PPBL is an uncommon disorder characterized by an indolent and benign clinical course with persistent polyclonal B-cell lymphocytosis and circulating binucleated lymphocytes as well as increased polyclonal serum IgM. There are only rare reports of PPBL in association with malignant lymphoma or with secondary solid cancers [2, 3, 13]. Since the first description in 1982, about 200 cases have been reported in the literature.
The majority of the reports focus on the study of PPBL pathogenesis, which remains unclear. Although most frequently detected in smokers, PPBL is also occasionally observed in non-smokers. The association with viral infections, such as Epstein-Barr virus, is still a matter of debate [3, 14–16]. The polyclonal B cells which are expanded in this disorder appear to be CD27+/IgM+/IgD + memory B cells, which may result from chronic antigenic stimulation [4, 17]. PPBL is frequently linked with HLA-DR7 haplotype [18–20]. Cases of familial PPBL and the incidence of PPBL in monozygotic twins are suggestive of a strong genetic predisposition [21, 22]. It is reasonable to speculate that the interaction of genetic predisposition with chronic antigenic stimulation may lead to the development of PPBL. Very recently, whole genome microarray expression analysis was done in 14 PPBL patients, which demonstrated over-expression of AP-1 transcription complex and downregulation of Fas-apoptotic and TGFβ pathway . The polyclonality of the lymphocyte population evidenced by flow cytometry in this disorder is challenged by rare reports of clonal IGHD-IGHJ immunoglobulin rearrangement in patients otherwise meeting diagnostic criteria of PPBL [6, 23]. These findings suggest that polyclonal expansion may be followed by the emergence of predominant clone in rare cases.
PPBL mimics malignant lymphoma morphologically. Variable amount of hallmark atypical lymphocytes are invariably present in peripheral circulation. Bone marrow changes in the PPBL patients described earlier demonstrate an interstitial, particularly intrasinusoidal B cells mimicking those seen in B-cell lymphoproliferative disorders especially in splenic marginal zone lymphoma . However, the intravascular or intrasinusoidal pattern of the B cell distribution in the bone marrow is most likely a reflection of the peripheral lymphocytosis and the recirculating nature of the lymphocytes in this benign disorder. Mild splenomegaly is the most frequently reported physical finding, which is detected in about 10% of patients according to the largest case series . Massive splenomegaly is rare among these patients. Our PPBL patient reported here manifested slowly progressive splenomegaly during six years of follow-up. Her spleen contained massive amount of CD20+/BCL-2+ B cells within the red and white pulp mimicking B-cell lymphoma. In their series of 5 patients Del Giudice et al. from Italy recently reported very similar findings to ours in three of their five PPBL patients who developed massive splenomegaly and underwent splenectomy . The B cells present both in bone marrow and spleen show same immunophenotype including expression of BCL-2 [7, 8]. In addition, the B cells in our patient were also positive for CD43. CD43 expression was not studied by Del Giudice et al. and CD43 was negative in the bone marrow reported by Feugier et al.. Although expression of CD43 by B cells is often used as a marker in favor of a B-cell lymphoproliferative disorder, it has been recognized that CD43 can be expressed by B cells in benign conditions [24, 25]. Except splenomegaly, no other abnormal physical or radiographic findings suggestive of malignant lymphoma transformation were detected in our patient and the five patients reported by Del Giudice et al. Therefore, the histological and immunophenotypic findings observed in the spleens of these PPBL patients are most likely a reflection of their underlying benign PPBL process.
PPBL also mimics lymphoma at cytogenetic and molecular level. The chromosomal abnormalities are frequently reported in PPBL patients. Isochromosome + i(3q) is the most common chromosomal abnormality and is present in 71% of cases when using the most sensitive fluorescence in situ hybridization (FISH) method . Other less common chromosomal abnormalities include trisomy 3, premature chromosome condensation (PCC) and chromosome instability [2, 9, 10]. Among the above mentioned chromosomal abnormalities, trisomy 3 has been reported to be associated with marginal zone lymphomas (MZL) and mantle cell lymphoma (MCL) [26, 27]. Cytogenetic studies on our patient using FISH were performed on the peripheral blood sample collected during one of the follow up visits and demonstrated no abnormalities of chromosome 3. Although not detected in our patient, BCL2/IgH gene rearrangements as seen in follicular lymphoma have been reported in some PPBL patients by using PCR technique [7, 10, 28].