Universal germline genetic testing in patients with hematologic malignancies using DNA isolated from nail clippings.

Not available.

Osteopetrorickets: two contradictory patterns-one unifying diagnosis.

A 5-month-old infant with bone findings on x-ray presented an apparent contradiction including findings of both diffusely dense bones and rickets in the context of a history and laboratory investigation that suggested leukemia. Next generation gene panel sequencing revealed a TCIRG1 mutation which is consistent with autosomal recessive osteopetrosis. The paradoxical x-ray findings underscore a recently elucidated mechanism for the pathogenesis of a TCIRG mutation. This case highlights the importance of recognizing this radiographic, seeming contradictory, association in the context of a confusing clinical presentation. Failure to recognize this pattern promptly may lead to a delay in diagnosis, thus potentially permanent organ failure.

Free-breathing high isotropic resolution quantitative susceptibility mapping (QSM) of liver using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction.

PURPOSE: To enable free-breathing and high isotropic resolution liver quantitative susceptibility mapping (QSM) using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction. METHODS: Using 3D multi-echo UTE cones MRI, a respiratory motion was estimated from the k-space center of the imaging data. After sorting the k-space data with estimated motion, respiratory motion state-resolved reconstruction was performed for multi-echo data followed by nonlinear least-squares fitting for proton density fat fraction (PDFF), R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , and fat-corrected B0 field maps. PDFF and B0 field maps were subsequently used for QSM reconstruction. The proposed method was compared with motion-averaged (gridding) reconstruction and conventional 3D multi-echo Cartesian MRI in moving gadolinium phantom and in vivo studies. Region of interest (ROI)-based linear regression analysis was performed on these methods to investigate correlations between gadolinium concentration and QSM in the phantom study and between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM in in vivo study. RESULTS: Cones with motion-resolved reconstruction showed sharper image quality compared to motion-averaged reconstruction with a substantial reduction of motion artifacts in both moving phantom and in vivo studies. For ROI-based linear regression analysis of the phantom study, susceptibility values from cones with motion-resolved reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.31 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.05, R 2 $$ {R}^2 $$ = 0.999) and Cartesian without motion ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.32 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.04, R 2 $$ {R}^2 $$ = 1.000) showed linear relationships with gadolinium concentrations and showed good agreement with each other. For in vivo, motion-resolved reconstruction showed higher goodness of fit ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.00261 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.524, R 2 $$ {R}^2 $$ = 0.977) compared to motion-averaged reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.0021 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.572, R 2 $$ {R}^2 $$ = 0.723) in ROI-based linear regression analysis between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM. CONCLUSION: Feasibility of free-breathing liver QSM was demonstrated with motion-resolved 3D multi-echo UTE cones MRI, achieving high isotropic resolution currently unachievable in conventional Cartesian MRI.

Slipped capital femoral epiphyses: A major on-target adverse event associated with FGFR tyrosine kinase inhibitors in pediatric patients.

Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) are increasingly being used off label in pediatrics. Long-term safety data are limited, and serious toxicities unique to pediatrics may emerge. In a retrospective analysis of patients less than 18 years of age with recurrent/refractory FGFR altered gliomas treated with FGFR TKIs at MSKCC (n = 7), we observed slipped capital femoral epiphyses in three of seven patients along with increased linear growth velocity. Clinicians should closely monitor bone health and have a low index of suspicion for serious orthopedic complications including slipped capital femoral epiphyses and inform patients of related risks as part of consent when treating with FGFR TKIs.

Imaging of pediatric pancreas tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Primary pancreatic tumors in children are rare with an overall age-adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm, followed by pancreatoblastoma. This paper describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow-up.

Imaging of pediatric adrenal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up.

Imaging of pediatric ovarian tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Ovarian tumors in children are uncommon. Like those arising in the adult population, they may be broadly divided into germ cell, sex cord, and surface epithelium subtypes; however, germ cell tumors comprise the majority of lesions in children, whereas tumors of surface epithelial origin predominate in adults. Diagnostic workup, including the use of imaging, requires an approach that often differs from that required in an adult. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary ovarian malignancy at diagnosis and during follow-up.

