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Pareja F, Bhargava R, Borges VF, Brogi E, Canas Marques R, Cardoso F, Desmedt C, Harigopal M, Lakhani SR, Lee A, Leone JP, Linden H, Lord CJ, Marchio C, Merajver SD, Rakha E, Reis-Filho JS, Richardson A, Sawyer E, Schedin P, Schwartz CJ, Tutt A, Ueno NT, Vincent-Salomon A, Weigelt B, Wen YH, Schnitt SJ, Oesterreich S. Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes. NPJ Breast Cancer 2025; 11:6. [PMID: 39856067 PMCID: PMC11760369 DOI: 10.1038/s41523-025-00719-w] [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: 05/30/2024] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases. Uncommon BC presentations like male, inflammatory and pregnancy-related BC pose challenges. Emerging therapeutic strategies targeting genetic alterations or immune microenvironment are being explored.
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Affiliation(s)
- Fresia Pareja
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Rohit Bhargava
- Department of Pathology, University of Pittsburgh School of Medicine, UPMC Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Virginia F Borges
- Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Edi Brogi
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Fatima Cardoso
- Breast Unit, Champalimaud Clinical Centre/Champalimaud Foundation, Lisbon, Portugal
| | - Christine Desmedt
- Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium
| | - Malini Harigopal
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sunil R Lakhani
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, and Pathology Queensland, Brisbane, QLD, Australia
| | - Adrian Lee
- Women's Cancer Research Center, Magee-Womens Research Institute, UPMC Hillmann Cancer Center, Pittsburgh, PA, USA
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jose Pablo Leone
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Hannah Linden
- Division of Hematology and Oncology, Fred Hutchinson Cancer Center/University of Washington, Seattle, WA, USA
| | - Christopher J Lord
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
| | - Caterina Marchio
- Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Turin, Italy
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Sofia D Merajver
- Breast and Ovarian Cancer Risk Evaluation Program, Department of Internal Medicine, Michigan Medicine, Ann Arbor, MI, USA
| | - Emad Rakha
- Department of Pathology, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Jorge S Reis-Filho
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- AstraZeneca, Cambridge, UK
| | | | - Elinor Sawyer
- School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, Guy's Cancer Centre, King's College London, London, UK
| | - Pepper Schedin
- Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
| | - Christopher J Schwartz
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrew Tutt
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
| | - Naoto T Ueno
- Breast Medical Oncology, University of Hawaii Cancer Center, Honolulu, HI, USA
| | - Anne Vincent-Salomon
- Department of Pathology, Curie Institute, Paris Sciences Lettres University, Paris, France
| | - Britta Weigelt
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Y Hannah Wen
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Stuart J Schnitt
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
| | - Steffi Oesterreich
- Women's Cancer Research Center, Magee-Womens Research Institute, UPMC Hillmann Cancer Center, Pittsburgh, PA, USA.
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
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Alshwayyat S, Abu Al Hawa MB, Alshwayyat M, Alshwayyat TA, Sawan S, Heilat G, Hammouri HM, Mheid S, Al Shweiat B, Hanifa H. Personalized treatment strategies for breast adenoid cystic carcinoma: A machine learning approach. Breast 2025; 79:103878. [PMID: 39826386 PMCID: PMC11786111 DOI: 10.1016/j.breast.2025.103878] [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: 11/20/2024] [Revised: 12/29/2024] [Accepted: 01/08/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Breast adenoid cystic carcinoma (BACC) is a rare subtype of breast cancer that accounts for less than 0.1 % of all cases. This study was designed to assess the efficacy of various treatment approaches for BACC and to create the first web-based tool to facilitate personalized treatment decisions. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was used for this study's analysis. To identify the prognostic variables, we conducted Cox regression analysis and constructed prognostic models using five Machine Learning (ML) algorithms to predict the 5-year survival. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to validate the accuracy and reliability of ML models. We also performed a Kaplan-Meier (K-M) survival analysis. RESULTS This study included 1212 patients. The median age was 60 years, with most tumors being localized and less than 2 cm in size. The 5-year overall survival (OS) rates were highest for surgery + radiotherapy (RT) (94.9 %) and lowest for surgery + chemotherapy (CTX) + RT (80.1 %). Positive estrogen receptor (ER) status and younger age were associated with better survival outcomes. ML models identified key predictive features for survival, including age, nodal status, and ER status. CONCLUSION Age, lymph node metastasis, and ER status are crucial prognostic indicators for BACC. Although postoperative RT enhances survival, the advantages of adjuvant CTX are uncertain, implying that it may be eschewed to avert adverse effects. Our online tool offers essential resources for prognostication and treatment optimization.
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Affiliation(s)
- Sakhr Alshwayyat
- King Hussein Cancer Center, Amman, Jordan; Princess Basma Teaching Hospital, Irbid, Jordan; Research Fellow, Applied Science Research Center, Applied Science Private University, Amman, Jordan.
| | | | - Mustafa Alshwayyat
- Faculty of Medicine, Jordan University of Science & Technology, Irbid, Jordan.
| | | | - Siya Sawan
- Faculty of Medicine, University of Jordan, Amman, Jordan.
| | - Ghaith Heilat
- Breast Oncoplastic and General Surgery, Department of General Surgery and Urology, Jordan University of Science & Technology, King Abdullah University Hospital, Irbid, Jordan.
| | - Hanan M Hammouri
- Department of Mathematics and Statistics, Faculty of Arts and Science, Jordan University of Science and Technology, Irbid, Jordan.
| | - Sara Mheid
- Radiation Oncology Department, King Hussein Cancer Center, Amman, Jordan.
| | - Batool Al Shweiat
- Breast Imaging Fellow, Department of Radiology, King Hussein Cancer Center, Amman, Jordan.
| | - Hamdah Hanifa
- Faculty of Medicine, University of Kalamoon, Al_Nabk, Syria.
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Abdellateif MS, Bayoumi AK, Mohammed MA. c-Kit Receptors as a Therapeutic Target in Cancer: Current Insights. Onco Targets Ther 2023; 16:785-799. [PMID: 37790582 PMCID: PMC10544070 DOI: 10.2147/ott.s404648] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 09/19/2023] [Indexed: 10/05/2023] Open
Abstract
c-Kit is a type III receptor tyrosine kinase (RTK) that has an essential role in various biological functions including gametogenesis, melanogenesis, hematopoiesis, cell survival, and apoptosis. c-KIT aberrations, either overexpression or loss-of-function mutations, have been implicated in the pathogenesis and development of many cancers, including gastrointestinal stromal tumors, mastocytosis, acute myeloid leukemia, breast, thyroid, and colorectal cancer, making c-KIT an attractive molecular target for the treatment of cancers. Therefore, a lot of effort has been put into investigating the utility of tyrosine kinase inhibitors for the management of c-KIT mutated tumors. This review of the literature illustrates the role of c-KIT mutations in many cancers, aiming to provide insights into the role of TKIs as a therapeutic option for cancer patients with c-KIT aberrations. In conclusion, c-KIT is implicated in different types of cancer, and it could be a successful molecular target; however, proper detection of the underlying mutation type is required before starting the appropriate personalized therapy.
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Affiliation(s)
- Mona S Abdellateif
- Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt
| | - Ahmed K Bayoumi
- Paediatric Oncology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt
- Children’s Cancer Hospital 57357, Cairo, 11617, Egypt
| | - Mohammed Aly Mohammed
- Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt
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Matsumoto H, Harada H, Tsuruta Y, Yasutomi Y, Nakada N, Kondo S, Koki A, Unesoko M, Abe N, Zaha H, Tan PH. Unusual presentation of breast adenoid cystic carcinoma resembling adenomyoepithelioma with multiple distinct foci. Pathol Res Pract 2023; 248:154650. [PMID: 37392549 DOI: 10.1016/j.prp.2023.154650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/23/2023] [Accepted: 06/25/2023] [Indexed: 07/03/2023]
Abstract
We describe an unusual case of multifocal breast adenoid cystic carcinoma (AdCC) with adenomyoepitheliomatous morphology. Most breast AdCCs are unifocal and only four cases of multifocal AdCC have been reported previously, however, to our best knowledge, multifocality in AdCC confirmed by molecular analysis has not been reported, so this report adds to the literature on this unique presentation. An 80-year-old woman presented with a left breast mass at 1 o'clock and non-mass enhancement lesion at 5 o'clock on imaging. Incisional biopsy at 1 o'clock showed AdCC based on histopathological features and MYB rearrangement by fluorescent in situ hybridization (FISH). As AdCC involved the margins and the non-mass enhancing lesion remained, mastectomy was performed. Microscopically, the lesion at 5 o'clock demonstrated multinodularity and a biphasic epithelial-basaloid/myoepithelial pattern. Although histological features resembled adenomyoepithelioma, MYB rearrangement was identified on FISH, so the 5 o'clock lesion was also diagnosed as AdCC showing an adenomyoepitheliomatous pattern. This unusual presentation is a potential diagnostic pitfall, so pathologists should consider AdCC as a possible differential diagnosis of multifocal basaloid breast tumors with adenomyoepitheliomatous features.
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Affiliation(s)
| | - Hiroshi Harada
- Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Yuma Tsuruta
- Department of Pathology, Nakagami Hospital, Okinawa, Japan
| | - Yuiko Yasutomi
- Department of Pathology, Nakagami Hospital, Okinawa, Japan
| | | | - Sakiko Kondo
- Department of Breast Surgery, Nakagami Hospital, Okinawa, Japan
| | - Ayako Koki
- Department of Breast Surgery, Nakagami Hospital, Okinawa, Japan
| | - Mikiko Unesoko
- Department of Breast Surgery, Nakagami Hospital, Okinawa, Japan
| | - Norie Abe
- Department of Breast Surgery, Nakagami Hospital, Okinawa, Japan
| | - Hisamitsu Zaha
- Department of Breast Surgery, Nakagami Hospital, Okinawa, Japan
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Vijapura C, Rosen L, Wahab R. Adenoid Cystic Carcinoma of the Breast: Radiologic-Pathologic Correlation. JOURNAL OF BREAST IMAGING 2022; 4:625-631. [PMID: 38416992 DOI: 10.1093/jbi/wbac045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Indexed: 03/01/2024]
Abstract
Adenoid cystic carcinoma (ACC) is an uncommon malignancy occurring most frequently in the salivary glands. Breast ACC is rare. Pain is common at the site of ACC; otherwise, presentation is similar to other primary breast cancers. Adenoid cystic carcinomas classically lack calcifications; the imaging manifestations of ACC are otherwise highly variable, likely related to multiple pathologic growth patterns. While ACC in other regions of the body tends to be more aggressive, ACC involving the breast typically has less aggressive biologic characteristics. Classic-type breast ACC has a lower tendency to recur locally with radiation, metastasize to regional lymph nodes, and spread to other parts of the body. Perineural spread of disease can be seen but is not common. The rarer solid basaloid-type has a higher tendency for local or distant spread and recurrence. Although ACC is usually triple receptor-negative (estrogen receptor, progesterone receptor, human epidermal growth factor-2 receptor), the indolent nature of this tumor dictates its management. With classic-type ACC, the inclusion of axillary surgery has no consensus and the use of chemotherapy or hormonal therapy is rare. Axillary nodal surgery and chemotherapy are often included in management of the more aggressive solid basaloid-type. An understanding of the breast imaging, histopathology, and clinical course is key for appropriate treatment and follow-up of ACC.
