# Composite lymphoma composed of follicular lymphoma and nodal T-follicular helper cell lymphoma: report of 3 cases highlighting histopathologic zonation of each neoplastic component

## TL;DR

This paper reports three rare cases of composite lymphoma involving two types of lymphoma with distinct locations in the lymph node, emphasizing the need for detailed diagnostic methods.

## Contribution

The study identifies unique histopathologic zonation patterns in composite lymphoma cases involving follicular lymphoma and T-follicular helper cell lymphoma.

## Key findings

- Composite lymphoma cases showed distinct geographic zonation of B-cell and T-cell components in lymph nodes.
- T-cell components in composite lymphoma showed cytologic atypia and immunophenotypic aberrancy not seen in controls.
- Genomic sequencing confirmed pathogenic mutations in T-cell lymphoma components, supporting the diagnosis of nTFHL.

## Abstract

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.

We retrospectively analyzed 3 CL cases compared with 6 control cases of FL with expanded reactive T-follicular helper cells.

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.

This series highlights the unique histopathologic characteristics of CL and underscores the importance of a multifaceted approach to diagnosis.