Despite the intensification of obstetric surveillance, stillbirth (SB) rate at >20 weeks has remained constant in the past decades. However, it has been suggested that the rate of unexplained SB can be minimized with an appropriate work-up protocol (ReCoDe). We have compared the rates of unexplained SB using the 2 most commonly used classification protocols in a cohort of SB. From January 1995 to December 2006 all SB at our hospital underwent a uniform and comprehensive work-up inclusive of fetal ultrasonography, amniocentesis for karyotype and cultures, placental histology, autopsy, skin biopsy and total body X ray, maternal testing for inherited and acquired thrombophilias, TORCH, Parvovirus, thyroid function, indirect Coombs, Kleiheuer-Betke test, and genital cultures. The SB rate during the study period was 0.4% (147/36366). After exclusion of 2 cases due to lack of consent for autopsy, the remaining 145 cases were classified according to the protocol of Wigglesworth and of ReCoDe. The latter protocol allowed identification of a causative process in 84% of cases (n=122) vs 50% (n=73) with the former protocol. In particular, 47% (n=68) had a fetal pathology, 21% (n=14) had an umbilical cord pathology, 20% (n=29) had placental pathology, 6% (n=9) had amniotic fluid pathology, and 1% (n=1) had maternal causes. In the remaining 23 cases (16%) the cause of SB was unexplained. Mean gestational age at SB was similar for unexplained and explained SB (31.6±5.4 weeks vs 31.5±5.1 weeks, P=1), but all cases of unexplained SB were above 26 weeks. Adoption of a consistent and appropriate work-up protocol can reduce the rate of unexplained SB. Appropriate identification of the causative processes in SB may allow a more targeted preventative strategy in subsequent pregnancies.

Fetal mosaicism can be suspected at prenatal diagnosis if a trisomy is detected in just a few cells in chorionic villus or colonies in amniocytes in at least two separate flasks and is confirmed if found in other analyzed fetal/neonatal tissues. Trisomic conditions for some chromosomes are clinically recognized whereas rare trisomy mosaicisms in amniocytes, such as trisomy 2, 3, 5, 9, 12, 14, 15, 16, 22, create some problems in interpretation. There are reports in the literature where only a few cells showing abnormal karyotype with a rare trisomy were seen later to be clinically significant in the newborn infant [Daniel et al., 2004]. The risk of abnormal pregnancy outcome varies depending on the chromosome involved in trisomic mosaic and on the presence of uniparental disomy (UPD). Phenotypic abnormalities in the offspring, IUGR and/or fetal demise or stillbirth, range frommoderate to severe [Hsu et al., 1997]. At the reference Regional Center for pregnancies complicated by IUGR (HSGerardo, Monza, Italy), we encountered a 28-year-old primiparous woman with insulin-dependent diabetes mellitus (IDDM type I) at the 26th week of gestation and showing ultrasound diagnosis of intrauterine growth retardation (IUGR) in a morphologically normal fetus. Amniotic fluid analysis showed 41 clones from 9 independent cultures with normal female karyotype (46,XX) and 5 clones from 3 independent cultures with trisomy 5 (47,XX,þ5). Fetal heart monitoring at 30 weeks showed severe variable decelerations. The patient delivered a female infant by Caesarean with Apgar scores of 5/1 and 9/5 and 7.33 cord blood pH. At birth trisomy 5 was also observed in metaphases from three placental biopsies whereas all analyzed metaphases from cord and peripheral blood (100 and 320, respectively) were normal. Dual color FISH analysis using D5S23 cosmidic probe and the a-satellite centromeric probe for chromosome 16 as control on interphasic placental nuclei confirmed the mosaicism: 64.2% (52/81) of nuclei showed three signals for chromosome 5 and two signals for chromosome 16 and 14.8% (12/81) of nuclei presented normal patterns. The peripheral blood showed disomy in all analyzed cells (174) (parents declined giving permission for biopsy of their baby’s skin). Because of the discrepancy observed between placental and fetal karyotypes, UPD5 was tested and excluded. Physical examination at birth showed: a weight of 740 g (3rd centile), a length of 34 cm (<10th centile), and a head circumference of 26 cm (10th centile). Clinodactyly of the fifth right toe and anterior anus were also noted in the baby. The histological examination of the complete placenta (150 g) showed a decidual vasculopathy. During admission to the neonatal intensive care unit the cerebral sonogram was normal, and a small interatrial shunt had completely disappeared at 11 months. The girl was discharged at 3 months of age, with an increase in length and weight but remaining within the 3rd centile with normal

