Association of severe placental inflammation with death prior to discharge and cerebral palsy in preterm infants.

OBJECTIVE: The objective of our study was to identify placental patterns associated with death before discharge or cerebral palsy in a large cohort of preterm infants with a high follow-up rate at 2 years of corrected age. DESIGN: Population-based monocentric study. SETTINGS: Monocentric study in the maternity unit of the University Hospital of Angers, France between 24+0 and 33+6  weeks of gestation, between January 2008 and December 2011. POPULATION: All singleton infants born alive with a placental examination were eligible. METHODS: Clinical data (obstetric and neonatal) were collected prospectively through the LIFT cohort. Placental data were collected retrospectively from medical records. The main outcome measure was death before discharge or cerebral palsy. RESULTS: We did not find any significant association between severe inflammatory lesions on the placenta and death [odds ratio (OR) 1.49; 95% CI 0.55-4.01; P = 0.43] or cerebral palsy (OR 1.41; 95% CI 0.43-4.62; P = 0.57). This lack of significant association persisted even after adjustment (aOR 0.9; 95% CI 0.20-2.30; P = 0.54; aOR 0.98; 95% CI 0.27-3.58; P = 0.97). CONCLUSION: Our results do not provide evidence for a significant association between severe inflammatory placental lesions and either death before discharge or cerebral palsy at 2 years of corrected age in preterm infants born at <34 weeks of gestational age. Further studies remain necessary to confirm this result. TWEETABLE ABSTRACT: We found no significant association between inflammatory placental lesions and death or cerebral palsy.

In Utero Diagnosis of Niemann-Pick Type C in the Absence of Family History.

Niemann-Pick type C (NPC) disease is a recessive disorder that results in unesterified cholesterol accumulating in the lysosomal and late endosomal system. It is caused by mutations in NPC1 or NPC2 genes and leads to systemic and neurodegenerative symptoms. Few cases of prenatal presentation of NPC have been reported and only two cases in the absence of previous family history, indicating the diagnosis is particularly difficult in such a situation. We report a prenatal diagnosis of NPC in a couple without family history. An ultrasound screening at 22 weeks of gestation (WG) detected fetal ascites and hepatomegaly, which were still present at 25, 27, and 29 WG, and a splenomegaly progressively appeared. No placentomegaly or other signs of hydrops fetalis were observed. The diagnostic of NPC was prenatally confirmed by a filipin test and NPC1 sequencing and multiplex ligation-dependent probe amplification assay which revealed a maternal missense mutation (c.2608T>C; p.Ser870Pro) and a paternal deletion of exons 5 to 25. This additional prenatal case of NPC suggests that even in the absence of family history, fetal ascites associated with splenomegaly but no hydrops should nonetheless arouse suspicion concerning this disease as a possible diagnosis.

Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours.

BACKGROUND: The human death-associated protein 3 (hDAP3) is a GTP-binding constituent of the small subunit of the mitochondrial ribosome with a pro-apoptotic function. METHODS: A search through publicly available microarray data sets showed 337 genes potentially coregulated with the DAP3 gene. The promoter sequences of these 337 genes and 70 out of 85 mitochondrial ribosome genes were analysed in silico with the DAP3 gene promoter sequence. The mitochondrial role of DAP3 was also investigated in the thyroid tumours presenting various mitochondrial contents. RESULTS: The study revealed nine transcription factors presenting enriched motifs for these gene promoters, five of which are implicated in cellular growth (ELK1, ELK4, RUNX1, HOX11-CTF1, TAL1-ternary complex factor 3) and four in mitochondrial biogenesis (nuclear respiratory factor-1 (NRF-1), GABPA, PPARG-RXRA and estrogen-related receptor alpha (ESRRA)). An independent microarray data set showed the overexpression of ELK1, RUNX1 and ESRRA in the thyroid oncocytic tumours. Exploring the thyroid tumours, we found that DAP3 mRNA and protein expression is upregulated in tumours presenting a mitochondrial biogenesis compared with the normal tissue. ELK1 and ESRRA were also showed upregulated with DAP3. CONCLUSION: ELK1 and ESRRA may be considered as potential regulators of the DAP3 gene expression. DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis.

Influence of ultrasonographers training on prenatal diagnosis of congenital heart diseases: a 12-year population-based study.

