Pascale Philippe-Chomette

Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease

Diagnosis of Hirschsprung disease (HD) is quite entirely based on the histopathological analysis of suction rectal biopsies. This hematoxylin and eosin approach has some limitations, despite the help of acetylcholinesterase staining. The aim of this study was to assess the diagnostic value of calretinin immunochemistry as a simple and reliable method in the diagnosis of HD. A total of 131 initial rectal biopsies carried out for suspicion of HD in children were retrieved, and calretinin immunohistochemistry was carried out on paraffin-embedded biopsies. Diagnosis of HD was made when no staining was observed. The results were statistically analyzed in comparison with our standard method (histology and acetylcholinesterase staining). 130 biopsies were accurately diagnosed on the basis of the positivity or negativity of calretinin staining. The senior pathologists diagnosed all cases of HD with no false positives. Furthermore, 12 additional cases initially considered as doubtful for HD using the standard method, were accurately diagnosed using calretinin immunohistochemistry. The false negative was a case of HD with a calretinin-positive biopsy. We also demonstrate the ease of calretinin interpretation compared with acetylcholinesterase for the junior pathologist. Calretinin immunohistochemistry overcomes most of the difficulties encountered using the combination of histology and acetylcholinesterase staining, and detects almost all cases of HD with confidence, with no false positives. Thus, we demonstrate that calretinin is superior to acetylcholinesterase to complete histology and could advantageously substitute for acetylcholinesterase.

Laparoscopic resection of abdominal neuroblastoma.

BackgroundSince indications for laparoscopic adrenalectomy have progressively expanded to pediatric surgery, preliminary reports have studied the laparoscopic approach for abdominal neuroblastoma (NB). We aimed to report on the indications and the results of laparoscopic resection in a large series of abdominal NBs.MethodsA retrospective multicenter study included 45 children with abdominal NBs (28 localized, 11 stage 4, 6 stage 4s) and laparoscopic resection of their abdominal primary tumor. Primary site of the tumor was the adrenal gland in 41 cases and retroperitoneal space in 4. The median age at surgery was 12 months (1–122); median tumor size was 37 mm (12–70). Resection was performed through transperitoneal laparoscopy (n = 38) or retroperitoneoscopy (n = 7).ResultsComplete macroscopic resection was achieved in 43 of 45 children (96%). The median duration of pneumoperitoneum was 70 min (30–160), and the length of hospital stay was 3 days (2–9). Four procedures (9%) were converted to open surgery, and tumor rupture occurred in three cases. Of the 28 children with localized disease, there was a 96% overall survival (OS) rate after a median follow-up of 28 months (4–94). There was one local relapse in this subgroup, with subsequent complete remission. For the entire 45-children cohort, four children died and three presented a recurrence resulting in OS, disease-free survival, and event-free survival rates of 84% ± 8.1, 84% ± 8.2, and 77% ± 9.1 respectively.ConclusionLaparoscopic resection of abdominal primary allows effective local control of the disease in a wide range of clinical situations of neuroblastoma, with an acceptable morbidity.

Desmoplastic small round cell tumors with EWS-WT1 fusion transcript in children and young adults†‡

The presence of the EWS‐WT1 gene fusion transcript (GFT) is characteristic of desmoplastic small round cell tumor (DSRCT), a rare and very aggressive disease for which the treatment has not yet been clearly standardized.

Mosaicism for oncogenic G12D KRAS mutation associated with epidermal nevus, polycystic kidneys and rhabdomyosarcoma

Background Epidermal nevus (EN) is a congenital disorder characterised by hyperpigmented epidermal thickening following a Blaschkos line. It is due to somatic mutations in either FGFR3 or PIK3CA in half of the cases, and remains of unknown genetic origin in the other half. EN is also seen as part of complex developmental disorders or in association with bladder carcinomas, also related to FGFR3 and PIK3CA mutations. Mosaic mutations of these genes have been occasionally found in syndromic EN. Case report The co-occurrence of EN, rhabdomyosarcoma, polycystic kidneys and growth retardation in an infant is described. Results An oncogenic G12D KRAS mutation was detected in both the epidermal component of the EN and in the rhabodmyosarcoma but not in the dermal component of the EN lesion or in unaffected tissues, including normal skin or blood. Conclusion This report shows for the first time that a KRAS mutation in epiderma causes EN. Observation of the same G12D KRAS mutation in two distinct regions of the body strongly suggests a somatic mosaicism. Finally, this report highlights the potentially underestimated importance of mosaic oncogene mutations in childhood cancers.

