Assuntos
Anatomia/história , Ilustração Médica/história , Pediatria/história , Obras Médicas de Referência , Adolescente , Fatores Etários , Anatomia/educação , Criança , Pré-Escolar , Educação Médica/história , Feminino , História do Século XIX , História do Século XX , Humanos , Lactente , Recém-Nascido , Masculino , Pediatria/educaçãoRESUMO
BACKGROUND: Intra-operative tumor spill increases the risk of local recurrence of Wilms tumor, and adversely impacts relapse-free (RFS) and overall survival (OS) rates. METHODS: Surgical checklists, operative notes, institutional pathology reports, central pathology review and flow sheets of 602 patients registered between August 1986 and September 1994 on National Wilms Tumor Study-4 as randomized, followed or switched and coded as Final Stage II, favorable histology (FH) were reviewed. RFS and OS were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated using the Cox model and tested for statistical significance by the log-rank test. RESULTS: Four hundred ninety-nine patients were found after review to have Stage II, FH Wilms tumor. The 8-year RFS percentages were 85.0% (95% confidence interval (CI): 81.1%, 88.1%) for those with no spill compared to 75.7% (65.8%, 83.2%) for those with spill. The 8-year OS percentages were 95.6% (93.1%, 97.3%) for those with no spill compared to 90.3% (82.2%, 94.9%) for those with spill. The HR for relapse among those with spill was 1.55 ((95%CI: 0.97,2.51), P = 0.067) and the HR for death was 1.94 ((0.92,4.09), P = 0.077). CONCLUSIONS: RFS and OS were lower for patients who had intra-operative tumor spill. The majority of NWTS Stage II, FH patients with intra-operative tumor spill have an overall excellent outcome when treated with two drug chemotherapy (vincristine and actinomycin D) and no abdominal irradiation.
Assuntos
Neoplasias Renais/cirurgia , Inoculação de Neoplasia , Nefrectomia/efeitos adversos , Tumor de Wilms/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Dactinomicina/administração & dosagem , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Radioterapia , Resultado do Tratamento , Vincristina/administração & dosagem , Tumor de Wilms/mortalidade , Tumor de Wilms/patologiaRESUMO
Here, we report two extraordinarily severe cases of Teacher Collins syndrome. Initially, amniotic bands and plical fold disruption were considered, but downslanting eyes made us consider severe Treacher Collins syndrome. A TCOF1 mutation in exon 24 was identified in Patient 1 (c.4355_4356ins14, resulting in p.1456Thrfs*18). Patient 2, who expired on day 4, is so similar to Patient 1 that severe Treacher Collins syndrome may be inferred in this instance. Neither the TCOF1 mutation nor the well-known variability in the expression in affected families with Treacher Collins syndrome (â¼40% of reported cases) can explain the severity of these cases; otherwise, we would be aware of such cases within families from time to time. We are unaware of any recent sporadic cases (â¼60% of reported cases) exactly like ours either with a single exception in the case reported by Writzl et al. [2008] with a TCOF1 mutation. The case described by Otto in 1841 is spectacular. We propose several hypotheses to be considered in explaining this developmental amplification, including some promoter effect on the gene, some position effect on the gene, a polymorphism elsewhere in the gene, a point mutation elsewhere in the gene, a polymorphism in another gene, or a point mutation in another gene, such as POLR1C (which maps to 6p21.1) or POLR1D (which maps to13q12.2). We also review the etiology and pathogenesis of Treacher Collins syndrome, and discuss several other severe cases from the past.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Disostose Mandibulofacial/diagnóstico por imagem , Anormalidades Múltiplas/genética , Evolução Fatal , Feminino , Humanos , Mutação INDEL , Recém-Nascido , Disostose Mandibulofacial/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Ultrassonografia Pré-NatalRESUMO
