Development of Lymphoma in Autoimmune Lymphoproliferative Syndrome (ALPS) and its Relationship to Fas Gene Mutations

@article{Poppema2004DevelopmentOL,
  title={Development of Lymphoma in Autoimmune Lymphoproliferative Syndrome (ALPS) and its Relationship to Fas Gene Mutations},
  author={Sibrand Poppema and Ewerton Marques Maggio and Anke van den Berg},
  journal={Leukemia \& Lymphoma},
  year={2004},
  volume={45},
  pages={423 - 431}
}
Autoimmune Lymphoproliferative Syndrome (ALPS) is generally the result of a mutation in genes associated with apoptosis, like Fas, Fas ligand, Casp 8 and Casp 10. As a result, the normal homeostasis of T- and B-lymphocytes is disturbed and a proliferation of polyclonal T lymphocytes occurs. This leads to hepatosplenomegaly and lymphadenopathy and in most patients also to autoimmune phenomena like anemia and thrombocytopenia. The proliferating T cells are TCRαβ and/or TCRγδ positive but lack… 
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Recognition of ALPS is critical, as treatment with immunosuppressive therapies can effectively reduce or ameliorate symptoms for most patients.
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It is determined that patients with germline mutations of the intracellular domain of Fas protein have a significantly increased risk of developing Hodgkin and non-Hodgkin lymphoma (NHL), underscoring the critical role played by cell surface receptor-mediated apoptosis in eliminating redundant proliferating lymphocytes with autoreactive and oncogenic potential.
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Studying ALPS may improve the understanding of normal tolerance and more common, sporadic autoimmune disorders, and shed light on the pathophysiology of this rare and fascinating condition.
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On the basis of novel advances, the diagnostic algorithm and recommended treatment for ALPS have changed significantly, improving quality of life for many patients and better defining the pathophysiology of ALPS.
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TLDR
The best approaches to diagnosis, follow-up, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented.
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TLDR
Individuals with ALPS frequently suffer autoimmune complications, primarily hemolytic anemia and thrombocytopenia and they also have an elevated incidence of Hodgkin’s and non-Hodgkins lymphoma.
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Though ALPS is a rare disorder, it should be suspected and ruled out in children presenting with chronic and refractory multilineage cytopenias associated with nonmalignant lymphoproliferation, and sirolimus and mycophenolate mofetil should be considered first-line therapy for patients who need chronic treatment.
Accessory spleen: Differential diagnosis for lymphoma in autoimmune lymphoproliferative syndrome
TLDR
The histology of the removed tumor revealed that it was an accessory spleen exhibiting typical features of ALPS involvement, as shown by the presence of a large excess of CD3+CD4−CD8− T cells and plasma cells without a detectable monoclonal population.
Autoimmune Lymphoproliferative Syndrome
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Patients with ALPS have a defect in the Fas–FasL apoptotic pathway, leading to chronic lymph proliferation, autoimmune manifestations, and a propensity to develop malignancies, particularly B-cell lymphomas.
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