, complete sampling, and full use of immunohistochemical assessment. The risk of lymph node and distant metastasis is low, and the current treatment is based on complete surgical resection. The efficacy of systemic radiotherapy and chemotherapy is not clear.
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Affiliation(s)
- Wei-Yu Bao
- Department of Breast Surgery I, Gansu Provincial Cancer Hospital, Lanzhou 730050, Gansu Province, China
| | - Jiang-Hong Zhou
- Department of Nursing, Gansu Provincial Cancer Hospital, Lanzhou 730050, Gansu Province, China
| | - Yan Luo
- Department of Pathology, Gansu Provincial Cancer Hospital, Lanzhou 730050, Gansu Province, China
| | - Yun Lu
- Functional Department, Gansu Provincial Cancer Hospital, Lanzhou 730050, Gansu Province, China
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6
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Papatheodoridi A, Papamattheou E, Marinopoulos S, Ntanasis-Stathopoulos I, Dimitrakakis C, Giannos A, Kaparelou M, Liontos M, Dimopoulos MA, Zagouri F. Metaplastic Carcinoma of the Breast: Case Series of a Single Institute and Review of the Literature. Med Sci (Basel) 2023; 11:medsci11020035. [PMID: 37218987 DOI: 10.3390/medsci11020035] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/08/2023] [Accepted: 05/17/2023] [Indexed: 05/24/2023] Open
Abstract
Metaplastic carcinoma of the breast (MpBC) is a very rare and aggressive type of breast cancer. Data focusing on MpBC are limited. The aim of this study was to describe the clinicopathological features of MpBC and evaluate the prognosis of patients with MpBC. Eligible articles about MpBC were identified by searching CASES SERIES gov and the MEDLINE bibliographic database for the period of 1 January 2010 to 1 June 2021 with the keywords metaplastic breast cancer, mammary gland cancer, neoplasm, tumor, and metaplastic carcinoma. In this study, we also report 46 cases of MpBC stemming from our hospital. Survival rates, clinical behavior, and pathological characteristics were analyzed. Data from 205 patients were included for analysis. The mean age at diagnosis was 55 (14.7) years. The TNM stage at diagnosis was mostly stage II (58.5%) and most tumors were triple negative. The median overall survival was 66 (12-118) months, and the median disease-free survival was 56.8 (11-102) months. Multivariate Cox regression analysis revealed that surgical treatment was associated with decreased risk of death (hazard ratio 0.11, 95% confidence interval 0.02-0.54, p = 0.01) while advanced TNM stage was associated with increased risk of death (hazard ratio 1.5, 95% confidence interval 1.04-2.28, p = 0.03). Our results revealed that surgical treatment and TNM stage were the only independent risk factors related to patients' overall survival.
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Affiliation(s)
- Alkistis Papatheodoridi
- Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, 115 28 Athens, Greece
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, 115 28 Athens, Greece
| | - Eleni Papamattheou
- Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, 115 28 Athens, Greece
- 1st Department of Obstetrics & Gynecology, "Alexandra" Hospital, Medical School, University of Athens, 115 28 Athens, Greece
| | - Spyridon Marinopoulos
- 1st Department of Obstetrics & Gynecology, "Alexandra" Hospital, Medical School, University of Athens, 115 28 Athens, Greece
| | - Ioannis Ntanasis-Stathopoulos
- Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, 115 28 Athens, Greece
| | - Constantine Dimitrakakis
- 1st Department of Obstetrics & Gynecology, "Alexandra" Hospital, Medical School, University of Athens, 115 28 Athens, Greece
| | - Aris Giannos
- 1st Department of Obstetrics & Gynecology, "Alexandra" Hospital, Medical School, University of Athens, 115 28 Athens, Greece
| | - Maria Kaparelou
- Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, 115 28 Athens, Greece
| | - Michalis Liontos
- Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, 115 28 Athens, Greece
| | - Meletios-Athanasios Dimopoulos
- Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, 115 28 Athens, Greece
| | - Flora Zagouri
- Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, 115 28 Athens, Greece
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7
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Quinn C, Maguire A, Rakha E. Pitfalls in breast pathology. Histopathology 2023; 82:140-161. [PMID: 36482276 PMCID: PMC10107929 DOI: 10.1111/his.14799] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/11/2022] [Accepted: 09/12/2022] [Indexed: 12/13/2022]
Abstract
Accurate pathological diagnosis is the cornerstone of optimal clinical management for patients with breast disease. As non-operative diagnosis has now become the standard of care, histopathologists encounter the daily challenge of making definitive diagnoses on limited breast core needle biopsy (CNB) material. CNB samples are carefully evaluated using microscopic examination of haematoxylin and eosin (H&E)-stained slides and supportive immunohistochemistry (IHC), providing the necessary information to inform the next steps in the patient care pathway. Some entities may be difficult to distinguish on small tissue samples, and if there is uncertainty a diagnostic excision biopsy should be recommended. This review discusses (1) benign breast lesions that may mimic malignancy, (2) malignant conditions that may be misinterpreted as benign, (3) malignant conditions that may be incorrectly diagnosed as primary breast carcinoma, and (4) some IHC pitfalls. The aim of the review is to raise awareness of potential pitfalls in the interpretation of breast lesions that may lead to underdiagnosis, overdiagnosis, or incorrect classification of malignancy with potential adverse outcomes for individual patients.
