Placental mesenchymal dysplasia with hepatic mesenchymal hamartoma: a case report and literature review.

Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly and grapelike vesicles resembling a partial molar pregnancy and in most cases, a phenotypically normal fetus. Hepatic mesenchymal hamartoma (HMH) is a benign hamartomatous proliferation of mesenchymal liver tissue. PMD has been associated with HMH. Although rare, in combination, it is known to carry a poorer prognosis than in fetuses without structural abnormalities. There are only a few reported cases of PMD and associated HMH with varying management strategies and outcomes, precluding ascertainment of the most appropriate treatment plan. We present a case of PMD with associated cystic HMH resulting in fetal death. We also reviewed the published literature on this issue and explored possible management strategies to prevent adverse fetal and neonatal outcomes.

[Placental pathology of uteroplacental vascular deficiency]. / Anatomie pathologique de l'insuffisance vasculaire utéroplacentaire.

The indications of the pathological examination of the placenta are mainly represented by uteroplacental vascular deficiency. The clinical context is often evocative, but it can sometimes be solely an intra-uterine growth retardation or an unexplained in utero fetal death. So, the pathological lesions of this uteroplacental vascular deficiency must be well-known to be correctly interpreted, for none of these lesions is truly specific. The pathological diagnosis is based on a group of macroscopic and microscopic arguments. Various physiopathological mechanisms, often imperfectly known, can be at the origin of an uteroplacental vascular insufficiency, but in the current position, the pathological examination does not allow etiopathogenic orientation. The development of the trophoblastic biopsies gives us access to a new material which, in parallel with the cytogenetic analysis, often allows us, in front of an unexplained intra-uterine growth retardation, to direct the diagnosis towards uteroplacental vascular insufficiency. The histological analysis of the chorionic villous sampling taken precociously during pathological pregnancies is thus a major diagnostic contribution. But especially, this analysis gives access to new information which, in the near future, will enable us to better define the pathological evolution of the lesions of hypoxic chorionic villous and to contribute to a better knowledge of this pathology which, under many aspects, still conceals many mysteries.

Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion.

BACKGROUND: Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in missed abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in missed abortion. METHODS: Women with missed abortion (n=27) and healthy controls (n=26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry. RESULTS: Compared with induced abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in missed abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positively correlated with Notch1. CONCLUSIONS: The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in missed abortion.

Fetus papyraceus: congenital pulmonary anomalies associated with congenital aplasia cutis on the surviving twin.

Aplasia cutis congenita (ACC) can be associated with fetus papyraceus. We report here the first case of ACC linked to fetus papyraceus with pulmonary anomalies. At birth, the patient presented with skin lesions of the trunk consisting of well-defined, symmetrically distributed, bilateral atrophic ulcerations. Physical examination was otherwise normal. Persistent bronchospasm occurred at the age of 7 months; computed tomography images showed small bilateral pulmonary bullae. At the age of 5 years, skin and pulmonary lesions had not extended. Although the mechanisms of ACC linked to fetus papyraceus are unclear, vascular ischemia is strongly suggested, and could explain the bilateral and symmetric congenital skin and lung aplasia.

Effect of estrogen on rat placental development depending on gestation stage.

We examined the sequential histopathological changes in the placenta from rats exposed to estrogen. 17 ß-estrogiol-3-benzoate was intraperitoneally administered at 100 µg/animal/day during GD 6 to GD 8 (GD6-8 treated group), GD 9 to GD 11 (GD9-11 treated group) and GD 12 to GD 14 (GD12-14 treated group), and the placentas were sampled on GDs 11, 13, 15, 17, and 21. Fetal mortality rates were increased up to approximately 50% in the GD6-8 and 9-11 treated groups, but there was no change of fetal weight on GD 21. An increase in placental weight and a reduction in fetal/placental weight ratio were detected during GD 17 to GD 21 in the GD6-8 treated group. Histopathologically, hypoplasia of metrial gland was detected with defective development of spiral arteries in the GD6-8 and GD9-11 treated groups. A decrease in the thickness of metrial gland was observed from GD 11 onwards in the GD6-8 treated group and from GD 13 onwards in the GD9-11 treated group. The endovascular trophoblasts invaded into the spiral arteries in the deep part of metrial gland in these treated groups. The number of phospho-histone H3 positive cells was decreased on GD 11 or GD 13 in these groups. In the decidua basalis, transitory necrosis was observed with hemorrhage on GD 13 in the GD6-8 and GD9-11 treated groups. In the labyrinth zone, cystic dilatation of the sinusoid was observed with congestion in the GD6-8 treated group, resulting in an increased placental weight. Therefore, we consider that estrogen inhibits the proliferation of decidualized endometrial stromal cells in the metrial gland, and leads to metrial gland hypoplasia with less development of the spiral arteries. The reduced utero-placental blood flow is supposed to be one of the important factors for poor reproductive performance.

