Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Patrón de Herencia/genética , Leucemia Linfocítica Crónica de Células B/genética , Trastornos Linfoproliferativos/genética , Femenino , Genoma Humano , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Linaje , Polimorfismo de Nucleótido Simple/genética , PronósticoRESUMEN
BACKGROUND: Human papillomavirus (HPV) type 16 is associated with oropharyngeal carcinomas (OPC). Antibodies (Abs) to HPV16 E6 and E7 oncoproteins have been detected in patient sera; however, Abs to other early HPV-derived proteins have not been well explored. METHODS: Antibodies to the HPV16 proteome were quantified using a novel multiplexed bead assay, using C-terminal GST-fusion proteins captured onto Luminex beads. Sera were obtained from untreated patients with OPC (N=40), partners of patients with HPV16+ OPC (N=11), and healthy controls (N=50). RESULTS: Oropharyngeal carcinomas patients with known virus-like capsid particle+ Abs had elevated serum Abs to HPV16 E1, E2, E4, E6, and E7, and L1 antibody levels, but not E5. The ratios of specific median fluorescence intensity to p21-GST compared with controls were E1: 50.7 vs 2.1; E4: 14.6 vs 1.3; E6: 11.3 vs 2.4; E7: 43.1 vs 2.6; and L1: 10.3 vs 2.6 (each P≤0.01). In a validation cohort, HPV16 E1, E2, and E7 antibody levels were significantly elevated compared with healthy control samples (P≤0.02) and partners of OPC patients (P≤0.01). CONCLUSION: Patients with HPV16+ OPC have detectable Abs to E1, E2, and E7 proteins, which are potential biomarkers for HPV-associated OPC.
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Anticuerpos Antivirales/sangre , Biomarcadores de Tumor/sangre , Papillomavirus Humano 16/inmunología , Proteínas Oncogénicas Virales/inmunología , Neoplasias Orofaríngeas/virología , Proteínas E7 de Papillomavirus/inmunología , Proteoma/inmunología , Proteínas Represoras/inmunología , Anciano , Anciano de 80 o más Años , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/diagnósticoRESUMEN
Cutaneous follicular lymphomas (FLs) and cutaneous B-cell lymphomas of extranodal marginal zone (MZL)/mucosal-associated lymphoid tissue (MALT) type may have morphologic overlap, despite the fact that they are thought to be of distinct derivation (germinal center vs. postgerminal center). The problem is compounded by the reported absence of bcl-2 expression by many cutaneous FLs, leading to speculation that cutaneous FL may be unrelated to nodal FL. The authors analyzed the expression of the germinal center-associated antigens bcl-6 and CD10 and of bcl-2 in 18 cutaneous B-cell lymphomas (10 FLs and eight MZLs), in relationship to CD21+ follicular structures, to clarify the relationship of nodal to cutaneous FLs and to explore the value of these antigens in differential diagnosis. The authors studied 10 cutaneous FLs (seven primary and three secondary) and eight MZLs (six primary and two secondary). The FLs (found in six men and four women age 45-75 years) involved the trunk (n = 3) and scalp, face and neck (n = 7). The MZLs (found in five women and three men age 34-81 years) involved the trunk (n = 4), face and neck (n = 2), and arm (n = 2). Immunostaining for CD21, bcl-6, CD10, and bcl-2 allowed the delineation of compartments within the tumors and yielded distinct patterns of staining in FL and MZL. In both follicular and interfollicular/diffuse areas of FL the neoplastic cells were bcl-6+ (10 of 10), often CD10+ (seven of 10, four of seven primary), and bcl-2+ (nine of 10, six of seven primary). Only three of seven cases (one of five primary) had bcl-2 rearrangement detectable by polymerase chain reaction. In the MZLs, the neoplastic B-cells were bcl-6-, CD10-, and bcl-2+ (eight of eight). Three patterns of CD21+ follicles were identified in MZL: reactive germinal centers, uniformly bcl-6+, CD10+, and bcl-2- (five of eight MZLs); colonized follicles, both bcl-6-, bcl-2+, and L26+ cells, and bcl-6+ and bcl-2- cells (five of eight MZLs); and expanded/colonized follicular dendritic cell meshworks, bcl-6- and bcl-2+ B cells with rare residual bcl-6+ and bcl-2- cells (four of eight MZLs). The authors conclude that cutaneous FLs express bcl-6 uniformly, usually express CD10 and bcl-2, and have a follicular pattern similar to nodal FL and consistent with a germinal center origin. The immunophenotype of cutaneous FL is distinct from that of cutaneous MZL, which is negative for bcl-6 and CD10. Colonized follicles in MZL, identified by CD21+ follicular dendritic cell meshworks, contained numerous bcl-6- and bcl-2+ B cells, and were readily distinguished from neoplastic follicles in FL. Conversely, CD21- interfollicular and diffuse areas in FLs contained bcl-6+ and CD10+ cells, which were not seen in diffuse areas of MZLs. Thus, the combination of bcl-2, bcl-6, and CD21 staining is useful for the distinction of cutaneous MZL from cutaneous FL.
