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Lobular Neoplasia of the Breast Revisited With Emphasis on the Role of E-Cadherin Immunohistochemistry

Dabbs, David J. MD*; Schnitt, Stuart J. MD; Geyer, Felipe C. MD; Weigelt, Britta PhD§; Baehner, Frederick L. MD; Decker, Thomas MD; Eusebi, Vincenzo MD#; Fox, Stephen B. MD, PhD**; Ichihara, Shu MD††; Lakhani, Sunil R. MBBS, BSc, PhD, FRCPath‡‡; Palacios, Jose MD§§; Rakha, Emad MD, PhD∥∥; Richardson, Andrea L. MD, PhD¶¶; Schmitt, Fernando C. MD, PhD##; Tan, Puay-Hoon MBBS, FRCPA, FAMS, MD, FRCPath, MIAC***; Tse, Gary M. MD†††; Vincent-Salomon, Anne MD, PhD‡‡‡; Ellis, Ian O. MD∥∥; Badve, Sunil MD, FRCPath§§§; Reis-Filho, Jorge S. MD, PhD, FRCPath§

The American Journal of Surgical Pathology: July 2013 - Volume 37 - Issue 7 - p e1–e11
doi: 10.1097/PAS.0b013e3182918a2b
Special Article

Lobular neoplasia (LN) is a term that encompasses both lobular carcinoma in situ and atypical lobular hyperplasia. These lesions have been shown to constitute both risk indicators and nonobligate precursors of invasive breast cancer, they are relatively uncommon, and are most often identified in specimens taken for other reasons. Their incidence has increased in the last 2 decades, and novel variants, including a pleomorphic type, have been described. Loss of E-cadherin expression is recognized as a hallmark diagnostic feature of LN and invasive lobular carcinomas, and immunohistochemical (IHC) analysis using anti-E-cadherin antibodies has been proven to be a useful method to differentiate between lobular and ductal lesions. The frequent use of E-cadherin IHC analysis in routine diagnostic histopathology, however, has resulted in confusion with regard to the actual value of IHC with antibodies against E-cadherin and other proteins of the cadherin-catenin complex. This review provides an update on recent clinicopathologic and molecular data on LN and invasive lobular carcinoma and a discussion about the use and limitations of IHC with E-cadherin in diagnostic breast pathology.

*Department of Pathology, Magee-Women’s Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA

Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School

¶¶Department of Pathology, Brigham and Women’s Hospital, Boston, MA

§Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY

Department of Anatomic Pathology, University of California, San Francisco, CA

§§§Indiana University Health Pathology Laboratory, Department of Pathology and Internal Medicine, Indiana University, Indianapolis, IN

Department of Pathology, Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa, São Paulo, Brazil

Dietrich-Bonhoeffer Medical Center Neubrandenburg, Neubrandenburg, Germany

#Sezione Anatomia Istologia e Citologia Patologica ‘M Malpighi’, Università-ASL Ospedale Bellaria, Bologna, Italy

**Pathology Department, Peter MacCallum Cancer Centre, East Melbourne, Vic.

‡‡University of Queensland, UQ Centre for Clinical Research, School of Medicine and Pathology Queensland, The Royal Brisbane and Women’s Hospital, Herston, Brisbane, QLD, Australia

††Department of Pathology, Nagoya Medical Center, Nagoya, Japan

§§Servicio de Anatomía Patológica, Hospital Universitario Ramón y Cajal, Madrid, Spain

∥∥Department of Histopathology, Nottingham City Hospital NHS Trust, Nottingham University, Nottingham, UK

##Medical Faculty, Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal

***Department of Pathology, Singapore General Hospital, Singapore, Singapore

†††Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China

‡‡‡Department of Tumor Biology, Institut Curie, Paris, France

The authors are an independent international group of academic surgical pathologists with an interest in breast pathology, who hold informal annual meetings to discuss contentious issues in diagnostic breast pathology. The opinions expressed in this article do not represent those of any organizations or professional bodies the authors are affiliated with as individuals.

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Jorge S. Reis-Filho, MD, PhD, FRCPath, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail:

© 2013 by Lippincott Williams & Wilkins.