PAX stains in hematologic malignancies, a diagnostic pitfall: a comparative study evaluating monoclonal PAX8s, polyclonal PAX2, and PAX5

Paired-box (PAX) genes constitute a family of genes involved in development. PAX5 is expressed in B lineage lymphomas. Recent studies report positive staining of polyclonal PAX8 in B cell proliferations due to N-terminus homology between PAX5 and PAX8. However, the expression of PAX2 or monoclonal antibodies against the N-terminus of PAX8 (PAX8N) in these neoplasms has not been fully evaluated. The goal of this study was to evaluate the expression of PAX8N, monoclonal C-terminus PAX8 (PAX8C), and polyclonal PAX2 in hematologic malignancies and to compare the results with PAX5. Immunohistochemical (IHC) staining for PAX5, PAX8N, PAX8C, and PAX2 was performed on follicular lymphoma grades 1–3 (FL1–FL3), diffuse large B cell lymphoma (DLBCL), small lymphocytic lymphoma (SLL), nodal marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), classical Hodgkin lymphoma (cHL), plasmacytoma, anaplastic large cell lymphoma (ALCL), and peripheral T cell lymphoma (PTCL). Expression was scored based on percentage of nuclear staining in neoplastic cells. PAX8N staining correlated with PAX5 and was positive in all B cell neoplasms examined, while PAX8C was negative. PAX2 had sporadic expression in FL2, FL3, DLBCL, and MCL. All PAX stains were nearly or entirely negative in plasmacytomas, ALCL, and PTCL. PAX8N stains B cell neoplasms and its positivity parallels PAX5. PAX8C does not stain any of the aforementioned neoplasms, and PAX2 shows no distinct pattern. While PAX8C has a role in discriminating lymphoid and epithelial malignancies, PAX8N, polyclonal PAX8, and PAX2 do not. This study illustrates the importance of knowing specific IHC targets to avoid misdiagnosis.