Intestinal congenital/infantile fibrosarcoma: a new clinico-pathological entity?

Congenital/infantile fibrosarcoma (IFS) is a relatively rare form of fibrosarcoma diagnosed at birth or during early years of life and that differs from its adult counterpart because of a more favorable behavior. IFS is also known as cellular congenital mesoblastic nephroma, when it affects the kidney and is often but not always characterized by the ETV6-NTRK3 fusion transcript. We report herein the first series of an exceptional tumor of the small intestine occurring in newborns. The four patients shared a stereotyped clinico-pathological presentation with early and acute onset, intestinal perforation, and an infiltration by a highly cellular spindle cell tumor within the dilated intestinal wall exhibiting pathologic features typical of IFS. Molecular studies for the ETV6-NTRK3 translocation were negative in the three cases tested. Patients were treated by surgical wide resection alone and are alive and well (follow-up: 36 months-25 years). Thus, this new clinico-pathological entity, even with lack of documented evidence of the ETV6-NTRK3 translocation, should be included in the differential diagnosis of congenital bowel perforation or obstruction and may represent an intestinal counterpart of IFS.

Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.

Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/beta-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. beta-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy.

Advantages of intraoperative semiquantitative evaluation of myenteric nervous plexuses in patients with Hirschsprung disease.

BACKGROUND: The reappearance of an occlusive syndrome after surgical treatment of patients with Hirschsprung disease is often caused by incomplete resection of the affected segment. Intraoperative examination of frozen biopsies assists surgery, but interpretation of biopsies in the transitional zone is difficult. METHODS: We performed retrospective semiquantitative evaluations of myenteric nervous plexuses at the proximal limits of resection specimens from 41 children who were treated for rectocolic Hirschsprung disease using intraoperative examination of transparietal biopsies. The results of the evaluations were correlated with the postoperative courses of the children. RESULTS: After formalin fixation, the mean length of the aganglionic segments was 8.9 cm (range, 1-37.5 cm). At the proximal limit, the percentage of the circumference of the muscularis propria that was composed of plexuses with ganglion cells was more than 95% in 7 children, 90% to 95% in 21 children, 40% to 80% in 6 children, and 30% or less in 7 children (17%), 4 of whom subsequently developed occlusive syndromes. CONCLUSIONS: Semiquantitative intraoperative examination of the entire circumference of resected segments facilitates precise evaluation of intrinsic innervation at the level of the anastomosis and may reduce the frequency of recurrence of occlusive symptoms after surgery.

Gastropathy and gastritis in children with portal hypertension.

The aim of this study was to determine the frequency of portal hypertensive gastropathy (PHG) and gastritis in children with portal hypertension and related factors. The study included 24 children with portal hypertension secondary to liver disease or extrahepatic venous obstruction. PHG was seen in 14 of 24 patients. PHG was significantly associated with the presence of esophageal varices and a history of hematemesis. Histologically, gastritis was identified in 14 of 24 patients and was significantly associated with cirrhosis. PHG is frequently found in children with portal hypertension, and it develops regardless of the cause of the portal hypertension.

Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry.

OBJECTIVE: To characterize the association of pleuropulmonary blastoma (PPB) with cystic nephroma (CN) and other renal tumors. STUDY DESIGN: Complete clinicopathologic review of cases from the International PPB Registry and literature. RESULTS: We identified 18 patients with PPB associated with 20 renal tumors (15 CN), either in themselves or family members. All patients with PPB were <5 years of age. All but one of the renal diagnoses were made before 4 years of age. Eleven children had both PPB and renal tumor, one of whom also had a sibling with CN. Six children with PPB alone had one or more family members with CN. The mother of one child with PPB had Wilms' tumor. Pulmonary disease was bilateral in four patients. Renal disease was bilateral in three patients. Two children with PPB and bilateral renal cystic tumors also had intussusceptions because of small bowel juvenile polyps. In six families, dysplasia/neoplasia affected organs other than lung and kidney. CONCLUSIONS: CN or related tumors were found in 9.2% of 152 Registry-reviewed PPB cases. The occurrence of rare pulmonary and renal tumors together in patients and/or family members, the early age of onset, and the multiplicity of tumors is compatible with a constitutional genetic predisposition.

[Complexity of pathological interpretation in megacystis-microcolon-intestinal hypoperistalsis syndrome]. / Complexité de l'interprétation anatomopathologique dans le syndrome mégavessie-microcôlon-hypopéristaltisme intestinal.

