Mature B-cell leukemias/lymphomas in the bone marrow: beyond chronic lymphocytic leukemia and mantle cell lymphoma

Differentiating between reactive B-cell infiltrates, clonal non-lymphomatous B-cell proliferations and small B-cell lymphomas in the bone marrow (BM) can be a challenging task, especially in consideration of the high number of potential differential diagnoses, the rather subtle morphological differences and the often non-specific phenotypes. It requires a high degree of integration of clinical, laboratory, morphological, immunophenotypical and genetic information to define a definitive diagnosis. Besides the well-defined lymphomas involving the bone marrow, like follicular lymphoma (FL) and lymphoplasmacytic lymphoma (LPL), diagnostic clues to distinguish more difficult entities, such as splenic marginal zone lymphoma (SMZL), splenic diffuse red pulp B-cell lymphoma (SDRPBL) and splenic small B-cell lymphoma with prominent nucleoli/hairy cell leukemia variant (SBCLPN/HCLV) are discussed; also, the BM patterns of non-lymphomatous clonal B-cell lymphoproliferations, such as monoclonal B-cell lymphocytosis (MBL) and primary cold agglutinin disease (PCAD) are described. This review is intended to guide a diagnostically-oriented pathologist through the conundrum of possible entities presenting in the bone marrow. A practical approach is presented, which can be implemented in daily routine. We will also highlight the limitations of the bone marrow biopsy in establishing a primary diagnosis of lymphoma, especially in absence of the ancillary information.