Placental histology related to fetal brain sonography.

BACKGROUND: Chronic hypoxia and inflammatory processes can induce placental disturbances that may indirectly lead to perinatal brain injury. OBJECTIVE: To study histological features of the placenta in relation to echogenicity changes in the periventricular white matter, ventricular system and basal ganglia/thalami of the fetal brain. DESIGN: Prospective study of 77 fetuses between 26 and 34 weeks gestational age with their placentas. The pregnancies were complicated by hypertensive disorders (n=42) or preterm labour (n=35). RESULTS: Of the placentas 79% showed uteroplacental hypoperfusion, inflammation or a combination. Transvaginal ultrasound examination of the brain revealed echogenicity changes in 73% of the fetuses (44 mild, 29 moderate). Moderate brain echogenicity changes (periventricular echodensity (PVE) grade IB: increased echogenicity brighter than choroid plexus, intraventricular echodensity (IVE) grade II and III: echodensity filling ventricle respectively <50% and ≥50%; basal ganglia/thalamic echodensity (BGTE): locally increased echogenicity within basal ganglia/thalami) were equally distributed over cases with uteroplacental hypoperfusion and inflammatory features in the placenta. PVE grade IB was always associated with placental pathology. The sensitivity and negative predictive value of placental pathology for moderate echogenicity changes were high (0.91 and 0.88, respectively), while the specificity and positive predictive value were low (0.27 and 0.34, respectively). CONCLUSIONS: Normal placental histology predicted no or mild echogenicity changes, supporting the view that the latter are physiological. Placental pathology was always present in cases with grade IB PVE, presumed to represent mild or early forms of white matter injury. Both uteroplacental hypoperfusion and inflammatory features were seen in placentas from pregnancies with hypertensive disorders.

Hepatoblastoma--evolution of management and outcome and significance of histology of the resected tumor. A 31-year experience with 40 cases.

BACKGROUND/PURPOSE: The aim of this study was to retrospectively evaluate and compare the clinical features, treatment strategy, pathology, and outcome of all patients with hepatoblastoma treated at an African hospital over a 31-year period (1970 to 2001). METHODS: Forty patients with hepatoblastoma were divided into 3 groups according to the treatment given. Group I (1970 to 1983, 14 patients) had no protocol therapy; group II (1984 to 1988, 6 patients) received protocol treatment according to Children's Study Group (CCSG) guidelines; group III (1989 to 2001, 20 patients) received SIOPEL protocol therapy. All available clinical, surgical, radiologic, and pathologic data were reviewed and analyzed. RESULTS: Overall patient survival was as follows: group I, 14%; group II, 50%, and group III, 80%. Deaths in group II were caused by chemotherapy-induced immunosuppression only. Prognostic data for group III showed that all tumor-related deaths could be predicted by identifying multifocal disseminated growth patterns (P =.001) or vascular invasion (P =.001) in resected tumors. Of the 40 diagnostic tumor biopsies performed, 2 significant complications (1 death, 1 intraperitoneal tumor seeding) occurred. Histologic criteria evaluating these biopsies were not predictive of overall survival. CONCLUSIONS: The introduction of protocol therapy has resulted in a marked improvement in survival. Immunosuppression-related sepsis in our setting resulted in unacceptable mortality in patients treated according to CCSG guidelines. A diagnostic biopsy in hepatoblastoma is of value but not without complications. Preoperative chemotherapy followed by complete surgical excision according to International Society of Paediatric Oncology guidelines yields excellent results with a current survival rate of 80%.

Unusual variations of gastrointestinal smooth muscle abnormalities associated with chronic intestinal pseudo-obstruction.

