The stromal composition of malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B-cell tumours

Abstract

We present evidence that different B-cell tumours, in bone marrow, have different relationships to stroma. Marrow core biopsies from 46 patients with B-cell tumours were immunostained with antibodies for distinct stromal cells. Cases included follicular lymphoma (FL), chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma (LPL), and nodal, extranodal and splenic marginal zone lymphoma (NMZL, MALT, SMZL). In normal marrow, low-affinity nerve growth factor receptor (LNGFR) highlighted a fine network of adventitial reticular cells (ARC). The nodular aggregates of CLL/SLL, NMZL, MALT and SMZL were characterized by distortion of the ARC network and downregulation of LNGFR. In contrast, the aggregates of FL, LPL and MCL were composed of linear arrays of ARC in tight association with individual tumour cells. LNFGR+ was upregulated in ARC associated with the aggregates in FL, LPL and focally in MCL. Upregulation of CD35, vascular cell adhesion molecule (VCAM-1) and CD40 on ARC was noted exclusively in FL. Marrow lymphoid aggregates in CLL/SLL, NMZL, MALT and SMZL probably grow by displacing the pre-existing marrow stroma, while FL and LPL maintain a close association with the ARC network. In FL, expression of follicular dendritic cell-associated markers is modulated in pre-existing marrow stromal cells.