RESUMO
Ependymomas account for 10% of all malignant pediatric central nervous system tumors. Standard therapy includes maximal safe surgical resection, followed by focal radiation. Despite the aggressive therapy, progression-free survival is poor. Most ependymoma relapses occur locally at the original tumor site. Extraneural presentations of ependymoma are extremely rare, and no standard of care treatment exists. We present a single-institution case series of 3 patients who experienced extraneural relapses of supratentorial ependymoma and describe their treatment and outcome. These cases of extraneural relapse highlight the possible modes of extraneural spread, including hematogenous, lymphatic, and microscopic seeding through surgical drains and shunts. In addition, they illustrate the increase in histologic grade and mutational burden that may occur at the time of relapse. These cases illustrate the role of aggressive, individualized treatment interventions using a combination of surgery, radiation, and chemotherapy.
Assuntos
Ependimoma , Recidiva Local de Neoplasia , Humanos , Criança , Ependimoma/patologia , Terapia CombinadaAssuntos
Epigênese Genética/genética , Neoplasias Neuroepiteliomatosas/patologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Pré-Escolar , Metilação de DNA , Epilepsia/etiologia , Epilepsia/genética , Feminino , Humanos , Masculino , Proteínas de Fusão Oncogênica , Adulto JovemRESUMO
The recognition of pulmonary manifestations of inflammatory bowel disease (IBD) is important as these diseases can be confused with infectious etiologies (e.g., tuberculosis or fungal infection) and, as a result, may unnecessarily delay institution of appropriate therapy (e.g., infliximab). Furthermore, they are a source of morbidity that may be overlooked and, like other IBD-related pathologies, are often responsive to treatment with corticosteroids, immunomodulators, or biologic therapies. The purpose of this paper is to describe the cases of six children at a single institution with differing presentations, treatments, and responses to treatment of their IBD-related lung disease to improve recognition of this uncommon process.
RESUMO
Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.
Assuntos
Encéfalo/metabolismo , Regulação da Expressão Gênica , Transtornos Mentais/genética , Conjuntos de Dados como Assunto , Aprendizado Profundo , Elementos Facilitadores Genéticos , Epigênese Genética , Epigenômica , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Humanos , Locos de Características Quantitativas , Análise de Célula Única , TranscriptomaRESUMO
Three related males presented with a newly recognized x-linked syndrome associated with neurodegeneration, cutaneous abnormalities, and systemic iron overload. Linkage studies demonstrated that they shared a haplotype on Xp21.3-Xp22.2 and exome sequencing was used to identify candidate variants. Of the segregating variants, only a PIGA mutation segregated with disease in the family. The c.328_330delCCT PIGA variant predicts, p.Leu110del (or c.1030_1032delCTT, p.Leu344del depending on the reference sequence). The unaffected great-grandfather shared his X allele with the proband but he did not have the PIGA mutation, indicating that the mutation arose de novo in his daughter. A single family with a germline PIGA mutation has been reported; affected males had a phenotype characterized by multiple congenital anomalies and severe neurologic impairment resulting in infantile lethality. In contrast, affected boys in the family described here were born without anomalies and were neurologically normal prior to onset of seizures after 6 months of age, with two surviving to the second decade. PIGA encodes an enzyme in the GPI anchor biosynthesis pathway. An affected individual in the family studied here was deficient in GPI anchor proteins on granulocytes but not erythrocytes. In conclusion, the PIGA mutation in this family likely causes a reduction in GPI anchor protein cell surface expression in various cell types, resulting in the observed pleiotropic phenotype involving central nervous system, skin, and iron metabolism.