Imaging of pediatric testicular tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Primary intratesticular tumors are uncommon in children, but incidence and risk of malignancy both sharply increase during adolescence. Ultrasound is the mainstay for imaging the primary lesion, and cross-sectional modalities are often required for evaluation of regional or distant disease. However, variations to this approach are dictated by additional clinical and imaging nuances. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary testicular malignancy at diagnosis and during follow-up.

Lumps and bumps: What not to miss.

The evaluation of pediatric patients with subcutaneous nodules remains a diagnostic challenge. Pediatric dermatologists are regularly confronted with patients who have a nonspecific nodule. Though most masses that require evaluation are ultimately benign, the possibility of a more aggressive process, including borderline or malignant neoplasms, underscores the pivotal role of the pediatric dermatologist in recognizing these lesions. The aim of this review is to provide an overview of lumps and bumps that are important to recognize to prevent delay in diagnosis or treatment of a serious underlying condition. Clinical clues that may lead the pediatric dermatologist to have a higher index of suspicion for more aggressive lesions are reviewed. Suggestions for evaluation and workup, as well as tips for the difficult to discern lesion, are proposed.

Patient-adapted organ absorbed dose and effective dose estimates in pediatric 18F-FDG positron emission tomography/computed tomography studies.

BACKGROUND: Organ absorbed doses and effective doses can be used to compare radiation exposure among medical imaging procedures, compare alternative imaging options, and guide dose optimization efforts. Individual dose estimates are important for relatively radiosensitive patient populations such as children and for radiosensitive organs such as the eye lens. Software-based dose calculation methods conveniently calculate organ dose using patient-adjusted and examination-specific inputs. METHODS: Organ absorbed doses and effective doses were calculated for 429 pediatric 18F-FDG PET-CT patients. Patient-adjusted and scan-specific information was extracted from the electronic medical record and scanner dose-monitoring software. The VirtualDose and OLINDA/EXM (version 2.0) programs, respectively, were used to calculate the CT and the radiopharmaceutical organ absorbed doses and effective doses. Patients were grouped according to age at the time of the scan as follows: less than 1 year old, 1 to 5 years old, 6 to 10 years old, 11 to 15 years old, and 16 to 17 years old. RESULTS: The mean (+/- standard deviation, range) total PET plus CT effective dose was 14.5 (1.9, 11.2-22.3) mSv. The mean (+/- standard deviation, range) PET effective dose was 8.1 (1.2, 5.7-16.5) mSv. The mean (+/- standard deviation, range) CT effective dose was 6.4 (1.8, 2.9-14.7) mSv. The five organs with highest PET dose were: Urinary bladder, heart, liver, lungs, and brain. The five organs with highest CT dose were: Thymus, thyroid, kidneys, eye lens, and gonads. CONCLUSIONS: Organ and effective dose for both the CT and PET components can be estimated with actual patient and scan data using commercial software. Doses calculated using software generally agree with those calculated using dose conversion factors, although some organ doses were found to be appreciably different. Software-based dose calculation methods allow patient-adjusted dose factors. The effort to gather the needed patient data is justified by the resulting value of the characterization of patient-adjusted dosimetry.

Proportion and Clinical Relevance of Intraspinal Air in Patients With Pneumomediastinum.