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Affiliation(s)
- Cecily Quinn
- Irish National Breast Screening Programme and Department of Histopathology, St. Vincent's University Hospital, Dublin, Ireland.,School of Medicine, University College Dublin, Dublin, Ireland
| | - Aoife Maguire
- Irish National Breast Screening Programme and Department of Histopathology, St. Vincent's University Hospital, Dublin, Ireland
| | - Emad Rakha
- Department of Histopathology, The University of Nottingham, Nottingham City Hospital, Nottingham, UK
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8
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Fibromatosis-like metaplastic carcinoma: A rare case report. Asian J Surg 2022; 46:2125-2127. [PMID: 36428135 DOI: 10.1016/j.asjsur.2022.11.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 11/11/2022] [Indexed: 11/24/2022] Open
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9
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Pham KH, Nguyen CV, Do TA, Pham HT, Do KH, Le DT. Fibromatosis-Like Metaplastic Carcinoma: A Triple-Negative Breast Cancer with Clinically Indolent Behavior. Case Rep Oncol 2022; 15:816-826. [PMID: 36825103 PMCID: PMC9941779 DOI: 10.1159/000526535] [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: 06/29/2022] [Accepted: 08/04/2022] [Indexed: 11/19/2022] Open
Abstract
Fibromatosis-like metaplastic carcinoma is a special variant of spindle cell carcinoma, a type of metaplastic carcinomas. It has a favorable prognosis, unlike other metaplastic carcinomas, with a particular clinical behavior characterized by frequent local recurrence, the meager potential for axillary lymph nodes, and distant metastases. We presented the case of a 51-year-old female with a large mass on the left breast, which was successfully removed by surgical resection. The pathological diagnosis was fibromatosis-like metaplastic carcinoma with the help of morphology and immunohistochemistry adjustment.
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Affiliation(s)
| | - Chu Van Nguyen
- aNational Cancer Hospital, Hanoi, Vietnam,bHanoi Medical University, Hanoi, Vietnam,*Chu Van Nguyen,
| | - Tu Anh Do
- aNational Cancer Hospital, Hanoi, Vietnam
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10
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Russell DH, Montgomery EA, Susnik B. Low to Intermediate (Borderline) Grade Breast Spindle Cell Lesions on Needle Biopsy: Diagnostic Approach and Clinical Management. Adv Anat Pathol 2022; 29:309-323. [PMID: 35838633 DOI: 10.1097/pap.0000000000000353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Spindle cell proliferations of the breast are a heterogeneous group of lesions ranging from benign or reactive lesions to aggressive malignant neoplasms. Diagnosis on core biopsy can be particularly challenging as lesions displaying different lineages associated with variable outcomes share overlapping morphologies (scar vs. fibromatosis-like metaplastic carcinoma) whereas individual entities can exhibit a large variety of appearances (myofibroblastoma). In this review, lesions are grouped into lineage, when possible, including those showing fibroblastic/myofibroblastic differentiation, ranging from entities that require no additional management, such as scar and nodular fasciitis, to those with unpredictable clinical outcomes such as fibromatosis and solitary fibrous tumor or locally aggressive behavior such as dermatofibrosarcoma protuberans. The review of low-grade vascular lesions includes atypical vascular lesion and low-grade angiosarcoma. Also discussed are various adipocytic lesions ranging from lipoma to liposarcoma, and rare smooth muscle and neural entities more commonly encountered in locations outside the breast, such as leiomyoma, neurofibroma, schwannoma, or granular cell tumor. Optimal histological evaluation of these entities merges clinical and radiologic data with morphology and ancillary testing. We present our approach to immunohistochemical and other ancillary testing and highlight issues in pathology correlation with imaging. Recent updates in the management of breast spindle cell lesions are addressed. In a well-sampled lesion with radiographic concordance, the core biopsy diagnosis reliably guides management and we advocate the inclusion of management recommendations in the pathology report. Precise characterization using up to date guidelines is important to identify a subset of patients who may safely avoid unnecessary surgical procedures. A multidisciplinary approach with close collaboration with our clinical colleagues is emphasized.