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Affiliation(s)
- Charmi Vijapura
- University of Cincinnati Medical Center, Department of Radiology, Cincinnati, OH, USA
| | - Lauren Rosen
- University of Cincinnati Medical Center, Department of Pathology, Cincinnati, OH, USA
| | - Rifat Wahab
- University of Cincinnati Medical Center, Department of Radiology, Cincinnati, OH, USA
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Hara Y, Yamaguchi R, Yano H, Iwasaki K. Adenoid Cystic Carcinoma, Solid-Basaloid Subtype of the Breast: A Case Report. Int J Surg Pathol 2022; 31:460-463. [PMID: 35635208 DOI: 10.1177/10668969221102548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We present a rare tumor of adenoid cystic carcinoma, solid-basaloid subtype of the breast. Solid-basaloid adenoid cystic carcinoma may have a worse prognosis than classical adenoid cystic carcinoma. A 70-year-old woman presented with a mass in her left breast. Malignancy was suspected on imaging and confirmed via core needle biopsy. Left breast partial mastectomy and sentinel lymph node biopsy were performed. Histologically, the tumor was composed of basaloid cells with hyperchromatic nuclei and frequent mitotic figures, as are small-cell neuroendocrine carcinomas. Immunohistochemical analysis of the tumor cells showed high expression of KIT and CD10 and focal expression of keratin 7. Synaptophysin, chromogranin A, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were not expressed. This patient should be followed up carefully for distant metastases and recurrences.
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Affiliation(s)
- Yuki Hara
- Department of Breast Surgery, Sasebo City General Hospital, Sasebo, Nagasaki, Japan
| | - Rin Yamaguchi
- Department of Pathology and Laboratory Medicine, Kurume University Medical Center, Kurume, Fukuoka, Japan
| | - Hiroshi Yano
- Department of Breast Surgery, Sasebo City General Hospital, Sasebo, Nagasaki, Japan
| | - Keisuke Iwasaki
- Department of Pathology, Sasebo City General Hospital, Sasebo, Nagasaki, Japan
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Tan BY, Lim EH, Tan PH. Special Histologic Type and Rare Breast Tumors - Diagnostic Review and Clinico-Pathological Implications. Surg Pathol Clin 2022; 15:29-55. [PMID: 35236633 DOI: 10.1016/j.path.2021.11.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Breast cancer is the most common malignant tumor in females. While most carcinomas are categorized as invasive carcinoma, no special type (NST), a diverse group of tumors with distinct pathologic and clinical features is also recognized, ranging in incidence from relatively more common to rare. So-called "special histologic type" tumors display more than 90% of a specific, distinctive histologic pattern, while a spectrum of tumors more often encountered in the salivary gland may also arise in the breast. Metaplastic carcinomas can present diagnostic challenges. Some uncommon tumors harbor pathognomonic genetic alterations. This article provides an overview of the key diagnostic points and differential diagnoses for this group of disparate lesions, as well as the salient clinical characteristics of each entity.
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Affiliation(s)
- Benjamin Yongcheng Tan
- Department of Anatomical Pathology, Singapore General Hospital, Level 10, Academia, 20 College Road, Singapore 169856, Singapore
| | - Elaine Hsuen Lim
- Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore 169610, Singapore
| | - Puay Hoon Tan
- Division of Pathology, Singapore General Hospital, Level 7, Diagnostics Tower, Academia, 20 College Road, Singapore 189856, Singapore.
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Vohra P, Chen YY, Krings G. Less Common Triple-Negative Breast Cancers. A COMPREHENSIVE GUIDE TO CORE NEEDLE BIOPSIES OF THE BREAST 2022:463-573. [DOI: 10.1007/978-3-031-05532-4_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Marco V, Garcia F, Rubio IT, Soler T, Ferrazza L, Roig I, Mendez I, Andreu X, Mínguez CG, Tresserra F. Adenoid cystic carcinoma and basaloid carcinoma of the breast: A clinicopathological study. REVISTA ESPAÑOLA DE PATOLOGÍA : PUBLICACIÓN OFICIAL DE LA SOCIEDAD ESPAÑOLA DE ANATOMÍA PATOLÓGICA Y DE LA SOCIEDAD ESPAÑOLA DE CITOLOGÍA 2021; 54:242-249. [PMID: 34544554 DOI: 10.1016/j.patol.2020.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 08/05/2020] [Accepted: 09/15/2020] [Indexed: 11/28/2022]
Abstract
Adenoid cystic carcinoma of the breast (ACCB) is a rare triple negative tumor (TNT) with an excellent prognosis in most cases. Three different histologic types are recognized: classic ACCB, solid basaloid ACCB (SB-ACCB), and ACCB with high-grade transformation. A majority of these tumors show characteristic molecular and immunohistochemical (IHC) features, with fusion of MYB and NFIB genes and overexpression of MYB, respectively. Basaloid carcinomas of the breast (BCB) are infrequently described. They resemble SB-ACCB and TNT of no special type (TNT-NST). We have studied the clinicopathological features of 17 ACCB and 9 BCB, investigating the expression of MYB by IHC and the rearrangements of MYB by fluorescence in situ hybridization (FISH). MYB was expressed by IHC in 15 ACCB and in 3 BCB. MYB FISH detected rearrangements in 11 ACCB and in 2 BCB. After a mean follow-up of 90 months, with a range of 12-204 months, 2 patients with ACCB with high-grade transformation and 1 patient with BCB developed metastases and died of disease. In summary, most ACCB have a good prognosis, but tumors with adverse histopathological features may metastasize. BCB may overlap with ACCB and TNT-NST, and their prognosis should be further studied.
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Affiliation(s)
- Vicente Marco
- Hospital Quironsalud Barcelona, Pathology, Barcelona, Spain.
| | - Felip Garcia
- Hospital Quironsalud Barcelona, Pathology, Barcelona, Spain
| | | | - Teresa Soler
- Hospital Universitari Bellvitge/ICO/IDIBELL, Hospitalet de Llobregat, Spain
| | - Laura Ferrazza
- Hospital Universitari Bellvitge/ICO/IDIBELL, Hospitalet de Llobregat, Spain
| | - Ignasi Roig
- Consorci Sanitari de Terrassa, Pathology, Terrassa, Spain
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An JK, Woo JJ, Kim EK, Kwak HY. Breast adenoid cystic carcinoma arising in microglandular adenosis: A case report and review of literature. World J Clin Cases 2021; 9:7579-7587. [PMID: 34616829 PMCID: PMC8464440 DOI: 10.12998/wjcc.v9.i25.7579] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/13/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Breast adenoid cystic carcinoma (AdCC) is a rare invasive carcinoma composed of epithelial and myoepithelial cells. Microglandular adenosis (MGA) is a rare benign proliferative lesion consisting of small, uniform, and round glands formed by a single layer of epithelial cells and basement membrane without a myoepithelial cell layer. MGA may progress to atypical MGA and carcinoma arising in MGA. Among various invasive carcinomas from MGA, AdCC has been rarely reported. Here, we report a case of AdCC arising in MGA.
CASE SUMMARY A 59-year-old woman was diagnosed with a newly developed density on a routine mammogram. The density was similar to or slightly lower than that of the breast parenchyma. Sonography showed an irregular mass with a slightly higher echo than that of fat. Magnetic resonance imaging showed an irregular mass with a similar T1 signal intensity and a slightly higher T2 signal intensity compared to muscles or the breast parenchyma. The lesion showed heterogeneous internal enhancement with an initially slow and delayed persistent enhancing pattern. Microscopically, the tumor was composed of invasive AdCC, in situ AdCC, and MGA. AdCC is composed of basaloid and ductal epithelial cells forming cribriform or solid sheets, or haphazardly scattered small cribriform or tubular glands. MGA showed small glands with a single epithelial lining and retained lumen. S-100 staining was strongly positive in MGA area. The patient underwent breast-conserving surgery with sentinel lymph node biopsy.
CONCLUSION Breast AdCC arising in MGA showed unique imaging findings that was different from usual invasive cancer.
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Affiliation(s)
- Jin Kyung An
- Department of Radiology, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, South Korea
| | - Jeong Joo Woo
- Department of Radiology, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, South Korea
| | - Eun Kyung Kim
- Department of Pathology, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, South Korea
| | - Hee Yong Kwak
- Department of Surgery, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, South Korea
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p63 expression in human tumors and normal tissues: a tissue microarray study on 10,200 tumors. Biomark Res 2021; 9:7. [PMID: 33494829 PMCID: PMC7830855 DOI: 10.1186/s40364-021-00260-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/05/2021] [Indexed: 02/08/2023] Open
Abstract
Background Tumor protein 63 (p63) is a transcription factor of the p53 gene family involved in differentiation of several tissues including squamous epithelium. p63 immunohistochemistry is broadly used for tumor classification but published data on its expression in cancer is conflicting. Methods To comprehensively catalogue p63 expression, tissue microarrays (TMAs) containing 12,620 tissue samples from 115 tumor entities and 76 normal tissue types were analyzed. Results p63 expression was seen in various normal tissues including squamous epithelium and urothelium. At least occasional weak p63 positivity could be detected in 61 (53%) of 115 different tumor types. The frequencies of p63 positivity was highest in squamous cell carcinomas irrespective of their origin (96–100%), thymic tumors (100%), urothelial carcinomas (81–100%), basal type tumors such as basal cell carcinomas (100%), and various salivary gland neoplasias (81–100%). As a rule, p63 was mostly expressed in cancers derived from p63 positive normal tissues and mostly not detectable in tumors derived from p63 negative cancers. However, exceptions from this rule occurred. A positive p63 immunostaining in cancers derived from p63 negative tissues was unrelated to aggressive phenotype in 422 pancreatic cancers, 160 endometrium cancers and 374 ovarian cancers and might be caused by aberrant squamous differentiation or represent stem cell properties. In 355 gastric cancers, aberrant p63 expression occurred in 4% and was linked to lymph node metastasis (p = 0.0208). Loss of p63 in urothelial carcinomas - derived from p63 positive urothelium - was significantly linked to advanced stage, high grade (p < 0.0001 each) and poor survival (p < 0.0001) and might reflect clinically relevant tumor dedifferentiation. Conclusion The high prevalence of p63 expression in specific tumor types makes p63 immunohistochemistry a suitable diagnostic tool. Loss of p63 expression might constitute a feature of aggressive cancers. Supplementary Information The online version contains supplementary material available at 10.1186/s40364-021-00260-5.
