Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group.

Pediatric germ cell tumors (n = 135) with a major component of immature teratoma (IT) registered on Pediatric Oncology Group/Children's Cancer Group treatment protocols from 1990 to 1995 were reviewed. Sixty cases were pure IT with no malignant component and 75 were mixed tumors with a major component of IT. Foci of yolk sac tumor (YST) were present in all 75 mixed tumors; additional malignant components were present in 15. The IT component was as follows: 47% grade 3, 29% grade 2, 24% grade 1. There were no significant correlations between tumor grade and patient age by specific subsets or overall (all p > 0.10). Significant correlations were detected between stage and the presence of foci of YST (p = 0.0145) and grade and the presence of foci of YST (p < 0.001). Serum alpha-fetoprotein concentrations were elevated at diagnosis in 96% of ovarian tumors with foci of YST and were mildly elevated (< 60 ng/dL) in only 16% of tumors without YST. Overall 2- to 6-year survival rate was 96% and was related to the presence of YST. Central pathologic review revealed aspects of morphologic diagnosis that were most frequently misinterpreted by contributing pathologists. These included the classification of differentiating tissues as immature and the failure to recognize two well-differentiated patterns of YST (the hepatoid pattern resembling fetal liver and the well-differentiated glandular pattern resembling fetal lung or intestine). Such foci were often overlooked. The authors conclude that the presence of microscopic foci of YST, rather than the grade of IT, per se, is the only valid predictor of recurrence in pediatric IT at any site.

Gastrointestinal abnormalities: a significant cause of feeding difficulties and failure to thrive in Brachmann-de Lange syndrome.

Gastroesophageal abnormalities occur with increased frequency in patients with Brachmann-de Lange syndrome (BDLS) and contribute to problems with feeding, emesis and failure to thrive. Comprehensive evaluation including longitudinal assessment of growth and development of 8 patients with BDLS was performed. Clinically significant feeding problems occurred in 6 of the 8 patients and the affected children were subsequently evaluated for gastrointestinal abnormalities. Findings in these patients included tracheal aspiration, esophageal dysmotility, gastroesophageal reflux, hiatal hernia, and esophagitis. Medical treatment was instituted where appropriate, and surgical treatment was performed if the problems did not resolve with medical treatment. Improvement in weight centiles occurred in all patients fed by nasogastric or feeding gastrostomy tube but only one patient appeared to experience increase in rate of linear growth. Careful monitoring of symptoms and growth parameters, and prompt institution of appropriate medical and surgical measures can improve the health and physical outcome of many patients with BDLS.

Necrotizing funisitis and herpes simplex infection of placental and decidual tissues: study of four cases.

Necrotizing funisitis (NF) is a macroscopically and microscopically distinctive pattern of umbilical cord inflammation recently heralded as presumptive of congenital syphilis. Four nonsyphilitic cases are presented in which herpes simplex virus (HSV) 2 antigen was demonstrated in the placenta by immunohistochemistry. The clinicopathologic findings in one case, including HSV 2 antigen in amniotic epithelium, subamniotic chorion, and Wharton jelly, indicate that NF was caused by chronic ascending primary HSV 2 infection, whereas those of the other three cases with HSV 2 Ag confined to decidual cell clusters suggest that NF was caused by chronic ascending bacterial infection and that latent endometrial HSV 2 infection was fortuitous. We conclude that (1) NF is caused by protracted inflammation of a structure whose normal anatomy precludes removal of inflammatory debris; (2) no single pathogen causes NF; and (3) NF is strongly associated with latent endometrial HSV 2 infection, which should be sought in all instances. Although latent HSV 2 endometrial infection may be more prevalent than currently recognized, we speculate that its strong association with NF may be more than causal; whereas the usual ascending bacterial infection leads to labor before NF has had sufficient time to develop, latent endometrial HSV 2 infection may alter local paracrine factors and delay parturition for the time sufficient to permit NF, a morphological hallmark of chronicity, to become apparent.

The prepubertal testis (prenatal and postnatal): its relationship to intratubular germ cell neoplasia: a combined Pediatric Oncology Group and Children's Cancer Study Group.

