Enucleation for intestinal duplications: a comparative study with intestinal resection and anastomosis.

PURPOSE: Duplication enucleation (DE) has been described as an alternative to intestinal resection with primary anastomosis (IRA) for intestinal duplications, but no comparative study exists. The aim of this study was to compare both surgical procedures for intestinal duplication. METHODS: A retrospective study was performed, including all children treated for intestinal duplication (2005-2023). Patients that underwent DE were compared to those that underwent IRA. Statistical significance was determined using p < 0.05. Ethical approval was obtained. RESULTS: A total of 51 patients (median age: 5 months) were treated for intestinal duplication, including 27 patients (53%) that underwent DE and 24 IRA (47%). A cystic image was detected prenatally in 19 patients (70%) with DE and 11 patients (46%) with IRA (p = 0.09). Enucleation was performed using laparoscopy in 7 patients (14%). Patients that underwent DE had shorter time to first feed (1 vs 3 days, p = 0.0001) and length of stay (4 vs 6 days, p < 0.0004) compared to IRA. A muscular layer was identified in 68% of intestinal resection specimens. CONCLUSION: Compared to intestinal resection with anastomosis, duplication enucleation is associated with decreased postoperative length of stay and delay to first feeds without increasing post-operative complications. Regarding histological analysis, enucleation seems feasible in most cases.

Intravenous Immunoglobulins for Recurrent Chronic Histiocytic Intervillositis: A Series of Case Studies.

INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases. PATIENTS AND METHODS: We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients. RESULTS: For three patients, intravenous immunoglobulins were initiated at the ßHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG. CONCLUSION: This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.

Successful lung transplantation in genetic methionyl-tRNA synthetase-related alveolar proteinosis/lung fibrosis without recurrence under methionine supplementation: Medium-term outcome in 4 cases.

Pulmonary alveolar proteinosis (PAP) results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages, and can be associated with pulmonary fibrosis, with a need for lung transplantation (LTx). Causes of PAP are autoimmune (90%-95%), secondary (5%), or hereditary (<1%). Patients with hereditary PAP are generally not considered for isolated LTx, due to the high probability of recurrence after LTx, and only a challenging scenario with sequential LTx followed by hematopoietic stem cell transplantation (HSCT) was reported as successful. Recently, a new genetic cause of PAP linked to mutations in the methionyl-tRNA synthetase (MARS) gene has been reported, with a highly variable clinical presentation. Because clinical correction of the defective MARS activity with methionine supplementation has been reported in nontransplanted children, we reassessed the feasibility of LTx for candidates with MARS-related PAP/fibrosis. We report 3 cases of LTx performed for MARS-related pulmonary alveolar proteinosis-pulmonary fibrosis without recurrence under methionine supplementation, whereas another fourth case transplanted without supplementation had fatal PAP recurrence. These results suggest the effectiveness of methionine in correcting defective MARS activity and also looking for this very rare diagnosis in case of unclassified PAP/fibrosis. It argues for not excluding the feasibility of isolated LTx in patients with MARS mutation.

Pulmonary mucoepidermoid carcinoma in a 7-year-old child.

A 7-year-old boy presented with exertional dyspnea and cough, initially misdiagnosed as asthma. Imaging revealed a mass obstructing the left main bronchus, later identified as a pulmonary mucoepidermoid carcinoma (MEC). Following surgical sleeve resection, complete tumor removal occurred without malignancy in surrounding lymph nodes, resulting in symptom resolution without additional therapy. Pulmonary MEC, uncommon in pediatric patients, poses diagnostic challenges due to nonspecific symptoms, resulting in delayed diagnosis. Typically managed via complete surgical resection, MEC offers a favorable prognosis, primarily affecting central airways and requiring conservative surgical approaches to preserve lung tissue. This case underscores the diagnostic challenges of primary pulmonary MEC in pediatric patients. It stresses the need to consider unusual causes in pediatric respiratory symptoms and highlights the critical role of precise diagnostic methods and personalized surgical strategies in managing such rare pulmonary malignancies for optimal outcomes.

Massive perivillous fibrin deposition: Diagnosis, obstetrical features, and treatment.

