Persistent Polyclonal B-Cell Lymphocytosis
Description
Persistent polyclonal B-cell lymphocytosis (PPBL) is characterized by chronic, stable, persistent, and polyclonal lymphocytosis, the presence of binucleated lymphocytes in the peripheral blood, and a polyclonal increase in serum IgM. It is significantly associated with cigarette smoking (summary by Cornet et al., 2009).
Clinical FeaturesPersistent polyclonal B-cell lymphocytosis was described by Gordon et al. (1982) and Mossafa et al. (1999) as a rare and presumably benign peripheral proliferative disorder diagnosed predominantly in women. Patients, usually cigarette smokers, presented with persistent polyclonal lymphocytosis of B-cell origin. The lymphoid cell population was composed mostly of atypical lymphocytes with abundant cytoplasm and mature nuclei and binucleated lymphocytes. Elevated polyclonal serum IgM was found in all patients, and there was a close association with the HLA-DR7 allele. Although a patient with PPBL who developed a diffuse large-cell lymphoma had been reported (Roy et al., 1998), association between the 2 disorders is not clear.
To determine possible genetic predisposition to PPBL, Delage et al. (2001) studied the large family of a patient with PPBL. Among the first-degree relatives, 3 individuals presented all the criteria for the diagnosis of PPBL. A slight increase in serum IgM without evidence of B-cell proliferation was found in 2 additional sibs. Multiple bcl2/Ig gene rearrangements were identified in 8 of 10 individuals among first-degree relatives. A statistically significant association was found between the presence of these rearrangements and a paternal HLA haplotype. Delage et al. (2001) noted that the presence of bcl2/Ig gene rearrangements in normal individuals increases with age and heavy smoking. In their family, bcl2/Ig gene rearrangements were found in 9 (56%) of 16 cigarette-smoking individuals but in only 1 (9%) of 11 nonsmoking relatives. Delage et al. (2001) concluded that PPBL has a familial occurrence based on a genetic difference. A contributing factor, such as cigarette smoking, appeared to be involved.
Cornet et al. (2009) reported the long-term follow-up of 111 patients with PPBL, including 91 (82%) women and 20 men. Most (98%) were smokers and were either asymptomatic or had minor nonspecific complaints, such as fatigue. Peripheral blood smear showed binucleated lymphocytes, polyclonal B-cell expansion, and increased IgM. Conventional cytogenetic analysis showed isochromosome i(3q) in 34% of patients, premature chromosome condensation in 8% of patients, and both abnormalities in 31% of patients. Fluorescence in situ hybridization (FISH) in 84 cases showed isochromosome 1(3q) in 71%. The majority (89%) of patients had a stable clinical and biologic course after a median follow-up of 4.4 years. Four patients had asymptomatic monoclonal gammopathy of undetermined significance (MGUS), 2 developed pulmonary cancer, 1 developed cervical cancer, and 2 developed non-Hodgkin lymphoma. Cornet et al. (2009) questioned whether PPBL should be considered a benign pathology, and suggested that patients should be followed.
Lesesve et al. (2014) studied peripheral blood smears of 26 patients with PPBL, 50% of whom had isochromosome i(3q) and 60% of whom had HLA-DR7. Binucleated lymphocytes were detected in all patients, and tended to be medium-sized with a moderately abundant basophilic cytoplasm, sometimes vacuolated. The chromatin was mature in an asymmetrically bilobed nucleus showing 1 to 2 nucleoli.