Bone Marrow Histopathology in the Diagnostic Evaluation of Splenic Marginal-zone and Splenic Diffuse Red Pulp Small B-cell Lymphoma

Abstract

Primary splenic small B-cell lymphomas mostly comprise the distinct entity of splenic marginal-zone lymphoma (SMZL) and the provisional category of splenic lymphoma/leukemia unclassifiable, mainly represented by the hairy cell leukemia variant and splenic diffuse red pulp small B-cell lymphoma (SDRL). Until recently, histopathologic examination of splenectomy specimens was considered mandatory for the diagnosis of SMZL. However, nowadays, mainly because of advances in chemoimmunotherapy, splenectomy is performed much less frequently. We evaluated the diagnostic efficacy of bone marrow biopsy (BMB) histopathology in the diagnostic approach toward SMZL and SDRL and tested whether it may serve as a substitute for spleen histopathology in the differential diagnosis between these 2 entities. To this end, we conducted a paired assessment of BMB and spleen diagnostic samples from 46 cases with a diagnosis of SMZL (n=32) or SDRL (n=14) based on spleen histopathology. We demonstrate that detailed immunohistopathologic BMB evaluation offers adequate evidence for the confirmation of these entities and their differential diagnosis from other small B-cell lymphoma histotypes. Notably, the immunophenotypical profile of SMZL and SDRL was identical in both BMB and spleen specimens for 21 evaluated markers. Paired assessment of BMB and spleen specimens did not identify discriminating patterns of BMB infiltration, cytology, and/or immunohistology between SMZL and SDRL. Accordingly, bone marrow histopathology contributes significantly in confirming the diagnosis of SMZL and SDRL. However, presently it is not possible to distinguish SMZL from SDRL on the basis of BMB evaluation alone; hence, histopathologic examination of the spleen remains the "gold standard" approach.

Clonal B-cell lymphocytosis exhibiting immunophenotypic features consistent with a marginal-zone origin: is this a distinct entity?

“…The presence of villous lymphocytes, lymphocytes with plasmacytoid differentiation, an intrasinusoidal pattern of BM infiltration, 33 and cytogenetic abnormalities of chromosome 7q 34 observed in many cases of the present series are all seen in splenic MZ lymphomas 35 and lend support to an MZ origin. Although none of the above features are pathognomonic of MZ lymphomas, our cohort did not have features to suggest alternative diagnoses.…”

Pathology of nodal marginal zone lymphomas

“…Since an intrasinusoidal infiltration may be seen in NMZLs as well, although it is less common than splenic MZL ( [17,18], it is confirmed also in this situation that this growth pattern on bone marrow biopsy per se is not pathognomonic for splenic MZL, since it could be encountered also in other B-cell lymphoproliferative disorders [19].…”

Splenic marginal zone lymphoma: from genetics to management

“…17 However pathologists must be aware that this pattern may also be observed, although less frequently, in several low-grade B-cell lymphomas. A careful evaluation of cytology and immunophenotype, including a search for the dendritic meshwork more commonly present and disrupted in SMZL, 18 is helpful in many instances.…”

“…Differentiating splenic diffuse red pulp lymphoma 23 and HCL-v 24 may be very difficult or even impossible with only blood or BM biopsy, 17 because they represent two recognized entities with ill-defined clinicopathologic and immunophenotypic features that partially overlap those of SMZL (Tables 1 and 2). Thus, a definite diagnosis may require detailed clinical information, a comprehensive phenotype, and spleen histology, which usually shows a typical diffuse pattern of infiltration with preserved or atresic white pulp follicles.…”