Macrophage activation syndrome: an autopsy case of sudden death.

In a context of viral gastroenteritis, we report an unusual case of sudden death in an 8-year-old child. The only macroscopic abnormality observed in the autopsy was a diffuse mesenteric adenitis. Organ samples were taken for histopathological examination and a diffuse lymphocytic infiltration was observed. A sinusoidal histiocytic hyperplasia was found in the lymph nodes. Microscopic examination of the lungs and the lymph nodes revealed haemophagocytic lesions (lymphocytes within the cytoplasm of histiocytic macrophages). Immunohistochemical studies demonstrated that the histiocytes were CD68+ PS100- CD1A-. Following this microscopic examination macrophage activation or haemophagocytic syndrome was diagnosed. The syndrome is a distinct clinical entity characterised by fever, pancytopaenia, splenomegaly, and haemophagocytosis in the bone marrow, liver and lymph nodes. It is a clinical entity that is very difficult to diagnose due to the lack of specific clinical signs. It is generally a complication of an infectious process, an aggravation of an auto-immune disease or a complication of a neoplastic process. The physiopathology involves a disregulation of T lymphocytes and particularly T helper lymphocytes. To make this diagnosis the anatomopathological examination must be performed by an experienced practitioner. The presence of a lymphocyte infiltrate of macrophagic histiocytes in myeloid organs and especially positive CD68+ immune markers are the anatomopathological proofs of diagnosis. The autopsy examination must be carefully performed and include systematic sample harvesting for anatomopathological examination. The results of all these examinations taken together allow the diagnosis of haemophagocytic syndrome to be finally made.

Central nervous system malformations and early end-stage renal disease in oro-facio-digital syndrome type I: a review.

Intracerebral cysts and porencephaly or arachnoid cysts are rarely but are repeatedly reported in orofaciodigital (OFD) syndrome type 1. We report on 2 families in which OFD syndrome type 1 was observed with central nervous system (CNS) malformations and 3 sporadic cases of OFD with CNS defects, most likely representing fresh mutations for OFD 1. In one case, vermis hypoplasia was present; in another, periventricular heterotopiae were noted. We review the literature on CNS anomalies in OFD syndromes and stress the difficulties in genetic counseling and functional prognosis for children of OFD 1 female carriers prenatally diagnosed with a malformation of the brain. As for CNS malformations, renal cystic disease is an often overlooked complication specific to OFD 1. In 1 family, cystic medullary disease was noted in OFD 1 carriers, leading 1 patient to dialysis by age 35 years and the other to severe renal insufficiency by age 28 years. Longitudinal follow-up of OFD 1 carriers should be performed, and renal function should be assessed in those with cysts because the functional prognosis of this developmental anomaly may be worse than usually reported in the literature.

Omenn's syndrome--pathologic arguments in favor of a graft versus host pathogenesis: a report of nine cases.

Histologic, histochemical, and histoenzymatic investigations of nine cases of Omenn's disease showed generalized lymphoid depletion, including B cells and all T-cell subpopulations; an apparent proliferation of alpha-naphthyl acetate esterase-, acid phosphatase-, OKM1-positive macrophages and T6 interdigitating cells; a thymic hypoplasia with arrest of hassallian epithelial maturation; starlike fibrinous deposits in the bone marrow; and extensive cutaneous lesions characterized by hyperkeratosis, apoptotic cell death associated with the intraepidermal presence of T4+ and T8+ cells, localized necrosis of the basement membrane, expression of Ia antigens by malpighian cells, and progressive loss of the T6+ Langerhans' cells. These lesions, mainly the skin and bone marrow changes, are reminiscent of those observed in acute graft versus host reaction. Although a blood chimerism has never been demonstrated, these pathologic observations support the hypothesis of graft versus host disease in a primary cellular immunodeficiency and the persistence of the proliferating maternal cells in the peripheral target organs.

Ex vivo and in situ PLGA microspheres uptake by pig ileal Peyer's patch segment.