Assuntos
Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação em Linhagem Germinativa , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Sobrecarga de Ferro/genética , Proteínas de Membrana/genética , Espasmos Infantis/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Autopsia , Sequência de Bases , Biópsia , Encéfalo/patologia , Encéfalo/ultraestrutura , Análise Mutacional de DNA , Fácies , Evolução Fatal , Genes Ligados ao Cromossomo X , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Transtornos Heredodegenerativos do Sistema Nervoso/diagnóstico , Humanos , Lactente , Sobrecarga de Ferro/diagnóstico , Rim/patologia , Fígado/patologia , Linfócitos/ultraestrutura , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana/química , Dados de Sequência Molecular , Linhagem , Alinhamento de Sequência , Pele/patologia , Espasmos Infantis/diagnóstico , Baço/patologia , SíndromeRESUMO
Ewing sarcoma (ES) is the second most common bone tumor in children and young adults, with dismal outcomes for metastatic and relapsed disease. To better understand the molecular pathogenesis of ES and to identify new prognostic markers, we used molecular inversion probes (MIPs) to evaluate copy number alterations (CNAs) and loss of heterozygosity (LOH) in formalin-fixed paraffin-embedded (FFPE) samples, which included 40 ES primary tumors and 12 ES metastatic lesions. CNAs were correlated with clinical features and outcome, and validated by immunohistochemistry (IHC). We identified previously reported CNAs, in addition to SMARCB1 (INI1/SNF5) homozygous loss and copy neutral LOH. IHC confirmed SMARCB1 protein loss in 7-10% of clinically diagnosed ES tumors in three separate cohorts (University of Utah [N = 40], Children's Oncology Group [N = 31], and University of Michigan [N = 55]). A multifactor copy number (MCN)-index was highly predictive of overall survival (39% vs. 100%, P < 0.001). We also identified RELN gene deletions unique to 25% of ES metastatic samples. In summary, we identified both known and novel CNAs using MIP technology for the first time in FFPE samples from patients with ES. CNAs detected by microarray correlate with outcome and may be useful for risk stratification in future clinical trials.
Assuntos
Neoplasias Ósseas/genética , Dosagem de Genes , Sondas Moleculares , Sarcoma de Ewing/genética , Adolescente , Adulto , Neoplasias Ósseas/patologia , Moléculas de Adesão Celular Neuronais/genética , Criança , Pré-Escolar , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Proteínas da Matriz Extracelular/genética , Feminino , Deleção de Genes , Humanos , Imuno-Histoquímica , Lactente , Perda de Heterozigosidade , Masculino , Proteínas do Tecido Nervoso/genética , Inclusão em Parafina , Proteína Reelina , Proteína SMARCB1 , Sarcoma de Ewing/patologia , Serina Endopeptidases/genética , Fatores de Transcrição/genética , Adulto JovemRESUMO
The detection of chromosomal translocations has important implications in the diagnosis, prognosis and treatment of patients with cancer. Current approaches to translocation detection have significant shortcomings, including limited sensitivity and/or specificity, and difficulty in application to formalin-fixed paraffin-embedded (FFPE) clinical samples. We developed a new approach called antibody detection of translocations (ADOT) that avoids the shortcomings of current techniques. ADOT combines a transcriptional microarray-based approach with a novel antibody-based detection method. ADOT allows for the accurate and sensitive identification of translocations and provides exon-level information about the fusion transcript. ADOT can detect translocations in poor-quality unprocessed total ribonucleic acid (RNA). Furthermore, the technique is readily generalizable to detect any potential fusion transcript, including previously undescribed fusions. We demonstrate the feasibility of ADOT by examples in which both known and unknown Ewing sarcoma translocations are identified from cell lines, tumour xenografts and FFPE primary tumours. These results demonstrate that ADOT may be an effective approach for translocation analysis in clinical specimens with significant RNA degradation and may offer a novel diagnostic tool for translocation-based cancers.