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Affiliation(s)
- Daniel H Russell
- Departments of Pathology University of Miami Hospital and Jackson Health Systems, Miami, FL
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11
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Fusco N, Sajjadi E, Venetis K, Ivanova M, Andaloro S, Guerini-Rocco E, Montagna E, Caldarella P, Veronesi P, Colleoni M, Viale G. Low-risk triple-negative breast cancers: Clinico-pathological and molecular features. Crit Rev Oncol Hematol 2022; 172:103643. [PMID: 35217131 DOI: 10.1016/j.critrevonc.2022.103643] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/18/2022] [Accepted: 02/19/2022] [Indexed: 12/18/2022] Open
Abstract
Triple-negative breast cancers (TNBC) comprise biologically and clinically heterogeneous diseases characterized by the lack of hormone receptors (HR) and HER2 expression. This subset of tumors accounts for 15-20% of all breast cancers and pursues an ominous clinical course. However, there is a spectrum of low-risk TNBCs with no/minimal metastatic potential, including the salivary gland-type tumors, those with extensive apocrine differentiation and/or high tumor-infiltrating lymphocytes, and small-sized, early-stage (pT1a/bN0M0) TNBCs. De-escalating the treatment in low-risk TNBC, however, is not trivial because of the substantial lack of dedicated randomized clinical trials and cancer registries. The development of new diagnostic and/or prognostic biomarkers based on clinical and molecular aspects of low-risk TNBCs would lead to improved clinical treatment. Here, we sought to provide a portrait of the clinicopathological and molecular features of low-risk TNBC, with a focus on the diagnostic challenges along with the most important biological characteristics underpinning their favorable clinical course.
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Affiliation(s)
- Nicola Fusco
- Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy.
| | - Elham Sajjadi
- Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy
| | - Konstantinos Venetis
- Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy
| | - Mariia Ivanova
- Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy
| | - Silvia Andaloro
- Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy
| | - Elena Guerini-Rocco
- Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy
| | - Emilia Montagna
- Division of Medical Senology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy
| | - Pietro Caldarella
- Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy
| | - Paolo Veronesi
- Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy; Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy
| | - Marco Colleoni
- Division of Medical Senology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy
| | - Giuseppe Viale
- Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy
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12
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Han J, Liu S, Shioya A, Kumagai M, Morioka E, Noguchi M, Inokuchi M, Yamada S. Recurrent malignant phyllodes tumor of the breast: An extremely rare case of recurrence with only rhabdomyosarcoma components. SAGE Open Med Case Rep 2022; 10:2050313X221116667. [PMID: 35958881 PMCID: PMC9358339 DOI: 10.1177/2050313x221116667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/11/2022] [Indexed: 12/03/2022] Open
Abstract
Rhabdomyosarcoma is a rare disease that typically occurs in children. Rhabdomyosarcoma
seldom occurs in the breast, and its diagnosis and treatment have infrequently been
reported. The present case is a rare one of a recurrent malignant phyllodes tumor of the
breast with only rhabdomyosarcoma components. A 69-year-old woman received a diagnosis of
borderline phyllodes tumor of the left breast and underwent partial mastectomy. During
follow-up, a left breast mass was found 1 year and 8 months after the previous surgery.
Based on examination findings, it was suspected to be recurrent phyllodes tumor, so total
left mastectomy was performed in our hospital. After the surgery, immunostaining failed to
determine the epithelial component which may be produced by the proliferative part of
stromal cells of previous phyllodes tumors. However, we could not exclude the possibility
that this was a new tumor. After comparing samples with specimens from the first
operation, it was finally determined to be a malignant phyllodes tumor with a
rhabdomyosarcoma component. Therefore, chemotherapy was given, and vincristine,
actinomycin D, and cyclophosphamide therapy was introduced. At the same time, radiation
therapy was planned. Among phyllodes tumors, cases involving rhabdomyosarcoma components
are very rare, especially those where the recurrence morphology only shows the same
rhabdomyosarcoma components. This was a rare case with unique characteristics and great
reference value.