Wilms tumors (WT) have provided broad insights into the interface between development and tumorigenesis. Further understanding is confounded by their genetic, histologic, and clinical heterogeneity, the basis of which remains largely unknown. We evaluated 224 WT for global gene expression patterns; WT1, CTNNB1, and WTX mutation; and 11p15 copy number and methylation patterns. Five subsets were identified showing distinct differences in their pathologic and clinical features: these findings were validated in 100 additional WT. The gene expression pattern of each subset was compared with published gene expression profiles during normal renal development. A novel subset of epithelial WT in infants lacked WT1, CTNNB1, and WTX mutations and nephrogenic rests and displayed a gene expression pattern of the postinduction nephron, and none recurred. Three subsets were characterized by a low expression of WT1 and intralobar nephrogenic rests. These differed in their frequency of WT1 and CTNNB1 mutations, in their age, in their relapse rate, and in their expression similarities with the intermediate mesoderm versus the metanephric mesenchyme. The largest subset was characterized by biallelic methylation of the imprint control region 1, a gene expression profile of the metanephric mesenchyme, and both interlunar and perilobar nephrogenic rests. These data provide a biologic explanation for the clinical and pathologic heterogeneity seen within WT and enable the future development of subset-specific therapeutic strategies. Further, these data support a revision of the current model of WT ontogeny, which allows for an interplay between the type of initiating event and the developmental stage in which it occurs.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Proteínas Supressoras de Tumor/genética , Proteínas WT1/genética , Tumor de Wilms/genética , beta Catenina/genética , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Transformação Celular Neoplásica , Criança , Variações do Número de Cópias de DNA , Metilação de DNA , Perfilação da Expressão Gênica , Genes do Tumor de Wilms , Humanos , Rim/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Perda de Heterozigosidade , Mutação , Proteínas Supressoras de Tumor/biossíntese , Proteínas WT1/biossíntese , Tumor de Wilms/metabolismo , Tumor de Wilms/patologia , beta Catenina/biossínteseRESUMO
PURPOSE: We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease. MATERIALS AND METHODS: End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions. RESULTS: The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend). CONCLUSIONS: Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall.
Assuntos
Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Neoplasias Renais/complicações , Tumor de Wilms/complicações , Pré-Escolar , Genes do Tumor de Wilms , Humanos , Lactente , Neoplasias Renais/genética , Fatores de Risco , Tumor de Wilms/genéticaRESUMO
OBJECTIVE: To determine the event-free survival (EFS) and overall survival (OS) of children with very low risk Wilms tumor (VLRWT) treated with surgery only. BACKGROUND: Previous studies suggested that postoperative chemotherapy had not improved the prognosis of children with VLRWT. A total of 77 children <24 months of age with small (<550 g) Stage I favorable histology Wilms tumors were treated with surgery only. This study was closed based on stopping rules to ensure that the 2-year EFS was > or =90%. METHODS: A total of 77 children were assessed for EFS and OS. Of these patients, 21 enrolled at the time of closure were recalled, treated with dactinomycin and vincristine (regimen EE4A), and censored for analysis thereafter. About 111 children subsequently treated with EE4A were available for comparison. RESULTS: Median follow-up of surviving patients was 8.2 years for surgery only (range, 1.9-11.8 years) and 5.2 years for the EE4A group (range, 1.6-8.9 years). The estimated 5-year EFS for surgery only was 84% (95% confidence interval [CI]: 73%, 91%); for the EE4A patients it was 97% (95% CI: 92%, 99%, P = 0.002). One death was observed in each treatment group. The estimated 5-year OS was 98% (95% CI: 87%, 99%) for surgery only and 99% (95% CI: 94%, 99%) for EE4A (P = 0.70). CONCLUSION: The surgery-only EFS was lower than anticipated but, coupled with a much higher than anticipated salvage rate of the chemotherapy naive patients whose disease recurred, led to an observed long-term OS equivalent to that seen with 2-drug chemotherapy. This approach to the treatment of patients with VLRWT eliminates the toxic side-effects of chemotherapy for a large majority of patients. A follow-up study is underway to confirm these findings.
Assuntos
Neoplasias Renais/cirurgia , Tumor de Wilms/cirurgia , Humanos , Lactente , Neoplasias Renais/mortalidade , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Tumor de Wilms/mortalidadeRESUMO
Beckwith-Wiedemann syndrome (BWS) is a model disorder for the study of imprinting, growth dysregulation, and tumorigenesis. Unique observations in this disorder point to an important embryonic developmental window relevant to the observations of increased monozygotic twinning and an increased rate of epigenetic errors after subfertility/assisted reproduction.
