Regina Schultz

Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers

Ianez R F, Buim M E, Coutinho‐Camillo C M, Schultz R, Soares F A & Lourenço S V
(2010) Histopathology 57, 410–417
Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers

A case-control study of histological chorioamnionitis and neonatal infection

The authors report a prospective study of the correlation between histopathological alterations in the placenta and the umbilical cord and neonatal infection in 223 newborns. The pathological studies were specifically concerned with the presence of infection as shown by a polymorphonuclear infiltrate at these sites. Inflammatory lesions were demonstrated in 26.9% of specimens and were highest in those with prolonged premature rupture of membranes and in the least mature placentas. Among the cases of histological chorioamnionitis, only 23.3% of infants had documented infection. Neonatal infection was diagnosed in 7.2% of the newborns and was 10 times more frequent in preterm newborns. Among the cases of infected newborns, 87.5% of placentas had histological chorioamnionitis. Pneumonia and septicemia were the most frequent conditions found among infected newborns. There was a strong correlation between histological chorioamnionitis and neonatal infection. The data obtained in this investigation suggest that histological chorioamnionitis is an important indicator of neonatal infection.

Conjoined twins pregnancies: experience with 36 cases from a single center.

To review a single center´s experience in the management of twin pregnancies with conjoined fetuses.

Vascular endothelial growth factor and β-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy

OBJECTIVE To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and β-hCG and to assess its predictive value. DESIGN Prospective study. SETTING Tertiary care university hospital. PATIENT(S) Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. INTERVENTION(S) Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. MAIN OUTCOME MEASURE(S) The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and β-hCG serum concentrations on the day of surgery. RESULT(S) An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and β-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. CONCLUSION(S) Maternal serum VEGF and β-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall.

A risk factor for early-onset infection in premature newborns: invasion of chorioamniotic tissues by leukocytes.

The authors report a prospective study of correlation between histopathological alterations of the placenta, risk factors and early-onset bacterial infections in 224 premature newborns. They used a mathematical model for evaluation and prediction of neonatal bacterial infection according to the localization in chorioamniotic tissues (chorioamniotic plate, amniotic membranes and umbilical cord) invaded by leukocytes. Septicemia, pneumonia or omphalitis were documented in 45 (20%) infected premature newborns and inflammatory lesions in the placenta were observed in all of them. In order of statistical significance, the most important variables for early-onset bacterial neonatal infection were invasion of the chorioamniotic plate, amniotic membranes and umbilical cord tissues by PMNL (P < 0.0000), premature rupture of membranes (P < 0.0000), birthweight lower than 1500 g (P < 0.0000), gestational age under 34 weeks (P < 0.0001), foul smell (P < 0.0038), no antibiotics before delivery (P < 0.0066) and intrapartum fever (P < 0.0087). By logistic stepwise multiple regression analysis, invasion of fetal chorioamniotic plate and of amniotic membranes by leukocytes were the only statistically significant variables. The probability of neonatal infection in premature newborns, when polymorphonuclear neutrophils were present in chorioamniotic plate and in amniotic membranes, was 62.5%, while the probability was 0.5% when these tissues were normal. These data suggest that histological chorioamnionitis has to be considered as an important risk factor for early-onset infection in premature newborns.

Sonographic appearance of gestational trophoblastic disease evolving into epithelioid trophoblastic tumor

