Maternal and fetal Toll-like receptor 4 genotype and chorionic plate inflammatory lesions.

OBJECTIVE: The objective of the study was to explore the relation between maternal and fetal genetic variation in Toll-like receptor 4 (TLR4) and chorionic plate inflammation STUDY DESIGN: In this prospective observational cohort of 109 women with singleton gestations, 13 tag single nucleotide polymorphisms (SNPs) were genotyped in the TLR4 gene. The diagnosis of chorionic plate inflammation was made by a single blinded perinatal pathologist. RESULTS: After adjustment for multiple comparisons, 1 maternal SNP (rs10759932) and 1 fetal SNP (rs1554973) in the TLR4 gene demonstrated highly significant association with chorionic plate inflammation. After adjustment for race, smoking, and bacterial vaginosis, carriage of these alleles was associated with chorionic plate inflammation (maternal rs1554973: odds ratio [OR] 5.2, 95% confidence interval, 3.2-6.4, P = .006; fetal rs10759932: OR 4.95, 95% confidence interval, 3.0-5.6, P = .005). There was no evidence of interaction between these 2 SNPs. CONCLUSION: Maternal and fetal genetic variation in TLR4 is strongly associated with chorionic plate inflammation. This maternal and fetal genotypic effect are independent of each other as well as other environmental covariates.

P57KIP2 immunostaining and molecular cytogenetics: combined approach aids in diagnosis of morphologically challenging cases with molar phenotype and in detecting androgenetic cell lines in mosaic/chimeric conceptions.

Although molar pregnancies are typically defined by morphological, histologic, and genetic criteria, most cases are diagnosed solely on histologic findings. Recently, several studies have demonstrated the usefulness of p57KIP2 immunostaining as an ancillary diagnostic tool for molar pregnancies. The p57KIP2 gene is paternally imprinted and maternally expressed; therefore, the positive staining of its protein indicates the presence of a functional maternal allele. Because complete hydatidiform moles (CHMs) lack a maternal genome, p57KIP2 immunostaining is absent. Previous studies have validated this staining technique by demonstrating differential nuclear expression in CHMs versus non-CHMs; however, these studies have not included cytogenetic analysis. We report on 58 cases of hydropic placentas, correlating cytogenetic and p57KIP2 immunostaining results. In addition, cases with unusual p57KIP2 staining patterns are discussed. Also included are 2 mosaic conceptions (1 diploid/triploid and 1 diploid/tetraploid), 6 chimeric/mosaic conceptions with androgenetic/biparental cell lines, and 2 cases of placental mesenchymal dysplasia.

The fetal anterior cruciate ligament: an anatomic and histologic study.

PURPOSE: The purposes of this study were to better understand the fetal development of the anterior cruciate ligament (ACL); to identify the gross anatomy of the ACL; to perform a complete histologic evaluation of the ligament, particularly with respect to the distinction between bundles; and to evaluate ACL length, diameter, cellularity, vascularity, and insertion sites. METHODS: By use of 40 intact knee joints of human fetuses, the gross anatomy of the ACL was inspected under a stereomicroscope (n = 40). The histologic evaluation was performed on the sagittal (n = 20) and transverse (n = 10) sections. RESULTS: The gross observations revealed the presence of 2 distinct bundles: anteromedial (AM) and posterolateral (PL). The femoral origin of each ACL bundle was located in the posterior aspect of the medial surface of the lateral femoral condyle. The footprint of the tibial insertion was ovoid, with the AM bundle located anterior and medial to the PL bundle. The mean length of the ACL was 3.7 mm, the mean width was 1.1 mm, and the mean thickness was 0.9 mm. There was high cellularity, with approximately 5,600 cells/mm2, and intense vascularity. The AM and PL bundles were divided by a well-defined septum. The femoral origin had less dense connective tissue compared with the tibial insertion. CONCLUSIONS: From the time of fetal development, the ACL is composed of 2 bundles, AM and PL. The gross morphology of the ACL in fetuses is similar to that reported in adults; the histology is diverse in cellularity and vascularity. CLINICAL RELEVANCE: This study provides useful information about the anatomy and histology of the fetal ACL.

Persistent gestational trophoblastic disease after an androgenetic/biparental fetal chimera: a case report and review.

We present a case of a dichorionic/diamniotic twin pregnancy in which one twin presented with ultrasound findings suggestive of molar changes in the placenta. The placenta of twin A seemed to be grossly enlarged and cystic, and twin A was small for gestation. After an inevitable abortion, a detailed histological and genetic evaluation was performed on the fetus and placenta from twin A, including traditional cytogenetic techniques, microsatellite marker analysis, fluorescent in situ hybridization, and p57 immunostaining. It was determined that twin A was a chimera with a biparental XX cell line and an androgenetic XY cell line. The 2 cell lines were present in both the placenta and the fetus. The patient later developed and was treated for persistent gestational trophoblastic disease, which has been shown to have an increased risk after an androgenetic conception. Cases of mosaicism or chimerism involving an androgenetic cell line may be difficult to diagnose histologically but are critical to identify because of the increased risk for persistent gestational trophoblastic disease. Therefore, we emphasize the importance of using multiple molecular, cytogenetic, and immunohistochemical techniques when diagnosing cases involving such unusual placental abnormalities. To our knowledge, this is the first reported case of persistent gestational disease after a fetal chimera.