Seminiferous tubules adjacent to germ cell tumors (GCT) in prepubertal boys frequently contain increased germ cells with abundant, clear cytoplasm. These cells are placental alkaline phosphatase (PLAP) negative and are usually not considered to represent intratubular germ cell neoplasia (ITGCN). A recent case report found p53 and proliferating cell nuclear antigen (PCNA) positivity in such cells and equated these PLAP-negative cells with ITGCN. Because the proto-oncogene c-kit is also a marker of ITGCN, immunohistochemical tests for c-kit and PLAP were performed on 28 testes adjacent to prepubertal GCT in children aged 2 to 45 months. Additional slides from testes not associated with GCT from 18 preterm infants and children ages 19 weeks to 7 years were also tested. An adult testis with seminoma and ITGCN served as a positive control. PCNA, PLAP, and p53 were tested on available slides. No intratubular germ cells adjacent to GCT in prepubertal children were positive for PLAP or c-kit; five of seven were positive for PCNA; p53 was present in the two examined. These results indicate that germ cells adjacent to infantile GCT are proliferative but not neoplastic and offer additional evidence that intratubular germ cells and GCT in prepubertal boys are different from those of adolescents and adults.

Fetal tissue derived from spontaneous pregnancy losses is insufficient for human transplantation.

OBJECTIVE: To determine if sufficient fetal tissue with desirable transplant characteristics can be obtained from spontaneous abortions. METHODS: A survey of fetal tissues collected from newly diagnosed spontaneous pregnancy losses from three Indianapolis hospitals was conducted from December 1992 to September 1993. Forty-nine of 356 mothers (13.8%) with spontaneous abortions or ectopic pregnancies consented to the evaluation of their products of conception by gross and microscopic pathologic examination, bacterial culture, cytogenetic analysis, cell culture, and maternal serologic tests. RESULTS: Forty-nine pregnancies (gestational age range 5-30 weeks) provided four identifiable embryos, 12 second-trimester fetuses, and one third-trimester fetus. Nine samples (18.4%) were of excellent or good quality on pathologic grading. Twenty-five of 38 samples tested (66%) grew pathogenic bacteria. Maternal serologic tests were negative for antibodies to human immunodeficiency virus, human T-cell lymphotropic virus, syphilis, and hepatitis B in all cases. One of 43 sera was reactive for hepatitis C, and 33 (77%) were positive for cytomegalovirus. Cytogenetic abnormalities were found in 25% of cultured samples. Five fetal brain samples had cell viabilities of 50% or more. Few viable fetal hepatocytes were found. Only two fetal brain samples (4.1%) were potential candidates for human transplantation. CONCLUSION: Spontaneous pregnancy losses yield minimal usable tissue for human transplantation because of a lack of embryonic or fetal tissues, delayed collection, decomposition, genetic abnormality, and bacterial contamination.

Ovarian neoplasms in children.

OBJECTIVE: To review the clinical presentation, treatment, and outcome in a series of children with ovarian neoplasms. DESIGN: A retrospective review of the medical records in a case series of 29 girls with ovarian neoplasms. The length of follow-up ranged from 6 months to 7 1/2 years and averaged 3.0 years in the girls with malignant tumors. SETTING: The patients were treated at a large referral children's hospital. PATIENTS: Twenty-nine girls with ovarian neoplasms were treated from 1976 to 1992. The average age of the patients was 10 years and ranged from 2 to 16 years. MAIN OUTCOME MEASURES: The principal outcomes examined were mortality and surgical morbidity. RESULTS: The most common presenting symptoms for these ovarian tumors in pediatric patients included chronic abdominal pain, an abdominal mass, or distention. Three girls presented with precocious puberty or hirsutism. In 27 cases, the tumor was a primary ovarian lesion. In two patients, the ovarian mass was the presenting finding for a stage IV non-Hodgkin's lymphoma. Seventeen tumors were benign and 12 were malignant. Tumors originating from the germ-cell line predominated (n = 17). Seven of the 10 ovarian malignant neoplasms were stage I at the time of diagnosis. All but one of the girls with malignant tumors received either adjunctive radiation therapy or multiple-agent chemotherapy. Two girls with sex cord/stromal cell tumors who presented with stage I disease ultimately developed widespread metastases. Both girls with large epithelial tumors survived. All of the girls with benign tumors and seven (70%) of 10 with malignant lesions survived. CONCLUSION: Ovarian tumors are unusual lesions in the pediatric population. Unlike in adults, such neoplasms generally originate from the germ-cell line. Whereas most ovarian tumors in girls are benign, some children have malignant tumors that are very aggressive and do not respond well to adjuvant therapy. In particular, malignant sex cord/stromal cell tumors, even when they present at an early stage, may behave unpredictably.