HOW ACCURATE IS THE PRENATAL DIAGNOSIS OF ABNORMAL GENITALIA

PURPOSE The prenatal diagnosis of abnormal genitalia may have a major impact on prenatal counseling and postnatal outcome. We studied the accuracy and clinical implications of the prenatal diagnosis of abnormal genitalia. MATERIALS AND METHODS Between 1991 and 1999 the prenatal and/or postnatal diagnosis of abnormal genitalia in 53 cases was made at our institution. All cases were prenatally assessed at our Obstetrics and Fetal Medicine Department. Outcome was confirmed postnatally or by a fetopathologist in the case of pregnancy termination. RESULTS A genital anomaly was prenatally diagnosed in 43 cases and was accurate in 34, while in 9 cases anomalies were absent at birth. In 10 cases ambiguous genitalia were not detected prenatally. The primary anomalies suspected were male pseudohermaphroditism in 19 cases and female pseudohermaphroditism in 12, including 2 cases of congenital adrenal hyperplasia. Male pseudohermaphroditism was detected prenatally in 17 cases and diagnosis was confirmed at birth. Female pseudohermaphroditism was detected prenatally in 12 cases and only 5 were confirmed and the anomaly was discovered at birth in 6. The prognosis was highly altered when many malformations or aneuploidy was associated with ambiguous genitalia. Of the 15 patients with many malformations only 3 survived, and pregnancy was terminated in 3 of 4 cases of aneuploidy. CONCLUSIONS When pseudohermaphroditism was detected in a male fetus by an experienced ultrasonographer at a tertiary center the prenatal diagnosis was accurate in 100% of cases. The prenatal diagnosis was less accurate (46% correct) in a female fetus.

Glial cell-derived neurotrophic factor expression in normal human lung and congenital cystic adenomatoid malformation.

CONTEXT It has been recently suggested that dysregulation of developmental factors and disruption of cell turnover could play a role in the pathogenesis of congenital cystic adenomatoid malformation of the lung (CCAM). The glial cell-derived neurotrophic factor (GDNF) is a growth factor involved in organogenesis, and the temporal pattern of GDNF expression suggests that this factor may play a role in lung development. DESIGN We studied GDNF expression by immunohistochemistry in postnatally resected CCAM of the lung (n = 10), normal fetal lung (n = 5), and normal postnatal lung (n = 5). We also studied the association between GDNF expression and both cell proliferation and apoptosis. RESULTS GDNF was expressed in both epithelial and endothelial compartments of normal fetal lung, whereas no expression was found in normal postnatal lung. In contrast, in CCAM tissue, there was strong GDNF immunostaining that was restricted to epithelial cells. The percentage of proliferating epithelial cells was higher in CCAM tissue than in normal postnatal lung (6.3% vs 1.7%, P <.005). Apoptotic bodies were found in the mesenchyme of both normal fetal lung and CCAM tissue, whereas virtually no apoptotic bodies were detected in normal postnatal lung. CONCLUSIONS Abnormal GDNF expression in CCAM suggests a dysregulation of the GDNF signaling pathway and argues in favor of a focal arrest in maturation during development. GDNF expression in lung tissue seems to be correlated with cell proliferation, suggesting that this factor could play a role in the growth of both fetal lung and CCAM.

Malformations, genetic abnormalities, and Wilms tumor.

