#00060956

A 46-year-old female presented with isolated lymphocytosis (4.67 × 10^9/L) without concomitant anemia, granulocytopenia or thrombocytopenia. Lymphocytosis was first noticed at routine investigation 14 months before, it remained stable. No splenomegaly nor adenomegalies were felt. A polyclonal increase of serum IgM (3,020 mg/dl) was also present. Lymphocytes in peripheral smear had abundant faintly basophilic cytoplasm and included a low percentages (3%) of cells displaying bi-lobed nuclei, (panel A and B). Flow cytometry showed an increase in absolute number of B cells in PB (CD19+, CD5-,CD22+/CD79b+, FMC7+,CD29+,CD31+,CD49d+) that were polyclonal (both kappa and lambda light chains were expressed). Bone marrow biopsy revealed only mild interstitial B-cell lymphocytosis (15%).

Conventional cytogenetic analysis (CCA) shoved a normal karyotype, however, FISH techniques revealed various abnormalities of chromosome 3: Trisomy 3 was detected in 8% of metaphase (panel C), a isochromosome 3q in 1% (panel D);  tetrasomy of chromosome 3 in 8%,. Diagnosis of persistent polyclonal B-cell lymphocytosis (PPBL) was made. In this case, bi-lobed nucleated lymphocytes in PB were rare and cytogenetic changes of chromosome 3 helped to confirm the diagnostic suspect.

PPBL was first reported in 1982, it is a uncommon type of lymphocytosis of unknown etiology, features include female gender, cigarette smoking, polyclonal increase in immunoglobulin M (IgM), presence of circulating binucleated lymphocyte, as well as an HLA DRB1*07 haplotype; cytogenetic abnormalities of chromosome 3 is a common occurrence in PPBL and chromosome instability or other independent abnormalities could be also observed.

There is potential for confusion with lymphoid neoplasia, (B-CLL) / B-PLL / splenic marginal zone lymphoma etc.) given the presence of lymphocytosis and possibly of splenomegaly. In PPBL however, B-cells are neither surface light chain restricted nor carry underlying clonal Ig gene rearrangements. The disorder is usually benign although emergence of a malignant proliferative disorder has been reported in rare cases.  A careful and continued clinical and biological long-term follow-up therefore is recommended.