-The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.

Hyperinsulinism of infancy (HI), also known as persistent hyperinsulinemic hypoglycemia of infancy, is a rare genetic disorder that occurs in ~1 of 50,000 live births. Histologically, pancreases from HI patients can be divided into 2 major groups. In the first, diffuse HI, ␤-cell distribution is similar to that seen in normal neonatal pancreas, whereas in the second, focal HI, there is a discrete region of ␤-cell adenomatous hyperplasia. In most patients, the clinical course of the disease suggests a slow progressive loss of ␤-cell function. Using double immunostaining, we examined the proportion of ␤-cells undergoing proliferation and apoptosis during the development of the normal human pancreas and in pancreases from diffuse and focal HI patients. In the control samples, our findings show a progressive decrease in ␤-cell proliferation from 3.2 ± 0.5% between 17 and 32 weeks of gestation to 0.13 ± 0.08% after 6 months of age. In contrast, frequency of apoptosis is low (0.6 ± 0.2%) in weeks 17-32 of gestation, elevated (1.3 ± 0.3%) during the perinatal period, and again low (0.08 ± 0.3%) after 6 months of age. HI ␤-cells showed an increased frequency of proliferation, with focal lesions showing particularly high levels. Similarly, the proportion of apoptotic cells was increased in HI, although this reached statistical significance only after 3 months of age. In conclusion, we demonstrated that islet remodeling normally seen in the neonatal period may be primarily due to a wave of ␤-cell apoptosis that occurs at that time. In HI, our findings of persistently increased ␤-cell proliferation and apoptosis provide a possible mechanism to explain the histologic picture seen in diffuse disease. The slow progressive decrease in insulin secretion seen clinically in these patients suggests that the net effect of these phenomena may be loss of ␤-cell mass. Diabetes 49: 1325-1333, 2000 H yperinsulinism of infancy (HI), also known as persistent hyperinsulinemic hypoglycemia of infancy, is a rare genetic disorder, the molecular basis of which was recently elucidated. Most cases are caused by mutations in either the sulfonylurea receptor (SUR1) or the inward rectifying potassium channel (Kir6.2), 2 subunits of the ␤-cell K ATP channel (1-5). A minority of patients have glucokinase or glutamate dehydrogenase mutations, whereas in 40-50% of the patients, the genetic cause of the disease is still not known (4-7).The histologic appearance of the pancreases from affected children can be subdivided into 2 major forms: diffuse HI and focal HI (8-10). The former is more common and bears some characteristics of nesidioblastosis, a phenomenon observed in the healthy fetus and newborn but which normally evolves during the first year of life into the adult-type architecture (9,11,12). In diffuse HI, the neonatal-type ␤-cell distribution persists (8,13).Focal HI is generally easily recognized as a discrete region of adenomatous hyperplasia (8), whereas the rest of the pancreas appears normal for its age. Focal HI is caused by the somatic l...

The purpose of this study was to assemble and test the reliability of a complete set of the placental reaction patterns seen with chronic fetal vascular obstruction in the hope that this might provide a standardized diagnostic framework useful for practicing pathologists. Study cases (14 with fetal vascular obstructive lesions, 6 controls) were reviewed blindly by seven pathologists after agreement on a standard set of diagnostic criteria. Majority vote served as the gold standard and 80% of the 180 diagnoses rendered (9 diagnoses each for 20 cases) were agreed upon by at least six of the seven scores. The sensitivity of individual diagnosis relative to the group consensus averaged 83% (range, 69-100%) and specificity averaged 91% (range, 86-100%). Reproducibility was measured by unweighted kappa-values and interpreted as follows: < 0.2, poor; 0.2-0.6, fair/moderate; > 0.6, substantial. Kappa values for lesions of distal villi were generally superior to those for lesions involving large fetal vessels: avascular villi (0.49), villous stromal-vascular karyorrhexis (0.58), and villitis of unknown etiology (VUE) with stem villitis and avascular villi (0.65) versus large vessel thrombi (any vessel, 0.34; chorionic plate vessel, 0.40) and intimal fibrin cushions (recent, 0.47; remote, 0.78). Reproducibility for a global impression of any villous change consistent with chronic fetal vascular obstruction was substantial (0.63), while that for a more severe subgroup was moderate (0.44). Three points are worthy of emphasis. Our system separately recognizes, but later combines, uniformly avascular villi and villous stromal-vascular karyorrhexis as manifestations of the same underlying process. We propose that this combined group of villous lesions be dichotomized with the terms fetal thrombotic vasculopathy or extensive avascular villi (and/or villous stromal-vascular karyorrhexis) being reserved for the group with 15 or more affected terminal villi per section. Scattered foci of avascular villi (and/or villous stromal-vascular karyorrhexis) could be used to describe less severe cases. Finally, we distinguish VUE with stem villitis and avascular villi (obliterative fetal vasculopathy) as a distinct process with substantial perinatal morbidity.