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Affiliation(s)
- Jia Han
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku, Japan
- Department of Diagnostic Pathology, Kanazawa Medical University Hospital, Kahoku, Japan
| | - Shuice Liu
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku, Japan
- Department of Diagnostic Pathology, Kanazawa Medical University Hospital, Kahoku, Japan
| | - Akihoro Shioya
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku, Japan
- Department of Diagnostic Pathology, Kanazawa Medical University Hospital, Kahoku, Japan
| | - Motona Kumagai
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku, Japan
- Department of Diagnostic Pathology, Kanazawa Medical University Hospital, Kahoku, Japan
| | - Emi Morioka
- Department of Breast and Endocrine Surgery, Kanazawa Medical University Hospital, Kahoku, Japan
| | - Miki Noguchi
- Department of Breast and Endocrine Surgery, Kanazawa Medical University Hospital, Kahoku, Japan
| | - Masafumi Inokuchi
- Department of Breast and Endocrine Surgery, Kanazawa Medical University Hospital, Kahoku, Japan
| | - Sohsuke Yamada
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku, Japan
- Department of Diagnostic Pathology, Kanazawa Medical University Hospital, Kahoku, Japan
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13
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Cserni G, Quinn CM, Foschini MP, Bianchi S, Callagy G, Chmielik E, Decker T, Fend F, Kovács A, van Diest PJ, Ellis IO, Rakha E, Tot T, European Working Group for Breast Screening Pathology. Triple-Negative Breast Cancer Histological Subtypes with a Favourable Prognosis. Cancers (Basel) 2021; 13:5694. [PMID: 34830849 PMCID: PMC8616217 DOI: 10.3390/cancers13225694] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/03/2021] [Accepted: 11/09/2021] [Indexed: 12/21/2022] Open
Abstract
Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.
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Affiliation(s)
- Gábor Cserni
- Department of Pathology, University of Szeged, 6725 Szeged, Hungary
- Department of Pathology, Bács-Kiskun County Teaching Hospital, 6000 Kecskemét, Hungary
| | - Cecily M. Quinn
- Department of Histopathology, BreastCheck, Irish National Breast Screening Programme & St. Vincent’s University Hospital, D04 T6F4 Dublin, Ireland
- School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland
| | - Maria Pia Foschini
- Unit of Anatomic Pathology, Department of Biomedical and Neuromotor Sciences, Bellaria Hospital, University of Bologna, 40139 Bologna, Italy;
| | - Simonetta Bianchi
- Department of Health Sciences, Division of Pathological Anatomy, University of Florence, 50134 Florence, Italy;
| | - Grace Callagy
- Discipline of Pathology, School of Medicine, National University of Ireland Galway, H91 TK33 Galway, Ireland;
| | - Ewa Chmielik
- Tumor Pathology Department, Maria Sklodowska-Curie Memorial National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland;
| | - Thomas Decker
- Department of Surgical Pathology, Dietrich Bonhoeffer Medical Centre, 17036 Neubrandenburg, Germany;
- Reference Centre for Mammography Münster, University Hospital Münster, 48149 Münster, Germany
- Reference Center for Mammography, 10623 Berlin, Germany
| | - Falko Fend
- Department of Pathology, University of Tübingen, 72076 Tübingen, Germany;
| | - Anikó Kovács
- Department of Clinical Pathology, Sahlgrenska University Hospital, 41 345 Gothenburg, Sweden;
| | - Paul J. van Diest
- Department of Pathology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands;
| | - Ian O. Ellis
- Department of Histopathology, University of Nottingham and The Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham NG5 1PB, UK; (I.O.E.); (E.R.)
| | - Emad Rakha
- Department of Histopathology, University of Nottingham and The Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham NG5 1PB, UK; (I.O.E.); (E.R.)
