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p57 immunostaining is performed on hydropic products of conception to diagnose hydatidiform moles (HMs), which can progress to gestational trophoblastic neoplasia. Partial hydatidiform mole (PHM) and hydropic abortion (HA) display positive staining in stromal and cytotrophoblastic cells, whereas complete hydatidiform mole (CHM) is characterized by loss of p57 expression in both cell types. In some cases, an aberrant pattern is observed, called discordant p57 expression, with positive cytotrophoblast staining and negative stromal staining, or vice versa. The aim of this study was to describe the clinical, biological, and pathological characteristics of p57-discordant villi (p57DV) and other associated populations in cases of divergent p57 expression and to compare the evolutions of p57DV-associated and classic CHMs. Seventy cases of p57DV diagnosed by referent pathologists were divided into two groups, G1: p57DV ± non-CHM component (n = 22) and G2: p57DV + CHM component (n = 48). p57DV morphology was similar in the two groups. Observation of more than two populations and hybrid villi on p57 immunostaining were significantly more frequent in G2. The clinical, ultrasound, and biological presentations of p57DV-associated and classic CHMs were similar. The initial pathological diagnosis was more frequently incorrect, missing the CHM component, for the p57DV-associated CHMs. Molecular genotyping was informative in seven cases and identified as androgenetic/biparental mosaicism in four cases. These results show that p57DV are a diagnostic challenge for pathologists and that most are associated with a CHM component. However, the clinical management of p57DV-associated CHMs should be the same as that of classic CHMs.

Context and Objective: Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). Methods: A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. Results: 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). Conclusion: This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.

We report the prenatal diagnosis of a 12q22q23.2 de novo interstitial deletion performed by array based comparative genomic hybridization (array CGH) in a fetus with cystic hygroma colli, intrauterine growth retardation, microcephaly and micrognathism. Haploinsufficiency for insuline-like growth factor 1 gene ( IGF 1), which is mapped in the deleted region, is suggested because of its implication in prenatal and postnatal growth and in neuronal maturation. This case demonstrates the contribution of array CGH in prenatal diagnosis for detecting small unbalanced chromosomal abnormalities in malformed fetuses and, subsequently, for genetic counselling.

Cobblestone lissencephaly represents a peculiar brain malformation with characteristic radiological anomalies, defined as cortical dysplasia combined with dysmyelination, dysplastic cerebellum with cysts and brainstem hypoplasia. Cortical dysplasia results from neuroglial overmigration into the arachnoid space, forming an extracortical layer, responsible for agyria and/or ‘cobblestone’ brain surface and ventricular enlargement. The underlying mechanism is a disruption of the glia limitans, the outermost layer of the brain. Cobblestone lissencephaly is pathognomonic of a continuum of autosomal recessive diseases with cerebral, ocular and muscular deficits, Walker–Warburg syndrome, muscle–eye–brain and Fukuyama muscular dystrophy. Mutations in POMT1 , POMT2 , POMGNT1 , LARGE , FKTN and FKRP genes attributed these diseases to α-dystroglycanopathies. However, studies have not been able to identify causal mutations in the majority of patients and to establish a clear phenotype/genotype correlation. Therefore, we decided to perform a detailed neuropathological survey and molecular screenings in 65 foetal cases selected on the basis of histopathological criteria . After sequencing the six genes of α-dystroglycanopathies, a causal mutation was observed in 66% of cases. On the basis of a ratio of severity, three subtypes clearly emerged. The most severe, which we called cobblestone lissencephaly A, was linked to mutations in POMT1 (34%), POMT2 ( 8%) and FKRP (1.5%). The least severe, cobblestone lissencephaly C, was linked to POMGNT1 mutations (18%). An intermediary type, cobblestone lissencephaly B, was linked to LARGE mutations (4.5%) identified for the first time in foetuses. We conclude that cobblestone lissencephaly encompasses three distinct subtypes of cortical malformations with different degrees of neuroglial ectopia into the arachnoid space and cortical plate disorganization regardless of gestational age. In the cerebellum, histopathological changes support the novel hypothesis that abnormal lamination arises from a deficiency in granule cells. Our studies demonstrate the positive impact of histoneuropathology on the identification of α-dystroglycanopathies found in 66% of cases, while with neuroimaging criteria and biological values, mutations are found in 32–50% of patients. Interestingly, our morphological classification was central in the orientation of genetic screening of POMT1 , POMT2 , POMGNT1 , LARGE and FKRP . Despite intensive research, one-third of our cases remained unexplained; suggesting that other genes and/or pathways may be involved. This material offers a rich resource for studies on the affected neurodevelopmental processes of cobblestone lissencephaly and on the identification of other responsible gene(s)/pathway(s). * Abbreviations : MDDGA : muscular congenital α-dystroglycanopathy with brain and eye anomalies OMIM : Online Mendelian Inheritance in Man

