Histiocytic Differentiation and Loss of B-Cell Identity in Follicular Lymphoma
E Haralambieva, T Nedeva, H Horn, E Hartmann, EM Maggio, HK Mueller-Hermelink, A Zettl. University of Wuerzburg, Wuerzburg, Germany
Background: Hematopoetic lineage differentiation is considered a stepwise process of irreversible lineage commitments. In disagreement with this, however consistent with in vitro reprogramming experiments, Feldman et al. reported recently on follicular lymphoma (FL) patients developing genetically related tumors with histiocytic differentiation.
Design: Similarly, we identified in our pathology files four patients with meta- or synchronous histiocytic/dendritic cell sarcoma (HS) and FL. One patient had medical records of FL and only HS sample was available for further studies.Six of the coupled samples were submitted to comparative genomic hybridization (CGH) and sequence analysis of immunoglobulin heavy chain (IgH) rearrangement. Extensive immunohistochemistry, fluorescence in situ hybridization (FISH) for detection of translocation breakpoints in BCL2 gene and IgH clonality PCR and GenScan assays were performed in all samples. Ten randomly selected samples of histiocytic lesions were used as a control group.
Results: All HS lacked CD20 and CD79a and expressed variably CD68, CD163 and CD123.Only one tumor showed weak PAX5 expression in occasional cells, however B-cell transcriptional factor Oct2 was positive in all HS. In keeping with the data of Feldman et al., all HS harboured a chromosomal breakpoint into BCL2 gene as well as clonally rearranged IgH genes. In contrast, no clonal IgH rearrangement and BCL2 chromosomal breakpoints were identified in control group. CGH analysis indicated that at least in two out of three patients HS and FL shared common chromosomal imbalances.
FL - follicular lymphoma, HS - histiocytic sarcoma, NA - not applicable
|HS||1q41-qter, 2cen-p14, 2cen-q22, 8p22-pter||2q24-q33, 9p21-pter, 13q14-q22|
|2||f/55||FL||2q36-qter, 6p, 11p, 11cen-q13||6cen-q21|
|HS||6p, 6q25-qter||2q24-q33, 6cen-q21, 13q14-q21|
|3||m/50||FL||2p23-pter, 6p, 12q24-qter||6q24-qter|
Sequence analysis of IgH gene confirmed in the coupled samples of 2 patients sequence homology with the same VH family usage and similar mutation rate.
Conclusions: On genetic level all four HS are consistent with mature B cell neoplasia, demostrating however loss of B cell phenotype and morphological, immunophenotypic and functional (phagocytosis in one case) features of histiocytic differentiation. The patients had progressive disease with significantly longer overal survival than common HS patients.
Monday, March 9, 2009 9:00 AM
Platform Session: Section D, Monday Morning