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Massé J, Truntzer C, Boidot R, Khalifa E, Pérot G, Velasco V, Mayeur L, Billerey-Larmonier C, Blanchard L, Charitansky H, Soubeyran I, Iggo R, Arnould L, MacGrogan G. Solid-type adenoid cystic carcinoma of the breast, a distinct molecular entity enriched in NOTCH and CREBBP mutations. Mod Pathol 2020; 33:1041-1055. [PMID: 31857685 DOI: 10.1038/s41379-019-0425-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 10/29/2019] [Accepted: 10/30/2019] [Indexed: 12/14/2022]
Abstract
Adenoid cystic carcinoma (ACC) of the breast with a predominant solid pattern is difficult to diagnose with certainty and differentiate from more common triple-negative breast cancers (TNBCs) of basal-phenotype. To better characterize solid ACC, we performed a clinical, morphological, immunohistochemical, and molecular comparative analysis of 33 ACCs of the breast comprising 17 solid variant ACCs and 16 conventional ACCs. Solid ACCs displayed basaloid morphology with an exclusive or predominant epithelial cell population associated with decreased myoepithelial differentiation, while demonstrating MYB protein overexpression similar to the more common type of ACC. Strong and diffuse MYB expression by immunochemistry was observed in 14/17 (82%) of solid ACCs while MYB rearrangements were detected by break apart fluorescence in situ hybridization (FISH) in only 3/16 (19%) of solid ACCs. Conversely, weak MYB immunohistochemical expression was observed in only 7/204 (3%) of TNBC. Solid ACCs displayed a transcriptomic profile distinct from conventional ACCs with 549 genes showing a highly significant differential expression between conventional and solid ACC [false discovery rate (FDR) < 0.01; log2FC > |1|]. EnrichR and Kegg Pathway analyses identified PI3K-Akt and focal adhesion signaling pathways as significantly overexpressed in conventional ACCs compared with solid ACCs which significantly overexpressed the nitrogen metabolism pathway. CREBBP mutations and NOTCH activating gene mutations were only present in solid ACCs, concerning 5/16 (31%) of cases for each gene. Tumors with NOTCH activating mutations displayed a strong diffuse nuclear NICD1 staining, an established marker of Notch pathway activation. Solid ACCs also differed from basal-type TNBC, with fewer TP53 mutations and a more stable genomic profile on array comparative genomic hybridization (CGH). In summary, solid-type ACC of the breast is a distinct molecular entity within the ACC family and is different from common basal-type TNBC. MYB is a diagnostically useful biomarker of solid ACC and NOTCH could be a novel potential therapeutic target in 30% of cases.
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Affiliation(s)
- Julie Massé
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France.,University of Bordeaux, F-33076, Bordeaux, France
| | - Caroline Truntzer
- Department of Tumor Biology and Pathology, Centre Georges-François Leclerc, Comprehensive Cancer Centre, F-21000, Dijon, France
| | - Romain Boidot
- Department of Tumor Biology and Pathology, Centre Georges-François Leclerc, Comprehensive Cancer Centre, F-21000, Dijon, France
| | - Emmanuel Khalifa
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France
| | - Gaëlle Pérot
- INSERM U1037, Cancer Research Center Toulouse (CRCT), F-31000, Toulouse, France.,Department of Pathology, Institut Claudius Regaud, IUCT-Oncopole, F-31000, Toulouse, France
| | - Valérie Velasco
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France
| | - Laétitia Mayeur
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France
| | - Claire Billerey-Larmonier
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France
| | - Larry Blanchard
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France
| | - Hélène Charitansky
- Department of Surgical oncology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France
| | - Isabelle Soubeyran
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France
| | - Richard Iggo
- University of Bordeaux, F-33076, Bordeaux, France.,INSERM U1218, F-33076, Bordeaux, France
| | - Laurent Arnould
- Department of Tumor Biology and Pathology, Centre Georges-François Leclerc, Comprehensive Cancer Centre, F-21000, Dijon, France
| | - Gaëtan MacGrogan
- Department of Biopathology, Institut Bergonié, Comprehensive Cancer Centre, F-33076, Bordeaux, France. .,INSERM U1218, F-33076, Bordeaux, France.
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13
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Ginter PS, Tang X, Shin SJ. A review of mucinous lesions of the breast. Breast J 2020; 26:1168-1178. [PMID: 32419267 DOI: 10.1111/tbj.13878] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 04/23/2020] [Indexed: 11/28/2022]
Abstract
Mucinous lesions of the breast include a variety of benign and malignant epithelial processes that display intracytoplasmic or extracellular mucin, including mucocele-like lesions, mucinous carcinoma, solid papillary carcinoma, and other rare subtypes of mucin-producing carcinoma. The finding of free-floating or stromal mucin accumulations is a diagnostic challenge of which the significance depends on the clinical, radiologic, and pathologic context. This article emphasizes the differential diagnosis between benign and malignant mucin-producing lesions, with a brief consideration of potential mimics, such as biphasic and mesenchymal lesions with associated with mucinous, myxoid, or matrix material.
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Affiliation(s)
- Paula S Ginter
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Xiaoyu Tang
- Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY, USA
| | - Sandra J Shin
- Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY, USA
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14
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Yang C, Zhang L, Sanati S. SOX10 Is a Sensitive Marker for Breast and Salivary Gland Adenoid Cystic Carcinoma: Immunohistochemical Characterization of Adenoid Cystic Carcinomas. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2019; 13:1178223419842185. [PMID: 31105427 PMCID: PMC6501487 DOI: 10.1177/1178223419842185] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 03/11/2019] [Indexed: 12/29/2022]
Abstract
Breast adenoid cystic carcinomas (AdCCs) can pose diagnostic difficulty due to their rarity, particularly on limited biopsy material. Given that these tumors are triple-negative breast cancers with favorable prognosis, accurate diagnosis is critical for clinical management. A total of 12 cases of breast AdCCs were studied; 17 age-matched salivary gland AdCCs and 5 metastatic AdCCs (1 breast and 4 salivary gland primaries) were also examined. Immunohistochemical stains for SOX10, Ki-67, c-KIT, β-catenin, epithelial membrane antigen (EMA), p63, cytokeratin 7 (CK7), cytokeratin 5/6 (CK5/6), and androgen receptor (AR) were performed. All breast (100%) and metastatic (100%) AdCCs and all but 2 salivary gland AdCCs showed diffuse nuclear staining (>50% of cells) for SOX10. Epithelial membrane antigen showed lowest expression in breast AdCCs and the highest expression in metastatic AdCCs (P < .01). Except one case of salivary gland AdCC that showed loss of β-catenin expression and developed subsequent metastasis, all AdCCs showed strong and diffuse membranous β-catenin expression. There were no significant differences in expression of CK7, p63, CK5/6, AR, Ki-67, and c-KIT (P > .05) among breast, salivary gland, and metastatic AdCCs. We investigated the immunophenotypic features of breast AdCCs in comparison with salivary gland and metastatic AdCCs. Despite the contrast in prognosis, these tumors are immunophenotypically similar. SOX10 is a sensitive diagnostic marker in all AdCCs, which could potentially aid in diagnosis of these tumors on limited material.
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Affiliation(s)
- Chen Yang
- Department of Pathology & Immunology, Barnes-Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA
| | - Lingxin Zhang
- Department of Pathology & Immunology, Barnes-Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA
| | - Souzan Sanati
- Department of Pathology & Immunology, Barnes-Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA
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15
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Adenoid cystic carcinoma of the breast: Experience at a tertiary care centre of Northern India. Int J Surg Case Rep 2018; 51:204-209. [PMID: 30189404 PMCID: PMC6126082 DOI: 10.1016/j.ijscr.2018.08.035] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Revised: 08/15/2018] [Accepted: 08/17/2018] [Indexed: 01/13/2023] Open
Abstract
INTRODUCTION Adenoid cystic carcinoma of the breast (breast-ACC) is a rare tumor with a favorable prognosis, despite its triple-negative status and special type of basal-like tumor for which scant population-based descriptive data exist. We sought to provide new population-based information on breast-ACC in India. Due to the paucity of the number of cases, the natural history of the disease is not fully understood. This study was undertaken to examine the clinico-pathological characteristics of the disease and to evaluate the outcome of surgical intervention in a tertiary referral care centre. MATERIALS AND METHODS A retrospective analysis of all patients diagnosed and treated for ACC Breast in our hospital over the past 10 years was carried out (2005-2015). A database of the characteristics of these patients was developed. In all, 14 patients were identified. The investigations performed included routine blood investigations, chest X-ray, bone scan and either an ultrasound or a CT scan. RESULTS During the time period of 10 years, of 2347 with breast malignancy admitted to our department, only 14 were diagnosed as having ACC (3.15%). All patients were women (100%). The patients had a median age of 60.7 years (range 37-81). The most common symptom was lump in the breast. Two patients (14.2%) presented with nipple and skin retraction and two patients (14.2%) were asymptomatic with the diagnosis made by an incidental finding on routine examination. The CT and/or magnetic resonance imaging (MRI) showed the typical features of carcinoma breast. All the 14 patients were taken up for surgery. Nine patients underwent Modified radical mastectomy and five patients underwent Breast conservation surgery. Axillary lymph node dissection was carried out in seven patients and sentinel lymph node biopsy in the remaining. Tumor cells had a characteristic histologic pattern of ACC of the breast. Perineural invasion was present in six cases. DISCUSSION ACC of the breast is a very rare malignancy, accounting for less than 0.1% of all breast neoplasms. It affects the left and right breasts equally and tumors arise irrespective of the breast quadrants. However, in about 50 percent of patients, lesions are found in subareolar region. Pain or tenderness described in the minority of cases has not been correlated with histologically-confirmed perineural invasion. ACC is categorized as a basal-like subtype of breast carcinoma. Most cases are macroscopically well-circumscribed. Occasionally, pink, tan, or gray microcysts are evident. A tumor typically consists of a dual-cell population of luminal and myoepithelial-basal cells which may be arranged in one or more of three architectural patterns: tubular-trabecular, cribriform, and solid-basaloid. There is no consensus on the optimal management for patients with ACC of the breast. Based on its indolent clinical course and favorable outcome, ACC of the breast is generally cured by breast-conserving surgery, such as wide excision or quadrantectomy with or without radiotherapy. CONCLUSION Breast-ACC among women is characterized by ER-negative/PR-negative expression, rare regional lymph node involvement, a favorable prognosis with excellent survival, and absence of associated cancers. These findings reinforce the importance of tailored treatments for breast-ACC and the apparent heterogeneity of basal-like breast cancers.
