Bone marrow - nonneoplastic
Benign changes
Persistent polyclonal lymphocytosis

Author: Xiangrong (Alex) Zhao, M.D., Ph.D. (see Authors page)

Revised: 11 July 2017, last major update January 2014

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PubMed Search: Persistent polyclonal lymphocytosis

Cite this page: Persistent polyclonal lymphocytosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/bonemarrowpersistantpolyclonal.html. Accessed October 22nd, 2017.
Definition / general
Terminology
  • Also known as persistent polyclonal B lymphocytosis (PPBL), B cell expansion with NFKB and T cell anergy (BENTA)
Sites
  • Peripheral blood, bone marrow
  • May also involve spleen and lymph node
Pathophysiology
  • Familial cases have germline heterozygous mutation in CARD11 gene → constitutive NFκB activation (gain of function) (J Exp Med 2012;209:2247)
  • Due to increase in bone marrow B cells, not proliferation of B cells in periphery or increased survival
Clinical features
  • Variable fatigue, consistent with chronic fatigue syndrome or post EBV fatigue
  • 10% present with splenomegaly and lymphadenopathy but may also be asymptomatic
  • Usually benign clinical course but may evolve toward a clonal proliferation (Leukemia 2009;23:419)
Diagnosis
  • Peripheral blood evaluation including CBC, flow cytometric analysis for immunophenotype and clonality and molecular / cytogenetic analysis
  • Bone marrow biopsy
  • Laboratory and radiologic studies as indicated
Laboratory
  • Persistent, often mild lymphocytosis
  • Elevated polyclonal IgM
  • Defective T cell response to mitogens
  • Decreased peripheral survival of B cells
Radiology description
  • May detect lymphadenopathy, splenomegaly and (less commonly) hepatomegaly
Case reports
Treatment
  • No definitively established treatment; recommended to avoid aggressive treatment
Microscopic (histologic) description
  • Bone marrow biopsies show lymphoid hyperplasia in a background of normal trilineage maturation
  • Intrasinusoidal distribution of B cells resembles splenic marginal zone lymphoma (SMZL)
  • Spleen, when involved, may show features similar to SMZL, including expansion of white pulp nodules and significant infiltration of red pulp by small, mature appearing lymphocytes with minimal cytologic atypia; occasional binucleated lymphocytes in the splenic sinusoids
Microscopic (histologic) images

Images hosted on other servers:

Peripheral blood and bone marrow

Spleen

Spleen: scattered T cells

Peripheral smear description
  • Heterogeneous morphology with plasmacytoid, blastoid, small lymphocytes
  • Up to 50% of lymphocytes have abundant basophilic cytoplasm, enlarged, often indented nucleus or apparently two completely separated nuclei
  • No anemia or thrombocytopenia
Peripheral smear images

Images hosted on other servers:

A: enlarged; B: slightly indented;
C: deeply indented or
D: fully binucleated nucleus

Positive stains
  • Tissue sections: pan B cell markers, including CD19, CD20, PAX5, CD79a; also IgD, CD25, CD21
  • Flow cytometry: pan B cell markers, including CD19, CD20, CD79b; also CD22, CD24, FMC7, CD27, CD148
  • Variable CD11c
  • Expression of CD27, CD148, IgD indicates that PPBL represents an expansion of memory B cells
Negative stains
  • Negativity for CD5 and CD23 suggests that PPBL is not derived from nave B cells
  • Negativity for CD10 and CD38 suggests that PPBL is not derived from germinal center B cells
Flow cytometry description
  • Polyclonal B cell lymphocytosis, with expansion of CD19+ and CD5- lymphocyte pool
  • Significant increase in circulating CD27+ B cells
  • Mature B cell subsets can be characterized by expression of cell surface immunoglobulin and CD27
  • In healthy individuals, CD27+ memory B cells represent 40% of total peripheral B cell population
  • 3 categories of memory B cells: class switched, IgM only, IgM+IgD+ (each 30 - 40%, Br J Haematol 2001;114:400)
Molecular / cytogenetics description
  • Germline heterozygous mutation in CARD11 gene → constitutive NFκB activation (gain of function) (J Exp Med 2012;209:2247)
  • Closely associated with HLA-DR7, a variant normally present in 26% of Caucasian population
  • Associated with isochromosome 3q, with or without premature chromosome condensation; also t(14;18)(q22;21) - IgH / BCL2 rearrangement, common in follicular lymphoma, subset of diffuse large B cell lymphoma and gray zone lymphoma
Differential diagnosis
  • Clonal B cell lymphoproliferative disorders (monoclonal B cell lymphocytosis, B cell leukemia / leukemic lymphoma): use molecular studies or flow cytometric analysis to evaluate clonality
  • Reactive, transient B cell lymphocytosis: must rule out infections, inflammation