Pediatric Lymphedema: Study of 180 Patients Referred to a Tertiary Lymphedema Clinic.

BACKGROUND: Lymphedema is due to dysfunction of the lymphatic system. It can be primary or secondary. Pediatric lymphedema is more often primary and is a chronic disease with a heavy burden on quality of life. METHODS: Medical records of patients under 18 years of age referred between 1996 and 2021 to the specialized lymphedema clinic at the Sainte-Justine University Hospital Center were reviewed. Demographic data, sex, age at presentation, location of the lymphedema, clinical features, genetic testing, symptoms, complications, investigations, and treatment were collected. RESULTS: Of 180 referred patients, lymphedema was confirmed in 151, and 137 were primary lymphedema. Median age of apparition of primary lymphedema was 7.00 years and was significantly lower in boys than in girls. Primary congenital lymphedema was more frequent in boys (51.0%, 27.3% in girls, P = .007), and onset of primary lymphedema during adolescence was more frequent in girls (53.4%, 25.0% in boys, P = .001). Lower limbs were the most impacted (88.3%). Sixty patients had genetic testing, and 38 (63.3%) of them were discovered to have a pertinent genetic mutation. The most common mutated gene was the FLT4 gene (in 9 patients). Seven patients (5.1%) had associated extensive/central lymphatic malformation and 24 (17.6%) had a polymalformative syndrome/syndromic lymphedema. CONCLUSIONS: Pediatric lymphedema is more frequent in girls, usually involves lower limb, and is most often sporadic, but often associated with a genetic mutation, and genetic testing should be performed.

Evaluation of physiological Waldeyer's ring, mediastinal blood pool, thymic, bone marrow, splenic and hepatic activity with 18F-FDG PET/CT: exploration of normal range among pediatric patients.

INTRODUCTION: While 18F-FDG PET/CT pediatrics applications have increased in number and indications, few studies have addressed normal maximum standardized uptake values (SUVmax) of referral organs in children. The purpose of this study is to assess these in a cohort of pediatric patients. MATERIAL AND METHODS: 285 18F-FDG PET/CT scans in 229 patients were reviewed. SUVmax were assessed for mediastinal blood pool (MBP), thymus (T), liver (L), spleen (S), bone marrow (BM) and Waldeyer's Ring (Wald). L/MBP and S/L ratios were calculated. Same day complete blood counts (CBC) were available for 132 studies and compared to BM and S. Means, standard deviations and correlation coefficients with age, weight and body surface area (BSA) were calculated. RESULTS: Weak correlation with age, weight or BSA was found for Wald. Strong correlations with weight/BSA more than with age were demonstrated for MBP, L and BM and moderate for S and T. After initial decrease between age 0 and 2, thymic activity peaked at age 11 years then involuted. No correlation was found between CBC ad BM or S. In 28 studies, L was less or equal to MBP. In 74 S was superior to L. CONCLUSIONS: Referral organs 18F-FDG uptake varies in children more in relation with weight and BSA than with age for key referral organs, such as L, S and MBP. In a significant number of studies, L activity may impede evaluation of treatment response in comparison with MBP or inflammation/infection evaluation in comparison with S.

New interinstitutional, multimodal presurgical evaluation protocol associated with improved seizure freedom for poorly defined cases of focal epilepsy in children.

OBJECTIVE: In an attempt to improve postsurgical seizure outcomes for poorly defined cases (PDCs) of pediatric focal epilepsy (i.e., those that are not visible or well defined on 3T MRI), the authors modified their presurgical evaluation strategy. Instead of relying on concordance between video-electroencephalography and 3T MRI and using functional imaging and intracranial recording in select cases, the authors systematically used a multimodal, 3-tiered investigation protocol that also involved new collaborations between their hospital, the Montreal Children's Hospital, and the Montreal Neurological Institute. In this study, the authors examined how their new strategy has impacted postsurgical outcomes. They hypothesized that it would improve postsurgical seizure outcomes, with the added benefit of identifying a subset of tests contributing the most. METHODS: Chart review was performed for children with PDCs who underwent resection following the new strategy (i.e., new protocol [NP]), and for the same number who underwent treatment previously (i.e., preprotocol [PP]); ≥ 1-year follow-up was required for inclusion. Well-defined, multifocal, and diffuse hemispheric cases were excluded. Preoperative demographics and clinical characteristics, resection volumes, and pathology, as well as seizure outcomes (Engel class Ia vs > Ia) at 1 year postsurgery and last follow-up were reviewed. RESULTS: Twenty-two consecutive NP patients were compared with 22 PP patients. There was no difference between the two groups for resection volumes, pathology, or preoperative characteristics, except that the NP group underwent more presurgical evaluation tests (p < 0.001). At 1 year postsurgery, 20 of 22 NP patients and 10 of 22 PP patients were seizure free (OR 11.81, 95% CI 2.00-69.68; p = 0.006). Magnetoencephalography and PET/MRI were associated with improved postsurgical seizure outcomes, but both were highly correlated with the protocol group (i.e., independent test effects could not be demonstrated). CONCLUSIONS: A new presurgical evaluation strategy for children with PDCs of focal epilepsy led to improved postsurgical seizure freedom. No individual presurgical evaluation test was independently associated with improved outcome, suggesting that it may be the combined systematic protocol and new interinstitutional collaborations that makes the difference rather than any individual test.