Assuntos
Anticorpos , Patologia Molecular/métodos , Sarcoma de Ewing/patologia , Translocação Genética , Animais , Fusão Gênica , Humanos , Camundongos , Camundongos Nus , Análise em Microsséries/métodos , Sensibilidade e Especificidade , Transcrição GênicaRESUMO
This case report involved male infants of a size consistent with the estimated gestational age of 31 weeks. The mother of the twins was a 27-year-old, G4P3 woman with limited prenatal care who presented for cesarean delivery. Resuscitation efforts were initiated and continued until the infants became asystolic. Postmortem radiographs showed innumerable fractures of the limbs, ribs, and skull in various states of healing with callus formation; hence, the fractures were of prenatal origin. Despite the fractures, the growth of the long bones was not impaired. The radiographic findings were initially thought to represent osteogenesis imperfecta type IIC. However, there were also vascular anomalies not explained by this phenotype. Grossly, all arteries were elongated, thickened, and tortuous. The carotids, descending aorta, and iliac arteries were redundant to such an extent that they produced corkscrew patterns. There was also cutis laxa with loose, redundant skin over the entire body. Collagen genes did not show any mutations; however, when it was suggested Fibulin-4 be studied because of overlap with the condition described by Dasouki and colleagues in 2007, a homozygous premature stop codon mutation was found in that gene.
Assuntos
Anormalidades Múltiplas/genética , Artérias/anormalidades , Proteínas da Matriz Extracelular/genética , Mutação , Adulto , Cútis Laxa/genética , Feminino , Homozigoto , Humanos , Masculino , Osteogênese Imperfeita/patologia , Gravidez , Gêmeos MonozigóticosRESUMO
Myxopapillary ependymoma (MPE) is a rare subtype of ependymoma in children. Though classified as a Grade I tumor, their unpredictable behavior and propensity for local and disseminated recurrence poses a therapeutic challenge. Till date no predictive molecular markers exist for such recurrence, especially with dissemination. We demonstrated that Epidermal Growth Factor Receptor (EGFR) expression was seen in relapsed MPE both at diagnosis and at recurrence and none in the nonrecurring tumors. This finding suggests EGFR could be a predictive biomarker for recurrence in MPE.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias do Sistema Nervoso Central/diagnóstico , Ependimoma/diagnóstico , Receptores ErbB/análise , Neoplasias do Sistema Nervoso Central/patologia , Ependimoma/secundário , Feminino , Humanos , Proteínas Inibidoras de Apoptose/análise , Masculino , Recidiva Local de Neoplasia/diagnóstico , Prognóstico , Survivina , Ubiquitina-Proteína Ligases/análiseRESUMO
Denys-Drash syndrome, characterized by nephrosis, dysgenetic gonads and a predisposition to Wilms tumor, is due to germline mutations in the WT1 gene. We report the pathologic findings on monozygotic twins, both of whom presented with male pseudohermaphroditism, nephrotic syndrome, and progressed to renal failure and death within the first month of life. Sequence analysis of WT1 demonstrated a G-to-A substitution in exon 8 of the gene (c.1097G > A), resulting in an arginine-to-histidine (R366H) substitution in the second zinc finger domain. To the best of our knowledge, this is only the second set of monozygotic twins with Denys-Drash syndrome reported to date.
Assuntos
Síndrome de Denys-Drash/genética , Mutação Puntual , Insuficiência Renal/genética , Gêmeos Monozigóticos , Proteínas WT1/genética , Síndrome de Denys-Drash/patologia , Síndrome de Denys-Drash/fisiopatologia , Transtorno 46,XY do Desenvolvimento Sexual/genética , Evolução Fatal , Feminino , Humanos , Masculino , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologia , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Tumor de Wilms/genética , Tumor de Wilms/patologiaRESUMO
Timely communication of significant or unexpected findings in surgical pathology can significantly improve patient care. Although surgical pathology critical values have been published, no systematic assessment in pediatric surgical pathology has been published. We surveyed pediatric pathologists and pediatric subspecialists to develop pediatric surgical pathology critical values for verbal reporting before the final pathology report. A policy and process for reporting and documentation was implemented, with retrospective and prospective quality review. Critical values cases constituted 9.4% of surgical pathology accessions. Retrospective analysis revealed that 80% (73/91) had been reported and documented before policy implementation. Following implementation, 97.3% (402/413) were verbally reported and documented. A multidisciplinary group provided valuable information about critical values that might not have been obvious to pediatric pathologists but are important for patient care. Although the term critical values has become embedded in the surgical pathology literature, we would propose an alternative term for significant or unexpected findings that require timely communication and documentation.
