Abstract
Two types of benign persistent polyclonal B-cell Lymphocytosis have been reported: persistent polyclonal B-cell lymphocytosis (PPBL) in Western countries and hairy B-cell lymphoproliferative disorder (HBLD) in Japan. PPBL is characterized by B lymphocytosis with binucleated lymphocytes, polyclonal IgM, isolated splenomegaly, female sex, cigarette smoking and the presence of HLA-DR7 allele. Most patients with HBLD have atypical lymphocytes with microvilli and prominent membranous ruffles, serum polyclonal IgG, and splenomegaly. Only 9 patients with HBLD have been reported to date, and all of these patients are Japanese. Here, we report three new cases of HBLD. We performed HLA-DRB1 subtyping since the association between HBLD and HLA-DR4 has been suggested: 4 of 5 HBLD patients examined demonstrated the HLA allele. We also analyzed HLA-DRB1 alleles in a patient with hairy cell leukemia (HCL) and 3 with HCL Japanese variant (HCL-JV) to examine the possibility that polyclonal cell expansion in HBLD may be followed by transformation to these lymphoproliferative disorders. If the transformation were to occur, the patients should share the same HLA-DR allele.
Expanded B-lymphocytes in all HBLD cases displayed CD5− CD10− CD11c+ CD19+ CD20+ CD23− CD25− and CD103− cell surface phenotype and all patients exhibited a polyclonal increase in serum IgG. Phase-contrast microscopic and scanning electron microscopic examinations demonstrated lymphoid cells with many long surface microvilli. Analysis of immunoglobulin VH gene rearrangements showed a polyclonal pattern. Therefore, we diagnosed these patients as HBLD. HLA-DRB1 subtype analysis strengthened the close relation between HBLD and HLA-DR4: 2 patients having HLA-DRB1*0405 and one HLA-DRB1*0407. In the meanwhile one each patient with HCL and HCL-JV had HLA-DRB1*0405 allele.
Although the exact mechanism underlying the association between HBLD and HLAB1*04 needs to be elucidated, the presence of this HLA might be useful to establish correct diagnosis of the disease, and thus avoid patient exposure to unnecessary treatment. One each patient with HCL and HCL-JV has HLA-DRB1*0405, but a definitive conclusion cannot yet be drawn due to high HLA-DRB1*04 frequency in Japanese population (25.4%).
Long-term follow-up of 111 patients with persistent polyclonal B-cell lymphocytosis with binucleated lymphocytes