Polyclonal B Lymphocytosis with Binucleated Lymphocytes (PPBL)

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Polyclonal B Lymphocytosis with Binucleated Lymphocytes (PPBL)

Clinics and Pathology

Phenotype / cell stem origin Unknown. The polyclonal expansion of B-cells fit into the peripheral CD27+IgM+IgD+ B cell population. Cloning and sequencing of VH genes of PPBL IgVH genes showed a mutated profile suggesting like CD27 expression an expansion of memory B cells.

Etiology The etiology of polyclonal B lymphocytosis with binucleated lymphocytes (PPBL) remains unknown. An association with cigarette smoking was initially suggested. However PPBL was observed in non smokers patients. The morphology of binucleated lymphoid B-cells could suggest an association with viral infections, such as Epstein-Barr Virus. Biologic studies are not completely achieved to exclude and/or to confirm definitely the role of EBV in the pathogenesis of PPBL. The presence of characteristic binucleated lymphoid B-cells in asymptomatic family members and the description of familial PPBL cases suggest a genetic predisposition as a more likely possibility.

Epidemiology PPBL was first reported in 1982. We have no epidemiological data on the incidence of PPBL.

Clinics In a large series we reported on forty-three patients (9 males, 34 females: median age: 40 years, range 28-65), the clinical characteristics were splenomegaly in 16%, hepatomegaly in 0.5% and lymph nodes in 11.5% cases. An absolute lymphocytosis > 4 x 109/l is present in 80% of PPBL patients. A persistent, stable and polyclonal increase of IgM levels is usual and most PPBL patients express HLA-DR7. CYTOLOGY_IMAGE lymphocytosisFig1.jpg

Cytology PPBL is identified in all cases by the presence of a variable (1.5 to 9%) number of binucleated peripheral lymphoid cells (Fig 1). The majority of lymphoid cells are large with abundant faintly and basophilic cytoplasm. Characteristic nuclei with a rounded or more commonly irregular form are observed.
Immunologic markers: Both kappa and lambda light-chain are expressed, indicating a polyclonal expansion of the lymphocyte pool. The lymphocytosis is of the B-cell type: the lymphocytes react with CD19, CD20, CD22 and FMC7 antigens.

Morphologic features showing typical binucleated cells

Prognosis After a median follow-up of 5.5 years without treatment, 45 PPBL patients are alive.

Cytogenetics

Cytogenetics Morphological +i(3q) (Fig 2) is the most common abnormality and is observed in 70% cases, occurring as a single aberration in only a few patients. PCC (Fig 3) is observed in 40% cases and occur rarely as a sole abnormality. Both abnormalities associating +i(3q) and PCC are present in 37% cases.
Using alpha-satellite and telomere chromosome 3 specific probes, +i(3q) is more frequently detected by metaphase FISH studies. (Fig 2).
+i(3q) is rarely described as a recurrent cytogenetic abnormality in patients with hematologic malignancy. Trisomy 3 is reported to be associated with marginal zone B-cell lymphoma. Gain of chromosome 3 or 3q was described in patients with typical clonal b-cell chronic lymphoproliferative disorders, chronic lymphocytic leukemia, prolymphocytic leukemia or Waldenström macroglobulinemia.
A chromosomal instability is present in 67.5% patients These patients present various clonal [ del(6q), +der(8) or +8 or polyploid karyotype] and non clonal chromosomal abnormalities with structural and numerical abnormalities.
This chromosomal instability is variable over time but persist in most cases. In spite of genomic instability, a long follow-up of PPBL patients remains essential and chemotherapy unnecessary.

Partial karyotype showing +i(3q) -R-banding (left); Detection of I(3q) with telomere chromosome 3q and alpha satellite specific DNA probes (right)

Premature Chromosome Condensation (PCC)

Bibliography

Persistent polyclonal lymphocytosis of B-lymphocytes.

Gordon DS, Jones BM, Browing SW, Spira TJ, Laurence DN.

New Engl J Med 1982; 307: 232-236.

Chronic B-cell lymphocytosis of the young woman : clinical, phenotypic, and molecular studies.

Delage B, Darveau A, Jacques L, Huot A, Delage JM

Blood, 1992, 80, suppl 1, 447a.

Polyclonal lymphocytosis with binucleated lymphocytes: a genetic predisposition.

Troussard X, Valensi F, Debert C, Maydanie M, Schillinger F, Bonnet P, MacIntyre E, Flandrin G.

Brit J Haematol 1994; 88: 275-280.

Persistent polyclonal B-cell lymphocytosis is an expansion of functional IgD+CD27+ memory B-cells.

Himmelmann A, Gautschi O, Nawrath M, Bolliger u, Fehr J, Stahel RA.