Fibroblast growth factors (FGF), hepatocyte growth factor (HGF) and their receptors, FGFR and c-Met, are essential components of the regulatory networks between the epithelium and mesenchyme in embryonic lung, but their respective roles in tumour growth are not clear. We performed allelotyping at loci containing the candidate genes FGFR-1-2-3-4, FGF-1-2-7-10, c-Met and HGF in 36 non-small cell lung cancer (NSCLC) (20 squamous-cell carcinomas (SQC) and 16 adenocarcinomas (ADC)), by surrounding each locus with two microsatellites (MS), as close as possible to the genes of interest. Unexpectedly, SQC and ADC were frequently altered at all of these loci, and SQC showed more simultaneously altered loci. In ADC, alterations at the 15q13-22 locus (FGF7 candidate gene) were significantly more frequent. Thus, these loci showed different patterns of molecular alterations between SQC and ADC. Finally, alterations at loci containing FGFR and HGF candidate genes were inversely correlated to the lymph node status in SQC and ADC, respectively.

A distinct syndrome was ascertained in a 3-year-old girl and her brother. The proband was the first child of first cousin parents. She was born after an uneventful pregnancy. At birth, multiple congenital anomalies were noted: ptosis of the left eyelid, hypertelorism, anteverted nares, large fontanel, long philtrum, ungueal hypoplasia, polysyndactyly, single transverse crease, complex cardiopathy, and hepatic cysts. During another pregnancy of the mother, fetal ultrasonographic examination showed an hypertrophy of the right ventricle and atria, a dextroposition of the aorta, a bilateral renal pelvis dilatation, and a club foot. After termination of the pregnancy, necropsy showed facial anomalies, a small penis, a polysyndactyly, a ventricular septum defect, and a malformation of the ductal plate. Bonneau et al. [1983: J Genet Hum 2:93-105] described a family in which three sibs had a complex cardiac malformation, hexadactyly of the first toe, and syndactyly of the third and fourth fingers. Rajab [1997: Clin Dysmorphol 6:85-88] described two sibs with similar features in an Omani family. The sibs described in this report had anomalies of the ductal plate which were not reported in the two other families. These new findings are in favor of autosomal inheritance of this condition which is amenable to antenatal diagnosis.

The majority of lung cancer patients have tumor-derived genetic alterations in circulating plasma DNA that could be exploited as a diagnostic tool. We used fluorescent microsatellite analysis to detect alterations in plasma and tumor DNA in 34 patients who underwent bronchoscopy for lung cancer, including 11 small cell lung cancer (SCLC) and 23 nonsmall cell lung cancer (NSCLC) (12 adenocarcinomas, 11 squamous cell carcinomas) and 20 controls. Allelotyping was performed with a selected panel of 12 microsatellites from 9 chromosomal regions 3p21, 3p24, 5q, 9p, 9q, 13q, 17p, 17q and 20q. Plasma DNA allelic imbalance (AI) was found in 88% (30 of 34 patients), with a similar sensitivity in SCLC and NSCLC. In the 24 paired available tumor tissues, 83% (20 of 24) presented at least 1 AI. Among these patients, 85% (17 of 20) presented also at least 1 AI in paired plasma DNA, but the location of the allelic alterations in paired plasma and tumor DNA could differ, suggesting the presence of heterogeneous tumor clones. None of the 20 controls displayed plasma or bronchial DNA alteration. A reduced panel of six markers (at 3p, 5q, 9p, 9q) showed a sensitivity of 85%. Moreover, a different panel of microsatellites at 3p and 17p13 in SCLC and at 5q, 9p, 9q and 20q in NSCLC patients could be specifically used. Analysis of plasma DNA using this targeted panel could be a valuable noninvasive test and a useful tool to monitor disease progression without assessing the tumor.

