Bone Marrow Histology in a Cohort of HIV+ Patients with Multicentric Castleman's Disease (MCD) Associated with Kaposi's Sarcoma-Associated Herpesvirus
G Venkataraman, TS Uldrick, R Little, R Yarchoan, S Pittaluga, I Maric. National Cancer Institute, NIH, Bethesda, MD
Background: Multicentric Castleman disease (MCD) is a rare systemic disorder that presents with splenomegaly, generalized lymphadenopathy and inflammatory symptoms. Profound cytopenias are common. The prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) is universal (100%) in HIV+ cases. However, very little information is available regarding the bone marrow findings in MCD in the setting of HIV.
Design: Of 22 patients enrolled in a clinical trial for patients with histologically confirmed KSHV-MCD, at least one bone marrow study was available in 16 (8 African-american, 7 Caucasian, 1 unknown). Bone marrow histology and immunostains for CD20, CD3, CD79a, CD38, CD138, HHV-8, and kappa/lambda insitu hybridization were examined. Specific morphologic features sought for included serous atrophy, dysplasia, presence of lymphoid aggregates and plasmacytosis.
Results: There were 20 males and 2 females (median age 45.68 years; range 29-59), all of whom were HIV+ at diagnosis of KSHV-MCD. Bone marrow cellularity ranged from 20-95% with varying plasmacytosis (5-25%) seen with CD38/CD138. Most of the cases showed mild-moderate interstitial T-cell lymphocytosis that correlated with presence of large granular lymphocytes in the peripheral smear. Four of 16 cases showed scattered lymphoid aggregates comprising an admixture of B- and T-cells without light chain restriction (LCR) or plasmablasts in examined cases. Four of 13 tested cases showed singly scattered HHV-8+ mononuclear cells; one additionally showed scattered polyclonal lymphoid aggregates and lambda LCR plasma cells. One of 14 showed kappa predominance, while one another showed focal clusters of atypical lambda-positive plasma cells; all other 11/14 tested cases were polyclonal. Occasional naked megakaryocytes and micromegakaryocytes with minimal atypia were noted in several biopsies; however, serous atrophy or significant myeloid/erythroid dysplasia were not noted.
Conclusions: Our study shows a broader spectrum of histological changes in the bone marrows of well documented MCD cases. KSHV infected mononuclear cells in the marrow are seen in about 1/3 of cases and a proportion of them demonstrate lymphoid aggregates (25%) or lambda LCR plasma cells (14%); however, reactive germinal centers typically seen in KSHV-MCD lymph node tissues are rarely seen in the bone marrow.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 201, Wednesday Afternoon