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16
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Wang H, Liu F, Gu R, Li Y, Su F. Rare imaging appearance of adenoid cystic carcinoma of the breast: A case report. Mol Clin Oncol 2017; 7:473-475. [PMID: 28781820 DOI: 10.3892/mco.2017.1322] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Accepted: 05/26/2017] [Indexed: 01/15/2023] Open
Abstract
Adenoid cystic carcinoma (ACC) of the breast is a rare tumor comprising <0.1% of all breast malignancies. The present study reports the case of a 66-year-old woman who underwent multiple imaging techniques, including mammography, ultrasonography and magnetic resonance imaging (MRI). The patient reported gradual enlargement of a mass in the left breast. Mammography identified a high-density, irregular mass, with nipple retraction. Ultrasonography revealed an irregular, complex cystic and solid mass with an unclear margin in the subareolar region. The internal vascularity was seen on Doppler examination. The lesion on MRI was also mixed cystic and solid, with an irregular shape and irregular margins. The solid part of the lesion appeared heterogeneously isointense on T1-weighted imaging (WI) and a slightly high signal on T2WI, and exhibited internal septations with a low signal on T2WI. Following injection of contrast agent, the enhancement of the solid part was rapid and heterogeneous. The cystic parts of lesion appeared as high-signal on T1WI and T2WI. The tumor infiltrated the left nipple and adjacent skin. The patient underwent a left modified radical mastectomy with axillary lymph node dissection. The pathological examination confirmed the tumor as ACC of the left breast. The axillary lymph nodes were negative for tumor metastasis. Therefore, the differential diagnosis of mixed cystic and solid breast masses with unclear margins and internal septations on T2WI exhibiting delayed enhancement, must include ACC.
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Affiliation(s)
- Hongli Wang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.,Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510288, P.R. China
| | - Fengtao Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.,Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510288, P.R. China
| | - Ran Gu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.,Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510288, P.R. China
| | - Yong Li
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.,Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510288, P.R. China
| | - Fengxi Su
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.,Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510288, P.R. China
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17
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Peng Y, Butt YM, Chen B, Zhang X, Tang P. Update on Immunohistochemical Analysis in Breast Lesions. Arch Pathol Lab Med 2017; 141:1033-1051. [PMID: 28574279 DOI: 10.5858/arpa.2016-0482-ra] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT - The utility of immunohistochemistry (IHC) in breast lesions needs to be updated with exceptions among these lesions. Biomarker studies with IHC in triple-negative breast carcinoma may help develop targeted therapies for this aggressive breast cancer. The distinction of metastatic lung adenocarcinoma to the breast and invasive breast carcinoma has significant prognostic and therapeutic implications. The determination can be challenging because both primary tumors can express estrogen receptor and/or HER2 by IHC, creating a diagnostic dilemma. OBJECTIVES - To provide a practical update on the use of IHC markers in differential diagnoses in breast lesions, including benign, atypical, precancerous, and malignant tumors; to highlight recently published research findings on novel IHC markers in triple-negative breast carcinoma cases; and to reinforce the importance of IHC use as an ancillary tool in distinguishing metastatic lung adenocarcinoma to the breast from primary breast carcinoma using real case examples. DATA SOURCES - PubMed (US National Library of Medicine, Bethesda, Maryland) literature review and authors' research data and personal experiences were used in this review. CONCLUSIONS - Immunohistochemistry has an important role in making differential diagnoses in breast lesions in morphologically equivocal settings; recognizing IHC expression status in the exceptions among these lesions will aid in the correct diagnosis of challenging breast cases. Studies suggest that androgen receptor, p16, p53, GATA3, and PELP1 may have potential diagnostic, prognostic, and predictive value in triple-negative breast carcinoma cases; these findings may provide insight and a greater understanding of the tumor biology in triple-negative breast carcinomas. In distinguishing metastatic estrogen receptor-positive or HER2+ lung adenocarcinoma to the breast from primary breast carcinoma, napsin A, TTF-1, and GATA3 comprise a useful IHC panel.
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Affiliation(s)
| | | | | | | | - Ping Tang
- From the Department of Pathology, University of Texas Southwestern Medical Center, Dallas (Drs Peng and Butt); the Department of Pathology, Mayo Clinic and Foundation, Rochester, Minnesota (Dr Chen); the Department of Pathology, Cooper Medical School of Rowan University, Camden, New Jersey (Dr Zhang); and the Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, New York (Dr Tang)
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18
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Treitl D, Radkani P, Rizer M, El Hussein S, Paramo JC, Mesko TW. Adenoid cystic carcinoma of the breast, 20 years of experience in a single center with review of literature. Breast Cancer 2017; 25:28-33. [PMID: 28466440 DOI: 10.1007/s12282-017-0780-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 04/23/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Adenoid cystic carcinoma (ACC) of the breast is a rare type of breast cancer, which presents inconsistencies in the optimal management strategy. METHODS A retrospective review of prospectively collected data, spanning the last 20 years, was performed using the cancer registry database at our institution. RESULTS Six patients were diagnosed with ACC of the breast, out of 5,813 total patients diagnosed with breast cancer (0.1%). Our identified patients had a median age of 66, all with the early stage cancer (Stage I/II). The average size of the breast lesion was 1.62 cm, and nodal status was negative for all cases. All patients had resection as primary therapy (partial or total mastectomy), with one patient also undergoing external beam radiation and tamoxifen hormonal therapy. Median follow-up was 85 months, with all patients being disease-free at last follow-up. CONCLUSIONS ACC of the breast has an indolent course, despite triple negative status. Our study suggests that radiation may not be warranted and confirms the rarity of axillary node metastases, indicating that sentinel node excision may also not be necessary. Ultimately, the hope is that our findings along with the reviewed literature will aid in determining the most appropriate options for management of ACC of the breast.
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Affiliation(s)
- Daniela Treitl
- Mount Sinai Medical Center, Department of Surgery, 4300 Alton Road, Miami Beach, FL, 33140, USA.
| | - Pejman Radkani
- Mount Sinai Hospital, E 101st St, New York, NY, 10029, USA
| | - Magda Rizer
- Mount Sinai Medical Center, Department of Surgery, 4300 Alton Road, Miami Beach, FL, 33140, USA
| | - Siba El Hussein
- Mount Sinai Medical Center, Department of Surgery, 4300 Alton Road, Miami Beach, FL, 33140, USA
| | - Juan C Paramo
- Mount Sinai Medical Center, Department of Surgery, 4300 Alton Road, Miami Beach, FL, 33140, USA
| | - Thomas W Mesko
- Mount Sinai Medical Center, Department of Surgery, 4300 Alton Road, Miami Beach, FL, 33140, USA
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19
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Toll A, Joneja U, Palazzo J. Pathologic Spectrum of Secretory and Mucinous Breast Lesions. Arch Pathol Lab Med 2017; 140:644-50. [PMID: 27362569 DOI: 10.5858/arpa.2015-0250-ra] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT -The morphologic spectrum of secretory breast lesions encompasses benign, borderline, and malignant lesions. They are characterized by luminal pink, proteinaceous secretions and variable degrees of cytologic atypia ranging from low grade to high grade, with frequent papillary formations. Other lesions, benign and malignant, can also show luminal and extraluminal secretions and share similar features with secretory lesions, making them diagnostically challenging. OBJECTIVE -To discuss the differential diagnosis of secretory breast lesions, emphasizing the most important diagnostic features of benign and malignant lesions. Lesions with intraluminal secretions discussed at length in this review include pregnancy-like hyperplasia, cystic hypersecretory hyperplasia, collagenous spherulosis, microglandular adenosis, hypersecretory carcinoma, and secretory carcinoma. Lesions with extravasated mucin, such as mucocele-like lesions and mucinous carcinoma, are also briefly discussed. DATA SOURCES -Published articles obtained from a PubMed search of the English literature were the primary source for this review. CONCLUSIONS -Lesions with secretory features described in this review show a pathologic spectrum, sometimes even within the same lesion. As a consequence, one should employ a low threshold for recommending reexcision on a core biopsy containing benign-appearing hypersecretory glands and use all ancillary data, including clinical presentation, imaging findings, morphology, immunohistochemistry, and molecular pathology, to render a final diagnosis.
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Affiliation(s)
- Adam Toll
- From the Department of Pathology, St Luke's University Health Network, Bethlehem, Pennsylvania (Dr Toll); and the Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (Drs Joneja and Palazzo)
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20
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Foschini MP, Morandi L, Asioli S, Giove G, Corradini AG, Eusebi V. The morphological spectrum of salivary gland type tumours of the breast. Pathology 2017; 49:215-227. [PMID: 28043647 DOI: 10.1016/j.pathol.2016.10.011] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 10/23/2016] [Accepted: 10/30/2016] [Indexed: 12/16/2022]
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21
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Torous VF, Schnitt SJ, Collins LC. Benign breast lesions that mimic malignancy. Pathology 2017; 49:181-196. [PMID: 28069257 DOI: 10.1016/j.pathol.2016.12.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Accepted: 12/15/2016] [Indexed: 12/15/2022]
Abstract
Many benign and reactive lesions of the breast show morphological overlap with malignant lesions. These benign mimics of malignancy often present diagnostic challenges to even the most experienced pathologists. This review focuses on several benign lesions of the breast that mimic malignant entities. For each of these lesions, we describe the key morphological and immunohistochemical features, potential diagnostic pitfalls, and our approach to arriving at the correct diagnosis.
