RESUMEN
B-cell chronic lymphocytic leukemia (CLL) accounts for 95% of chronic leukemia cases and 25% of all leukemia. Despite the prevalence of CLL, progress in its treatment has been only modest over the past three decades. Based upon the ability of fludarabine to produce high-grade remissions especially among patients with low initial tumor mass, and the ability of alkylators to reduce tumor mass, we hypothesized that sequential administration of a limited number of cycles of intermediate-dose cyclophosphamide followed by fludarabine could result in a larger percentage of patients with complete remissions (CRs). In all, 27 of the 49 eligible patients achieved overall responses of CR, unconfirmed complete remission (UCR), or PR, for a total response rate of 55% (95% confidence interval (CI) 40-69%). Considering the confounding medical issues of this patient population with advanced aggressive disease, the regimen was generally well tolerated. This study demonstrates that high-dose cyclophosphamide followed by fludarabine was relatively well tolerated in this group of advanced CLL patients. The study's criterion for testing whether the regimen is sufficiently effective to warrant further investigation was met: 14 (32%) of the first 44 eligible patients achieved CR or UCR.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
This article describes a case of nodular fasciitis with the karyotype 47,XY,+4/46,XY,add(15)(p11.2), t(16;16)(p13.3;p11.2). The presence of clonal chromosomal abnormalities in this case, as well as in three previously reported cases, indicates that nodular fasciitis is a benign neoplasm and not a reactive lesion.
Asunto(s)
Cromosomas Humanos Par 15/ultraestructura , Cromosomas Humanos Par 16/ultraestructura , Fascitis/patología , Fibroblastos/ultraestructura , Neoplasias de los Tejidos Blandos/patología , Transformación Celular Neoplásica , Bandeo Cromosómico , Cromosomas Humanos Par 3/ultraestructura , Células Clonales/ultraestructura , Fascitis/clasificación , Fascitis/genética , Traumatismos de la Mano/patología , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Neoplasias de los Tejidos Blandos/clasificación , Neoplasias de los Tejidos Blandos/genética , Cicatrización de HeridasRESUMEN
We describe a case of botryoid rhabdomyosarcoma with the karyotype 53,XX,+2,+5,+8,+12,+13, i(17)(q10),+19,+20. Only two cytogenetically analyzed cases of this tumor were previously reported and structural chromosomal abnormalities in each tumor were different.
Asunto(s)
Aberraciones Cromosómicas/genética , Cromosomas Humanos Par 17/genética , Isocromosomas/genética , Rabdomiosarcoma/genética , Neoplasias Vaginales/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas/patología , Trastornos de los Cromosomas , Análisis Citogenético , Femenino , Humanos , Pronóstico , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/patología , Neoplasias Vaginales/tratamiento farmacológico , Neoplasias Vaginales/patologíaRESUMEN
We describe a case of low-grade myxofibrosarcoma with the karyotype 46,XX,t(2;15)(p23;q21.2), del(7)(q?11.2q?22). Only six of these tumors have been previously studied and all were cytogenetically different.
Asunto(s)
Cromosomas Humanos Par 15 , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 7 , Fibrosarcoma/genética , Eliminación de Gen , Translocación Genética , Anciano , Neoplasias Óseas/secundario , Neoplasias Óseas/cirugía , Mapeo Cromosómico , Femenino , Fibrosarcoma/patología , Fibrosarcoma/secundario , Fibrosarcoma/cirugía , Humanos , Cariotipificación , Neoplasias de los Músculos/secundario , Neoplasias de los Músculos/cirugía , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaRESUMEN
A case of sclerosing epithelioid fibrosarcoma was studied. The tumor cells expressed vimentin, focally epithelial membrane antigen and CD34, contained cisternae of rough endoplasmic reticulum, large Golgi apparatus, many pinocytotic vesicles, and were devoid of basal lamina. Their composite karyotype was 45,Y,t(X;6)(q13;q15), t(6;13)(p11.2;q13),-22¿2/46,Y,t(X;6)(q13;q15),add(13)(p12), add(22)(q13)¿3/44 approximately 46,der(X)t(X;6)(q13;q21),-Y, t(13;14)(q10;q10),-22,add(22)(q13)¿7/46,XY¿8.
Asunto(s)
Fibrosarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Antígenos CD34/análisis , Biomarcadores de Tumor/análisis , Cromosomas Humanos Par 12/genética , Células Clonales , Fibrosarcoma/química , Fibrosarcoma/clasificación , Fibrosarcoma/inmunología , Amplificación de Genes , Humanos , Cariotipificación , Antígeno Ki-67/análisis , Pierna , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Neoplasias de los Tejidos Blandos/química , Neoplasias de los Tejidos Blandos/inmunología , Transactivadores/genéticaRESUMEN
A case of malignant rhabdoid tumor of the liver associated with hypercalcemia of malignancy was studied. The karyotype of the liver primary was 46,XY,t(8;13)(q24.2;q33)[7]/46,XY[13], and of the brain metastasis 46,XY,t(8;13)(q24;q33)[5]/46,XY,t(7;13)(p14;q22) [3]/46,XY,t(1;2;3)(q25;q21;p21) [2]/46,XY[13], respectively. Band 8q24 was previously reported to be rearranged in two malignant rhabdoid tumors, one renal and one hepatic.
