A Subset of Kaposi Sarcoma Cases Harbors Clonal Immunoglobulin Heavy Chain Gene Rearrangement: A Novel Finding Which Raises the Question of Transdifferentiation
Julia T Geyer, Gianna Ballon, Kui Nie, Y Lynn Wang, Ethel Cesarman. Weill Cornell Medical College, New York, NY
Background: Kaposi sarcoma herpersvirus (KSHV/HHV-8) vFLIP oncoprotein expression in B cells produced a B cell-derived histiocytic/dendritic cell sarcoma (DCS) with monoclonal IgH gene rearrangement and downregulation of B cell-associated antigens (transdifferentiation), proving plasticity between B cell and macrophage/dendritic cell lineages in mice. Others achieved myeloid conversion of B cells in vitro. There are also reported cases of follicular lymphoma patients transdifferentiating into histiocytic/DCS and CLL patients with clonally related interdigitating DCS. Kaposi sarcoma (KS) is the most common neoplasm associated with KSHV. It is considered a tumor of endothelial origin. It usually contains a mixed infiltrate of histiocytes, lymphocytes and plasma cells (PCs). Monoclonality has been documented in some cases of KS. KSHV infects B lymphocytes, lymphatic and vascular endothelial cells. We hypothesized that infected B cells could transdifferentiate and be part of the spindle cell compartment of KS, with evidence of B cell monoclonality in a subset of cases.
Design: 21 patients with KS and 3 patients with other skin lesions were selected. Immunohistochemistry (IHC) for Pax-5, CD138, kappa, lambda, CD34, CD31, CD68, CD163 and KSHV was performed. PCR for IgH and Jk gene rearrangement was done. Cases with evidence of B-cell clonality were further manually laser microdisected (LCM) and PCR was performed to rule out contamination by B cells.
Results: IHC results showed that 10 KS patients had no B cells/PCs, while 11 had 1+ to 3+ B cells/PCs. Three of 17 cases (18%) with good quality DNA had a monoclonal IgH gene rearrangement. One patient had 3+ PCs; 2 had no B-cells/PCs. With LCM, cases 1 and 2 had a positive but polyclonal pattern. Case 3 had a persistent monoclonal band, similar to the original band.
Conclusions: We have identified 3 patients with KS and evidence of clonal IgH gene rearrangement in the spindle cells. In the absence of B cells, no rearrangements should be present. After LCM where only spindle cells were selected, two patients had a polyclonal B-cell pattern consistent with a B cell origin in at least some spindle cells, without showing monoclonality. One patient had a persistent monoclonal band with no evidence of B-cells or PCs by IHC and a pure population of spindle cells achieved with LCM. These results raise the possibility of occasional transdifferentiation in human cells infected with KSHV. This is a novel finding which sheds new light on the pathogenesis of KS.
Monday, March 4, 2013 1:00 PM
Poster Session II # 277, Monday Afternoon