Assuntos
Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/terapia , Diagnóstico Diferencial , Aconselhamento Genético , Testes Genéticos , HumanosRESUMO
PURPOSE: We undertook this study to determine (1) the frequency with which spilled tumor cells of favorable histology produced intra-abdominal disease in patients treated with differing chemotherapy regimens and abdominal radiation therapy (RT) and (2) the patterns of relapse and outcomes in such patients. METHODS AND MATERIALS: The influence of RT dose (0, 10, and 20 Gy), RT fields (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2 drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence rates was analyzed by logistic regression in 450 patients. Each patient was considered at risk for two types of failure: flank and subdiaphragmatic beyond-flank recurrence, with the correlation between the two outcomes accounted for in the analyses. RESULTS: The crude odds ratio for the risk of recurrence relative to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates with and without spillage, respectively, were 79% and 87% for relapse-free survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04). CONCLUSIONS: Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor spillage. Tumor spillage in Stage II patients reduced relapse-free survival and overall survival, but only the latter was of statistical significance. These data provide a basis for assessing the risks vs. benefits when considering treatment for children with favorable histology Wilms tumor and surgical spillage.
Assuntos
Neoplasias Abdominais/prevenção & controle , Neoplasias Abdominais/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Renais , Inoculação de Neoplasia , Tumor de Wilms/secundário , Criança , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Seguimentos , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Modelos Logísticos , Estadiamento de Neoplasias , Razão de Chances , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Dosagem Radioterapêutica , Medição de Risco/métodos , Vincristina/administração & dosagem , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/radioterapiaRESUMO
PURPOSE: Recent studies suggest that children <24 months with stage I favorable histology Wilms tumors <550 g [very low risk Wilms tumors (VLRWT)] have an excellent prognosis when treated with nephrectomy only, without adjuvant chemotherapy. The identification of risk categories within VLRWT may enable refinement of their definition and optimization of their therapy. EXPERIMENTAL DESIGN: To define biologically distinct subsets, global gene expression analysis was done on 39 VLRWT that passed all quality-control parameters and the clusters identified were validated in an independent set of 11 VLRWT. Validation of select differentially expressed genes was done with immunohistochemistry on a tissue microarray from 20 of 39 tumors. Loss of heterozygosity (LOH) for 11p15, 1p, and 16q was analyzed in 52 tumors using PCR. RESULTS: Two distinctive clusters were identified. One cluster included 9 tumors with epithelial differentiated tubular histology, paucity of nephrogenic rests, lack of LOH for 1p, 16q, and 11p, absence of relapse, and a unique gene expression profile consistent with arrest following mesenchymal-to-epithelial transition. The second cluster included 13 tumors with mixed histology, intralobar nephrogenic rests, and decreased expression of WT1. Three of 6 relapses occurred in this cluster. Of 43 informative tumors, 11p LOH was present in 5 of 5 relapses and 11 of 38 nonrelapses. CONCLUSIONS: Two subsets comprising a total of 56% of VLRWT are identified that have pathogenetic and molecular differences and apparent differences in risk for relapse. If these predictors can be prospectively validated, this would enable the refinement of clinical stratification and less arbitrary definition of VLRWT.