Asunto(s)
Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 8/genética , Neoplasias Hepáticas/genética , Tumor Rabdoide/genética , Translocación Genética/genética , Humanos , Hipercalcemia/complicaciones , Lactante , Cariotipificación , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Tumor Rabdoide/complicaciones , Tumor Rabdoide/patología , Tumor Rabdoide/terapiaRESUMEN
A solitary fibrous tumor of the pleura was studied. Its karyotype was 46,XY,t(6;17) (p11.2;q23),ins(9;12)(q22;q15q24.1),inv(16)(p13.1q24). The rearrangement of 12q13-15 was also described in a subset of hemangiopericytomas of soft tissue and meninges. Because both types of tumors are morphologically and immunophenotypically quite similar, and because some of them share rearrangement of 12q13-15, the possibility of their histogenetical relatedness should be considered.
Asunto(s)
Aberraciones Cromosómicas , Fibroma/genética , Neoplasias Pleurales/genética , Anciano , Antígenos CD34/metabolismo , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 17 , Cromosomas Humanos Par 6 , Colágeno/metabolismo , Fibroma/patología , Fibroma/cirugía , Reordenamiento Génico , Humanos , Masculino , Neoplasias Pleurales/patología , Neoplasias Pleurales/cirugía , Translocación Genética , Vimentina/metabolismoAsunto(s)
Cromosomas Humanos Par 17 , Cromosomas Humanos Par 22 , Dermatofibrosarcoma/genética , Neoplasias Cutáneas/genética , Translocación Genética , Adulto , Mapeo Cromosómico , Dermatofibrosarcoma/patología , Dermatofibrosarcoma/ultraestructura , Femenino , Humanos , Metafase , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/ultraestructuraRESUMEN
We identified seven patients with hematologic disorders and trisomy 6 as the sole karyotypic aberration in bone marrow aspirates or unstimulated peripheral blood. Five patients were male and two were female; all were adults with ages ranging from 22 to 74 years. Three of the seven patients presented with manifestations of peripheral cytopenia. Their bone marrows were hypocellular with slight or no dysplastic changes and without an increase in blasts. One of these patients subsequently developed acute myeloid leukemia (AML-M1). The four remaining patients were initially diagnosed with AML--three consistent with French-American-British classification of M1 and M4 in the fourth patient. These results suggest that trisomy 6 is a nonrandom primary numerical anomaly of myeloid disorders. The association of cytopenia and hypoplastic bone marrow with trisomy 6 may constitute a new, distinctive variant among myelodysplastic syndromes.
Asunto(s)
Cromosomas Humanos Par 6 , Enfermedades Hematológicas/genética , Trisomía , Adulto , Anciano , Médula Ósea/patología , Femenino , Enfermedades Hematológicas/patología , Humanos , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Masculino , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Preleucemia/genética , Preleucemia/patologíaAsunto(s)
Aberraciones Cromosómicas/genética , Cromosomas Humanos Par 15/genética , Fibroma/genética , Neoplasias Cardíacas/genética , Músculos Papilares/patología , Aberraciones Cromosómicas/patología , Trastornos de los Cromosomas , Fibroma/patología , Neoplasias Cardíacas/patología , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Infarto del Miocardio/genética , Infarto del Miocardio/patologíaRESUMEN
A pigmented choroid plexus carcinoma was studied. The pigment was Fontana-positive, and the neoplastic cells focally expressed melanosomal marker HMB45 and contained probable aberrant melanosomes. The tumor was composed of two pseudodiploid clones, having the karyotypes 46,XY,inv(4)(q12q35),t(6;15)(q21;q22),inv(7)(p11.2q22),t(19; 22) (q13.4;q11.2)[15]/46,XY,t(4;14)(q31.1; p11.2),t(12;13)(p11.1;q34)[6]. The available data seem to indicate that rearrangements of 7p11-12, 9q11-12, 15q22, and 19q13.4 may play a role in the development of choroid plexus carcinomas.