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Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B/patología , Linfoma Folicular/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Unión al ADN/análisis , Diagnóstico Diferencial , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/química , Linfoma Folicular/química , Masculino , Persona de Mediana Edad , Neprilisina/análisis , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-6 , Receptores de Complemento 3d/análisis , Neoplasias Cutáneas/química , Factores de Transcripción/análisis , Dedos de ZincRESUMEN
A truly follicular pattern is thought to be restricted to B-cell lymphomas. We observed a prominent follicular growth pattern in three cases of nodal peripheral T-cell lymphomas, of which two were initially diagnosed as follicular lymphomas. All three patients were male, ranged in age from 50 to 70 years, and had generalized lymphadenopathy at the time of diagnosis. The follicles were sharply demarcated in two cases and large and vague in one case; in all cases, they contained abundant follicular dendritic cells. Neoplastic cells were small to medium, with irregular cleaved or round nuclei and clear cytoplasm, which was abundant in one case. Lymphoma cells in all cases were CD4+ CD8- CD57- bcl-6, with CD10 coexpression in 2 cases. Clonal rearrangement of the gamma chain of the T-cell receptor gene was demonstrated in each case. These cases expand the differential diagnosis of lymphomas with a follicular growth pattern and suggest that neoplastic T cells may have the capacity to induce or home to follicular structures.
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Antígenos CD4/metabolismo , Proteínas de Unión al ADN/metabolismo , Linfoma Folicular/patología , Linfoma de Células T Periférico/patología , Proteínas Proto-Oncogénicas/metabolismo , Factores de Transcripción/metabolismo , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Antígenos CD8/metabolismo , Células Clonales , ADN de Neoplasias/análisis , Células Dendríticas/metabolismo , Células Dendríticas/patología , Diagnóstico Diferencial , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Técnicas para Inmunoenzimas , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Linfoma Folicular/genética , Linfoma Folicular/inmunología , Linfoma Folicular/metabolismo , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/inmunología , Linfoma de Células T Periférico/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neprilisina/metabolismo , Fenotipo , Proteínas Proto-Oncogénicas c-bcl-6RESUMEN
Genetic markers for leukemias and lymphomas include chromosomal translocations and antigen-receptor gene rearrangements. Clonal rearrangements of immunoglobulin or T cell receptor (TCR) genes reflect clonal proliferations of lymphocytes, a characteristic feature of lymphoid neoplasia. These rearrangements can be detected as described in this unit by Southern blot hybridization or, in many instances, the polymerase chain reaction (PCR). Specific chromosomal translocations can also serve as markers for clonality, for malignant transformation, and for various defined subtypes of hematopoietic cancers. PCR protocols are described for detection of the two most commonly assayed translocations, t(9;22) of chronic myelogenous leukemia or acute lymphoblastic leukemia, and t(14;18) of follicular lymphomas.
