Review ArticlesPractical Approach to the Histologic Diagnosis of Gastrointestinal Lymphomas Through the First-line Marker Battery of CD20, CD3, CD30, and Epstein-Barr Virus–encoded RNAsKim, Eun Kyung MD, PhD*,†; Yang, Woo Ick MD, PhD*; Ryu, Hyang Joo MD*; Ji, Hee Lee MD*; Yoon, Sun Och MD, PhD*Author Information *Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul †Department of Pathology, National Health Insurance Service Ilsan Hospital, Goyang, South Korea Supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. NRF-2019R1A2C1002370). This study was approved by the Institutional Review Board of Severance Hospital (Protocol No.4-2018-0933). The authors have no conflicts of interest to disclose. Reprints: Sun Och Yoon, MD, PhD, Department of Pathology, Yonsei University College of Medicine, Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea (e-mail: [email protected]). Advances In Anatomic Pathology: March 2020 - Volume 27 - Issue 2 - p 75-86 doi: 10.1097/PAP.0000000000000260 Buy SDC Metrics Abstract The gastrointestinal (GI) tract is a prevalent site for extranodal lymphomas. Some subtypes of GI tract lymphomas are aggressive and have dismal clinical outcomes. Therefore, prompt histopathologic detection of such types can be very important. We thus introduce a practical approach in the histopathologic diagnosis of GI lymphomas according to the revised World Health Organization (WHO) classification. When lymphocyte proliferation is found in the GI tract, a stepwise approach can help narrow down the differential diagnoses. When considering subtype incidence, macroscopic findings, and microscopic patterns, applying a first-line marker battery of CD20, CD3, CD30, and Epstein-Barr virus–encoded RNAs can effectively narrow down the top differential diagnoses at the initial step. Generally, the most common subtype among GI tract lymphomas is B-cell non-Hodgkin lymphoma identified by CD20 expression, followed by T-cell and NK-cell non-Hodgkin lymphomas identified by the CD3 expression, and some subtypes are defined by Epstein-Barr virus infection or CD30 expression. Macroscopically, lymphomas present as various gross types, such as large masses, small lesions, superficial and shallow lesions, polyp-like or polyposis-like features, or ulcer/necrosis/perforation. Microscopically, large pleomorphic cells or small to medium-sized tumor cells grow with various architectures and tumor microenvironments. Incorporation of macroscopic and microscopic features and the stepwise immunophenotyping may be a practical approach to the differential diagnosis of aggressive lymphoma, indolent/low-grade lymphoma, or benign to indolent lymphoproliferative disease. Exceptions always exist; this approach focuses on the relatively prevalent circumstances of lymphomatous lesions initially encountered in the GI tract. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.