MPVFD (Massive perivillous fibrin deposition) is placental lesion characterized by extensive massive deposits of fibrin in the intervillous space, extending over at least 25 % of the placental volume. Currently, this pathology can only be detected through histopathological examination of the placenta after a pregnancy has ended. The underlying mechanisms are poorly studied, there is no biomarker available for the diagnosis of MPVFD and treatment protocols are experimental and still lacking. The objective of this study is to systematically review the literature on the associated clinicopathologic features, treatment, and prognosis of MPVFD. We ended up with 17 studies, of these 12 studies were considered relevant for this article and included in the final analysis. All studies reporting MPVFD are retrospective. MPVFD is associated with recurrent miscarriage, intra uterine fetal death (IUFD), intra uterine growth restriction (IUGR) and preterm delivery. The prevalence in pregnancies with a delivery after 22 weeks of gestation was at 1.1 % and even higher to 2.7 % in recurrent early miscarriages. The reported risk of fetal death in MPVFD ranges mainly from 15 to 80 %. Preterm delivery is spontaneous in 50 to 70 % of cases and induced by of a severe intrauterine growth restriction (IUGR) in 30 to 50 % of cases depending on the study. Its causes and treatment are still poorly understood, although several avenues have been explored. This review summarizes current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology, and potential prophylaxis against recurrence in this chronic inflammatory placental syndrome.

Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors.

Wilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell models. We identify histone deacetylase and/or WEE1 inhibitors as potential therapeutic vulnerabilities in these tumors, which might also restore tumor immunogenicity and potentially enhance the effects of immunotherapy. These insights offer a foundation for predicting outcomes and personalizing treatment strategies for aggressive pediatric Wilms tumors, tailored to individual immunological landscapes.

Hypomorphic pathogenic variant in SFTPB leads to adult pulmonary fibrosis.

Biallelic pathogenic variants in the surfactant protein (SP)-B gene (SFTPB) have been associated with fatal forms of interstitial lung diseases (ILD) in newborns and exceptional survival in young children. We herein report the cases of two related adults with pulmonary fibrosis due to a new homozygous SFTPB pathogenic variant, c.582G>A p.(Gln194=). In vitro transcript studies showed that this SFTPB synonymous pathogenic variant induces aberrant splicing leading to three abnormal transcripts with the preservation of the expression of a small proportion of normal SFTPB transcripts. Immunostainings on lung biopsies of the proband showed an almost complete loss of SP-B expression. This hypomorphic splice variant has thus probably allowed the patients' survival to adulthood while inducing an epithelial cell dysfunction leading to ILD. Altogether, this report shows that SFTPB pathogenic variants should be considered in atypical presentations and/or early-onset forms of ILD particularly when a family history is identified.

Pediatric Tumors and Developmental Anomalies: A French Nationwide Cohort Study.

OBJECTIVE: To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with cancer and congenital abnormalities. STUDY DESIGN: Tumeur Et Développement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking. RESULTS: From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm. CONCLUSIONS: In the first Tumeur Et Développement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.

Imaging of Pediatric Testicular and Para-Testicular Tumors: A Pictural Review.

Pre- and post-pubertal testicular tumors are two distinct entities in terms of epidemiology, diagnosis and treatment. Most pre-pubertal tumors are benign; the most frequent are teratomas, and the most common malignant tumors are yolk-sac tumors. Post-pubertal tumors are similar to those found in adults and are more likely to be malignant. Imaging plays a pivotal role in the diagnosis, staging and follow-up. The appearance on ultrasonography (US) is especially helpful to differentiate benign lesions that could be candidates for testis-sparing surgery from malignant ones that require radical orchidectomy. Some specific imaging patterns are described for benign lesions: epidermoid cysts, mature cystic teratomas and Leydig-cell tumors. Benign tumors tend to be well-circumscribed, with decreased Doppler flow on US, but malignancy should be suspected when US shows an inhomogeneous, not-well-described lesion with internal blood flow. Imaging features should always be interpreted in combination with clinical and biological data including serum levels of tumor markers and even intra-operative frozen sections in case of conservative surgery to raise any concerns of malignity. This review provides an overview of imaging features of the most frequent testicular and para-testicular tumor types in children and the value of imaging in disease staging and monitoring children with testicular tumors or risk factors for testicular tumors.

International Comparisons of Clinical Demographics and Outcomes in the International Society of Pediatric Oncology Wilms Tumor 2001 Trial and Study.