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Affiliation(s)
- Vanda F Torous
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
| | - Stuart J Schnitt
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
| | - Laura C Collins
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
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22
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Special Types of Breast Cancer and Non-epithelial Tumors. Breast Cancer 2017. [DOI: 10.1007/978-3-319-48848-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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23
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Nakai T, Ichihara S, Kada A, Ito N, Moritani S, Kawasaki T, Uchiyama T, Itami H, Morita K, Takano M, Takeda M, Hatakeyama K, Ohbayashi C. The unique luminal staining pattern of cytokeratin 5/6 in adenoid cystic carcinoma of the breast may aid in differentiating it from its mimickers. Virchows Arch 2016; 469:213-22. [PMID: 27240462 DOI: 10.1007/s00428-016-1963-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 04/14/2016] [Accepted: 05/17/2016] [Indexed: 12/12/2022]
Abstract
Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n = 14) and in collagenous spherulosis (n = 5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity) at threshold settings of 0, 10, 50, and 70 %. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis.
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Affiliation(s)
- Tokiko Nakai
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
| | - Shu Ichihara
- Department of Pathology, Clinical Research Center, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, Japan.
| | - Akiko Kada
- Department of Clinical Trials and Research, Clinical Research Center, Nagoya Medical Center, Nagoya, Aichi, Japan
| | - Noriko Ito
- Department of Clinical Research Management, Clinical Research Center, Nagoya Medical Center, Nagoya, Aichi, Japan
| | - Suzuko Moritani
- Department of Pathology, Shiga Medical University, Otsu, Shiga, Japan
| | - Tomonori Kawasaki
- Department of Molecular Diagnostic Pathology, Iwate Medical University School of Medicine, Morioka, Japan
| | - Tomoko Uchiyama
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
| | - Hiroe Itami
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
| | - Kouhei Morita
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
| | - Masato Takano
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
| | - Maiko Takeda
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
| | - Kinta Hatakeyama
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
| | - Chiho Ohbayashi
- Department of Pathology, Nara Medical University, Kashihara, Nara, Japan
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24
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Lee S, Oh SY, Kim SH, Lee JH, Kim DC, Cho SH, Lee M, Kim HJ. Malignant Adenomyoepithelioma of the Breast and Responsiveness to Eribulin. J Breast Cancer 2015; 18:400-3. [PMID: 26770248 PMCID: PMC4705093 DOI: 10.4048/jbc.2015.18.4.400] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 12/07/2015] [Indexed: 12/28/2022] Open
Abstract
Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by its dual differentiation into luminal cells and myoepithelial cells. In most cases these tumors have a benign clinical course, but distant metastases have been reported. We present the case of a 51-year-old woman diagnosed with malignant AME. The patient underwent a right modified radical mastectomy, and pathological examination confirmed the diagnosis of malignant AME. Ten months after the operation, multiple hepatic, pleural, and abdominal wall metastases were detected. A number of palliative chemotherapeutic agents were tried, including anthracycline and taxanes. However, the disease continued to progress, and superior vena cava syndrome developed as a result of direct tumor invasion. The patient received salvage eribulin monotherapy. After two cycles of this treatment, her clinical symptoms were ameliorated, and a computed tomography scan showed a partial response. Eribulin chemotherapy was thus effective in treating malignant AME in this case.
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Affiliation(s)
- Suee Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Sung-Hyun Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Ji Hyun Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Dae Cheul Kim
- Department of Pathology, Dong-A University College of Medicine, Busan, Korea
| | - Se Heon Cho
- Department of Surgery, Dong-A University College of Medicine, Busan, Korea
| | - Miri Lee
- Department of Surgery, Dong-A University College of Medicine, Busan, Korea
| | - Hyo-Jin Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
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25
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Foschini MP, Rizzo A, De Leo A, Laurino L, Sironi M, Rucco V. Solid Variant of Adenoid Cystic Carcinoma of the Breast. Int J Surg Pathol 2015; 24:97-102. [DOI: 10.1177/1066896915606973] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Adenoid cystic carcinoma (ACC) of the breast is a low-grade malignancy “triple negative” breast tumor. ACC of the breast can present a great variety of morphological features having a prognostic impact. Recently, cases of ACC having solid-basaloid features (SBACC) have been described. In the present study, 6 cases of SBACC have been reported. All the cases affected female patients aged 47 to 69 years (mean = 54 years). Two patients had metastases to the axillary lymph nodes, and 2 patients experienced local recurrences. No deaths due to the tumor were observed. A review of the literature on breast SBACC showed that local recurrences and lymph node metastases are more frequent than in the ACC conventional type; nevertheless, no deaths due to the tumor are registered at the moment. On the contrary, cases of ACC with features of malignant transformation are on record. Therefore, a new grading system on breast ACC is proposed.
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Affiliation(s)
- Maria P. Foschini
- Section of Anatomic Pathology, Department of Biomedical and Neuromotor Sciences of the University of Bologna, Bellaria Hospital, Bologna, Italy
| | - Antonio Rizzo
- Operative Unit of Anatomic Pathology, S. Giacomo Hospital, Castelfranco Veneto, Italy
| | - Antonio De Leo
- Section of Anatomic Pathology, Department of Biomedical and Neuromotor Sciences of the University of Bologna, Bellaria Hospital, Bologna, Italy
| | - Licia Laurino
- Operative Unit of Anatomic Pathology, Treviso General Hospital, Treviso, Italy
| | - Maria Sironi
- Operative Unit of Anatomic Pathology, Department of General Pathology, ASL4 Chiavarese, Sestri Levante, Genoa
| | - Vittorio Rucco
- Operative Unit of Anatomic Pathology, ASL5 Arzignano (VI) ULSS5-Ovest Vicentino
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26
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Abstract
Breast carcinoma is a heterogenous disease. Carcinomas lacking expression of estrogen, progesterone, and HER2/neu receptors by immunohistochemistry and Her2 amplification are designated as triple negative. This group of carcinomas comprises approximately 10% to 20% of all breast carcinomas and is characterized by an aggressive nature with shorter rates of disease-free and overall survival. This aggressive behavior is further compounded by the lack of available targeted therapies. Patients receive cytoxic chemotherapy regimens. Although tumors are initially sensitive to this therapy, drugs are toxic and ineffective in maintaining long-term response thereby providing limited benefit. Much effort is being spent on this group of cancers for the identification of appropriate molecular targets, an effort that is proving challenging due to the presence of marked heterogeneity, both at the morphologic and molecular levels. An understanding of the advances in this field is crucial for developing targeted therapies and tailored patient management protocols. This report summarizes the pathologic subtypes of breast cancer that are commonly of a triple-negative immunophenotype and recent molecular advances in this field.
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Ilkay TM, Gozde K, Ozgur S, Dilaver D. Diagnosis of adenoid cystic carcinoma of the breast using fine-needle aspiration cytology: A case report and review of the literature. Diagn Cytopathol 2015; 43:722-6. [PMID: 26183224 DOI: 10.1002/dc.23272] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Revised: 12/27/2014] [Accepted: 03/20/2015] [Indexed: 01/25/2023]
Abstract
Adenoid cystic carcinoma (ACC) of the breast is a rare variant of breast malignancy and is associated with an excellent prognosis. ACC accounts for 0.1% of all breast carcinomas. It has favorable biological characteristics and an excellent prognosis. A 77-year-old woman presented with a lump in the right breast. Ultrasonography and mammography showed a 12-mm, well-defined, lobulated mass in the retroareolar region of the right breast. The lump was diagnosed as ACC on the basis of immunohistochemical staining results for c-kit (CD117), muscle-specific actin, p63, estrogen receptor, and progesterone receptor using a fine-needle aspiration cytology (FNAC) specimen. This diagnosis was subsequently confirmed by excision biopsy. To the best of our knowledge, this is the first case of ACC of the breast to date to be diagnosed on the basis of immunohistochemical staining of an FNAC cell block material. From our experience, we recommend the usage of cell block material for immunohistochemical studies to accurately diagnose ACC of the breast.
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Affiliation(s)
- Tosun M Ilkay
- Department of Pathology, Umraniye Education and Research Hospital, Istanbul, Turkey
| | - Kir Gozde
- Department of Pathology, Umraniye Education and Research Hospital, Istanbul, Turkey
| | - Sarica Ozgur
- Department of Radiology, Umraniye Education and Research Hospital, Istanbul, Turkey
| | - Demirel Dilaver
- Department of Pathology, GATA Haydarpasa Education Hospital, Istanbul, Turkey
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Kumar BR, Padmanabhan N, Bose G, Paneer V. A Case Report of Adenoid Cystic Carcinoma of Breast- So Close Yet So Far from Triple Negative Breast Cancer. J Clin Diagn Res 2015; 9:XD01-XD03. [PMID: 26393191 DOI: 10.7860/jcdr/2015/14283.6164] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 05/04/2015] [Indexed: 02/02/2023]
Abstract
Adenoid cystic carcinoma (ACC) of breast is a rare tumour with a low malignant potential. Though negative for oestrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (Her2/neu), it is different from triple negative breast cancer (TNBC); ACC has an indolent course with a good prognosis.We present a case of a 40 year old premenopausal female initially diagnosed with ductal carcinoma in situ (DCIS) on core needle biopsy. She underwent breast-conserving surgery (BCS) and her final histopathological diagnosis was ACC. She subsequently underwent adjuvant external beam radiotherapy. The patient is on follow-up for more than a year with no recurrence till date.