OBJECTIVE: Since 1998, French multidisciplinary prenatal diagnosis centers (CPDPN) offer a training opportunity to first-level screening sonographers. This study measures the impact of this training on prenatal detection rates of congenital heart diseases (CHDs). METHODS: We analyzed the sensitivity of screening sonographers by comparing CHD prenatal diagnoses and CHDs observed after birth in the area of Angers from 1994 to 2006. Two groups of sonographers were compared, those who attended the training (n=19) and those who did not (control group. n=21). The evolution of CHD detection rate was compared between two successive periods of 6 years each. RESULTS: Of 947 CHDs, 438 (46%) were detected prenatally. The control group sensitivity was 16 versus 37% for the sonographers who had attended the training course (p<0.001).Between the two study periods, detection rates for all CHDs and significant CHDs remained unchanged in the control group, whereas they improved significantly in the other group (respectively 54% vs 33% and 75% vs 38%, p<0.05). CONCLUSION: This study supports the hypothesis of a beneficial effect of CPDPN on prenatal diagnosis of CHDs. These centers not only fulfill their primary purpose but also operate as learning centers in which screening sonographers may improve their practice.

High-grade mucoepidermoid carcinoma of the mandibular salivary gland in a lion (Panthera leo).

A 13-year-old neutered male lion was presented with a primary neoplasm arising from the left mandibular salivary gland associated with metastases to regional lymph nodes, thoracic viscera (lungs, heart, esophagus, and diaphragm), and kidney. Histologic and immunohistochemical investigations led to a diagnosis of a high-grade mucoepidermoid carcinoma of the mandibular salivary gland. In this case report, we point out the importance of the immunohistochemical characterization for differential diagnosis between various types of carcinomas of the salivary gland.

Microarray analysis refines classification of non-medullary thyroid tumours of uncertain malignancy.

Conventional histology failed to classify part of non-medullary thyroid lesions as either benign or malignant. The group of tumours of uncertain malignancy (T-UM) concerns either atypical follicular adenomas or the recently called 'tumours of uncertain malignant potential'. To refine this classification we analysed microarray data from 93 follicular thyroid tumours: 10 T-UM, 3 follicular carcinomas, 13 papillary thyroid carcinomas and 67 follicular adenomas, compared to 73 control thyroid tissue samples. The diagnosis potential of 16 selected genes was validated by real-time quantitative RT-PCR on 6 additional T-UM. The gene expression profiles in several groups were examined with reference to the mutational status of the RET/PTC, BRAF and RAS genes. A pathological score (histological and immunohistochemical) was estimate for each of the T-UM involved in the study. The correlation between the T-UM gene profiles and the pathological score allowed a separation of the samples in two groups of benign or malignant tumours. Our analysis confirms the heterogeneity of T-UM and highlighted the molecular similarities between some cases and true carcinomas. We demonstrated the ability of few marker genes to serve as diagnosis tools and the need of a T-UM pathological scoring.

Molecular heterogeneity in fetal forms of type II lissencephaly.

Type II lissencephaly (type II LIS) is a group of autosomal recessive congenital muscular dystrophies (CMD) associated with defects in alpha-DG O-glycosylation, which comprises Walker-Warburg syndrome, Fukuyama cerebral and muscular dystrophy, or muscle-eye-brain disease. The most severe forms of these diseases often have a fetal presentation and lead to a pregnancy termination. We report here the first molecular study on fetal type II LIS in a series of 47 fetuses from 41 unrelated families. Sequencing of the different genes known to be involved in alpha-DG O-glycosylation allowed the molecular diagnosis in 22 families: involvement of POMT1 was demonstrated in 32% of cases, whereas POMGNT1 and POMT2 were incriminated in 15% and in 7% of cases, respectively. We found 30 different mutations in these three genes, 25 were described herein for the first time, 15 in POMT1, and five in POMT2 and POMGNT1. Despite sequencing of FKRP, FCMD, and LARGE, no definitive molecular diagnosis could be made for the other half of our cases. Preliminary results concerning genotype-phenotype correlations show that the choice of the first gene sequenced should depend on the clinical severity of the type II LIS; POMT1 and POMT2 for severest clinical picture and POMGNT1 for milder disease. The other genes, FKRP, FCMD, and LARGE, seem not to be implicated in the fetal form of CMD.

