Isochromosome +i(3)(q10) in a new case of persistent polyclonal B‐cell lymphocytosis (PPBL)

To the Editor: Persistent polyclonal B-cell lymphocytosis (PPBL) with binucleated or bilobulated lymphocytes is a disorder ®rst described by Gordon et al. (1982) in three patients. As far as we know, nearly 60 cases of PPBL have been reported since then (1±12). This entity usually affects young or middle-aged women who smoke heavily and are generally asymptomatic. Patients present moderate but sustained absolute lymphocytosis in the range (5±15)r10/L, with small numbers of circulating bilobulated forms detected in peripheral blood smears. Most patients show a polyclonal increase of serum IgM, with low to normal levels of IgA and IgG. Phenotypically, binucleated cells express both kappa and lambda light chains. Interestingly, most of the patients reported display the HLA-DR7 antigens on their lymphocytes, suggesting a genetic predisposition of the disease (2, 7, 10, 12). Cytogenetically, the presence of an additional isochromosome i(3)(q10) has been reported (3, 9, 11, 12). A 44-yr-old white female was referred to our institution for investigation of a persistent lymphocytosis present for more than 10 yr. The patient was a heavy cigarette smoker (more than 40 cigarettes a day) and presented hypercholesterolaemia. On physical examination, neither adenopathies nor hepatosplenomegaly were detected. Laboratory evaluation revealed: haemoglobin of 11 g/dL and platelet count of 219r10/L. Her leukocyte count was 10.3r10/L with 47% segmented neutrophils, 1% band forms, 48% lymphocytes, 1% monocytes, 2% eosinophils and 1% basophils. Peripheral blood smear evaluation of the lymphoid cells showed 50% mature lymphocytes, 40% large lymphocytes and 10% bilobulated lymphocytes. Blood chemistry was normal. Total serum protein was 6.4 g/dL and serum IgM was increased, reaching 794 mg/dL but without peak, while serum IgG and IgA were normal to slighly decreased (595 and 86 mg/dL, respectively). The patient's serum was studied for the presence of antibodies against hepatitis B virus, hepatitis C virus and human immunode®ciency virus, all of them being negative. Low titers of antibodies against Epstein±Barr virus (EBV) and cytomegalovirus (CMV) were found. HLA-DR typing revealed expression of DR3, DR7, DRw52 and DRw53. Regarding the morphology of the peripheral blood lymphocytes, nearly half of them had a normal appearance; 40% showed an enlarged size, presence of nucleoli and a blue-stained cytoplasm. A minority of nuclei were deeply indented and eventually split into two fragments. Binucleated or bilobulated nuclei connected or not by a slender internuclear bridge were recorded in approximately 10% of the lymphocytes. The most striking ultrastructural ®ndings were nuclear pockets, found in 6 out of 25 cross-sections of mainly bilobulated lymphocytes and an abundance of multivesicular bodies. Bundles of ®brils could also be observed. Bone marrow aspirate was moderately hypercellular; the myeloid series were qualitatively and quantitatively normal. Lymphocytic series represented only 13% of the total cellularity, and no bilobulated forms were seen. Immunology studies were performed by the alkaline phosphatase antialkaline phosphatase (APAAP) method on peripheral blood ®lms. The atypical lymphocytes found in peripheral blood were CD19, HLA-DR, CD25, IgM, CD11c, CD3, CD5, CD11b and CD23. These lymphocytes were clearly of the B-cell type, as they expressed reaction with the CD19 antigen, and both kappa and lambda light-chains were expressed, indicating a polyclonal expansion of the B-lymphocyte pool (Fig. 1). Chromosome studies were carried out on lymphoid cells from peripheral blood according to standard methods. Karyotypes were described according to the International System for Human Cytogenetic Nomenclature, 1995 (13). The patient demonstrated the presence of different clones (Fig. 2, Table 1). FISH studies, using a-satellite centromeric probe from chromosome 3 (CEP 3, Vysis, Downers Grove, USA), demonstrated the presence of three Eur J Haematol 2000: 64: 344±346 Printed in UK. All rights reserved Copyright # Munksgaard 2000