Hypergammaglobulinemia in an SIV-infected rhesus macaque with a B-cell neoplasm with plasma cell differentiation

Abstract

An SIV-infected rhesus macaque presented with anemia, hypercalcemia, and hyperglobulinemia. Neoplastic round cells with plasma cell morphology infiltrated multiple organs and stained immunohistochemically positive for CD45, MUM1/IRF4, CD138, VS38C, and Kappa light chain and variably positive for CD20 and CD79a, consistent with a B-cell neoplasm with plasma cell differentiation.

Figure 1

Graph of CD20 B cells/μL and serum electrophoresis results. Fig 1a. CD20 B cells/μL as a function of time post SIV infection. Fig 1b. Serum electrophoresis at baseline (point “b” on B cell graph). Peaks correspond to albumin, alpha 1, alpha 2, beta and gamma globulin fractions. Fig 1c. Serum electrophoresis at peak B cell levels (58 weeks post SIV infection, point “c” on B cell graph) shows a broad peak in the gamma globulin fraction. Fig 1d. Serum electrophoresis after B cell levels returned to baseline (79 weeks post inoculation, point “d” on B cell graph) showing development of a monoclonal peak in the gamma globulin fraction.

Figure 2

Microscopic and immunohistochemical findings. Fig 2A. Bone marrow; rhesus macaque. Infiltrate of neoplastic plasma cells. HE. Fig 2B. Bone marrow; rhesus macaque. Numerous cells throughout the bone marrow stain positive for the plasma cell marker CD138. Anti-CD138 immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2C. Bone marrow; rhesus macaque. Numerous cells throughout the bone marrow stain positive for the plasma cell marker VS38C. Anti-VS38C immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2D. Bone marrow; rhesus macaque. CD20 staining is largely absent from the bone marrow with only scattered CD20+ cells. Anti-CD20 immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2E. Bone marrow; rhesus macaque. Most neoplastic cells stain positive for MUM1/IRF-4. Anti-MUM1 immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2F. Bone marrow; rhesus macaque. A large number of neoplastic cells stain strongly positive for kappa light chain. Anti-Kappa light chain immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2G. Bone marrow; rhesus macaque. The bone marrow is nearly completely negative for lambda light chain. Anti-Lambda light chain immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2H. Bone marrow; rhesus macaque. The bone marrow is nearly completely negative for IgM. Anti-IgM immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2I. Spleen; rhesus macaque. Marked infiltrate of neoplastic round cells with plasma cell morphology. HE. Fig 2J. Spleen; rhesus macaque. Numerous CD138+ plasma cells throughout the neoplastic infiltrate. Anti-CD138 immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2K. Spleen; rhesus macaque. Numerous VS38C+ plasma cells throughout the neoplastic infiltrate. Anti-VS38C immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2L. Spleen; rhesus macaque. Neoplastic cells are variably CD20+ with some areas (upper part of image) being strongly positive while others (lower half of image) have only scattered CD20+ cells. Anti-CD20 immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2M. Spleen; rhesus macaque. Most neoplastic cells stain positive for MUM1/IRF-4. Anti-MUM1 immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2N. Spleen; rhesus macaque. Many neoplastic cells are strongly positive for kappa light chain. Anti-Kappa light chain immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2O. Spleen; rhesus macaque. Neoplastic cells are diffusely negative for lambda light chain. Lambda light chain immunohistochemistry, DAB chromogen, hematoxylin counterstain. Fig 2P. Spleen; rhesus macaque. Neoplastic cells are negative for IgM. A few, scattered, individual cells stained IgM+ but this is insignificant overall. Anti-IgM immunohistochemistry, DAB chromogen, hematoxylin counterstain.