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ADN de Neoplasias/genética , Leucemia/metabolismo , Linfoma no Hodgkin/genética , Reordenamiento Génico , Genética Médica , Humanos , Leucemia/inmunología , Linfoma no Hodgkin/inmunología , Reacción en Cadena de la Polimerasa , Translocación GenéticaRESUMEN
The most common hereditary hypercoaguable states are factor V(Leiden) (FVL) and prothrombin mutations (PRO). FVL and PRO present with an incidence of approximately 5% in a heterogeneous population, and 45% to 63% of the thrombophilic population. The frequency of these mutations in the fetal population and their clinical importance is unknown. Fetal side thromboembolic events (FST) include congenital stroke and renal vein thromboses. In some cases, FST can be diagnosed by placental histopathology when avascular (infarcted) villi are present in a patent maternal vascular space. FST can present as placenta-fetal-vascular or fetal-visceral-vascular lesions. Causes include vascular damage from cord compression or inflammation, but most remain unclear. Potential causes of FST include FVL and PRO. We describe the incidence of FVL and PRO from a prospective group of 169 consecutive placentas and in a retrospective group of archived placentas diagnosed with placental FST. One each of FVL and PRO heterozygosity was found in the prospective set (< 1% incidence for each). Five prospective placentas were diagnosed with placental FST, for an incidence of 3%; all were wild-type for FLV and PRO. Twenty-seven of 65 archived FST cases had analyzable DNA to find 5 FVL heterozygotes (18.5%); all were wild-type for PRO. Twenty-one of 65 retrospective archived controls analyzable found 1 case of FVL heterozygosity (< 5%). We find that the frequency of FVL and PRO may be decreased in the pregnant population but increased in cases of placental FST. Because factor V Leiden heterozygosity carries an increased risk for thrombotic complications, we suggest placental diagnosis of fetal side thromboemboli warrants clinical evaluation for FVL in infant and potentially the parents.
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Factor V/genética , Frecuencia de los Genes , Enfermedades Placentarias/genética , Mutación Puntual/genética , Protrombina/genética , Tromboembolia/genética , Adolescente , Adulto , ADN/análisis , Análisis Mutacional de ADN , Cartilla de ADN/análisis , Femenino , Edad Gestacional , Humanos , Masculino , Massachusetts/epidemiología , Enfermedades Placentarias/patología , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , Tromboembolia/patología , Cordón Umbilical/químicaRESUMEN
Tumor growth is dependent on the balance between cell proliferation and cell death, and these events occur heterogenously within an individual tumor. We present a methodology that provides integrative information about cell kinetics, cell death, and cell growth within individual tumors in animals treated with cytotoxic chemotherapeutic agents. Using HCT-116 and NCI-H460 cells, human colonic adenocarcinoma and non-small cell lung cells, respectively, traditional xenograft studies were performed. The tumor-bearing animals were treated with cyclophosphamide (Cytoxan), gemcitabine (Gemzar), or mitomycin C, and extensive analysis of the tumors was studied. Cell kinetics were evaluated by measuring the apoptotic and proliferation indices. The ability to image an entire tumor section using "tiling" by creating a large montage from many high-resolution images makes it possible to identify regional differences within areas of tumor and to demonstrate differences in these tumor regions after treatment with selected chemotherapeutic agents. Two specific areas within tumors have been identified: (a) areas of viable cells within the cell cycle, determined by bromodeoxyuridine and/or morphological characteristics determined by hematoxylin staining; and (b) areas of necrosis determined by the absence of bromodeoxyuridine and proliferating cell nuclear antigen-labeled cells coupled with morphological changes. By standardizing the tumor size to 100 mm2, different patterns of tumor responses to chemotherapeutic agents were determined. By creating such tiled images and by quantitating cell cycle kinetics, it is possible to gain a more complete understanding of tumor growth and response to treatment, leading to the development of more reliable methods for assessing the clinical behavior of anticancer drugs.