Systematic review of sonographic findings of placental mesenchymal dysplasia and subsequent pregnancy outcome.

OBJECTIVE: To describe the sonographic features and pregnancy outcomes of placental mesenchymal dysplasia (PMD), an entity often misdiagnosed as molar pregnancy. METHODS: We reviewed PMD cases from our institution and performed a systematic review of the existing literature. Inclusion criteria for the review were diagnosis of PMD as defined by placental pathology, description of placental morphology on antenatal ultrasound and reporting of pregnancy outcomes. RESULTS: We found three cases of PMD at our institution. Patient 1 had elevated human chorionic gonadotropin (hCG) and an enlarged, hydropic placenta at 13 weeks, suggestive of a molar pregnancy. Patient 2 also had elevated hCG with large, vascular placental lakes on ultrasound suggesting placenta accreta or molar pregnancy. Case 3 involved placentomegaly and fetal anomalies suggestive of Beckwith-Wiedemann syndrome. From the literature review, 61 cases met the inclusion criteria. The most common sonographic features included enlarged (50%) and cystic (80%) placenta with dilated chorionic vessels. Biochemical aneuploidy screening abnormalities were relatively common as were fetal anomalies, Beckwith-Wiedemann syndrome and other genetic abnormalities. Pregnancy complications included intrauterine growth restriction (IUGR; 33%), intrauterine fetal death (IUFD; 13%), and preterm labor (33%). Pregnancies without fetal anomalies, IUGR, IUFD or preterm labor had normal neonatal outcomes despite PMD (9%). CONCLUSIONS: The differential diagnosis of PMD includes molar pregnancy and other placental vascular anomalies. PMD is associated with adverse pregnancy outcome, so heightened surveillance with genetic evaluation, serial growth scans and third-trimester assessment of wellbeing should be considered. PMD must be differentiated from gestational trophoblastic disease because management and outcomes differ.

Aplasia cutis congenita with fetus papyraceus: report and review of the literature.

We report a case of a 2-week-old white female who presented with large stellate atrophic skin defects on bilateral thighs and knees at birth. The pregnancy was complicated by the death of monozygotic twin at the 16th week of gestation. This represents aplasia cutis congenita with fetus papyraceus. This rare condition is defined as the congenital skin defect and intrauterine death of fetus with or without a stillborn fetus pressed flat by the growing twin (fetus papyraceus) at delivery time. Aplasia cutis congenita coexisting with fetus papyraceus has a distinctive and reproducible distribution pattern of bilateral symmetrical truncal, buttock, and thigh lesions related to fetal death during the late first to early second trimester. There are at least 44 reported cases of this disorder in the English literature. We discuss our case and review the literature.

In utero copper treatment for Menkes disease associated with a severe ATP7A mutation.

Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect. In an affected fetus whose parents found termination unacceptable and who understood the associated risks, we began in utero copper histidine treatment at 31.5 weeks gestational age. Copper histidine (900 µg per dose) was administered directly to the fetus by intramuscular injection (fetal quadriceps or gluteus) under ultrasound guidance. Percutaneous umbilical blood sampling enabled serial measurement of fetal copper and ceruloplasmin levels that were used to guide therapy over a four-week period. Fetal copper levels rose from 17 µg/dL prior to treatment to 45 µg/dL, and ceruloplasmin levels from 39 mg/L to 122 mg/L. After pulmonary maturity was confirmed biochemically, the baby was delivered at 35.5 weeks and daily copper histidine therapy (250 µg sc b.i.d.) was begun. Despite this very early intervention with copper, the infant showed hypotonia, developmental delay, and electroencephalographic abnormalities and died of respiratory failure at 5.5 months of age. The patient's ATP7A mutation (Q724H), which severely disrupted mRNA splicing, resulted in complete absence of ATP7A protein on Western blots. These investigations suggest that prenatally initiated copper replacement is inadequate to correct Menkes disease caused by severe loss-of-function mutations, and that postnatal ATP7A gene addition represents a rational approach in such circumstances.

Fetal liver calcifications: an autopsy study.