We describe the case of a young woman showing yolk sac tumors (YST) and a Sertoli–Leydig cell tumor (SLCT) in the right ovary, with recurrences in the right adnexum and with hepatic metastasis. To our knowledge, YST and SLCT have never been described as components of the same tumor or reported as associated in the same patient. The patient's karyotype showed the presence of Y chromosome inserted into the 1qh region; the inserted region corresponded to Yq12 heterochromatin. LOH analysis revealed 1p36 paternal allele loss in the proband tumor, thus supporting a germ cell origin for the tumor. The presence of Y heterochromatin in 1qh DNA might induce disturbances in the normal regulation of oncogenes located in 1q.

ObjectiveGestational cholestasis is associated with increased risk of perinatal mortality as well as spontaneous preterm delivery, yet no information is available on placental histologic findings in this condition. We have studied correlations between histopathology placental lesions and clinical or laboratory markers of gestational cholestasis.Study designPlacentas of women with gestational cholestasis delivered between January 1994 and December 1997 were collected for histopathology examination. Clinical (e.g. severity of pruritus and interval from diagnosis of cholestasis to delivery) and laboratory variables (e.g. serum levels of transaminases, bile acids and bilirubin) were correlated with presence of histologic evidence of acute inflammatory lesions or placental vascular pathology. Statistical analysis included Kruskall Wallis test with P < .05 considered significant.ResultsOf the 111 patients with gestational cholestasis during the study period, 54 had placentas available for examination. Gestational age at diagnosis was 32.6 ± 3.9 weeks (range 21-38) and at delivery 36.2 ± 1.8 weeks (range 34-39). 15 women were treated with ursodeoxycholic acid (n = 9), S-Adenosyl-L-methionine (n = 6) or cholestyramine (n = 5). No associations were observed between severity of pruritus, duration of cholestasis, maximum serum levels of transaminases, bile acids or bilirubin, or maternal therapy, and placental vascular or acute inflammatory lesions. As expected, gestational age at delivery and birth weight were inversely correlated with the presence of placental vascular lesions.ConclusionIn patients with intrahepatic cholestasis of pregnancy, placental pathology is largely unaffected by cholestasis-related clinical or laboratory indicators of disease severity and duration. ObjectiveGestational cholestasis is associated with increased risk of perinatal mortality as well as spontaneous preterm delivery, yet no information is available on placental histologic findings in this condition. We have studied correlations between histopathology placental lesions and clinical or laboratory markers of gestational cholestasis. Gestational cholestasis is associated with increased risk of perinatal mortality as well as spontaneous preterm delivery, yet no information is available on placental histologic findings in this condition. We have studied correlations between histopathology placental lesions and clinical or laboratory markers of gestational cholestasis. Study designPlacentas of women with gestational cholestasis delivered between January 1994 and December 1997 were collected for histopathology examination. Clinical (e.g. severity of pruritus and interval from diagnosis of cholestasis to delivery) and laboratory variables (e.g. serum levels of transaminases, bile acids and bilirubin) were correlated with presence of histologic evidence of acute inflammatory lesions or placental vascular pathology. Statistical analysis included Kruskall Wallis test with P < .05 considered significant. Placentas of women with gestational cholestasis delivered between January 1994 and December 1997 were collected for histopathology examination. Clinical (e.g. severity of pruritus and interval from diagnosis of cholestasis to delivery) and laboratory variables (e.g. serum levels of transaminases, bile acids and bilirubin) were correlated with presence of histologic evidence of acute inflammatory lesions or placental vascular pathology. Statistical analysis included Kruskall Wallis test with P < .05 considered significant. ResultsOf the 111 patients with gestational cholestasis during the study period, 54 had placentas available for examination. Gestational age at diagnosis was 32.6 ± 3.9 weeks (range 21-38) and at delivery 36.2 ± 1.8 weeks (range 34-39). 15 women were treated with ursodeoxycholic acid (n = 9), S-Adenosyl-L-methionine (n = 6) or cholestyramine (n = 5). No associations were observed between severity of pruritus, duration of cholestasis, maximum serum levels of transaminases, bile acids or bilirubin, or maternal therapy, and placental vascular or acute inflammatory lesions. As expected, gestational age at delivery and birth weight were inversely correlated with the presence of placental vascular lesions. Of the 111 patients with gestational cholestasis during the study period, 54 had placentas available for examination. Gestational age at diagnosis was 32.6 ± 3.9 weeks (range 21-38) and at delivery 36.2 ± 1.8 weeks (range 34-39). 15 women were treated with ursodeoxycholic acid (n = 9), S-Adenosyl-L-methionine (n = 6) or cholestyramine (n = 5). No associations were observed between severity of pruritus, duration of cholestasis, maximum serum levels of transaminases, bile acids or bilirubin, or maternal therapy, and placental vascular or acute inflammatory lesions. As expected, gestational age at delivery and birth weight were inversely correlated with the presence of placental vascular lesions. ConclusionIn patients with intrahepatic cholestasis of pregnancy, placental pathology is largely unaffected by cholestasis-related clinical or laboratory indicators of disease severity and duration. In patients with intrahepatic cholestasis of pregnancy, placental pathology is largely unaffected by cholestasis-related clinical or laboratory indicators of disease severity and duration.

