Electron microscopy of chorionic villus samples for prenatal diagnosis of lysosomal storage disorders.

Some lysosomal storage disorders cause progressive prenatal accumulation of undegradable metabolites that manifest as membrane-bound vacuoles in endothelial cells, fibroblasts, and trophoblast, identifiable by electron microscopic examination of chorionic villus samples (CVS). There were 111 CVS, which had ultrastructural examination for suspected storage disorders at Great Ormond Street Hospital (1988-2005). There were 31 positive diagnoses, including glycogen storage disease type II, gangliosidosis type 1, mucopolysaccharidosis type 1, MPS not specified, Niemann-Pick type A, sialidosis/mucolipidosis type 1, neuronal ceroid lipofuscinoses (including variant forms), Wolman disease, sialic acid storage disease, and storage disease not specified. In most of these cases the indication was a previously affected individual. Seventy-seven cases showed no evidence of storage disease; 3 samples were inadequate for ultrastructural diagnosis. In selected cases, one-third of CVS may demonstrate distinctive ultrastructural features allowing prenatal diagnosis of a range of storage diseases.

Histomorphometric features of hydatidiform moles in early pregnancy: relationship to detectability by ultrasound examination.

OBJECTIVE: The majority of partial (PHM) and complete (CHM) hydatidiform moles are diagnosed in early pregnancy. About half are identified as molar on ultrasonographic examination prior to evacuation. It is uncertain whether unsuspected cases represent an intrinsically different molar phenotype or are simply dependant on sonographer expertise. We measured a microscopic parameter, average villus diameter, of evacuated PHMs and CHMs to ascertain the cause of non-detection on ultrasound. METHODS: Fifty-four molar pregnancies were examined from the files of the Trophoblastic Disease Unit, in which results of an ultrasound examination prior to evacuation were known. In each, the average cross-sectional diameter of the largest 10 villi was recorded. Maximum villus diameters were compared between gestational age groups (<14 weeks and >or=14 weeks), and ultrasound detection groups (detected (d) and not detected (nd)). RESULTS: The average maximum villus diameter of the largest hydropic villi was significantly less in the first trimester for both PHMs and CHMs that were undetected by ultrasound examination compared to those identified as molar sonographically (P<0.001 and P<0.001, respectively). There was no significant difference in the maximum villus diameter between PHMs and CHMs that were not detected sonographically in the first trimester (P=0.44). Beyond 14 weeks of gestation, there was no significant difference between PHMs detected and undetected sonographically (P=0.88). CONCLUSION: The average diameter of the largest, most hydropic villi, is significantly greater in cases of PHMs and CHMs detected by ultrasound examination in the first trimester compared to that of those not detected sonographically, but beyond 14 weeks such differences are minimal. These findings suggest that, although sonographer expertise could potentially increase ultrasound detection rates somewhat for PHMs and CHMs, a significant proportion of cases demonstrate minimal hydropic change in the first trimester and are therefore likely to remain unidentifiable by ultrasound examination prior to evacuation, even with improved sonographer expertise.

Primary thoracic myxoid variant of extrarenal rhabdoid tumor in childhood.

Primary extrarenal rhabdoid tumors (RT) are now recognized as a specific entity in pediatric oncological pathology practice. We present an unusual case of a small cell myxoid variant of a thoracic RT in an infant and highlight the importance of recent molecular developments in the diagnosis of these tumors. An 8-month-old child presented with a short history of cough and shortness of breath. Imaging demonstrated a large mass occupying the majority of the thoracic cavity on the right side. A percutaneous needle biopsy of the mass showed fragments of tissue composed of malignant tumor with a predominant "small ovoid cell" phenotype and extensive myxoid change, with small nests and islands of tumor cells; occasional cells demonstrated open vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasmic inclusions. Immunohistochemical staining revealed focal strong cytoplasmic positivity for cytokeratin, focal strong paranuclear cytoplasmic vimentin positivity, and INI1 staining showed normal nuclear positivity in control tissues but was negative in tumor cell nuclei. Electron microscopy demonstrated characteristic paranuclear whorls of intermediate filaments confirming the diagnosis of extrarenal malignant RT. The diagnosis of malignant rhabdoid tumor may be difficult, particularly in cases, such as the present, with a predominant small-cell myxoid phenotype. The characteristic expression patterns of cytokeratin and vimentin provide strong clues to the diagnosis, and the use of INI1 antibody now makes definitive diagnosis possible even on needle core biopsies.