Cystic masses of the mediastinum are well-marginated round lesions that contain fluid and are lined with epithelium. Major cystic masses include congenital benign cysts (ie, bronchogenic, esophageal duplication, neurenteric, pericardial, and thymic cysts), meningocele, mature cystic teratoma, and lymphangioma. Many tumors (eg, thymomas, Hodgkin disease, germ cell tumors, mediastinal carcinomas, metastases to lymph nodes, nerve root tumors) can undergo cystic degeneration-especially after radiation therapy or chemotherapy-and demonstrate mixed solid and cystic elements at computed tomography (CT) or magnetic resonance (MR) imaging. If degeneration is extensive, such tumors may be virtually indistinguishable from congenital cysts. A mediastinal abscess or pancreatic pseudocyst also appears as a fluid-containing mediastinal cystic mass. However, clinical history and manifestations, anatomic position, and certain details seen at CT or MR imaging allow correct diagnosis in many cases. Familiarity with the radiologic features of mediastinal cystic masses facilitates accurate diagnosis, differentiation from other cystlike lesions, and, thus, optimal patient treatment.

The 49,XXXXY syndrome is a rare sex chromosome anomaly with an approximate incidence of 1 in 85 000 male live births. The diagnosis is usually ascertained postnatally by the association of mental retardation, variable growth deficiency, Down syndrome-like facial dysmorphy, hypogenitalism and other malformations, especially involving the heart and skeleton. Prenatal diagnosis of the pentasomy 49,XXXXY is generally fortuitous and sonographic features have rarely been described in the literature. We report here on two cases of 49,XXXXY syndrome diagnosed prenatally because of sonographic abnormalities. In the first, amniocentesis was performed at 26 weeks' gestation for polyhydramnios, unilateral clubfoot and micropenis. In the second, a karyotype was carried out on chorionic villi at 13 weeks' gestation for cystic hygroma. These observations and the six previously reported cases demonstrate that cystic hygroma in first or second trimester of pregnancy may be associated with sex chromosome aneuploidy other than Turner syndrome. Moreover, they emphasize the importance of detailed sonographic examination in the second trimester, as small penis and abnormal posturing of the lower extremities are very suggestive of the 49,XXXXY syndrome. Copyright © 2002 John Wiley & Sons, Ltd.

Objective: This retrospective study evaluates probability of survival and mode of recurrence in patients with a microscopically positive bronchial resection margin following resection for primary bronchogenic carcinoma, as well as influence of radiotherapy on survival. Methods: From January 1986 to July 1997, 40 patients had a microscopically positive bronchial resection margin following a macroscopically complete resection (17 lobectomies, three bilobectomies, four sleeve-lobectomies, and 16 pneumonectomies). Tissue diagnosis was squamous cell carcinoma in 32 patients, adenocarcinoma in four, adenosquamous carcinoma in two and neuroendocrine carcinoma in two. Lymph node status was N0 in 14 patients, N1 in 10, and N2 in 16. The bronchial margin contained carcinoma in situ in 20 patients, invasive mucosal carcinoma in five, and peribronchial infiltration in 15. All patients except the three most recent underwent adjuvant radiation therapy. Results: At the conclusion of the study (January 31st, 1999), 30 patients had died: two with post-operative complications, 17 with progressive disease, ten without relation to cancer, and one under undefined circumstances. Six of 10 unrelated deaths were interpreted as respiratory complications of radiotherapy. Recurrent disease appeared in 24 patients (60%). Nineteen had progression of initial disease (47.5%): metastatic spread in 12 (30%), isolated local recurrence in four (10%), and combined local recurrence and metastases in three (7.5%). Five patients developed metachronous cancer, with bronchial location in four (10%) and laryngeal in one (2.5%). 5-year survival (Kaplan‐Meier) in 20 patients with carcinoma in situ was 38:7 ^ 13:7% (median 31 months), but rose to 55:0 ^ 16:6% when excluding seven deaths not related to cancer (five of whom were secondary to radiotherapy) (x 2 a 3:080; Pa 0:0792). Survival in 13 patients classified N0 was 51:3 ^ 16:3% (median 61 months), and 71:1 ^ 18:0% following exclusion of unrelated deaths (x 2 a 3:939; Pa 0:0472). Adverse prognosis of peribronchial infiltration was correlated to a positive N status (13 N2 and 2 N1), 5-year survival being 20:0 ^ 10:3% (median: 18 months). Conclusions: Prognosis of peribronchial infiltration is similar to N2 disease. In situ carcinoma does not influence survival per se. Local control of disease is probably in part due to radiotherapy. However, the high prevalence of unrelated late deaths suggests an adverse impact of radiotherapy on survival. q 2000 Elsevier Science B.V. All rights reserved.

