RESUMEN
The BCL2 gene was identified through molecular analysis of the breakpoints involved in the t(14;18)(q32;q21) found in the majority of follicular lymphomas (FL). Variant translocations leading to juxtaposing of the BCL2 with either the IGK or IGL gene have been recognized in B-cell malignant lymphoma, although they are rare. We identified seven lymphoma cases that had variant translocations. Three cases had simple translocations involving two chromosomal regions: t(18;22)(q21;q11.2) in two cases and t(2;18)(p11.2;q21) in the third case. Complex translocations affecting more than two chromosomes were seen in the remaining four cases. Fluorescence in situ hybridization using the LSI IGH/BCL2 DNA probes revealed rearrangements of the BCL2 gene locus in all cases. In addition, expression of BCL2 protein was seen in all cases; only five of the seven cases expressed BCL6 protein. Morphologically, the lymphomas were categorized as B-cell follicular lymphoma in six cases and in the seventh case as diffuse large cell lymphoma (Richter syndrome) transformed from preexisting chronic lymphocytic leukemia (CLL). In case 2, the variant t(18;22) was seen as a secondary aberration evolving from a trisomy 12 clone. The findings revealed that BCL2 rearrangements in some malignant lymphomas occur through variant simple or complex chromosomal translocations, but always involving the IGH, IGK, or IGL chromosomal site. In addition, fluorescence in situ hybridization proved to be an important tool in evaluating these cases by showing IGH/BCL2 gene fusion or repositioning of the BCL2 gene.
Asunto(s)
Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Linfoma/genética , Translocación Genética , Adulto , Anciano , Femenino , Genes bcl-2 , Genes myc , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana EdadRESUMEN
Two cases of follicular lymphoma (FL) with numerous large cells resembling the lacunar and Hodgkin and Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma were studied to determine clonal relationships between the HRS-like cells and centrocytic and centroblastic (CCCB) cells. In both cases, CCCB cells were typical of FL; CD45RB, CD20, CD10 and BCL-2 positive. In case 1, the HRS-like cells were positive for CD45RB, CD20, CD10, CD30, OCT2, and BOB.1 and negative for CD15 and bcl-2. In case 2, the HRS-like cells were positive for CD30, fascin, CD20, OCT2, and BOB.1 and negative for CD45RB, CD10, CD15, and bcl-2. CCCB and single HRS-like cells were isolated by laser capture microdissection followed by polymerase chain reaction amplification and sequencing of immunoglobulin heavy chain gene rearrangements. In both cases, identical sequences were obtained from CCCB and HRS-like cells. These findings confirm that although the HRS cells and CCCB cells in these cases demonstrate morphologic and immunophenotypic divergence, they share a common cell of origin. These cases further highlight the potential diagnostic pitfall presented by FL with HRS-like cells.
Asunto(s)
Ganglios Linfáticos/patología , Linfoma Folicular/genética , Linfoma Folicular/patología , Células de Reed-Sternberg/patología , Anciano , Antígenos CD/metabolismo , Células Clonales , Diagnóstico Diferencial , Femenino , Citometría de Flujo , Reordenamiento Génico de Cadena Pesada de Linfocito B/genética , Genes de Inmunoglobulinas/genética , Humanos , Inmunohistoquímica , Inmunofenotipificación , Rayos Láser , Ganglios Linfáticos/metabolismo , Linfoma Folicular/metabolismo , Microdisección , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Células de Reed-Sternberg/metabolismoRESUMEN
A 56-year-old man presented with fever, disorientation, and testicular pain. He was receiving azathioprine immunosuppression for autoimmune hepatitis. Orchiectomy identified occlusion of spermatic cord vessels by intravascular large B-cell lymphoma (IVLBL) and ischemic changes in the testis. Tumor cells were positive for CD 10, CD 20, CD 30, and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) and early region RNA (EBER). He was treated with the cessation of azathioprine, chemotherapy, anti-CD 20 immunotherapy, and radiotherapy. Twenty months after diagnosis, he is alive with no evidence of lymphoma or hepatitis. This is the first report of IVLBL presenting with testicular ischemia. It highlights the importance of prompt diagnosis and intervention to achieve durable response. That this lymphoma arose in the setting of immunosuppressive therapy introduces additional complexity relating to pathogenesis, clinical behavior, and treatment.
Asunto(s)
Huésped Inmunocomprometido , Isquemia/etiología , Linfoma de Células B/inmunología , Enfermedades Testiculares/inmunología , Neoplasias Vasculares/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Azatioprina/uso terapéutico , Biomarcadores de Tumor/análisis , Ciclofosfamida/uso terapéutico , Diagnóstico Diferencial , Doxorrubicina/uso terapéutico , Infecciones por Virus de Epstein-Barr/fisiopatología , Fiebre/etiología , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Hibridación in Situ , Linfoma de Células B/patología , Linfoma de Células B/terapia , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Radioterapia , Rituximab , Cordón Espermático/irrigación sanguínea , Cordón Espermático/patología , Enfermedades Testiculares/patología , Enfermedades Testiculares/terapia , Infecciones Tumorales por Virus/fisiopatología , Neoplasias Vasculares/patología , Neoplasias Vasculares/terapia , Vincristina/uso terapéutico , Proteínas de la Matriz Viral/metabolismoRESUMEN
Only a few blastic natural killer (NK) cell leukemias and lymphomas have been reported. As such, the clinicopathologic spectrum of this disease is incompletely understood. We report 7 cases of blastic NK cell lymphoma/leukemia. All patients were men, 5 white and 2 Arab American. All cases exhibited blastic morphologic features and were CD3- and CD56+ with germline T-cell receptor genes. Five cases were CD4+ and involved the skin. Both CD4- cases never involved the skin. Other markers of mature NK cells such as CD16, CD57, and TIA-1 were expressed infrequently. Three cases were CD33+. One CD33+ case had a clonal rearrangement of the immunoglobulin heavy chain gene. Skin and lymph nodes were involved most often, with frequent evolution to a leukemic phase. Initial responses to therapy were achieved in most patients, but the tumors invariably recurred.