Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia

Abstract

Indolent lymphomas in the pediatric population were discussed during the 2014 European Association for Haematopathology/Society of Hematopathology workshop in Istanbul, Turkey. This session was focused on pediatric-type follicular lymphoma (FL), and its differential diagnosis with the newly recognized entity of IRF4/MUM1+ lymphomas mainly involving Waldeyer's ring. The differential diagnosis between t(14;18) negative FL grade 1/2 and pediatric-type FL in adults was highlighted. The overlapping pathological and clinical features between FL and nodal marginal zone lymphoma (NMZL) in children and young adults were recognized and morphologic and immunophenotypical criteria helpful for the differential diagnosis were presented. Both pediatric-type FL and NMZL are indolent processes that should be distinguished from atypical lymphoid hyperplasia of the tonsils and lymph nodes. The demonstration of a B cell monoclonal population by molecular studies is strongly recommended for the diagnosis. Recognition of these indolent variants to avoid overtreatment was emphasized. Whereas most indolent lymphomas in the pediatric population show characteristic clinical, pathologic, and genetic features that differ from the adult counterpart, other rare indolent lymphoid tumors such as chronic lymphocytic leukemia (CLL) have similar characteristics. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be discussed.

Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene

“…It has been suggested that t(14;18) 2 FL in adults often presents with low clinical stage and excellent prognosis, and therefore might represent a form of PTFL. 6,20 However, a recent study reported similar clinical features in FL with and without t(14;18) translocation. 21 The aim of this study was to perform a Polymerase chain reaction (PCR) amplifications for detecting monoclonal IGH chain gene rearrangements were performed according to the BIOMED-2 protocol 24 using a D4 fluorescent dye modified JH consensus primer (SigmaAldrich, St. Louis, MO) and 2 different concentrations (30 or 60 ng) of genomic DNA.…”

“…20,27 In contrast, the nodal counterpart is mostly follicular; does not express IRF4/MUM1 and rarely BCL2; and the genetic alterations are largely unknown. In the present study, we analyzed a large cohort with characteristic clinical and morphological features and demonstrated that the most frequent genetic alterations in nodal PTFL are mutations/ deletions in the TNFRSF14 gene.…”

Lymphadenectomy Specimens in a Large Retrospective Cohort of Pediatric Patients Reveal No in situ Lymphomas but a Broad Spectrum of Reactive Changes

“…Of note, this study did not specifically look at potential precursor lesions for the now clearly recognized pediatric type follicular lymphoma, an indolent type of follicular lymphoma mainly affecting children and young adults, notably lacking the classical t(14; 18) translocation and bcl-2 protein expression [24] .…”

Pediatric-type Follicular Lymphoma

“…The atypical follicles are comprised of a mixture of intermediate and larger-sized centroblastic lymphocytes with more immature chromatin often lending to an interpretation of higher-grade cytology and aggressive disease. Notably, these morphologic features are often not entirely specific and can show overlap with other lymphomas including pediatric marginal zone lymphoma (Quintanilla-Martinez et al, 2016). By the 2016 WHO classification, diffuse areas suggesting progression or transformation, exclude a diagnosis of pFL.…”