R. Paul Guillerman

Leukemia and Lymphoma

Leukemia and lymphoma are the most common and third most common pediatric malignancies, respectively, and share cell lineages, but the clinical and imaging manifestations of these malignancies vary substantially. Along with providing pertinent details on classification, epidemiology, and treatment, this article reviews the current roles of imaging in the management of childhood leukemia and lymphoma, with attention to diagnosis, staging, risk stratification, therapy response assessment, and surveillance for disease relapse and adverse effects of therapy. Advances in functional imaging are also discussed to provide insights into future applications of imaging in the management of pediatric patients with leukemia and lymphoma.

Neuroendocrine Cell Hyperplasia of Infancy: Diagnosis With High-Resolution CT

OBJECTIVE Neuroendocrine cell hyperplasia of infancy is a form of childhood interstitial lung disease originally reported as persistent tachypnea of infancy. Reports of small series of cases and anecdotal experience have suggested that this disorder may have a consistent CT pattern. The purpose of this study was to review the CT findings in children with neuroendocrine cell hyperplasia of infancy to determine the findings at high-resolution CT, the diagnostic accuracy of CT compared with biopsy, and interrater reliability. MATERIALS AND METHODS Images from 23 CT examinations of children with biopsy-proven neuroendocrine cell hyperplasia of infancy and six CT examinations of children with other childhood interstitial lung diseases were reviewed by two pediatric radiologists with special expertise in thoracic imaging. Identifying digital data were removed, and images were reviewed without clinical data. A CT assessment form was completed for each patient. RESULTS Ground-glass opacification was the most common finding in patients with neuroendocrine cell hyperplasia of infancy. The right middle lobe and lingula were most commonly involved. Air trapping with a mosaic pattern was the second most common finding. Interrater reliability was very good with a kappa value of 0.93. The sensitivity and specificity of CT in the diagnosis of neuroendocrine cell hyperplasia of infancy were at least 78% and 100%. CONCLUSION Neuroendocrine cell hyperplasia of infancy can have a characteristic appearance on high-resolution CT scans, the imaging findings being useful in differentiating neuroendocrine cell hyperplasia of infancy from other types of childhood interstitial lung disease. The appearance aids radiologists in suggesting a specific diagnosis but does not exclude this diagnosis; in 17-22% of cases, the readers in this study did not suggest the diagnosis of neuroendocrine cell hyperplasia of infancy when it was present.

Exploring the Association Between DICER1 Mutations and Differentiated Thyroid Carcinoma

CONTEXT Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Thyroid abnormalities are a common finding in DICER1 syndrome with multinodular goiter frequently present in many families in which a germline DICER1 mutation is segregating. Differentiated thyroid carcinoma (DTC) is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 ribonuclease IIIb catalytic domain in several tumor types. OBJECTIVE We aimed to determine whether such characteristic somatic DICER1 mutations are present in DTCs that arise within germline DICER1 mutation carriers. DESIGN AND SETTING The study involved an opportunistic collection of 3 cases of DTC arising in individuals suspected to have DICER1 syndrome and hospital-based ascertainment and testing was implemented. RESULTS We identified somatic DICER1 mutations in 3 DTCs arising in unrelated germline DICER1 mutation carriers, all of whom had been diagnosed in infancy with pleuropulmonary blastoma (PPB), were treated with chemotherapy, exposed frequently to diagnostic radiation, and subsequently developed DTC. The somatic mutations occurred within the DICER1 ribonuclease IIIb domain, affecting highly conserved amino acid residues central to the catalytic activity of the domain. CONCLUSION This report of somatic DICER1 mutations in DTC strengthens the association between DTC and the DICER1 syndrome. The possible association between germline DICER1 mutations, PPB treatment, and the risk of subsequent DTC must be considered by clinicians when treating PPB.

Optimal imaging strategy for community-acquired Staphylococcus aureus musculoskeletal infections in children.

BackgroundInvasive musculoskeletal infections from community-acquired methicillin-resistant and methicillin-susceptible Staphylococcus aureus (CA-SA) are increasingly encountered in children. Imaging is frequently requested in these children for diagnosis and planning of therapeutic interventions.ObjectiveTo appraise the diagnostic efficacy of imaging practices performed for CA-SA osteomyelitis and its complications.Materials and methodsA retrospective review was conducted of the clinical charts and imaging studies of CA-SA osteomyelitis cases since 2001 at a large children’s hospital.ResultsOf 199 children diagnosed with CA-SA osteomyelitis, 160 underwent MRI examination and 35 underwent bone scintigraphy. The sensitivity of MRI and bone scintigraphy for CA-SA osteomyelitis was 98% and 53%, respectively. In all discordant cases, MRI was correct compared to bone scintigraphy. Extraosseous complications of CA-SA osteomyelitis detected only by MRI included subperiosteal abscesses (n = 77), pyomyositis (n = 43), septic arthritis (n = 31), and deep venous thrombosis (n = 12).ConclusionMRI is the preferred imaging modality for the investigation of pediatric CA-SA musculoskeletal infection because it offers superior sensitivity for osteomyelitis compared to bone scintigraphy and detects extraosseous complications that occur in a substantial proportion of patients.