Crohn’s disease can be associated with several respiratory manifestations. We report here a case of pulmonary migratory infiltrates associated with bilateral pleural thickening and peripheral eosinophilia. The histopathological findings show an association of necrotizing nodules, eosinophilic infiltration in the non-abscessed lung tissue, areas of non-caseating epithelioid granulomas, and an extensive pleural fibrosis. The different histopathological findings are detailed and the responsibility of either Crohn’s disease or treatment by mesalazine is discussed.

Pathologic processes that may involve the chest wall include congenital and developmental anomalies, inflammatory and infectious diseases, and soft-tissue and bone tumors. Many of these processes have characteristic radiologic appearances that allow definitive diagnosis. Sternal deformities can be visualized at radiography and their severity quantified with computed tomography (CT). In cervical rib, CT with multiplanar reconstruction may demonstrate relevant anatomic detail and the relationship between bone deformity and arterial compression. In Poland syndrome, radiography reveals an area of hyperlucency on the affected side, whereas CT demonstrates the absence of the greater pectoral muscle and clearly depicts associated musculoskeletal anomalies. Tuberculosis typically manifests at radiography and CT as osseous and cartilaginous destruction and soft-tissue masses with calcification and rim enhancement. Aspergillosis involving the chest wall manifests as pulmonary consolidations and permeative osteolytic changes of the rib and spine at CT and as an area of increased signal intensity at T2-weighted magnetic resonance (MR) imaging. Neurogenic tumors and hemangiomas also typically have high signal intensity at T2-weighted MR imaging. Apparent mass extension or unequivocal bone destruction seen at CT or MR imaging may indicate chest wall involvement by lymphoma. Radiologically, soft-tissue sarcomas typically appear as areas of soft-tissue density or attenuation, often associated with necrotic areas of low density or attenuation. At radiography, plasmacytoma typically manifests as well-defined, "punched-out" lytic lesions with associated extrapleural soft-tissue masses. Chondrosarcoma frequently appears as a large, lobulated excrescent mass arising from a rib with scattered flocculent calcifications characteristic of its cartilaginous mix. Familiarity with these radiologic features facilitates accurate diagnosis and optimal patient treatment.

Four cases of placental candidiasis, an uncommon complication of rupture of the membranes, are presented. In addition to chorioamnionitis, in one of these cases villitis was also observed. Villitis is a rare occurrence in Candida infection and this represents only the second case in the literature. The involvement of villi may be suggestive of blood-borne infection. However, since neither the mother nor the foetus presented any signs of systemic dissemination, the authors suggest a hypothesis of contamination of the villi from foci of chorioamnionitis.

Laser energy is able to ablate, coagulate, and vaporize tissues. Its transmissibility in thin optical fibers makes it an ideal tool for use in percutaneous procedures. This article describes two applications in interventional musculoskeletal radiology. In percutaneous laser disc decompression the laser source is used to vaporize a small portion of the nucleus pulposus. In interstitial laser photocoagulation of osteoid osteoma the laser energy is used to coagulate and destroy the tumor by direct heating.

Beta-blockers may induce several types of adverse respiratory reaction such as asthma, interstitial lung disease with or without pleural effusion, systemic lupus erythematosus or hypersensitivity pneumonitis. More recently, bronchiolitis obliterans with organizing pneumonia (BOOP) has been described. We report here on pulmonary migratory infiltrates with combined histopathological features of both BOOP and eosinophilic pneumonia in a woman treated with sotalol long-term. The patient improved only partially with steroids. Tapering off corticosteroid dosage resulted in relapse, and complete recovery was only obtained after sotalol was stopped.