Endocrine tumors of the duodenum. A study of 55 cases relative to clinicopathological features and hormone content.

BACKGROUND/AIMS: Study of prognosis of duodenal endocrine tumors. METHODOLOGY: Retrospective study concerned 55 duodenal endocrine tumors discovered in biopsy or surgical specimens. Follow-up records available for 49 patients indicated that inconspicuous associated clinical manifestations were often found subsequently. Seven patients were classified as Zollinger-Ellison syndrome and seven as multiple endocrine neoplasia (6 MEN I and 1 MEN II). RESULTS: Tumors were small (mean 1.28cm) and located preferentially in the first and second part of the duodenum. Fifty-four were well-differentiated and one poorly differentiated. Immunochemistry revealed 30 G-cell tumors (54.6%), 15 D-cell (27.3%), two plurihormonal (EC cell and G cell), and one GRH-cell, whereas seven could not be classified. Fifteen patients died (five in relation to their disease). Twenty-one had metastases (liver, nodes, lung), eight of whom are still alive. CONCLUSIONS: Eighty-eight percent of duodenal endocrine tumors were gastrinomas, small plurifocal tumors and somatostatinomas preferentially located in the ampullar region and diagnosed because of hematemesis or icterus. Size is an important prognostic factor in determining whether surgery is required. The prognosis is better for D- and G-cell tumors than pancreatic endocrine tumors. Duodenal endocrine tumors in multiple endocrine neoplasia have a good prognosis, but can be associated with pancreatic plurihormonal tumors and metastases.

[Solid-pseudopapillary tumor of the pancreas: a clinical study of five cases, and review of the literature]. / Tumeurs pseudopapillaires et solides du pancréas : à propos de cinq cas et revue de la littérature.

INTRODUCTION: Solid pseudopapillary tumors of the pancreas are rare and their origin is unknown. The aim of this work was to report five new cases. MATERIAL AND METHODS: Retrospective study of data from patients operated on from 1983 to 2002 in a university hospital specialized in pancreatic surgery. Patients were identified in a prospectively constituted database of pathologic examinations. RESULTS: Five patients (three men and two women, aged from 15 to 69 years) underwent pancreatectomy for a solid pseudopapillary tumor, which was discovered fortuitously by imaging in three cases. Tumor diameter ranged from 4 to 15 cm. Diagnosis was made preoperatively in only one patient. There were three pancreaticoduodenectomies and two left pancreatectomies, with extension to the transverse colon due to vascular reasons in two cases. Only one significant complication occurred (one colonic fistula). With a follow-up ranging from 6 months to 6 years, all patients are alive without recurrence. CONCLUSIONS: Solid pseudopapillary tumors are not exceptional in men. Complete resection can need extension to neighboring organs but allows good long-term survival.

[Systemic necrobiotic xanthogranuloma with initial pericardial and pulmonary involvement]. / Xanthogranulome nécrobiotique révélé par une atteinte péricardique et pulmonaire.

INTRODUCTION: Necrobiotic xanthogranuloma is a rare disease, usually associated with a monoclonal gammapathy. We report a case with pericardial and pulmonary involvement that preceded the appearance of the cutaneous lesions. OBSERVATION: A 58 year-old woman was hospitalized for cardiac tamponade. She has a past history of a ductal carcinoma of the right breast that had been completely cured. Pericardial and pulmonary samples showed a predominantly histiocyte monomorphous infiltrate. Twelve months later, indurated papular-like cutaneous lesions appeared around the eye orbits and on the thorax. The histological examination of the skin revealed a necrobiotic xanthogranuloma and the diagnosis of cutaneous and visceral necrobiotic xanthogranuloma was retained. The patient exhibited an IgG Kappa monoclonal gammapathy of undetermined significance. Sequential treatment with melphalan and general corticosteroids moderately improved the cutaneous lesions but did not modify the monoclonal peak. DISCUSSION: To our knowledge, this is the first case of pericardial involvement of a necrobiotic xanthogranuloma. The discovery of the disease, revealed by a visceral manifestation at the onset is uncommon. The subsequent appearance of typical cutaneous lesions permits the retrospective diagnosis of systemic necrobiotic xanthogranuloma. Because its diagnosis is difficult in the absence of concomitant cutaneous involvement, visceral localizations of the disease must be recognized.