RESUMO
Purpose: A delay in diagnosing and treating ocular surface squamous neoplasia (OSSN) with an atypical manifestation can lead to a progression to more advanced stages, resulting in a decrease in cure rates and treatment effectiveness. Observations: This case report describes a 21-year-old white male who presented to our Cornea Division with peripheral nasal corneal and scleral thinning with prolapse of uveal tissue in the right eye for over four months and who had received a sclerocorneal patch graft. The patient underwent systemic immunosuppressive therapy for presumed Mooren's ulcer after laboratory evaluation eliminated a collagen vascular disorder. Approximately three months after the procedure the patient returned with an inferior and superior sclerocorneal perforation. Six months after the first visit to our department, he returned to our ophthalmological emergency department with self-evisceration of the intraocular contents. He underwent an emergency evisceration procedure, and histopathological analysis of the intraocular contents revealed a poorly differentiated nodulo-ulcerative squamous cell carcinoma of the conjunctiva with intraocular invasion. A tomographic evaluation suggested orbital invasion. Subsequently, he underwent exenteration. Conclusions and Importance: OSSN should be considered in the differential diagnosis of corneal or scleral thinning, perforation, and inflammation of an unknown cause even in young patients, especially after systemic disorders have been excluded.
RESUMO
Glioblastoma (GBM) is the most frequent tumor of the central nervous system, and its heterogeneity is a challenge in treatment. This study examined tumoral heterogeneity involving PDGFRA, KIT, and KDR gene amplification (GA) in 4q12 and its association with clinical parameters. Specimens from 22 GBM cases with GA for the 4q12 amplicon detected by FISH were investigated for homogeneous or heterogeneous coamplification patterns, diffuse or focal distribution of cells harboring GA throughout tumor sections, and pattern of clustering of fluorescence signals. Sixteen cases had homogenously amplification for all three genes (45.5%), for PDGFRA and KDR (22.7%), or only for PDGFRA (4.6%); six cases had heterogeneous GA patterns, with subpopulations including GA for all three genes and for two genes - PDGFRA and KDR (13.6%), or GA for all three and for only one gene - PDGFRA (9.1%) or KIT (4.6%). In 6 tumors (27.3%), GA was observed in focal tumor areas, while in the remaining 16 tumors (72.7%) it was diffusely distributed throughout the pathological specimen. Amplification was universally expressed as double minutes and homogenously stained regions. Coamplification of all three genes PDGFRA, KIT, and KDR, age ≥ 60 years, and total tumor resection were statistically associated with poor prognosis. FISH proved effective for detailed interpretation of molecular heterogeneity. The study uncovered an even more diverse range of amplification patterns involving the 4q12 oncogenes in GBM than previously described, thus highlighting a complex tumoral heterogeneity to be considered when devising more effective therapies.
Assuntos
Glioblastoma , Humanos , Pessoa de Meia-Idade , Sistema Nervoso Central , Aberrações Cromossômicas , Relevância Clínica , Amplificação de Genes , Glioblastoma/genética , Receptores Proteína Tirosina Quinases , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismoAssuntos
Infecções por Vírus Epstein-Barr/etiologia , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Úlcera Cutânea/etiologia , Azatioprina/efeitos adversos , Tratamento Conservador , Desprescrições , Infecções por Vírus Epstein-Barr/imunologia , Dermatoses Faciais/etiologia , Dermatoses Faciais/imunologia , Feminino , Testa , Humanos , Transtornos Linfoproliferativos/imunologia , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Úlcera Cutânea/imunologiaRESUMO
We investigated 113 adult Brazilian patients with glioblastoma (GBM) for comparison with patients from distinct geographical areas and evaluation of suitability for novel targeted therapies. Patients were assessed for clinical features and tumor genomic characteristics such as ROS1 and NTRK1 rearrangements, KIT, PDGFRA, and KDR amplification, and RB1 deletion using multicolor fluorescence in situ hybridization. The majority of patients were male (53%), over 40 years (94%), with tumor located in single site (64%), in the right cerebral hemisphere (60%), and underwent partial resection (71%); 14% presented complications after surgery. The main clinical sign at diagnosis was focal abnormality (57%); frontal (31%); and temporal (20%) regions were most commonly affected. Median hospitalization time was 20 days, median survival was 175 days. One tumor was positive for rearrangement in NTRK1 and another in ROS1 (0.9% each). PDGFRA was amplified in 20% of cases, often co-amplified with KDR (>90%) and KIT (>60%). RB1 was deleted in 16% of patients. There was no association between these molecular abnormalities and patient survival. However, older age, complications after surgery, and right-sided tumors were independent variables associated with patient survival. This study contributes information on the molecular profile of glioblastomas in Latin America possibly supporting new target therapies.