Splenic lymphoma with villous lymphocytes (SLVL)

Clinics and Pathology

Phenotype / cell stem origin	Light chain restriction surface immunoglobulin. Most cases express IgM and IgD. B-cells express CD19+, CD20+, CD22+, CD24+, CD79b+, FMC7+ and DBA44+. Lack expression of CD5 (85%), CD10, CD23, CD103 and CD123.
Epidemiology	In 1987, the term SLVL was introduced; 1-2% of non-Hodgkin lymphomas ; occurs in the elderly (med 70 yrs) ; sex ratio 2M/1F.
Clinics	splenomegaly without hepatomegaly nor enlarged lymph nodes; monoclonal Ig in a third of cases, autoimmune phenomena in 10% of patients, transformation to high grade lymphoma in 10% of cases.
	Peripheral blood lymphocytosis in 75% of patients and villous lymphocytes on peripheral blood smears (Fig 1).
Pathology	Spleen. Nodular replacement of the white pulp with a central core of small lymphocytes and larger cells in the peripheral marginal zone. Invasion of the splenic red pulp is inconstant. Bone marrow morphology showing intrasinusoidal lymphoma cells.
Treatment	Only in symptomatic patients : splenectomy or chemotherapy with purine analogues. Antiviral therapy (IFN) in patients with SLVL and hepatitis C.
Prognosis	Indolent B-cell malignancy with 5-yr survival : 80%; no consensus on adverse prognostic factors: WBC > 30 x 109/l, low lymphocyte count; cases treated with chemotherapy have shorter survival.

Cytogenetics

Cytogenetics Morphological	A low mitotic activity is present in SLVL and most chromosomal banding analyses of SLVL have been based on cell cultures stimulated with different B-cell mitogens. The cytogenetic abnormalities are heterogeneous and often complex, with several recurrent abnormalities. The most common abnormalities are those involving structural abnormalities of chromosome 7q22-q32 [20-40% of cases] in the form of translocation, mainly unbalanced, and 7q deletion (see Fig 2). Some cases have been reported to show t(11;14)(q13;q32) [10-15%]. Structural abnormalities, and microdeletion of 13q14 were found in 50% of cases. The 13q14 allelic loss at the RB1 locus deletion have been detected by interphase FISH. Other abnormalities, in particular trisomy 3 [10-15%], i(17)(q10), t(6;14)(p21;q32) and 2p11 translocations, t(2;7)(p12;q21) were also observed in a few cases. Immunoglobulin gene sequencing 43% of patients have an unmutated profile (>98% homology to the gem line sequence) and 57% of patients a mutated profile. Overuse of the VH1-2 gene segment is present in mutated and unmutaded cases.
	t(11;14)(q13;q32) R-Banding (top left); del(7q) (top right); 13q14 allelic loss at the RB1 locus deletion detected by interphase FISH (bottom)

Genes involved and Proteins

Note

del(7q): gene unknown t(11;14)(q13;q32)BCL1 in 11q13 and IgH in 14q32 are involved in 20% of cases, with or without visible (11;14); BCL1 encodes the cyclin D1; role in the cell cycle control (G1 progression and G1/S transition); 5' BCL1 translocated on chromosome 14 near JH, resulting in promoter exchange; the immunoglobulin gene enhancer stimulates the expression of BCL1, and overexpression of BCL1 which accelerates passage through the G1 phase. trisomy 3: gene unknown but region 3q13.q32-q29 over-represented. t(6;14)(p21;q32) cyclin D3 is located on 6p21 and, as CDK6, is implicated in the progression through the G1 phase of the cell cycle. t(2;7)(p12;q21). CDK6 is located on 7q21 and dysregulation of CDK6 gene expression could be contribute to the pathogenesis of SLVL and SMZL.

Bibliography

Cytogenetic studies in splenic lymphoma with villous lymphocytes.

Oscier DG, Matutes E, Gardiner A, Glide S, Mould S, Brito-Babapulle V, Ellis J, Catovsky D

British journal of haematology. 1993 ; 85 (3) : 487-491.

PMID 8136270

Splenic lymphoma with villous lymphocytes: clinical presentation, biology and prognostic factors in a series of 100 patients. Groupe Francais d'Hˆ©matologie Cellulaire (GFHC).

Troussard X, Valensi F, Duchayne E, Garand R, Felman P, Tulliez M, Henry-Amar M, Bryon PA, Flandrin G

British journal of haematology. 1996 ; 93 (3) : 731-736.

PMID 8652403

Molecular cytogenetic analysis in splenic lymphoma with villous lymphocytes: frequent allelic imbalance of the RB1 gene but not the D13S25 locus on chromosome 13q14.

Garcˆ‚a-Marco JA, Nouel A, Navarro B, Matutes E, Oscier D, Price CM, Catovsky D

Cancer research. 1998 ; 58 (8) : 1736-1740.

PMID 9563492

Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course.

Algara P, Mateo MS, Sanchez-Beato M, Mollejo M, Navas IC, Romero L, Solˆ© F, Salido M, Florensa L, Martˆ‚nez P, Campo E, Piris MA

Blood. 2002 ; 99 (4) : 1299-1304.

PMID 11830479

Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection.

Hermine O, Lefrˆ®re F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Saudreau V, Delmas B, Valensi F, Cacoub P, Brechot C, Varet B, Troussard X

The New England journal of medicine. 2002 ; 347 (2) : 89-94.

PMID 12110736

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PMID 15572216

Contributor(s)

Written	10-1998	Jean-Loup Huret, Hossain Mossafa
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated	02-2005	Xavier Troussard, Hossain Mossafa
		Laboratoire d'Hématologie, CHU de Caen, 14 000 Caen, France

Citation

This paper should be referenced as such :

Huret JL, Mossafa H . Splenic lymphoma with villous lymphocytes (SLVL). Atlas Genet Cytogenet Oncol Haematol. October 1998 . URL : http://AtlasGeneticsOncology.org/Genes/splenvillousID2063.html

Troussard X, Mossafa H . Splenic lymphoma with villous lymphocytes (SLVL). Atlas Genet Cytogenet Oncol Haematol. February 2005 . URL : http://AtlasGeneticsOncology.org/Genes/splenvillousID2063.html

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