Pediatric-Type Indolent B-Cell Lymphomas With Overlapping Clinical, Pathologic, and Genetic Features

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric indolent B-cell lymphomas (PedIBCL).
• These lymphomas differ from adult forms, making diagnosis challenging and risking overtreatment.
• The genetic landscape of PTFL is known, but PNMZL's genetics remain less understood.

Purpose of the Study:

• To investigate the clinicopathologic and genetic features of PedIBCL, including PTFL, PNMZL, and mixed-type tumors.
• To compare the genetic profiles of these pediatric lymphomas with adult B-cell lymphomas exhibiting similar features.
• To clarify the diagnostic challenges and disease spectrum of PedIBCL.

Main Methods:

• Clinicopathologic analysis of 21 PedIBCL cases (11 PTFL, 2 PNMZL, 8 mixed-type) and 2 adult B-cell lymphoma cases.
• Targeted sequencing of 121 lymphoma-related genes.
• Comparison of genetic mutations and clinical features across different groups.

Main Results:

• PedIBCL patients had a median age of 16 years, predominantly male, and presented with limited-stage disease.
• Frequently mutated genes across all PedIBCL groups included MAP2K1, TNFRSF14, KMT2C, IRF8, and NOTCH2.
• Genetic profiles of PTFL, PNMZL, and mixed-type tumors were similar to the known PTFL mutational landscape.
• Adult cases with similar histology also harbored MAP2K1, TNFRSF14, and IRF8 mutations but lacked typical pediatric clinical features.

Conclusions:

• PTFL and PNMZL are clinically, pathologically, and genetically similar, indicating they may represent a spectrum of the same disease.
• Mixed-type tumors also share these overlapping features.
• The findings suggest the disease spectrum of PedIBCL is broader than currently recognized, and adult cases with similar histology exist.