Assuntos
Hospitais Pediátricos , Patologia Clínica/normas , Patologia Cirúrgica/normas , Pediatria , Adolescente , Criança , Sistemas de Informação em Laboratório Clínico , Sistemas de Comunicação no Hospital , Humanos , Lactente , Comunicação Interdisciplinar , Padrões de ReferênciaRESUMO
Oligodendroglioma is an uncommon childhood tumor and is more chemosensitive than other malignant glial neoplasms. Treatment involves gross total resection, and if anaplastic, radiation and chemotherapy. Distinct genetic alterations are associated with improved prognosis. We report a child with a low-grade oligodendroglioma that recurred as a high-grade oligodendroglioma and ultimately as extraneural systemic relapse. It was initially responsive to temozolomide, cyclophosphamide, etoposide, and carboplatin, perhaps predicted by combined loss of heterozygosity at 1p and 19q. This chemotherapy may be promising in treating malignant oligodendroglioma. However, he succumbed to progressive systemic disease. Positron emission spectroscopy scan was useful in sequentially assessing his disease.
Assuntos
Neoplasias Encefálicas/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Oligodendroglioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Progressão da Doença , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Oligodendroglioma/genética , Oligodendroglioma/terapia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/terapia , Neoplasias Pleurais/secundário , Neoplasias Pleurais/terapia , Tomografia por Emissão de Pósitrons/métodos , RecidivaRESUMO
Gardner fibroma (GAF) is a benign soft tissue lesion with a predilection for childhood and adolescence and an association with familial adenomatous polyposis (FAP) and desmoid type fibromatosis (desmoid). We report 45 patients with GAF with clinicopathologic correlation and immunohistochemical analysis for beta-catenin and related proteins. Forty-five patients with 57 GAFs were identified from surgical pathology and consultation files. Immunohistochemistry for beta-catenin, cyclin-D1, and C-myc was performed on formalin-fixed, paraffin-embedded tissues using standard techniques in 25 GAFs from 24 patients. Information about family history, intestinal polyps, colon cancer, and soft tissue tumors was available in 23 patients. Sixty-nine percent had known FAP or adenomatous polyposis coli (APC), 22% had no history of familial polyps or soft tissue tumors, and 13% had an individual or family history of soft tissue masses and/or desmoids, with follow-up periods of 6 months to 26 years (median 3 y, mean 5 y). The age range at initial diagnosis was 2 months to 36 years. Seventy-eight percent were diagnosed in the first decade, 15% in the second decade, and 7% in the third decade. Eight patients (18%) had documented desmoids concurrently or later; 4 of these had FAP and 1 had familial desmoids. Sites of GAF included the back and paraspinal region in 61%, the head and neck in 14%, the extremities in 14%, and the chest and abdomen in 11%. All displayed a bland hypocellular proliferation of haphazardly arranged coarse collagen fibers with a bland hypocellular proliferation of inconspicuous spindle cells, small blood vessels, and a sparse mast cell infiltrate. Immunohistochemically, 64% showed nuclear reactivity for beta-catenin (9 patients with known APC, 5 without definite information about FAP). One hundred percent showed nuclear reactivity for both cyclin-D1 and C-myc. beta-catenin reactivity had no correlation with age, site, or recurrence. Two beta-catenin-negative GAFs were from FAP patients. In conclusion, GAF has a predilection for childhood and early adulthood, a strong association with FAP/APC, an association with concurrent or subsequent development of desmoids, and overexpression of beta-catenin and other proteins in the APC and Wnt pathways. The proportion of sporadic GAFs that have APC mutation remains to be determined.