Fetal liver calcifications are occasionally found in fetal autopsies. However, the incidence, associated findings, clinical significance, and presumed pathogenesis of fetal liver calcifications are not well documented. This study analyzed the characteristics and significance of fetal liver calcifications found on fetal autopsies. Cases of fetal liver calcifications were collected from a fetal autopsy database. Their clinical and pathological characteristics were analyzed in comparison to the remaining cases in the database. Thirty-five cases (4.2%) of fetal liver calcifications were found among 827 consecutive fetal autopsies that had been performed in our hospital during the 16-year period from January 1, 1994 through December 31, 2009. Twenty-nine cases had nodular calcifications, predominantly subcapsular. Calcification in portal spaces and porta hepatis were present in six cases. Twenty cases were missed abortions and intrauterine fetal death. Missed abortion at or earlier than 23 weeks had significantly more subcutaneous edema and other evidence of circulatory abnormalities. Calcifications in older fetuses (>23 weeks) were located more commonly in portal spaces and in other organs. Fetal liver calcification is an incidental finding during autopsies. The significance of fetal liver calcifications has to be assessed in combination with other clinical and pathological parameters, including location and number of the lesions, signs of circulatory compromise, and abnormalities of placenta, umbilical cord, and fetal malformations. Fetal liver calcifications are commonly associated with conditions related to impaired circulation, including umbilical cord abnormalities and subcutaneous edema. We suggest that fetal liver calcifications might attest to circulatory compromise preceding death, especially if subcutaneous edema is present and even when no other abnormal findings are seen.

Anatomical and pathological findings in hearts from fetuses and infants with cardiac manifestations of neonatal lupus.

OBJECTIVE: The autopsy and clinical information on children dying with anti-SSA/Ro-associated cardiac manifestations of neonatal lupus (cardiac NL) were examined to identify patterns of disease, gain insight into pathogenesis and enhance the search for biomarkers and preventive therapies. METHODS: A retrospective analysis evaluating reports from 18 autopsies of cardiac NL cases and clinical data from the Research Registry for Neonatal Lupus was performed. RESULTS: Of the 18 cases with autopsies, 15 had advanced heart block, including 3 who died in the second trimester, 9 in the third trimester and 3 post-natally. Three others died of cardiomyopathy without advanced block, including two dying pre-natally and one after birth. Pathological findings included fibrosis/calcification of the atrioventricular (AV) node, sinoatrial (SA) node and bundle of His, endocardial fibroelastosis (EFE), papillary muscle fibrosis, valvular disease, calcification of the atrial septum and mononuclear pancarditis. There was no association of pathology with the timing of death except that in the third-trimester deaths more valvular disease and/or extensive conduction system abnormalities were observed. Clinical rhythm did not always correlate with pathology of the conduction system, and the pre-mortem echocardiograms did not consistently detect the extent of pathology. CONCLUSION: Fibrosis of the AV node/distal conduction system is the most characteristic histopathological finding. Fibrosis of the SA node and bundle of His, EFE and valve damage are also part of the anti-Ro spectrum of injury. Discordance between echocardiograms and pathology findings should prompt the search for more sensitive methods to accurately study the phenotype of antibody damage.

Neuropathology of the area postrema in sudden intrauterine and infant death syndromes related to tobacco smoke exposure.

The area postrema is a densely vascularized small protuberance at the inferoposterior limit of the fourth ventricle, outside of the blood-brain barrier. This structure, besides to induce emetic reflex in the presence of noxious chemical stimulation, has a multifunctional integrative capacity to send major and minor efferents to a variety of brain centers particularly involved in autonomic control of the cardiovascular and respiratory activities. In this study we aimed to focus on the area postrema, which is so far little studied in humans, in a large sample of subjects aged from 25 gestational weeks to 10 postnatal months, who died of unknown (sudden unexplained perinatal and infant deaths) and known causes (controls). Besides we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant deaths and maternal smoking. By the application of morphological and immunohistochemical methods, we observed a significantly high incidence of alterations of the area postrema in fetal and infant victims of sudden death as compared with age-matched controls. These pathological findings, including hypoplasia, lack of vascularization, cystic formations and reactive gliosis, were related to maternal smoking. We hypothesize that components from maternal cigarette smoke, particularly in pregnancy, could affect neurons of the area postrema connected with specific nervous centers involved in the control of vital functions. In conclusion, we suggest that the area postrema should be in depth examined particularly in victims of sudden fetal or infant death with smoker mothers.

Effects of chronic carbon monoxide exposure on fetal growth and development in mice.

BACKGROUND: Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. METHODS: Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. RESULTS: Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. CONCLUSIONS: Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

Intrauterine fetal death due to cardiac rhabdomyomas.

A 21-year-old patient, in her first and regularly controlled uneventful pregnancy, was admitted to hospital due to lower leg edema, hypertension, proteinuria, and weight gain. Fetal death occurred the next day and a female nonhydropic fetus, 40 cm CH, 1460 grams, at 29-week gestation was delivered. An autopsy showed no visible gross abnormalities except in the heart. The heart was enlarged, with five intramural and subendocardial nodules, 0.3 to 1 cm in size, three in the left ventricular free wall, and one in the right ventricle and right atrium, sharply demarcated, reddish-gray, moderately firm, with the typical appearance of rhabdomyoma.