Melanotic neuroectodermal tumor of infancy: clinical, radiological, and pathological features.

We present a case of a 4-month-old female infant with a maxillary melanotic neuroectodermal tumor of infancy (MNTI) and review the pooled data from previous publications on this entity. The literature to date comprises 378 reported cases from 1918 to the present, from which data on the presence or absence of metastatic disease was available in 311, and on the presence or absence of local recurrence in 165. These pooled data suggest a local recurrence rate of 36% with metastasis occurring in 7% of cases. At present, the optimal management includes complete surgical excision with clear margins, but there are no reliable histopathological or molecular features to predict the biological behavior in individual cases.

Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center.

OBJECTIVES: To examine the accuracy of sonographic findings of routine ultrasound examinations in patients with a proven histological diagnosis of complete or partial hydatidiform mole referred to a supra-regional referral center, and to examine the relationship of sonographic findings to gestational age across the first and early second trimesters. METHODS: Review of consecutive cases referred to a trophoblastic disease unit from June 2002 to January 2005 with a diagnosis of possible or probable hydatidiform mole in whom results of a pre-evacuation ultrasound examination were documented. Ultrasound detection rates for partial and complete hydatidiform moles were calculated and comparison of detection rates between complete and partial mole, and gestational age groups carried out. RESULTS: 1053 consecutive cases were examined. The median maternal age was 31 (range, 15-54) years and the median gestational age was 10 (range, 5-27) weeks. 859 had a final review diagnosis of partial or complete hydatidiform mole (82%), including 253 (29%) complete moles and 606 (71%) partial moles. Non-molar hydropic miscarriage was diagnosed following histological review in 194 (18%). Overall, 378 (44%) cases with a final diagnosis of complete or partial hydatidiform mole had a pre-evacuation ultrasound diagnosis suggesting hydatidiform mole, including 200 complete moles and 178 partial moles, representing 79% and 29%, respectively, of those with complete (253) or partial (606) moles in the final review diagnosis. The ultrasound detection rate was significantly better for complete versus partial hydatidiform moles (Z = 13.4, P < 0.001). There was a non-significant trend towards improved ultrasound detection rate with increasing gestational age, with an overall detection rate of 35-40% before 14 weeks' gestation compared to around 60% after this gestation. The sensitivity, specificity, positive predictive value and negative predictive value for routine pre-evacuation ultrasound examination for detection of hydatidiform mole of any type were 44%, 74%, 88% and 23%, respectively. CONCLUSIONS: Routine pre-evacuation ultrasound examination identifies less than 50% of hydatidiform moles, the majority sonographically appearing as missed or incomplete miscarriage. Detection rates are, however, higher for complete compared to partial moles, and improve after 14 weeks' gestation. Histopathological examination of products of conception remains the current gold standard for the identification of gestational trophoblastic neoplasia.

Ultrastructural features of gaucher disease treated with enzyme replacement therapy presenting as mesenteric mass lesions.

The classical ultrastructural features of Gaucher disease include large numbers of intracytoplasmic, membrane-bound lysosomal inclusions containing characteristic tubular structures on an electron-lucent background, representing the periodic acid schiff (PAS)-positive Gaucher cells identifiable on light microscopy. Following enzyme replacement therapy (ERT), many of the manifestations of the condition are ameliorated, but persistent mesenteric lymphadenopathy has been reported, the ultrastructural features of which previously have not been described. Two children, aged 4 and 8 years old, respectively, both presented with persistent abdominal lymphadenopathy whilst receiving ERT for Gaucher disease. Needle core biopsies were carried out, that demonstrated collections of macrophages and only scattered storage-type cells on light microscopy. PAS staining was negative in one case and only focally positive in the other Electron microscopic examination, however, confirmed the cells represented macrophages, the cytoplasm of which contained scattered abnormal inclusions containing occasional twisted tubular structures of the type reported in classic Gaucher disease. ERT in Gaucher disease appears to reduce accumulation of the metabolic products at many sites. But for uncertain reasons, abdominal lymphadenopathy may occur containing macrophages that do not form granulomas or classic Gaucher cells on light microscopy. These probably represent incomplete clearance, incomplete/partial enzyme replacement, or possibly an unusual response to a relatively small amount of storage material.

