PAX-5: A Valuable Immunohistochemical Marker in the Differential Diagnosis of Lymphoid Neoplasms

Abstract

Undifferentiated tumors and hematolymphoid neoplasms can be diagnostically challenging due to potential overlap of morphologic features and variant antigen expression. PAX-5, a transcription factor expressed throughout B-cell maturation, is detected in most B-cell neoplasms including those that lack expression of mature B-cell markers, such as classical Hodgkin lymphoma (cHL), B-lymphoblastic leukemia and B-cell lymphomas following rituximab therapy. The lack of PAX-5 expression in most CD30-positive non-hematopoietic malignancies (embryonal carcinoma and seminoma) and T-cell lymphomas, such as anaplastic large cell lymphoma (ALCL), suggests that the absence of PAX-5 may be used to confirm non-B-cell lineage. The goal of this study was to retrospectively assess PAX-5 immunoreactivity in diagnostic samples of hematolymphoid and other non-hematopoietic malignancies. Diagnostic lymph node, decalcified core bone marrow biopsies and tissue sections from 111 archived paraffin-embedded tissue blocks and a tissue lymphoma microarray were immunostained using a monoclonal antibody to PAX-5. The corresponding hematoxylin and eosin stained tissue sections and additional immunostains were simultaneously evaluated. PAX-5 immunoreactivity in neoplastic cells was scored as positive or negative. This study was exempted by the Institutional Review Board for Human Research. Nuclear PAX-5 immunoreactivity was detected in 88% (36/41) of Hodgkin lymphoma, all cases of diffuse large B-cell lymphoma (n=72), small B-cell lymphomas (n=5), B-lymphoblastic leukemia/lymphoma and mixed phenotype acute leukemia with B-cell lineage (n=5). PAX-5 was not detected in ALCL (n=22), T-cell lymphoblastic leukemia/lymphoma, mixed phenotype acute leukemia with T-cell lineage (n=5), acute myeloid leukemia (n=4), carcinoid tumors with typical morphology (n=5), melanoma (n=3), and undifferentiated/metastatic tumors (n=8). Non-neoplastic bone marrow sections showed scattered nuclear staining in small B-cell lymphocytes/hematogones. The detection of PAX-5 immunoreactivity resulted in the reclassification of two cases of ALCL to cHL. Overall, our results demonstrate that including PAX-5 in a panel with other immunomarkers helps establish B-cell lineage and increases diagnostic yield.