Liver Tumors: Pediatric Population

Liver tumors in childhood are rare and are typically not detected clinically until they reach a large size and often spread within the organ or metastasize. This can make surgical resection problematic, and almost all of them require extirpation for cure. With very effective chemotherapy for hepatoblastoma and to some extent for sarcomas, many cancers can be shrunk to permit partial hepatectomy, but for most hepatocarcinomas, some of the other malignancies, and even some benign proliferations, their location at the hilum and multiplicity of masses in multiple lobes make transplantation the treatment of choice. Major advances in diagnostic imaging, especially enhanced computed tomography and magnetic resonance imaging, permit a preoperative choice of resection versus transplantation to be achieved in almost all instances, and for the remainder, intraoperative ultrasonography can further help to determine the most desirable approach. The outcome is very much better in the case of hepatoblastoma when transplantation is a primary modality rather than following unsuccessful attempts at resection. In this review, transplantation for liver tumors in children is considered from all aspects, including the importance of screening for tumors whenever possible to avoid the need for transplantation. Liver Transpl 14:1545–1556, 2008.

Prospective Comparison of MR Imaging and US for the Diagnosis of Pediatric Appendicitis

PURPOSE To prospectively compare nonenhanced magnetic resonance (MR) imaging and ultrasonography (US) for the diagnosis of pediatric appendicitis. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained from the patients parent or guardian. Eighty-one patients (34 male, 47 female; mean age, 12.3 years ± 3.5 [standard deviation]; range, 4-17 years) were enrolled in this prospective study. All patients underwent right lower quadrant US and nonenhanced, nonsedated abdominopelvic MR imaging examinations. Two pediatric radiologists blinded to US results independently reviewed the MR images. MR imaging and US findings were designated positive, negative, or equivocal for acute appendicitis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MR imaging and US and compared by using two-sided McNemar test or the score statistics specified by Leisenring. Kappa statistics were generated to determine intertechnique agreement between MR imaging and US and interobserver agreement between the two primary MR imaging readers. RESULTS Thirty (37%) patients had pathologically proved acute appendicitis. When equivocal interpretations were designated positive, sensitivity was 93.3% for MR imaging (95% confidence interval [CI]: 77.9%, 99.2%) and 90.0% for US (95% CI: 73.5%, 97.9%), P > .99; specificity was 98% for MR imaging (95% CI: 89.6%, 100%) and 86.3% for US (95% CI:73.7%, 94.3%), P = .03; PPV was 96.5% for MR imaging (95% CI: 82.2%, 99.9%) and 79.4% for US (95% CI: 62.1%, 91.3%), P = .007; and NPV was 96.2% for MR imaging (95% CI: 86.8%, 99.5%) and 93.6% for US (95% CI: 82.4%, 98.7%), P = .45, with substantial intertechnique (κ = 0.77; 95% CI: 0.63, 0.90) and interobserver (κ = 0.76; 95% CI: 0.61, 0.91) agreement. When equivocal interpretations were designated negative, MR imaging sensitivity, specificity, PPV, and NPV were unchanged. For US, sensitivity was 86.7% (95% CI: 69.3%, 96.2%), P = .5; specificity was 100% (95% CI: 93.0%, 100%), P > .99; PPV was 100% (95% CI: 86.8%, 100%), P = .31; and NPV was 92.7% (95% CI: 82.4%, 98.0%), P = .16, with almost perfect intertechnique (κ = 0.92; 95% CI: 0.83, 1.00) and substantial interobserver (κ = 0.72; 95% CI: 0.58, 0.87) agreement. CONCLUSION Nonenhanced MR imaging demonstrates high diagnostic performance similar to that of US for suspected pediatric appendicitis.

