The clinical value of rearrangement of IgH gene and bcl-2/J(H) fuse gene in the diagnosis of orbital lymphoproliferative disorders.

OBJECTIVE

To determine whether polymerase chain reaction (PCR) for the assay of B-cell gene rearrangement in patients with orbital lymphoproliferative disorders could be useful in the diagnosis of lymphoma, especially in differentiating a benign lesion from a malignant one.

METHODS

In addition to clinical, pathological and immunohistochemical evaluations, 48 cases of orbital lymphoproliferative disorders were examined for immunoglobulin heavy chain (IgH) gene rearrangement and bcl-2/J(H) fuse gene rearrangement by means of PCR to amplify the third frame work region (FR3) and bcl-2/J(H) fuse gene with formalin-fixed and paraffin-embedded tissues.

RESULTS

The PCR using primer FR3A showed that 22 cases had discrete single products, which were within the molecular weight range of 100 to 120 bp, and were therefore interpreted as monoclonal. The positive rates of FR3 region of IgH gene rearrangement in patients with malignant lymphoma, benign reactive lymphoid hyperplasia and lymphocytic inflammatory pseudotumor were 75.0% (15/20), 40.0% (4/10) and 16.7% (3/18) respectively. The four patients with simultaneously bilateral ocular adnexal lymphoid neoplasm exhibited identical clonal IgH gene rearrangement patterns. A faint smear pattern or no band at all was demonstrated in the remaining 26 cases, representing polyclonal populations of lymphoid cells. The PCR using bcl-2 primer showed that 6 cases had discrete single products that were within the molecular weight range of 100 to 300 bp, and were interpreted as having bcl-2/J(H) fuse gene. They were 2 cases of follicular B-cell lymphomas, 1 case of diffuse mixed large and small cell B-lymphoma and 3 cases of diffuse small cell B-lymphoma. A faint smear pattern or no band at all was demonstrated in the remaining 17 cases of lymphomas, lymphocytic inflammatory pseudotumor and benign reactive lymphoid hyperplasia. The positive rates of bcl-2/J(H) fuse gene rearrangement in patients with malignant lymphoma, benign reactive lymphoid hyperplasia and lymphocytic inflammatory pseudotumor were 30.0% (6/20), 0% (0/10), and 0% (0/18), respectively.

CONCLUSIONS

Molecular genetic analysis by PCR using the FR3A primer is helpful in the diagnosis of orbital lymphoproliferative disorders, especially those in which the diagnosis can not be made by routine histopathological finding and immunohistochemistry evaluation. However, the rate of bcl-2/J(H) fuse gene rearrangement is too low to be suitable for clinical diagnosis of orbital lymphoproliferative disorders.