DESCRIPTION

• Non-Hodgkin lymphoma (NHL) arises from the malignant proliferation of developing or mature B or T lymphocytes.
• Extent of disease is determined using the Murphy staging system:
  • Stage I: single tumor (extranodal) or single nodal area, excluding mediastinum or abdomen
  • Stage II: single tumor with regional nodal involvement, two or more tumors or nodal areas on the same side of the diaphragm, or a primary gastrointestinal (GI) tract tumor (resected) with or without regional node involvement
  • Stage III: tumors or lymph node (LN) areas on both sides of the diaphragm, any primary intrathoracic or extensive intra-abdominal disease (unresectable), or any paraspinal or epidural tumors
  • Stage IV: bone marrow or central nervous system (CNS) disease regardless of other sites; marrow involvement defined as 0.5–25% malignant cells

EPIDEMIOLOGY

• Third most common childhood malignancy (~7% cancers in individuals <20 years of age in developed countries)
• Male-to-female ratio: 3:1
• Higher frequency of endemic Burkitt-type lymphoma in equatorial African countries (40 to 50 per 1 million children aged <18 years; peaks at age 6 years)
• Incidence increases steadily with age; in children, usually seen in 2nd decade of life (unusual in those <3 years of age)
• Incidence is higher among White children compared to Black children

RISK FACTORS

Environmental factors

• Drugs: immunosuppressive therapy
• Radiation: atomic bomb survivors and ionizing radiation
• Viruses: Epstein-Barr virus (EBV) present in >95% of cases of endemic Burkitt versus 20–30% cases of sporadic and HIV-associated cases

PATHOPHYSIOLOGY

• Unlike adults, low- and intermediate-grade NHL is uncommon in children (~7% of cases).
• NHL in children and adolescent can be divided into three major categories according to the National Cancer Institute (NCI):
  • Mature B-cell NHL (Burkitt and Burkitt-like lymphoma, diffuse large B-cell lymphoma [DLBCL], primary mediastinal B-cell lymphoma [PMBCL])
    • 50% of childhood NHL
    • Express mature B-cell markers (CD20, surface immunoglobulin [Ig])
    • Terminal deoxynucleotidyl transferase (TdT) negative
    • Burkitt lymphoma has a characteristic translocation of MYC to the Ig heavy or light chain. The most common translocation is t(8;14); t(8;22) or t(2;8) can also been seen.
    • DLBCL usually of the germinal center B-cell phenotype; t(14:18) translocations and 8q24 MYC rearrangements are common.
    • PMBCL is most common in the adolescent and young adult population and usually has strong expression of PD-L1 and PD-L2.
  • Lymphoblastic lymphomas (LL)
    • 30% of childhood NHL; in children, 70–80% T cell and 20–25% B-cell origin
    • Morphologically identical to acute lymphoblastic leukemia; TdT-positive; express early T (CD5, CD7, cytoplasmic CD3) or B (CD19, CD10) cell markers; bone marrow involvement of >25% blasts is considered leukemia.
    • Early thymic progenitor (ETP) subtype arises earlier in T-cell ontogeny. Most recent studies indicate it has a slower response to therapy but does not have a worse prognosis.
  • Anaplastic large cell lymphoma (ALCL) (mature T-cell or null-cell lymphomas):
    • 10% of childhood NHL
    • Express CD30 (Ki-1); contain chromosomal rearrangement involving the ALK gene (85% t2;5)
• Posttransplantation lymphoproliferative disorders (PTLDs) develop following hematopoietic stem cell transplantation or solid organ transplantation in the setting of decreased T-cell function; most commonly of B-cell origin and associated with EBV