Rare mature B‐cell lymphomas in children and adolescents

Abstract

Pediatric-type follicular lymphoma (PTFL), pediatric nodal marginal zone lymphoma (pnMZL), and large B-cell lymphoma (LBCL) with IRF4 rearrangement have been introduced into the current World Health Organization (WHO) classification. They account for 5% to 10% of mature B-cell lymphomas in children and adolescents. Both PTFL and pnMZL predominantly affect male adolescents and usually present with localized lymphadenopathy in the head and neck region. The cells within the follicles of PTFL typically show high-grade cytology, IGH monoclonality and lack the t(14;18) chromosomal alteration. In contrast, pnMZL is characterized by progressive transformation of germinal center (PTGC)-like features and interfollicular proliferation of the cells with expansion of the marginal zones with diffuse areas. Watch and wait after complete resection seems an adequate therapy with chemotherapy restricted to incompletely resected disease. All children with PTFL and pnMZL reported, so far, survived. B-cell lymphomas presenting in the Waldeyer's ring are characterized by the expression of IRF4/MUM1 and often associated with IRF4 rearrangements. Because of the frequent diffuse component, treatment often follows current protocols for mature B-NHL. The prognosis is excellent. Follicular lymphoma (FL) in children differs from the adult counterpart clinically, morphologically, immunophenotypically, and genetically. 1

Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements

“… 15,16 LBCL- IRF4 predominates in children and young adults, shows frequent involvement of the Waldeyeŕs ring and gastrointestinal tract, and shows excellent outcome in patients after chemotherapy. 13 , 17-19 A recent study demonstrated that LBCL- IRF4 in children and young adults has a distinct molecular profile different from other LBCL characterized by frequent mutations in IRF4 and NF-κB–related genes ( CARD11 , CD79B , and MYD88 ), despite a GCB-transcriptional program, and losses in 17p13 and gains of chromosome 7 and 11q12.3-q25. 20 LBCL- IRF4 shows mostly a GCB phenotype according to the Hans algorithm (HA), 21 with expression of CD10 (60%) and BCL6 but with strong MUM1/IRF4 expression.…”

Distinct molecular profile of IRF4-rearranged large B-cell lymphoma

“…15,16 LBCL with IRF4 rearrangement (LBCL-IRF4) predominates in pediatric population, has a favorable outcome after therapy, and consistently expresses IRF4 due to translocation. [17][18][19][20] These cases display a complex pattern of chromosomal changes, but their mutational profile and possible relationship to other LBCLs is not known. 21 The last WHO classification has also recognized the category of HGBCL that encompasses a spectrum of morphological appearances from blastoid to cases with intermediate features between BL and DLBCL.…”

Molecular Update and Evolving Classification of Large B-Cell Lymphoma

“…Only a few cases are reported involving sites below the diaphragm (abdominal lymph nodes and gastrointestinal tract [116,118]). Patients with LBCL-IRF4 have a favorable prognosis after treatment with immunochemotherapy with or without radiation [116,119].…”

“…Morphologically, most LBCL-IRF4 cases have at least a partial follicular growth pattern resembling FL grade 3B, although diffuse areas [2,119], with medium to large neoplastic cells that can show blastoid appearance and high-grade features are consistent with DLBCL. Follicular areas are characterized by large, tightly packed follicles without polarization and indistinct or absent mantle zones.…”