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , División Celular/efectos de los fármacos , División Celular/fisiología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Ciclofosfamida/farmacología , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Mitomicina/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
BACKGROUND: This report describes a 16-year-old patient with gastric rugal hypertrophy caused by a primary gastric plasmacytoma. She had a 3-month history of nausea and burning abdominal pain. Radiographic studies showed giant rugal hypertrophy. Superficial endoscopic gastric biopsies showed mild inflammation with plasma cells of polyclonal origin in the mucosa. When symptoms persisted, she underwent laparoscopic full-thickness gastric biopsy. There was monoclonal plasma cell infiltration histologically diagnostic of plasmacytoma and inconsistent with Helicobacter pylori-associated mucosa-associated lymphoid tissue (MALT) lymphoma. There was no evidence for involvement of the bone marrow or regional lymph nodes. The tumor did not respond to radiotherapy, necessitating total gastrectomy. METHODS: Blood samples were analyzed for interleukin (IL)-6 by enzyme-linked immunosorbent assay. Gastric biopsy and gastrectomy specimens were subjected to immunophenotyping for kappa and lambda light chains, CD45, CD20, and LN1 and to polymerase chain reaction analysis for herpes virus HHV8. RESULTS: There was no elevation in circulating IL-6 levels, militating against a pathogenesis akin to that of Castleman's disease. There was no evidence for infection with the Kaposi's sarcoma-associated herpes virus HHV8, which has recently been found in patients with multiple myeloma. CONCLUSIONS: This diagnosis and the characteristics of the tumor are very unusual, if not unique, for a patient of this age. The diagnostic evaluation of this patient also demonstrates the importance of deep endoscopic or full-thickness biopsies in some children with hypertrophic gastritis.
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Gastritis Hipertrófica/etiología , Plasmacitoma/complicaciones , Neoplasias Gástricas/complicaciones , Adolescente , Biopsia , Endoscopía del Sistema Digestivo , Femenino , Gastritis Hipertrófica/patología , Humanos , Plasmacitoma/patología , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Transfusion of cells harvested from patients with chronic myelogenous leukemia (CML) as a therapeutic measure for patients with granulocytopenia was popular in the 1970s, when studies examining the persistence of transfused donor cells were limited by a lack of molecular techniques. Blood samples from a patient who recently received an inadvertent transfusion of CML cells were evaluated for the presence of the bcr/abl translocation characteristic of CML. CASE REPORT: The patient, a 67-year-old man with a history of congestive heart failure, myocardial infarct, hypertension, diabetes mellitus, and chronic renal failure, was transfused for bleeding from colonic angiodysplasia. A volunteer blood donor reported that he had been diagnosed with CML 10 days after his donation. Three days after the donation, blood components from the donor with CML had been administered to the patient as nonirradiated red cells and platelets. Evaluation of donor blood by a reverse-transcriptase polymerase chain reaction showed the b3a2 transcript, indicating a bcr/abl translocation. Periodic testing of the patient's peripheral blood by the same technique demonstrated the presence of the b3a2 transcript on Days 74 and 75 after transfusion. The patient died of congestive heart failure 8 months after the transfusion. CONCLUSION: In this rare case of accidental transfusion of neoplastic cells, the findings document the persistence of the donor's neoplastic clone in the recipient for 75 days.