OBJECTIVE: The purposes of this study were to determine the incidence of pneumorrhachis among patients with pneumomediastinum, determine whether its proportion correlates with the extent of pneumomediastinum, and ascertain its clinical relevance. MATERIALS AND METHODS: The radiologic database was searched for CT reports between January 2009 and September 2013 containing the term "pneumomediastinum" or "mediastinal air." Scans were examined for pneumomediastinum, pneumorrhachis, pneumothorax, sternotomy, and distribution of pneumomediastinum. The age and sex of the patient and probable cause of the abnormality were recorded. Cases that might have had another cause were excluded. RESULTS: The search yielded 422 CT scans. Among these, 242 instances of pneumomediastinum in 241 patients were found. Fifteen of these patients had pneumorrhachis. One was excluded because of recent traumatic spinal penetration. There was no significant difference in age or sex between patients with and those without pneumorrhachis. After application of the exclusion criteria, there were 14 cases of pneumorrhachis, yielding a proportion of 5.8%. Pneumorrhachis was observed more frequently in cases of the most severe grade (grade C) of pneumomediastinum; however, that relationship was not statistically significant (11 cases [8.2%]; p = 0.304). Pneumorrhachis was found significantly more frequently in patients with distribution of air in all three mediastinal compartments (13 cases, 16.2%, p < 0.001). Pneumorrhachis was overrepresented among subjects with spontaneous compared with those with secondary pneumomediastinum, although the trend did not reach statistical significance. CONCLUSION: Pneumorrhachis was present in 5.8% of patients. It is significantly more common in patients with the broadest distributions of mediastinal air and nonsignificantly more common in association with spontaneous as opposed to secondary pneumomediastinum. Pneumorrhachis in patients with pneumomediastinum is a generally benign, self-resolving condition.

A Convex Hull-Based New Metric for Quantification of Bladder Wall Irregularity in Pediatric Patients With Congenital Anomalies of the Kidney and Urinary Tract.

OBJECTIVES: Early identification and quantification of bladder damage in pediatric patients with congenital anomalies of the kidney and urinary tract (CAKUT) is crucial to guiding effective treatment and may affect the eventual clinical outcome, including progression of renal disease. We have developed a novel approach based on the convex hull to calculate bladder wall trabecularity in pediatric patients with CAKUT. The objective of this study was to test whether our approach can accurately predict bladder wall irregularity. METHODS: Twenty pediatric patients, half with renal compromise and CAKUT and half with normal renal function, were evaluated. We applied the convex hull approach to calculate T, a metric proposed to reflect the degree of trabeculation/bladder wall irregularity, in this set of patients. RESULTS: The average T value was roughly 3 times higher for diseased than healthy patients (0.14 [95% confidence interval, 0.10-0.17] versus 0.05 [95% confidence interval, 0.03-0.07] for normal bladders). This disparity was statistically significant (P < .01). CONCLUSIONS: We have demonstrated that a convex hull-based procedure can measure bladder wall irregularity. Because bladder damage is a reversible precursor to irreversible renal parenchymal damage, applying such a measure to at-risk pediatric patients can help guide prompt interventions to avert disease progression.

Sonographic Prediction of Pediatric Renal Scarring With Full Parameter Normalization.

OBJECTIVES: To predict the chronic kidney disease (CKD) state for pediatric patients based on scaled renal cortical echogenicity. METHODS: Sonograms from a cohort of 26 patients, half of whom had stage 4 or 5 CKD, whereas the other half had normal renal function, were analyzed. For each patient image, a region of interest (ROI) was drawn around the renal cortex for comparison with an ROI drawn around the hepatic parenchyma. The latter ROI was shifted spatially to normalize the signal attenuations and time-gain compensations of the two organs' ROIs. Then the average pixel intensity of the renal ROI was divided by the corresponding hepatic value, resulting in scaled renal cortical echogenicity. RESULTS: The average scaled renal cortical echogenicity was higher for diseased than healthy kidneys by roughly a factor of 2 (2.01 [95% confidence interval, 1.62-2.40] versus 1.05 [95% confidence interval, 0.88-1.23] for normal kidneys). This difference was statistically significant (P < .001). CONCLUSIONS: Our results show that the pediatric CKD state correlates with rigorously calculated scaled renal cortical echogenicity.

Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma.

Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.

Clinical spectrum of capillary malformation-arteriovenous malformation syndrome presenting to a pediatric dermatology practice: a retrospective study.

