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.

Synopsis

 splenomegaly
 prominent adenopathy
 hypergammaglobulinemia
 autoimmune phenomena
 sinus histiocytosis with massive lymphadenopathy (SHML) features (#15958855#)

Types

 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 2a (ALPS2a): CASP10 germline mutations
• ALPS type 2b (ALPS2b): CASP8 germline mutations

 ALPS type 3 (ALPS2) (unknown gene)

Differential diagnosis

 sinus histiocytosis with massive lymphadenopathy (SHML) features (#15958855#)

References

 Maric I, Pittaluga S, Dale JK, Niemela JE, Delsol G, Diment J, Rosai J, Raffeld M, Puck JM, Straus SE, Jaffe ES. Histologic features of sinus histiocytosis with massive lymphadenopathy in patients with autoimmune lymphoproliferative syndrome. Am J Surg Pathol. 2005 Jul;29(7):903-11. PMID: #15958855#

 van den Berg A, Tamminga R, de Jong D, Maggio E, Kamps W, Poppema S. FAS gene mutation in a case of autoimmune lymphoproliferative syndrome type IA with accumulation of gammadelta+ T cells. Am J Surg Pathol. 2003 Apr;27(4):546-53. PMID: #12657942#

 Strobel P, Nanan R, Gattenlohner S, Muller-Deubert S, Muller-Hermelink HK, Kreth HW, Marx A. Reversible monoclonal lymphadenopathy in autoimmune lymphoproliferative syndrome with functional FAS (CD95/APO-1) deficiency. Am J Surg Pathol. 1999 Jul;23(7):829-37. PMID: #10403307#

 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#