Summary

Objective. In B-cell lymphomas, the presence of abundant T-follicular helper (TFH) cells is rarely reported but can pose significant diagnostic challenges, potentially leading to misdiagnosis. The limited literature underscores the importance of detailed characterization of this phenomenon. This study presents the largest series of non-Hodgkin B-cell lymphomas with notable TFH cell hyperplasia, broadening the recognized spectrum of lymphomas associated with abundant TFH cells hyperplasia, and aims to enhance awareness and understanding of this phenomenon. 

Methods. We investigated 15 cases of non-Hodgkin B-cell lymphomas with notable TFH cell hyperplasia, analyzing clinical information, morphology, immunophenotypic findings, PCR-based clonality, and next-generation sequencing (NGS) results. 

Results. Among these, follicular lymphoma was the most common type (n = 7), followed by diffuse large B-cell lymphoma (n = 5), and rare types such as pediatric-type follicular lymphoma (n = 1), small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 1), and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n = 1). Shared features across these lymphoma subtypes included significant proliferation of TFH cells, and frequently accompanied by prominent paracortical vascularity, with occasional cases exhibiting eosinophilia. However, the absence of concomitant expansion of follicular dendritic cell (FDC) meshworks and EBER negativity argued against a diagnosis of nodal TFH cell lymphoma, angioimmunoblastic type (nTFHL-AI). 

Conclusions. TFH cell hyperplasia can occur in various types of non-Hodgkin B-cell lymphomas, making it crucial for pathologists to recognize reactive TFH cells. This study emphasizes the importance of integrating morphological, immunohistochemical, and molecular findings for accurate diagnosis in these cases.

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Authors

Xuan Wang - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Teng Yu - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Haimin Xu - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Binshen Ouyang - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Anqi Li - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Yimin Li - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Xia Shen - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Yuxiu Zhang - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Lei Zhang - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Yang Liu - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Xu Wang - Department of Pathology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Chaofu Wang - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Hongmei Yi - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Copyright (c) 2026 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Wang, X., Yu, T., Xu, H., Ouyang, B., Li, A., Li, Y., Shen, X., Zhang, Y., Zhang, L., Liu, Y., Wang, X., Wang, C., & Yi, H. (2026). Non-Hodgkin B-cell lymphomas with significant proliferation of T follicular helper T cell: a diagnostic pitfall. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 118(4). https://doi.org/10.32074/1591-951X-1148
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