We investigated the ability of pig ileal Peyer's patch segments to transport intestinal poly (D,L-lactide-co-glycolide) microspheres (PLGA MS) from intestinal lumen across the mucosae using in situ and ex vivo segments with confocal laser scanning microscopy (CLSM) and transmission electronic microscopy (TEM). From a global aspect, CLSM suggested that PLGA MS were translocated by M cells labelled with a FITC-conjugated anti-cytokeratin peptide 18, and transported through the follicle-associated epithelium (FAE) in the dome area in both types of experiments. At the ultrastructural level, TEM showed the traffic of PLGA MS throughout M cells, their transport into the basolateral invaginations of the M cells and their subsequent migration into the dome area and the follicular area in contact with macrophages and lymphatic vessels. Although in situ experiments allowed following the migration of PLGA MS until mesenteric lymph nodes, an ex vivo model could be used as a useful tool to study the targeting ability of PLGA MS formulations to the gut-associated lymphoid tissue (GALT).

Renal cystic tumours in children--a diagnostic challenge.

A series of 8 cystic renal tumours is reported in seven-months to four-years-old children. The final diagnosis was cystic nephroma (multilocular cyst) in 4, cystic, partially differentiated nephroblastoma in 3 and partially cystic nephroblastoma in one. Pre-operative distinction between those three types is difficult and inadequate therapeutic approach may result from a wrong diagnosis. Progress in imaging techniques allows a better analysis of cysts and septa. If no solid part can be detected in the tumour, total nephrectomy is sufficient to obtain a favourable outcome.

[Langerhans cell granulomatosis of the orbit. Apropos of an anatomo-clinical case]. / Granulomatose à cellules de Langerhans monotissulaire de l'orbite. A propos d'une observation anatomo-clinique.

Langerhans' cell granulomatosis of the orbit was observed in a 7-year-old boy successfully treated by a simple biopsy. Recovery can be established one year after the biopsy on the basis of bone defect healing on the standard X-ray of the skull.

[Hemorrhagic colitis in exclusively breast-fed infants]. / Colite hémorragique chez les nourrissons en allaitement maternel exclusif.

INTRODUCTION: Authors report clinical, biological and endoscopic data of six children aged less 3 months with bloody stools while they were exclusively breast-fed. RESULTS: Two girls and four boys aged 1 to 2 months presented with isolated but recurrent rectal bleeding. All were explored by fiberoptic rectosigmoidoscopy between 1 and 3,2 months. Macroscopic aspects were congestion (6 cases), petechial and ecchymotic (4 cases), with normal mucosal areas (5 cases). Histopathology showed eosinophilic infiltrates in all 5 children with rectal biopsy. Evolution was satisfactory after cow's milk protein exclusion in maternal diet for five children and after weaning in 1. All children were weaned with protein hydrolysate. Cow's milk protein were later introduced without adverse reactions at 6 to 23 months. CONCLUSION: Food allergy can be considered in proctocolitis including exclusive breast-fed children. Evolution after maternal diet is, as usual, simple.

[Orbital rhabdomyosarcoma in children. Apropos of 2 cases]. / Rhabdomyosarcome orbitaire de l'enfant. A propos de 2 observations.

Rhabdomyosarcoma accounts for 5% of childhood malignant tumours; in 10% it occurs in the orbit where it is the most frequent malignant tumour. Rhabdomyosarcoma is a mesenchymatous tumour with striated muscular differentiation. However, this myogenous differentiation is sometimes undiscernable on standard histological examination and requires immunohistochemical and ultrastructural studies to be shown. Treatment depends on the assessment of local extension, principally based on tomodensitometry. When the tumour is limited to the orbit, survival rate may reach 100% with todays therapeutic protocols. When the orbital walls are invaded the tumour is parameningeal and recovery can only be achieved by increasing chemotherapy at the cost of long-term side effects. Hence, this tumour must be diagnosed and treated very early. The authors report two cases of rhabdomyosarcoma dealing with the two main histological forms of the tumour and with their evolutive risks.

[Contribution of post mortem skull scanning for the study of sudden infant death]. / Contribution du scanner crânien post-mortem à l'étude de la mort subite du nourrisson.

