autoimmune lymphoproliferative syndrome
Tuesday 6 April 2004
Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder associated with defects in Fas-mediated apoptosis, characterized most often by childhood onset of lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune phenomena.
early childhood onset
prominent nonmalignant lymphadenopathy,
expanded populations of CD4− CD8− (double-negative T cells)
in vitro defects in lymphocytes apoptosis.
- architecture distorted but not totally effaced.
- marked paracortical expansion by lymphocytes in variable stages of immunoblastic transformation
- paracortex expanded by numerous CD3+ T cells with pale cytoplasm (medium-sized clear cells, CD3+ T lymphocytes, plasma cells, immunoblasts with mitotic activity)
- hyperplastic as well as regressive follicles
- reactive follicles in the cortex
- +/- large histiocytes with round nuclei and emperipolesis (Rosai-Dorfman disease-like)
- population of CD4− CD8− cells, mostly around lymphoid follicles (ie, CD4+ cells and CD8+ cells together being less than CD3+ cells)
- sheets of CD57+ cells, especially around the follicles
- high Ki-67 cell proliferation index in the interfollicular and paracortical areas
ALPS type 1 (FAS or FAS-L related ALPS)
- ALPS type 1a (ALPS1A): mutations in TNFRSF6 gene encoding Fas (CD95/Apo-1).
- ALPS type 1b (ALPS1B): mutations in TNFSF6 at 1q23 (Fas-ligand mutations) (MIM.134638) (CD178)
ALPS type 2 (ALPS2) (caspases-related ALPS)
ALPS type 3 (ALPS2) (unknown gene)
In most patients, there is a genetic defect in FAS (APT1/TNFRSF-6) gene, which encodes Fas protein (also called APO-1 or CD95), a cell-surface receptor that regulates lymphocyte survival by triggering programmed cell death or apoptosis.
In a low percentage of ALPS cases, the genetic mutation involves CASPASE-8 (CASP8), CASPASE-10 (CASP10), or FAS LIGAND genes.
sinus histiocytosis with massive lymphadenopathy (SHML) features (15958855)
Development of disseminated histiocytic sarcoma in a patient with autoimmune lymphoproliferative syndrome and associated Rosai-Dorfman disease. Venkataraman G, McClain KL, Pittaluga S, Rao VK, Jaffe ES. Am J Surg Pathol. 2010 Apr;34(4):589-94.PMID: 20216376
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Lim MS, Straus SE, Dale JK, Fleisher TA, Stetler-Stevenson M, Strober W, Sneller MC, Puck JM, Lenardo MJ, Elenitoba-Johnson KS, Lin AY, Raffeld M, Jaffe ES. Pathological findings in human autoimmune lymphoproliferative syndrome. Am J Pathol. 1998 Nov;153(5):1541-50. PMID: 9811346
Pathological findings in human autoimmune lymphoproliferative syndrome. Lim MS, Straus SE, Dale JK, Fleisher TA, Stetler-Stevenson M, Strober W, Sneller MC, Puck JM, Lenardo MJ, Elenitoba-Johnson KS, Lin AY, Raffeld M, Jaffe ES. Am J Pathol. 1998 Nov;153(5):1541-50. PMID: 9811346