eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, Lymphoblastic

Author: Joseph M Tuscano, MD, Associate Professor of Medicine, Chief, Hematologic Malignancies, Clinical Trials Program, Department of Internal Medicine, Division of Hematology/Oncology, University of California at Davis School of Medicine
Coauthor(s): Theodore Wun, MD, FACP, Professor of Medicine, Professor of Pathology and Laboratory Medicine, University of California Davis School of Medicine; Chief of Hematology/Oncology, Program Director, Veterans Affairs Northern California Health Care System; Medical Director, University of California Davis CCRC; Stephen E Wang, MD, Consulting Staff, Department of Internal Medicine, Division of Hematology/Oncology, Kaiser Permanente
Contributor Information and Disclosures

Updated: Oct 1, 2008

Introduction

Background

Lymphoblastic leukemias/lymphomas are neoplasms of precursor T cells and B cells, or lymphoblasts. The term lymphoblastic lymphoma (LBL) has been used to describe predominantly lymph node–based disease; however, clinical distinction between lymphoblastic lymphoma and acute lymphoblastic leukemia (ALL) has been arbitrary and has varied among different studies and institutions.^1,2

Because it is now known that lymphoblastic lymphoma and ALL represent the same disease entity based on morphologic, genetic, and immunophenotypic features, the World Health Organization (WHO) classification has unified these entities as precursor B-cell and T-cell lymphoblastic leukemia/lymphoma. However, because this unification is relatively recent and the majority of the clinical literature describing these entities has treated these entities as distinct, this article focuses on the disease entity previously designated as lymphoblastic lymphoma.

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lymphoma.

Pathophysiology

Lymphoblastic lymphoma arises from immature T cells in 85-90% of cases and immature B cells in the remainder of cases. The lymphoblasts infiltrate nodal structures or extranodal structures, especially the bone marrow, spleen, and central nervous system (CNS).¹

Lymphoblastic lymphoma is aggressive and progresses rapidly, presenting as stage IV disease in more than 70% of patients. Gross lymphadenopathy impairs immunity, allows opportunistic infections, and may compress adjacent structures. In 30-50% of patients, the lymphoblasts infiltrate bone marrow, causing ineffective hematopoiesis. Many investigators have suggested that both lymphoblastic lymphoma and ALL may be part of one clinical spectrum of a single malignant lymphoproliferative disorder.

Pathogenesis

Much of what is known about the molecular pathogenesis of lymphoblastic lymphoma has arisen from T-cell receptor analysis as well as nonrandom, recurrent chromosomal translocations. Approximately one third of tumors have translocations involving the alpha and delta T-cell receptor loci at band 14q11.2, the beta locus at band 7q35, and the gamma locus at band 7p14-15. These translocations result in juxtaposition T-cell receptor promoter and enhancer elements with various transcription factors, such as HOX11/TLX1, TAL1/SCL, TAL2, and LYL1, which lead to high levels of expression in precursor thymocytes. Molecular array studies have identified subtypes of the above noted abnormalities that may have distinct prognoses.^3,4

Frequency

United States

Lymphoblastic lymphoma is relatively rare, comprising only 2% of all non-Hodgkin lymphomas (NHLs). The T-cell phenotype accounts for 80-90% of cases, with the remainder of B-cell origin.

T-lymphoblastic lymphoma (T-LBL) accounts for 25-30% of childhood NHL and is closely related to T-lymphoblastic leukemia (T-ALL).⁴ Lymphoblastic lymphoma predominates in young adults and adolescents with a median age at diagnosis of 20 years and a slight male predominance.

International

• In a Brazilian study in 96 districts of Sao Paolo that evaluated 507 children aged 0-14 years who were diagnosed with ALL between 1997 and 2002, the investigators found a correlation between the children's Social Exclusion Index (SEI) categories—based on the district of residence at diagnosis, as well as 4 categories from high to low that included the indicators of poverty, employment, inequality, education, and violence—and the districts of residence and areas in which there were high percentages of crowded households.⁵
  • The age-adjusted incidence rate was 3.68/100,000 for males and 2.87/100,000 for females.⁵
  • Children who lived in areas with the lowest SES had a significantly lower risk of ALL compared with those living in the wealthiest districts.⁵
  • There was a strong correlation between SEI and crowding (rho = -0.95, P <0.001). Lower incidence rates of childhood ALL were noted in areas with high percentages of households with >7 persons (>5.7%) compared with those in which there had percentages less than or equal to 2.2%.⁵
  • The authors concluded that population-based attributes for SES and household size may be useful surrogate markers of early exposure to childhood infections, which has been found to decrease the risk of ALL.⁵

Mortality/Morbidity

• With current treatments, the overall survival rate at 5 years in children with lymphoblastic lymphoma is 80-90%, and the overall survival rate in adults is 45-55%.
• Disease-free survival rates at 5 years range from 70% to 90% in children and from 45% to 55% in adults.

Race

No racial predilection exists for lymphoblastic lymphoma.

Sex

The male-to-female ratio of those with lymphoblastic lymphoma is 2:1.

Age

• Lymphoblastic lymphoma is more common in children and adolescents than in adults.
• In adults, the median age at presentation is 27 years for men and 50 years for women.

Clinical

History

• Patients with lymphoblastic lymphoma usually present with painless lymphadenopathy.
• A mediastinal mass occurs in 50-75% of patients and may cause dyspnea and chest pain or may progress to life-threatening compression of the superior vena cava or tracheobronchial tree. B-cell subtypes usually lack a mediastinal mass.
• Constitutional B symptoms include 1 or more of the following:
  • Fever higher than 38ºC
  • Drenching night sweats
  • Weight loss of more than 10% of body weight within 6 months
• Patients may have fatigue from anemia or bleeding and bruising from thrombocytopenia.
• Dyspnea or chest pain may result from pleural disease.
• Neurologic deficits may be present from central nervous system (CNS) disease.
• Patients may have a gonadal mass or gonadal dysfunction.

Physical

Mediastinal adenopathy in a young adult is the predominant finding (60-70% of patients with lymphoblastic lymphoma, likely reflecting the thymic origin of most of these lymphomas and, therefore, is an uncommon feature of B-cell lymphoblastic lymphoma. Pleural, pericardial, and superior vena cava syndrome are also frequent presenting features. Peripheral lymph node involvement is present in 60-80% of patients at diagnosis.

Lymphoblastic lymphoma has a predilection for the bone marrow with a reported incidence at diagnosis of 21%, as well as a reported incidence of 5-10% for the CNS. CNS involvement is more frequent at relapse, particularly in the absence of adequate CNS prophylaxis, with one series reporting 31% CNS involvement at relapse.⁶

Peripheral blood involvement is also common, but the true incidence is confounded by the previous inconsistencies in the distinction between lymphoblastic lymphoma and ALL.

Other rarer sites of involvement include the liver, spleen, and testes. Skin and oropharyngeal involvement is more common in children with B-cell LBL. Signs of involvement include the following:

• Painless lymphadenopathy
• Pallor
• Petechiae
• Ecchymoses
• Splenomegaly
• Neurologic deficits
• Gonadal masses

Causes

Like all NHLs, LBL is associated with exposure to radiation or pesticides and congenital or acquired immunosuppression.

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