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Donantes de Sangre , Genes abl , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Proteínas Oncogénicas/genética , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Reacción a la Transfusión , Translocación Genética , Anciano , Humanos , Masculino , Proteínas Proto-Oncogénicas c-bcr , Factores de TiempoRESUMEN
OBJECTIVE: To compare functional and molecular biological tests for resistance to activated protein C (APC)/factor V R506Q, the most common cause of familial thrombosis. METHODS: We developed functional and molecular biological tests for resistance to APC/factor V R506Q at our institution and correlated the results for 370 patients studied by both methods. The functional method is based on addition of exogenous APC to an activated partial thromboplastin time-based assay. The molecular biological method is based on polymerase chain reaction followed by endonuclease digestion. RESULTS: Considering the molecular biological test as definitive for detecting the factor V R506Q mutation, the sensitivity of the functional assay was 100%, and the specificity was 74%. The prevalence of the factor V mutation in the population studied was 12% (41 heterozygotes, two homozygotes), and the positive predictive value of the functional assay was 34%. Although a normalized sensitivity ratio (nAPC-SR) less than 0.84 is considered evidence of resistance to APC by functional testing, we found that all patients with factor V R506Q had an nAPC-SR less than or equal to 0.71. When this alternative positive cutoff was used, the specificity of the functional test for factor V R506Q increased to 87%, and the positive predictive value increased to 52%, which constituted a significant improvement. We compared clinical findings from patients with resistance to APC with or without the presence of factor V R506Q, and found that as a group, those with factor V R506Q had a higher incidence of hypercoagulability, but fewer additional risk factors for hypercoagulability. The mechanism of resistance to APC in factor V R506Q-negative individuals is unclear, but may be related to other risk factors for hypercoagulability. CONCLUSIONS: The functional assay for resistance to APC is an excellent screening test for factor V R506Q, but confirmatory molecular biological testing is necessary when the functional test is positive, because of the high false-positive rate.
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Trastornos de la Coagulación Sanguínea/genética , Análisis Mutacional de ADN , Resistencia a Medicamentos , Factor V/genética , Mutación Puntual , Proteína C/farmacología , Adulto , Anciano , Trastornos de la Coagulación Sanguínea/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina ParcialRESUMEN
BACKGROUND: An unusual case of a peripheral T-cell lymphoma of T gamma/delta hepatosplenic type (Tgamma/deltaHSL) that arose in a child 5 years after she received a heart transplant and 9 months after she developed Epstein-Barr virus (EBV) positive, B-cell lymphoid hyperplasia involving the tonsils is presented. The majority of the reported cases of Tgamma/deltaHSL have been described in young adult men without antecedent immunodeficiency; several well documented cases of Tgamma/deltaHSL in the posttransplant setting have been described previously, but none has been described in a child (or an adult) with a previously diagnosed EBV+ B-cell lymphoid hyperplasia. METHODS: Standard histologic, immunohistochemical, flow cytometric, and molecular genetic techniques were used in the evaluation of diagnostic material. RESULTS: The patient's Tgamma/deltaHSL involved the spleen in a predominantly cordal pattern, and infiltrated the liver in an exclusively sinusoidal distribution. Bone marrow involvement was focal and interstitial. In all locations, malignant cells were of intermediate or large size and had oval nuclei with coarse chromatin, with a scant or moderate amount of eosinophilic cytoplasm. This Tgamma/deltaHSL expressed the characteristic CD2+, CD3+, [CD4- CD8-], Tdelta1+ phenotype, and malignant cells also expressed the natural killer cell marker CD56. Cytogenetic studies demonstrated isochromosome 7q with the addition of trisomy 8 as the tumor progressed. Southern blot analysis demonstrated clonal rearrangements of the gamma, delta, and beta loci of the T-cell receptor but did not identify EBV DNA within the tumor cells. CONCLUSIONS: This case highlights the fact that a full range of lymphoid proliferations is possible in the posttransplantation period, and that a prior diagnosis of a B-cell disorder does not preclude the development of a subsequent T-cell posttransplant lymphoproliferative disorder (PTLD), which should be formally evaluated, especially if clinical circumstances appear atypical for a PTLD of the "usual" (EBV-related, B-cell) type.