Multimodality Imaging of Tracheobronchial Disorders in Children

The trachea and bronchial airways in children are subject to compromise by a number of extrinsic and intrinsic conditions, including congenital, inflammatory, infectious, traumatic, and neoplastic processes. Stridor, wheezing, and respiratory distress are the most common indications for imaging of the airway in children. Frontal and lateral chest and/or neck radiography constitute the initial investigations of choice in most cases. Options for additional imaging include airway fluoroscopy, contrast esophagography, computed tomography (CT), and magnetic resonance (MR) imaging. Advanced imaging techniques such as dynamic airway CT, CT angiography, MR angiography, and cine MR imaging are valuable for providing relevant vascular and functional information in certain settings. Postprocessing techniques such as multiplanar reformatting, volume rendering, and virtual bronchoscopy assist in surgical planning by providing a better representation of three-dimensional anatomy. A systematic approach to imaging the airway based on clinical symptoms and signs is essential for the prompt, safe, and accurate diagnosis of tracheobronchial disorders in children.

Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis

Cystic fibrosis (CF) clinical care guidelines exist for the care of infants up to age 2 years and for individuals ≥6 years of age. An important gap exists for preschool children between the ages of 2 and 5 years. This period marks a time of growth and development that is critical to achieve optimal nutritional status and maintain lung health. Given that disease often progresses in a clinically silent manner, objective and sensitive tools that detect and track early disease are important in this age group. Several challenges exist that may impede the delivery of care for these children, including adherence to therapies. A multidisciplinary committee was convened by the CF Foundation to develop comprehensive evidence-based and consensus recommendations for the care of preschool children, ages 2 to 5 years, with CF. This document includes recommendations in the following areas: routine surveillance for pulmonary disease, therapeutics, and nutritional and gastrointestinal care.

Radiographic Abnormalities in Rothmund-Thomson Syndrome and Genotype–Phenotype Correlation with RECQL4 Mutation Status

OBJECTIVE The purpose of this study was to summarize the radiographic skeletal findings in patients with Rothmund-Thomson syndrome (RTS) and to determine whether there is an association between the presence of skeletal abnormalities and the mutational status of the RECQL4 gene. SUBJECTS AND METHODS Twenty-eight subjects with RTS underwent skeletal surveys and RECQL4 DNA mutation testing. Radiographs were reviewed by two radiologists. RECQL4 mutation testing by DNA sequencing of the gene was performed by a diagnostic laboratory. Genotype-phenotype analysis by Fishers exact test was performed to investigate whether there was a correlation between mutation status and skeletal abnormalities. RESULTS Twenty-one (75%) of the subjects had at least one significant skeletal abnormality, the more common being abnormal metaphyseal trabeculation, brachymesophalangy, thumb aplasia or hypoplasia, osteopenia, dislocation of the radial head, radial aplasia or hypoplasia, and patellar ossification defects. Three subjects had a history of destructive bone lesion (osteosarcoma). Genotype-phenotype analysis showed a significant correlation between RECQL4 mutational status and the presence of skeletal abnormalities (p < 0.0001). CONCLUSION Skeletal abnormalities are frequent in persons with RTS. Many of these abnormalities are not clinically apparent but are detectable on radiographs. The presence of skeletal abnormalities correlates with RECQL4 mutation status, which has been found to correlate with risk of osteosarcoma. Skeletal surveys aid in both diagnosis and management of RTS.

Revised International Pediatric Non-Hodgkin Lymphoma Staging System

PURPOSE Treatment and prognosis of pediatric non-Hodgkin lymphoma (NHL) have improved dramatically in the last 30 years. However, the St Jude NHL staging classification for pediatric NHL was developed more than 35 years ago. The most recent Lugano lymphoma staging classification focused on adult lymphoma. Furthermore, major limitations of the current pediatric NHL staging classification include lack of consideration of new distinct pediatric NHL histologic entities; absence of recognition of frequent skin, bone, kidney, ovarian, and other organ involvement; and lack of newer precise methods to detect bone marrow and CNS involvement, minimal disease quantification, and highly sensitive imaging technologies. METHODS An international multidisciplinary expert panel convened in Frankfurt, Germany, in 2009 at the Third International Childhood, Adolescent and Young Adult NHL Symposium to develop a revised international pediatric NHL staging system (IPNHLSS), addressing limitations of the current pediatric NHL staging system and creating a revised classification. Evidence-based disease distribution and behavior were reviewed from multiple pediatric cooperative group NHL studies. RESULTS A revised IPNHLSS was developed incorporating new histologic entities, extranodal dissemination, improved diagnostic methods, and advanced imaging technology. CONCLUSION This revised IPNHLSS will facilitate more precise staging for children and adolescents with NHL and facilitate comparisons of efficacy across different treatment strategies, various institutions, multicenter trials, and cooperative groups by allowing for reproducible pediatric-based staging at diagnosis and relapse.