Assuntos
Fibroma/patologia , Síndrome de Gardner/patologia , Neoplasias de Tecidos Moles/patologia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/metabolismo , Polipose Adenomatosa do Colo/patologia , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Criança , Pré-Escolar , Ciclina D , Ciclinas/metabolismo , Feminino , Fibroma/complicações , Fibroma/metabolismo , Fibromatose Agressiva/complicações , Fibromatose Agressiva/metabolismo , Fibromatose Agressiva/patologia , Síndrome de Gardner/complicações , Síndrome de Gardner/metabolismo , Humanos , Imuno-Histoquímica , Lactente , Masculino , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/metabolismo , beta Catenina/metabolismoRESUMO
We describe a case of inflammatory myofibroblastic tumor with an unusual constellation of clinical, pathologic, and genetic findings. A 7-year-old girl had an 11-cm abdominopelvic mass accompanied by thrombocytosis, anemia, elevated erythrocyte sedimentation rate, and elevated C-reactive protein. The inflammatory myofibroblastic tumor displayed unusual histologic features of zonal coagulative necrosis, high cellularity with a herringbone pattern, and tumor-associated osteoclast-like giant cells. The complex tumor karyotype included a translocation t(1;2)(q21; p23). Following resection, the laboratory abnormalities resolved. The patient is well and free of recurrence at 3 years following resection. This case raises interesting questions about clinical, pathologic, prognostic, and molecular genetic interrelationships in inflammatory myofibroblastic tumor.
Assuntos
Neoplasias Abdominais/patologia , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 2/genética , Granuloma de Células Plasmáticas/patologia , Proteínas Tirosina Quinases/genética , Trombocitose/patologia , Translocação Genética/genética , Neoplasias Abdominais/complicações , Neoplasias Abdominais/genética , Neoplasias Abdominais/cirurgia , Quinase do Linfoma Anaplásico , Criança , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Rearranjo Gênico , Granuloma de Células Plasmáticas/complicações , Granuloma de Células Plasmáticas/genética , Granuloma de Células Plasmáticas/cirurgia , Humanos , Hibridização in Situ Fluorescente , Proteínas Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases , Trombocitose/complicações , Trombocitose/genéticaRESUMO
Osseous abnormalities, including long-bone dysplasia with pseudarthrosis (PA), are associated with neurofibromatosis type 1 (NF1). Prospectively acquired tissue from the PA site of two individuals with NF1 was used for immunohistochemical characterization and genotype analysis of the NF1 locus. Typical immunohistochemical features of neurofibroma were not observed. Genotype analysis of PA tissue with use of four genetic markers (D17S1863, GXALU, IN38, and 3NF1-1) spanning the NF1 locus demonstrated loss of heterozygosity. These results are the first to document double inactivation of NF1 in PA tissue and suggest that the neurofibromin-Ras signal transduction pathway is involved in this bone dysplasia in NF1.
Assuntos
Inativação Gênica , Genes da Neurofibromatose 1 , Pseudoartrose/genética , Tíbia/patologia , Sequência de Bases , Primers do DNA , Humanos , Imuno-Histoquímica , Recém-Nascido , MasculinoRESUMO
CONTEXT: Previous reports suggest that the human epidermal growth factor 2 (HER-2/neu) receptor may be overexpressed in osteosarcoma. OBJECTIVE: To determine whether osteosarcomas have amplifications of the HER-2/neu gene. DESIGN: We studied a series of osteosarcomas by fluorescence in situ hybridization (FISH) and by 2 real-time polymerase chain reaction assays that measure the amount of HER-2/neu DNA relative to a control gene. The HER-2/ neu monoplex and multiplex assays were capable of identifying those cases of breast cancer that were known to overexpress HER-2/neu as assessed by FISH. We initially studied 21 cases of osteosarcoma by FISH analysis (using a technique that included a probe for chromosome 17), 11 of which had their HER-2/neu gene amplification status previously reported. RESULTS: None of these osteosarcoma cases showed HER-2/neu amplification by our FISH analysis and subsequent quantitative (multiplex) polymerase chain reaction. Apparent expression of HER-2/neu protein was observed in several of the cases but the immunoreactivity was localized to the cytoplasm and was not membranous in character. An additional 35 osteosarcoma specimens were subjected to monoplex polymerase chain reaction analysis, and amplifiable DNA was recovered from 19 specimens (54%). None of these samples had HER-2/neu amplification by monoplex PCR analysis and only one case had membranous immunoreactivity graded as 1+. CONCLUSION: Although a small subset of osteosarcomas had weak noncircumferential membranous immunoreactivity for HER-2/neu protein, no osteosarcomas demonstrated positive (2+ or 3+) immunoreactivity for HER-2/ neu protein and none showed HER-2/neu gene amplification by either FISH or polymerase chain reaction.