PURPOSE: International comparisons of patient demographics, tumor characteristics, and survival can shed light on areas for health care system improvement. The International Society of Pediatric Oncology Wilms Tumor 2001 trial/study registered patients through national clinical study groups in Western Europe and Brazil. This retrospective post hoc analysis of the International Society of Pediatric Oncology Wilms Tumor 2001 database aims to make visible and suggest reasons for any variations in outcomes. METHODS: All patients with unilateral Wilms tumor (WT), age > 6 months, treated with preoperative chemotherapy as per protocol, and registered between 2001 and 2011 were eligible. Countries were grouped to give comparable case numbers and geographical representation. Cox univariable and multivariable (MVA) statistics were applied, with the German collaborative group (Gesellschaft für Pädiatrische Onkologie und Hämatologie-Austria, Germany, and Switzerland) as reference for hazard ratios for event-free survival (EFS) and overall survival (OS). RESULTS: A total of 3,176 eligible patients were registered from 24 countries assigned into six groups. Age and histologic risk group distribution were similar across all groupings. The distribution of WT stage varied by country grouping, with 14.9% (range, 11.1%-18.2%) metastatic at diagnosis. Median follow-up was 78.9 months. For localized WT, 5-year EFS varied from 80% (Brazilian group) to 91% (French group; P < .0001), retaining significance only for Brazil in MVA (P = .001). Five-year OS varied from 89% (Brazilian group) to 98% (French group; P < .0001). In MVA, only superior OS in France was significant (P = .001). Five-year EFS/OS for stage IV did not vary significantly. High-risk histology and tumor volume at surgery were significantly associated with increased risk of death in MVA for metastatic disease. CONCLUSION: International benchmarking of survival rates from WT within a large trial/study database has demonstrated statistically significant differences. Clinical interpretation should take account of variation in tumor stage but also treatment factors.

Renal cell carcinoma in children and adolescents: a retrospective study of a French-Italian series of 93 cases.

AIMS: Renal cell carcinomas (RCCs) represent 2-5% of kidney malignancies in children and adolescents. Appropriate diagnostic and classification are crucial for the correct management of the patients and in order to avoid inappropriate pre-operative chemotherapy, which is usually recommended if a Wilms' tumour is suspected. METHODS AND RESULTS: A French-Italian series of 93 renal cell carcinomas collected from 1990 to 2019 in patients aged less than 18 years was reclassified according to the 2016 World Health Organization (WHO) classification and the latest literature. TFE3 and TFEB fluorescence in-situ hybridisation (FISH) analyses and a panel of immunohistochemical stains were applied. The median age at diagnosis was 11 years (range = 9 months-17 years). MiT family (MiTF) translocation RCCs accounted for 52% of the tumours, followed by papillary (20%) and unclassified RCCs (13%). Other subtypes, such as SDHB-deficient and fumarate hydratase-deficient RCCs, represented 1-3% of the cases. We also described a case of ALK-rearranged RCC with a metanephric adenoma-like morphology. CONCLUSION: A precise histological diagnosis is mandatory, as targeted therapy could be applied for some RCC subtypes, i.e. MiTF-translocation and ALK-translocation RCC. Moreover, some RCC subtypes may be associated with a predisposition syndrome that will impact patients' and family's management and genetic counselling. A precise RCC subtype is also mandatory for the clinical management of the patients and inclusion in new prospective clinical trials.

[Chronic aqueous diarrhea in children: An unusual etiology]. / Diarrhée aqueuse chronique chez l'enfant : une étiologie à ne pas méconnaître.

Peripheral neuroblastic tumors are the most common extracranial solid tumors in children. On the other hand, diarrheal neuroblastic tumors are quite rare and not easy to diagnose in the early stage. We report a case of neuroblastic tumor in a 2-year old girl presenting with aqueous diarrhea caused by paraneoplasic secretion of VIP.

Epstein-Barr Virus in Childhood and Adolescent Classic Hodgkin Lymphoma in a French Cohort of 301 Patients.