BACKGROUND: Despite post-mortem examination and autopsy, many cases of sudden infant death (SID) remain unexplained. The aim of this study was to assess usefulness of CT-scan in the Sudden Infant Death Syndrome (SIDS). POPULATION: Twenty-three cases of SIDS had a post-mortem CT-scan evaluation of skull and brain. The pictures were retrospectively reviewed by several independent radiologists who were unaware of the circumstances of death and results of autopsy. RESULTS: Aspects of pneumatocele, probably due to lumbar puncture were found in 6 cases. The subarachnoid spaces appeared inexplically hyperdense, as they were not correlated to the results of lumbar puncture and autopsy. The ventricles were normal in size or density. Density of the dural sinuses (superfical and deep) was often increased, an aspect possibly artefactual, due to post-mortem thrombosis. The cerebral parenchyma was often slighty hypodense; microcalcifications due to congenital toxoplasmosis were found in one case. CONCLUSION: There was no correlation between the CT-scan imaging and the delay of death and lumbar puncture. Infants with or without subarachnoid hemorrage had the same CT scan findings. The CT-scan has a poor value when autopsy is performed; in its absence, it could be useful for diagnosing post-traumatic intracerebral hematoma.

[Fetal death toward the end of pregnancy]. / Les morts foetales en fin de grossesse.

This study is on 171 late fetal deaths. These arose from 508 cases histories that the Group for the Study of Neonatology in Rennes brought together when they were conducting a systematic enquiry into perinatal mortality in Ille-and-Vilaine. These concerned events that occurred from the 37th week of pregnancy onwards and had nothing to do with labour. Their study should make it possible to understand better the importance and the details of fetal deaths occurring in the last weeks of pregnancy. Four facts can be established: 1. The number of fetal deaths occurring at the end of pregnancy seems to be higher than had been thought. They represent 38.39% of fetal deaths occurring independent of labour which the Study Group have registered. 2. In most cases they were unexpected. Their discovery was a surprise. 3. Almost half were due to specific causes: accidents to do with the umbilical cord (21 cases); going past biological term (53 cases) following a theory that the authors suggest should be used in place of the commonly held concept of post-maturity, and based solely on the duration of the pregnancy. 4. In order to reduce this perinatal mortality, which is avoidable in many cases, it is important that the pregnancy should be monitored much more thoroughly at its end and this requires, among other things, that the patients themselves should participate.

[Indications for therapeutic interruption of pregnancy in Ille-et-Villaine from 1982 to 1986. Apropos of 222 cases]. / Les indications des interruptions thérapeutiques de grossesse en Ille-et-Vilaine de 1982 à 1986. A propos de 222 cas.

The authors have made the census of all the Medical Terminations of Pregnancy (MTP) which have been carried out in the Department of Ille et Vilaine from 1982 to 1986, i.e. 222 cases, in order to precise the different indications and the diagnosis tools which were used. 132 MTP concern women who live in the Department of Ille et Vilaine. By referring this figure to the total number of pregnancies in this area, one can see that the average incidence is of 1.9%; MTP account for 1% of the total number of Terminations of Pregnancies. Foetal indications are more frequent (188 cases; i.e. 84.7%) than maternal ones (34 cases, 15.3%); these figures remained stable over the 5-year period of study. Chromosomal aberrations and closing defects of the neural tubule are the main causes of MTP (22.9% of foetal indications). Among the 43 chromosomal aberrations, trisomies are the most frequent ones (34.9%) because all women aged 38 or more are proposed a detection. The diagnosis of trisomy was made in 24 cases after tests were programmed either because of the age of the mother or because of family antecedents (amniocentesis: 22 times, punction of foetal blood: once, biopsy of chorion villosities: once), in 6 cases after tests were carried out on the basis of suspect clinical signs amniocentesis: once, punction of foetal blood: 5 times), and in 13 cases after the echography had revealed a major syndrome. Closing defects of the central nervous system mainly concern anencephaly (17.6% of foetal indications) since the echography enables an easy diagnosis. All anencephaly have actually been detected during the reference period of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Reflections on 10 years of medically induced abortions in Ille-et-Vilaine]. / Réflexions sur 10 ans d'interruptions médicales de grossesse (IMG) en Ille-et-Vilaine.