To evaluate interstitial laser photocoagulation (a minimally invasive percutaneous technique of thermal destruction of deep-seated tumors, with low-power laser energy) in local destruction of osteoid osteoma, with computed tomographic (CT) guidance.Fifteen patients (age range, 8-48 years) with presumed osteoid osteoma were treated with CT-guided interstitial laser photocoagulation of the nidus. A high-power semiconductor diode laser (805 nm) with a 400-microm optical fiber was used. The fiber was introduced into the nidus through an 18-gauge needle. Around the fiber tip, well-defined coagulative necroses from 5 to 9 mm (energy delivery, 400-1,000 J) were obtained.Fourteen patients had complete pain relief, which was apparent within 24 hours in eight patients. One patient had recurrence of pain after 6 weeks. The remaining nidus was treated a second time, with complete relief. Treatment was unsuccessful in one patient, and surgical excision was performed. Daily activities were not restricted after the intervention. All patients were followed up for more than 1 year, with no sign of recurrence. The only notable complication was a mild reflex sympathetic dystrophy of the wrist in one patient. Sclerosis of the nidus was observed 4-6 months after the procedure.Percutaneous interstitial laser photocoagulation of osteoid osteoma seems to be a promising, simple, precise, and minimally invasive alternative to traditional surgical and percutaneous ablations.

Background. We examined the prognostic value of histologic indices in non-small cell lung cancer with particular interest in major blood vessel invasion. Methods. We studied 593 patients who had curative resection between November 1983 and December 1988. We determined the histology, T and N status, peritumoral lung tissue invasion, tumor stroma, necrosis, mitotic rate, and blood vessel invasion. Results. The median patient survival of the whole series was 3.2 years, with a 5-year survival of 38.9%. In univariate analysis, a high T stage, a high percentage of necrosis, blood vessel invasion, and N stage significantly worsened the survival. In multivariate analysis, only blood vessel invasion and, less significantly, T stage and lymph node metastasis remained independent prognostic factors. Conclusions. These results highlight the negative prognostic value of blood vessel invasion in non-small cell lung cancer and suggest that blood vessel invasion, T stage, and node metastasis are three unrelated and distinctive characteristics of resected non-small cell lung cancer.

The association of a normal and a molar egg within a twin pregnancy is extremely rare. The key to diagnosis is the fetal karyotype, thus allowing elimination of its principal differential diagnosis: partial triploid mole. We report a case where the evolution of the pregnancy was complicated by severe toxemia. Interruption of pregnancy was then necessary, even though a conservative attitude had first been considered. Throughout this case, we discuss the means of diagnosis and the clinical handling of this rare entity.

The authors describe the case of a simultaneous mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy in a 40-year-old woman. Four years before, she underwent a mitral valve replacement after the diagnosis of mitral regurgitation during benfluorex treatment (150 mg/day). This drug was reintroduced postoperatively. She presented with exercise and sometimes resting dyspnoea. The bioprosthesis and aortic valves exhibited similar histopathological lesions. Thickening and plaque deposits made by smooth muscle alpha actin- and vimentin-positive cells in a glycosaminoglycan matrix were observed. The study discusses the putative contribution of circulating progenitor cells activated by 5-HT(2B) receptor agonists in the development of drug-induced heart disease.

To analyse the expression of several mucins (MUC1, MUC2, MUC3, MUC5AC and MUC6), epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukaemia viral oncogene homologue 2 (HER2), thyroid transcription factor-1 (TTF-1), caudal type homeobox 2 (CDX2) and cytokeratin 20 (CK20), and the presence of mutations of EGFR, KRAS and HER2 in congenital pulmonary airway malformations (CPAM). Forty-one cases of CPAM and six pulmonary sequestrations were included. TTF-1 expression was observed in all cases but was not seen in mucinogenic growths in CPAM. CDX2 expression was completely negative. MUC1 expression was noted in 12 (29%) CPAM and in 33% sequestrations. MUC5AC was noted in only five cases (26%) by immunohistochemistry and was found in the mucinogenic proliferations of type 1 CPAM. No immunolabelling was noted for the other mucins. EGFR was expressed variably in almost all cases, while HER2 and CK20 was seen exclusively in the mucinogenic proliferations. All mucinous growths were characterized by KRAS mutations. No EGFR and HER2 gene alterations were identified. KRAS mutations and MUC5AC, CK20 and HER2 expression was seen in all mucinogenic proliferations, supporting the neoplastic nature of these cytologically bland growths. These findings emphasize the importance of complete surgical resection of such lesions.