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is an autosomal dominant disorder caused by RASA1 mutations. The prevalence and phenotypic spectrum are unknown. Evaluation of patients with multiple CMs is challenging because associated AVMs can be life threatening. The objective of this study was to describe the clinical characteristics of children presenting with features of CM-AVM to an academic pediatric dermatology practice. After institutional review board approval was received, a retrospective chart review was performed of patients presenting between 2009 and 2012 with features of CM-AVM. We report nine cases. Presenting symptoms ranged from extensive vascular stains and cardiac failure to CMs noted incidentally during routine skin examination. All demonstrated multiple CMs, two had Parkes Weber syndrome, and two had multiple infantile hemangiomas. Seven patients had family histories of multiple CMs; three had family histories of large, atypical CMs. Six had personal or family histories of AVMs. Genetic evaluation was recommended for all and was pursued by six families; four RASA1 mutations were identified, including one de novo. Consultations with neurology, cardiology, and orthopedics were recommended. Most patients (89%) have not required treatment to date. CM-AVM is an underrecognized condition with a wide clinical spectrum that often presents in childhood. Further evaluation may be indicated in patients with multiple CMs. This study is limited by its small and retrospective nature.

A comparison of bronchoalveolar lavage versus lung biopsy in pediatric recipients after stem cell transplantation.

Bronchoalveolar lavage (BAL) has been a useful initial diagnostic tool in the evaluation of pulmonary complications after hematopoietic stem cell transplantation (HSCT); however, the diagnostic sensitivity, prevalence, and outcome after BAL versus lung biopsy (LB) in pediatric HSCT patients remains to be determined. We reviewed 193 pediatric HSCT recipients who underwent a total of 235 HSCTs. Sixty-five patients (34%) underwent a total of 101 BALs for fever, respiratory distress, and/or pulmonary infiltrates on chest radiograph and/or computed tomography scan. The 1-year probability of undergoing BAL was 43.0% after allogeneic stem cell transplantation (alloSCT) and 8.5% after autologous stem cell transplantation (autoSCT) (P = .001). Sixteen of the 193 patients (8%) patients underwent 19 LBs. The probability of undergoing LB at 1 year after HSCT was 9.3%. No grade III or IV adverse events related to either procedure were observed. Of the 101 BALs performed, 40% (n = 40) were diagnostic, with a majority revealing a bacterial pathogen. Among the 19 LBs performed, 94% identified an etiology. In multivariate analysis, myeloablative conditioning alloSCT conferred the highest risk of requiring a BAL (hazard ratio [HR],8.5; P = .0002). The probability of 2-year overall survival was 20.2% in patients who underwent BAL, 17.5% for patients who underwent biopsy, and 67.4% for patients who had neither procedure. In multivariate analysis, only the requirement of a BAL was independently associated with an increased risk of mortality (HR, 2.96; P < .0001). In summary, in this cohort of pediatric HSCT recipients, BAL and LB were used in approximately 35% and 8% of pediatric HSCTs with diagnostic yields of approximately 40% and 94%, respectively, and were both associated with poor long-term outcomes.

Martin 'Dick' Wittenborg 1914-1969: a legacy.

The life of Martin H. Wittenborg was short. During his tenure at Boston Children's Hospital, he wrote brilliant papers based on his observations regarding such entities as intestinal malrotation and vascular rings and slings. He wrote about his extensive experience using radiotherapy in the treatment of neuroblastoma and its effects on the growing spine. This article reflects the memories of some of his students, who describe him as a brilliant teacher. His effect on so many and his contributions are all the more remarkable considering the fact that Wittenborg was deaf.

Molecular Imaging with PET-CT and PET-MRI in Pediatric Musculoskeletal Diseases.

Molecular imaging has emerged as an integral part of oncologic imaging. Given the physiologic changes that precede anatomic changes, molecular imaging can enable early detection of disease and monitoring of response. [18F] Fluorodeoxyglucose (FDG) Positron emission tomography (PET) is the predominant molecular imaging modality used in oncologic assessment and can be performed using PET/CT or PET/MR. In pediatric patients, PET/MRI imaging is generally preferred due to low radiation exposure and PET/MRI is particularly advantageous for imaging musculoskeletal (MSK) diseases, as MRI provides superior characterization of tissue changes as compared to CT. In this article, we provide an overview of the typical role of PET CT/MRI in assessment of some common pediatric malignancies and benign MSK diseases with case examples. We also discuss the relative advantages of PET/MRI compared to PET/CT, and review published data with a primary focus on the use of PET/MR.

Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.

ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.