RESUMEN
Cyclin D1(-) mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1(-) variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1(-) SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1/SOX11 MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1(-) MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1(+) MCL and provides a basis for the proper identification and clinical management of these patients.
Asunto(s)
Ciclina D1/genética , Ciclina D2/genética , Reordenamiento Génico/genética , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Adulto , Anciano , Anciano de 80 o más Años , Ciclina D1/metabolismo , Ciclina D2/metabolismo , Ciclina D3/genética , Ciclina D3/metabolismo , Variaciones en el Número de Copia de ADN/genética , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células del Manto/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Translocación Genética/genéticaRESUMEN
The differential diagnosis between neoplastic and reactive lymphoid proliferations is a relatively common situation, which in most cases is resolved using conventional morphological and phenotypic criteria. In the last years, a number of studies have identified different types of lymphoid lesions sharing pathological and molecular features of both benign and malignant processes that are difficult to interpret. A group of these lesions correspond to atypical lymphoid hyperplasias, including follicular hyperplasias, atypical marginal zone hyperplasias, and florid reactive lymphoid hyperplasias of the lower female genital tract in which immunoglobulin light chain restriction with or without clonal IGH rearrangements may be found in some cases. However, these lesions are usually self-limited and do not evolve to an overt lymphoid neoplasia. A second group of lesions are clonal expansions of cells with phenotypic or molecular features of well-defined lymphoid neoplasias, such as chronic lymphocytic leukemias, follicular lymphomas, or mantle cell lymphomas, occurring in otherwise healthy individuals or in the context of reactive lymphoid tissues. In this review, we discuss the criteria to distinguish these lesions from overt lymphomas and the current recommendations for the management of the individuals in which these lesions are found.
Asunto(s)
Linfoma/diagnóstico , Trastornos Linfoproliferativos/diagnóstico , Diagnóstico Diferencial , Diagnóstico Precoz , Humanos , Tejido Linfoide/patología , Seudolinfoma/diagnósticoRESUMEN
BACKGROUND: Cyclin D1-positive B cells are occasionally found in the mantle zones of reactive lymphoid follicles, a condition that has been called "in situ mantle cell lymphoma". The clinical significance of this lesion remains uncertain. DESIGN AND METHODS: The clinical and pathological characteristics, including SOX11 expression, of 23 cases initially diagnosed as in situ mantle cell lymphoma were studied. RESULTS: Seventeen of the 23 cases fulfilled the criteria for in situ mantle cell lymphoma. In most cases, the lesions were incidental findings in reactive lymph nodes. The t(11;14) was detected in all eight cases examined. SOX11 was positive in seven of 16 cases (44%). Five cases were associated with other small B-cell lymphomas. In two cases, both SOX11-positive, the in situ mantle cell lymphoma lesions were discovered after the diagnosis of overt lymphoma; one 4 years earlier, and one 3 years later. Twelve of the remaining 15 patients had a follow-up of at least 1 year (median 2 years; range, 1-19.5), of whom 11 showed no evidence of progression, including seven who were not treated. Only one of 12 patients with an in situ mantle cell lymphoma lesion and no diagnosis of mantle cell lymphoma at the time developed an overt lymphoma, 4 years later; this case was also SOX11-positive. The six remaining cases were diagnosed as mantle cell lymphoma with a mantle zone pattern. Five were SOX11-positive and four of them were associated with lymphoma without a mantle zone pattern. CONCLUSIONS: In situ mantle cell lymphoma lesions are usually an incidental finding with a very indolent behavior. These cases must be distinguished from mantle cell lymphoma with a mantle zone pattern and overt mantle cell lymphoma because they may not require therapeutic intervention.
Asunto(s)
Hallazgos Incidentales , Linfoma de Células del Manto/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Factores de Transcripción SOXC/genéticaRESUMEN
La neuropatía óptica hereditaria de Leber (LHON) es una enfermedad de herencia materna que se caracteriza por la pérdida subaguda bilateral de la visión central, predominantemente en hombres jóvenes. Esta enfermedad es causada por mutaciones puntuales del ADN mitocondrial, afectando el complejo I de la cadena respiratoria. Se discutirá sobre la genética, la bioquímica y la clínica con el objetivo de dar a conocer esta enfermedad a la comunidad médica nacional a propósito del diagnóstico de la primera familia afectada.