In 12–19 weeks old human fetuses, LHRH-immunoreactive (LHRH-Ir) cells were detected in the nerve fascicles arising from the vomeronasal organ (VNO), from their origin to their end point at the medial aspect of the olfactory bulb (vomeronasal and/or terminal nerves). In one 22-weeks-old fetus, LHRH-Ir cells were present only in the upper part of the nasal septum, in the nerve fascicles crossing the cribriform plate. No LHRH cells could be detected in two fetuses, 23 and 36 weeks old. Our results are discussed with regard to the migratory hypothesis of LHRH cells from the medial olfactory placode to the brain.

The authors describe the first case of an isolated bilateral radial ray reduction occurring in a fetus exposed in utero to valproic acid; the diagnosis was made by ultrasound during the second trimester. This case of an isolated radial ray reduction associated with valproic acid use in pregnancy is a reminder for sonographers to carefully examine not only the cardiac and neurologic system, but also the extremities, when a fetus is exposed in utero to valproic acid.

OBJECTIVE To evaluate the contribution of referent pathologists (RPs) to the quality of diagnosis of trophoblastic diseases and to study the level of diagnostic agreement between the initial pathologists and the RPs. METHODS This observational retrospective study was carried between 1 November 1999 and 11 January 2011 using the database of the French Trophoblastic Disease Reference Centre in Lyon. All files for hydatiform moles (HMs), trophoblastic tumours and non-molar pregnancies for which there was an initial suspicion of trophoblastic disease were included, whenever there was rereading of the slides by an RP. A total of 1851 HMs and 150 gestational trophoblastic tumours were analysed. RESULTS When the initial pathologist diagnosed a complete mole, the RP confirmed the diagnosis in 96% of cases. When the initial pathologist diagnosed a partial mole, the RP confirmed the diagnosis in only 64% of cases. For trophoblastic tumours, when the initial pathologist diagnosed a choriocarcinoma, the RP confirmed the diagnosis in 86% of cases. When the initial anatomopathology suggested an invasive mole, the diagnosis was confirmed in 96% of cases. Finally, when the initial diagnosis was a placental site trophoblastic tumour or an epithelioid trophoblastic tumour, the RP confirmed the diagnosis in 60 and 100% of cases, respectively. CONCLUSION A systematic policy of rereading of slides for all suspicious moles improves the quality of management of trophoblastic diseases at a national level.

The vomeronasal organ (VNO) was studied in ten human foetuses, 12 to 36 weeks old. At 12 to 23 weeks, it was lined by a smooth pseudostratified epithelium, with neurone-specific enolase (NSE) positive cells looking like olfactory receptors. Clusters of NSE-positive cells were seen in relation with the posterosuperior end of the organ and along nerve fascicles in the nasal septum. At 36 weeks, the organ was lined by a respiratory epithelium and did not show any receptor-like cells; some pear-shaped NSE-positive cells of unknown significance were seen at the upper part of the respiratory epithelium. Our results suggest that during the early foetal period, the VNO could have some, as yet unknown, sensory function.

An evaluation of nephrogenesis according to fetal age was performed by quantifying the state of the nephrogenic blastema (NB) and the number of glomeruli (GN) on frontal renal sections in 99 control fetuses (gestational age ranging from 9 to 40 weeks) and in 17 aborted fetuses with low urinary tract obstruction (gestational age ranging from 14 to 36 weeks). In the control group, GN increases slowly from the 10th to the 18th week, then abruptly from the 18th to the 32nd week, reaching an upper limit with NB disappearance by the 32nd week. In the uropathy group, the renal changes show a wide range of severity clearly accounted for by the impairment of both NB and GN. The dysplastic effect of urinary backpressure is the more consistent pathogeny with the spectrum of observed renal changes. It is likely, from GN used as a time-dependent marker of renal development, that the most severe dysplasia is the result of early obstruction with abnormal disappearance of NB and subsequent arrest of nephrogenesis.