Anterior pericardial tracheoplasty for congenital tracheal stenosis: intermediate to long-term outcomes.

BACKGROUND: Although several techniques for the treatment of long-segment stenosis of the trachea have been reported, including slide tracheoplasty, rib grafting, and use of a pericardial patch, the optimal repair remains controversial because of a lack of midterm to long-term follow-up data. METHODS: To assess the intermediate and long-term outcomes of patients having repair with anterior pericardial tracheoplasty, we reviewed case histories of 12 patients (1984 to present). The median age was 6.7 months (range, 1 to 98 months), and the median weight was 6.0 kg (range, 0.97 to 42 kg). All patients underwent anterior pericardial tracheoplasty through a median sternotomy during partial normothermic cardiopulmonary bypass. An average of 13 tracheal rings (range, five to 23) were divided anteriorly, and a patch of fresh autologous pericardium was used to enlarge the trachea by 1.5 times the predicted diameter for patient age and weight. RESULTS: There was one hospital death, and all but 2 patients are long-term survivors. All but 1 current survivor remain asymptomatic, with no bronchoscopic evidence of airway obstruction or granulation on the pericardial patch. All survivors examined have normal tracheal growth and development, with a median follow-up of 5.5 years (range, 1 to 11 years). CONCLUSIONS: Anterior pericardial tracheoplasty for congenital tracheal stenosis provides excellent results at intermediate to long-term follow-up.

Urethral polyp presenting as interlabial mass in young girls.

We describe two young girls who presented with an interlabial mass. Histologic examination of each excised mass revealed a benign urethral polyp covered with transitional and squamous epithelium. Urethral polyps should be included in the differential diagnosis of an interlabial mass in young female patients.

Persistence of Barrett's esophagus in children after antireflux surgery: influence on follow-up care.

Adenocarcinoma arising in Barrett's esophagus has recently been described in two children aged 11 and 14 years. The long-term follow-up of Barrett's esophagus in children is not well described. We evaluated 16 cases of Barrett's esophagus in children treated at this institution during the last 16 years. Ages ranged from 1.2 to 16 years (mean, 10.3 years). There were 11 boys and 5 girls. Barrett's esophagus was documented by endoscopy in 14 instances and at autopsy in 2 patients with secretory diarrhea and tetralogy of Fallot who died of sepsis. Two children had cancer (neuroblastoma, leukemia) and died of their malignant disease. Five patients had cerebral palsy, 1 esophageal atresia, 1 Fanconi's anemia, and 5 were otherwise normal children. Six were treated medically. Eight patients underwent Nissen fundoplication for complications of gastroesophageal reflux (GER). Five patients were available for follow-up endoscopy (mean, 2 years; range, 1.1 to 5.4 years). Endoscopy was performed on a yearly basis, obtaining biopsy specimens from multiple levels of the esophagus. Four children had satisfactory clinical response to an antireflux procedure including the resolution of a stricture in one case. However, in all 5 cases persistent metaplastic epithelium was documented and showed no evidence of regression. Although there has been speculation that Barrett's esophagus in children may be more likely to revert to normal squamous epithelium than in the adult, there has been only one case of regression in 180 cases of Barrett's esophagus occurring in children described in 37 reports in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue distribution of ethosuximide and clobazam in a seizure related fatality.

The case of a six-year-old male who died in a hospital while receiving several anticonvulsant drugs is described. Phenytoin, desmethyldiazepam, clobazam (an experimental 1,5 benzodiazepine), and desmethylclobazam were quantitated in serum, liver, and brain tissue by high performance liquid chromatography. Ethosuximide was quantitated by gas chromatography. To our knowledge, this is one of few reports describing tissue concentrations of ethosuximide collected at autopsy and the first report of clobazam/desmethylclobazam tissue distribution in man.

Strangulation of the umbilical cord by amniotic bands: report of 6 cases and literature review.

