Clinicopathologic analysis of nodal T-follicular helper cell lymphomas, a multicenter retrospective study from China

Abstract

Background: Nodal T-follicular helper cell lymphomas (nTFHLs) represent a new family of peripheral T-cell lymphomas (PTCLs), and comparative studies of their constituents are rare.

Methods: This study retrospectively enrolled 10 patients with nTFHL-F and 30 patients with nTFHL-NOS diagnosed between December 2017 and October 2023 at six large comprehensive tertiary hospitals; 188 patients with nTFHL-AI were diagnosed during the same period at the First Affiliated Hospital of Zhengzhou University for comparison.

Results: Compared with nTFHL-AI, nTFHL-NOS patients exhibited better clinical manifestations, lower TFH expression levels, and a lower Ki-67 index. However, no differences in clinicopathological features were observed between nTFHL-F and nTFHL-AI patients as well as nTFHL-NOS patients. According to the survival analysis, the median OS for patients with nTFHL-NOS, nTFHL-AI, and nTFHL-F were 14.2 months, 10 months, and 5 months, respectively, whereas the median TTP were 14 months, 5 months, and 3 months, respectively. Statistical analysis revealed differences in TTP among the three subtypes(P=0.0173). Among the population of patients receiving CHOP-like induction therapy, there were significant differences in the OS and TTP among the nTFHL-NOS, nTFHL-AI, and nTFHL-F patients (P=0.0134, P=0.0205). Both the GDPT and C-PET regimens significantly improved the ORR, OS, and PFS in nTFHL patients.

Conclusion: There are significant differences in the clinical manifestations, pathology, and survival outcomes among the three subtypes of nTFHLs. However, further research with a larger sample size, and involving clinical pathology and molecular genetics is needed to determine the distinctive biological characteristics of these tumors.

Keywords: clinical features; clinicopathology; nodal T-follicular helper cell lymphoma; peripheral T-cell lymphoma; prognostic analysis.

Figure 1

nTFHL-AI: H&E shows that the neoplasm is diffuse and composed of a heterogeneous cell infiltrate associated with numerous HEVs, inflammatory cells (A × 200). The tumor cells are positive for CD3 (B × 10), CD4 (C × 200), PD-1 (E × 10), BCL-6 (F × 200) and CXCL13 (G × 200) and negative for CD8 (D × 10). CD21 (H × 10) highlights hyperplastic and dilated FDC networks.

Figure 2

nTFHL-F: H&E shows effacement of lymph nodal architecture by monomorphic nodules (A × 100); the nodule comprises small to intermediate size tumor cells. These cells are immunopositive for CD3 (B × 10), CD4 (C × 100), BCL-6 (E × 10), CXCL13 (G × 100) and PD-1 (F × 100) while negative for CD8 (D × 100). CD21 staining shows mild expansion of FDC meshworks (H × 10).

Figure 3

nTFHL-NOS: H&E staining showed that the nodal structure was destroyed, and the tumor cells are diffusely infiltrative (D × 4, A × 400). IHC staining showed that the tumor cells express CD3 (B × 10), CD4 (C × 100), BCL-6 (E × 10), PD-1 (F × 100) and CXCL13 (G × 100). A small amount of residual atrophic FDC are positive for CD21 (H × 10).

Figure 4

OS (A) and TTP (B) Kaplan–Meier survival curves of all patients; OS (C) and TTP (D) Kaplan–Meier survival of all patients with CHOP-like induction therapy; Kaplan–Meier survival curves of OS according to prognostic index for T-cell lymphoma; IPI (E), PIT (F); Kaplan–Meier survival curves of OS (G) and PFS (H) of all patients with C-PET, GDPT and CHOP-like induction therapy. AI, nTFHL-AI; F, nTFHL-F; NOS, nTFHL-NOS; CHOP, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone; GDPT, Gemcitabine, Cisplatin, Prednisone, Thalidomide; C-PET, Chidamide plus Prednisone, Etoposide, and Thalidomide.