OBJECTIVE: The aim was to analyze the role of Epstein-Barr virus (EBV) in the bioclinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France. METHODS: Biopathologic data of 301 patients treated for a cHL in/or according to the EuroNet PHL-C1 trial between November 2008 and February 2013 were centrally reviewed. RESULTS: Median age at diagnosis was 14 (3 to 18) years and the F/M ratio 0.86, 0.47 before 10 years and 0.9 from 11 to 18. CHL subtypes were nodular sclerosis for 266/301 (88%) patients, mixed cellularity for 22/301 (7%), lymphocyte rich for 2/301 (1%), and 11/301 were unclassified. EBV positivity by in situ hybridization was observed for 68/301 (23%) patients, significantly associated with mixed cellularity subtype and male sex, particularly overrepresented in boys below 10 years: 15/23 (65%) versus 28/139 among other male patients (20%). EBV viral load was detectable in 22 of 108 (22%) tested cases and was overrepresented in EBV cHL (13/28) versus non-EBV cHL (9/80) patients. Detailed semiquantitative histologic analysis showed a high number of B-cell residual follicles in EBV cHL relative to EBV-negative HL. CONCLUSION: Distribution of EBV cHL in children and adolescents is associated with young age and male sex, suggesting a specific physiopathology and may require a differential therapeutic approach.

Nephron Sparing Surgery in Bilateral Wilms Tumors With Botryoid Growth Pattern.

Botryoid growth pattern (BGP) is a polypoid mass growing into the renal pelvis, rarely seen in bilateral Wilms tumors where it represents a surgical challenge. We report our experience of nephron sparing surgery in 3 patients with BGP in bilateral Wilms tumor. Surgical en bloc removal was performed after calyx opening with no complications. The histology of the BGP was Intralobar Nephrogenic Rest in all cases while all Wilms tumors were of intermediate risk. One patient early recurred. At a follow-up of 9 months, 22 and 23 years, all patients were alive with a moderate renal insufficiency and hypertension.

Chronic Villitis of unknown etiology (VUE): Obstetrical features, outcome and treatment.

Villitis of unknown etiology (VUE) is characterized by lympho-histiocytic infiltrates, which are predominant within the villous stroma. VUE can be of low grade i.e. affecting less than 10 contiguous villi or high grade with either patchy or diffuse subgroups (the later concerning more than 30 % of distal villi). Several other placental lesions could be associated with VUE, in particular in diffuse subgroups, such as diffuse perivillous fibrin deposition and chronic intervillositis. One of the most characteristic features of VUE is the late onset of fetal growth restriction after 32 weeks of gestation, and earlier detection of villitis should first raise an infectious origin. High grade VUE has been associated with fetal growth restriction, prematurity, fetal deaths, recurrent pregnancy loss, central nervous system injury and is characterized by relatively high risk of recurrence (25-50 %). Prospective and well-designed studies are necessary to determine the real prevalence of these adverse pregnancy events associated with VUE. Data about the management of VUE are extremely scarce and thus no recommendation based on the literature review could be actually done.

Frequent altered distribution of peripheral B-lymphocyte subsets in pediatric and adolescent patients with classical Hodgkin lymphoma.

Peripheral lymphopenia is a well-known negative prognostic marker in classical Hodgkin lymphoma (cHL). We characterized the peripheral B-cell compartment in a prospective cohort of 83 pediatric cHL patients. We observed significantly low total B-cell counts (<100 cells/µl) in 31 of 83 patients (37%). More specifically, there was a smaller peripheral IgDhighCD27- naïve B-cell pool among B-cell lymphopenic patients than for non-B-cell lymphopenic patients (p < 0.01). The B-cell count was lower in patients without in situ Epstein Barr Virus (EBV) expression than among those with in situ EBV expression (p = 0.03). Peripheral B-cell lymphopenia was associated with the presence of poor prognostic features, such as advanced lymphoma stage (p < 0.01) and the presence of B symptoms (p = 0.04). Of interest, B-cell lymphopenia resolved in all six studied patients in long-term remission. Our findings support that cHL tumor-associated factors interfere with the distribution of peripheral B-cell subsets.

Wilms tumors and their precursors: Radiological diagnosis versus histology.

The radiological distinction of Wilms tumor (WT) nodules from nephrogenic rests (NR) in patients with multifocal unilateral WT or bilateral disease is challenging. The study aims to compare the radiology assessment of kidney nodules with their final histology in 48 patients. The final histology of 118 nodules corresponded to the initial radiological diagnosis while 40 (25%) nodules were misdiagnosed, 20 being initially diagnosed WT on imaging were proved to be NR at histology. The size of nodules at diagnosis might help to distinguish WT from NR before surgery. Homogeneity did not seem to be a key feature.