Pediatric lymphomas: overview and diagnostic challenges.

Only 10% of new lymphoma diagnoses in the USA occur in children < 15 years. Although the same diagnostic criteria apply to both adult and pediatric lymphomas, there are important differences in some lymphoma subtypes. These differences are recognized by the World Health Organization (WHO) with the recent 2022 classification of pediatric tumors including pediatric hematopoietic tumors.

Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young.

Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease.

Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing.

Laboratory Aspects of Minimal / Measurable Residual Disease Testing in B-Lymphoblastic Leukemia.

Minimal residual disease detection provides critical prognostic predictor of treatment outcome and is the standard of care for B lymphoblastic leukemia. Flow cytometry-based minimal residual disease detection is the most common test modality and has high sensitivity (0.01%) and a rapid turnaround time (24 hours).

Laboratory Aspects of Minimal / Measurable Residual Disease Testing in B-Lymphoblastic Leukemia.

Minimal residual disease detection provides critical prognostic predictor of treatment outcome and is the standard of care for B lymphoblastic leukemia. Flow cytometry-based minimal residual disease detection is the most common test modality and has high sensitivity (0.01%) and a rapid turnaround time (24 hours).

Clinicopathologic and prognostic features of TdT-negative pediatric B-lymphoblastic leukemia.

Little is known about B-lymphoblastic leukemia (B-ALL) that lacks expression of terminal deoxynucleotidyl transferase (TdT). To address this, we performed the largest study to date of TdT-negative B-ALL using data from St. Jude Total XV and XVI clinical trials.

Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma.

Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin.

The Comparative Sensitivity of Immunohistochemical Markers of Megakaryocytic Differentiation in Acute Megakaryoblastic Leukemia.

Objectives: Immunohistochemistry (IHC) staining of core biopsy sections often plays an essential role in the diagnosis of acute megakaryoblastic leukemia (AMKL). The goal of this study was to define the relative sensitivities of commonly used stains for markers of megakaryocytic differentiation.

Methods: The sensitivities of IHC stains for CD42b, CD61, and von Willebrand factor (vWF) were compared in 32 cases of pediatric AMKL.

CD30 Expression in Pediatric Neoplasms, Study of 585 Cases.

CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8), and its normal expression is restricted to activated T and B cells. In tumor cells, CD30 expression is most commonly associated with lymphoid malignancies (Hodgkin and non-Hodgkin lymphomas) and is a therapeutic target using anti-CD30 antibody. CD30 expression has been reported also in mostly adult non-lymphoid malignancies, raising the possibility of CD30-targeted therapy for additional tumors.

Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.

Purpose: Histologic markers that differentiate benign and malignant pediatric adrenocortical tumors are lacking. Previous studies have implicated an association of MHC class II expression with adrenocortical tumor prognosis. Here, we determined the expression of MHC class II as well as the cell of origin of these immunologic markers in pediatric adrenocortical tumor.

Pediatric MLBL: challenges remain.

In this issue of Blood, Gerrard et al report the outcome and histologic classification of children and adolescents with mediastinal large B-cell lymphoma (MLBL), and highlight the need for new treatment strategies.

Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells.

Patients with Down syndrome (trisomy 21, T21) have hematologic abnormalities throughout life. Newborns frequently exhibit abnormal blood counts and a clonal preleukemia. Human T21 fetal livers contain expanded erythro-megakaryocytic precursors with enhanced proliferative capacity.

α-Hemoglobin-stabilizing protein is a sensitive and specific marker of erythroid precursors.

α-Hemoglobin-stabilizing protein (AHSP) is an abundant erythroid-specific chaperone protein that facilitates incorporation of nascent α-globin into hemoglobin A. We characterized AHSP expression by immunohistochemistry in a panel of 100 neoplastic and reactive bone marrow biopsies and splenic tissue with extramedullary hematopoiesis and compared it with established erythroid markers CD71 and CD235a. In all cases, AHSP expression was limited to physiological nucleated erythroid precursors (EPs) and blasts in erythroid leukemias.

Self-renewing endodermal progenitor lines generated from human pluripotent stem cells.

The use of human pluripotent stem cells for laboratory studies and cell-based therapies is hampered by their tumor-forming potential and limited ability to generate pure populations of differentiated cell types in vitro. To address these issues, we established endodermal progenitor (EP) cell lines from human embryonic and induced pluripotent stem cells. Optimized growth conditions were established that allow near unlimited (>10(16)) EP cell self-renewal in which they display a morphology and gene expression pattern characteristic of definitive endoderm.

Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways.

Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor.

Cell division rates of primary human precursor B cells in culture reflect in vivo rates.

Bone marrow stroma-based cultures provide a powerful model for studying cell division and apoptosis of primary human precursor B cells. Studies using this model are elucidating the mechanisms by which stromal cells inhibit apoptosis of cultured normal precursor B cells and have demonstrated that the apoptotic rate of cultured leukemic precursor B cells can predict clinical outcome in acute lymphoblastic leukemia. In contrast to apoptosis, cell division in this model has not been well characterized.

Early molecular detection of central nervous system relapse in a child with systemic anaplastic large cell lymphoma: case report and review of the literature.

We report a case of anaplastic large cell lymphoma (ALCL) with central nervous system relapse in an 11-year-old boy. The relapse was suspected on morphologic examination of the cytospin preparations of the cerebrospinal fluid (CSF) with a WBC of 10 cells/microl. CSF relapse was confirmed using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcriptase-polymerase chain reaction (RT-PCR) for abnormal ALK expression or gene structure.

Identification of cyclin D3 as a direct target of E2A using DamID.

The transcription factor E2A can promote precursor B cell expansion, promote G(1) cell cycle progression, and induce the expressions of multiple G(1)-phase cyclins. To better understand the mechanism by which E2A induces these cyclins, we characterized the relationship between E2A and the cyclin D3 gene promoter. E2A transactivated the 1-kb promoter of cyclin D3, which contains two E boxes.