Bone Marrow Manifestations of IgG4-Related Disease
Aliyah R Sohani, Anuj Mahindra, Arezou Khosroshahi, John H Stone, Vikram Deshpande, Robert P Hasserjian. Massachusetts General Hospital, Boston
Background: IgG4-related disease (IgG4-RD) is a non-neoplastic fibroinflammatory condition initially described in the pancreas and now known to involve multiple different organs. However, bone marrow (BM) findings in IgG4-RD have not been previously reported.
Design: We identified 4 pts with a confirmed or probable diagnosis of IgG4-RD who underwent BM sampling during their disease course and reviewed their biopsy sections, aspirate smears, and immunohistochemical-stained slides. Features assessed in all cases were marrow cellularity, presence of lymphoid aggregates or infiltrates, proportion and distribution of plasma cells (PCs), and reticulin fiber content. PCs were assessed for IgG and IgG4 expression and for clonality by light chain immunohistochemistry.
Results: The 4 pts (2 M, 2 F) had a median age of 62.5 y (range 27 to 66). The diagnosis of IgG4-RD was established or suspected by tissue biopsy of kidney and lymph node (1 pt), liver and gallbladder (1 pt), retroperitoneum and minor salivary gland (1 pt), and multiple lymph nodes (1 pt). The pt with renal disease also had elevated serum IgG4, while serum IgG4 was normal in the other 3. Reasons for BM biopsy included evaluation for cytopenias (2 pts) or for a suspected PC neoplasm (1 pt with elevated serum free light chains and 1 pt with lymph node biopsy findings initially suspicious for a clonal PC proliferation). In all 4 cases, there was maturing trilineage hematopoiesis without lymphoid aggregates, increased fibrosis, increased eosinophils or prominent vascularity. Median BM cellularity was 60% and overall cellularity was increased for age in 2 cases. Flow cytometry showed <1-2% polytypic B cells, 3-9% T cells with a CD4:CD8 ratio of 0.4-0.9 and <1-3% NK cells; 1 case contained increased hematogones (11%). PCs ranged from 2-15% of all cells in the aspirate, were increased (≥5%) in 2 cases, and occurred singly or in small perivascular clusters in the biopsies. Light chain immunophenotyping confirmed the PCs to be polytypic. Less than 10% of IgG+ PCs were IgG4+ in the 3 pts with ≤5% PCs and normal serum IgG4 levels, while 41% of IgG+ PCs were IgG4+ (average 8.5 IgG4+ PCs/HPF) in the pt with 15% PCs and an elevated serum IgG4.
Conclusions: Based on this small series, IgG4-RD pts have normal or reactive findings on BM examination without histological manifestations that characterize IgG4-RD at other sites. Marrow plasmacytosis is present in a subset of cases, but PCs are polytypic and do not form large aggregates or sheets. The single case with an elevated serum IgG4 also had an elevated BM IgG4:IgG PC ratio, suggesting that the BM IgG4+ PC population may reflect serum IgG4 levels in IgG4-RD.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 241, Wednesday Afternoon