Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis.
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.
Lazzi
Stefano
S
Department of Human Pathology and Oncology, University of Siena, 53100 Siena, Italy.
Bellan
Cristiana
C
Onnis
Anna
A
De Falco
Giulia
G
Sayed
Shahin
S
Kostopoulos
Ioannis
I
Onorati
Monica
M
D'Amuri
Alessandro
A
Santopietro
Rosa
R
Vindigni
Carla
C
Fabbri
Alberto
A
Righi
Simona
S
Pileri
Stefano
S
Tosi
Piero
P
Leoncini
Lorenzo
L
D000368:Aged; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D019175:DNA Methylation; D017809:Fatal Outcome; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D000941:Antigens; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D051757:PAX5 Transcription Factor