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

Stefano Lazzi, Cristiana Bellan, Anna Onnis, Giulia De Falco, Shahin Sayed, Ioannis Kostopoulos, Monica Onorati, Alessandro D'Amuri, Rosa Santopietro, Carla Vindigni, Alberto Fabbri, Simona Righi, Stefano Pileri, Piero Tosi, Lorenzo Leoncini

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1252-1261
Number of pages10
JournalHuman Pathology
Issue number9
Publication statusPublished - Sept 2009
Externally publishedYes


  • Aberrant expression of B- and T-cell markers
  • Extranodal NK/T-cell lymphoma
  • Immunohistochemistry
  • Immunophenotype
  • Molecular analysis
  • Pax5


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