Purpose: KRAS mutations are found in f25% of lung adenocarcinomas inWestern countries and, as a group, have been strongly associated with cigarette smoking.These mutations are predictive of poor prognosis in resected disease as well as resistance to treatment with erlotinib or gefitinib. Experimental Design: We determined the frequency and type of KRAS codon 12 and 13 mutations and characterized their association with cigarette smoking history in patients with lung adenocarcinomas. Results: KRAS mutational analysis was done on 482 lung adenocarcinomas, 81 (17%) of which were obtained from patients who had never smoked cigarettes. KRAS mutations were found in 15% (12 of 81; 95% confidence intervals, 8-24%) of tumors from never smokers. Similarly, 22% (69 of 316; 95% confidence intervals, 17-27%) of tumors from former smokers, and 25% (21 of 85; 95% confidence intervals, 16-35%) of tumors from current smokers had KRAS mutations. The frequency of KRAS mutation was not associated with age, gender, or smoking history. The number of pack years of cigarette smoking did not predict an increased likelihood of KRAS mutations. Never smokers were significantly more likely than former or current smokers to have a transition mutation (G!A) rather than the transversion mutations known to be smokingrelated (G!Tor G!C; P < 0.0001).Conclusions: Based on our data, KRAS mutations are not rare among never smokers with lung adenocarcinoma and such patients have a distinct KRAS mutation profile.The etiologic and biological heterogeneity of KRAS mutant lung adenocarcinomas is worthy of further study.Since the identification of somatic epidermal growth factor receptor (EGFR) mutations, there has been heightened interest in the molecular basis of lung cancer in patients who never smoked cigarettes (1 -3). Somatic mutations in EGFR have been identified in f15% of all patients with lung adenocarcinoma, with the proportion increasing to 50% in patients who never smoked cigarettes. There is an inverse relationship between cigarette smoking history and frequency of EGFR mutations, with the frequency of EGFR mutations decreasing significantly among patients who smoked more than 15 pack years (4). Such refined understanding of the relationship between smoking history and presence of EGFR mutations has allowed the design of clinical trials which use smoking history to enrich the number of patients with somatic EGFR mutations (5-7).In contrast to EGFR mutations, KRAS mutations were initially identified in patients with lung adenocarcinoma who had a history of heavy cigarette smoking and were thought to be uncommon in patients without a history of smoking cigarettes (8). These mutations are found in f25% of lung adenocarcinomas in western countries but are less common in Asian populations (9, 10). KRAS mutations have been associated with poor prognosis in resected non -small cell lung cancer (NSCLC; refs. 11-13), lack of survival benefit from adjuvant chemotherapy (14), and resistance to erlotinib or gefitinib (15). More than 95% of KRAS ...
We present a case of NUT midline carcinoma (NMC) mimicking lymphoma in an adolescent boy, with attention to multidetector CT appearance and pattern of metastasis on [F-18]2-fluoro-2-deoxyglucose positron emission tomography (FDG PET/CT). Few case reports have focused on the imaging characteristics of this rare tumor in the pediatric imaging literature. A newly described but increasingly recognized disease entity, NMC should enter the differential of pediatric midline tumors displaying particularly aggressive characteristics on imaging.
Developmental dysplasia of the hip is a spectrum disorder of hip development that ranges in severity from abnormal acetabular morphology to complete hip dislocation. While treatment with a Pavlik harness is highly effective in infants younger than 6 months, older infants and children and those with orthotic failure often warrant surgical reduction and placement of a spica cast, which limits subsequent imaging evaluation. Magnetic resonance (MR) imaging has been described in the evaluation of the adequacy of hip reduction for more than 2 decades, but the practice is still not widespread and is performed routinely at relatively few centers. MR imaging is a robust tool for outcome assessment after hip reduction and placement of a spica cast, facilitating multiplanar confirmation of concentric reduction independent of an ossific nucleus or orthopedic hardware. Excellent image contrast of soft tissues allows identification of obstacles to concentric reduction, which may be extra-articular or intra-articular. Extra-articular obstacles include tightening of the adductor muscles and tightening of the iliopsoas tendon with constriction of the joint capsule. Intra-articular obstacles include limbus formation, labral inversion, an enlarged pulvinar, and hypertrophy of the ligamentum teres and/or the transverse acetabular ligament. Intravenous contrast material administration may demonstrate altered epiphyseal blood flow and help identify patients at risk for early ischemia. Imaging technique and image interpretation can be optimized to facilitate the performance of postreduction MR imaging studies where they may be of benefit. (©)RSNA, 2016.
Poorly differentiated chordoma (PDC) is a recently recognized subtype of chordoma characterized by expression of the embryonic transcription factor, brachyury, and loss of INI1. PDC primarily affects children and is associated with a poor prognosis and limited treatment options. Here we describe the molecular and immune tumour microenvironment profiles of two paediatric PDCs produced using whole-genome, transcriptome and whole-genome bisulfite sequencing (WGBS) and multiplex immunohistochemistry. Our analyses revealed the presence of tumour-associated immune cells, including CD8+ T cells, and expression of the immune checkpoint protein, PD-L1, in both patient samples. Molecular profiling provided the rationale for immune checkpoint inhibitor (ICI) therapy, which resulted in a clinical and radiographic response. A dominant T cell receptor (TCR) clone specific for a brachyury peptide–MHC complex was identified from bulk RNA sequencing, suggesting that targeting of the brachyury tumour antigen by tumour-associated T cells may underlie this clinical response to ICI. Correlative analysis with rhabdoid tumours, another INI1-deficient paediatric malignancy, suggests that a subset of tumours may share common immune phenotypes, indicating the potential for a therapeutically targetable subgroup of challenging paediatric cancers.
With the emerging use of ultrasound in the evaluation of children with Crohn disease presenting with acute abdominal symptoms, there is a need to become familiar with the sonographic features of this disease. Our aim is to provide a primer of the characteristic intramural and extramural US findings in children with Crohn disease to serve as a practical and systematic guide to interpretation.
Contrast-enhanced MRI can differentiate perforated from non-perforated appendicitis. The presence of multiple findings increases diagnostic accuracy, with a threshold of any four findings optimally discriminating between perforated and non-perforated cases. These results may help guide management decisions as MRI assumes a greater role in the work-up of pediatric appendicitis.
Children with terminal ileal Crohn disease requiring surgical bowel resection demonstrate more severe manifestations of imaging features traditionally associated with both active inflammation and chronic fibrosis than those managed medically on US and MRE, findings that are corroborated by histopathology. These features may potentially serve as imaging biomarkers indicating the necessity for surgical intervention.
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