Assuntos
Regulação Neoplásica da Expressão Gênica , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Pré-Escolar , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Lactente , Perda de Heterozigosidade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Controle de Qualidade , Recidiva , Risco , Proteínas WT1/biossíntese , Proteínas WT1/genética , Tumor de Wilms/diagnósticoRESUMO
PURPOSE: We reviewed the long-term local tumor control in patients with bilateral Wilm's tumor (BWT) who received no definitive surgical therapy to one kidney after complete radiographic resolution after initial chemotherapy. METHODS: National Wilm's Tumor Study 4 (NWTS-4) enrolled 3335 patients (pts) during the period August 1986 to August 1994. There were 188 pts with BWT or 5.6% of the total enrolled. The treatment records and imaging reports were reviewed to ascertain those children who had documented tumors without definitive surgical therapy after initial treatment. Patients who did not have renal surgery because of progression of tumor were excluded from this study. RESULTS: Eleven children had no definitive surgical treatment of renal lesions in one kidney (right, 6; left, 5) after initial treatment with chemotherapy and/or radiation therapy. The pretreatment size of the lesions were less than 3 cm (4 pts), 3 to 6 cm (5 pts), more than 6 cm (1 pt), and unknown (1 pt). Prechemotherapy biopsy was performed in 6 of 11 patients. Lesions were less than 3 cm (1 pt), 3 to 6 cm (3 pts), more than 6 cm (1 pt), and unknown (1 pt). Four biopsy specimens showed favorable Wilm's histologic findings. One lesion (4 cm) showed an intralobar nephrogenic rest, another lesion of unknown size was read as favorable histologic findings vs perilobar nephrogenic rest. Biopsy was not performed on 5 lesions (4 pts, <1 cm; 1 pt, 3cm). Only 2 children in this study received radiation treatment. One child received 1050 cGy whole abdominal radiation, and 1 child received 1060 cGy to the left flank postnephrectomy. Radiation therapy was not given to any patient because of failure of the tumor to respond to chemotherapy. Five patients received treatment regimen EE-4A, dactinomycin, and vincristine. The duration of therapy ranged from 24 to 102 weeks for an average of 55.6 weeks. Three patients received treatment regimen DD-4A, dactinomycin, vincristine, and doxorubicin for 28, 52, and 52 weeks, respectively. Three patients received 2 separate regimens of chemotherapy. One child was treated with dactinomycin, vincristine, and cyclophosphamide for 60 weeks and then received regimen EE-4A for 24 weeks. Another patient received regimen EE-4A for 16 weeks and then regimen DD4-A for 36 weeks. One child received regimen EE-4-A for 12 weeks and then regimen DD4A for 40 weeks. Management of the contralateral kidney was complete nephrectomy in all 11 patients. There were no local relapses in the renal tumor bed. All patients were alive at a median follow-up of 9 years (range, 9 months to 15 years). CONCLUSION: Children with synchronous BWT or Wilm's tumor and contralateral nephrogenic rests that have radiographic resolution, after initial treatment, have a low risk for local relapse. These children should be followed by serial imaging.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Tumor de Wilms/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Seguimentos , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/radioterapia , Nefrectomia , Radiografia , Radioterapia Adjuvante , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/administração & dosagem , Tumor de Wilms/diagnóstico por imagem , Tumor de Wilms/radioterapia , Tumor de Wilms/cirurgiaRESUMO
OBJECTIVE: We evaluated the use of alternating cycles of cyclophosphamide/etoposide and carboplatin/etoposide in children entered on National Wilms Tumor Study (NWTS)-5 who were diagnosed between August 1, 1995 and May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D, and doxorubicin (VAD) and radiation therapy (DD-4A). PATIENTS AND METHODS: One hundred three patients who relapsed or had progressive disease after initial VAD chemotherapy and radiation therapy were registered on stratum C of the NWTS-5 Relapse protocol. Twelve patients were not evaluable: five due to insufficient data, six due to major protocol violations, and one for refusal of therapy. Among the 91 remaining patients, 14 with stage V Wilms tumor (WT), 1 with contralateral relapse, and 16 who did not achieve a complete response (CR) to the initial three-drug chemotherapy were not included in this analysis. Relapse treatment included alternating courses of the drug pairs cyclophosphamide/etoposide and carboplatin/etoposide, surgery, and radiation therapy. RESULTS: The outcomes of 60 patients were analyzed. The lung was the only site of relapse for 33 patients; other sites of relapse included the operative bed, the abdomen, and liver. Four-year event-free survival (EFS) and overall survival (OS) were 42.3 and 48.0% respectively for all patients and were 48.9 and 52.8% for those who relapsed in the lungs only. Thrombocytopenia was the most frequent toxicity. CONCLUSION: These results demonstrate that approximately one-half of children with unilateral WT who relapse after initial treatment with VAD and radiation therapy can be successfully retreated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Tumor de Wilms/tratamento farmacológico , Carboplatina/administração & dosagem , Pré-Escolar , Terapia Combinada , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Masculino , Estadiamento de Neoplasias , Recidiva , Tumor de Wilms/patologia , Tumor de Wilms/radioterapia , Tumor de Wilms/cirurgiaRESUMO
Though relatively neglected in the age of molecular biology, the older literature of teratology includes superb illustrations and descriptions of malformations, and other information of permanent value to science and medicine. Accessing that literature can be challenging, as most is in works that are rare, published in languages other than English, and not available in digital form. This article describes some valuable sources of information concerning the antiquarian literature of descriptive teratology.