Asunto(s)
Carcinoma/genética , Neoplasias del Plexo Coroideo/genética , Carcinoma/ultraestructura , Niño , Neoplasias del Plexo Coroideo/ultraestructura , Humanos , Cariotipificación , Masculino , Microscopía ElectrónicaRESUMEN
OBJECTIVE: Although most methods for selecting the sex of offspring by sorting spermatozoa are ineffective at shifting the ratio of Y- to X-containing cells, some commercial sources continue to offer such services. Our objective was to evaluate commercially "sorted" samples with use of dual-color fluorescence in situ hybridization and to identify variations in assessment by comparing motile and total sperm populations, donors, observers, and fluorescence in situ hybridization probes. STUDY DESIGN: Cryopreserved sperm from seven anonymous donors were processed as for insemination. Sperm cells from each total sample or motile subfraction were prepared for fluorescence in situ hybridization by incubation with disulfide-reducing agents to expand sperm nuclei. Two sets of X and Y chromosome-specific, fluorophore-labeled deoxyribonucleic acid probes were used. At least 400 nuclei from each preparation were classified independently by three blinded observers. Hybridization efficiency, aneuploidy, and sex chromosome content were evaluated in subsets of five unsorted, five female-oriented, and five male-oriented samples. Total and motile subfractions were compared with eight samples. Fluorescence in situ hybridization probes were compared in five paired unsorted samples. RESULTS: No differences were detected between washed samples and paired motile subfractions. No differences in hybridization and aneuploidy were detected between groups of sorted samples. The Y/X ratio was significantly different between the sorted groups. However, male-oriented samples had a lower Y/X ratio than female-oriented samples did. Observer and probe choice accounted for small but significant variations that did not alter conclusions about the X/Y ratio for sorted samples. CONCLUSION: In a series of 10 sorted samples from one commercial source, dual-color fluorescence in situ hybridization demonstrated a small but significant shift in the sex chromosome ratios among samples. However, this shift was opposite to that expected by the orientation of the sorted samples.
Asunto(s)
Hibridación Fluorescente in Situ/métodos , Cromosomas Sexuales/ultraestructura , Preselección del Sexo , Espermatozoides/ultraestructura , Análisis de Varianza , Criopreservación , ADN/análisis , ADN/genética , Sondas de ADN , Humanos , Masculino , Preservación de Semen , Recuento de Espermatozoides , Motilidad Espermática/fisiología , Espermatozoides/química , Espermatozoides/citología , Cromosoma X/ultraestructura , Cromosoma Y/ultraestructuraRESUMEN
Chromosomal cytogenetic abnormalities are common in tumor cells and are often the basis for more detailed chromosomal mapping of tumor suppressor and oncogenes. Chromosome 11 abnormalities are frequently recognized in various neoplasms. We report a case of Bowen disease (squamous cell carcinoma in situ) of the vulva with an isolated 11p cytogenetic abnormality. A chromosome 11 paint confirmed two copies of chromosome 11 in all analyzed metaphases. An 11p subtelomeric probe confirmed an abnormality of 11p15-->pter indicative of a deletion. Previous studies of invasive vulvar cancers also frequently show 11p cytogenetic abnormalities, but never as an isolated finding. The patient suffered from other diseases that may also be related to this locus. Breakage and p53 studies were normal. It is possible that an 11p abnormality in Bowen's disease is a precursor in the evolution of invasive vulva cancer.
Asunto(s)
Enfermedad de Bowen/genética , Aberraciones Cromosómicas/genética , Cromosomas Humanos Par 11/genética , Neoplasias Cutáneas/genética , Neoplasias de la Vulva/genética , Enfermedad de Bowen/patología , Trastornos de los Cromosomas , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Neoplasias de la Vulva/patologíaRESUMEN
A case of mesenchymal chondrosarcoma was studied. The tumor was near-tetraploid and the clonal structural chromosomal abnormalities included add(7)(p13), add(22)(q13), markers, and double minutes. The ultrastructural and immunohistochemical findings were consistent with the diagnosis. Strong immunoreactivity for desmin was an unusual, not previously reported, feature of the neoplasm.
Asunto(s)
Neoplasias Óseas/genética , Condrosarcoma Mesenquimal/genética , Neoplasias Óseas/patología , Neoplasias Óseas/ultraestructura , Condrosarcoma Mesenquimal/patología , Condrosarcoma Mesenquimal/ultraestructura , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 7 , Humanos , Inmunohistoquímica , Lactante , Cariotipificación , Masculino , PloidiasRESUMEN
We have performed cytogenetic studies on five renal oncocytic neoplasms (three grade 2 tumors and two grade 1 tumors) identified histologically by light microscopy. One grade 1 tumor failed to produce mitotic cells. The other four tumors exhibited both normal and abnormal cell lines. Numerical abnormalities were found in both the single grade 1 and two of the grade 2 tumors whereas structural abnormalities were limited to grade 2 tumors. Aneuploidy of chromosome 12 was observed in both grade 1 and 2 tumors. Grade 2 tumors showed more extensive numerical change than the grade 1 tumors. Abnormalities of chromosome 3 characteristic of renal cell carcinoma were not found in any tumor in this series. A combination of C-banding and HaeIII endonuclease banding was used to identify an ambiguous marker. In our four cases and in the cases previously reported, loss of a sex chromosome, abnormalities of chromosomes 1 and 22, and trisomy 12 are findings most often observed in renal oncocytoma.