ABSTRACT
Lymphoma involving the placenta or fetus remains a very rare event. All cases reported to date have shown the lymphoma cells to be of maternal origin in that the tumor cells have preferentially involved the intervillous spaces with sparing of the villi and fetal circulation. We report a novel case of a monoclonal primary placental Epstein-Barr virus (EBV)-associated B-cell lymphoma of fetal origin. The placenta of a 20-week stillborn fetus born to a 19-year-old gravida 1 para 0 woman, presenting with oligohydramnios, showed a large cell infiltrate confined within villi and sparing the intervillous spaces, indicative of preferential involvement of the fetal circulation. Necropsy did not show any other site of involvement by malignant lymphoma or other abnormalities. Immunophenotypic studies showed the tumor cells to be of B-cell phenotype with a relatively high proliferation rate. EBV EBER1 RNA was identified in more than 95% of tumor cells, and polymerase chain reaction studies showed EBV EBNA1 strain type A and wildtype EBV LMP1. Analysis of the immunoglobulin heavy chain by polymerase chain reaction showed a monoclonal B-cell population. In situ hybridization studies using a commercially available probe directed at repeated sequences on the human Y chromosome showed a single intense signal within trophoblastic epithelium and lymphoma cells, indicative of male origin. The mother remains in good health 11 months after delivery.
Subject(s)
Fetal Diseases/diagnosis , Herpesvirus 4, Human , Lymphoma/diagnosis , Oligohydramnios/etiology , Trophoblastic Tumor, Placental Site/diagnosis , Diagnosis, Differential , Female , Fetal Death , Fetal Diseases/pathology , Fetal Diseases/virology , Gene Deletion , Gene Rearrangement , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Humans , Immunoglobulins/genetics , In Situ Hybridization , Lymphoma/complications , Lymphoma/pathology , Lymphoma/virology , Male , Oligohydramnios/virology , Polymerase Chain Reaction , Pregnancy , Pregnancy Trimester, Second , Trophoblastic Tumor, Placental Site/complications , Trophoblastic Tumor, Placental Site/pathology , Trophoblastic Tumor, Placental Site/virology , Y Chromosome/geneticsABSTRACT
The teratogenic potential of three bunyaviruses, two California serogroup bunyaviruses, LaCrosse virus and San Angelo virus, and a Bunyamwera serogroup member, Main Drain virus, in sheep was studied following in utero inoculation of ewes in early gestation. Although Main Drain virus appeared to be most teratogenic, all three viruses induced a range of lesions including arthrogryposis, hydrocephalus, fetal death, axial skeletal deviations, anasarca, and oligohydramnios. The teratogenic effects of these viruses are identical to those described in ovine infections by Cache Valley and Akabane viruses. Demonstration of a common bunyaviral tropism for fetal tissue infection that results in congenital brain and musculoskeletal malformations provides evidence that human in utero infection by bunyaviruses could result in similar malformations in human infants.
Subject(s)
Abnormalities, Multiple/veterinary , Bunyamwera virus/pathogenicity , Bunyaviridae Infections/veterinary , Encephalitis Virus, California/pathogenicity , Fetus/abnormalities , Pregnancy Complications, Infectious/veterinary , Sheep Diseases/virology , Abnormalities, Multiple/embryology , Abnormalities, Multiple/virology , Animals , Arthrogryposis/embryology , Arthrogryposis/veterinary , Arthrogryposis/virology , Bunyamwera virus/isolation & purification , Bunyaviridae Infections/complications , Bunyaviridae Infections/embryology , Chlorocebus aethiops , Encephalitis Virus, California/isolation & purification , Encephalitis, California/complications , Encephalitis, California/embryology , Encephalitis, California/veterinary , Female , Fetal Death/veterinary , Fetal Death/virology , Hydrocephalus/embryology , Hydrocephalus/veterinary , Hydrocephalus/virology , La Crosse virus/isolation & purification , La Crosse virus/pathogenicity , Oligohydramnios/veterinary , Oligohydramnios/virology , Pregnancy , Sheep , Sheep Diseases/embryology , Vero CellsABSTRACT
Studies with a simian immunodeficiency virus (SIV)-infected fetal monkey model were conducted with a focus on fetal growth and viral pathogenesis. Twenty-six fetuses were inoculated in utero via ultrasound guidance with an uncloned pathogenic strain of SIV or vehicle during the second or third trimesters [gestational day (GD) 65, 110, or 130], sonographically monitored weekly (biometrics, blood flow), then necropsied at incremental time points postinfection. Peripheral blood hematologic (complete blood counts, clinical chemistries), immunologic (immunophenotyping), and endocrine studies [insulin-like growth factor (IGF), IGF-binding proteins (IGFBP)] were conducted. Severe intrauterine growth restriction (IUGR), oligohydramnios, and altered lymphocyte counts were noted for fetuses infected on GD 65. Less severe effects were detected for fetuses inoculated at the later time points, with severity dependent upon the length of SIV infection in utero. IGF studies indicated significant reductions in IGF-I and elevated immunoreactive levels of IGFBP-3 in infected fetuses during the third trimester. Parallel studies conducted with four fetuses infected on GD 65 with a nonpathogenic, molecularly cloned virus (SIVmac1A11) resulted in normal fetal growth, with no effects on hematopoiesis or IGF/IGFBP levels, and no evidence of clinical disease. Taken together, these studies show that (1) infection of fetuses during the early second trimester with an uncloned pathogenic strain of SIV results in severe IUGR and a disruption in the molar ratio of IGF:IGFBP-3, and (2) outcome of fetal SIV infection is determined by the timing of infection and the virulence of the viral inoculum.