Rearrangements of immunoglobulin gene and oncogenes in ocular adnexal pseudolymphoma

Abstract

The organization of immunoglobulin heavy chain (IgH), light chain (kappa and lambda) and T cell receptor (TCR) beta chain gene loci in 10 patients with ocular adnexal pseudolymphoma was investigated. Eight of them showed IgH gene rearrangement in at least one of the 3 restriction enzymes-digested DNAs extracted from ocular adnexal neoplasms. In contrast, none of them exhibited clonal TCR beta chain gene rearrangement. The configuration of bcl-1, bcl-2 and c-myc oncogenes was also studied by Southern blot technique. Two patients had a rearranged joining region, IgH-containing fragment that comigrated with the rearranged bcl-1 fragment. C-myc gene rearrangement was found in only one patient who also had bcl-1 gene rearrangement. In ocular adnexal pseudolymphoma, none demonstrated bcl-2 gene rearrangement; however, in bone marrow cells, one patient with systemic lymphadenopathy exhibited both IgH and bcl-2 gene rearrangements. Three genotypic subsets of these ocular adnexal pseudolymphoma can be identified by the configuration of IgH gene and related oncogenes: with germline configuration of IgH gene and bcl-1, bcl-2 and c-myc oncogenes; with rearrangement of IgH gene but germline configuration of these oncogenes; and with recombination between rearranged IgH and bcl-1 genes. These results suggest in ocular adnexal pseudolymphoma a spectrum of clonal change evolving from polyclonal to monoclonal B-population, and further to monoclonal B-population with rearranged bcl-1, c-myc and/or bcl-2 oncogenes.

Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival

“…FCL accounted for 11% of localised ocular adnexal lymphomas, which demonstrates that systemic nodal B cell lymphomas may first present in the ocular adnexa. Bcl-2 rearrangements in genomic DNA have previously been reported in patients with “lymphoid hyperplasia”,26 27 and it is possible that, in the absence of systemic disease to suggest neoplasia, the follicular changes in these biopsies were misinterpreted as “reactive”.…”

Progression of Cutaneous B-Cell Pseudolymphoma to Cutaneous B-Cell Lymphoma

“…15,22,27,36,[40][41][42][43][44][45] These reports include orbital pseudolymphomas 40,46,47 and lymphoepithelial lesions common to the rheumatologic manifestations of Mikulicz's disease and Sjogren's syndrome. [48][49][50][51][52] Likewise, the documentation of progression from CBPL to CBCL in the literature 5,6,15,[22][23][24]27,[34][35][36] and in our four patients provides further evidence for this phenomenon.…”