The clinicopathological spectrum of gastrointestinal (GI) smooth-muscle abnormalities associated with chronic intestinal pseudo-obstruction (CIPO) includes numerous heterogeneous conditions that are often ill-defined and poorly understood. Primary GI smooth-muscle abnormalities include familial and sporadic forms. Secondary involvement of GI smooth-muscle may result from associated GI and systemic conditions, but is less frequent than in adults. This study documents the clinicopathological findings observed in 12 South African patients with unusual forms of visceral smooth-muscle abnormalities not conforming to the diagnostic criteria of known primary visceral myopathies at the Tygerberg and Red Cross Childrens' Hospitals over a 14-year period (July 1985 through January 1999). Congenital muscle defects occurred in 5 patients where layers of bowel-wall muscle were absent or attenuated. Idiopathic fibrosis and ultrastructural features of perinuclear and mitochondrial vacuolisation were noted in 2 patients. A 21-year-old female with long-standing pseudo-obstruction demonstrated diminished immunohistochemical expression of enteric alpha-smooth-muscle actin without associated muscular degeneration or fibrosis. A secondary complication of dermatomyositis (bowel perforation) occurred twice in 1 patient. In 3 further patients (1 each with anorectal malformation, long-segment Hirschsprung's disease, and intestinal neuronal dysplasia), muscle fibrosis appeared during progression of the pre-existing disease. Visceral myopathies are poorly understood conditions that may present with CIPO. Unusual variations occur that do not conform to the usual recognised histological patterns. Secondary involvement may also be more common than anticipated in children. The challenge to further understanding these uncommon conditions lies in timely diagnosis and identification of early, subtle signs. Optimal and extensive application of various diagnostic modalities, including the development of new diagnostic tools, is of considerable importance in identifying hitherto unexplained CIPO due to GI smooth-muscle abnormalities.

Intestinal ulceration, obstruction, and haemorrhage in congenital syphilis.

Intestinal obstruction and bleeding are uncommon complications of congenital syphilis (CS). A VDRL-positive infant developed incomplete intestinal obstruction and rectal bleeding. Despite conservative management, his symptoms continued. At laparotomy, terminal ileal inflammation and stenosis were demonstrated. He underwent ileal resection and primary end-to-end anastomosis with resolution of his symptoms. Histopathological examination demonstrated heavy plasmacytic infiltration of the lamina propria and submucosa with ulceration of the mucosa, consistent with syphilitic ileitis. This report documents for the first time bleeding from ileal ulcers associated with intestinal obstruction in CS and highlights an unusual presentation of the disease.

Pluripotential melanoblastoma, a unifying concept on malignancies arising in congenital melanocytic nevi: report of two cases.

Congenital melanocytic nevi are benign lesions present at birth and considered to be caused by a maldevelopment of the neural crest. The malignant potential of the congenital melanocytic nevi have been extensively addressed by several authors, and malignant melanoma is the most frequent neoplasm arising in these lesions. The present report describes two patients with congenital melanocytic nevi in which malignant melanoma with undifferentiated areas showing rhabdomyoblastic differentiation developed. The findings suggest that these mixed neoplasms may be recapitulating the differentiation potential of the ectomesenchyme-neural crest cells. We advocate the term "melanoblastoma" when referring to them.

Malignant ectomesenchymoma in childhood.

Five childhood malignant ectomesenchymomas are reported from three centers in three countries. The children were all younger than 3 years (four less than 12 months), four were boys, and four tumors were sited in the pelvis or external genitalia. All tumors had distinctive light microscopic features of rhabdomyosarcoma and three also demonstrated small numbers of included neuronal cells. Immunohistochemical studies and transmission electron microscopy revealed the additional presence of neurogenic components in the remaining two patients. An additional epithelial component was found by immunohistochemistry in one tumor, which suggests a pluripotential origin that still requires karyotypic investigation. Aggressive chemotherapy and adequate surgical excision have thus far been effective in providing disease-free follow-up for periods of 7 to 50 months. It is implied that because the biological behavior and morphology closely resemble those of rhabdomyosarcoma and because the neurogenic component is often inconspicuous, many malignant ectomesenchymomas may be misdiagnosed as rhabdomyosarcomas.

Castleman's disease in children: the experience of a children's hospital in Africa.

As the incidence of childhood Castleman's disease (CD) is reported to be rare in Western communities, the recent occurrence of three cases in non-HIV infected prepubertal children stimulated a 10-year (1983-1993) retrospective investigation into the conditions at a children's hospital that serves a predominantly developing community. Retrospective histologic examination revealed six cases of CD among children 3-11 years of age and another five probable cases having histological features of CD without adequate clinical and laboratory data. Three CD cases were associated with malignancy (Kaposi's sarcoma in two and a gastric B cell lymphoma in the other). Two CD cases were plasma cell type, one hyaline vascular, and three intermediate. One child with recurrent plasma cell-type features in a groin node had a Kaposi's sarcoma in the thigh. The five probable cases of CD all had intermediate histological features. Four of the 11 cases being reported came from a geographic locality that provides about 3% of the laboratory's case material and these included both cases that developed Kaposi's sarcoma. All patients who developed malignancy had the plasma cell variant. As all cases have been identified in developing communities, where the disease may often be misdiagnosed as nonspecific reactive lymphadenopathy, and there is an evident association with malignancy, it is recommended that children in these areas with the plasma cell variant of CD be closely monitored for subsequent malignancy.

