Françoise Boman

Hepatic Stem-like Phenotype and Interplay of Wnt/β-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.

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.

Mucin gene transcripts in benign and borderline mucinous tumours of the ovary: an in situ hybridization study.

Mucinous tumours of the ovary are characterized by mucin‐secreting cells exhibiting a variable endocervical, intestinal, gastric or pancreatobiliary phenotype as ascertained by microscopy, electron microscopy, histochemistry or immunohistochemistry. The molecular mechanisms underlying the tumourigenesis process are not well understood. The mucin glycoproteins expressed by ovarian mucinous tumours have not been fully characterized, but mucins are known to be implicated in tumour progression in various epithelial neoplasms. The purpose of this study was to evaluate the expression of mucin genes (MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6) in ovarian mucinous tumour cells, to relate MUC gene expression to the histological diagnosis, and to compare the expression patterns with those observed in normal tissues. The expression of mucin genes was evaluated by in situ hybridization in 21 mucinous tumours (11 adenomas and ten borderline tumours). Heterogeneity of expression correlated with morphological heterogeneity. Intense expression of the MUC5AC gene, suggesting a gastric surface cell phenotype, was demonstrated in 18/21 tumours (86%). Goblet cells expressing the MUC2 gene and columnar cells expressing the MUC3 gene were consistent with an intestinal phenotype, which was observed in 15 tumours (71%) including nine adenomas and six borderline tumours. Major expression of MUC4 and MUC5B consistent with an endocervical phenotype was observed in seven benign (64%) and three borderline (30%) tumours. In all, the MUC profiles suggested gastrointestinal‐type cells in 13 cases (62%), gastric‐type cells in five cases (24%), and intestinal‐type cells in two cases (one benign, one borderline) (9%); the results were inconclusive in one borderline tumour (5%). It is concluded that gastric and, to a lesser degree, intestinal differentiation are early and almost constant events in ovarian mucinous tumourigenesis. Copyright

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. Pediatr Blood Cancer 2005;44:673–675.

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.

Complexité de l’interprétation anatomopathologique dans le syndrome mégavessie-microcôlon-hypopéristaltisme intestinal

Resume Le syndrome megavessie-microcolon-hypoperistaltisme intestinal, tres rare, est la plus severe des pseudo-obstructions intestinales chroniques. Le diagnostic est habituellement porte en periode neonatale. Il est clinique et radiologique, et precise par les etudes manometriques. Les lesions anatomopathologiques sont variees, inconstantes et aspecifiques. Elles toucheraient plus souvent le muscle lisse que l’innervation intrinseque au niveau enterique et vesical. L’observation se caracterisait, chez une petite fille actuellement âgee de sept ans, par une megavessie decouverte a l’echographie prenatale realisee a 21 semaines d’amenorrhee. Le liquide amniotique etait d’abord en quantite normale pour l’âge gestationnel, puis un hydramnios est apparu a 30 semaines d’amenorrhee. Un microcolon etait decouvert a la naissance, avec microgrele distal et dilatation duodenale et jejunale proximale, malposition intestinale, et hypoperistaltisme severe de tout le tube digestif necessitant une enterostomie et une nutrition parenterale totale depuis la naissance. A l’examen anatomopathologique, la biopsie rectale et les plexus nerveux enteriques etaient d’aspect normal. Il existait une hypoplasie de la couche longitudinale externe de la musculeuse au niveau colique et au niveau ileal. Les cellules de Cajal n’etaient pas mises en evidence en immunohistochimie au niveau colique. Cette observation souligne la complexite et les difficultes de l’interpretation anatomopathologique dans ce syndrome, et la necessite d’une large serie de temoins a differents âges et a differents niveaux du tube digestif et de la vessie.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.

Virilizing ovarian dermoid cyst with peripheral steroid cells. A case study with immunohistochemical study of steroidogenesis.

A case of virilizing ovarian dermoid cyst with peripheral steroid cells and virilization is reported in a 62-year-old woman. The level of testosterone dropped to normal after oophorectomy. The cyst wall was bordered by a discontinuous band of steroid cells focally accompanied by smooth muscle cells. Immunohistochemically, the steroid cells were enzymatically active and displayed a profile similar to the internal theca cells of ovarian follicles. These steroid cells were most probably modified stromal cells associated with smooth muscle metaplasia of the ovarian stroma.

Maladie de Hirschsprung : attitude pratique

Resume La maladie de Hirschsprung (1/5 000 naissances) est definie par l’absence congenitale de cellules ganglionnaires neuronales dans les plexus nerveux a l’extremite distale du tube digestif. Le segment atteint est rectosigmoidien dans 80 % des cas, ou plus etendu. La maladie de Hirschsprung est suspectee en cas d’occlusion digestive basse neonatale ou de constipation chronique severe chez l’enfant. Son diagnostic repose sur l’examen anatomopathologique de biopsies rectales comportant la sous-muqueuse. Les cellules neuronales sont recherchees sur sections multiples en coloration standard. La coloration acetylcholinesterasique est pratiquee sur fragment congele afin de rechercher l’hyperplasie des fibres cholinergiques tres evocatrice de la maladie de Hirschsprung. Cette hyperplasie decroit du rectum a l’angle gauche. L’hyperplasie des fibres nerveuses extrinseques et la rarefaction des jonctions neuromusculaires au cours de la maladie de Hirschsprung peuvent etre mises en evidence en immunohistochimie. Le diagnostic differentiel inclut les pseudo-obstructions intestinales chroniques. Le traitement de la maladie de Hirschsprung consiste en l’anastomose du tube digestif normalement innerve au canal anal. Les biopsies per- ou pre-operatoires permettent de guider la chirurgie. Elles sont d’interpretation difficile en zone transitionnelle. L’examen de la piece d’exerese permet de mesurer le segment aganglionnaire et la zone transitionnelle. Differents genes (le plus souvent la gene RET) peuvent etre impliques dans la maladie de Hirschsprung sporadique ou familiale. La maladie de Hirschsprung est associee a d’autres anomalies, digestives ou extra-digestives, dans 5 a 30 % des cas. Les associations lesionnelles peuvent retarder le diagnostic et le traitement de la maladie de Hirschsprung.

