Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations

Abstract

Key Points PTNFL is a biologically distinct indolent lymphoma characterized by common MEK/ERK pathway mutations. The biology of PTNFL is not defined by age, as the mutational profile is similar in pediatric and adult cases.

Diagnosis and classification of hematologic malignancies on the basis of genetics

“…At a molecular level, pediatric-type FL is characterized by lack of BCL2, BCL6, or MYC rearrangements, low genomic complexity, and a low frequency of mutations in epigenetic modifiers but a high prevalence of MAPK pathway mutations (frequently MAP2K1, and rarely MAPK1 and RRAS, mutations). 82,83 In addition, a new provisional entity of large B-cell lymphoma with IRF4 rearrangement is also now recognized. This entity also occurs in children and young adults, and lacks BCL2 rearrangement, but needs to be distinguished from pediatric-type FL.…”

Recurrent mutations and targeted therapy in FL

“…2 The best recognized inherited bleeding disorder involving the GPIb-IX-V complex is the Bernard-Soulier syndrome (BSS), an autosomal recessive disorder arising from homozygous or compound heterozygous variants of GP1BA, GP1BB, and GP9. 3 In 1948, 2 French physicians, Jean Bernard and Jean-Pierre Soulier, first reported a severe bleeding disorder associated with thrombocytopenia and giant platelets, later shown to be characterized by decreased ristocetin-induced platelet agglutination. 3,4 To date, 45, 39, and 28 variants in GP1BA, GP1BB, and GP9, respectively, have been identified in the BSS.…”

“…3 In 1948, 2 French physicians, Jean Bernard and Jean-Pierre Soulier, first reported a severe bleeding disorder associated with thrombocytopenia and giant platelets, later shown to be characterized by decreased ristocetin-induced platelet agglutination. 3,4 To date, 45, 39, and 28 variants in GP1BA, GP1BB, and GP9, respectively, have been identified in the BSS. 4 GP5 variants have not been implicated in the BSS.…”

“…In contrast to these loss-of-function variants, some GP1BA variants have conferred an increase in affinity of the platelet complex for VWF, resulting in the platelet-type vWD associated with a secondary decrease in plasma high molecular weight VWF multimers. 3 More recently, an association between monoallelic variants in GP1BA and an autosomal dominant macrothrombocytopenia has emerged (see figure). [4][5][6] The most frequent of these is the GP1BA variant (p.Ala172Val), labeled as the "Bolzano" variant, associated with mild thrombocytopenia and increased platelet volume, with or without mild bleeding symptoms.…”

“…These include pediatric-type FL and primary intestinal FL, each of which has been found to be biologically distinct from typical nodal FL cases. 3,4 The t(14;18) is present in the majority of FLs and serves as a defining molecular feature. This translocation, which results in constitutive expression of the antiapoptotic BCL2 protein, appears to be an early genetic event that alone is insufficient to result in lymphomagenesis.…”