Ploidy analysis on Wilms' tumour touch imprints using ethidium bromide and automated image analysis integrated confocal laser scanning microscopy.

Although image analysis (IA) is increasingly being used to quantitate nuclear DNA, comparative data between fluorescence methods of IA and flow cytometry (FCM) is limited. In this study fluorescence IA was compared with FCM data in a series of Wilms' tumour touch preparations. Airdried touch imprints that had previously been Giemsa stained were restained with ethidium bromide. Confocal fluorescence images were obtained with a confocal laser scanning microscope and assessed by a fully automated IA package. Data was collected from 400 nuclei per imprint. The resulting DNA histograms were analysed and ploidy status and DNA indices determined using standard criteria. Results were compared with those derived from FCM analysis of nuclear suspensions. Ten of twelve tumours were concordant by both techniques. However in two cases assessed as diploid by FCM, IA identified aneuploidy. Excellent correlation between DNA indices as assessed by both techniques was observed (r = 0.987). In the three cases for which both unstained and Giemsa stained touch imprints were available for IA, the histogram configurations did not differ significantly. Fluorescence IA is an accurate and sensitive technique for DNA quantitation, which appears at least comparable to FCM assessment and which has a number of important advantages.

A histological grading system for the evaluation of co-existing NID with Hirschsprung's disease.

The significance of dysplastic features in the surgical pullthrough segment of bowel in patients with Hirschsprung's disease (HD) has not yet been clarified. The aim of this study was to evaluate prospectively the ganglionated proximal bowel in 26 patients with HD (January 1988 through January 1991). The significance of dysplastic features and their influence on post operative outcome were evaluated by means of a newly devised histological scoring system based on the morphological features. Functional outcome was assessed clinically at follow-up interview. Comparison was with control specimens from 22 patients undergoing unrelated bowel surgery and a further 5 patients with neuronal intestinal dysplasia (NID). Results indicated a wide spectrum of histologically identified dysplastic features in patients with NID, the ganglionated bowel of HD and controls. Although individual abnormal features were noted in the control group, significant degrees of dysplasia were absent. The overall degree of dysplasia was less striking than that observed in NID and in the 5 patients in whom NID co-existed with HD. Dysplasia of the ENS in residual bowel could be correlated with postoperative dysfunction in 4 out of 5 patients (80%) with HD and features of co-existing NID. In addition, milder symptoms were noted in 50% of patients having a borderline score (5-6/12). This study emphasizes the relationship between clinical obstructive symptoms and a high degree of dysplasia within the ENS. A histological grading system is of value in evaluating the spectrum of abnormal findings and prospectively identifying those with functional significance in patients with NID co-existing with HD.

Morphologic features of the myopathy associated with chronic renal failure.

Our previous studies indicate that impaired function of skeletal muscle limits the exercise tolerance of patients with end-stage renal failure who are either maintained on dialysis or undergo renal transplantation. To study the morphology of the condition, muscle biopsies were performed on eight patients with renal failure-associated myopathy. Control samples were taken from seven healthy athletes undergoing knee surgery and from five otherwise healthy but untrained subjects. Tissues were examined by routine light and transmission electron microscopy. Histochemical staining of frozen sections for myosin adenosine triphosphatase and quantitative computer-assisted morphometry of the fiber type and size was performed. The mean (+/- SD) size for type I fibers in patients was 61.2 +/- 11.8 microns, while type II fibers measured 46.7 +/- 11.4 microns. The mean percentage of type II fibers was 67% +/- 12%. These values are within the normal population range and were not different from controls. Significant changes were found on light microscopy of patient samples. These included fiber splitting, internalized nuclei, nuclear knots, moth-eaten fibers, fiber degeneration and regeneration, increased content of lipid droplets, and fiber-type grouping. Electron microscopy showed a large variety of nonspecific abnormalities, including mitochondrial changes, Z-band degeneration, myofilament loss, and accumulation of intracellular glycogen. Ten of 12 control subjects showed no such changes; minor abnormalities were noted on both light and electron microscopy in the remaining two subjects. Muscle oxidative capacity (19.5 +/- 5.1 microL O2/min) for patients with end-stage renal failure was not different from values for those who had undergone renal transplantation, but was lower than values found in trained athletes.(ABSTRACT TRUNCATED AT 250 WORDS)

Degenerative leiomyopathy in African children: a review of current perspectives.

