How I Diagnose Angioimmunoblastic T-Cell Lymphoma

Yi Xie, MD, PhD; Elaine S. Jaffe, MD

Disclosures

Am J Clin Pathol. 2021;156(1):1-14. 

In This Article

Abstract and Introduction

Abstract

Objectives: Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma derived from T-follicular helper cells. For pathologists, diagnosing AITL may be challenging due to its wide clinical and histopathologic spectrum, which can mimic a variety of reactive and neoplastic processes.

Methods: We summarize and discuss the clinicopathologic features of AITL, emphasizing diagnostic tools available to the practicing pathologist. Common diagnostic dilemmas are discussed.

Results: AITL exhibits various histologic patterns and is often associated with a prominent microenvironment that can obscure the neoplastic cells. Atypical B-cell proliferations, which can take a number of forms, are common in AITL, and clonal B-cell expansion can be seen. The atypical B cells can closely resemble Hodgkin/Reed-Sternberg cells, leading to misdiagnosis as classic Hodgkin lymphoma. Molecular studies have revealed recurrent genetic alterations, which can aid in differential diagnosis, particularly in problematic cases.

Conclusions: Given the complex diagnostic challenges in AITL, an integrated approach, incorporating clinical, morphologic, immunophenotypic, and molecular findings, is helpful to reach an accurate diagnosis.

Introduction

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL) with unique clinicopathologic and genetic features. While AITL accounts for only 1% to 2% of all non-Hodgkin lymphomas, it is the second most common subtype of PTCL, representing approximately 15% to 20% of all PTCLs.[1–3] When first described, it was considered an abnormal immune reaction or atypical lymphoid hyperplasia.[4,5] Subsequent identification of cytogenetic abnormalities and clonality of the T cells led to the current view of AITL as a T-cell lymphoma.[6–8] Over the past two decades, advances in gene expression profiling and next-generation sequencing technologies have brought tremendous progress in our understanding of AITL. Today, AITL is recognized as a neoplasm derived from T-follicular helper (TFHs) cells, a finding that links together many of its clinical and pathologic features.[9,10] Studies have also identified follicular T-cell lymphoma (FTCL) and other nodal PTCLs with phenotypic and molecular overlap with AITL.[11–13] These lymphomas are now grouped with AITL in the 2016 revised World Health Organization (WHO) classification in the new category of nodal T-cell lymphoma of TFH-cell origin.[14]

Despite these advances, diagnosis of AITL in many instances remains challenging. Due to the functional properties of the neoplastic TFH cells, the lymphoma is polymorphic and contains variable proportions of tumor cells and inflammatory cells. The neoplastic T cells often constitute a minor part of the cellular infiltrate and may be difficult to identify. Moreover, concomitant expansion of B cells or other immune cells may simulate diverse reactive and neoplastic conditions. The histopathologic spectrum of AITL is broad, and sometimes morphologic features can be misleading. Some borderline lesions may pose a challenge to even experienced pathologists. This article summarizes clinical and pathologic features of AITL, with particular emphasis on commonly encountered problems and unique aspects of AITL that may aid in accurate diagnosis.

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