Epstein-Barr virus in non-Hodgkin's lymphomas and lymphoid tissue in children.

In developed countries the majority of adolescent children show serological evidence of past Epstein-Barr virus (EBV) infection. This virus is associated with non-Hodgkin's lymphomas in immunocompromised children, but the relationship of EBV DNA to these tumors in children without documented immunodeficiency has not been investigated by the polymerase chain reaction (PCR). We used a PCR method with primers from the Bam W and Bam HI regions to study non-Hodgkin's lymphomas in children, with tonsillar tissue of age-matched children as controls for the presence of EBV DNA. Six of the 20 tonsils were positive using the Bam W primers; another four showed this DNA with Bam HI primers. EBV DNA was detected in only one tumor (a lymphoblastic lymphoma) by both primer sets. The demonstration of EBV DNA in the tonsils reflects past infections and the incidence is in accordance with that expected from serologic epidemiological studies. The absence of demonstrable EBV DNA in 19 lymphomas suggests that this virus is of little consequence in the pathogenesis of non-Hodgkin's lymphomas in children who are not known to be immunocompromised. The lymphoblastic lymphoma had a mixed cell population, and the virus was not necessarily related to the malignancy.

Myocardial failure and shock in iron poisoning.

Shock is a well-known complication of iron poisoning. Its aetiology is multifactorial with hypovolaemia due to gastrointestinal blood loss and myocardial depression due to systemic acidosis contributing to its genesis. Primary myocardial dysfunction has not been considered to play a role. Our clinical experiences and autopsy findings in three fatal cases of iron poisoning support myocardial dysfunction and damage as contributing factors to their cardiovascular collapse. The three patients, all female, were 3 1/2, 16 and 28-years-old. Onset of shock occurred at 1, 2 and 5 days post-ingestion. There was no response to vigorous fluid replacement therapy and aggressive catecholamine infusions. Central venous pressures were elevated. Microscopic examination of postmortem tissue showed myocardial damage and the presence of stainable iron. It is speculated that the myocardial depression is mediated by lipid peroxidation of myocyte organelle membranes due to iron catalysed free radical generation. The presence of myocardial dysfunction has therapeutic implications. Patients with severe iron poisoning require early and serial measurements of arterial blood pressure, central venous pressure and cardiac output. If primary myocardial dysfunction is documented then fluid replacement, inotropic support and afterload reduction should be considered.

A new autosomal recessive lethal chondrodystrophy with congenital hydrops.

Two sibs, the offspring of consanguineous parents, presented with severe short-limb dwarfism and distinct chondro-osseous, radiologic, and histologic appearance. The first sib presented at 30 wk with severe hydrops following fetal death; the second was detected by ultrasonography at 20 wk. Radiologic abnormalities included an unusual "moth-eaten" appearance of the markedly short long bones, bizzare ectopic ossification centers, and marked platyspondyly with unusual ossification centers. Marked extramedullary erythropoiesis was present in both fetuses, and chondro-osseous histology was characterized by marked disorganization of tissue with interspersed masses of cartilage, bone, and mesenchymal tissue. These sibs appear to have a distinct previously unreported autosomal recessive skeletal dysplasia, which can present as hydrops fetalis.

Demonstration of Epstein-Barr virus in immunoblastic sarcoma of B-cells arising in a child with primary immunodeficiency disease.

The subject of this investigation was an 11-month-old infant girl who presented with a pathological fracture of the right femur due to a metastasis from an abdominal immunoblastic sarcoma. Her past history included recurrent, intractable bacterial and fungal infections. Investigations of her immune status revealed low numbers of T-lymphocytes, a reversed T-helper (TH)/T-suppressor (TS) cell ratio, no response of her peripheral blood lymphocytes to pokeweed mitogen, phytohemagglutinin, concanavalin A, and Candida albicans, and an inability of her cells to react in a mixed lymphocyte culture. Serum levels of IgG, IgM, and IgA were all below normal. No thymic shadow was visible on the chest radiograph. There was no evidence of adenosine deaminase or nucleoside phosphorylase deficiencies. The tumor cells exhibited both surface IgM and IgG, and many of the cells contained large amounts of cytoplasmic IgM. Light chain specificity was restricted to lambda chain for both surface and cytoplasmic immunoglobulin. Ultrastructural study of the tumor cells revealed the presence of both intranuclear and cytoplasmic virions in roughly 1% of the tumor cells. These viral particles strongly resembled herpes viruses. DNA-hybridization studies on the neoplasm revealed the presence of 7-10 genome equivalents of Epstein-Barr virus-DNA per tumor cell.

Congenital ependymoblastoma presenting as a sacrococcygeal mass in a newborn: an immunohistochemical, light and electron microscopic study.