The syndrome of degenerative leiomyopathy causing intestinal obstruction clinically manifests in young indigenous African children as massive megacolon without aganglionosis. Eighteen children have been seen over a 16 year period from a localized geographic area. There were 10 males and 8 females having a mean age of 9.5 years at presentation and a mean duration of symptoms of 4.3 years. The youngest was 6 months old. All had progressive abdominal distension and infrequent stooling but 11 had intermittent diarrhoea and 9 had colicky abdominal pain. Gross gaseous distension of the large bowel with extension into small intestine occurred in 9 and this extended into stomach and oesophagus in 4. Biopsy of the dilated, thin walled bowel showed smooth muscle degeneration and necrosis with replacement by fibrous tissue. Neuronal cells of Auerbach's plexus tend to be displaced into the circular layer of smooth muscle with mild inflammatory changes. Some small arteries show medial fibrosis with subintimal fibroblastic proliferation. Acetylcholinesterase and immunohistochemical staining with neural and muscle markers are within normal limits. One child died while 14 have been maintained on prokinetic agents, low residue diets, laxatives and enemas. Nine children have required surgical intervention of whom 4 had volvulus and 3 adhesive bowel obstruction. Degenerative leiomyopathy is a distinctive entity with classical clinical and histological features. The aetiology is still obscure.

Acquired aganglionosis following surgery for Hirschsprung's disease: a report of five cases during a 33-year experience with pull-through procedures.

Acquired Hirschsprung's disease is a rare and controversial form of colonic aganglionosis. Little is known about its aetiology and pathogenesis. We report five cases encountered amongst 173 long-term follow-up patients treated for classical Hirschsprung's disease between 1957 and 1990 at the Red Cross Children's Hospital, Cape Town, and review the current literature. The clinical and pathological findings of the cases have been studied to explore possible aetiological mechanisms. Our cases, like most of those previously reported, developed obstructive symptoms and acquired aganglionosis in pulled-through bowel which had been previously confirmed as ganglionated. Two patients had histological evidence of hyaline fibrosis of blood vessels in the segment of bowel with acquired aganglionosis. Such fibrosis and other features attributable to regional hypoxia were not found in the other three cases. It is suggested that ischaemia with fibrosis may have a pathogenetic role in some, but not all, cases of acquired Hirschsprung's disease. A plea is made for patients developing recurrent symptoms of Hirschsprung's disease, after adequate surgical correction, to be fully studied with repeated sequential biopsies in order to gain a better understanding of the entity.

Fatal meningococcal disease in childhood: an autopsy study of 86 cases.

A retrospective study of the pathology in 86 consecutive autopsies of fatal meningococcal infection in children, performed at the Red Cross War Memorial Children's Hospital during the 19-year period from 1973 to 1991, was undertaken. The most prominent pathological changes found at autopsy were those of an overwhelming bacterial infection with evidence of disseminated intravascular coagulopathy in many organs of the body. The skin, adrenal glands and central nervous system were most commonly involved. Acute myocarditis occurred in 23 cases (27%) and was diagnosed almost exclusively histologically. In only one case was it diagnosed clinically. In addition, the nutritional status and the morphological expression of immune reactivity of our hospital population was better than expected.

Primary pulmonary tumors in childhood: a review of 31 years' experience and the literature.

