Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis

Authors

Stefano Lazzi, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Cristiana Bellan, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Anna Onnis, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Giulia De Falco, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Shahin Sayed, Aga Khan UniversityFollow
Ioannis Kostopoulos, Department of Pathology, Aristotle University of Thessaloniki, 57022 Thessaloniki, Greece
Monica Onorati, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Alessandro D'Amuri, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Rosa Santopietro, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy
Carla Vindigni, Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy

Document Type

Article

Department

Pathology (East Africa)

Abstract

Summary We report 3 cases of lymphoid neoplasms with mixed lineage features of T-, NK-, or B-cell marker expression and clonal gene rearrangement for both T-cell receptor and immunoglobulin light chain IgK. A characteristic of our cases was the lack of expression of the specific B-cell transcription factor, Pax5, which is essential for maintaining the identity and function of mature B cells during late B lymphopoiesis. In the absence of Pax5, B cells in vitro can differentiate into macrophages, dendritic cells, granulocytes, and T/NK cells. Methylation analysis of the Pax5 gene in our cases suggests that its inactivation by this epigenetic event in a committed or mature B cell, before plasma cell differentiation, may well be a common pathogenetic mechanism in mature lymphoid neoplasms with expression of multilineage antigens. In particular, case 1 may represent a mixed NK- and B-cell lineage; and cases 2 and 3 may represent mixed T and B-cell lineage, respectively. Aberrations in the DNA methylation patterns are currently recognized as a hallmark of human cancer. Cases with aberrant phenotypes require molecular analysis for lineage assignment. Studies of such cases may be helpful to better elucidate whether they represent a distinct entity with clinical, immunophenotypic, and molecular characteristics or an incidental phenomenon during malignant transformation. Interestingly, these cases were all characterized by poor clinical outcome.

Publication (Name of Journal)

Human pathology

Recommended Citation

Lazzi, S., Bellan, C., Onnis, A., De Falco, G., Sayed, S., Kostopoulos, I., Onorati, M., D'Amuri, A., Santopietro, R., Vindigni, C. (2009). Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis. Human pathology, 40(9), 1252-1261.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_pathol/247