RESUMO
We investigated 16 lymphoid proliferations occurring in the ocular adnexa, salivary glands, breast, and thyroid gland and satisfying the histopathologic and immunophenotypic criteria of benign lymphoid hyperplasia for the presence of clonal rearrangements of the antigen receptor, c-myc, bcl-1, and bcl-2 genes and Epstein-Barr virus (EBV) DNA sequences. Each of these 16 extranodal, noncutaneous lymphoid neoplasms exhibited clonal immunoglobulin heavy and/or light chain and lacked T-cell receptor (TCR) beta-chain gene rearrangements. The patterns of immunoglobulin gene rearrangements included solitary and multiple barely perceptible to faint bands, solitary clear and definite bands, and solitary high-intensity bands superimposed on a background of multiple less-intense bands. Three ocular adnexal lymphoid neoplasms exhibited bcl-1 or bcl-2 gene rearrangements. None of the 16 lymphoid neoplasms contained EBV DNA sequences. Two patients developed a histopathologically confirmed malignant lymphoma in an extranodal site. None of the remaining 14 patients developed additional lymphoid neoplasms during a mean follow-up period of 30 months, despite conservative therapy. These results demonstrate that extranodal, noncutaneous lymphoid neoplasms meeting the histopathologic and immunophenotypic criteria for benign lymphoid hyperplasia frequently contain occult monoclonal and oligoclonal B-cell populations representing a continuous and progressive spectrum of B-cell neoplasia up to and including malignant lymphoma.
Assuntos
Linfócitos B/fisiologia , Rearranjo Gênico , Genes de Imunoglobulinas , Linfoma não Hodgkin/genética , Transtornos Linfoproliferativos/genética , Proteínas Proto-Oncogênicas/genética , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos T/genética , Antígenos de Diferenciação/análise , DNA Viral/análise , Herpesvirus Humano 4/genética , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/patologiaRESUMO
Each of three individuals with acquired immunodeficiency syndrome (AIDS) developed a pleomorphic malignant neoplasm in which a precise histopathologic diagnosis could not be rendered. In each case, the tumor cells expressed leukocyte common antigen and a variable constellation of antigens associated with B- and T-cell activation (HLA-DR, T9, T10, BL2, BL3, Ki-24, BLAST-2). They lacked all B cell, T cell, myeloid, and monocyte lineage-restricted antigens, resulting in their classification as hematopoietic neoplasms of uncertain lineage. However, antigen receptor gene rearrangement analysis demonstrated that each of these three neoplasms exhibited clonal immunoglobulin heavy chain and kappa light chain gene rearrangements and lacked T-cell receptor beta chain gene rearrangements and therefore were B cell-derived non-Hodgkin's lymphomas (NHL) representative of an equivalent, relatively mature stage of B-cell differentiation. In contrast with most AIDS-associated NHLs, each of these three neoplasms lacked c-myc gene rearrangements and contained Epstein-Barr virus (EBV) proteins and/or sequences. These studies demonstrate that these three AIDS-associated neoplasms of uncertain lineage exhibit a strikingly similar constellation of distinctly uncommon morphologic, immunophenotypic, and molecular genetic characteristics that distinguishes them substantially from the vast majority of NHLs that have been reported to occur in association with AIDS. The consistent presence of EBV proteins and/or DNA sequences suggests that the Epstein-Barr virus played a pathogenetic role in the development of these three AIDS-associated neoplasms. Finally, these studies further illustrate the utility of antigen receptor gene rearrangement analysis in the diagnosis and classification of hematopoietic neoplasms of uncertain lineage.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Linfoma não Hodgkin/etiologia , Adulto , Antígenos de Diferenciação/análise , Antígenos de Neoplasias/análise , Antígenos Virais/genética , Linfócitos B , DNA Viral/análise , Antígenos Nucleares do Vírus Epstein-Barr , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Rearranjo Gênico de Cadeia Leve de Linfócito B , Herpesvirus Humano 4/patogenicidade , Humanos , Cadeias kappa de Imunoglobulina/genética , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos B/genéticaRESUMO
We describe a primary splenic neoplasm composed of cytomorphologically malignant-appearing erythrophagocytic histiocytoid cells reminiscent of those seen in malignant histiocytosis. However, this neoplasm displayed certain distinctive clinicopathologic features--including localization to the spleen, where it grew as separate discrete nodules--that distinguish it from all previously reported cases of malignant histiocytosis. The cells expressed a monocyte/histiocyte immunophenotype and lacked clonal immunoglobulin and T-cell receptor beta-chain gene rearrangements. Our results suggest that this neoplasm represents a clinicopathologically distinctive and possibly unique tumor derived from the tissue macrophage lineage.
Assuntos
Histiócitos/patologia , Neoplasias Esplênicas/patologia , Adulto , Humanos , Técnicas Imunológicas , Masculino , Microscopia Eletrônica , Biologia Molecular , Fenótipo , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/ultraestruturaRESUMO
Ig and T cell receptor rearrangements have been used as irreversible markers of lineage and clonality in the study of B- and T-lymphoid populations. We have addressed the issue of lymphoid lineage specificity of these rearrangements by analyzing a panel of 25 TdT- acute myelogenous leukemias, 13 TdT+ AMLs, and 4 TdT+ undifferentiated leukemias. We report that while gene rearrangements represent extremely rare events in classical TdT- AML (less than 8%), rearrangements of either the Ig or T beta locus or both were detectable in the majority of the TdT+ AMLs (greater than 60%), and rearrangements of both loci were detectable in all of the TdT+ undifferentiated leukemias. These data demonstrate a significant association between TdT expression and Ig or T beta gene rearrangements even outside the lymphoid lineage, further supporting a role for TdT in Ig and T cell receptor gene assembly. These data also indicate that a coordinated program of lymphoid gene expression involving TdT-CD7-expression and Ig/T beta rearrangements can be activated before myeloid commitment. Whether the activation of this program represents a normal, albeit rare, event in early myelopoiesis or a transformation-related event present only in leukemic cells remains to be determined.