Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective

Abstract

The synovial tissue stands at the epicenter of joint pathology in rheumatoid arthritis (RA). As a primary target of the disease, studies on the synovium have provided invaluable insights into the mechanisms involved in disease pathogenesis. Recent work has, however, revealed the importance of a previously unseen anatomic compartment in direct contact with the joint space, namely the subchondral bone marrow. Bone marrow edema (BME) visible on magnetic resonance imaging (MRI) is clinically meaningful in both early and late RA as it associates with future development of bone erosions and poor functional outcomes. Although the histopathologic correlates of MRI-based BME in early RA remain obscure, studies in advanced disease are consistent in describing lymphocytic inflammatory infiltrates within the subchondral marrow cavity of affected joints. In this review, we discuss the nature of bone marrow lesions in patients with RA, analyze their relationship with synovitis, and explore their potential contribution to the pathological processes of the disease.

Figure 1

Subchondral bone marrow lymphocytic follicles in rheumatoid arthritis. A representative example of the inflammatory infiltrate in the subchondral bone marrow of a patient with rheumatoid arthritis undergoing joint replacement surgery of the hip. (A) Hematoxylin and eosin-stained section showing a mononuclear cell aggregate in the subchondral bone marrow adjacent to synovial tissue invasion into the marrow cavity through established cortical erosions. Note that the synovial tissue at the synovium-marrow boundary is mainly fibrous and acellular, whilst dense cellular infiltration can be observed within the marrow space. st, synovial tissue; e, erosion; b, bone; m, marrow. (B, C) Serial histologic sections of a mononuclear cell aggregate in the subchondral bone marrow stained for the B-cell marker CD20 (B) and the T-cell marker CD3 (C). Note the abundance of CD20 expression in the subchondral bone marrow aggregate. (A) Original magnification ×10; (B, C) original magnification ×40.

Figure 2

Bone cells in the synovial and subchondral compartment in rheumatoid arthritis. (A) Hematoxylin and eosin-stained section of a subchondral bone specimen with histologic evidence of erosions and intra-marrow inflammation. The different distribution of osteoclasts and osteoblasts is shown. Areas with osteoclast accumulation are visible on both the synovial (i) and the subchondral (ii) side of the joint. Osteoblasts and bone lining cells are instead located on the endosteal surface (iii). st, synovial tissue; b, bone; m, marrow. (B, C) Immunostainings for the osteoclast marker tartrate-resistant acid phosphatase (TRAP) showing TRAP-positive multinucleated osteoclasts resorbing bone from the synovium (B) as well as from the subchondral bone (C). (D) Immunostaning for parathytoid hormone receptor (PTH-R) showing PTH-R-positive cuboid osteoblasts and bone-lining cells in the subchondral compartment. (A) Original magnification ×10; (B-D) original magnification ×100.