PNMZL and PTFL: Morphological Variants with a Common Molecular Profile - A Unifying Hypothesis. PNMZL and PTFL: Morphological Variants with a Common Molecular Profile - A Unifying Hypothesis

Pediatric nodal marginal zone lymphoma (PNMZL) is an uncommon B-cell neoplasm affecting mainly male children and young adults. This indolent lymphoma has distinct characteristics that differ from conventional nodal marginal zone lymphoma (NMZL). Clinically, it shows overlapping features with pediatric-type follicular lymphoma (PTFL). To explore the differences between PNMZL and adult NMZL and its relationship to PTFL, a series of 45 PNMZL cases was characterized morphologically and genetically using an integrated approach including whole exome sequencing in a subset of cases, targeted next generation sequencing, and copy number (CN) and DNA methylation arrays. Fourteen cases (31%) were diagnosed as PNMZL, whereas 31 cases (69%) showed overlapping histological features between PNMZL and PTFL including a minor component of residual serpiginous germinal centers reminiscent of PTFL and a dominant interfollicular B-cell component characteristic of PNMZL. All cases displayed low genomic complexity (1.2 alterations/case) with recurrent 1p36/TNFRSF14 copy number-neutral loss of heterozygosity alterations and CN loss (11%). Similar to PTFL, the most frequently mutated genes in PNMZL were MAP2K1 (42%), TNFRSF14 (36%), and IRF8 (34%) DNA-methylation analysis showed no major differences between PTFL and PNMZL. Genetic alterations typically seen in conventional NMZL, were absent in PNMZL. In summary, overlapping clinical, morphological and molecular findings including low genetic complexity, recurrent alterations in MAP2K1, TNFRSF14 and IRF8, and similar methylation profiles indicate that PNMZL and PTFL are likely part of a single disease with variation in the histological spectrum. The term "pediatric-type follicular lymphoma with and without marginal zone differentiation" is suggested.