Validation of modified diuretic drainage times criteria in congenital hydronephrosis.

INTRODUCTION AND OBJECTIVE: The value of diuretic renography drainage times in congenital hydronephrosis (AHN) decision making is controversial. Recently, a group suggested a modification to the classically described diuretic drainage time cut-off values. They found that a drainage half-time (T1/2) < 5 min was normal whereas a T1/2 exceeding 75 min predicted pyeloplasty. In addition, they reported on the benefit of a delayed drainage image obtained with gravity assistance. We sought to evaluate the ability of these modified T1/2 criteria to predict pyeloplasty, alone or in combination with a delayed drainage image referred to as Global Washout (GWO). METHODS: We retrospectively reviewed 113 patients, including consecutive pyeloplasties for AHN from 2004 to 2018. Patients who underwent pyeloplasty due to low differential renal function (DRF) < 30% or infection were excluded. The control group comprised high grade AHN managed non-operatively. The initial renal ultrasound and MAG 3 Lasix renogram were reviewed for grade, differential renal function (DRF), T1/2 and GWO. A ROC curve was used to evaluate the T1/2 and GWO cut-off points that can predict pyeloplasty, using a p-value of less than 0.05. RESULTS: The pyeloplasty group consisted of 62 patients and the control group consisted of 51 patients. Two patients (3%) in the pyeloplasty group had a T1/2 < 5 min whereas 21 (34%) had T 1/2 > 75 min (p < 0.001). In the control group, 25 patients (49%) had T 1/2 < 5 min and none had T1/2 >75 min (P < 0.001). The ROC curve for T1/2 < 5 min demonstrated 94% sensitivity and 51% specificity whereas a T1/2 >75 min demonstrated 100% specificity and 34% sensitivity. Analysis of the GWO using a ROC curve revealed that a cut-off of 50% GWO has 100% specificity and 52% sensitivity for pyeloplasty. Overall, a T1/2 > 75 min or GWO <50% predicted 53% of pyeloplasties (Fig A) and was absent in all conservatively managed cases. DISCUSSION: The limitations of the present study include its retrospective nature. Secondly, the lack of a gold standard diagnostic test for uretero-pelvic junction obstruction hampers objective quantification of diagnostic test utility performance. CONCLUSIONS: We confirm the utility of the modified diuretic half-time criteria and delayed gravity assisted imaging. A T1/2 > 75 min or GWO <50% are indicators of severity whereas a T1/2 of <5 min or GWO >90% is reassuring. Gravity assisted delayed imaging can be especially helpful in cases with indeterminate T 1/2 times and should be included in the standard assessment of hydronephrotic kidneys. These parameters can be used to tailor the frequency and invasiveness of imaging within observation protocols.

Case Report 18F-FDG PET/CT of Pseudomyogenic Hemangioendothelioma.

Hemangioendotheliomas are a heterogeneous group of vascular neoplasm that may affect the liver, bone, and soft tissues. Among its variants, pseudomyogenic hemangioendothelioma is rarely encountered. Pseudomyogenic hemangioendothelioma is usually characterized by multiple soft tissue lesions, with occasional bone lesions. Fewer than 20 cases with exclusive involvement of bone structures have been reported. We describe a case of pseudomyogenic hemangioendothelioma involving multiple bony structures but without soft tissue involvement in a 7-year-old girl, imaged with F-FDG PET/CT at diagnosis and during treatment with mammalian target of rapamycin inhibitors.

Children with vesicoureteric reflux have joint hypermobility and occasional tenascin XB sequence variants.