Epithelioid trophoblastic tumor is a distinctive but rare trophoblastic tumor. It derives from intermediate trophoblastic cells of the chorion laeve and is usually associated with a previous gestational event. We report the case of a patient who had undergone dilatation and curettage for a missed miscarriage. Three months later gestational trophoblastic disease was suspected because of persistent vaginal bleeding and high levels of β‐human chorionic gonadotropin (β‐hCG). Transvaginal ultrasound revealed irregular echolucent lacunae within the myometrium, some of them filled with low‐resistance, turbulent blood flow on Doppler examination, emphasizing the diagnosis of gestational trophoblastic disease. The patient was treated with 12 courses of multiagent chemotherapy. After a 2‐year remission, a low rise in serum β‐hCG was observed. Transvaginal ultrasound revealed a well‐circumscribed echogenic lesion with a diameter of 1.8 cm in the uterine fundus, with no detectable blood flow on Doppler imaging. A diagnosis of tumor of intermediate trophoblastic cells was suspected and total hysterectomy was performed. On pathological examination, the histological and immunohistochemical features were characteristic of epithelioid trophoblastic tumor. Most reported cases of epithelioid trophoblastic tumor have solitary nodules with sharp margins, which is consistent with our ultrasound findings. Ultrasound may be helpful in differentiating epithelioid trophoblastic tumor from placental‐site trophoblastic tumor, another tumor of intermediate trophoblastic cells, which shows infiltrative growth insinuating between muscle fibers. Copyright

Tumorigenic Factor CRIPTO-1 Is Immunolocalized in Extravillous Cytotrophoblast in Placenta Creta

CRIPTO-(CR)1 is a protein associated with tumorigenesis and metastasis. Here we demonstrate that CR-1 expression in normal and creta placentas is associated with various degrees of uterine invasion. Cytokeratin (CK) and CR-1 protein expression was visualized by immunohistochemical staining of formalin-fixed, paraffin-embedded placental specimens (control placentas, n = 9; accreta, n = 6; increta, n = 10; percreta, n = 15). The pattern of extravillous trophoblast (EVT) cell morphology was distinctive in creta placentas: densely-compacted cell columns and large star-shaped cells with a typically migratory phenotype, not common among third trimester control placentas. Quantification revealed higher CR-1 immunoreactivities in accreta (P = 0.001), increta (P = 0.0002), and percreta placentas (P = 0.001) than in controls. In contrast to controls, there was a significant positive relationship between CR-1 and CK reactivity in all creta placentas (accreta, P = 0.02; increta, P = 0.0001, and percreta, P = 0.025). This study demonstrated CR-1 expression in the placental bed, its increased expression in creta placentas, and EVT cells as the main CR-1-producing cell type. Morphological examination revealed an immature and invasive trophoblast profile in creta placentas, suggesting impairment of the trophoblast differentiation pathway. These findings provide important new insights into the pathophysiology of abnormal creta placentation and its gestational consequences.

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy

Predictive factors of damage to the Fallopian tube may guide the treatment of patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonography (TVS) in women with ampullary pregnancy.

Post-mortem cytogenomic investigations in patients with congenital malformations.

Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.

Association between ultrasound findings and serum levels of vascular endothelial growth factor in ampullary pregnancy

OBJECTIVE To assess the association between ultrasound images and serum concentrations of vascular endothelial growth factor (VEGF) in ampullary pregnancies. DESIGN Prospective study. SETTING University hospital. PATIENT(S) Fifty patients with ampullary pregnancy. INTERVENTION(S) Criteria for inclusion in the study were: singleton pregnancy from spontaneous conception; diagnosis of tubal pregnancy in the ampullary region; radical surgical treatment (salpingectomy); and measurement of serum VEGF, human chorionic gonadotropin, and progesterone on the day of surgery. An additional criterion was description of an ectopic mass by transvaginal ultrasound, as follows: [1] ectopic gestational sac containing an embryo with cardiac activity; and [2] tubal ring: a paraovarian formation similar to a gestational sac, not containing a viable embryo (an anechoic structure surrounded by a peripheral hyperechogenic halo); an empty ectopic gestational sac; a sac containing an embryo without cardiac activity; or a vitelline vesicle. MAIN OUTCOME MEASURE(S) Association between ultrasound images and serum concentrations of VEGF. RESULT(S) An association was found between ultrasonographic images and VEGF serum concentrations. Ectopic embryos with cardiac activity were associated with higher levels of serum VEGF. CONCLUSION(S) In ampullary pregnancy, higher serum levels of VEGF are associated with the finding of an embryo with cardiac activity on transvaginal ultrasound. Greater production of VEGF likely creates development conditions more conducive to ectopic embryos.