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Affiliation(s)
- Barath Raj Kumar
- Registrar, Department of Surgical Oncology, Apollo Speciality Hospital , Chennai, India
| | - Naveen Padmanabhan
- Registrar, Department of Surgical Oncology, Apollo Speciality Hospital , Chennai, India
| | - Gajasaraj Bose
- Registrar, Department of Surgical Oncology, Apollo Speciality Hospital , Chennai, India
| | - Venkat Paneer
- Consultant, Department of Surgical Oncology, Apollo Speciality Hospital , Chennai, India
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29
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Miyai K, Schwartz MR, Divatia MK, Anton RC, Park YW, Ayala AG, Ro JY. Adenoid cystic carcinoma of breast: Recent advances. World J Clin Cases 2014; 2:732-41. [PMID: 25516849 PMCID: PMC4266822 DOI: 10.12998/wjcc.v2.i12.732] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 09/03/2014] [Accepted: 09/18/2014] [Indexed: 02/05/2023] Open
Abstract
Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features.
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D'Alfonso TM, Mosquera JM, MacDonald TY, Padilla J, Liu YF, Rubin MA, Shin SJ. MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features. Hum Pathol 2014; 45:2270-80. [PMID: 25217885 DOI: 10.1016/j.humpath.2014.07.013] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Revised: 07/15/2014] [Accepted: 07/23/2014] [Indexed: 02/01/2023]
Abstract
Adenoid cystic carcinomas (ACCs) from various anatomical sites harbor a translocation t(6;9)(q22-23;p23-24), resulting in MYB-NFIB gene fusion. This gene fusion is not well studied in mammary ACCs, and there are no studies examining this abnormality in solid variant of ACC with basaloid features (SBACC), a high-grade variant thought to behave more aggressively than ACCs with conventional histologic growth. Our aim was to investigate the frequency of MYB-NFIB gene fusion in mammary ACCs with a focus paid to SBACC. MYB rearrangement and MYB-NFIB fusion were assessed by fluorescence in situ hybridization and reverse-transcription polymerase chain reaction, respectively. Histologic features and the presence of MYB rearrangement were correlated with clinical outcome. MYB rearrangement was present in 7 (22.6%) of 31 mammary ACCs (5/15 [33.3%] ACCs with conventional growth; 2/16 [12.5%] SBACCs). One patient with conventional ACC developed distant metastasis, and no patients had axillary lymph node involvement by ACC (mean follow-up, 34 months; range, 12-84 months). Two patients with SBACC had axillary lymph node involvement at initial surgery, and 2 additional patients experienced disease recurrence (1 local, 1 distant; mean follow-up, 50 months; range, 9-192 months). MYB-NFIB fusion status did not correlate with clinical outcome in studied patients. We confirm that MYB-NFIB gene fusion is observed in mammary ACCs and that a subset lacks this abnormality. This study is the first to confirm the presence of MYB rearrangement in SBACC. Additional validation with long-term follow-up is needed to determine the relationship, if any, between MYB-NFIB gene fusion and clinical outcome.
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Affiliation(s)
- Timothy M D'Alfonso
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065.
| | - Juan Miguel Mosquera
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065; Institute for Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065
| | - Theresa Y MacDonald
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065
| | - Jessica Padilla
- Institute for Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065
| | - Yi-Fang Liu
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065
| | - Mark A Rubin
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065; Institute for Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065
| | - Sandra J Shin
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065
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Malignant adenomyoepithelioma combined with adenoid cystic carcinoma of the breast: a case report and literature review. Diagn Pathol 2014; 9:148. [PMID: 25056281 PMCID: PMC4222729 DOI: 10.1186/1746-1596-9-148] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Accepted: 07/07/2014] [Indexed: 01/22/2023] Open
Abstract
Background Malignant adenomyoepithelioma and adenoid cystic carcinoma are both rare malignant epithelial-myoepithelial tumors of the breast. We report a very rare case with a malignant adenomyoepithelioma combining with adenoid cystic carcinoma in a single mass. Case presentation A 61-year-old female presented with a palpable painless mass in the right breast. Mammography revealed a large irregular dense shadow without obvious internal calcification. A simple lumpectomy was performed, and a 1.6cm well-circumscribed pale-tan nodule was presented. Histologically, the nodule was composed of two obscure lobules. One exhibited typical histological image of adenoid cystic carcinoma, the other one showed the image of epithelial-myoepithelial carcinoma of salivary gland, and support the diagnosis of biphasic malignant adenomyoepithelioma. Transition between the two lobules was gradual. Immunohistochemically, CK18 and P63 highlighted the epithelial and myoepithelial cells respectively in both lesions. CD117 was positive in the epithelial cells of adenoid cystic carcinoma, but was totally negative in malignant adenomyoepithelioma. Conclusion This report is, to our knowledge, the first case that combines these two tumors in a single mass. In addition, we present a review of the literature. The histogenesis of these tumors is also discussed. Virtual Slides The virtual slide(s) for this article can be found here: http://med.motic.com/MoticGallery/Slide?id=D562817E-23C2-4F72-9823-86EF6DA40005&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025 and http://med.motic.com/MoticGallery/Slide?id=38BB7126-6FFB-4B66-A208-B8C0F528DCA8&user=2C69F0D6-A478-4A2B-ABF0-BB36763E8025
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Boecker W, Stenman G, Loening T, Andersson MK, Sinn HP, Barth P, Oberhellmann F, Bos I, Berg T, Marusic Z, Samoilova V, Buchwalow I. Differentiation and histogenesis of syringomatous tumour of the nipple and low-grade adenosquamous carcinoma: evidence for a common origin. Histopathology 2014; 65:9-23. [PMID: 24382117 DOI: 10.1111/his.12358] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Accepted: 12/27/2013] [Indexed: 01/09/2023]
Abstract
AIMS Syringomatous tumour of the nipple and low-grade adenosquamous carcinoma (LGAdSC) of the breast are regarded as distinct entities. To clarify the nature of these two lesions, we compared the expression of different lineage/differentiation markers in 12 syringomatous tumours of the nipple, nine LGAdSCs, and normal breast epithelium. METHODS AND RESULTS Using triple immunofluorescence labelling and quantitative RT-PCR for keratins, p63, and smooth muscle actin, we demonstrated that syringomatous tumour and LGAdSC contain p63+/K5/14+ tumour cells, K10+ squamous cells, and K8/18+ glandular cells, with intermediary cells being found in both lineages. Identical p63+/K5/14+ cells were also found in the normal breast duct epithelium. CONCLUSIONS Our data provide evidence that syringomatous tumour of the nipple and LGAdSC are identical or nearly identical lesions. They contain p63+/K5/14+ cells as the key cells from which the K10+ squamous lineage and the K8/18+ glandular lineage arise. On the basis of our findings in normal breast tissue and associated benign lesions, we suggest that p63+/K5/14+ cells of the normal breast duct epithelium or early related cells might play a key role in the neoplastic transformation of both syringomatous tumour and LGAdSC. We propose that the differentiation patterns found in both lesions reflect the early ontogenetic stages of the normal breast epithelium.
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Affiliation(s)
- Werner Boecker
- Institute for Hematopathology, Reference Centre for Gynaeco- and Breast Pathology, Hamburg, Germany; Gerhard-Domagk-Institute of Pathology, University of Muenster, Münster, Germany
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Zhao L, Yang X, Khan A, Kandil D. Diagnostic role of immunohistochemistry in the evaluation of breast pathology specimens. Arch Pathol Lab Med 2014; 138:16-24. [PMID: 24377808 DOI: 10.5858/arpa.2012-0440-ra] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT Immunohistochemistry plays a vital role in the evaluation of breast pathology specimens. OBJECTIVE To discuss the role of myoepithelial cell markers in the evaluation of various breast lesions. Other markers, such as E-cadherin and those used to differentiate mammary carcinoma from metastatic tumors to the breast, and markers used in the differential diagnosis of Paget disease, are also discussed. DATA SOURCES Data were obtained from review of the pertinent peer-reviewed literature. CONCLUSIONS Myoepithelial cell markers vary in their sensitivity and specificity, and one should be aware of the potential pitfalls in interpretation. Using panels of 2 or more myoepithelial cell markers is always recommended, either singly or in cocktail forms. Although negative E-cadherin staining supports the diagnosis of lobular origin, positive staining does not rule it out. Immunohistochemistry can be helpful in differentiating Paget disease from its mimics. Although metastatic tumors to the breast are rare, a triple-negative immunophenotype and absence of an in situ component should be a "red flag" for such possibility, especially in patients with clinical history of an extramammary malignancy.
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Affiliation(s)
- Larry Zhao
- From the Department of Pathology, University of Massachusetts, UMass Memorial Medical Center, Worcester, Massachusetts
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34
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Tan PH, Ellis IO. Myoepithelial and epithelial-myoepithelial, mesenchymal and fibroepithelial breast lesions: updates from the WHO Classification of Tumours of the Breast 2012. J Clin Pathol 2013; 66:465-70. [PMID: 23533258 DOI: 10.1136/jclinpath-2012-201078] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
In the 4th edition of the WHO Classification of Tumours of the Breast, myoepithelial lesions are retitled myoepithelial and epithelial-myoepithelial lesions in order to better reflect the dual participation of luminal and myoepithelial compartments in some key entities. Malignant myoepithelioma, described as a section within the chapter on myoepithelial lesions in the 3rd edition, is recognised in the 4th edition as part of metaplastic carcinoma. Adenomyoepithelioma with malignancy is categorised in terms of the cellular component undergoing malignant transformation. The list of antibodies that can be used for identifying myoepithelial cells is updated. Among mesenchymal lesions, new additions are nodular fasciitis and atypical vascular lesions, while the haemangiopericytoma is removed. The 3rd edition stated that pathological prediction of behaviour of phyllodes tumours is difficult in the individual case. In the 4th edition, some progress has been made in prioritisation and weighting of histological parameters that can potentially estimate probability of recurrence. The WHO Working Group advocates leaning towards a diagnosis of fibroadenoma in cases where there is histological uncertainty in distinction from a benign phyllodes tumour, or adopting the neutral term 'benign fibroepithelial neoplasm', as the clinical behaviour of fibroadenoma overlaps with that of benign phyllodes tumour. The 3rd edition terminology of 'periductal stromal sarcoma' is revised to 'periductal stromal tumour', akin to the widespread consensus to avoid the use of the term 'cystosarcoma' in the context of phyllodes tumours.