INTRODUCTION: To consider alternative mechanisms that give rise to a refluxing ureterovesical junction (UVJ), we hypothesized that children with a common heritable urinary tract defect, vesicoureteric reflux (VUR), may have a defect in the extracellular matrix composition of the UVJ and other tissues that would be revealed by assessment of the peripheral joints. Hypermobile joints can arise from defects in the extracellular matrix within the joint capsule that affect proteins, including tenascin XB (TNXB). METHODS: We performed an observational study of children with familial and non-familial VUR to determine the prevalence of joint hypermobility, renal scarring, and DNA sequence variants in TNXB. RESULTS: Most children (27/44) exhibited joint hypermobility using the Beighton scoring system. This included 15/26 girls (57.7%) and 12/18 boys (66.7%), which is a significantly higher prevalence for both sexes when compared to population controls (p<0.005). We found no association between joint hypermobility and renal scarring. Seven of 49 children harbored rare pathogenic sequence variants in TNXB, and two also exhibited joint hypermobility. No sequence variants in TNXB were identified in 25/27 children with VUR and joint hypermobility. Due to the observational design of the study, there was missing data for joint hypermobility scores in six children and for dimercaptosuccinic acid (DMSA) scans in 17 children. CONCLUSIONS: We observed a high prevalence of VUR and joint hypermobility in children followed within a tertiary care pediatric urology clinic. While mutations in TNXB have been reported in families with VUR and joint hypermobility, we identified only two children with these phenotypes and pathogenic variants in TNXB. We, therefore, speculate that VUR and joint hypermobility may be due to mutations in other extracellular matrix genes.

18F-Flurodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) findings in children with encephalitis and comparison to conventional imaging.

PURPOSE: FDG PET/CT is emerging as a new tool for the evaluation of acute encephalitis (AE). However, to date, there are no exclusively pediatric studies on the use of FDG PET for suspected AE. The objective of this study was to compare qualitative and quantitative brain PET to conventional brain imaging in a cohort of children, and to identify patterns of metabolic abnormalities characteristic of AE. METHODS: This retrospective study included 34 children imaged with PET/CT, CT and magnetic resonance imaging (MRI). The positivity rate of all three imaging modalities was measured. Besides visual assessment, quantification of relative regional brain metabolism (RRBM) was performed and compared to a database of normal pediatric brains. RESULTS: Fourteen subjects had a clinical diagnosis of autoimmune encephalitis (AIE) or encephalitis of unknown origin (EX), six of anti-N-methyl-D-aspartate receptor (anti-NMDAr) encephalitis, three of Hashimoto's encephalopathy, three of neurolupus and eight had other subtypes of encephalitis. Quantitative PET was abnormal in 100% of cases, visually assessed PET in 94.1% of subjects, MRI in 41.2% and CT in 6.9%. RRBM quantification demonstrated multiple hyper and hypo metabolic cortical regions in 82.3% of subjects, exclusively hypermetabolic abnormalities in 3%, and exclusively hypometabolic abnormalities in 14.7%. The basal ganglia were hypermetabolic in 26.5% of cases on visual assessment and in 58.8% of subjects using quantification. CONCLUSION: In our pediatric population FDG PET was more sensitive than conventional imaging for the detection of AE, and basal ganglia hypermetabolism was frequently encountered.

Gray Zone Lymphoma Arising in the Neck of a Teenager With a Germline Mutation in TP53.

Gray zone lymphoma is an aggressive disease for which appropriate management is still debated. We report a 15-year-old girl with a cervical mass, an enlarged ipsilateral tonsil, and anemia. Both sites showed hypermetabolism on F18-FG positron emission tomography/CT. Surgical resection was diagnostic of Epstein-Barr virus-negative gray zone lymphoma cervical and tonsillar involvement. No abnormality was found in cytogenetic analysis on tumor cells. However, exome sequencing in peripheral blood DNA revealed a germline mutation in TP53. Complete response was achieved after surgery and 6 cycles of rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin regimen.

Solid Pseudo-Papillary Tumor Mimicking as Complicated Pseudocyst: Multimodality Imaging and Pathological Correlation.

Pancreatic neoplasm is very rare in the pediatric population. Malignant tumors represent less than 0.2% of pediatric cancer-related mortality. Pancreas lesions can be from exocrine or endocrine origin or present themselves as cystic masses. Clinical, biological, and radiological findings usually are sufficient to establish diagnosis, but in some cases, they may be misleading. We present the case of a young patient presenting a pancreatic mass where anatomical and metabolic characteristics of the lesion were discordant to the final diagnosis.

Lymphoscintigraphy of Chylous Anomalies: Chylothorax, Chyloperitoneum, Chyluria, and Lymphangiomatosis-15-Year Experience in a Pediatric Setting and Review of the Literature.