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioblastoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Serological screening for celiac disease (CD) allows the identification of individuals genetically predisposed, as type 1 diabetes mellitus (T1DM). However, the diagnosis is confirmed by intestinal biopsy. The aim was to determine the prevalence of immunoglobulin-A anti-tissue transglutaminase antibodies (IgA-tTG) and CD in a large cohort of young T1DM patients. METHODS: Screening for CD was randomly conducted in 881 T1DM by IgA-tTG and total IgA. Individuals with positive antibodies were referred to endoscopy/duodenal biopsy. RESULTS: The age of the cohort at the screening was 14.3 ± 5.9 years and at T1DM onset was 7.9 ± 4.4 years. The prevalence of positive serology was 7.7%. Median IgA-tTG levels were 117.7 U/mL (interquartile range [IQR] 35.7-131.5 U/mL). Of the 62 duodenal biopsy, CD was diagnosed in 79.0%, yielding an overall prevalence of 5.6%. The mean age of CD patients was 15.6 ± 6.5 years and, at T1DM onset was 6.3 years (4.0-9.9 years). The modified Marsh-Oberhuber histological classification was 22.5% (3a), 36.7% (3b), and 40.8% (3c). In the biopsy-proven patients, T1DM onset occurred at slightly younger ages (6.3 vs 9.7 years, P = 0.1947), gastrointestinal (GI) manifestations, predominantly abdominal pain and distension, were more prevalent (71.4% vs 38.5%, P = 0.027) and higher IgA-tTG titers (128.0 vs 26.3 U/mL, P = 0.0003) were found than in those with negative-biopsies. CONCLUSION: Our results demonstrate the prevalence of 7.7% of IgA-tTG and 5.6% of CD in T1DM patients in South Brazil and, emphasize the importance of the screening in high-risk individuals. Furthermore, the presence of GI manifestations and higher IgA-tTG titers strongly suggest the diagnosis of CD.
Assuntos
Doença Celíaca/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Doença Celíaca/complicações , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Programas de Rastreamento , Prevalência , Adulto JovemRESUMO
Glioblastoma stands out as the most frequent central nervous system neoplasia, presenting a poor prognosis. The aim of this study was to verify the frequency and clinical significance of the aneuploidy of chromosomes 7 and 10, EGFR amplification, PTEN and TP53 deletions and 1p/19q deficiency in adult patients diagnosed with glioblastoma. The sample consisted of 40 patients treated from November 2011 to March 2015 at two major neurosurgery services from Southern Brazil. Molecular cytogenetic analyses of the tumor were performed through fluorescent in situ hybridization (FISH). The clinical features evaluated consisted of age, sex, tumor location, clinical symptoms, family history of cancer, type of resection and survival. The mean age of the patients was 59.3 years (ranged from 41 to 83). Most of them were males (70%). The median survival was 145 days. Chromosome 10 monosomy was detected in 52.5% of the patients, chromosome 7 polysomy in 50%, EGFR amplification in 42.5%, PTEN deletion in 35%, TP53 deletion in 22.5%, 1p deletion in 5% and 19q deletion in 7.5%. Age was shown to be a prognostic factor, and patients with lower age presented higher survival (p = 0.042). TP53 and PTEN deletions had a negative impact on survival (p = 0.011 and p = 0.037, respectively). Our data suggest that TP53 and PTEN deletions may be associated with a poorer prognosis. These findings may have importance over prognosis determination and choice of the therapy to be administered.
Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Brasil , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 7 , Receptores ErbB/genética , Feminino , Glioblastoma/epidemiologia , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , PTEN Fosfo-Hidrolase/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
ABSTRACT CONTEXT: Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT: A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION: It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.
RESUMO CONTEXTO: A doença de Hirschsprung é uma desordem do desenvolvimento do sistema nervoso entérico, que é caracterizada pela ausência de células ganglionares no intestino distal, ocorrendo em cerca de 1 a cada 500.000 nascimentos. O hepatoblastoma é uma neoplasia maligna do fígado que geralmente ocorre em crianças de 6 meses a 3 anos, com prevalência de 0,54 casos por 100.000. RELATO DE CASO: Um menino com diagnóstico de atresia intestinal na primeira semana de vida evoluiu com diagnóstico concomitante de doença de Hirschsprung. Catarata congênita e surdez neurossensorial foram diagnosticadas. Surgiu lesão hepática com posterior confirmação de hepatoblastoma, tratado com ressecção cirúrgica de 70% do volume hepático e quimioterapia neoadjuvante (ifosfamida, cisplatina e doxorubicina). CONCLUSÃO: Sabe-se que a doença de Hirschsprung pode estar associada a síndromes de predisposição ao câncer, da mesma forma que o hepatoblastoma já foi correlacionado a certas síndromes congênitas malformativas. No entanto, até o momento, a associação de hepatoblastoma com a doença de Hirschsprung não foi descrita. Relatamos o caso de um menino que nasceu com atresia ileal, doença de Hirschsprung, catarata congênita bilateral e com posterior diagnóstico de hepatoblastoma.