We describe a case of congenital ependymoblastoma presenting as a subcutaneous mass in the sacrococcygeal area of a newborn male. The tumor was composed of primitive cells disposed in compact sheets and cords and exhibiting focal ependymal differentiation. No other line of cellular differentiation was identified by either immunohistochemistry or ultrastructural study. Elevated serum alpha-fetoprotein was found, which decreased following surgical extirpation of the tumor. We propose that this tumor had its origin in the ependymal medullary vestige, similar to other sacrococcygeal ependymomas.

An autosomal dominant form of adolescent multinodular goiter.

Eighteen members of an extended pedigree have been found to have a form of euthyroid adolescent multinodular goiter. Histological examination showed multiple adenomata with areas of epithelial hyperplasia, hemorrhage, and calcification. In two subjects there were focal areas of epithelial hyperplasia reminiscent of low-grade papillary carcinoma, but capsular and vascular invasion was not found. The pattern of inheritance appeared to be autosomal dominant, with diminished penetrance in males. Although the patients were euthyroid, the likely basis for this disorder is an abnormality in thyroglobulin structure and function.

Structures mimicking sex cord-stromal tumours and gonadoblastomas in the ovaries of normal infants and children.

A chance finding of structures resembling gonadoblastomas in the ovaries of a child with lissencephaly prompted a detailed review of all ovarian histology obtained at autopsy over a 12 month period. Fifty-five stillbirths, infants and children were studied ranging from 20 weeks gestational age to 2.5 years post-natal age. In 19 infants structures mimicking gonadoblastomas and sex cord tumours with annular tubules were seen. In all but one case these structures were found in association with follicular cysts and they closely resembled the atretic follicles often seen in the stroma surrounding the follicular cysts. They differed from the atretic follicles only by virtue of their being larger. In addition, in several infants structures resembling Sertoli cell tubules or clusters of Leydig cells were found. When present, these structures always co-existed with sex cord tumours with annular tubules and gonadoblastoma-like lesions. The abnormal stromal lesions and follicular cysts were found most frequently at the stage of development when a massive 'physiological' reduction of oocytes occurs. It is suggested that the 'abnormal' structures identified in this report represent the 'first hit' of oncogenesis and could serve as the precursor of many of the sex cord-stromal tumours, and possibly germ cell neoplasms, seen in childhood.

Mucosal metaplasia and chronic inflammation in the middle ear of infants receiving intensive care in the neonatal period.

The histological findings in the middle ear cavity of 72 infants of varying gestations, birthweights, and ages are presented. All infants died after receiving ventilatory support and oxygen for longer than 14 days. In 5 infants there was no detectable histological abnormality. In the remainder, a wide range of lesions was seen including glandular metaplasia, retained squamous debris, squamous polyps, otitis media, and destruction of ossicles. None of the cases of otitis media was diagnosed before necropsy; all were associated with pneumonia. No single specific infectious agent predominated. Several factors could contribute to the spectrum of lesions, and these include persistent amniotic squamous debris, infection, and the effects of oxygen and a nasal airway. The possible implications of these findings are discussed, and it is argued that similar changes of lesser severity could be present in survivors in whom otitis media and conduction hearing defects could be expected.

Adenocarcinoma of the appendix.

The experience in Hamilton, Ontario, with adenocarcinoma of the appendix, between 1974 and 1980, is reviewed and the findings are compared with those of a previous report from Hamilton. There were seven patients (five men and two women) in the current series. The average age was 55.6 years. The unusual presenting signs and symptoms of this tumour are noted; the diagnosis is rarely made preoperatively. This tumor often cannot be distinguished from cecal or ileal malignant tumours. Detailed histologic examination of all specimens is essential to identify epithelial types and to plan treatment. While appendectomy alone may suffice for tumours confined to the appendiceal mucosa, radical right hemicolectomy is still the standard therapy. The authors' study shows no improvement in preoperative diagnosis, or in prognosis, over the earlier report. The authors recommend (a) that this condition be considered in the diagnosis of any appendiceal mass that is not obviously inflammatory, and (b) the frequent use of frozen-section examination to confirm the diagnosis.

Placental involvement in congenital neuroblastoma.

We describe two cases of congenital neuroblastoma involving the placenta and review previously reported cases. The placentae in congenital neuroblastoma have a bulky, hydropic appearance, and contain tumour cells which are confined to the fetal circulation. The tumour emboli are not macroscopically identifiable. Pathophysiological mechanisms of placental involvement by fetal and maternal malignancies are considered. The rarity of this lesion may be artefactual, and may result from failure to examine grossly enlarged placentae in cases of stillbirth and hydrops fetalis. Congenital malignancy must be considered in the differential diagnosis of an abnormally large placenta.

Adriamycin cardiotoxicity: report of an unusual case with features resembling endomyocardial fibrosis.