The amniotic band syndrome is the triad of amnion-denuded placenta; fetal attachment to or entanglement by amniotic remnants; and fetal deformation, malformation, or disruption. Theories of pathogenesis and etiology of the syndrome are discussed. Amniotic bands occur in 1 of every 5000-15,000 births and are demonstrable in 1-2% of malformed infants. Nearly 10% of cases include umbilical cord strangulation. Six cases of umbilical cord strangulation by amniotic bands are presented, and 57 previously reported cases are reviewed. Two of the 63 were liveborn and 61 were stillborn, 3 of whom died intrapartum. Thirty had associated fetal abnormalities. Five were from multiple gestations. Outcome of the co-twin was determined by its presence within the same amniotic sac. Four fetuses beyond 28 weeks had short cords and were the only malformed fetuses in this age group. The earlier in gestation that amniotic bands form, the greater the likelihood of associated fetal abnormalities. All but 2 of 28 less than 32 weeks and only 4 of 35 greater than 32 weeks were malformed. A marked male predominance was noted in the former group, perhaps because the larger size and/or more vigorous movements of male fetuses promote early amnion rupture.

Single umbilical artery. A statistical analysis of 237 autopsy cases and review of the literature.

Two hundred thirty-seven autopsy cases of SUA and 1,242 unselected perinatal autopsies from military hospitals were reviewed and statistically analyzed. Results were correlated with those found in a comprehensive literature review. Incidence: The incidence of SUA in prospective deliveries is about 1%. Incidence is related to the portion of the umbilical cord examined, the method of cord examination (gross or microscopic), and to the race of the population base. The incidence of SUA in autopsy series is about twice the incidence in prospective series. SUA has a much higher incidence amont malformed, stillborn, or spontaneous abortuses than among apparently normal, liveborn, or induced abortuses. The incidence of SUA is less among very early embryos than among newborns because of the likelihood that SUA results from secondary atrophy of a preexisting normally formed second artery. As gestation proceeds, more cases will have become manifest to increase the incidence of SUA. There is no evidence of a familial tendency for SUA. SUA occurs slightly more frequently in females than in males, although there is a greater tendency for males with SUA to be malformed. The prognosis for SUA males is worse than for SUA females but no worse than that for male infants, in general. There is no relationship between the incidence of SUA and the month of the mother's last menstrual period. SUA and multiple births: The incidence of twins among SUA infants is at least three times greater than the overall incidence of twins. SUA occurs three to four times more frequently among twins than among Singletons. Although twin infants are subject to twice the expected incidence of malformations, twin SUA infants have no greater incidence of associated malformations than SUA singletons. Most SUA twins are discordant for the anomaly with SUA occurring in the smaller twin. The increased incidence of SUA among twin infants is not due to a greater incidence among monozygotic twins, since there is little difference from the usual proportion of monozygotic and dizygotic twins among twins with SUA. Mortality: In prospective series the mean perinatal mortality is about 20.0%. Approximately two-thirds of the perinatal deaths are stillborn and one-third are liveborn; and of the stillborn SUA infants, approximately three-quarters die antepartum and one-quarter die intrapartum. Mortality of SUA infants is related to associated fetal and placental malformations, prematurity and low birth weight, and intrauterine growth retardation. Although associated malformations are the primary cause of the high perinatal mortality, even nonmalformed SUA infants have an increased mortality rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Thrombosis of the umbilical cord: analysis of 52 cases and literature review.

Fifty-two cases of umbilical cord thrombosis from 3 patients populations are analyzed and compared with 68 cases from the literature. The incidence of cord thrombosis is approximately 1/1300 deliveries, 1/1000 perinatal autopsies, and 1/250 high-risk gestations. There is a slight male predominance. Umbilical vein thrombosis occurs more frequently than thrombosis of one or both umbilical arteries, but poor fetal outcome is more likely with arterial thrombosis. The mechanism of fetal death when only one umbilical artery is thrombosed is illustrated and discussed. The strong association between cord thrombosis and perinatal morbidity and mortality is not noted among prospective cases but, when present, is related to additional umbilical cord abnormalities, obstetrical complications, or systemic fetal conditions that are the likely cause of both the thrombosis and the poor fetal outcome. The pathogenetic relationship between cord thrombosis and these associated conditions is discussed, and it is concluded that cord thrombosis is a marker of both the severity of these conditions and the likelihood of poor fetal outcome.