The medical files of 532 patients who underwent medically induced abortion over a 10-year period (1982-1991) in the French department of Ille-et-Vilaine were studied in order to evaluate the indications and outcomes. Among the patients, 358 resided in the department (67%). Comparatively with the number of births during the 10-year period, there was a relative increase in the number of medically induced abortions from 3.5/1000 to 5.5/1000. This parameter was taken into consideration for the interpretation of a parallel decrease in the perinatal mortality during the same period, from 5.9/1000 to 5.1/1000. There was a maternal indication in 91 cases which correspond to the former category of therapeutic induced abortions. There was a clear increase in 1991 corresponding to abortions induced because of extremely premature rupture of the membranes which were formerly allowed to continue to dead births. Foetal indications were frequent: 441 cases (83%). Exogenous causes were lower (15.6%), particularly due to the disappearance of indications resulting from maternal irradiation. For indications related to infection, the vaccination against rubella and improved prenatal diagnosis resulted in the disappearance of rubella as an indication during the last three years of the study and a clear decrease in the number of toxoplasmosis indications. There were few indications due to maternal infection by human immunodeficiency virus (4 cases). Chromosomal abnormalities were the main cause of medically induced abortion among the foetal indications (27.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Selective interruption of pregnancy and embryonic malformations of the limbs]. / Interruption sélective de grossesses et malformations embryonnaires des extrémités.

The authors report 3 cases of fetal malformations consisting of amputation of the limbs. These were found in their cases of selective abortion carried out around the 10th week of amenorrhoea by injection under ultrasonic needle guidance of hypertonic saline into selected sacs. These malformations seem to be associated with either the existence of amniotic bands or with a toxic mechanism (direct contact of the limbs of the embryo with neighbouring hyperosmolar membranes). This technique is to be given up in favour of transcervical aspiration, or direct needling of the fetus. The different techniques for selective abortion have been reviewed as well as the so-called "alternative" techniques (such as follicular aspiration) which are preferable.

[Spontaneous abortion of male fetuses with incontinentia pigmenti (apropos of a family)]. / L'interruption spontanée des grossesses de foetus mâles atteints dans l'incontinentia pigmenti (a propos d'une famille).

We report a family with incontinentia pigmenti. One affected woman had seven pregnancies, seven miscarriages; a prenatal diagnosis by molecular biology was undertaken in the last four cases (two males, two females). In the last two males, a miscarriage occurred at the beginning of the second trimester with cystic hygroma in a case. In the first two males a miscarriage was observed also at the beginning of the second trimester after chorionic biopsy or amniocentesis. These two miscarriages would not be a complication of prenatal diagnosis but spontaneous abortion of an affected male. The date of the miscarriage of affected males (the beginning of the second trimester) and the role of a cystic hygroma for the diagnosis of incontinentia pigmenti in this mother of a fetus karyotyped 46,XY are discussed.

[Intrinsic congenital stenoses of the trachea]. / Les sténoses congénitales intrinsèques de la trachée.

The authors report about one case of intrinsic congenital stenosis of the trachea in a newborn. The prognosis of tracheal stenosis in infants is poor, more so when it is congenital and intrinsic, because it is often extensive and associated with other malformations, especially of the right mainstem bronchus and of the right lung. The prognosis of such extensive stenoses, for which surgery constantly resulted in death, has been improved by a new type of tracheoplasty (Kimura-Tsugawa, 1982). However, these children can only be operated with this procedure once they are through intensive care and acute respiratory distress, often in the neonatal period.

[Gliomatosis peritonei, an unusual abdominal carcinomatosis: report of two cases]. / La gliomatose péritonéale: un aspect inhabituel de carcinomatose: à propos de deux cas.

We report on 2 cases of ovarian teratoma associated with gliomatosis peritonei in 2 young girls aged 9 and 14 years. Gliomatosis peritonei is an unusual miliary-like peritoneal carcinomatosis of glial tissue. In our experience, follow-up was important to detect abdominal recurrence of glial implants, which had to be removed by iterative surgery. We report a 14-year follow-up and an unusual pleural metastatic disease.

[Can we explain the sudden infant death syndrome? About a series of 80 cases with an autopsy in Rennes University Hospital, France in the period 1994-2007]. / Peut-on expliquer la mort inattendue du nourrisson? Réflexions à partir d'une série de 80 cas autopsiés au CHU de Rennes entre 1994 et 2007.

