What is the pathophysiology of lymphoblastic lymphoma?

Updated: Sep 10, 2019
  • Author: Joseph M Tuscano, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Lymphoblastic lymphoma is associated with exposure to radiation or pesticides and congenital or acquired immunosuppression and is more common in children and young adults. This condition arises from immature T cells in more than 80% of cases and immature B cells in the remainder of cases. The lymphoblasts infiltrate nodal structures or extranodal structures and is commonly associated with large mediastinal masses with a high predilection for disseminating to bone marrow and the central nervous system (CNS). [3]

Lymphoblastic lymphoma is aggressive and progresses rapidly, presenting as stage IV disease in more than 70% of patients (see Staging). 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 acute lymphoblastic leukemia (ALL) may be part of one clinical spectrum of a single malignant lymphoproliferative disorder. [4]

Although several subtypes of T-cell lymphoblastic leukemia/lymphoma exist, early T-cell precursor lymphoblastic leukemia (ETP-ALL) is the only subtype recognized as an entity in the revised 2016 WHO tumor classification. [1]  ETP-ALL frequently has mutations in RUNX1 and/or ETV6 in addition to genes that are more commonly associated with myeloid neoplasms and are otherwise rare in T-cell lymphoblastic leukemia/lymphoma (such as FLT3IDH1/2TET2, and DNMT3A mutations). [5]

Non-ETP subtypes of T-cell lymphoblastic leukemia/lymphoma, in contrast, are associated with activating NOTCH1 mutations in over half of all patients and an additional 10% to 15% of cases have FBXW7 mutations, which also result in increased NOTCH signaling. Mutations in PHF6 are also seen in 20% to 40% of T-ALL and are largely restricted to non-ETP cases. Chromosomal alterations are also common and include loss of CDKN2A/B through chromosome 9 deletion in 50% to 60% of non-ETP T-ALL patients. Finally, translocations and noncoding region mutations such as TAL1, TAL2, LYL1, LMO1LMO2TLX1TLX3ZEB2MYB, and MYC are common but their clinical relevance is not known. [5]


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