Assuntos
Neoplasias Ósseas/genética , Amplificação de Genes , Genes erbB-2 , Hibridização in Situ Fluorescente/métodos , Osteossarcoma/genética , Reação em Cadeia da Polimerase/métodos , Receptor ErbB-2/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Primers do DNA/química , Sondas de DNA/química , DNA de Neoplasias/análise , Feminino , Humanos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Receptor ErbB-2/metabolismoRESUMO
CONTEXT: Intraoperative consultations, including frozen sections (FSs), are essential for patient care and are a key quality component in anatomic pathology. Little data exists about the use, frequency, and type of discrepancies and deferral rates of FS diagnoses in pediatric and adolescent surgical pathology. OBJECTIVE: The purpose of this study was to analyze indications, discrepancies, and deferrals for all FSs performed at a children's hospital during a 10-year period. DESIGN: All FSs for 1995-2004 were reviewed for indications, discrepancies, deferred diagnoses, and turnaround time. Discrepancies were categorized into major and minor subtypes according to potential impact on patient care. RESULTS: A total of 35,611 surgical pathology cases were accessioned, with 2839 intraoperative consultations, which included 2783 FSs and 56 nonmicroscopic consultations. Most frequent indications included questions related to neoplasms (tumor detection, specimen adequacy, triage, classification, and margins) and suspected Hirschsprung disease. In these consultations, 115 discrepancies (4%) were identified, of which 7 (0.2%) were major, with potentially significant clinical impact, and 108 (3.9%) were minor. The major discrepancies included tumor, ganglion cell, or organism detection. The minor discrepancies involved sampling error, reclassification of benign or malignant neoplasms without clinical consequences, tumor typing or grading, and ganglion cell identification without clinical impact. Deferrals in 718 FSs (25% deferral rate) included tumor classification from generic to specific, identification of organisms, and evaluation of lymph node biopsies for lymphoma. Turnaround time exceeded 20 minutes in 403 cases (14%). CONCLUSIONS: The FS rate of 7.8% overall and 5% of surgical pathology cases is similar in children's and general hospitals. The major discrepancy (discordance) rate is lower, which may reflect the different indications for FS in children and adolescents. Evaluation of colonic biopsies for ganglion cells is a diagnostic pitfall. The deferral rate of 25% reflects the definition of a deferred diagnosis. Traditional definitions of deferred and discordant FS diagnoses should be refined to reflect the increasing use of adjunct techniques, especially in tumor classification. These findings emphasize that, in children and adolescents, most FSs are performed for tumor classification, triage, detection, and specimen adequacy, and for possible Hirschsprung disease. In children and adolescents, FSs are used infrequently to identify normal or unknown tissue, to analyze a lesion in a radiographically directed specimen, or to detect lymph node metastases. The differences in pediatric and adolescent FS indications and use underscore the importance of focused education in pediatric surgical pathology.