Megacystis-microcolon-intestinal hypoperistalsis syndrome is very rare, and is the most severe of the chronic intestinal pseudoobstructions. Diagnosis is usually made in the neonatal period, is clinical and radiological, and is confirmed by manometric studies. Microscopic abnormalities are variable, inconstant and nonspecific. They involve the smooth muscle more often than the intrinsic innervation of the gut and the bladder. A girl, currently seven years old, presented with megacystis observed on prenatal ultrasound at 21 weeks of gestation. At first, amniotic fluid volume was appropriate for gestational age, and then hydramnios appeared at 30 weeks of gestation. Microcolon was discovered at birth, with microileum, dilatation of the duodenum and proximal jejunum, intestinal malposition, and severe hypoperistalsis of the entire gastrointestinal tract, which indicated enterostomy and total parenteral nutrition from birth. At pathological examination, rectal biopsy and enteric nervous plexuses were normal. There was hypoplasia of the external longitudinal layer of the muscularis propria in the colon and ileum. Cajal cells could not be demonstrated immunohistochemically in the colon. This case highlights the complexity and difficulties of pathological interpretation in this syndrome, and the necessity of a large study of controls at different ages and different levels of the digestive tract and the bladder.

High rate of Helicobacter pylori reinfection in children and adolescents.

AIMS: Primary Helicobacter pylori infection occurs predominantly in childhood. The aims of this study were to establish the rate of H. pylori reinfection after successful eradication in children and adolescents and to determine the risk factors associated with reinfection. PATIENTS AND METHODS: This retrospective study involved 45 children (20 girls, 25 boys) who met the following criteria: eradication of H. pylori confirmed at least 4 weeks after the completion of therapy, and the search for reinfection at least one year after control of eradication of H. pylori. Demographic data, socioeconomic status and living conditions were recorded. RESULTS: Forty-five children aged 1.2-17.6 years (median, 10.9 years) at the time of H. pylori treatment were reviewed 1 to 9 years after H. pylori eradication. Eight children (18%) had been reinfected (5.4% to 6% per patient-year). Six of 25 (24%) children older than 10 years at the time of diagnosis became reinfected. None of the studied risk factors was associated with reinfection. However, having a sibling younger than 5 years was found in four of seven (57%) reinfected children versus five of 24 (21%) nonreinfected children (p = .08). CONCLUSION: Children become reinfected more frequently than adults. Adolescents become reinfected, whereas acquisition of primary H. pylori infection occurs predominantly in early childhood. Close contact with young children, especially siblings, younger than 5 years could be a more important risk factor than the age of the patient at the time of treatment for the high rate of reinfection in childhood.

Mucoepidermoid carcinoma of the parotid gland in a child previously treated for acute lymphoblastic leukemia.

Occurrence of second cancers is a major concern for the care of children cured of cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased risk for developing mucoepidermoid carcinomas (MEC) of the parotid gland. The latent period ranges from 5 to 16 years. A 3-year-old boy presented with pre-B ALL. Treatment included multidrug chemotherapy and prophylactic intrathecal injections of methotrexate and prednisolone. Low-grade MEC of the left parotid gland was diagnosed at the age of 7 years, only 1 year after completing treatment. Local lymph nodes were not metastatic, and course was favorable 8 years after complete surgical excision. This case report is remarkable for the early diagnosis of second cancer, only 4 years after diagnosis of ALL, and its occurrence in parotid gland without previous head and neck irradiation. It highlights the need for concern about second cancers of the parotid gland in children treated for ALL.

Separate occurrence of extra-adrenal paraganglioma and gastrointestinal stromal tumor in monozygotic twins: probable familial Carney syndrome.

The nonfamilial Carney triad includes paraganglioma, gastrointestinal stromal tumor (GIST), and pulmonary chondroma. Some paraganglioma-GIST diads are familial and inherited in an apparent autosomal dominant manner. The familial paraganglioma-GIST syndrome differs from the Carney triad by the absence of female predilection and predominance of paragangliomas. We report the cases of a 12-year-old boy with a paraganglioma of the organ of Zuckerkandl, and his 13-year-old monozygotic twin with a gastric GIST. These two patients, to our knowledge, are the first to be reported as likely having the familial paraganglioma-GIST syndrome following its description by Carney and Stratakis (Am J Med Genet 2002;108:132-139) in 12 patients from five families. A lifetime follow-up and a periodic search for both tumors are indicated in these patients and their families.

Brain involvement in multicentric Epstein-Barr virus-associated smooth muscle tumours in a child after kidney transplantation.

Epstein-Barr virus (EBV)-associated smooth muscle tumours (SMT) have been reported in young patients with induced immunosuppression associated with organ transplantation, acquired immunodeficiency syndrome or congenital immunodeficiencies. EBV-associated SMT are frequently multicentric or multifocal and often occur in unusual locations. We are reporting a case of EBV-associated multicentric SMT that occurred after kidney transplantation in a 2-year-old boy with a history of oligomeganephrony. Headaches and left VIth cranial nerve paralysis led to the discovery of a brain tumour 3 years after transplantation. There were multiple pulmonary, hepatic and splenic nodules and enlarged mesenteric lymph nodes. Histological examination revealed multicentric SMT of uncertain malignant potential. Further investigations using in situ hybridisation demonstrated EBV early RNAs in the nucleus of most tumour cells. The immunosuppressive therapy was reduced, and the child was treated with chemotherapy, but died 2 months later, due to neurological complications.