In the pediatric setting, lymphoscintigraphy is used mostly for the evaluation of lymphedema. Only a few cases of chylous anomalies and lymphatic malformations imaged with lymphoscintigraphy have been reported in the literature. The aim of this study was to review the use of lymphoscintigraphy in those pathologies. Methods: All lymphoscintigraphy studies performed for chylous anomalies between 2001 and 2017 in our hospital were retrospectively reviewed. The results were correlated to clinical and radiologic findings. Lymphoscintigraphy consisted of sequential imaging after injection of 3.7-9.25 MBq (100-250 µCi) of 99mTc-filtered sulfur colloid at the level of the feet or hands. Results: Twenty-five studies were performed on 21 patients. Fourteen studies were obtained for the evaluation of chylothorax. Eleven were performed for chyloperitoneum, chyluria, chylopericardium, exudative enteropathy, or lymphangiomatosis. Ten studies were positive for lymphatic leakage, and 1 had uncertain results. After correlation with radiologic findings and follow-up, there were 7 true-negative and 5 false-negative results (previous 67Ga-interfering activity in 1, injection in only the hands in 3, and a low-fat diet in 1). One study became positive after injection in the feet, and another became positive after a switch to a high-fat diet. Conclusion: Lymphoscintigraphy is a useful tool for imaging lymphatic anomalies in children. Suggestions to optimize results include placing the patient on a high-fat diet, withholding octreotide, injecting the 4 extremities, and imaging with SPECT/CT.

Modeling the Effects of Age and Sex on Normal Pediatric Brain Metabolism Using 18F-FDG PET/CT.

Reference databases of pediatric brain metabolism are uncommon, because local brain metabolism evolves significantly with age throughout childhood, limiting their clinical applicability. The aim of this study was to develop mathematic models of regional relative brain metabolism using pediatric 18F-FDG PET with CT data of normal pediatric brains, accounting for sex and age. Methods: PET/CT brain acquisitions were obtained from 88 neurologically normal subjects, aged 6 mo to 18 y. Subjects were assigned to either a development group (n = 59) or a validation group (n = 29). For each subject, commercially available software was used to quantify the relative metabolism of 47 separate brain regions using whole-brain-normalized (WBN) and pons-normalized (PN) activity. The effects of age on regional relative brain metabolism were modeled using multiple linear and nonlinear mathematic equations, and the significance of sex was assessed using the Student t test. Optimal models were selected using the Akaike information criterion. Mean predicted values and 95% prediction intervals were derived for all regions. Model predictions were compared with the validation dataset, and mean predicted error was calculated for all regions using both WBN and PN models. Results: As a function of age, optimal models of regional relative brain metabolism were linear for 9 regions, quadratic for 13, cubic for 6, logarithmic for 12, power law for 7, and modified power law for 2 using WBN data and were linear for 9, quadratic for 25, cubic for 2, logarithmic for 6, and power law for 4 using PN data. Sex differences were found to be statistically significant only in the posterior cingulate cortex for the WBN data. Comparing our models with the validation group resulted in 94.3% of regions falling within the 95% prediction interval for WBN and 94.1% for PN. For all brain regions in the validation group, the error in prediction was 3% ± 0.96% using WBN data and 4.72% ± 1.25% when compared with the PN data (P < 0.0001). Conclusion: Pediatric brain metabolism is a complex function of age and sex. We have developed mathematic models of brain activity that allow for accurate prediction of regional pediatric brain metabolism.

Imaging of Acquired Demyelinating Syndrome With 18F-FDG PET/CT.

Acquired demyelinating syndromes include acute disseminated encephalomyelitis, transverse myelitis and may progress to multiple sclerosis (MS). Acute disseminated encephalomyelitis is characterized by impairment of level of consciousness and multifocal neurological deficits and transverse myelitis by back pain, weakness and sphincter dysfunction. Only a few cases of acquired demyelinating syndrome have been imaged with F-FDG PET/CT. We present two such cases.

H Syndrome: A Rare Genodermatosis Imaged With 18F-FDG PET/CT.

H syndrome (OMIM 612391) is an extremely rare autosomal recessive genodermatosis, characterized by extensive skin infiltration. We report a case imaged with F-FDG PET/CT.

False Negative 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Primary B-cell Lymphoma of the Bone.

We present a case of a 15-year-old male with primary bone lymphoma who was initially referred for suspicion of chronic osteomyelitis of the mandible. A bone scan and gallium scan demonstrated congruent uptake in the mandible, suggestive of chronic osteomyelitis. A biopsy subsequently showed B-cell lymphoma of the bone with low Ki-67. A fluorodeoxyglucose positron emission tomography (FDG-PET) scan performed before therapy for staging revealed no increased uptake in the mandible. This case shows an atypical presentation of a rare disorder and is presented to emphasize the importance of baseline FDG-PET.