Assuntos
Secções Congeladas/métodos , Hospitais Pediátricos , Patologia Cirúrgica/métodos , Pediatria , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/cirurgia , Humanos , Período Intraoperatório , Neoplasias/classificação , Neoplasias/diagnóstico , Neoplasias/cirurgia , Encaminhamento e ConsultaRESUMO
PURPOSE: Development and differentiation of the human fetal prostate are androgen dependent and follow a specific pattern of solid bud-ductal morphogenesis, which involves stromal-epithelial interactions. Androgen receptor associated protein 55 (ARA55) an androgen receptor coactivator localized in stromal cells, binds to androgen receptor (AR) and regulates androgen receptor translocation and transcriptional activity. We investigated whether ARA55 has a role in human prostate development. MATERIALS AND METHODS: ARA55 expression was examined in 25 human prostates from fetuses at gestational ages 10 to 40 weeks and compared to the expression of 34betaE12 (a basal cell marker), smooth muscle actin, desmin (a smooth muscle marker), vimentin (a mesenchymal marker) and Ki-67 (a proliferation marker) by immunohistochemistry. RESULTS: Prostatic epithelium appeared as solid epithelial buds from the urogenital sinus. It underwent arborization and ductal differentiation from the center to the periphery. ARA55 was expressed in stromal cells with a zonal pattern, primarily in the peripheral zone surrounding the noncanalized acini. Most cells in solid buds were positive for 34betaE12, while only basal layer cells in the centrally located epithelial ducts stained with 34betaE12. Solid buds also had a higher proliferation index than ducts. In addition, ARA55 expressing stromal cells but not ARA55 negative stromal cells showed smooth muscle differentiation. CONCLUSIONS: The intimate relationship between ARA55 expressing stromal cells and mitotically active, noncanalized acini suggests that ARA55 has a role in the stromal-epithelial interaction involved in fetal prostate development.
Assuntos
Proteínas do Citoesqueleto/análise , Proteínas de Ligação a DNA/análise , Próstata/embriologia , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Epitélio/patologia , Feminino , Idade Gestacional , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas com Domínio LIM , Masculino , Gravidez , Próstata/patologia , Células Estromais/patologiaRESUMO
Central nervous system atypical teratoid/rhabdoid tumor (AT/RT) and choroid plexus carcinoma (CPC) are rare, highly malignant tumors that predominantly arise in infants and young children. Overlapping clinical, histologic, ultrastructural, or immunophenotypic features may obscure the diagnosis in some cases. AT/RT is characterized by deletions and/or mutations of the INI1 tumor-suppressor gene on chromosome band 22q11.2. We have recently developed an INI1 immunohistochemical staining assay. Negative staining of tumor cells resulting from inactivation of the INI1 gene is a consistent feature of AT/RT. Mutations of INI1 in some CPCs have been reported. The purpose of the present study was to determine if immunohistochemical staining with an INI1 antibody would provide a sensitive means of distinguishing between CPC and AT/RT. We examined 28 tumors with a submitted diagnosis of CPC. Twenty-one CPCs showed retained expression of INI1 and seven tumors showed loss of INI1 expression. Cytogenetic, FISH, and/or INI1 mutation results were also available for 13 tumors. In three of the seven cases, monosomy 22 was the only cytogenetic abnormality, suggestive of AT/RT. However, monosomy 22 was also identified in 3 tumors with complex karyotypes that retained INI1 expression. The 7 tumors that were immunonegative for INI1 had features that were consistent with AT/RT. Immunostaining for INI1 protein is retained in the majority of CPC and is lost in AT/RT. This expression pattern seems to better define the 2 groups of tumors than does light or electron microscopy, routine immunohistochemistry, or cytogenetic analysis alone.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Neoplasias do Plexo Corióideo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Teratoma/metabolismo , Adolescente , Apoptose , Biomarcadores Tumorais/genética , Carcinoma/patologia , Criança , Pré-Escolar , Neoplasias do Plexo Corióideo/patologia , Proteínas Cromossômicas não Histona , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Lactente , Masculino , Mucina-1/metabolismo , Proteína SMARCB1 , Coloração e Rotulagem/métodos , Teratoma/patologia , Fatores de TranscriçãoRESUMO
Dramatic improvements in survival for children with cancer have led to increased numbers of posttreatment pathologic specimens, particularly in bone and soft tissue sarcomas. Current therapeutic protocols in North America require specific pathologic classification and stratify patients based on clinical, biologic, and pathologic features. For osteosarcoma, the pathologic response to therapy predicts prognosis and modifies the treatment regimen. Ongoing studies aim to assess the response to therapy and outcome in other types of soft tissue and bone tumors. The pathologic evaluation of pretreatment and posttreatment specimens is critical for therapeutic decisions and prognostic assessment. A standardized approach to posttherapy pathologic specimens, with attention to appropriate use of ancillary tests, and assessment of clinical and biologic significance of therapy-induced pathologic changes has significance for patient management and treatment protocols.