ABSTRACT
BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed "DNET-like neoplasms of the septum pellucidum." Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series. METHODS: We collected 20 of these tumors for a comprehensive study of their clinical, radiological, and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n = 22) were also reviewed for comparative purposes. RESULTS: The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum/septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). Septal DNET showed a high frequency (~80%) of mutations of platelet derived growth factor receptor A (PDGFRA), and alterations in fibroblast growth factor receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group. CONCLUSIONS: Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity.
Subject(s)
Biomarkers, Tumor/genetics , Brain Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Magnetic Resonance Imaging/methods , Mutation , Neoplasms, Neuroepithelial/pathology , Biomarkers, Tumor/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Child , DNA Methylation , Female , Humans , Male , Neoplasms, Neuroepithelial/genetics , Neoplasms, Neuroepithelial/metabolism , Prognosis , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Survival RateABSTRACT
In this study, we report the first case of Mycobacterium tuberculosis endocarditis in an immunocompetent child born in the United States. Mass spectrometry of the vegetation identified coagulation, humoral immune proteins, neutrophil granule proteins, and histones. Few neutrophils on histopathology suggest that neutrophil extracellular traps may contribute to tuberculous endocardiac mass formation.
Subject(s)
Endocarditis, Bacterial/diagnostic imaging , Immunocompetence , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Cardiovascular/diagnostic imaging , Antitubercular Agents/therapeutic use , Bone Marrow/microbiology , Bone Marrow/pathology , Chromatography, Liquid , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/immunology , Endocardium/chemistry , Female , Humans , Infant , Lymphohistiocytosis, Hemophagocytic/microbiology , Lymphohistiocytosis, Hemophagocytic/pathology , Mass Spectrometry , Neutrophils/immunology , Protein S/analysis , Tuberculosis, Cardiovascular/complications , Tuberculosis, Cardiovascular/drug therapy , Tuberculosis, Cardiovascular/immunology , United StatesABSTRACT
We present a case of empirical treatment failure for chronic osteomyelitis in a previously healthy 11-year-old male involving the distal phalanx of the right first digit. After initial debridement, empiric antibiotics were started for presumed Staphylococcus aureus infection. Operative bacterial cultures yielded no growth. Despite three weeks of antistaphylococcal antibiotics the patient's symptoms worsened and the destruction of bone progressed. A repeat plain X-ray revealed a new lesion in the proximal phalanx of the right second digit. The recognition of multifocal osteomyelitis led to reexamination of bone tissue specimens using special stains which demonstrated rare broad-based budding yeast. Fungal cultures eventually grew Blastomyces dermatitidis. Treatment with amphotericin B led to rapid clinical improvement. This case illustrates that clinicians must remain vigilant for warning signs that empiric treatment may be failing for presumptive Staphylococcus aureus, provoking reconsideration of the differential diagnosis and an intensification of efforts to evaluate for alternative etiologies.
Subject(s)
Prenatal Diagnosis , Supratentorial Neoplasms/congenital , Teratoma/congenital , Adult , Brain Edema/etiology , Cesarean Section , Diabetes Insipidus/congenital , Diabetes Insipidus/etiology , Encephalocele/etiology , Fatal Outcome , Female , Humans , Hydrocephalus/diagnosis , Hydrocephalus/diagnostic imaging , Hydrocephalus/embryology , Hydrocephalus/etiology , Hypopituitarism/congenital , Hypopituitarism/etiology , Infant, Newborn , Magnetic Resonance Imaging , Male , Respiratory Distress Syndrome, Newborn/etiology , Supratentorial Neoplasms/complications , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/embryology , Teratoma/complications , Teratoma/diagnostic imaging , Teratoma/embryology , Tomography, X-Ray Computed , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: To evaluate in a prospective, controlled fashion the prevalence of umbilical artery Doppler waveform notching and its association with cord and placental abnormalities. METHODS: During a 6-month period, umbilical artery velocity waveforms were prospectively obtained on 1857 pregnancies at greater than 27 weeks' gestation. All pregnant patients with the presence of a persistent fetal umbilical artery waveform notch formed the study population (cases). Control patients, matched for gestational age, with normal umbilical artery waveforms, were selected for comparison (2 controls per case). After delivery, detailed pathologic examination was performed on all umbilical cords and placentas. RESULTS: The presence of an umbilical artery waveform notch was noted in 29 (1.6%) of 1857 pregnancies. Postnatal placental evaluation showed the presence of an accessory placental lobe in 5 (17%) of 29 cases compared with 1 (1.8%) of 54 controls (P = .018). Overall, the presence of an umbilical artery waveform notch was associated with umbilical cord abnormalities in 21 (72%) of 29 cases compared with 8 (14%) of 54 controls (odds ratio, 15; 95% confidence interval, 4.4-54.4). CONCLUSIONS: Umbilical artery waveform notching appears to be a strong predictor of cord and placental abnormalities. This finding may have important clinical implications.