18F-FDG-PET/CT Imaging of Thoracic and Extrathoracic Tuberculosis in Children.

Tuberculosis (TB) remains a major health problem, affecting approximately one-third of the world׳s population. The tubercle bacillus can affect virtually any organ of the human body and if left untreated can lead to severe morbidity and death. Diagnosis of active TB is challenging, especially in children. As a "great imitator," the disease can mimic numerous other pathologies, both clinically and at imaging. Although recognition of active TB is crucial to initiate adequate treatment in a timely fashion, thereby preventing transmission of disease, differentiation of active and quiescent disease is not always straightforward. Since the first reports more than 20 years ago, FDG-PET/CT imaging has been shown to detect active disease with accuracy equal or superior to other conventional imaging modalities. The role of FDG-PET in evaluating patients with TB is rapidly expanding. FDG-PET/CT can effectively identify foci of intrathoracic and extrathoracic TB, assess disease activity, differentiate between active and latent disease, monitor response to therapy, identify potential biopsy targets, and serve as a surrogate end point for new drug trials. Efficacy of FDG-PET/CT in the especially challenging pediatric population will be the focus of this review.

Timing of Hormone Withdrawal in Children Undergoing 131I Whole-Body Scans for Thyroid Cancer.

BACKGROUND: Little objective pediatric data exist to guide the optimal time needed to achieve thyroid-stimulating hormone (TSH) levels ≥30 µIU/mL prior to performing 131I or 123I whole-body scan (WBS) imaging in children with thyroid cancer in the post-thyroidectomy period or after hormone discontinuation. METHODS: Retrospective study of patients aged 5-19 years who underwent WBS. Patient data collection included type and duration of withdrawal (liothyronine [L-T3], levothyroxine [L-T4], or post-thyroidectomy status without hormonal replacement) and TSH measured prior to WBS (level and timing). RESULTS: A total of 175 TSH level measurements were performed in 68 patients. Thirty-five TSH values were obtained 2-7 weeks postoperatively and 101 values were obtained 2-8 weeks post L-T4 withdrawal. One patient in each group had a TSH level <30 µIU/mL. There was no difference in TSH levels between 3 weeks and 4 weeks postoperatively (p = 0.14) or post L-T4 cessation (p = 0.21). Thirty-nine TSH measurements were obtained 1-28 days post L-T3 withdrawal. Three patients had to be rescheduled due to inadequate TSH levels, including one after 14 days L-T3 withdrawal. CONCLUSION: TSH levels ≥30 µIU/mL were achieved at 3 weeks post thyroidectomy or after L-T4 withdrawal and after at least 2 weeks following L-T3 cessation.

Imaging Pediatric Plasmacytoid Dendritic Cell Neoplasm With FDG PET/CT: Atypical Presentation of a Rare Disease.

Blastic plasmacytoid dendritic cell neoplasm is a rare malignancy characterized by cutaneous involvement and hematological dissemination. Most affected patients are older, usually in the sixth or seventh decade of life, and this condition has rarely been described in the pediatric population. This report presents the case of a 9-year-old boy with blastic plasmacytoid dendritic cell neoplasm and demonstrates the utility of FDG PET/CT for staging and treatment follow-up.

Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT).

The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis.

A high prevalence of dual thyroid ectopy in congenital hypothyroidism: evidence for insufficient signaling gradients during embryonic thyroid migration or for the polyclonal nature of the thyroid gland?

BACKGROUND: Thyroid ectopy results from the failure of the thyroid precursor cells to migrate from the primordial pharynx to the anterior part of the neck. Most ectopic thyroids are revealed by congenital hypothyroidism and present as a single round mass at the base of the tongue, with no other thyroid tissue. However, some cases have dual ectopy, with part of the tissue having partially migrated. We hypothesized that this occurs more frequently than previously reported. METHODS: To determine the prevalence of dual ectopy, we reviewed the pertechnetate scintigraphies of 81 patients with congenital hypothyroidism from thyroid ectopy diagnosed between 2002 and 2011 at our institution. RESULTS: We report a series of seven cases (9%) of dual ectopy, representing an incidence ranging from 1:50,000 to 1:70,000. CONCLUSIONS: Almost one in 10 cases with congenital hypothyroidism due to thyroid ectopy has dual ectopy. This suggests that two populations of cells diverged at an early stage of development, which may arise from insufficient signaling gradients in surrounding tissues during early organogenesis or may indirectly support the polyclonal nature of the thyroid.