Imaging findings of children with PTEN-related hamartoma tumor syndrome: a 20-year multicentric pediatric cohort.

BACKGROUND: PTEN-related hamartoma tumor syndrome results from a mutation in the PTEN gene located at 10q23.31. This syndrome represents a spectrum of different phenotypes of variable expressions, now recognized as part of the same condition. Patients with this mutation have an increased risk of developing a wide range of findings, including malignancies. Although widely described in adults, there are no large series describing the imaging findings in patients before adulthood. Knowledge of the findings seen in children and adolescents with PTEN-related hamartoma tumor syndrome can help guide further management and improve surveillance recommendations. OBJECTIVE: To describe the spectrum of imaging abnormalities in pediatric patients with PTEN-related hamartoma tumor syndrome. MATERIALS AND METHODS: We performed a retrospective, cross-sectional, multicenter study conducted between January 2000 and October 2021 in three tertiary pediatric institutions evaluating the imaging findings in children and adolescents (≤ 18 years) with confirmed diagnoses of a PTEN mutation. For each patient, the imaging findings, histopathology reports, and at least a 2-year follow-up of clinical outcomes for non-operative cases were documented. RESULTS: The cohort included 78 children (37 girls), with a mean age at diagnosis of 7.5 years (range 0 days to 18 years). Benign brain findings included enlarged Virchow-Robin perivascular spaces, white matter changes, developmental venous anomalies, and cerebellar hamartomas. Benign thyroid findings were common, but 5/45 (11.1%) with thyroid abnormalities had a malignant nodule. Soft tissue adipocytic tumors, GI/GU polyps, other soft tissue abnormalities, along with vascular anomalies in various anatomic locations were common. CONCLUSION: Brain abnormalities, benign non-vascular soft tissue abnormalities, and vascular anomalies are commonly seen in children and adolescents with PTEN-related hamartoma tumor syndrome. However, malignancies involving the thyroid gland are not uncommon. Familiarity with the phenotype of PTEN-related hamartoma tumor syndrome in the pediatric population can improve diagnosis and prompt appropriate clinical surveillance of abnormal findings that warrant further management.

Denosumab-induced bone changes in a child: a case report.

We present the case of a 9-year-old girl who developed striking bone changes following two years of denosumab therapy for giant cell lesions of the jaw.

Thyroid hormone resistance and large goiter mimicking infiltrative carcinoma in a pediatric patient.

OBJECTIVES: Resistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ responsiveness to thyroid hormone. Here we describe a novel case of THR associated with large goiter mimicking infiltrative c. CASE PRESENTATION: A 13-year-old male with a hyperthyroid phenotype of RTH diagnosed as a toddler, on methimazole and nadolol therapies presented with an increase in goiter size and possible nodule. Thyroid ultrasound was concerning for a diffuse infiltrative process or malignancy. Methimazole was discontinued and he underwent further imaging, fine needle aspiration and core biopsies. Biopsy results were reassuring and imaging findings were subsequently attributed to RTH rather than malignancy. He started every other day liothyronine therapy, which led to a decrease in goiter size, thyroglobulin level, and improvement of hyperthyroid symptoms. CONCLUSIONS: This is the first case to our knowledge describing the above thyroid imaging findings in association with RTH. It also adds important information to the pediatric literature regarding management of the hyperthyroid phenotype of RTH, including the role of liothyronine therapy.

Conventional MR Imaging in Trauma Management in Pediatrics.

Traumatic brain injury (TBI) is a major cause of death and disability in children across the world. The aim of initial brain trauma management of pediatric patients is to diagnose the extent of TBI and to determine if immediate neurosurgical intervention is required. A noncontrast computed tomography is the recommended diagnostic imaging choice for all patients with acute moderate to severe TBI. This article outlines the current use of conventional MR imaging in the management of pediatric head trauma and discusses potential future recommendations.

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

Pediatric thyroid cancer is rare in children; however, incidence is increasing. Papillary thyroid cancer and follicular thyroid cancer are the most common subtypes, comprising about 90% and 10% of cases, respectively. This paper provides consensus imaging recommendations for evaluation of pediatric patients with thyroid cancer at diagnosis and during follow-up.

The White Matter Rounds experience: The importance of a multidisciplinary network to accelerate the diagnostic process for adult patients with rare white matter disorders.