Assuntos
Humanos , Masculino , Recém-Nascido , Hepatoblastoma/complicações , Doença de Hirschsprung/complicações , Atresia Intestinal/complicações , Catarata/congênito , Hepatoblastoma/diagnóstico por imagem , Doença de Hirschsprung/diagnóstico por imagem , Atresia Intestinal/diagnósticoRESUMO
BACKGROUND: Gastroschisis is the most common abdominal wall defect. It is characterized by herniation of the intestine and other abdominal organs through a defect in the abdominal wall. Neuroblastoma is the most common malignant tumor observed during the neonatal period. It is a neuroendocrine tumor derived from neural crest cells that develops into the adrenal gland. CASE: We report on the undescribed association between gastrochisis and congenital neuroblastoma, diagnosised during the prenatal period. The mother was a 20-year-old healthy pregnant woman in her second pregnancy. Obstetric ultrasound examination showed a fetus presenting an abdominal wall defect on the right side of the umbilical cord, compatible with gastroschisis, and a hyperechogenic and spherical solid lesion on the left adrenal gland. Fetal magnetic resonance imaging disclosed similar features associated to a heterogeneous aspect of the liver. The diagnosis of metastatic neuroblastoma was confirmed after birth through liver biopsy. At 2 days of life, the prothrombrin time was abnormal, and the patient needed vitamin K. CONCLUSION: We cannot rule out the possibility that a clotting defect, commonly observed in disseminated malignancies such as a metastatic neuroblastoma may be associated with the etiology of the gastroschisis, as this defect may result from a thrombosis occurring around 3 to 4 weeks of gestation, a period when neuroblasts development occurs into the adrenal medulla. However, we cannot exclude the possibility that both events may have occurred simultaneously by chance.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Gastrosquise/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neuroblastoma/diagnóstico , Trombose/diagnóstico , Parede Abdominal/anormalidades , Parede Abdominal/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Antifibrinolíticos/uso terapêutico , Feminino , Feto , Gastrosquise/patologia , Gastrosquise/cirurgia , Idade Gestacional , Humanos , Recém-Nascido , Neoplasias Hepáticas/secundário , Neuroblastoma/secundário , Neuroblastoma/cirurgia , Gravidez , Trombose/tratamento farmacológico , Trombose/patologia , Ultrassonografia Pré-Natal , Vitamina K/uso terapêutico , Adulto JovemRESUMO
CONTEXT: Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. CASE REPORT: A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). CONCLUSION: It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.
Assuntos
Hepatoblastoma/complicações , Doença de Hirschsprung/complicações , Atresia Intestinal/complicações , Catarata/congênito , Hepatoblastoma/diagnóstico por imagem , Doença de Hirschsprung/diagnóstico por imagem , Humanos , Recém-Nascido , Atresia Intestinal/diagnóstico , MasculinoRESUMO
OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .
OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .
Assuntos
Animais , Humanos , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Macrocíclicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Euphorbia/química , Compostos Macrocíclicos/química , Compostos Macrocíclicos/isolamento & purificação , Conformação Molecular , Fenótipo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ >500 mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10 mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable.
Assuntos
Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Tumor de Wilms/mortalidade , Tumor de Wilms/patologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Renais/terapia , Masculino , Prognóstico , Taxa de Sobrevida , Carga Tumoral , Tumor de Wilms/terapiaRESUMO
BACKGROUND: Wilms tumor (WT) is the most common renal malignancy of childhood. The aim of this study was to verify the epidemiological profile and prognosis of a sample of patients from Brazil and compare them to similar data from other Latin American studies. METHOD: The sample consisted of consecutive patients diagnosed with WT in an oncohematology service of a referral hospital in Southern Brazil, between 1989 and 2009. Clinical, radiological, pathological and survival data were collected from the medical records. Analysis was done using Excel and SPSS version 18.0. The significance level was set at P < 0.05. RESULTS: The final sample consisted of 45 patients. The male/female ratio was 1.25:1. Mean age at diagnosis was 43.9 months and all patients were of European descent. Thirty-three patients (73.3%) had both signs/symptoms of abdominal mass and hypertension. Malformation was observed in nine patients (20%) and there was one case of Fanconi's anemia (2.2%). Three patients had bilateral disease (6.7%). The majority of patients had stage III and IV (62.2%). Patients with malformation had an earlier age at diagnosis (P = 0.018) and a higher prevalence of bilateral disease (P = 0.044). Overall survival was 75%. Age at diagnosis was the only significant independent predictor associated with death. CONCLUSION: Death is closely related to late diagnosis in WT. Oncologic services should also be concerned about morbidity caused by therapeutic options in cases of late diagnosis, and the consequences for quality of life.
Assuntos
Neoplasias Renais/epidemiologia , Tumor de Wilms/epidemiologia , Brasil/epidemiologia , Pré-Escolar , Feminino , Hospitais , Humanos , Lactente , América Latina , Masculino , PrognósticoRESUMO
Os autores relatam o caso de uma paciente feminina, 37 anos, que durante a investigacao para infertilidade apresentou o diagnostico de ossificacao endometrial. A etiologia, patogenese e diagnosticos diferenciais de ossificacao endometrial sao...