Prenatal diagnosis and molecular cytogenetics in a case of partial trisomy 14 and monosomy 21.

We report an unbalanced translocation involving chromosomes 14 and 21 which presented as fetal ventriculomegaly at 33 weeks gestation. Second trimester ultrasound had indicated normal fetal anatomy, including normal intracranial structures. Parental karyotypes showed a paternal balanced translocation: 46,XY,t(14;21)(q12;q21). The unbalanced translocation in the fetus resulted in trisomy for 14pter-->q12 and monosomy for 21pter-->q21. Postnatal examination showed that the male infant had a cleft palate, but no cleft lip, and mild dysmorphic features. Postnatal MRI revealed bilateral and symmetric dilatation of the occipital horns, atria, and temporal horns of the lateral ventricles. Molecular cytogenetic techniques were used to delineate further the breakpoint on chromosome 14 to a site distal of the D14S1071 locus and the breakpoint on chromosome 21 to a region between D21S1918 and D21S1902. More precise definitions of chromosomal breakpoints in such clinical cases should provide more accurate prognosis for individuals with unbalanced karyotypes and assist in the identification of putative developmentally important genes.

Insulin-like growth factor binding protein-1 (IGFBP-1): a multifunctional role in the human female reproductive tract.

Insulin-like growth factor-1 (IGFBP-1) is particularly important in human female reproductive physiology, where it is involved with other factors in a complex system which regulates menstrual cycles, puberty, ovulation, decidualization, implantation and fetal growth. This has implications for clinical obstetrics and gynaecology, where there is evidence for a pathophysiological role for IGFBP-1 in pre-eclampsia, intrauterine growth restriction, polycystic ovarian syndrome and trophoblast and endometrial neoplasms.

The interrelationships between serotonin production and locomotion in different light regimes in southwestern Michigan opilionids, Leiobunum longipes.

The comparison was made of the effect of LL and DD with LD 14:10 photoperiods on the 24-h secretion cycle of serotonin secretion and the activity patterns of Leiobunum longipes from Southwestern Michigan. LL and DD altered the normal activity patterns but did not change the pattern of serotonin secretion. The activity pattern in normal photoperiod (LD 14:10) produced a 12-h cosinor pattern, resulting in a 24-h biphasic activity peak model. The activity peaked in both scotophase and photophase . The altered patterns in LL and DD were different. In LL a rhythmic component could not be statistically determined. A high, irregular level of activity was seen, higher than the mean level in LD. In DD a combined 24 and 48 h cosinor pattern best fit the observed data. The major peaks occurred in nature during every other photophase and alternate scotophase time in the constant photoperiod conditions. Serotonin secretion patterns in LD, LL, and DD statistically fitted a 24-h cosinor model. Peak secretion times occurred in mid photophase for LD and LL. A later photophase peak was seen in DD. LL animals showed a mean level of serotonin and secretion pattern which was not statistically different from LD. The hypothesis that LD photoperiods direct a peak of serotonin secretion which initiated the activity pattern could not be accepted.

Neurosecretory cells: daily rhythmicity in Leiobunum longipes.

A fluorometric-analysis procedure, used to quantitate indoles, confirmed the presence of 5-hydroxytryptamine (5-HT) in an arachnid; there was unimodal cyclic production of 5-HT in brain and intestinal tissues over a 24-hour period. The same tissues produced 5-HT after 80-day culture; bimodal cyclic output was indicated during continuous 24-hour study. One peak occurred at 0200 hours, at the same time as the peak in vivo, suggesting an endogenously controlled mechanism of secretion. The second peak occurred at midmorning, a time when production in vivo was lowest, suggesting that there is a possible feedback-control mechanism in the organism that inhibits the endogenous output of 5-HT.