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Trasplante de Corazón/efectos adversos , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4/patogenicidad , Neoplasias Hepáticas/virología , Linfoma de Células T Periférico/virología , Trastornos Linfoproliferativos/virología , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Neoplasias del Bazo/virología , Infecciones Tumorales por Virus/complicaciones , Antígenos CD/análisis , Preescolar , ADN Viral/análisis , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Linfoma de Células T Periférico/etiología , Linfoma de Células T Periférico/genética , Trastornos Linfoproliferativos/complicaciones , Tonsila Palatina/patología , Tonsila Palatina/virología , Neoplasias del Bazo/etiología , Neoplasias del Bazo/genéticaRESUMEN
PURPOSE: The prevalence of activated protein C resistance (APCR) and associated thrombotic morbidity among patients who undergo arterial reconstruction were investigated. METHODS: Preoperative assays for functional APCR and factor V (Leiden) mutation were performed on 262 patients who underwent arterial reconstructions that consisted of cerebrovascular surgery (109), aortic or iliofemoral procedures (76), or infrainguinal bypass procedures (77). Patients were monitored for thrombotic complications during the postoperative period. RESULTS: Depending on the stringency of the definition used, functional APCR was detected in 10.6% to 22.0% of patients tested. Factor V (Leiden) was found in 5.3% of patients. Thrombotic morbidity consisting of myocardial infarction, cerebrovascular event, or graft thrombosis occurred in 9.9% of patients, who were followed-up for a mean of 4.8 months. No significant overall correlations were found between APCR and thrombotic morbidity. Subgroup analysis revealed significant associations between functional APCR and total early postoperative thrombotic complications and early graft failure, and between factor V (Leiden) and early cerebrovascular events and late graft thrombosis (p < 0.03). CONCLUSIONS: Functional APCR is somewhat more prevalent among general vascular surgical patients than in the general population, but factor V (Leiden) is no more prevalent. APCR is not a prominent cause of thrombotic morbidity in contemporary vascular surgery. Nonetheless, it is a sufficiently important potential contributor to morbidity among some subgroups to warrant selective testing and directed therapy pending further study.
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Complicaciones Posoperatorias/sangre , Proteína C/metabolismo , Trombosis/sangre , Procedimientos Quirúrgicos Vasculares , Factor V/genética , Oclusión de Injerto Vascular/sangre , Oclusión de Injerto Vascular/epidemiología , Humanos , Morbilidad , Mutación , Complicaciones Posoperatorias/epidemiología , Prevalencia , Estudios Prospectivos , Proteína C/fisiología , Trombosis/epidemiologíaRESUMEN
T-cell blast crisis in chronic myelogenous leukemia is rare. We examined three patients (ages 35 to 72 years) in whom T-cell blast crisis developed 11 to 36 months (mean, 25 months) after diagnosis of chronic myelogenous leukemia and who died 4 to 12 months (mean, 7 months) thereafter. Two patients had diffuse lymphadenopathy, and the third had marked lymphocytosis (white blood cell count 217,000/microL, with 90% circulating blasts). In all three patients, neoplastic cells had the appearance of lymphoblasts and were immunoreactive for T-cell markers by immunohistochemical or flow cytometric analysis or both. Molecular diagnostic studies revealed the presence of a bcr-abl oncogene rearrangement in all three cases, but none exhibited a clonal T-cell receptor delta, beta, or gamma chain gene rearrangement. One case exhibited deletion of the J delta 1 region of both delta chain genes. The significance of these findings is discussed, and they are compared with those of other reported cases of T-cell blast crisis in chronic myelogenous leukemia.
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Crisis Blástica/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Activación de Linfocitos , Linfocitos T/patología , Adulto , Anciano , Biopsia , Crisis Blástica/etiología , Resultado Fatal , Femenino , Citometría de Flujo , Proteínas de Fusión bcr-abl/genética , Humanos , Inmunohistoquímica , Inmunofenotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/etiología , Ganglios Linfáticos/química , Ganglios Linfáticos/patología , MasculinoRESUMEN
T cells expressing the gamma delta T cell receptor have been implicated in anti-Epstein-Barr virus (EBV) immunity and in the pathogenesis of autoimmune diseases of the central nervous system. However, they have never been isolated from human brain tissue for direct analysis. We now report a 6-year-old girl with EBV-associated posttransplantation lymphoproliferative disease involving inflammatory brain lesions. A high proportion of gamma delta T cells was found in the blood and in a brain lesion. Cultured T cell lines were found to have a remarkably high frequency of responsiveness to an EBV-transformed line, with a 17-fold enrichment in the brain lesion. These T cells expressed predominantly the gamma delta T cell receptor and mediated non-MHC-restricted cytotoxicity against EBV-infected target cells. These results provide the first demonstration of an association of gamma delta T cells with a posttransplantation lymphoproliferative disease and suggest a role of gamma delta T cells in mediating inflammatory processes in the brain.