| | - Tibor Tot
- Pathology & Cytology Dalarna, Falun County Hospital, 791 82 Falun, Sweden;
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Rakha EA, Brogi E, Castellano I, Quinn C. Spindle cell lesions of the breast: a diagnostic approach. Virchows Arch 2021; 480:127-145. [PMID: 34322734 PMCID: PMC8983634 DOI: 10.1007/s00428-021-03162-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/27/2021] [Accepted: 07/12/2021] [Indexed: 12/13/2022]
Abstract
Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their rarity, they attract the attention of breast pathologists due to their overlapping morphological features and diagnostic challenges, particularly on core needle biopsy (CNB) specimens. Pathologists should recognise the wide range of differential diagnoses and be familiar with the diverse morphological appearances of these lesions to make an accurate diagnosis and to suggest proper management of the patients. Clinical history, immunohistochemistry, and molecular assays are helpful in making a correct diagnosis in morphologically challenging cases. In this review, we present our approach for the diagnosis of breast spindle cell lesions, highlighting the main features of each entity and the potential pitfalls, particularly on CNB. Breast spindle cell lesions are generally classified into two main categories: bland-appearing and malignant-appearing lesions. Each category includes a distinct list of differential diagnoses and a panel of immunohistochemical markers. In bland-appearing lesions, it is important to distinguish fibromatosis-like spindle cell metaplastic breast carcinoma from other benign entities and to distinguish fibromatosis from scar tissue. The malignant-appearing category includes spindle cell metaplastic carcinoma, stroma rich malignant phyllodes tumour, other primary and metastatic malignant spindle cell tumours of the breast, including angiosarcoma and melanoma, and benign mimics such as florid granulation tissue and nodular fasciitis.
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Affiliation(s)
- Emad A Rakha
- Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK.
| | - Edi Brogi
- Department of Pathology At Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Cecily Quinn
- Histopathology, BreastCheck, Irish National Breast Screening Programme and St. Vincent's University Hospital, Dublin, Ireland.,University College Dublin, Dublin, Ireland
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Breast carcinomas of low malignant potential. Virchows Arch 2021; 480:5-19. [PMID: 34292391 DOI: 10.1007/s00428-021-03163-w] [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] [Received: 06/03/2021] [Revised: 07/02/2021] [Accepted: 07/12/2021] [Indexed: 12/22/2022]
Abstract
Some breast carcinomas have a very low likelihood of metastasis to regional lymph nodes and distant sites and may be considered carcinomas of low malignant potential. In this article, we review the clinical, pathologic, immunophenotypic, and molecular features of selected breast carcinomas of low malignant potential including low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, encapsulated papillary carcinoma, solid papillary carcinoma, and tall cell carcinoma with reversed polarity.
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16
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Gadaleta-Caldarola G, Nenna R, Lanotte L, Doronzo A, Gadaleta-Caldarola A, Roma ID, Lombardi L, Infusino S. Metaplastic breast cancer: an old histotype but a current therapeutic problem. Future Oncol 2021; 17:955-963. [PMID: 33538176 DOI: 10.2217/fon-2020-0490] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Metaplastic breast cancer (MPBC) is a rare and aggressive tumor type in great need of satisfactory therapies. Although most cases of MPBC are 'triple negative', they are nonetheless related to worse outcomes compared with other triple-negative invasive tumors. MPBC presents high levels of genetic and molecular heterogeneity, suggesting that novel targeted therapies can be exploited. Overexpression of PD-L1 and high levels of tumor-infiltrating lymphocytes have also been observed in these tumors, suggesting a role for immunotherapy. We present an updated literature revision on clinical, histopathological and molecular features of MPBC and their significance to prognosis and therapy options. We discuss emerging efforts to improve and personalize prognostic and therapeutic approaches, exploiting the molecular signature of MPBC with targeted therapies and immunotherapies.
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Affiliation(s)
| | - Rosanna Nenna
- Anatomic Patology Unit, "L. Bonomo" Hospital, Andria (BT), ASL BT, 76123, Italy
| | - Laura Lanotte
- Medical Oncology Unit, "Mons. R. Dimiccoli" Hospital, Barletta (BT), ASL BT, 76121, Italy
| | - Antonio Doronzo
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria "Ospedali Riuniti", Foggia, 71100, Italy
| | | | - Ileana de Roma
- Medical Oncology Unit, "Mons. R. Dimiccoli" Hospital, Barletta (BT), ASL BT, 76121, Italy
| | - Lucia Lombardi
- Medical Oncology Unit, "Mons. R. Dimiccoli" Hospital, Barletta (BT), ASL BT, 76121, Italy
| | - Stefania Infusino
- Medical Oncology Unit, "SS. Annunziata" Hospital, Cosenza (CS), Azienda Ospedaliera di Cosenza, 87100, Italy
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