Purpose: Several B-cell-associated transcription factors and their coactivators, including BCL-6, BSAP/PAX5, BOB.1/OBF.1, Oct.2, MUM1/IRF4, and PU.1, have been detected in peripheral B-cell lymphomas. There are limited data on their expression in centrally located lymphoid neoplasms, such as primary intraocular lymphoma (PIOL) or primary central nervous system lymphoma (PCNSL). PIOL is a rare non-Hodgkin lymphoma, considered a subtype of PCNSL. Both are usually diffuse, large B-cell lymphoma (DLBCL), rarely manifest outside the CNS, and carry a poor prognosis.
Methods: Tissue biopsy specimens were examined from eight cases of PIOL and 42 cases of HIV-negative PCNSL, as well as 50 cases of peripheral DLBCL, for the above-mentioned transcription factors and for immunoglobulin heavy and light chains, using immunohistochemistry.
Results: Immunoglobulin expression was demonstrated in 46 (92%) of 50 cases of PIOL/PCNSL but in only 27 (54%) of 50 cases of peripheral DLBCL. Positivity for BOB.1/OBF.1 and Oct.2 was observed in all immunoglobulin-expressing PIOL and PCNSL. BSAP/PAX5 expression occurred in 98% of PIOL/PCNSL, and MUM1/IRF4 immunoreactivity in 45 (90%) of 50 of these cases. PU.1 expression was observed in only 10% of the PIOL/PCNSL group in contrast to 23 (46%) of 50 peripheral DLBCLs. Aberrant coexpression of MUM1/IRF4, PAX5, MUM1/IRF4, and BCL-6 was observed in most PIOLs/PCNSLs.
Conclusions: These data provide further support to the notion that peripheral and centrally located DLBCLs differ in clinical, immunophenotypic, and genotypic features, despite their similar morphologic characteristics. PIOL and PCNSL tumor cells are most likely to be derived from mature B-cells that have undergone the germinal center reaction.