Non‐leukemic pediatric mixed phenotype acute leukemia/lymphoma: Genomic characterization and clinical outcome in a prospective trial for pediatric lymphoblastic lymphoma

Abstract

Rare cases of hematological precursor neoplasms fulfill the diagnostic criteria of mixed phenotype acute leukemia (MPAL), characterized by expression patterns of at least two hematopoietic lineages, for which a highly aggressive behavior was reported. We present a series of 11 pediatric non‐leukemic MPAL identified among 146 precursor lymphoblastic lymphomas included in the prospective trial Euro‐LBL 02. Paraffin‐embedded biopsies of 10 cases were suitable for molecular analyses using OncoScan assay (n = 7), fluorescence in situ hybridization (FISH; n = 7) or both (n = 5). Except for one case with biallelic KMT2A (MLL) breaks, all cases analyzed by FISH lacked the most common translocations defining molecular subsets of lymphoblastic leukemia/lymphomas. Two non‐leukemic B‐myeloid MPALs showed the typical genomic profile of hyperdiploid precursor B‐cell lymphoblastic leukemia with gains of chromosomes 4, 6, 10, 14, 18, and 21. One B‐T MPAL showed typical aberrations of T‐cell lymphoblastic lymphoma, such as copy number neutral loss of heterozygosity (CNN‐LOH) at 9p targeting a 9p21.3 deletion of CDKN2A and 11q12.2‐qter affecting the ATM gene. ATM was also mutated in a T‐myeloid MPAL case with additional loss at 7q21.2‐q36.3 and mutation of NRAS, two alterations common in myeloid disorders. No recurrent regions of CNN‐LOH were observed. The outcome under treatment was good with all patients being alive in first complete remission after treatment according to a protocol for precursor lymphoblastic lymphoma (follow‐up 3‐10 years, median: 4.9 years). In summary, the present series of non‐leukemic MPALs widely lacked recurrently reported translocations in lymphoid/myeloid neoplasias and showed heterogeneous spectrum of chromosomal imbalances.

Frequency and prognostic implications of KMT2A rearrangements in children with precursor B-cell lymphoma

“…Due to limited biopsy material and suboptimal DNA quality in the archival FFPE tissue, we could not directly sequence the KMT2A breakpoint. No BCP-L with t(9;22) BCR::ABL1 rearrangements was detected in our cohort (data not shown), in keeping with our previous study on lymphomas with multi-lineage differentiation [10].…”

Non-Hodgkin lenfomanın farkı mukozal görünümleri: Olgu serisi

“…The most common lymphomas are BL and DLBCL, and the most frequent complaints are abdominal pain, loss of weight, and ileus. [1][2][3] In the present study, two of the five patients were BL and one was DLBCL.…”

“…Patients present with non-specific symptoms such as abdominal pain and weight loss. 2,5 BL is a highly aggressive and curable type of lymphoma, with one-third of cases diagnosed between the ages of five and nine. The endemic type BL usually occurs as a result of Epstein-Barr virus (EBV) infection and most frequently involves the jaw bone.…”

“…The ileocecal region is the most common site of involvement. 2…”

“…There are four main categories of childhood NHL: Lymphoblastic lymphoma (LL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and anaplastic large-cell lymphoma. 1,2 This study involves patients who were presented with various clinical and radiological findings and who were diagnosed with lymphoma. The cases include patients with LL referring with a preliminary diagnosis of eosinophilic granuloma (EG); with LL, with a preliminary diagnosis of odontogenic cyst; with BL, with lower gastrointestinal system (GIS) bleeding-acute gastroenteritis; with BL, with a preliminary diagnosis of ovarian tumor and with DLBCL, with a diagnosis of anemia.…”