Two Case Reports of Nodular Fasciitis: A Newly Recognized Placental Lesion.

We describe two occurrences of nontrophoblastic mesenchymal tumors of the placenta. The first placental tumor was found along the placental margin, and the second was identified close to the insertion of the fetal membranes along the placental disc. Microscopically both lesions demonstrated bland fibroblastic cells with intricate vasculature and inflammatory cells. Both lesions were negative for estrogen receptor (ER), progesterone receptor (PR), beta-HCG, PLAP, CD34, desmin, h-caldesmin, and smooth muscle actin by immunohistochemistry. Some cells were weakly positive for CD10, a nonspecific finding. The morphologic and immunohistochemical characteristics of these lesions were most consistent with nodular fasciitis, a tumor most commonly found in the soft tissues. FISH positive for USP6 gene rearrangement in our two patients confirmed the molecular similarity of these lesions to nodular fasciitis of soft tissue. Such lesions can be easily dismissed on gross placental examination as infarcts or thrombi, thus these rare entities are likely underreported.

ADAM "sequence" part II: hypothesis and speculation.

Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766; Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions, mutilations (ADAM) sequence remains causally and pathogenetically incognito. In 1930 Streeter stated " apodictically" that no evidence has been found that intra-uterine amputation is due to amniotic bands or adhesions …" and that his 16 cases provided (histological) evidence for a "germinal origin." He concluded that an amniotic cord was "not an adhesion or inflammatory product but … an anomalous developmental structure and present from the outset." In survivors the "traces" of damaged limb-buds "reveal the scars of poor germ-plasm." In 1958, Willis, in dismissing the amniotic origin of the ADAM defects (or "Streeter" or "Simonart" bands) quoted Keith [1940] to the effect that "(a)mniotic adhesions … are always produced by … the fetus ­ as a result of dysplasia in foetal tissues. They are the result, not the cause, of foetal malformations." Streeter [1930] mentions a potential familial case (56-year-old man and his mother), not controlled by photographs or other records and concluded "that the (ADAM) deformity is not easily transmissible," but "due to the constitution of the germ-plasm." Torpin [1968] concluded, as apodictically as Streeter and Willis, that "… proof of amnion rupture without damage to the chorionic sac is no longer "in question." Considering Torpin's decades-long study of the ADAM phenomenon and review of 494 references (missing many) it is surprising that he does not discuss the relationship between the apparent ADAM defects and other, internal anomalies that maybe present in an affected fetus or infant not evidently caused by the amniotic disruptions, adhesions or mutilations, unless his mind was made up. Our review of these internal and other presumed primary malformations in ADAM is ongoing. However, on a preliminary basis, it seems likely to us that: (1) there is an increased prevalence of such primary anomalies in the ADAM condition confirming the view and experience of others, for example Czeizel et al. [1993]; (2) these malformations (e.g., heterotaxy) may arise as early as gastrulation; (3) that, given the ADAM phenomenon is exclusively ascertained as the ADAM phenotype in fetuses and infants, that is, that its cause and ascertainment are completely congruent, then the apparent amniotic defect must also be regarded as a malformation; (4) that in such a case the ADAM phenomenon with associated primary malformation(s) is a form of syndromal pleiotropy due to one cause yet to be elucidated. To that end we recommend archiving DNA from all affected fetuses coming to autopsy and their parents and placentas and surgical tissues of all viable affected infants for ultimate exome or genome sequencing perhaps with special attention to the syncytin genes.

Postmortem ultrasonography of the macerated fetus complements autopsy following in utero fetal demise.

Postmortem evaluation following an in utero fetal demise is essential for determining cause of death and counseling regarding future pregnancies. Severe maceration and fetal size along with patient desires may limit the physician's ability to perform a complete autopsy. In the cases presented, we demonstrate the utility of postmortem ultrasonography as an adjunct to traditional autopsy following fetal demise.

De novo translocation t(5;9)(q11.2;p22) associated with hydrops fetalis and cystic hygroma.

We report on a case of a prenatally diagnosed non-immune hydrops fetalis and cystic hygroma associated with the balanced translocation t(5;9)(q11.2;p22), an association that to our knowledge has not been reported previously. Both parents had normal karyotypes. The infant was born prematurely at 33 and 3/7 weeks gestation and expired 12 h after delivery.

Clinicopathologic conference: multiple fetal demises, lactic acidosis and hepatic iron accumulation.

A case of a premature infant with lactic acidosis and hepatic iron accumulation, born to a mother with multiple fetal demises, is presented and discussed by both clinician and pathologist, in this traditional clinico-pathologic conference. The discussion includes the differential diagnoses of lactic acidosis and hepatic iron accumulation in infants.