Brit J Haematol 2001, 114, 400-405.

Analysis of expressed VH genes in persistent polyclonal B cell lymphocytosis reveals absence of selection in CD27+IgM+IGD+ memory B cells.

Loembe MM, Néron S, Delage R, Darveau A.

Eur J Immunol 2002; 32: 3678-3688.

Chromosomal instability and ATR Amplification Gene in Patients with persistent and polyclonal B-Cell Lymphocytosis (PPBL).

H. Mossafa, S. Tapia, G. Flandrin, X. Troussard and the Groupe Français d¹Hématologie Cellulaire (GFHC).

Leukemia Lymphoma 2004; 45: 1401-1406.

Contributor(s)

Written 06-2004 Xavier Troussard, Hossein Mossafa

Citation

This paper should be referenced as such :
Troussard X, Mossafa H . Polyclonal B Lymphocytosis with Binucleated Lymphocytes (PPBL). Atlas Genet Cytogenet Oncol Haematol. June 2004 .
URL : http://AtlasGeneticsOncology.org/Anomalies/PolyclonalLymphoID2040.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jan 5 14:00:31 2008

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Phenotype / cell stem origin	Unknown. The polyclonal expansion of B-cells fit into the peripheral CD27+IgM+IgD+ B cell population. Cloning and sequencing of VH genes of PPBL IgVH genes showed a mutated profile suggesting like CD27 expression an expansion of memory B cells.
Etiology	The etiology of polyclonal B lymphocytosis with binucleated lymphocytes (PPBL) remains unknown. An association with cigarette smoking was initially suggested. However PPBL was observed in non smokers patients. The morphology of binucleated lymphoid B-cells could suggest an association with viral infections, such as Epstein-Barr Virus. Biologic studies are not completely achieved to exclude and/or to confirm definitely the role of EBV in the pathogenesis of PPBL. The presence of characteristic binucleated lymphoid B-cells in asymptomatic family members and the description of familial PPBL cases suggest a genetic predisposition as a more likely possibility.
Epidemiology	PPBL was first reported in 1982. We have no epidemiological data on the incidence of PPBL.
Clinics	In a large series we reported on forty-three patients (9 males, 34 females: median age: 40 years, range 28-65), the clinical characteristics were splenomegaly in 16%, hepatomegaly in 0.5% and lymph nodes in 11.5% cases. An absolute lymphocytosis > 4 x 109/l is present in 80% of PPBL patients. A persistent, stable and polyclonal increase of IgM levels is usual and most PPBL patients express HLA-DR7. CYTOLOGY_IMAGE lymphocytosisFig1.jpg
Cytology	PPBL is identified in all cases by the presence of a variable (1.5 to 9%) number of binucleated peripheral lymphoid cells (Fig 1). The majority of lymphoid cells are large with abundant faintly and basophilic cytoplasm. Characteristic nuclei with a rounded or more commonly irregular form are observed. Immunologic markers: Both kappa and lambda light-chain are expressed, indicating a polyclonal expansion of the lymphocyte pool. The lymphocytosis is of the B-cell type: the lymphocytes react with CD19, CD20, CD22 and FMC7 antigens.
	Morphologic features showing typical binucleated cells

Prognosis	After a median follow-up of 5.5 years without treatment, 45 PPBL patients are alive.

Cytogenetics Morphological	+i(3q) (Fig 2) is the most common abnormality and is observed in 70% cases, occurring as a single aberration in only a few patients. PCC (Fig 3) is observed in 40% cases and occur rarely as a sole abnormality. Both abnormalities associating +i(3q) and PCC are present in 37% cases. Using alpha-satellite and telomere chromosome 3 specific probes, +i(3q) is more frequently detected by metaphase FISH studies. (Fig 2). +i(3q) is rarely described as a recurrent cytogenetic abnormality in patients with hematologic malignancy. Trisomy 3 is reported to be associated with marginal zone B-cell lymphoma. Gain of chromosome 3 or 3q was described in patients with typical clonal b-cell chronic lymphoproliferative disorders, chronic lymphocytic leukemia, prolymphocytic leukemia or Waldenström macroglobulinemia. A chromosomal instability is present in 67.5% patients These patients present various clonal [ del(6q), +der(8) or +8 or polyploid karyotype] and non clonal chromosomal abnormalities with structural and numerical abnormalities. This chromosomal instability is variable over time but persist in most cases. In spite of genomic instability, a long follow-up of PPBL patients remains essential and chemotherapy unnecessary.


	Partial karyotype showing +i(3q) -R-banding (left); Detection of I(3q) with telomere chromosome 3q and alpha satellite specific DNA probes (right)



	Premature Chromosome Condensation (PCC)