Lymphoblastic lymphoma makes up approximately 20% of childhood NHL.[2,3,20] Lymphoblastic lymphomas are usually positive for TdT, with more than 75% having a T-cell immunophenotype and the remainder having a precursor B-cell phenotype.[3,32] Chromosomal abnormalities are not well characterized in patients with lymphoblastic lymphoma. However, one study demonstrated that loss of heterozygosity on chromosome 6q in T-cell lymphoblastic lymphoma patients was associated with an increased risk of relapse.
As many as 75% of patients with lymphoblastic lymphoma will present with an anterior mediastinal mass, which may manifest as dyspnea, wheezing, stridor, dysphagia, or swelling of the head and neck. Pleural effusions may be present, and the involvement of lymph nodes, usually above the diaphragm, may be a prominent feature. There may also be involvement of bone, skin, bone marrow, CNS, abdominal organs (but rarely bowel), and occasionally other sites such as lymphoid tissue of Waldeyer ring and testes. Abdominal involvement is rare compared with Burkitt lymphoma. Low-stage lymphoblastic lymphoma may occur in lymph nodes, bone, and subcutaneous tissue. Lymphoblastic lymphoma within the mediastinum is not considered low-stage disease.
Involvement of the bone marrow may lead to confusion as to whether the patient has lymphoma with bone marrow involvement or leukemia with extramedullary disease. Traditionally, patients with more than 25% marrow blasts are considered to have leukemia, and those with fewer than 25% marrow blasts are considered to have lymphoma. It is not yet clear whether these arbitrary definitions are biologically distinct or relevant for treatment design.
Anaplastic large cell lymphoma
Anaplastic large cell lymphoma (ALCL) accounts for approximately 10% of childhood NHL. While the predominant immunophenotype of ALCL is mature T-cell, null-cell disease (i.e., no T-cell, B-cell, or NK-cell surface antigen expression) does occur. The WHO classification system classifies ALCL as a peripheral T-cell lymphoma (PTCL). Many view ALK-positive ALCL differently than other PTCL because prognosis tends to be superior to other forms of PTCL. More than 90% of pediatric ALCL cases are CD30-positive and have the translocation t(2;5)(p23;q35) leading to the expression of the fusion protein NPM/ALK, though variant ALK translocations have been reported.
Clinically, ALCL has a broad range of presentations, including involvement of lymph nodes and a variety of extranodal sites, particularly skin and bone and, less often, gastrointestinal tract, lung, pleura, and muscle. Involvement of the CNS and bone marrow is uncommon. ALCL is often associated with systemic symptoms (e.g., fever, weight loss) and a prolonged waxing and waning course, making diagnosis difficult and often delayed. Patients with ALCL may present with signs and symptoms consistent with hemophagocytic lymphohistiocytosis. There is a subgroup of ALCL with leukemic peripheral blood involvement. These patients usually exhibit significant respiratory distress with diffuse lung infiltrates or pleural effusions and have hepatosplenomegaly. Most of these patients have an aberrant T-cell immunophenotype with frequent expression of myeloid antigens. Patients in this ALCL subgroup may require more aggressive therapy.[37,38] In a retrospective subset analysis, there was evidence that submicroscopic bone marrow and peripheral blood involvement, detected by reverse transcriptase-polymerase chain reaction (RT-PCR) from NPM-ALK, was found in approximately 50% of patients and correlated with clinical stage; marrow involvement detected by PCR was associated with a 50% cumulative incidence of relapse.