Introduction: Adult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, a strong collaborative multidisciplinary network is beneficial for shortening the diagnostic odyssey of these patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) are multidisciplinary international online meetings attended by more than 30 physicians and scientists from 15 participating sites that gather every month to discuss patients with atypical white matter disorders. We aim to present the experience of the WM Rounds Network and demonstrate the value of collaborative multidisciplinary international case discussion meetings in differentiating and preventing misdiagnoses between genetic white matter diseases and atypical MS. Methods: We retrospectively reviewed the demographic, clinical and radiological data of all the subjects presented at the WM Rounds since their creation in 2013. Results: Seventy-four patients (mean age 44.3) have been referred and discussed at the WM Rounds since 2013. Twenty-five (33.8%) of these patients were referred by an MS specialist for having an atypical presentation of MS, while in most of the remaining cases, the referring physician was a geneticist (23; 31.1%). Based on the WM Rounds recommendations, a definite diagnosis was made in 36/69 (52.2%) patients for which information was available for retrospective review. Of these diagnosed patients, 20 (55.6%) had a genetic disease, 8 (22.2%) had MS, 3 (8.3%) had both MS and a genetic disorder and 5 (13.9%) had other non-genetic conditions. Interestingly, among the patients initially referred by an MS specialist, 7/25 were definitively diagnosed with MS, 5/25 had a genetic condition (e.g., X-linked adrenoleukodystrophy and hereditary small vessel diseases like Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and COL4A1-related disorder), and one had both MS and a genetic demyelinating neuropathy. Thanks to the WM Rounds collaborative efforts, the subjects who currently remain without a definite diagnosis, despite extensive investigations performed in the clinical setting, have been recruited in research studies aimed at identifying novel forms of genetic MS mimickers. Conclusions: The experience of the WM Rounds Network demonstrates the benefit of collective discussions on complex cases to increase the diagnostic rate and decrease misdiagnosis in patients with rare or atypical white matter diseases. Networks of this nature allow physicians and scientists to compare and share information on challenging cases from across the world, provide a basis for future multicenter research studies, and serve as model for other rare diseases.

Pediatric Petrous Apex Lesions: A Radiological Classification and Diagnostic Algorithm.

The petrous apex (PA) is involved in a myriad of pathological conditions, some of which are exclusive in children. Diagnosis may be difficult due to vague clinical presentation, and local examination is challenging owing to its inaccessible location. This is further complicated by multiple unfused sutures and ongoing PA pneumatization in children. Cross-sectional imaging is vital for the evaluation of the PA lesions, due to their precarious location and proximity to the major neurovascular structures. Several classification systems have been proposed for these lesions based on their site of origin, solid or cystic appearance, surgical or non-surgical (no touch lesions) management, and benign or malignant nature. In this article, we emphasize the distinctive role of different cross-sectional imaging modalities in the diagnosis of pediatric PA lesions, with special attention to normal variants that should not be mistaken for pathology. We also propose a radiological classification and algorithmic approach to aid in the precise diagnosis and facilitate appropriate management of the various PA lesions in children.

Infantile Idiopathic Intracranial Hypertension: A Case Study and Review of the Literature.

Idiopathic intracranial hypertension, or pseudotumor cerebri, is an increase in cerebrospinal fluid pressure of unknown etiology. It is mostly seen in adults, less frequently in adolescents, rarely in younger children. Only 5 infants meeting idiopathic intracranial hypertension criteria have been mentioned in the literature. We report a case of a previously healthy 9-month-old boy who presented with irritability, decreased appetite, and a bulging fontanelle. Computed tomography (CT) head imaging and cerebrospinal fluid studies revealed normal results. The patient's symptoms transiently resolved after the initial lumbar puncture, but 11 days later, his fontanelle bulged again. A second lumbar puncture revealed an elevated opening pressure of 35 cmH2O and led to a diagnosis of idiopathic intracranial hypertension in accordance with the modified Dandy Criteria. Treatment with acetazolamide at a dose of 25 mg/kg/d was initiated and the patient remained symptom-free for 6 weeks, followed by another relapse. His acetazolamide dose was increased to 37 mg/kg/d, with no further relapses to date. A diagnosis of idiopathic intracranial hypertension is challenging in infants, because the patients cannot yet verbalize typical idiopathic intracranial hypertension-related symptoms such as positional headaches, diplopia, or pulsatile tinnitus. Furthermore, it is more difficult to assess papilledema in that age group. If undetected and untreated, idiopathic intracranial hypertension may result in permanent visual deficits. Little is known about idiopathic intracranial hypertension in infants, and age-specific treatment guidelines are lacking. We discuss this rare case of infantile idiopathic intracranial hypertension and provide a review of the literature, including an overview of disease characteristics and outcomes of idiopathic intracranial hypertension in this very young age group.

Parental preferences on diagnostic imaging tests for paediatric appendicitis.