Sudden infant death syndrome (SIDS) is a huge hardship for parents, but also for health professionals. In 2007, 210 cases occurred in France, corresponding to a crude rate of 31.8 for 100,000 births. Between 1994 and 2007, 140 children of less than 2 years old were examined in the reference centre for SIDS in Rennes, France. We included in our study the children who were aged more than 28 days at death date, did not have a known lethal disease and were autopsied. A total of 80 children fulfilled those criteria. Post-mortem investigation included an autopsy, clinical and paraclinical exams (blood test, radiography, CT-scan...), and investigation of the circumstances of the death. Most of the cases were boys and were 2- to 5-month old. Ventral decubitus and gastrointestinal symptoms were often present. Autopsy gave elements about the causes of death in 23 cases and the other exams performed frequently showed an infectious viral context. Thanks to prevention and information campaigns about childcare done in the 1990s, SIDS incidence has largely decreased in France, but it is still too frequent. In our opinion, advice needs to be given again and again, especially concerning safe sleep practices, in order to increase adherence to these recommendations. Moreover, research should be continued to better understand this unexplained syndrome.

[Value of transient elastography in noninvasive assessment in children's hepatic fibrosis]. / Intérêt de l'élastométrie impulsionnelle dans l'évaluation non invasive du stade de fibrose hépatique chez l'enfant.

AIM: Transient elastography (FibroScan) is a novel, noninvasive, rapid bedside method to assess liver fibrosis by measuring liver stiffness. This study aimed to determine the feasibility and reliability of liver stiffness measurement in children with liver diseases. PATIENTS AND METHODS: Liver stiffness measurements were carried out on 72 children, from 4 to 18 years of age, with potential hepatic fibrosis disease. The clinical, biological, ultrasonographic, and endoscopic parameters were noted to identify children with portal hypertension syndrome. The APRI (ASAT-to-platelet ratio index) test was calculated according to the standard formula. An APRI test score higher than 1.5 indicates significant hepatic fibrosis. METAVIR scoring from 14 liver biopsies was compared to the liver stiffness using the Kappa statistic. RESULTS: Twenty-eight patients had viral hepatitis, 20 cystic fibrosis, 16 chronic liver cholestasis, 5 autoimmune hepatitis, and 3 patients had liver fibrosis with uncertain etiology. FibroScan measurements were available in all children. There was good agreement between FibroScan and pathological studies (weighted kappa=0.814). Only 9 children had portal hypertension syndrome with an average measurement of liver stiffness significantly higher than children without portal hypertension (26.5kPa vs 6.4kPa; p<0.01). The APRI test for 6 out of 9 patients scored higher than 1.5. CONCLUSION: These results indicate that liver stiffness measurement is feasible in children and seems to be related to liver fibrosis. Larger prospective studies are needed to validate this FibroScan method.

Fluorescent in situ hybridization (FISH) on paraffin-embedded placental tissues as an adjunct for understanding the etiology of early spontaneous abortion.

OBJECTIVES: An investigation of first-trimester spontaneous abortions (SAs) for those cases in which karyotype is not available was designed to test the efficiency of fluorescence in situ hybridization (FISH) on paraffin-embedded tissues combined with pathological examination for understanding the etiology of SAs. METHODS: Pathological examination of 202 placental tissues from SAs was performed. FISH analysis was then carried out on paraffin-embedded tissue sections from the same abortion products with probes specific for chromosomes 13, 16, 18, 21, X, Y. RESULTS: FISH could be achieved in 196 cases (97%). After pathological analysis alone, the etiology of SAs was evoked in 40 cases. The suspected diagnosis was confirmed by FISH in 26 cases (13.2%). After combined pathological and FISH analysis, the etiology of SAs was identified in 83 from the 196 cases (42.3%) with the probe set used. CONCLUSION: The present study demonstrates the value of FISH on paraffin-embedded tissues as an adjunct for understanding the etiology of SAs for those cases in which karyotype is not available. Combination of pathological and FISH analysis increases the yield of diagnosis by a factor of 3.2. The results also demonstrate that predictions of the karyotype from pathological examination should be avoided.