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Encefalopatías/inmunología , Infecciones por Herpesviridae/inmunología , Herpesvirus Humano 4 , Trasplante de Hígado/inmunología , Trastornos Linfoproliferativos/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos B/inmunología , Biopsia , Southern Blotting , Encefalopatías/virología , Niño , Citotoxicidad Inmunológica , ADN/análisis , Femenino , Antígenos HLA/inmunología , Infecciones por Herpesviridae/sangre , Humanos , Trasplante de Hígado/efectos adversos , Ganglios Linfáticos/patología , Trastornos Linfoproliferativos/sangre , Trastornos Linfoproliferativos/virologíaRESUMEN
Primary lymphoma of the colon, a rare and typically late complication of ulcerative colitis, exhibits high-grade morphology and behavior when it occurs. Recently, several reports of colonic lymphoma masquerading as ulcerative colitis have been described. These previous reports described inflammatory mucosal changes typical of ulcerative colitis as being present in superficial biopsies, leading to the initial diagnosis of ulcerative colitis; however, further workup resulted in a diagnosis of primary colonic lymphoma within several months in these cases, and all symptoms and mucosal changes resolved after treatment of the lymphoma. Herein we report a case of mantle cell lymphoma arising in the colon and rectum in a 71-year-old woman with a 4-year history of ulcerative colitis. Immunoglobulin heavy-chain gene rearrangements were detected using the polymerase chain reaction procedure in fixed tissue in the lymphoma as well as in a prior resection specimen that histologically appeared to show only changes of severe ulcerative colitis. This finding suggests that an indolent lymphoid proliferation may have been the underlying disease in this patient and raises questions about the role of colonic lymphoma in causing mucosal injury.
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Linfocitos B/patología , Colitis Ulcerosa/patología , Neoplasias del Colon/patología , Linfoma no Hodgkin/patología , Células Madre/patología , Anciano , Secuencia de Bases , Células Clonales , Neoplasias del Colon/química , Neoplasias del Colon/genética , Femenino , Humanos , Inmunohistoquímica , Linfoma no Hodgkin/genética , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
Posttransplant lymphoproliferative disorders (PTLD) are EBV-associated lymphoid neoplasms that are caused by the uncontrolled growth of EBV-infected B lymphocytes. The clinical presentation of PTLD can range from benign polygonal lymphoproliferative disorders to aggressive monoclonal immunoblastic lymphomas. In this report, we describe a seronegative lung transplant recipient who developed an immunoblastic lymphoma 4 months after lung transplantation from a seropositive donor. The neoplastic cells expressed B lymphocyte markers (CD19+, CD20+, sIgM+, kappa+) as well as the EBV antigen EBNA-2. A cell line with similar cytologic features spontaneously grew from in vitro cultures of the patient's peripheral blood mononuclear cells. The cell line and the lymphoma were EBV+, expressed a similar spectrum of B cell surface proteins, and had the donor's HLA haplotype. Analysis of immunoglobulin gene rearrangements and viral terminal repeat sequences revealed that the cell line and the tumor represented distinct B cell clones. Cultured peripheral blood mononuclear cells were restimulated in vitro with the EBV transformed cell line and tested for cytolytic activity. The host T cells demonstrated high levels of cytolytic activity against the tumor cell line that was abrogated by the addition of a anti-monomorphic HLA class I monoclonal antibody (mAb) (W6/32). These studies indicate that cells of donor origin can persist in the transplanted organ and may lead to an EBV-associated posttransplant lymphoma.
