- Lymphoproliferative disorders are a class of nonmalignant diseases characterized by uncontrolled growth of lymphoid tissues (spleen, bone marrow, liver, lymph nodes).
- Can be congenital or acquired
- Based on recent advances in next generation sequencing technology, new disorders are defined constantly.
- Most common in children include
- Autoimmune lymphoproliferative syndrome (ALPS)
- Castleman disease (CD)
- Rosai–Dorfman disease (RDD)
- EBV-associated lymphoproliferative disorder (ELD)
- X-linked lymphoproliferative syndrome (XLP)
- Rarer disorders (not discussed in detail)
- Angioimmunoblastic lymphadenopathy
- Caspase-8 deficiency syndrome (CEDS)
- Dianzani autoimmune lymphoproliferative disease
- Kikuchi-Fujimoto syndrome
- Lymphomatoid granulomatosis
- Lymphomatoid papulosis
- Ocular adnexal lymphoid proliferation
- RAS-associated leukoproliferative disorder (RALD)
- p110δ activating mutation causing senescent T cells lymphadenopathy and immunodeficiency (PASLI)
- CTLA-4 haploinsufficiency with autoimmune infiltration (CHAI)
- LRBA deficiency with autoantibodies, regulatory T-cell defects, autoimmune infiltration and enteropathy (LATAIE)
- X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (X-MEN)
- Interleukin-2-inducible T-cell kinase (ITK) deficiency
Often multifactorial with inherited genetic defect and acquired infection
- ALPS (80% of patients have identifiable mutation)
- 60–70% germline mutation in FAS (TNFRSF6)
- 10% somatic mutation in FAS
- 2% germline mutation in CASP10
- <1% germline mutation in FASL
- Majority of cases mutation in SH2DIA
- XLP-like syndrome caused by X-linked inhibitor of apoptosis protein (XIAP) mutations
- Defective FAS-mediated apoptosis leads to abnormal lymphocyte survival with subsequent lymphoproliferation, autoimmunity, and cancer.
- Largely unknown but can be triggered by HHV-8 infection, especially in immunocompromised patients
- EBV triggered lymphoproliferative disorder found in patients on chronic immune suppression typically after organ or bone marrow transplant (post-transplant lymphoproliferative disorder [PTLD]) or with inherited immune deficiency
- Mutation in SH2D1A leads to abnormal production of SAP protein in NK and T cells, leading to defective SAP-SLAM signaling and inability to appropriately respond to EBV infection.
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