Lesión «lymphoma-like» del cérvix con reordenamiento monoclonal del gen de cadena pesada de inmunoglobulina por PCR. Comunicación de un caso / Lymphoma-like lesion of the cervix with monoclonal immunoglobulin heavy chain gene rearrangement in PCR analysis. A case report

La lesión «lymphoma-like» del cérvix es una proliferación linfoide benigna que simula un linfoma B difuso de células grandes, por ello es causa de potencial error diagnóstico. Presentamos el caso de una mujer de 24 años con PAP atípico y conización subsecuente, identificándose una proliferación linfoide atípica. El infiltrado linfoide era polimórfico, con numerosas células grandes entremezcladas, sin necrosis ni esclerosis. El epitelio presentó displasia epitelial moderada. Las células grandes fueron inmunorreactivas para CD20, sin expresión de cadenas ligeras de inmunoglobulinas. La hibridación in situ para el virus de Epstein-Barr resultó positiva en escasas células grandes aisladas. Mediante técnica de PCR, para amplificación de la región FR3 de la cadena pesada de la IgH, se observaron 2 bandas monoclonales. Hasta el último seguimiento (24 meses), no se encontró evidencia de enfermedad sistémica/progresión(AU)

Lymphoma-like lesion of the cervix is an uncommon benign lymphoid proliferation that mimics large B-cell lymphoma (LBCL) and hence is a potential cause of misdiagnosis. We report a 24 year-old woman with an abnormal PAP smear and a subsequent cervical biopsy that showed an atypical lymphoid proliferation. Histopathologically, it was characterized by a superficial polymorphic lymphoid infiltrate with numerous scattered large cells, with no necrosis or sclerosis. Surface epithelium showed erosion and mild dysplasia. Immunohistochemically, the large atypical cells were positive for CD20 and the scattered large cells for CD30, with no expression of light chains. In situ hybridization for EBV was positive in a few isolated large cells. PRC amplification of the FR3 region of the IgH heavy chain showed 2 monoclonal bands. Two years later the patient is alive and well(AU)

Serie de 618 casos de gammapatías monoclonales de significado indeterminado (GMSI): factores predictivos de desaparición del componente monoclonal o de evolución a gammapatías malignas / A series of 618 of monoclonal gammopathy of undeterminated significance: variables asocciated with disappearance and progression

Introducción. La identificación de las gammapatíasmonoclonales de significado incierto (GMSI) conriesgo elevado de progresión se viene estudiandoen los últimos años.Objetivos. Evaluar la incidencia de las GMSI enun área de 300.000 habitantes y sus factoresasociados: la desaparición del componentemonoclonal (CM), gammapatías transitorias (GMT) ysu evolución a gammapatías malignas (GMM).Métodos. Estudio de 618 GMSI.Resultados. Incidencia: 30-40 casos nuevos/año, conun incremento en los últimos años de hasta 70 casospor año. Edad y sexo: 71,4 años (32-100); relaciónH/F 1,4. Patología asociada: infecciosa 328,cardiológica 249, reumatoidea 211, hepática 108,neoplasia 80 y neuropatía 43. Características del CM:IgG 407, IgA 93, IgM 78, IgD 2, biclonales 16,triclonal 1 y ninguna cadena pesada 21. Cadenasligeras: kappa 389 casos. Variables (media): CM 14 g/l, VSG 32,5 mm, MO porcentaje de células plasmáticas 5,9%, ß2-microglobulina 2,59 mg/l, albúmina 3,1 g/l, serie ósea normal 39,5%. Evolución: GMT 20 casos. Tiempo medio de desaparición 2,6meses (1,4-4,6), GM transformadas a GMM 24 casosTiempo medio de progresión 3 años (IC 1,82-4,3).Resultados. Se identifican como factoresasociados a transformación a GMM: cadena pesadaIgA (p < 0,002), VSG (p < 0,001), edad < 70 años(p < 0,05), porcentaje de CP (p < 0,002) yosteoporosis (p < 0,005). Se propone un modelo de seguimiento de GMSI