We report on a case of adriamycin cardiotoxicity occurring in a five-year-old boy treated for rhabdomyosarcoma. In addition to the usual features of myofibrillary degeneration associated with adriamycin, extreme endocardial fibrosis and mural thrombosis affecting the apical segments of both ventricles but particularly the left ventricle was seen at necropsy. The changes resembled classical endomyocardial fibrosis.

Ultrasound appearances of placental chorioangioma.

The ultrasound appearance of placental chorioangioma is described. The deleterious effects of this tumor on the mother and fetus are reviewed.

Bronchopulmonary dysplasia. A radiologic-pathologic correlation.

In 26 deaths from the neonatal unit with a histologic diagnosis of bronchopulmonary dysplasia (BPD), the histologic stage was compared to the radiologic stage according to the criteria described by Northway and Rosan. In 18 patients (69%), the histologic stage corresponded exactly to the radiologic stage. In the remaining eight patients (31%), there was a difference of one stage. If the 14 cases of Stages I and II were taken together there would be a discrepancy of one stage between the histologic and radiologic stages in 50%. However, with Stages III and IV the discrepancy was only 8.3%. There appears to be better correlation as the severity of BPD increases.

Benign oesophageal papillomatosis. A case report with a review of the literature.

An 18-year-old boy presented with a four-year history of dysphagia which had been treated repeatedly by endoscopic removal of papillomata of the oesophagus. Eventually, due to increasing dysphagia and repeated recurrences of the papillomata, resection of the affected lower third of the oesophagus was deemed necessary. The resected segment of the oesophagus was carpeted with numerous benign squamous papillomata. The clinical features, radiographic appearances, and pathology of this extremely rare tumour are presented. Only two acceptable cases of oesophageal papillomata can be found in the literature, making this the third case, and apparently the only one with multiple lesions.

Polypoidal organization of aspirated amniotic squamous debris(amnion nodosum) in middle-ear cavity of newborn infants.

The development of polypoidal structures, derived from organization of amniotic squamous debris, in the middle-ear cavity of 3 infants is described. The lesions mimicked the development of amnion nodosum lesions of the placenta and were attached to either the tympanic membrane or the head of the stapes. They were accompained by atypical metaplastic changes in the middle-ear epithelium. While the clinical significance of the structural changes is uncertain, they strengthen the case for histopathological examination of the middle ear in infant necropsies.

Myocardial changes in immature infants requiring prolonged ventilation.

Fourteen infants who had required prolonged ventilation with high concentrations of oxygen for 14 days or more, were studied at necropsy. 11 infants of immature gestation at birth had gross cardiac hypertrophy, defined as a heart weight greater than 2 SD above the mean for their age. No congenital malformation of valves or septum was found, and in the 7 youngest infants with hypertrophy, the ductus arteriosus was anatomically patent. 3 of these 7 infants had an accompanying nurmur. All 11 infants had severe bronchopulmonary dysplasia. The cardiac hypertrophy affected both ventricles and septum in an irregular fashion and was associated with areas of necrosis, progressing to coarse fibroelastotic scars. The intramural vessels showed marked intimal thickening but the main coronary vessels were normal. The 2 youngest infants with cardiac hypertrophy showed the presence of intravascular and endocardial platelet thrombi. In the 3 infants without cardiac hypertrophy less severe zones of necrosis and scarring were present, and only occasional bundles of hypertrophied muscle fibres were seen. In an attempt to understand these hitherto undescribed lesions, a group of 50 fresh stillbirths and 50 first-week neonatal deaths of comparable gestational age were studied. In 19 of these infants foci of myocardial fibre necrosis were present. It is suggested that the lesions in the older infants represent a more advanced and continuing stage of that seen in the younger infants, and that the foci of necrosis are the result of continuing hypoxia and related problems to a failing coronary circulation. The possibility of myocardial damage represents a serious hazard to the successful therapy of the immature asphyxiated infants.

Follicular ovarian cysts in stillbirths and neonates.

A review of the histology of 332 ovaries from stillbirths and neonatal deaths within the first 28 days of life showed that follicular cysts, lined by granulosa epithelium and having a diameter greater than 1 mm on a microscopical section, were present in 113 infants. In 48 cases multiple cysts were present, while in 65 only a single cyst satisfying the criteria was found. There was an excess number of infants of low birthweight score among those with multiple cysts and the results were highly significant. Cysts, whether single or multiple in distribution, were commoner with increasing gestation, and possibly occurred more commonly in the infants of diabetic mothers and in infants where pregnancy had been complicated by rhesus isoimmunization. The nature of the changes seen in the granulosa lining and theca internal layer surrounding the cysts suggested that these cysts were not some degenerative phenomenon but occured in response to stimulation. It is suggested that homologous changes may occur in the testis of the dysmature male. The possible significance of these findings with regard to hormonal imbalance in the growth-retarded infant is considered, and the need for closer attention to endocrine function in these infants stressed.