Autoimmune Lymphoproliferative Syndrome (ALPS) due to Fas mutation, Canale-Smith syndrome

Definition

ALPS is a hereditary condition characterised by generalised lymphadenopathy, splenomegaly, IgG and IgA hypergammaglobulinaemia and autoimmune disease. There is a germline mutation of the Fas (CD95, Apo-1) receptor.

Epidemiology

Most patients present in childhood, with an amelioration of the condition in adolescence.

Type 0 disease, due to homozygous mutations of the Fas protein is a severe form of the disease.

Type I is the heterozygous form of the disease with a partial defect in apoptosis.

The rare type Ib is due to heterozygous mutation of the gene for the Fas ligand.

Type II disease shows normal Fas and Fas ligand but caspase 8 or 10 mutation.

Type II shows normal FAs-mediated apoptosis and the underlying defect is unknown.

Sporadic ALPS occurs as a result of somatic Fas mutation.

Clinical features

TCRab+/CD4-/CD8- T-cells are to be found in the blood.

Histopathology

Lymph nodes show follicular and paracortical hyperplasia with a polyclonal plasmacytosis. Follicles may variously show progressive transformation or regression1. The paracortex is expanded by polyclonal blastoid T-cells that are TCRab+/CD4-/CD8- . In type Ia ALPS, sinus histiocytosis resembling Rosai-Dorfman disease with S-100-positive histiocytes and emperipolesis has been reported. Other cases show a sarcoid-like appearance1 with multiple perifollicular non-caseating granulomata and occasional Langhan's giant cells. Stains for organisms are negative. In type II ALPS, there may be an accumulation of dendritic cells in the paracortex.

Immunohistochemistry

	Perifollicular blastoid cells:
	CD2	partially lost
	CD3	positive
	CD4	negative
	CD5	positive
	CD7	partially lost
	CD8	negative
	CD10	negative
	CD20	negative
	CD21	negative
	CD22	negative
	CD30	negative
	CD79a	negative
	bcl-6	negative
	EMA	negative
	Perforin	positive
	Granzyme B	positive
	TIA-1	positive
	Alk-1	negative
	Ki-67	50% proliferation index
	Epithelioid histiocytes:
	CD1a	negative
	CD68	positive
	S-100	positive
	CD83	negative

Differential diagnosis

Rosai-Dorfman disease
Sarcoidosis

Prognosis

Patients with ALPS are at risk of developing B-cell lymphomas, nodular lymphocyte predominant and classical Hodgkin lymphoma.

References

1 Mullauer L, Emhofer J, Wohlfart S, et al. Autoimmune lymphoproliferative syndrome (ALPS) caused by Fas (CD95) mutation mimicking sarcoidosis. Am J Surg Pathol 2008; 32:329-34