Less nitric oxide (NO)-dependent vasodilation and excess formation of reactive oxygen species could explain poor placenta perfusion in preeclampsia, but the pathways involved are unknown. We tested the hypothesis that reduced NO activity and increased oxidative stress in preeclamptic placenta is related to a low bioavailability of l -arginine. Placental endothelial NO synthase (ecNOS) expression (by immunoperoxidase) and activity (by diaphorase and [ 3 H]L-citrulline formation) were comparable in normotensive pregnancy and in preeclampsia, whereas nitrotyrosine staining, a marker of peroxynitrite, was stronger in preeclamptic villi, confirming previously reported data. Oxidative tissue damage was documented in preeclamptic villi by strong 4-hydroxynonenal-lysine staining (by immunoperoxidase), which closely colocalized with nitrotyrosine. Concentration of the NO precursor l -arginine (by HPLC) in umbilical blood and in villous tissue was lower in preeclampsia than in normotensive pregnancy. This was not caused by a defective l -arginine transport, because gene expression of the CAT-1, 4F2hc, and LAT-1 cationic amino acid transporters (by real-time reverse-transcription polymerase chain reaction [RT-PCR]) was normal. Instead, gene expression (by real-time RT-PCR) and protein tissue content (by immunoperoxidase and Western blot) of arginase II—the enzyme that degrades arginine to ornithine—were higher in preeclamptic villi than in normotensive pregnancy. These results provide a biochemical explanation for defective NO activity and increased oxidative stress in preeclamptic placenta. In normal placenta, adequate concentration of l -arginine orients ecNOS toward NO. In preeclampsia, a lower than normal l -arginine concentration caused by arginase II overexpression redirects ecNOS toward peroxynitrite.

Sertoli-Leydig cell tumors (SLCTs) are rare neoplasms, accounting for less than 0.2% of ovarian tumors. The endometrioid-like variant of yolk sac tumor (YST) is very rare, and the most extensive series reported only 8 cases. We present a case of ovarian SLCT with endometrioid-like YST in a patient with a 46,XX karyotype with Y-chromosomal material. A 26-year-old woman had undergone a right salpingo-oophorectomy for SLCT with endometrioid-like YST. Chromosomal analysis revealed a 46,XX karyotype with Y-chromosomal material insertion into chromosome 1. The patient's father and sister, and 7 other paternal relatives (4 male and 3 female) presented the same chromosome variant without evidence of cancer. The YST component relapsed to the right side of the uterine wall and then metastasized to the peritoneum and liver, while SLCT was eradicated with primary surgery. Several chemotherapeutic regimens were totally ineffective to control tumor progression. She died of disease progression 54 months after the diagnosis. We adopted the policy of a close surveillance for ovarian neoplasms for the 22-year-old sister of the patient, who presented the same Y-chromosomal material in her karyotype. In very rare tumors, new methods, based on molecular and cytogenetic models, are requested to define recommended management.

We report a case of a squamous cell carcinoma in situ of the ovary in a patient previously submitted to radical hysterectomy and pelvic lymphadenectomy for an epidermoid carcinoma of the uterine cervix. The histogenesis of epider-moid tumors of the ovary and their association with squamous malignancies of the uterine cervix are discussed.