Introduction. How to identify monoclonalgammopathies of undeterminated significance(MGUS) at risk for progression has been studied forthe last years. Aims. To study the incidence ofMGUS in a region with 300,000 inhabitants andfactors which associate with a) monoclonalgammopathy disappearance (transient MGUS)b) evolution to malignant gammopathy.Methods. Study of 618 MGUS.Results. Incidence: 30/40 new cases a year withincrease to 70 cases a years in the latest years ofstudy. Age and gender: 71,4 y (32-100),male/female ratio 1.4. Associated pathology:infection 328, heart diseases 249, rheumaticdiseases 211, liver diseases 108, cancer 80,neuropathy 43. Monoclonal proteins: IgG 407,IgM 78, IgD 2, biclonal 16, triclonal 1; no heavychain 21, light chain Kappa 389. Variables (mean):monoclonal component: 14 g/l, ESR 32,5, bonemarrow: 5,9% plasma cells ß2-microglobulin: 2,59 mg/l, albumin: 3,1g/l, bone survey: normal 39,5%. Evolution: transient MGUS 20 cases. Time to disappearance 2,6 months (1,4-4,6). Evolution to malignant gammopathy 24 cases, time to progression 3 years (IC 1,82-4,3).Results. Several factors were associatedçwith malignant transformation: heavy chain IgA (p < 0,002), ESR (p < 0,001), age < 70 (p < 0,05), bone marrow percentage of plasma cells (p < 0,002) y ostheoporosis (p < 0,005). A MGUS follow up model is suggested

Linfoma del manto / Mantle cell lymphoma

El linfoma del manto representa el 7% de los linfomas no Hodgkin del adulto. Se trata de una neoplasia de células B monomorfas de talla pequeña o mediana con núcleo irregular. Las células tumorales expresan fuertemente IgM e IgD, así como los antígenos de clase B. La proteína nuclear ciclina D1 está presente en todos los casos, y es el “gold estándar” para el diagnóstico. La traslocación t(11;14) (q13;q32) en la mayoría de los casos da lugar a un reordenamiento del locus BCL-1 y una sobreexpresión del gen de ciclina D1. La mayoría de los pacientes presentan estadios avanzados. El linfoma del manto es una neoplasia incurable, pero puede ser tratada con diferentes esquemas de quimioterapia (R-Hyper-CVAD, R-CHOP, bortezomib) y los pacientes jóvenes podrían ser sometidos a quimioterapia de alta dosis y trasplante de médula ósea autólogo o alogénico

Mantle cell lymphoma accounts for approximately 7% of adult Non-Hodgkin Lymphomas. It is a neoplasm of monomorphous small to medium-sized B cells with irregular nuclei. The tumor cells express strong IgM and IgD, and B-cell-associated antigens. Nuclear cyclin D1 protein is present in all cases and is the gold standard for the diagnosis. The t(11;14) (q13;q32) in the majority of the cases results in rearrangement of the BCL-1 locus and overexpression of the cyclin D1 gene. Most patients present with disseminated disease. Mantle cell lymphoma is an incurable neoplasm, but it may be treated with different chemotherapy regimen (R-Hyper-CVAD, R-CHOP, bortezomib) and young patients should be considered for high-dose therapy and autologous or allogeneic bone marrow transplantation

Bortezomib induces different apoptotic rates in B-CLL cells according to IgVH and BCL-6 mutations

BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) is a remarkably heterogeneous disorder. Some patients have an indolent disease whereas others undergo a more agressive presentation needing treatment. New therapeutics approaches are necessary for the treatment of B-CLL. Bortezomib (Btz), is a proteasome inhibitor, currently undergoing clinical trials whose function, at least in part, by stabilizing the IkappaBalpha protein and inhibiting NFkappaB activation. OBJECTIVE: The objective of this work was to study the effects of Btz on isolated human B-CLL cells, in vitro, and to correlate the differential rates of apoptosis induction with biological variables. MATERIAL AND METHODS: 31 B-CLL samples, from patients in stage A of Binet were used for this study, and the apoptotic effect of Btz on these cells was measured. RESULTS: Our data show that Btz treatment of B-CLL cells induces apoptosis in a time and dose-dependent manner. The apoptosis induction is mediated in part by inhibition of NFkappaB and is dependent on caspases activation. Interesting, in IgVH mutated cells, Btz have statistically significant differences in their in vitro activity on B-CLL cells according to their BCL-6 mutational status. CONCLUSIONS: Btz is a promising pharmacologic agent for the treatment of B-CLL, but its efficacy seems to be related to IgVH and BCL-6 mutational status, therefore, it could be interesting to further investigate the mechanisms involved in the different behavior of the cells in response to apoptosis induction by this drug (AU)