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Affiliation(s)
- Puay Hoon Tan
- Department of Pathology, Singapore General Hospital, Singapore
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35
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A review of adenoid cystic carcinoma of the breast with emphasis on its molecular and genetic characteristics. Hum Pathol 2013; 44:301-9. [DOI: 10.1016/j.humpath.2012.01.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Revised: 01/04/2012] [Accepted: 01/06/2012] [Indexed: 02/07/2023]
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36
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Kulkarni N, Pezzi CM, Greif JM, Suzanne Klimberg V, Bailey L, Korourian S, Zuraek M. Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base. Ann Surg Oncol 2013; 20:2236-41. [PMID: 23456318 DOI: 10.1245/s10434-013-2911-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Adenoid cystic carcinoma (ACC) is a rare subtype of breast malignancy. METHODS Patients with ACC and infiltrating ductal carcinoma (IDC) reported to the National Cancer Data Base from 1998 to 2008 were reviewed for patient age, ethnicity, tumor size, nodal status, American Joint Committee on Cancer TNM Stage, tumor grade, initial treatment, hormone receptor status (for patients from 2004 to 2008), and survival (for patients from 1998 to 2003). RESULTS A total of 933 patients with ACC and 729,938 with IDC were identified. No differences were found for incidence by race/ethnicity (p = 0.97). The group with ACC was older (median 60 vs. 58 years), had larger tumors (median 18 vs. 16 mm), had more grade 1 tumors (46 vs. 18 %), was less likely to undergo axillary lymph node evaluation (75.9 vs. 96.3 %), had fewer node-positive patients (5.1 vs. 35.5 %), had fewer estrogen receptor-positive tumors (15.4 vs. 75.6 %), had fewer progesterone receptor-positive tumors (13.3 vs. 65.2 %), and underwent breast-conserving surgery more often (69.8 vs. 59.8 %). Chemotherapy was provided less often for ACC (11.3 vs. 46.4 %), as was hormone therapy (9.1 vs. 42.3 %). All of these differences were statistically significant (p < 0.0001). With a median follow-up of 65.7 months (ACC) and 64.9 months (IDC), 5-year overall survival (OS) was 88 % for ACC vs. 84 % for IDC (p = 0.02). Grade 1 OS (ACC, 91 % vs. IDC, 92 %; p = 0.50) and stage I OS (ACC, 90 % vs. IDC, 91 %; p = 0.93) were equal. CONCLUSIONS Compared with IDC, ACC has different characteristics (lower grade, hormone receptor negative, node negative), is treated differently (less axillary surgery, fewer mastectomies, less chemotherapy, less hormone therapy), and has an improved prognosis, with 88 % 5-year survival.
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Affiliation(s)
- Nandini Kulkarni
- Department of Surgery, Abington Memorial Hospital, Abington, PA, USA
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37
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Abstract
Invasive breast cancers constitute a heterogeneous group of lesions. Although the most common types are ductal and lobular, this distinction is not meant to indicate the site of origin within the mammary ductal system. The main purpose of the identification of specific types of invasive breast carcinoma is to refine the prediction of likely behavior and response to treatment also offered by the other major prognostic factors, including lymph node stage, histologic grade, tumor size, and lymphovascular invasion.
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Affiliation(s)
- Adriana D Corben
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
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38
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Cadoo KA, McArdle O, O'Shea AM, Power CP, Hennessy BT. Management of unusual histological types of breast cancer. Oncologist 2012; 17:1135-45. [PMID: 22826373 DOI: 10.1634/theoncologist.2012-0134] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
There is increased understanding of the heterogeneity of breast tumors, with greater emphasis now being placed on histological and molecular profiles and, in particular, their implications for prognosis and therapy. This review addresses breast cancers of unusual histological subtype with an approximate incidence ≤1%. Given the rarity of these tumors, the literature contains primarily case reports, small series, and population-based studies. Data are heterogeneous and almost entirely retrospective, frequently gathered over long time periods, in the context of changing pathological techniques and reporting. In addition, our understanding of the disease biology and therapeutic context has also evolved significantly over this time. There is often limited information about the specific therapies used and the rationale for choosing such an approach. Meaningful comparisons of treatment modalities are not feasible and it is not possible to define management guidelines. Instead, this review correlates the available information to give an impression of how each subgroup behaves-of the favored surgical technique, responses to therapy, and prognosis-as well as the emerging molecular data, highlighting new research areas for potential target in clinical trials. Each tumor subtype described represents a small but real cohort of patients with breast cancer, and although inferences may be made from this review, we are mindful of the paucity of data. The management of each patient must be considered in the context of their unique clinical presentation and correlated with the evidence-based principles that apply to more common breast cancer histologies.
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MESH Headings
- Adenocarcinoma/diagnosis
- Adenocarcinoma/pathology
- Adenocarcinoma/therapy
- Breast Neoplasms/classification
- Breast Neoplasms/diagnosis
- Breast Neoplasms/pathology
- Breast Neoplasms/therapy
- Carcinoma/diagnosis
- Carcinoma/pathology
- Carcinoma/therapy
- Carcinoma, Adenoid Cystic/diagnosis
- Carcinoma, Adenoid Cystic/pathology
- Carcinoma, Adenoid Cystic/therapy
- Carcinoma, Ductal, Breast/diagnosis
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Ductal, Breast/therapy
- Carcinoma, Papillary/diagnosis
- Carcinoma, Papillary/pathology
- Carcinoma, Papillary/therapy
- Female
- Humans
- Prognosis
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Affiliation(s)
- Karen A Cadoo
- Evelyn H. Lauder Breast Center, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA.
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Cabibi D, Giannone AG, Belmonte B, Aragona F, Aragona F. CD10 and HHF35 actin in the differential diagnosis between Collagenous spherulosis and adenoid-cystic carcinoma of the breast. Pathol Res Pract 2012; 208:405-9. [PMID: 22658481 DOI: 10.1016/j.prp.2012.05.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Revised: 03/31/2012] [Accepted: 05/03/2012] [Indexed: 10/28/2022]
Abstract
Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast consist of cribriform proliferations of epithelial and myoepithelial cells with an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed in the differential diagnosis of these two breast lesions. We performed an immunohistochemical study on 6 cases of CS and 9 cases of AdCC. We found CD10, muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) were positive in both. Our results also confirm that AdCC could be true basal-like neoplasia, probably arising from a basal stem line tending to divergent differentiation toward CK5/6/C-kit+, ER/PR-, epithelial basal-like cell type, and toward a myoepitelial-like cell type, with an incomplete SMA/p63+, CD10/HHF35- immunophenotype. By contrast, CS is a reactive, benign proliferation of two well-differentiated cell types: epithelial (ER/PR+, C-kit-) and myoepithelial cells with a complete immunophenotype including CD10/HHF35 positivity. Our study highlights the usefulness of CD10 and HHF35 in the differential diagnosis and helps to understand the histogenesis of the two lesions.
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Affiliation(s)
- Daniela Cabibi
- Department of Sciences for Health Promotion, Section of Anatomic Pathology, University of Palermo, Italy
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40
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Novel therapeutic strategies for malignant salivary gland tumors: lessons learned from breast cancer. Int J Otolaryngol 2011; 2011:187623. [PMID: 22164169 PMCID: PMC3227505 DOI: 10.1155/2011/187623] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2011] [Revised: 08/26/2011] [Accepted: 08/27/2011] [Indexed: 01/29/2023] Open
Abstract
Malignant salivary gland tumors (MSGTs) account for 2–6% of all head and neck cancers. Despite the rarity, MSGTs have been of great interest due to a wide variety of pathological features and high metastasis rates resulting in poor prognosis. Surgical resection followed by radiation therapy represents the main treatment of this malignancy. Adjuvant therapy is reserved for the management of local recurrence, no longer amenable to additional local therapy, and for metastasis. Based on the studies from other types of tumors, particularly breast cancer, the expression and function of sex steroid hormone receptors in cancer have been extensively studied and applied to diagnosis and treatment. Although a number of studies in MSGTs have been published, the rationale for hormone therapy is still controversial due to the disparate results and insufficient number of cases. However, some recent reports have demonstrated that certain salivary gland neoplasms are similar to breast cancer, not only in terms of the pathological features, but also at the molecular level. Here, we shed light on the biological similarity between MSGTs and certain types of breast cancer, and describe the potential use of hormone and additional therapies for MSGTs.
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41
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Wetterskog D, Lopez-Garcia MA, Lambros MB, A'Hern R, Geyer FC, Milanezi F, Cabral MC, Natrajan R, Gauthier A, Shiu KK, Orr N, Shousha S, Gatalica Z, Mackay A, Palacios J, Reis-Filho JS, Weigelt B. Adenoid cystic carcinomas constitute a genomically distinct subgroup of triple-negative and basal-like breast cancers. J Pathol 2011; 226:84-96. [PMID: 22015727 DOI: 10.1002/path.2974] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2011] [Revised: 07/17/2011] [Accepted: 07/18/2011] [Indexed: 12/20/2022]
Abstract
Adenoid cystic carcinoma (AdCC) is a rare form of triple-negative and basal-like breast cancer that has an indolent clinical behaviour. Four breast AdCCs were recently shown to harbour the recurrent chromosomal translocation t(6;9)(q22-23;p23-24), which leads to the formation of the MYB-NFIB fusion gene. Our aims were (i) to determine the prevalence of the MYB-NFIB fusion gene in AdCCs of the breast; (ii) to characterize the gene copy number aberrations found in AdCCs; and (iii) to determine whether AdCCs are genomically distinct from histological grade-matched or triple-negative and basal-like invasive ductal carcinomas of no special type (IDC-NSTs). The presence of the MYB-NFIB fusion gene was investigated in 13 AdCCs of the breast by fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR), and MYB and BRCA1 RNA expression was determined by quantitative RT-PCR. Fourteen AdCCs, 14 histological grade-matched IDC-NSTs, and 14 IDC-NSTs of triple-negative and basal-like phenotype were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). The MYB-NFIB fusion gene was detected in all but one AdCC. aCGH analysis demonstrated a relatively low number of copy number aberrations and a lack of recurrent amplifications in breast AdCCs. Contrary to grade-matched IDC-NSTs, AdCCs lacked 1q gains and 16q losses, and in contrast with basal-like IDC-NSTs, AdCCs displayed fewer gene copy number aberrations and expressed MYB and BRCA1 at significantly higher levels. Breast AdCCs constitute an entity distinct from grade-matched and triple-negative and basal-like IDC-NSTs, emphasizing the importance of histological subtyping of triple-negative and basal-like breast carcinomas.