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Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/inmunología , Linfoma Inmunoblástico de Células Grandes/etiología , Linfoma Inmunoblástico de Células Grandes/inmunología , Anticuerpos Monoclonales/farmacología , Linfocitos B/patología , Transformación Celular Viral , Células Cultivadas , ADN Viral/análisis , Haplotipos , Herpesvirus Humano 4/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Activación de Linfocitos , Linfoma Inmunoblástico de Células Grandes/patología , Fenotipo , Linfocitos T Citotóxicos/inmunología , Células Tumorales CultivadasRESUMEN
Telepathology affords the means to provide pathological diagnosis and consultation to remote sites. However, before telepathology can become an acceptable medical tool, it will be vital to determine the diagnostic accuracy of this technology. We report the results of a single-blind study of the accuracy of diagnosis performed using computerized still images obtained from a telepathology workstation used in a French telepathology network. Four pathologists, each working alone, reviewed a total of 200 cases of routine surgical pathology (50 cases each), and performed diagnosis based on both computer CD-ROM still images (CD) and conventional glass slides (GS). Concordance between GS and CD diagnosis, as well as accuracy, were determined. Other factors related to performance were also measured, including diagnostic certainty, reasons for uncertainty, and causes of diagnostic error. Overall, there was good agreement between CS and CD diagnosis. There was 87.5% concordance between CS and CD diagnosis, and comparison to consensus (correct) diagnosis showed accuracy of 95.5% and 88.5% for GS and CD diagnosis, respectively. Marked variability in accuracy of CD diagnosis was observed among the four pathologists, and issues related to image selection and/or quality appeared responsible for 60% of the diagnostic errors. The lack of sufficient images and clinical information were frequently cited as reasons for diagnostic uncertainty, as well as feelings of insufficient expertise. It is likely that the opportunity for interaction with the referring pathologist and the use of subspecialty consultants would likely improve the performance of telepathology.
Asunto(s)
Diagnóstico , Telepatología/normas , CD-ROM , Errores Diagnósticos , Estudios de Evaluación como Asunto , Humanos , Cooperación Internacional , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Método Simple Ciego , Telepatología/instrumentación , Telepatología/métodosRESUMEN
Pulmonary chondroid hamartomas (PCH) are benign tumors that contain mesenchymal and epithelial components. In this series, we identified clonal chromosome aberrations in mesenchymal cells from 10 of 17 PCH. Chromosome band 12q15 was rearranged most frequently (N = 4), and one case had a t(12;14)(q15;q24) that was identical cytogenetically to the characteristic translocation in uterine leiomyomas. Histologic review revealed diverse mesenchymal populations, including undifferentiated cells, cartilage, adipose tissue, and smooth muscle, in most of the PCH. These findings suggest that PCH result from neoplastic transformation of a primitive mesenchymal cell that differentiates along chondroid, adipose, and smooth muscle pathways.
Asunto(s)
Hamartoma/genética , Enfermedades Pulmonares/genética , Adulto , Anciano , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Aberraciones Cromosómicas , Bandeo Cromosómico , Femenino , Hamartoma/patología , Humanos , Leiomioma/genética , Lipoma/genética , Enfermedades Pulmonares/patología , Masculino , Mesodermo/patología , Persona de Mediana Edad , Neoplasias Uterinas/genéticaAsunto(s)
Artritis/patología , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/patología , Anciano , Aorta Torácica/diagnóstico por imagen , Artritis/diagnóstico por imagen , Biopsia , Femenino , Mano/diagnóstico por imagen , Humanos , Ganglios Linfáticos/patología , RadiografíaRESUMEN
An unusual case of small lymphocytic non-Hodgkin's lymphoma of suppressor/cytotoxic T-cell phenotype is described. The patient presented with significant involvement of the spleen, lymph nodes, and bone marrow, but without a leukemic phase. Most small lymphocytic lymphomas are of B-cell phenotype, and those of T-cell origin are overwhelmingly of T-helper/inducer phenotype. Furthermore, T-cell lymphoproliferative lesions of suppressor/cytotoxic phenotype generally present as leukemias comprising large granular lymphocytes. This case reveals that suppressor/cytotoxic T lymphocytes may give rise to a lymphoproliferative disorder with a distinctive phenotype and presentation.