OBJECTIVES: To determine parental preferences for diagnostic imaging tests (DITs) for paediatric appendicitis, to rank the attributes impacting the DIT selection and to identify DIT attributes that would cause parents to switch their DIT. METHODS: Parents of children who had an abdominal ultrasound (US) for right lower quadrant pain were interviewed. Two DITs were compared at a time, parents were asked to indicate their preferred test and to rank its attributes according to the impact each attribute had on their selection. The strength of their preference for the chosen DIT was measured by systematically adjusting attributes of the chosen DIT until the parent changed their choice. RESULTS: Fifty parents were interviewed. For US versus CT, more parents preferred US (68%, P=0.02) with higher importance ranks for cancer risk (P<0.0001), test accuracy (P=0.04), pain during test (P=0.3), and scan length (P<0.0001); and lower ranks for sedation (P=0.02), intravenous (IV) (P<0.02), and oral contrast (P=0.06). For US versus MRI, parents preferred MRI (78%, P<0.0001) with higher importance ranks for accuracy (P=0.2), pain during test (P=0.06), and scan length (P=0.06); and lower for noise (P<0.0001), claustrophobia (P<0.0001), use of IV contrast (P=0.06), and sedation (P=0.2). CONCLUSION: US and MRI were the DIT preferred by parents for the investigation of acute paediatric appendicitis.

Comparison of the diagnostic performance of the 2017 ACR TI-RADS guideline to the Kwak guideline in children with thyroid nodules.

BACKGROUND: The Kwak Thyroid Imaging Reporting and Data System (Kwak-TI-RADS) guideline (2011) and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) guideline (2017) were developed as ultrasound (US) risk stratification tools for detecting thyroid malignancy in adults. OBJECTIVE: The purpose of this study was to investigate the inter-rater reliability and diagnostic performance of the ACR TI-RADS guideline in the pediatric population and compare it to the Kwak guideline. MATERIALS AND METHODS: This retrospective study comprised 75 children who underwent thyroid US at a tertiary-level pediatric hospital. Three pediatric radiologists and one pediatric radiology fellow graded the US findings using the Kwak-TI-RADS and ACR TI-RADS guidelines. We assessed reliability of radiologists' ratings using percentage inter-rater agreement, and intra-class correlation coefficients (ICC2,1). We assessed area-under-the-receiver-operating-characteristic curve (AUROCC) to compare the discriminative diagnostic ability of the Kwak-TI-RADS and ACR TI-RADS scoring systems against histopathology/cytology, or stability on US over a 2-year follow-up period for cases without tissue diagnosis. RESULTS: The inter-rater agreement was significantly better for the ACR TI-RADS level compared to the Kwak-TI-RADS level (P<0.001) using the percentage pairwise agreement. The ROC curves for assessing the diagnostic performance of the two methods showed no significant difference between the methods. The AUROCCs for the Kwak-TI-RADS and ACR TI-RADS levels were 0.74 (95% confidence interval [CI] 0.67-0.82) and 0.72 (95% CI 0.61-0.82), respectively. CONCLUSION: Both the Kwak-TI-RADS and ACR TI-RADS guidelines provide moderate malignancy risk stratification for thyroid nodules in the pediatric population, with better inter-rater agreement for the ACR TI-RADS guideline. Further work to adjust the recommendations for pediatric patients is necessary.

Usefulness of diffusion-weighted MRI in the initial assessment of osseous sarcomas in children and adolescents.

BACKGROUND: Concern regarding gadolinium deposition in the brain after repeated administration of intravenous gadolinium-based contrast agents has prompted evaluation of imaging alternatives. OBJECTIVE: The study purpose was to determine if magnetic resonance imaging (MRI) using conventional sequences with diffusion-weighted imaging (DWI) instead of gadolinium-based contrast-enhanced MRI is valid for local staging and guiding biopsies in osseous sarcomas. MATERIALS AND METHODS: Initial pretreatment MRI with DWI and gadolinium-based contrast-enhanced images in patients ≤ 18 years with histopathologically proven osseous sarcomas were included. Two radiologists blinded to collated demographic and clinical data, independently reviewed conventional/DWI and conventional/gadolinium-based contrast-enhanced MRI then conventional sequences alone, recording tumor size, skip lesions, necrosis, neurovascular invasion, enlarged lymph nodes and diffusion restriction. Discrepancies were resolved by a third reader. A single reader measured apparent diffusion coefficient (ADC) values in non-necrotic tumors, then correlated minimum ADC values -- with and without normalization to skeletal muscle -- with relative enhancement. RESULTS: Twenty-one patients (mean age: 11.3±4.2 years, 15 [71%] females) had 14 osteosarcomas and 7 Ewing sarcomas, 50% centered in the femur. Conventional/DWI versus conventional/gadolinium-based contrast-enhanced MRI showed agreement for tumor size estimation with significant associations for necrosis (P=0.021), neurovascular involvement (P<0.001) and enlarged lymph nodes (P=0.005). Diagnostic accuracy of conventional/DWI is comparable to conventional/gadolinium-based contrast-enhanced MRI and superior to conventional sequences alone. Comparison between minimum ADC values and relative enhancement showed no correlation (P>0.05). CONCLUSION: Significant associations of key imaging features in the initial assessment of osseous sarcomas support DWI as an alternative to gadolinium-based contrast-enhanced MRI. The lack of association between ADC values and relative enhancement suggests that they measure independent constructs, DWI dependent upon tumor cellularity and perfusion.

