Lymphoproliferative Disorders
Basics
Description
- 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
Epidemiology
All uncommon
Risk Factors
Often multifactorial with inherited genetic defect and acquired infection
Genetics
- 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
- XLP
- Majority of cases mutation in SH2DIA
- XLP-like syndrome caused by X-linked inhibitor of apoptosis protein (XIAP) mutations
Pathophysiology
- ALPS
- Defective FAS-mediated apoptosis leads to abnormal lymphocyte survival with subsequent lymphoproliferation, autoimmunity, and cancer.
- CD
- Largely unknown but can be triggered by HHV-8 infection, especially in immunocompromised patients
- ELD
- 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
- XLP
- 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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Citation
Cabana, Michael D., editor. "Lymphoproliferative Disorders." 5-Minute Pediatric Consult, 8th ed., Wolters Kluwer, 2019. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617757/all/Lymphoproliferative_Disorders.
Lymphoproliferative Disorders. In: Cabana MDM, ed. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617757/all/Lymphoproliferative_Disorders. Accessed December 9, 2024.
Lymphoproliferative Disorders. (2019). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult (8th ed.). Wolters Kluwer. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617757/all/Lymphoproliferative_Disorders
Lymphoproliferative Disorders [Internet]. In: Cabana MDM, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. [cited 2024 December 09]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617757/all/Lymphoproliferative_Disorders.
* Article titles in AMA citation format should be in sentence-case
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T1 - Lymphoproliferative Disorders
ID - 617757
ED - Cabana,Michael D,
BT - 5-Minute Pediatric Consult
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PB - Wolters Kluwer
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DB - Pediatrics Central
DP - Unbound Medicine
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