Cellules épithéliales bénignes et protéine de Tamm-Horsfall dans les ganglions lymphatiques des pièces de néphrectomie pour néphroblastome : Un piège diagnostique

Resume Quand un nephroblastome s’accompagne de metastases ganglionnaires lymphatiques a l’examen de la piece operatoire, la tumeur est de stade III selon la classification de la Societe Internationale d’Oncologie Pediatrique (SIOP 2001), ce qui implique un traitement post-operatoire lourd comportant radiotherapie et chimiotherapie. Des cellules epitheliales benignes dans les ganglions lymphatiques de drainage d’une tumeur du rein chez l’enfant peuvent etre confondues avec des metastases. Elles sont le plus souvent associees a une accumulation de proteine de Tamm-Horsfall dans les sinus ganglionnaires lymphatiques. Nous rapportons une observation de cellules epitheliales benignes associees a des depots de proteine de Tamm-Horsfall au niveau d’un ganglion lymphatique latero-aortique chez une fille âgee de 16 mois operee pour nephroblastome apres chimiotherapie pre-operatoire. Le nephroblastome etait a predominance epitheliale et de stade SIOP I. Il existait une accumulation de proteine de Tamm-Horsfall dans les sinus ganglionnaires lymphatiques, dans les vaisseaux lymphatiques, dans le rein en dehors de la tumeur et dans le sinus renal. L’association des cellules epitheliales a des depots de proteine de Tamm-Horsfall et leur ressemblance avec les cellules des tubules contournes distaux sont des arguments en faveur de leur benignite. Celle-ci est reconnue par la petite taille des cellules, par l’aspect regulier de leur noyau et par leurs caracteristiques morphologiques differentes de celles des cellules tumorales, mais des depots de proteine de Tamm-Horsfall peuvent s’associer a d’authentiques metastases ganglionnaires lymphatiques.

So-called infantile haemangiopericytoma of the kidney

Dear Editor, Infantile myofibroma (myofibromatosis) may occur at visceral locations including the kidney [2], and haemangiopericytomas, as well as solitary fibrous tumours, are described as rare primary renal neoplasms [5]. These tumour types may be misdiagnosed as sarcomas, specifically clear cell sarcoma of the kidney, which is a high-risk malignant paediatric tumour. A 2-month-old boy presented with a well-circumscribed, encapsulated, centrally necrotic, and calcified 7 cm in diameter tumour of the right kidney (Fig. 1). Histologically, tumour tissue was densely cellular and made of tightly packed, elongated polygonal cells with a striking, quasiexclusive haemangiopericytic vascular pattern (Fig. 2a). The nuclei were oval with finely distributed chromatin and occasional small nucleoli (Fig. 2b). There were 16 mitotic figures in ten high-power fields and no abnormal mitotic figure. Some spindle cells with more eosinophilic cytoplasm (<1% of tumour tissue) were focally present in the peripheral parts of the tumour and, very scarcely, at some distance from the fibrous capsule, which circumscribed the tumour. Immunohistochemically, tumour cells were positive for CD34 (Fig. 2c), vimentin, and MIB1 (Ki67 index, 14%); they were negative for CD99, Bcl2, pan-actin HHF35, smooth muscle actin, desmin, myogenin, cytokeratin KL1, cytokeratin AE1/3, epithelial membrane antigen, CD10, CD56, chromogranin A, synaptophysin, S100 protein, CD117, ALK, and E-cadherin. No ETV6/NTRK3 transcript could be demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR), which was performed twice with appropriate controls. A retrospective study of 13 specimens of spindle cell paediatric renal tumours using the same primary antibodies was performed. Specimens included three clear cell sarcomas of the kidney, two stromal and four blastematous predominant nephroblastomas, two classical or mixed mesoblastic nephromas, and two metanephric stromal tumours. All tumours contained numerous vessels that expressed CD34. Clear cell sarcomas expressed vimentin and varied in their expression of Bcl2, CD56, and CD117. Nephroblastomas varied in their expression of mesenchymatous and epithelial markers, Bcl2, and CD56. Mesoblastic nephromas expressed vimentin and smooth muscle actin. Metanephric stromal tumours expressed vimentin (two of two cases) and CD117 (one case). The percentage of tumour nuclei immunoreactive for MIB1 varied from 3% (in a metanephric stromal tumour) to 91% (in a blastematous predominant nephroblastoma). In the case reported here, the renal tumour displayed morphological and immunohistochemical features distinct from those of clear cell sarcoma and nephroblastoma. Immunoreactivity for epithelial markers Virchows Arch (2007) 450:231–233 DOI 10.1007/s00428-006-0321-3