Teratogenic causes of malformations.

Crucial morphogenetic processes during the blastogenesis period, which extends throughout the first 4 wk of development, from fertilization until the end of the gastrulation stage (days 27 to 28 postconception), can be altered and result in structural abnormalities, including patterns of multiple congenital anomalies (MCAs) arising from developmental field defects. Severe damage may cause death of the product of conception or, because of the pluripotential nature of the cells, the damage may be compensated allowing development to continue in a normal fashion. Most investigators believe that the all-or-none rule applies to the first 2 wk of development. Because the fetus is less susceptible to morphologic alterations when the developmental process of the majority of organs has been completed, the most common anomalies associated with teratogenic exposures during the fetal period are fetal growth restriction (intrauterine growth retardation) and mild errors of morphogenesis (abnormalities of phenogenesis), such as epicanthic folds, clinodactyly, and others. Thus, teratogenic exposures result in a wide variety of effects that range from infertility, prenatal onset growth restriction, structural defects, and functional CNS abnormalities to miscarriage or fetal death.

A spectrum of phenotypical expression OF Neu-Laxova syndrome: Three case reports and a review of the literature.

Neu-Laxova syndrome is a rare autosomal recessive disorder characterized by severe intra-uterine growth restriction, extreme microcephaly, marked edema with skin restriction, ichthyosis, craniofacial anomalies, limb deformities, and a spectrum of central nervous system malformations. Less than 70 cases have been described since the first report in 1971. To this day the etiology and genetic basis remains unknown. Consanguinity has been reported. Some authors have postulated the syndrome to be a form of neuro-ectodermal dysplasia, while others suggest that it is a malformation syndrome secondary to severe skin restriction. Although the outcome of this syndrome is lethal, a single case of longer survival (6 months) has been reported. The majority of cases are stillborn or die shortly after birth. Thus, it is clear that Neu-Laxova exhibits a spectrum of disease, with varying degrees of phenotypic expression. We are presenting three new cases of Neu-Laxova syndrome; two were stillbirths and one lived for eleven weeks. Our microscopic and post-mortem findings in these three cases display the vast spectrum of this rare syndrome.

Spondyloepiphyseal dysplasia congenita.

We report a case of spondyloepiphyseal dysplasia congenita (SED congenita), diagnosed at autopsy of a term infant. Prenatal ultrasound at 20 weeks of gestation had shown shortening of all the fetal long bones, with bowing of the femora and humeri, clubfeet, and small thoracic cage. We discuss the diagnostic features of SED and the main differential diagnoses.

Massive pericardial effusion treated with in utero pericardioamniotic shunt in a fetus with intrapericardial teratoma.

Teratoma is the leading neoplasm diagnosed in neonates and infants. Although over 99% of teratomas found in the fetus and newborn are histologically benign, those tumors may cause death if vital structures are involved or if the airway is compromised. We review the literature on antenatal intrapericardial teratomas and report a case of intrapericardial teratoma, with massive pericardial effusion and fetal hydrops, diagnosed on antenatal ultrasound at 21 weeks of gestation. Pericardioamniotic shunt was placed at 22 weeks and 6 days gestational age. In spite of successful drainage of the pericardial effusion, fetal demise was documented 8 days later, likely due to tumor compression of the heart.

Fetal umbilical cord blood erythropoietin, interleukin-6, pH, pO(2), pCO(2), and base excess levels in histologic and/or clinical chorioamnionitis: is the response only inflammatory?

OBJECTIVE: To determine the correlation of histological chorioamnionitis (CA) with and without clinical CA with umbilical cord blood gases, erythropoietin (EPO), and interleukin-6 (IL-6) levels. METHODS: Umbilical artery blood gas analysis (pH, pO(2), pCO(2), BE) and umbilical vein EPO and IL-6 levels were measured in 202 infants from normal, histological, and no clinical CA and histological plus clinical CA pregnancies. RESULTS: Umbilical artery blood gas analyses were not different between normal controls and histological and clinical CA groups. Blanc Stage 1 histological CA had no abnormal EPO or IL-6 umbilical blood results. EPO in umbilical venous blood was elevated only in those infants with both histological and clinical CA. Umbilical vein IL-6 levels were elevated in all advanced microscopic and clinical CA. High and low EPO groups also have corresponding high and low IL-6 levels suggesting a common stimulus for these substances. CONCLUSIONS: Blanc stage I histological CA is probably clinically insignificant. CA is infrequently associated with abnormal umbilical artery blood gas levels. Advanced histological and clinical CA can elevate both EPO and IL-6 in umbilical blood and these may be key elements of mechanisms that effect fetal brain function.