Imaging findings of sterile pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome: differential diagnosis and review of the literature.

Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare autosomal-dominant autoinflammatory disease of incomplete penetrance and variable expression. PAPA syndrome is the result of a mutation in the proline serine threonine phosphatase-interacting protein 1 (PSTPIP1/CD2BP1) gene located on chromosome 15, which results in an abnormal overproduction of the pro-inflammatory cytokine interleukin-1ß (IL-1). This syndrome clinically manifests as early onset of recurrent episodes of acute aseptic inflammation of the joints, generally occurring in the first two decades of life, followed by manifestation of characteristic skin lesions in the third decade, after an obvious decline in the joint symptoms. Although uncommon, the potential clinical implications of PAPA syndrome warrant an appropriate diagnosis in a timely fashion.

Utility of adult-based ultrasound malignancy risk stratifications in pediatric thyroid nodules.

BACKGROUND: Individual ultrasound (US) features have limited ability to distinguish benign from malignant thyroid nodules. Adult-based systems have been developed to integrate the sonographic features in an effort to improve diagnostic accuracy. None, however, has been validated in children, in whom the likelihood of malignancy is 2-5 times higher than adults. OBJECTIVE: To assess the performance of two adult-based sonographic (US) stratification methods for assessment of thyroid nodules in children. MATERIALS AND METHODS: This retrospective study comprised 124 children who underwent thyroid US. Three radiologists reviewed the US data using the American Thyroid Association (ATA) and the Thyroid Image Reporting and Data System (TI-RADS). Radiologists' accuracy and agreement was assessed. The reference standard was histopathology/cytology or 2-year follow-up of clinical outcome for nonoperative cases. RESULTS: We assessed 71 benign and 52 malignant nodules and excluded 1 nodule. Using the ATA pattern descriptions, 80% of malignant nodules were classified as "high" 36/52 (69%) or "intermediate" 6/52 (11%) likelihood of malignancy. A total of 20/71 (28%) benign nodules were also classified within these two categories. Using the TI-RADS, malignant nodules were classified as 2, 3, 4a, 4b, 4c and 5, with rate of malignancy of 0%, 0%, 7/52 (13.5%), 7/52 (13.5%), 32/52 (61.5%) and 6/52 (11.5%), respectively. Benign nodules were also classified in the 4a (26/71; 36.6%), 4b (17/71; 24%), 4c (14/71; 19.7%) and 5 (1/71; 1.4%) categories. The positive and negative predictive values were 68.0% and 87.5% for ATA, and 71.7% and 80.0% for TI-RADS. CONCLUSION: We validated the use of ATA and TI-RADS methods in children and showed that they have test characteristics similar to those in adults, although neither is independently sufficient to discriminate nodules' likelihood of malignancy.

Benefit and clinical significance of retrospectively obtained spectral data with a novel detector-based spectral computed tomography - Initial experiences and results.

OBJECTIVES: To evaluate the benefits and clinical significance of retrospectively generated spectral image-datasets with the novel detector-based Spectral CT (SDCT). METHODS: A total of 118 body CTs from the SDCT prototype were included. Based on the clinical indication, two radiologists were asked if they would have opted for a dual-energy mode/scan if the patient was scanned in one of the other commercially-available dual-energy scanners, which need prospective selection of dual energy mode. They also reviewed the scans, identified cases that would benefit from spectral images and evaluated these images for clinical utility and significance on a five-point scale, with 1 being the least and 5 being the highest. RESULTS: Dual-energy mode would have been prospectively selected in 20 cases (17%) for Reader 1 and 25 cases (21%) for Reader 2. Additional spectral images were requested for 94 cases (80%) and 96 cases (81%) respectively. A total of 196 and 206 spectral image-sets were utilized respectively with 97% and 96% of these image-sets useful retrospectively. The distribution of scores on the five-point scale for Readers 1 and 2 were, 1-7% & 6%; 2-26% & 30%; 3-36% & 36%; 4-27% & 21% and; 5-4% & 7%. Clinically significant score (≥4) was noted in 31% and 28% respectively. CONCLUSIONS: Additional spectral datasets retrospectively reconstructed from SDCT enhanced the diagnostic capabilities by reducing artifacts, improving contrast and allowing lesion characterization.