Wilms Tumor (WT) can occur in association with tumor predisposition syndromes and/or with clinical malformations. These associations have not been fully characterized at a clinical and molecular genetic level. This study aims to describe clinical malformations, genetic abnormalities, and tumor predisposition syndromes in patients with WT and to propose guidelines regarding indications for clinical and molecular genetic explorations.

Cytoreductive surgery associated to hyperthermic intraperitoneal chemoperfusion for desmoplastic round small cell tumor with peritoneal carcinomatosis in young patients.

PURPOSE Desmoplastic round small cell tumor (DRSCT) is a rare intraabdominal mesenchymal tissue neoplasm in young patients and spreads through the abdominal cavity. Its prognosis is poor despite a multimodal therapy including chemotherapy, radiotherapy, and surgical cytoreduction (CS). hyperthermic intraperitoneal chemotherapy (HIPEC) is considered as an additional strategy in the treatment of peritoneal carcinomatosis; for this reason, we planned to treat selected cases of children with DRSCT using CS and HIPEC. METHODS Peritoneal disease extension was evaluated according to Gilly classification. Surgical cytoreduction was considered as completeness of cytoreduction-0 when no macroscopic nodule was residual; HIPEC was performed according to the open technique. RESULTS We described 3 cases: the 2 first cases were realized for palliative conditions and the last one was operated on with curative intent. There was no postoperative mortality. One patient was reoperated for a gallbladder perforation. There was no other complication related to HIPEC procedure. CONCLUSIONS Surgical cytoreduction and HIPEC provide a local alternative approach to systemic chemotherapy in the control of microscopic peritoneal disease in DRSCT, with an acceptable morbidity, and may be considered as a potential beneficial adjuvant waiting for a more specific targeted therapy against the fusion protein.

A Rare Case of Ectopic Intrathoracic Kidney in a 1-Year-old Child

Congenital thoracic ectopic kidney is a rare developmental anomaly, with the thorax being the rarest and higher location of ectopic kidneys. This anomaly is usually asymptomatic and discovered incidentally on routine chest radiography. At least 200 cases of thoracic kidney have been described, with the vast majority of cases documented in adults. To our knowledge, this is only the sixth case of congenital ectopic thoracic kidney described in a child. Herein, we report a rare case of a 1-year-old child exhibiting ectopic intrathoracic kidney. We further discuss the embryonic background and the current management of this pathology.

Post-Surgical Perforation of the Esophagus Can be Treated Using a Fully-Covered Stent in Children.

Objectives: Surgery and conservative treatment of esophageal or gastric perforations are both often associated with poor results and carry a high morbidity and mortality rate. The aim of the present study was to evaluate the effectiveness and safety of using fully covered self-expending metallic stents (SEMS) in children with upper digestive leaks. Methods: This retrospective study reviewed all children with esophageal or gastric perforation who were treated with placement of an SEMS from January 2011 to January 2015. Closure of the perforation was the primary outcome measured. Secondary outcomes were the duration of antibiotic therapy and parenteral nutrition, adverse events, and length of hospitalization. Results: A total of 19 SEMS were placed in 10 patients (median age: 5.5 years; 5 girls) treated for postanastomotic leaks of esophageal atresia (n = 3), esophagogastroplasty (n = 4), resection of esophageal duplication (n = 1) or perforation during Toupet surgical dismantling (n = 1), and gastric rupture after Nissen surgery (n = 1). The perforation closed in 9 out of 10 patients in a mean of 36 days after stenting (range: 13–158 days). All patients received antibiotic therapy for an average of 17.5 days (3–109 days) and parenteral nutrition for 49 days (17–266 days). During a median follow-up of 8.9 months, 4 out of 9 sealed perforations developed stenosis, which was efficiently treated by endoscopic dilations in 2 patients and surgical redo in 2 patients with dilation-resistant stenosis. Conclusions: Covered stents appear to be beneficial in closing esophageal perforations in children and can avoid the high morbidity of a surgical repair. Stenosis, however, occurred frequently after larger leakages.