Parvovirus B19 infection during pregnancy can be transmitted to the fetus through the placenta. The consequences for the health of the fetus are very variable and can be very serious. They include intrauterine fetal death (IUFD) and miscarriage, which can lead to medico-forensic questions. For the most part, cases of IUFD take place during the second trimester of gestation and present an anatomopathologic picture characteristic of fetal infection with hydrops, placental edema, serous effusion, and erythroblastosis with nuclear inclusions. Endocardial fibroelastosis, medullar and thymic hypoplasia, and hepatic hemosiderosis are frequently present. In the third trimester, the cases are less frequent, not accompanied by hydrops, and can depend more on placental compromise than on direct infection of the fetus. We present 5 cases of IUFD resulting from parvovirus B19 and we discuss the pathogenetic and anatomopathologic aspects and obstetric liability. In 4 cases, the IUFD took place suddenly, in the absence of symptoms, in women who had not previously shown any symptom of the viral infection. In one case, the patient was hospitalized following an ultrasound diagnosis of fetal hydrops and IUFD took place 5 days after admission. Of these cases 3 were verified in the second trimester and 2 in the third trimester. Only the cases of the second trimester and one of the 2 cases of the third trimester presented the characteristic aspects of fetal infection. The other case of third trimester was characterized by placental involvement.

BACKGROUND Determination of tumor clonality has implications for molecular characterization and the optimal treatment of cancer. Allelotyping allows detection of the two alleles, maternal and paternal, and provides additional information regarding clonal genetic defects. The presence of allelic imbalances (AI) in tumors is a general event, but is not necessary at the same allele (alternative AI). The authors' goal was to determine whether the presence of alternative AI (AA) was a marker of heterogeneity and prognosis. METHODS To further analyze the heterogeneity of lung tumors, tumor DNA released in the plasma was compared with primary tumor DNA from 24 lung carcinoma patients. The comparison was performed by allelotyping using 12 microsatellites targeting 9 chromosomal regions, taking in each case leukocyte DNA as reference. To extend and confirm these observations, 26 primary colorectal carcinomas with paired synchronous liver metastasis were analyzed using an enlarged panel of 33 microsatellites. RESULTS AA were observed in 40% (20 of 50) of all patients, in 25% (6 of 24) of lung carcinoma patients but at a higher level, and in 54% (14 of 26) of colorectal carcinoma patients. They affected different chromosome localizations and each tumor stage. In both types of cancer, patients with AA had a higher AI mean frequency in their primary tumor. CONCLUSIONS Detection of AA is an original marker of heterogeneous tumors, demonstrating that independent events occurred on specific genetic sites required for cancer progression. Cancer 2003;97:2308–17. © 2003 American Cancer Society. DOI 10.1002/cncr.11324

The first prenatal diagnosis of Pallister-Killian syndrome (PKS) was reported by Gilgenkrantz et al. in1985. Since this report, about 60 prenatal cases have been reported but both sonographic and cytogenetic diagnoses remain difficult. Although ultrasound anomalies such as congenital diaphragmatic hernia, polyhydramnios and rhizomelic micromelia in association with fetal overgrowth are very suggestive of the syndrome, they are inconstant and they may even be absent. The mosaic distribution of the supernumerary isochromosome 12p greatly increases these difficulties. No prenatal cytogenetic technique is sensitive enough to ensure prenatal diagnosis and false-negative results have been described on fetal blood, chorionic villi and amniocentesis. We report here two prenatal cases of PKS which illustrate the great variability of the fetal phenotype. In reviewing the 63 reported cases, we attempt to determine ultrasound indicators of the syndrome and to define a cytogenetic strategy. In cases where ultrasound indicators are present, our proposal is first to perform chorionic villus or placental sampling and then amniocentesis when the first cytogenetic result is normal. Fetal blood sampling is the least indicated method because of the low frequency of the isochromosome in lymphocytes. In this cytogenetic strategy, fluorescent in situ hybridization (FISH) and especially interphase FISH on non-cultured cells increases the probability or identifying the isochromosome. A misdiagnosis remains possible when ultrasound is not contributory; the identification of new discriminating ultrasound indicators would be very helpful in this context.