Pre-eclampsia, a common complication of first pregnancies, is thought to result from a poorly perfused placenta and may reflect an abnormal maternal immune reaction to the hemiallogenic fetus. Human leukocyte antigen (HLA)-G, a major histocompatibility tissue-specific antigen expressed in extravillous trophoblast cells (fetal-derived), may protect trophoblasts from maternal-fetal immune intolerance and allow these cells to invade the uterus. Through RNA in-situ hybridization analysis, we studied the expression pattern of HLA-G in normal placentae and placentae from pregnancies complicated by severe pre-eclampsia. In normal placenta we found HLA-G expression in the anchoring extravillous trophoblasts with an increasing gradient of expression in the more invasive cells. However, in nine out of 10 pre-eclamptic placentae HLA-G expression was absent or reduced. We conclude that HLA-G is normally expressed in invasive trophoblasts and HLA-G expression is defective in most pre-eclamptic placentae. We propose that trophoblasts lacking HLA-G are vulnerable to attack by the maternal immune system. These defective trophoblasts will be unable to invade the maternal spiral arteries effectively, thereby developing vessels which cannot adequately nourish the developing placenta. This poorly perfused placenta may initiate the systemic cascade of events associated with pre-eclampsia.

IntroductionVisceral smooth muscle (SM) originates from local mesenchymal cells that in early-midgestation begin to synthesize SM proteins, including SM α-actin, desmin, SM myosin, SM22, and calponin in a specific periairway distribution (1-5). In the mouse developing respiratory system, cells expressing SM proteins are first detected in the trachea on day 11 of gestation (3, 4), and then SM differentiation proceeds in a cranial-tocaudal fashion to form the bronchial musculature (1-5). The other type of visceral SM cells found in the lung are interstitial SM cells, also known as interstitial contractile cells, or myofibroblasts. Interstitial SM cells are originally located at the sites of future alveolar septae, and, in the mature organ, they form part of the septae tips (6). Except for the aorta, the development of the vascular musculature lags behind that of visceral SM by several days (4, 7-9).Unlike striated muscle differentiation, on which considerable information was gathered over the years, the mechanisms and genetic program that control SM myogenesis remain, for the most part, unknown. We and others have observed that lung mesenchymal cell precursors change their shape from round to elongated before undergoing bronchial SM differentiation (ref.3; Y. Yang and L. Schuger, unpublished observations). Based on this observation we recently examined whether changes in cell shape might play a role in airway myogenesis. Unexpectedly, our studies demonstrated that essentially all undifferentiated embryonic mesenchymal cells are potential SM precursors (10-12). These studies also confirmed the critical role of cell shape in myogenesis. Specifically, we found that cell rounding prezvents myogenesis, regardless of the normal fate of the cell in vivo, whereas cell spreading/elongation induces SM differentiation, even in mesenchymal cells from nonmuscular organs (10-12).Developing tubular tissues, such as those of the respiratory, gastrointestinal, and urinary systems, are filled with liquid. As a consequence, the periluminal mesenchymal cells are subjected to mechanical tension/stretch exerted by the liquid's hydrostatic pressure (13). These forces likely represent a significant factor in determining the periluminal mesenchymal cell shape. In the developing lung, cells are additionally subjected to repeated stretch caused by intrauterine breathing (13). The fact that mechanical stretch causes cell elongation and that cell elongation is likely to be sensed by the cell as a mechanical stimulus suggested to us that cell tension/stretch may play an important role in the process of visceral myogenesis.Here we used a combination of lung cell and organ cultures from fetal mouse and human origin to determine the effect of mechanical stretch upon SM myogenesis. Smooth muscle (SM) develops only in organs and sites that sustain mechanical tensions. Therefore, we determined the role of stretch in mouse and human bronchial myogenesis. Sustained stretch induced expression of SM proteins in undifferentiated mesenchymal cells and acc...

deliveries occurred in our hospital, including 752 (3%) deliveries of IVF pregnancies.Methods Placenta accreta was only diagnosed when there were histological findings from the placenta associated with the suitable clinical course. Demographic, obstetrical and fertility characteristics of these patients were retrieved from hospital files.Main outcome measure Rates of PA in pregnancies achieved with IVF versus rates of PA in spontaneous pregnancies.Results The rate of PA in the IVF group was 12/752 (16/1000) pregnancies, compared with 30/24 441 (1.2/1000) among spontaneous pregnancies (P < 0.0001; OR 13.2; 95% CI 6.7-25.8). Among the variables examined, parity, rate of caesarean delivery in the index pregnancy, and birthweight differed significantly between IVF and spontaneous pregnancies.Conclusions The odds of developing PA are significantly higher in IVF pregnancies than in spontaneous pregnancies. These differences may stem from differences in the endometrial environment, or from changes to the endometrium wrought by IVF treatment protocols.

Aims-To investigate the expression of the imprinted oncofetal H19 gene in human bladder carcinoma and to examine the possibility of using it as a tumour marker, similar to other oncofetal gene products.

miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.