[Hirschsprung's disease: practical considerations]. / Maladie de Hirschsprung: attitude pratique.

Hirschsprung's disease (1/5000 live births) is defined by the congenital absence of neuronal cells in the nervous plexuses in the distal part of the digestive tract. The disease affects the rectum and sigmoid colon in 80% of cases, or is more extensive. Hirschsprung's disease is suspected in cases of low gastrointestinal obstruction in the neonatal period, or in cases of chronic severe constipation in childhood. It is diagnosed by pathological examination of rectal biopsies that include the submucosa. After standard staining, multiple sections are scrutinized for neuronal cells. Acetylcholinesterase staining is performed on a frozen fragment to demonstrate the hyperplasia of cholinergic fibers that is very suggestive of Hirschsprung's disease. This hyperplasia decreases from the rectum to the splenic flexure of the colon. Hyperplasia of extrinsic nerve fibers and rarefaction of neuromuscular junctions in Hirschsprung's disease may be demonstrated immunohistochemically. Differential diagnosis includes chronic intestinal pseudo-obstructions. The treatment for Hirschsprung's disease is, most often, anastomosis of the normally innervated gut to the anal canal. Peri- or pre-operative biopsies assist surgery, but their interpretation is difficult in the transitional zone. The examination of the surgical specimen allows measurement of the aganglionic segment and transitional zone. Different genes (RET, most often) may be involved in sporadic or familial Hirschsprung's disease. Hirschsprung's disease is associated with other digestive or extra-digestive abnormalities in 5 to 30% of patients. Associated abnormalities may delay the diagnosis and treatment of Hirschsprung's disease.

[Benign epithelial cells and Tamm-Horsfall protein in lymph nodes from nephrectomy specimens with nephroblastoma: a diagnostic pitfall]. / Cellules épithéliales bénignes et protéine de Tamm-Horsfall dans les ganglions lymphatiques des pièces de néphrectomie pour néphroblastome: un piège diagnostique.

When a lymph node metastasis is discovered during the pathology examination of surgical specimens with nephroblastoma, the tumour is classified as stage III, according to the classification of the International Society of Paediatric Oncology (SIOP 2001), and post-operative intensive treatment of the patient includes irradiation and chemotherapy. Benign epithelial cells in perinephric lymph nodes in cases of renal tumours in childhood may be confused with metastases. They are often associated with an accumulation of Tamm-Horsfall protein in lymph node sinuses. This case illustrates latero-aortic lymph node complexes of benign epithelial cells and Tamm-Horsfall protein in a 16-month-old girl with surgical resection of a nephroblastoma after pre-operative chemotherapy. The nephroblastoma was predominantly epithelial and was classified as SIOP stage I. There were accumulations of Tamm-Horsfall protein in lymph node sinuses, in lymphatic vessels, in the kidney outside the tumour, and in the renal sinus. This association of epithelial cells with deposits of Tamm-Horsfall protein and their resemblance to cells of the distal convoluted tubules favour a diagnosis of benignity. A definitive diagnosis is supported by the small size of the cells, their bland nuclei, and morphological features differing from those of tumour cells, but deposits of Tamm-Horsfall protein may be associated with true lymph node metastases.

[Synaptophysin expression abnormalities in Hirschsprung's disease]. / Anomalies d'expression de la synaptophysine dans la maladie de Hirschsprung.

Hirschsprung's disease is defined by the congenital absence of ganglion cells in enteric plexuses. Immunostaining of synaptophysin after formalin fixation may be used to identify hyperplasia of nerve fibers and rarefaction of neuromuscular junctions in Hirschsprung's disease. The aim of the study was to evaluate semi-quantitatively the expression of synaptophysin in Hirschsprung's disease, in correlation with morphologic features. This retrospective study included 3 controls, 42 surgical rectal biopsies performed for suspicion of Hirschsprung's disease in children presenting with lower digestive occlusion or severe chronic constipation, including 18 Hirschsprung's disease, and 23 surgical specimens of Hirschsprung's disease. In the absence of Hirschsprung's disease, synaptophysin-positive fibers were numerous but thin in the muscularis mucosae, thin and scarce in the mucosa and submucosa. Neuromuscular junctions were thin and numerous in the muscularis propria. In Hirschsprung's disease, synaptophysin-positive fibers were coarse, and increased in number on each side of the muscularis mucosae. Plexuses were enlarged, weakly stained, and associated in the connective tissue of the muscularis propria with coarse and intensely stained fibers. In conclusion, staining for synaptophysin could be useful to demonstrate abnormalities of enteric innervation in rectal biopsies performed for suspected Hirschsprung's disease in the absence of acetylcholinesterase staining on frozen sections, in transmural biopsies performed for guiding surgery in Hirschsprung's disease, and in cases of extensive Hirschsprung's disease.