Primary pulmonary tumors are infrequent in childhood, therefore an accurate diagnosis and treatment is often delayed. We review the English language literature and report the clinical and pathological features of eight tumors arising in the lungs of pre-adolescent children, accessioned between 1960 and 1991 in the pathology department of a children's hospital in South Africa. The ratio of pulmonary primary tumors to secondary neoplasms and to non-neoplastic lesions of the lung examined during this period was 1:5:60. Over the last 31 years we received three plasma cell granulomas, two pleuro-pulmonary blastomas, a mucoepidermoid carcinoma, an endobronchial fibrosarcoma, and a hemangioma. All patients presented with cough unresponsive to medical treatment. The incidence and spread of primary lung tumors in children was similar to that reported from other centers. Plasma cell granuloma is the most common primary tumor in the lungs of children. Aggressive behavior is most frequently encountered with pleuro-pulmonary blastoma and rhabdomyosarcoma, and because of their association with cystic lesions careful examination of lungs is required in such cases. Most other malignant neoplasms, such as muco-epidermoid carcinoma and primary fibrosarcoma, are usually of a low grade of malignancy. A decreasing incidence of bronchogenic carcinoma seems to be reported during the first two decades of life.

Mesenchymal hamartoma of the chest wall: a cooperative study with review of the literature.

The clinicopathologic features of three examples of mesenchymal hamartoma of the chest wall are described. The entity has been recorded under a number of names including osteochondroma, osteochondrosarcoma, benign chondroblastoma, mesenchymoma, and chondromatous hamartoma. The condition is manifest at birth or shortly thereafter with deformity of the chest wall and respiratory distress. Radiographic examination reveals a well-defined, partly calcified mass involving one or more ribs. The tumor is composed predominantly of chondroid tissue with large endothelium-lined blood spaces and immature mesenchyme with osteoclastic giant cells and osteoid. We review the literature and suggest that the lesion should be distinguished from aneurysmal bone cyst, chondroma, and other mesenchymal neoplasms. In order to avoid local recurrence the recommended treatment is complete surgical resection.

Childhood pulmonary blastoma: a pleuropulmonary variant of the adult-type pulmonary blastoma.

Two fatal childhood cases of the rare pulmonary blastoma are reported. One was associated with a congenital cystic adenomatoid malformation. Both neoplasms extended to involve visceral pleura and were entirely composed of blastemal and mesenchymal elements without recognizable neoplastic epithelial components. The mesenchymal component in both instances consisted of malignant rhabdomyoblasts, undifferentiated mesenchyme, and differentiated, apparently benign, cartilage. Review of the literature suggests that these features may be specific for the childhood forms of pulmonary blastoma. It is further suggested that pulmonary blastoma, malignant mesenchymoma of the lung, and primary pulmonary rhabdomyosarcoma may have a common pathogenetic origin.

Placentae of light for dates infants born to underweight mothers at term: a morphometric study.

Fifteen light for dates infants and their placentae were compared to 15 well-grown infants and their placentae. The former were born to thin, underweight women while the latter were born to women of normal weight. The light for dates infants were symmetrically growth retarded but not wasted at delivery and their placentae had a reduced weight, volume, chorionic surface area, percentage parenchyma and total villous surface area. The peripheral villous surface area and volume of peripheral villous trophoblast, fetal capillaries and connective tissue was also reduced in the placentae of light for dates infants, suggesting retarded placental growth in the latter half pregnancy. In contrast, the stem villous surface area and volume of stem villous trophoblast, fetal capillaries and connective tissue was similar in both groups of placentae, suggesting the same rate of growth in early pregnancy. There were no differences in the volume of fibrin or infarcts. The ratio of total villous surface area to infant weight, length and head circumference was reduced in the light for dates infants. This may restrict the materno-fetal oxygen exchange, and thereby increase the risk of fetal hypoxia during labour. It is concluded that the placentae of light for dates infants born at term to underweight women are both absolutely and relatively small with a reduced villous surface area.

Intestinal obstruction in the newborn with congenital syphilis.

Four newborn patients with congenital syphilis and intestinal obstruction are discussed in this report. In three cases, the obstruction was due to inspissated meconium, simulating the features of meconium ileus in one, meconium plug in the second, and associated with perforation of the terminal ileum in the third. An exocrine pancreatic insufficiency and a motility disturbance of the intestine due to syphilitic infection during fetal life could be the probable etiologic factor. The fourth patient had multiple ileal stenoses. Ischemia due to the prenatal syphilitic arteritis of the bowel wall can be responsible for this pathology. Attention is drawn to the association between congenital syphilis and neonatal intestinal obstruction.