Pediatric imaging in DICER1 syndrome.

BACKGROUND: DICER1 syndrome, arising from a mutation in the DICER1 gene mapped to chromosome 14q32, is associated with an increased risk of a range of benign and malignant neoplasms. OBJECTIVE: To determine the spectrum of abnormalities and imaging characteristics in patients with DICER1 syndrome at a tertiary pediatric hospital. MATERIALS AND METHODS: This retrospective analysis evaluated imaging in patients ≤18 years with DICER1 germline variants between January 2004 and July 2016. An imaging database search including keywords pleuropulmonary blastoma, cystic nephroma, pineoblastoma, embryonal rhabdomyosarcoma, ovarian sex cord-stromal tumor, ovarian Sertoli-Leydig cell tumor and DICER1 syndrome, was cross-referenced against the institutional Cancer Genetics Program database, excluding patients with negative/unknown DICER1 gene testing. RESULTS: Sixteen patients were included (12 females; mean age at presentation: 4.2 years, range: 14 days to 17 years), with surveillance imaging encompassing the following modalities: chest X-ray and CT; abdominal, pelvic and neck US; and brain and whole-body MRI. Malignant lesions (68.8% of patients) included pleuropulmonary blastoma (5), pineoblastoma (3), ovarian Sertoli-Leydig cell tumor (1), embryonal rhabdomyosarcoma (1) and renal sarcoma (1); benign lesions (37.5% of patients) included thyroid cysts (2), thyroid nodules (2), cystic nephroma (2), renal cysts (1) and pineal cyst (1). A common lesional appearance observed across modalities and organs was defined as the "cracked windshield" sign. CONCLUSION: The spectrum of DICER1-related tumors and the young age at presentation suggest early surveillance of at-risk patients is critical, while minimizing exposure to ionizing radiation.

MRI in the evaluation of localization-related epilepsy.

This article covers the MRI evaluation of patients with epilepsy, with a focus on neuroimaging in those with localization-related epilepsy who may be potential epilepsy surgery candidates. The article includes structural MRI to identify a lesion, functional MRI to identify the eloquent cortex and diffusion tensor imaging to identify the eloquent white matter tracts. We consider the equipment, protocol or procedures, and reporting of MRI in patients with epilepsy. Recommendations for both adult and pediatric patients are described for protocols and procedures. The authors hope that this article will provide a standardized approach for clinical imaging of patients with suspected localization-related epilepsy who may be evaluated for epilepsy surgery. J. Magn. Reson. Imaging 2016.

Successful Dose Reduction Using Reduced Tube Voltage With Hybrid Iterative Reconstruction in Pediatric Abdominal CT.

OBJECTIVE: The purpose of this article is to assess radiation dose reduction, image quality, and diagnostic confidence using low tube voltage in combination with hybrid iterative reconstruction in contrast-enhanced pediatric abdominal CT. MATERIALS AND METHODS: CT examinations of 133 patients (median age, 10 years) were performed at sequentially reduced doses. The first group (group 1) was scanned using dimension-based protocols at 120 kV for all patient sizes. The optimized group (group 5) was scanned at 80 kV for less than 18 cm in the lateral dimension and 100 kV in the 19-30 cm lateral dimension. CT examinations reconstructed with filtered back projection (FBP) and four levels of hybrid iterative reconstruction were reviewed by four blinded readers for subjective image quality and diagnostic confidence. Objective noise, volume CT dose index (CTDIvol), and size-specific dose estimate (SSDE) were recorded. Data were analyzed using t tests, one and two-way ANOVA, and the intraclass correlation coefficient. RESULTS: Compared with group 1, the radiation dose was reduced for group 5 by 63% measured by SSDE (4.69 vs 10.00 mGy; p < 0.001). Subjective image noise was increased for FBP images (p < 0.001) but not was statistically significantly different for all levels of hybrid iterative reconstruction; artifacts were reduced and visibility of small structures was improved (both p < 0.001). Diagnostic confidence was improved for solid organ injury and metastatic disease (both p < 0.001) and was not statistically significantly different for appendicitis (p = 0.306). CONCLUSION: Use of hybrid iterative reconstruction with low-tube-voltage protocols enables substantial radiation dose reduction for pediatric abdominal CT with equivalent to improved subjective image quality and diagnostic confidence.