Assuntos
Teratologia/história , Teratologia/métodos , Animais , Anormalidades Congênitas , Bases de Dados Bibliográficas , Genética/história , História do Século XIX , História do Século XX , Humanos , LiteraturaRESUMO
We report 20 cases of a distinct, previously unrecognized renal neoplasm, anaplastic sarcoma of the kidney with polyphenotypic features. The tumors were identified by re-reviewing tumors with unusual anaplastic features from the National Wilms Tumor Study Pathology Center, the International Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group trials. Patients ranged in age from 10 months to 41 years (median age 5 y, mean age 12 y) and females predominated (1.5:1). Twelve tumors presented in the right kidney, and 5 in the left (laterality was unknown in 3 cases). The most common presentation was a renal mass. Grossly, most tumors were large, measured 4 to 21 cm (mean 12.7 cm) and weighed 115 to 1820 g (mean 835 g). Seven out of 12 tumors suitable for assessment had a distinct cystic component. The tumors involved the pelvi-calyceal system in 5 of the cases. Histologically, all tumors showed a spindle cell component which contained either multiple foci or diffuse, widespread anaplastic changes with bizarre pleomorphic cells and very atypical mitotic figures. Chondroid differentiation was seen in 16 cases, usually in the form of islands of hyaline cartilage (13 cases) or chondroid matrix (3 cases). The nodules of cartilage showed both benign and malignant features, often within the same tumor. In 2 cases small foci of osteoid were found whereas osteoclast-like giant cells were seen in 4 cases. Only 3 of the tumors exhibited a primitive blastema-like area. No neoplastic epithelial structures were identified. No nephrogenic rests were found. Limited immunohistochemical studies showed vimentin positivity in 5/5 cases, desmin was positive in 4/6 cases, MYF4 showed focal weak nuclear positivity in 1/4 cases, but MyoD1 was negative in all cases (0/5). PGP9.5 was focally, strongly positive in 4/5 cases and p53 was strongly positive in 3/6 cases. Cytokeratin, using the antibody CAM5.2, was uniformly negative within the tumor cells. Finally, CD56 was focally positive in 1/6 tumors, whereas all other markers were negative including NB84a (4/4), CD34 (5/6), CD99 (5/5), and WT1 (6/6 cases). In 4 tumors reverse transcriptase-polymerase chain reaction was performed to detect the SYT-SSX fusion transcript produced by the t(x;18), and the ETV6-NTRK3 fusion transcript using RNA extracted from archived paraffin blocks-results were negative in all 4 specimens. Tumor stage was known in 15 patients including 7 stage I, 4 stage II, 3 stage III, and 1 stage IV tumors. They were usually diagnosed as anaplastic Wilms tumors and treated accordingly. Of the 13 patients with a minimum of 2 years follow-up, 4 patients developed distant metastases and 1 had local recurrence including 1 patient with stage IV, 2 with stage III, and 2 with stage I at presentation. Three of them died and 2 were lost to follow-up. One patient with stage I tumor developed widespread metastases and died. Another stage I patient developed local recurrence after 3 months of diagnosis, but was lost to follow-up. Five stage I patients were alive and free of tumor at last follow-up. The most common sites of metastases were lung (3 cases), and liver and bones (2 cases each). These tumors showed pathologic features similar to the pleuropulmonary blastoma of childhood and undifferentiated (embryonal) sarcoma of the liver. In the differential diagnosis, anaplastic Wilms tumor, primary renal synovial sarcoma, malignant mesenchymoma, ectomesenchymoma, and mesenchymal chondrosarcomas have been considered but none of these tumors shared the same features as the 20 cases described here which represent a distinct clinicopathologic entity with morphologic features of a polyphenotypic anaplastic sarcoma of the kidney. Further molecular studies are needed to better understand its nature and more accurate classification.
