American journal of clinical pathology · 2026
Composite lymphoma composed of follicular lymphoma and nodal T-follicular helper cell lymphoma: report of 3 cases highlighting histopathologic zonation of each neoplastic component.
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Zhao Yue, Hajjali Ibrahim, Ju Yaping, Carrillo Luis, Feng Mark, Dong Qianze, Chen Dongjiang, Siddiqi Imran, Wang Endi
Аннотация
OBJECTIVES: Composite lymphoma (CL), composed of follicular lymphoma (FL) and nodal T-follicular helper cell lymphoma (nTFHL), is an uncommon and diagnostically challenging entity. We present a small series of such cases to characterize their clinicopathologic and diagnostic features.
METHODS: We retrospectively analyzed 3 CL cases compared with 6 control cases of FL with expanded reactive T-follicular helper cells.
RESULTS: Histologically, all 3 CL cases demonstrated geographic zonation of the 2 neoplastic components, with the B-cell lymphoma residing in follicle centers (B-zones) and the T-cell neoplasm confined to perifollicular/interfollicular areas (T-zones), in contrast to a predominantly (83%) intrafollicular distribution of T-follicular helper cells in the control cases. In all CL cases, FL was suggested by histopathologic features, and the diagnosis was supported by flow cytometry. All 3 cases (100%) showed cytologic atypia and immunophenotypic aberrancy in the T-cell component, whereas none (0%) were observed in the control group. In 2 cases (66.7%), scattered Epstein-Barr virus-positive cells were seen in the T-zone, suggesting latent infection in bystander cells, again compared to none (0%) in the control. Genomic sequencing was performed in 2 cases, both (100%) showing pathogenic mutations associated with nTFHL, while none (0%) of the controls showed such mutations. Biclonality was confirmed by B-cell and T-cell receptor gene rearrangement analyses in all 3 CL cases. All patients with CL presented with an aggressive clinical course.
CONCLUSIONS: This series highlights the unique histopathologic characteristics of CL and underscores the importance of a multifaceted approach to diagnosis.
METHODS: We retrospectively analyzed 3 CL cases compared with 6 control cases of FL with expanded reactive T-follicular helper cells.
RESULTS: Histologically, all 3 CL cases demonstrated geographic zonation of the 2 neoplastic components, with the B-cell lymphoma residing in follicle centers (B-zones) and the T-cell neoplasm confined to perifollicular/interfollicular areas (T-zones), in contrast to a predominantly (83%) intrafollicular distribution of T-follicular helper cells in the control cases. In all CL cases, FL was suggested by histopathologic features, and the diagnosis was supported by flow cytometry. All 3 cases (100%) showed cytologic atypia and immunophenotypic aberrancy in the T-cell component, whereas none (0%) were observed in the control group. In 2 cases (66.7%), scattered Epstein-Barr virus-positive cells were seen in the T-zone, suggesting latent infection in bystander cells, again compared to none (0%) in the control. Genomic sequencing was performed in 2 cases, both (100%) showing pathogenic mutations associated with nTFHL, while none (0%) of the controls showed such mutations. Biclonality was confirmed by B-cell and T-cell receptor gene rearrangement analyses in all 3 CL cases. All patients with CL presented with an aggressive clinical course.
CONCLUSIONS: This series highlights the unique histopathologic characteristics of CL and underscores the importance of a multifaceted approach to diagnosis.