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Affiliation(s)
- Daniel Wetterskog
- The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK
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Dewar R, Fadare O, Gilmore H, Gown AM. Best practices in diagnostic immunohistochemistry: myoepithelial markers in breast pathology. Arch Pathol Lab Med 2011; 135:422-9. [PMID: 21466356 DOI: 10.5858/2010-0336-cp.1] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT Numerous immunohistochemical stains have been shown to exhibit exclusive or preferential positivity in breast myoepithelial cells relative to their luminal/epithelial counterparts. These myoepithelial markers provide invaluable assistance in accurately classifying breast proliferations, especially in core biopsies. Although numerous myoepithelial markers are available, they differ in their sensitivity, specificity, and ease of interpretation, which may be attributed, to a large extent, to the variable immunoreactivity of these markers in stromal cells including myofibroblasts, vessels, luminal/epithelial cells, and tumor cells. OBJECTIVE To review commonly used myoepithelial markers in breast pathology and a selection of diagnostic scenarios where they may be useful. DATA SOURCES The information outlined in this review article is based on our experiences with routine cases and a review of English-language articles published between 1987 and 2008. CONCLUSIONS To demonstrate the presence or absence of myoepithelial cells, a panel-based approach of 2 or more markers is recommended. Markers that most effectively combine sensitivity, specificity, and ease of interpretation include smooth muscle myosin heavy chains, calponin, p75, p63, P-cadherin, basal cytokeratins, maspin, and CD10. These markers, however, display varying cross-reactivity patterns and variably reduced expression in the myoepithelial cells bordering in situ carcinomas. The choice of a myoepithelial marker should be dependent on a combination of factors, including published evidence on its diagnostic utility, its availability, performance characteristics that have been achieved in a given laboratory, and the specific diagnostic scenario. When its use is deemed necessary, immunohistochemistry for myoepithelial cells in breast pathology is most effective when conceptualized as supplemental, rather than central to routine morphologic interpretation.
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Affiliation(s)
- Rajan Dewar
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
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Role of p63 in cancer development. Biochim Biophys Acta Rev Cancer 2011; 1816:57-66. [PMID: 21515338 DOI: 10.1016/j.bbcan.2011.04.002] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2011] [Revised: 04/05/2011] [Accepted: 04/08/2011] [Indexed: 12/22/2022]
Abstract
Since their initial identification p53 homologues p63 and p73 have been expected to play a role in cancer development due to their close homology to p53, notoriously one of the most mutated genes in cancer. However soon after their discovery the awareness that these genes were rarely mutated in cancer seemed to indicate that they did not play a role in its development. However a large number of data collected in the following years indicated that altered expression rather than mutation could be found in different neoplasia and play a role in its biology. In particular p63 due to its fundamental role in epithelial development seems to play a role in a number of tumors of epithelial origin. In this review we summarize some of the evidence linking p63 to carcinogenesis.
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Righi A, Lenzi M, Morandi L, Flamminio F, De Biase D, Farnedi A, Foschini MP. Adenoid cystic carcinoma of the breast associated with invasive duct carcinoma: a case report. Int J Surg Pathol 2011; 19:230-4. [PMID: 19233861 DOI: 10.1177/1066896909332321] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Alberto Righi
- Department of Hematology and Oncology, L. and A. Seràgnoli, Section of Anatomic Pathology, University of Bologna, Bellaria Hospital, Bologna, Italy
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Abstract
CONTEXT Histologic diagnosis of renal neoplasm is usually straightforward by routine light microscopy. However, immunomarkers may be essential in several contexts, including differentiating renal from nonrenal neoplasms, subtyping of renal cell carcinoma (RCC), and diagnosing rare types of renal neoplasms or metastatic RCC in small biopsy specimens. OBJECTIVE To provide a comprehensive review of the diagnostic utility of immunomarkers for renal neoplasms. DESIGN This review is based on published literature and personal experience. CONCLUSIONS The following markers may have diagnostic utility in various diagnostic contexts: cytokeratins, vimentin, α-methylacyl coenzyme A racemase, carbonic anhydrase IX, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, S100A1, CD82, CD117, TFE3, thrombomodulin, uroplakin III, p63, and S100P. Cytokeratins are uniformly expressed by RCC, albeit in a somewhat limited amount in some subtypes, requiring broad-spectrum anti-CK antibodies, including both low- and high-molecular-weight cytokeratins. PAX2 and PAX8 are sensitive and relatively specific markers for renal neoplasm, regardless of subtype. CD10 and RCC marker are sensitive to renal cell neoplasms derived from proximal tubules, including clear cell and papillary RCCs. Kidney-specific cadherin, parvalbumin, claudin-7, and claudin-8 are sensitive markers for renal neoplasms from distal portions of the nephron, including chromophobe RCC and oncocytoma. CK7 and α-methylacyl coenzyme A racemase are sensitive markers for papillary RCC; TFE3 expression is essential in confirming the diagnosis of Xp11 translocation RCC. The potentially difficult differential diagnosis between chromophobe RCC and oncocytoma may be facilitated by S100A1 and CD82. Thrombomodulin, uroplakin III, p63, and S100P are useful markers for urothelial carcinoma. Together with high-molecular-weight cytokeratins, PAX2, and PAX8, they can help differentiate renal pelvic urothelial carcinoma from collecting duct RCC. A sensitive marker for sarcomatoid RCC is still not available. Immunomarkers are most often used for diagnosing metastatic RCC. Compared with primary RCC, expression of the above-mentioned markers is often less frequent and less diffuse in the metastatic setting. Recognizing the variable sensitivity and specificity of these markers, it is important to include at least CD10, RCC marker, PAX2, and PAX8 in the diagnostic panel.
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Affiliation(s)
- Luan D Truong
- Department of Pathology, The Methodist Hospital, 6565 Fannin St., Houston, TX 77030, USA.
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Jaggessarsingh D, Muram-Zborovski TM, Bemis L, Robinson WA, Finlayson C, Singh M. Unique Profile of Adenoid Cystic Carcinoma: A Triple Negative Breast Tumor With Paradoxical Features, a Case Report and Review of Literature. Lab Med 2010. [DOI: 10.1309/lmzauxkp4jdz5z9w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Carcinome adénoïde kystique du sein: à propos de deux cas. ONCOLOGIE 2010. [DOI: 10.1007/s10269-009-1112-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Vranic S, Frkovic-Grazio S, Lamovec J, Serdarevic F, Gurjeva O, Palazzo J, Bilalovic N, Lee LMJ, Gatalica Z. Adenoid cystic carcinomas of the breast have low Topo IIα expression but frequently overexpress EGFR protein without EGFR gene amplification. Hum Pathol 2010; 41:1617-23. [PMID: 20688355 DOI: 10.1016/j.humpath.2010.04.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2010] [Revised: 04/24/2010] [Accepted: 04/30/2010] [Indexed: 01/11/2023]
Abstract
Adenoid cystic carcinoma of the breast is a rare subtype of breast cancer with basal-like features. Published studies on breast adenoid cystic carcinoma are limited, resulting in relatively scarce information on the value of predictive tumor markers. We studied 20 primary cases of adenoid cystic carcinoma of the breast for expression of estrogen receptor, progesterone receptor, androgen receptor, epidermal growth factor receptor, HER-2/neu, and topoisomerase IIα using immunohistochemistry and fluorescent in situ hybridization methods. Estrogen and progesterone receptor expression were detected in 1 case each. All tumors were uniformly negative for Her-2/neu expression. Androgen receptor and topoisomerase IIα expression were weakly positive in three cases and 7 cases, respectively. Epidermal growth factor receptor overexpression was detected in 13 cases (65% of all cases). Amplification of TOP2A or HER-2/neu gene was not detected in any of the cases. Our study shows that the majority of adenoid cystic carcinomas of the breast do not overexpress Her-2/neu, topoisomerase IIα, or estrogen receptor, and thus, they are unlikely to respond to therapies targeting these proteins. However, these tumors frequently over-express epidermal growth factor receptor, indicating a potential benefit from anti-epidermal growth factor receptor therapy for patients with advanced adenoid cystic carcinomas of the breast.
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Affiliation(s)
- Semir Vranic
- Department of Pathology, Clinical Center of the University of Sarajevo, Bosnia and Herzegovina
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Ghabach B, Anderson WF, Curtis RE, Huycke MM, Lavigne JA, Dores GM. Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study. Breast Cancer Res 2010; 12:R54. [PMID: 20653964 PMCID: PMC2949643 DOI: 10.1186/bcr2613] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2010] [Revised: 07/11/2010] [Accepted: 07/23/2010] [Indexed: 01/11/2023] Open
Abstract
Introduction Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and special type of basal-like tumor for which scant population-based descriptive data exist. We sought to provide new population-based information on breast-ACC incidence, relative survival, and associated cancer risk in the United States. Methods Using data from the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), and relative survival for breast-ACC, and standardized incidence ratios (SIRs) for other cancers. Results Overall 338 women (IR = 0.92/1 million person-years) were diagnosed with breast-ACC during 1977 to 2006. Blacks had 39% lower IRs than Whites (IRR = 0.61, 95% confidence interval = 0.37 to 0.96), and IRs remained constant over the 30-year period. Ninety-five percent of cases presented with localized stage (n = 320; IR = 0.87), and the highest IRs were observed for estrogen receptor (ER)-negative/progesterone receptor (PR)-negative tumors (IR = 0.56). Like other typically ER-negative tumors, age-specific IRs increased until midlife and then plateaued. Five-year, 10-year, and 15-year relative survival was 98.1%, 94.9%, and 91.4%, respectively. The risk of female breast cancer was not increased following (SIR = 0.89, 95% confidence interval = 0.43 to 1.64) or preceding (SIR = 0.71, 95% confidence interval = 0.28 to 1.46) breast-ACC. Similarly, no association was observed for breast-ACC and risk of all other cancers combined, solid tumors, or lymphohematopoietic malignancies. Conclusions Breast-ACC among women is characterized by ER-negative/PR-negative expression, rare regional lymph node involvement, a favorable prognosis with excellent survival, and absence of associated cancers. These findings reinforce the importance of tailored treatments for breast-ACC and lend credence to the apparent heterogeneity of basal-like breast cancers.
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Affiliation(s)
- Bassam Ghabach
- Department of Veterans Affairs Medical Center, Medical Service (111), 921 NE 13th Street, Oklahoma City, OK 73104, USA.
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