Assuntos
Neoplasias Renais/patologia , Sarcoma/patologia , Adolescente , Adulto , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Desmina/análise , Intervalo Livre de Doença , Feminino , Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Lactente , Neoplasias Renais/química , Neoplasias Renais/genética , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Nefrectomia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fenótipo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma/química , Sarcoma/genética , Vimentina/análiseRESUMO
Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET) is a rare primary tumor of the kidney with morphologic features similar to those of other primitive tumors. Previous studies have shown that these tumors frequently stain positively with immunostains against CD99 and FLI-1 and negatively with stains against WT-1, suggesting that these markers may be used for the distinction between Wilms tumor and pPNET. We present 30 cases of primary malignant neuroepithelial tumor with immunohistochemical profiles and reverse transcriptase polymerase chain reaction (RT-PCR) analysis and show that immunophenotypic overlap exists between Wilms tumor and pPNET. A subset of 30 neuroepithelial tumors from the National Wilms Tumor Study originally categorized as putative pPNETs of the kidney was stained with FLI-1, WT-1, and thyroid transcription factor-1. Bicolor fluorescence in situ hybridization studies were performed on 19 of the cases. Other data on these tumors were available from a previous study (Am J Surg Pathol 2001;25:133). Of 7 primary tumors that had the EWS/FLI-1 fusion transcript by RT-PCR, 6 exhibited strong immunopositivity for FLI-1. Nine that were negative by RT-PCR stained positively with the FLI-1 stain. Five fusion-negative cases stained with both FLI-1 and WT-1. Three fusion-negative cases were negative for FLI-1 but positive for WT-1. Five fusion-negative cases were negative for both FLI-1 and WT-1. Of the 30 cases, 29 were positive for CD99. Seven cases that were negative for the EWS-FLI-1 fusion by RT-PCR were positive by fluorescence in situ hybridization. All cases were negative for thyroid transcription factor-1. Reliance upon immunohistochemistry as the sole means of ancillary diagnosis in renal pPNET can lead to confusing results. We recommend molecular fusion studies for clarification of primitive renal tumors with unexpected immunophenotypic results.
Assuntos
Imuno-Histoquímica/métodos , Neoplasias Renais/patologia , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Adulto , Criança , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica/normas , Hibridização in Situ Fluorescente , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas dos Microfilamentos/análise , Proteínas dos Microfilamentos/genética , Tumores Neuroectodérmicos Primitivos Periféricos/genética , Tumores Neuroectodérmicos Primitivos Periféricos/metabolismo , Proteínas Nucleares/análise , Proteínas de Fusão Oncogênica/genética , Proteína Proto-Oncogênica c-fli-1/genética , Proteína EWS de Ligação a RNA , Receptores Citoplasmáticos e Nucleares/análise , Receptores Citoplasmáticos e Nucleares/genética , Reprodutibilidade dos Testes , Fator Nuclear 1 de Tireoide , Transativadores , Fatores de Transcrição/análise , Proteínas WT1/análise , Proteínas WT1/genética , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Tumor de Wilms/patologiaRESUMO
PURPOSE: NWTS-5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. PATIENTS AND METHODS: Seventy-two patients who relapsed after immediate nephrectomy (stages I and II), initial chemotherapy with vincristine (VCR) and actinomycin D and no radiation therapy were registered on stratum B of the NWTS-5 relapse protocol. Four patients were not evaluable: one due to insufficient data and three due to major protocol violations. Among the 68 remaining patients, one who was 19 years of age at initial diagnosis of Wilms tumor, five with bilateral Wilms tumor at diagnosis, three who developed a contralateral relapse, and one with persistent disease were not included in this analysis. Relapse treatment included surgical excision, when feasible, radiation therapy and alternating courses of VCR, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. RESULTS: The outcomes of 58 patients were analyzed. The lung was the only site of relapse for 31 patients. Event-free survival 4 years after relapse was 71.1% and 4-year overall survival was 81.8% for all patients and were 67.8 and 81.0% for those who relapsed only to their lungs. The most frequent toxicities were hematological. CONCLUSIONS: These results demonstrate that a significant proportion of children with Wilms tumor who relapse after initial treatment with VCR and actinomycin D can be successfully re-treated.