A case report of an ectopic fetus in a cat.

An ectopic fetus was discovered in an 18-month-old uniparous queen that was admitted for an elective ovariectomy. Six months prior she had delivered three healthy kittens. During the preoperative examination, a mass similar in size to a full-term fetus was detected in the abdominal cavity. Ultrasound examination revealed the mass to be an ectopic fetus in the mid-abdominal region. A mummified fetus was removed by laparotomy. No rupture of the uterine wall was visible, but a small necrotic area was present on the left uterine horn, adjacent to the very proximal portion of the uterine horn. The fetus, which was fully developed and covered by a thin membrane, was carefully dissected. Histological examination did not enable us to definitively prove the extra-uterine development of the fetus; however, the ectopic development of the conceptus secondarily expelled into the peritoneal cavity could be assumed.

Symmetric aplasia cutis congenita associated with fetus papyraceus: report of two cases.

We present two cases of neonates born with symmetric aplasia cutis congenita associated with intrauterine fetal demise of cotwins during the early second trimester. Fetus papyraceus resulting in aplasia cutis congenita is a rare association with many clinical presentations, including extratruncal symmetric lesions and small linear, arcuate, and triangular lesions when twin intrauterine demise occurs after the first trimester.

Developmental alterations of the spinal trigeminal nucleus disclosed by substance P immunohistochemistry in fetal and infant sudden unexplained deaths.

We investigated the immunohistochemical expression of substance P (SP) in the brainstems of 56 subjects aged from 17 gestational weeks to 10 post natal months, who died of unknown (sudden unexplained fetal deaths and SIDS) and known causes (controls). The goals of this study were: (i) to obtain basic information about the expression of SP during the first phases of human nervous system development; (ii) to evaluate whether there are alterations of this neuromodulator in victims of sudden death; and (iii) to verify any correlation with maternal cigarette smoking. Immunohistochemistry demonstrated SP immunoreactivity in the caudal trigeminal nucleus area, with a progressive increase in the density of SP-positive fibers of the corresponding tract during normal development from fetal life to the first post natal months. Delineation of the structure of the human trigeminal nucleus, little investigated so far, provided essential data on its morphologic and functional development. Instead, a negative or low SP expression was detectable in the fibers of this tract in a wide subset of SIDS victims and, conversely, a high SP-expression in a wide subset of sudden fetal deaths. We postulate, on the basis of these results, that SP has a functional importance in the early phases of central nervous system development and in the regulation of autonomic functions. In addition, the observation of a significant correlation between sudden unexplained death, altered SP staining and maternal smoking leads us to suggest a close relation between the absorption of cigarette smoke in utero and a decreased functional activity of the trigeminal nucleus, that can trigger sudden death of the fetus during pregnancy or of the infant in the first months of life.

Multiple intestinal atresia and congenital bilateral perisylvian syndrome in a surviving monochorionic twin with intrauterine death of the co-twin.

This report presents a case of a surviving monochorionic twin with multiple intestinal atresia and congenital bilateral perisylvian syndrome, which developed after the intrauterine death of the cotwin. The pathology of the placenta demonstrated vein-to-vein communication between the twins and multiple intravascular thrombi in the dead cotwin.

[Thyroid morphology in a children population living in the environmentally polluted area].

Comprehensive study of the "normal" thyroid gland in fetuses and children of different age groups in the Chelyabinsk region revealed a number of changes characteristic of the so-called dysregulation pathology. The role of ecological factors and outcome of resuscitation and intensive therapy in these changes is discussed. It is shown that the development and manifestation of tumoral and non-tumoral diseases of thyroid gland prone to a combination of various diseases are delayed till the school age.

[Clinical autopsies. Practical approach, legal foundations and ethical considerations]. / Klinische Obduktionen. Praktisches Vorgehen, rechtliche Grundlagen und ethische Uberlegungen.

Only an autopsy can demonstrate topographical and morphological circumstances in detail and correlate the clinical and autopsy findings based on the examination of all organs. The practical approach in a fatality is described based on the example of the Lüdenscheid Hospital. A uniform legal regulation for dealing with corpses does not exist in Germany. There are two approaches to the question under which circumstances a clinical autopsy is allowed: the extended permission solution and the objection solution. Whether a clinical autopsy can be carried out is decided by the medical specialist selected on application. Autopsies can be necessary from insurance or administrative legal grounds or in the case of an anatomical autopsy is decided by the persons themselves. In order to guarantee the quality of an autopsy it is necessary to use a standardized approach with evaluation and assessment of the results, for example using a quality assurance protocol and the production of an autopsy report. Using this approach important information can be gained not only on the accuracy of the main diagnosis and cause of death but also on additional diseases, response to therapy and the course of the disease and under circumstances can lead to modifications in the approach.