Background: This study was designed to determine whether bronchoplastic resection could be an alternative to pneumonectomy in patients with operable primary lung cancer. Methods: From 1980 to 1996, 63 patients (59 males and four females; mean age 62 ^ 7 years) underwent a bronchoplastic lobectomy for non-small cell lung cancer, indicated because of a disabled respiratory function in 34 patients, and performed electively in 29 patients. There were 38 right upper lobectomies, four bilobectomies, one middle lobectomy combined with lower lobe apical segmentectomy, ten left upper and ten left lower lobectomies. The bronchoplasty was a full sleeve in 24 patients, and a bronchial wedge resection in 39. Results: A single patient died post-operatively (1.6%). Specific procedure-related complications are summarized as follows: six anastomotic complications managed conservatively (9.5%), 15 space problems (23.8%), nine sputum retentions (14.2%). Pathologic staging classified 30 patients in stage I, 21 patients in stage II, and 12 in stage IIIA. Estimated 5-year survival was 69:7 ^ 9:8% in stage I, 37:1 ^ 12:1% in stage II, and 8:3 ^ 8:0% in stage IIIA. Fourteen patients (22.2%) developed locoregional recurrence. Three of them died with local recurrence alone, whereas 10 developed metastatic progression; a single patient is alive following completion pneumonectomy. According to stage, three recurrences occurred in stage I (10%), six in stage II (28%), and five in stage IIIA (38%). Actuarial freedom from local recurrence was significantly higher after elective procedures (Pa 0:019); there was a trend towards improved outcome following right-sided procedures (Pa 0:079) and following wedge bronchoplasty (Pa 0:055). Five patients experienced a second primary cancer (7.9%), which was resected in four. Conclusion: Bronchoplastic resections achieve local control and long-term survival comparable to standard resections in patients with stage I or II disease, and may be considered as a valuable alternative to pneumonectomy. q 1999 Elsevier Science B.V. All rights reserved.

To gain insight into the role of transforming growth factor-beta 1 (TGF-beta 1) in the development of kidney pathology following fetal obstruction, we measured TGF-beta 1 gene expression, the active peptide, and the urinary concentration in a model of fetal bilateral urinary obstruction (BUO) in sheep. Fetal lambs underwent BUO at 60 (FO-60) or 80 days (FO-80) of gestation and were studied at 120 days. Independently of the onset or duration of obstruction, all fetuses developed type IV dysplasia (IV) associated with an arrest in the nephrogenesis or hydronephrosis. Fetal glomerular filtration rate was not significantly modified, whereas sodium tubular reabsorption was significantly decreased, and urinary TGF-beta 1 concentration was elevated in hydronephrosis but not in IV. Levels of TGF-beta 1 mRNA were increased in hydronephrosis compared with normal kidneys, and active TGF-beta 1 immunoreactivity was increased in both hydronephrotic and IV kidneys. In summary, TGF-beta 1 may play a role in the development of hydronephrosis and dysplasia in kidneys following fetal BUO. Its role in the arrest of nephrogenesis observed in the IV kidneys remains to be proved.

Persistent multiple pulmonary nodules were observed on the chest X ray of a nonimmunocompromised woman 6 months after she was treated with acyclovir for a varicella-related myelitis without respiratory symptoms. Early antiviral therapy given for varicella infections might decrease the intensity of clinical symptoms without actually preventing the occurrence of varicella-zoster virus-related lesions such as the persistent pulmonary nodules reported here.

A rare case of craniorachischisis associated with trisomy 18 is described. The diagnosis was made by endovaginal sonography during the first trimester of pregnancy. The case is interesting for two reasons. First, it confirms the importance of carrying out an accurate sonographic examination during the first trimester. Second, it shows us that the postmortem examination should be performed by an experienced anatomist: embryos need to be embedded in paraffin wax for microscopic observation and, at present, little is known about the abnormalities of embryo anatomy.

We report a case of congenital toxoplasmosis in a twin pregnancy at 21 weeks of gestation. The complete antenatal investigation included ultrasound examination, cordocentesis and amniocentesis. The ultrasonographic evaluation showed a distinct morphological aspect confirmed by the fetal biological profile. The time lag between placental and fetal infection, or the immunological fetal responses could explain the varying stages of the fetal disease. This is another case which early demonstrates that there may exist a distinct clinical pattern in bichorial pregnancy with varying biological fetal responses. It underlines the importance of cordocentesis in the case of maternal toxoplasma seroconversion, enabling us to gather a maximum number of biological data for complete appreciation of the fetal status. The information obtained permits a precise adaptation of the medical decision.

The present case report describes a case of invasive pulmonary aspergillosis with cerebromeningeal invasion in an asthmatic non-immunocompromised patient. This fatal complication occurred despite early anti-fungal antibiotherapy after a 2-week course of intravenous corticosteroid therapy for treatment of an exacerbated asthma. Diagnostic and therapeutic procedures are discussed.