Diagnostic algorithm The old diagnostic criteria for the illness included: Chronic non-malignant lymphoproliferation, elevated peripheral blood DNTs and defective in vitro Fas mediated apoptosis. The new criteria require chronic non-malignant lymphoproliferation (over six months lymphadenopathy and/or splenomegaly), elevated peripheral blood DNTs. A primary accessory in diagnosis is defective in vitro Fas mediated apoptosis and somatic or germline mutation in<unk>  causative gene (FAS, FASL, CASP10). The secondary accessory in diagnosis are elevated biomarkers (plasma sFASL over 200 pg/ml, plasma IL-10 >20 pg/ml, plasma or serum vitamin B12 >1500 ng/L, Plasma IL-18 >500pg/ml) and immunohistochemical findings on biopsy consistent with<unk>  as determined by an experienced hematopathologist. Another sign is<unk>  cytopenias and polyclonal hypergammaglobulinemia and a family history of<unk>  or non-malignant lymphoproliferation. A definitive diagnosis is chronic non-malignant lymphoproliferation and/or elevated peripheral blood DNTs plus one primary accessory criterion. A probable diagnosis is the same but with one secondary accessory criterion. Classification 2003 nomenclature * IA - Fas * IB - Fas ligand * IIA - Caspase 10 * IIB - Caspase 8 * III - unknown * IV - Neuroblastoma RAS viral oncogene homolog Revised nomenclature (2010) *<unk> -FAS: Fas. Germline FAS mutations. 70% of patients. Autosomal dominant. Dominant negative and haploinsufficient mutations described. *<unk> -sFAS: Fas. Somatic FAS mutations in DNT compartment. 10% of patients *<unk> -FASL: Fas ligand. Germline FASL mutations. 3 reported cases *<unk> -CASP10: Caspase 10. Germline CASP10 mutation. 2% of patients *<unk> -U: Undefined. 20% of patients * CEDS: Caspase 8 deficiency state. No longer considered a subtype of<unk>  but distinct disorder * RALD: NRAS, KRAS. Somatic mutations in NRAS and KRAS in lymphocyte compartment. No longer considered a subtype of<unk>  but distinct disease
Autoimmune lymphoproliferative syndrome
Diffuse infiltrative lymphocytosis syndrome
Thymoma with immunodeficiency
Bare lymphocyte syndrome
X-linked lymphoproliferative disease
Thymoma-associated multiorgan autoimmunity
Adult-onset immunodeficiency syndrome
Epstein–Barr virus–associated lymphoproliferative diseases