Extreme variant of enlarged heterochromatin region on chromosome 9Q in a normal child and multiple family members.

Heteromorphisms of chromosome 9 are among the most common variations in the human karyotype. The pericentromeric polymorphisms of chromosome 9 include variations in the size of q-arm heterochromatin, pericentric inversions, and rarely, additional C-band-negative, G-band-positive material. The finding of a polymorphic variant, either in prenatal screening or in chromosomal analysis for phenotypic abnormalities, may cause parental anxiety and initiate genetic counselling. We report a case of a 39-year-old primigravida with unremarkable pregnancy, who had amniocentesis due to advanced maternal age. Chromosomal analysis demonstrated a long arm (q) variant of chromosome 9 with an enlarged heteromorphic area, approximately three times longer than known reported variants. Prenatal analysis demonstated an identical variant in the probands phenotypically normal father, uncle, and paternal grandmother, confirming an apparently "normal" variant.

Thirteen-year-old child with a malignant chest tumor: clinicopathologic conference.

A case of pleuropulmonary blastoma in a 13-year-old child, exposed to the Chernobyl disaster while in-utero, is presented and discussed by both clinician and pathologist, in this traditional clinical-pathologic conference. The discussion includes the differential diagnoses of chest mass in children.

Discordant omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex and cardiac malformations in monochorionic twins.

The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex was first described by Carey et al. in 1978. It constitutes a specific combination of malformations. There are very few case reports of discordant OEIS in monozygotic twins and very few reports of OEIS in association with both hypoplastic left heart and ventricular septal defect. Our case represents the fifth reported case of cardiac malformations in a fetus with OEIS complex.

Expression of the insulin-like growth factor receptor 1 during human embryogenesis.

Insulin-like growth factor 1 and its receptor (IGF-1/IGF-2) may play important roles in the development of human fetal tissue, and its ligands IGF-1 and IGF-2 have been found in fetuses older than 3 months. Our objective was to study the immunohistochemical distribution of IGF 1-R in tissues obtained from human normal embryos following abortion or natural termination of pregnancy. Immunohistochemical staining was performed on autostainer, using an anti-IGF1-R rabbit polyclonal antibody (dilution 1:75), and the avidin-biotin peroxidase complex method. The embryos ranged between 28 days to 8 weeks gestation. Fully 3 cases were 28 days old, 1 case 32 days old, 2 cases 6 weeks old and 2 cases 8 weeks old. The IGF1-R stain decorated the surface ectoderm, the optic cup, and the lens placode, pharynx, respiratory diverticulum, foregut, liver cords, mesonephros, and metanephric blastema. Mesodermal structures, including limb mesoderm, and neural crest derivatives were IGF-1R negative. On study shows the preferential IGF-1R immunolocalizatrion in specific areas of the developing embryo, suggesting a role of IGF1-R for the optimal maturation of those areas, during developing human embryos.

Congenital perineal hernia in a fetus with trisomy 18.

Perineal hernias are very rare and mostly reported in adults, with only 7 cases reported in children. We report a female fetus, terminated at 18 weeks of gestation due to trisomy 18. In addition to multiple typical findings of trisomy 18, this fetus had perineal hernia with defect of the perineal skin and prolapse of multiple bowel loops. To our knowledge there are no reported cases of perineal hernia presenting antenatally nor are there reported cases of perineal hernia associated with trisomy 18.

Cerebellar migration defects in aicardi syndrome: an extension of the neuropathological spectrum.

The Aicardi syndrome is characterized by infantile spasms, corpus callosum agenesis, and chorioretinal lacunae and almost exclusively affects females (very rarely, 47, XXY males). The crucial genetic mishap likely occurs in the postzygotic stage, but the variable clinical phenotype among the approximately 450 known cases has not been explained. No consistent mutations or deletions exist among patients. We encountered a baby girl with early onset infantile spasms. She had left-sided cleft lip/palate, costovertebral defects, scoliosis, callosal agenesis, and microphthalmia. She expired at the age of 3 months of respiratory infection. On autopsy she had thoracic hemivertebrae with rib defects, bilateral microphthalmia, microcornea, posterior colobomata, abnormalities of the retinal pigment epithelium, absence of normal ganglion cells in the retina, gross asymmetry of the brain with cerebral polymicrogyria, total callosal agenesis, cerebral subcortical and subependymal nodular heterotopias, cerebellar nodular heterotopias, and tegmental/basal unilateral brainstem hypoplasia. Cerebellar and retinal migration defects have not been described before in Aicardi syndrome and may have had a bearing on this patient's eventual outcome.