Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents.

BACKGROUND: Inflammatory myofibroblastic tumors (IMT) are rare, intermediate malignant tumors harboring frequent somatic molecular rearrangements. The management of IMT has not been standardized. METHODS: A retrospective multicenter study was conducted on all pediatric patients treated for IMT between 2000 and 2019. RESULTS: This series included 39 cases of IMT, with a median age at diagnosis of 7 years (range 20 days to 16 years). Tumor location included pelvis-abdomen (n = 16), thorax (n = 14), head and neck (n = 7), and limbs (n = 2). One patient had metastatic disease. Immunochemistry showed 21/39 (54%) anaplastic lymphoma kinase (ALK)-positive tumors. Somatic tyrosine kinase rearrangement was present in 31/36 (86%) of the tumors analyzed: 21 ALK, five ROS1, and five NTRK. Immediate surgery was performed in 24 patients (62%), with adjuvant therapy for three patients. Delayed surgery after neoadjuvant therapy was possible in 10 cases. Exclusive systemic therapy was delivered to four patients; one patient with orbital IMT was managed by watchful waiting. After a median follow-up of 33 months (range 5-124), eight (20%) recurrences/progressions occurred after surgery (seven after primary surgery and one after delayed surgery), after a median interval of 7 months (range 2-21), all in thoracic locations. The 3-year overall and disease-free survivals were 96.8% (95% CI: 79.2%-94.0%) and 77.4% (95% CI: 59.6%-88.1%), respectively. Relapses/progressions were more common in patients with a thoracic primary (p < .001) or after incomplete surgery with no adjuvant therapy (p = .027). CONCLUSION: Surgery is effective in most cases of pediatric IMT. Systematic analysis of tyrosine kinase rearrangement is recommended. When the tumor is deemed only partially resectable to preserve organs and function, neoadjuvant therapy may be proposed to allow adequate conservative surgery.

Biopsy-Induced Duodenal Hematoma Is Not an Infrequent Complication Favored by Bone Marrow Transplantation.

OBJECTIVES: Intraduodenal hematoma (IDH) is an uncommon complication of endoscopic duodenal biopsy that can cause severe obstruction of the digestive, biliary, or pancreatic tracts. We aimed to analyze the risk factors and outcomes of biopsy-induced IDH in our series. METHODS: Between 2010 and 2014, a retrospective chart review was conducted for all children younger than 18 years of age treated for IDH. We collected their data in our tertiary pediatric center and compared them to those of controls matched for age, sex, and pathology. RESULTS: Among 2705 upper nontherapeutic endoscopies and 1163 duodenal biopsies, 7 IDH occurred in 6 children suspected of developing graft-versus-host disease (GVHD) after bone marrow transplantation (BMT) and in 1 patient with Noonan syndrome. The IDH prevalence was significantly higher after BMT compared to children who did not undergo grafting (7% vs 0.1%; P = 7.9 × 10; odds ratio = 82). After a median delay of 48 hours, patients developed intestinal obstruction with abdominal pain and vomiting. The diagnosis was confirmed by using ultrasonography or computed tomography scans. Acute pancreatitis was determined in 3 out of 7 patients. Conservative treatment allowed complete resolution in all patients. CONCLUSIONS: IDH is not an infrequent complication of endoscopic duodenal biopsy, especially in patients who undergo BMT. Endoscopists should be especially careful during the duodenal biopsy procedure in these patients. With no early perforation due to post-biopsy IDH reported, the prognosis is good and conservative management generally leads to resolution of the symptoms in 2 to 3 weeks.

Apparent diffusion coefficient measurements of the fetal brain during the third trimester of pregnancy: how reliable are they in clinical practice?

OBJECTIVE: The objective of this study was to determine the reproducibility, the inter-hemispheric difference and the reference apparent diffusion coefficient (ADC) values of the fetal brain according to gestational age. METHOD: One hundred and one normal fetal brain (29.4-38.4 weeks) were analysed with diffusion-weighted MR imaging. ADC was measured in frontal white matter (FWM), occipital white matter (OWM), centrum semi-ovale (CSO), basal ganglia (BG), cerebellar hemisphere (CBM) and pons. ADC ratios (fronto-occipital, fronto-cerebellar and occipito-cerebellar) were calculated. Inter-observer reproducibility was assessed on 27 studies, using intra-class correlation coefficient and Bland-Altman plot. Inter-hemispheric difference was evaluated with Bland-Altman plot. Gestation-specific reference intervals were estimated for each brain region. RESULTS: Inter-observer bias was near zero. Limits of agreement (LOA) were clinically acceptable (-0.17; 0.20 to -0.38; 0.31 × 10(-3) mm(2) /s) for all brain regions except for CSO and pons. Inter-hemispheric bias was near zero. Smallest LOA were for FWM (±0.09 mm(2) /s) and BG (±0.019 mm(2) /s). ADC values decreased, whereas ADC ratio increased with gestational age, reflecting normal maturation. Fronto-occipital, fronto-cerebellar and occipito-cerebellar ratios were consistently above 0.8, 1 and 1, respectively. CONCLUSION: The fetal brain regions with the highest reproducibility and smallest inter-hemispheric differences are the frontal, occipital, cerebellar white matter and BG. ADC ratio could be useful to assess differential temporo-spatial maturation.

Isolated remethylation disorders: do our treatments benefit patients?

Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR), the very rare methionine synthase reductase (CblE) and methionine synthase (CblG) defects, and the recently identified CblD-variant-1 defect are primary remethylation defects characterized by an isolated defect in methionine synthesis without methylmalonic aciduria. The clinical signs are mainly neurological, and hematological signs are seen in CblE, CblG, and CblD-variant-1 defects. Patients with neonatal or early-onset disease exhibit acute neurological distress. Infants and children have unspecific mental retardation, often with acquired microcephaly. Without appropriate therapy, they may experience acute or rapidly progressive neurological deterioration, which may be fatal. Adolescents and adults show normal development or mild developmental delay initially and then experience rapid neurological or behavioral deterioration. A few patients may have signs of subacute combined degeneration of the spinal cord. Adults may be asymptomatic or present with isolated thromboembolism. All patients with suspected remethylation disorders should receive emergency treatment with parenteral administration of hydroxocobalamin and folate supplements combined with betaine orally. The long-term treatment of CblE, CblG, and CblD-variant-1 defects consists of parenterally administered hydroxocobalamin and orally administered folate and betaine supplements, whereas patients with MTHFR deficiency require long-term oral folate and betaine supplements. Long-term oral methionine therapy should also be considered. Early treatment may lead to a favorable outcome with developmental recovery and prevention of further neurological deterioration. In contrast, most late-treated patients have severe and irreversible neuromotor impairments. Hematological abnormalities are easily corrected.

Prophylactic hydrocortisone in extremely preterm infants and brain MRI abnormality.

OBJECTIVE: To determine whether early low-dose hydrocortisone treatment in extremely preterm infants is associated with brain damage assessed by MRI at term equivalent of age (TEA). PATIENTS AND OUTCOMES: This is a predefined secondary analysis of brain abnormalities, observed by MRI at TEA, of patients randomly assigned to receive either placebo or hydrocortisone in the PREMILOC trial. Outcomes were based on brain abnormalities graded according to Kidokoro scores. RESULTS: Among 412 survivors at TEA, 300 MRIs were performed and 295 were suitable for analysis. Kidokoro scoring was completed for 119/148 and 110/147 MRIs in the hydrocortisone and placebo groups, respectively. The distribution of the Kidokoro white matter (WM) subscore and other subscores was not significantly different between the two groups. There was, however, a significant association between a higher overall Kidokoro score and hydrocortisone treatment (5.84 (SD 3.51) for hydrocortisone and 4.98 (SD 2.52) for placebo; mean difference, 0.86; 95% CI 0.06 to 1.66; p=0.04). However, hydrocortisone was not statistically associated with moderate-to-severe brain lesions (Kidokoro overall score ≥6) in a multivariate logistic regression model accounting for potential confounding variables (adjusted OR (95% CI) 1.27 (0.75 to 2.14), p=0.38). Bronchopulmonary dysplasia at 36 weeks postmenstrual age significantly predicted both WM damage (adjusted OR (95% CI) 2.70 (1.03 to 7.14), p=0.04) and global brain damage (adjusted OR (95% CI) 2.18 (1.19 to 3.99), p=0.01). CONCLUSIONS: Early hydrocortisone exposure in extremely preterm infants is not statistically associated with either WM brain damage or overall moderate-to-severe brain lesions when adjusted for other neonatal variables. TRIAL REGISTRATION NUMBER: EudraCT number 2007-002041-20, NCT00623740.

Small bowel stenosis: a manifestation of chronic graft-versus-host disease in children?

Digestive graft-versus-host disease (GVHD) is a frequent complication after bone marrow transplantation, but small bowel obstruction is an extremely rare event. We present herein the first pediatric series of 4 cases of small bowel obstruction after bone marrow transplantation with detailed gross, histological data and their genetic status of the NOD2 gene. All patients had a history of severe acute GVHD treated by immunosuppressive agents and/or infliximab (in 3 cases). Acute or progressively worsening abdominal pain accompanied by small bowel occlusion occurred 5-16 months after graft, and computed tomographic scan revealed multiple small intestinal stenoses. Failure of intensive medical treatment led to surgical resection of affected loops. Stigmata of acute (apoptosis of crypts and satellitosis) and chronic GVHD features (submucosal fibrosis and serosae sclerolipomatosis), as well as extensive ulcerations, were observed in all ileal specimens. NOD2 mutation was found in only 1 patient. The follow-up showed successful outcome after surgery.

Contribution of fetal MRI to the diagnosis of inner ear abnormalities: report of two cases.

We report two cases of fetal inner ear abnormalities diagnosed by MRI. Cerebral MRI was performed on two fetuses, at 32 and 30 weeks gestation, following US that demonstrated multiple malformations suggestive of CHARGE syndrome in one fetus and ventriculomegaly and poor visibility of the posterior fossa in the other. MRI revealed vestibular hypoplasia and agenesis of the semicircular canals in one fetus and cystic cochleas, partial vermian agenesis and an occipital meningocele in the second fetus. Both pregnancies were terminated and there was good correlation between fetal MRI, ex utero CT and fetopathological findings. The inner ears should be carefully examined when performing fetal cerebral MRI because abnormalities of the inner ear may be associated with cerebral anomalies.

Prenatal diagnosis of horseshoe lung: contribution of MRI.

Horseshoe lung is a very rare pulmonary anomaly that is characterized by an isthmus of lung parenchyma bridging the right and left lungs and extending through the mediastinum. We report on the prenatal diagnosis of such a malformation in a 33-week-gestation fetus. The diagnosis was initially suspected on antenatal ultrasonography performed at 33 weeks and confirmed by fetal MRI and subsequent pathological examination after termination of pregnancy. To our knowledge, this is the first reported case of antenatal diagnosis of horseshoe lung.