Johanson-Blizzard syndrome: clinical and pathological findings in 2 sibs.

Here we report on 2 sibs with the Johanson-Blizzard syndrome (JBS). The first child died in the neonatal period, the autopsy showing presence of pancreatic ducts and islets surrounded by connective tissue and a total absence of acini. Morphologic changes suggested dysplasia leading to developmental failure, but early acinar destruction could not be ruled out. The second child had a constellation of abnormalities consistent with JBS, was managed surgically, and is maintained on replacement for his pancreatic enzyme and thyroid hypofunction. At 10 years, he is in a school for the hearing-impaired and is performing appropriately for his age.

Subdural hematoma following open-heart operations.

Six patients who died following open-heart operations were found at postmortem examination to have acute subdural hematomas. On the basis of the clinical and postmortem findings, two factors in the pathogenesis of the hemorrhage are postulated. In the presence of intraoperative heparin administration, significant hematoma formation may result from damage to the bridging dural veins from minor, inadvertent head trauma or alterations in cerebral volume from fluid shifts. Manipulation of the head in patients who have been given heparin should be undertaken with extreme care, particularly in infants. In any patient with neurological dysfunction who has also had an open-heart operation, the possibility of an expanding subdural hematoma must be considered.

Unusual arteritis causing myocardial infarction in a child.

A 5-year-old girl presented with a diffuse inflammatory disease that consisted of fever, lymphadenopathy, splenomegaly, and anterior uveitis. A chest x-ray film indicated an apparently nodular infiltrate. Her condition deteriorated abruptly, and she died of acute myocardial infarction. Autopsy revealed an extensive vasculitis that involved the aorta, pulmonary arteries, and coronary vessels. An aneurysm of the left coronary artery was noted. We present and discuss this case as an unusual arteritis in childhood, closely resembling Takayasu's disease. The presence of extensive erythrophagocytosis in sinus histiocytes hinted at a viral or immunologic origin for this child's disease.

Dysplastic cardiac development presenting as cardiomyopathy.

Multiple manifestations of disordered or arrested cardiac muscle development are reported in a 14-year-old boy with clinical evidence of heart disease. These include persistent noncommunicating intramyocardial sinusoids, anomalous right ventricular muscle bands, muscular deficiency of ventricular septum, and papillary muscle underdevelopment. To our knowledge, this complex of findings has not been previously described.

Leiomyoma of the tongue presenting as congenital airway obstruction.

Leiomyoma is a benign tumor of smooth muscle origin that is most commonly found in the uterus, gastrointestinal tract, and skin. Intraoral leiomyomas are rare, usually asymptomatic, and, most often present in the fifth decade of life. A review of the literature since 1884 yielded only 125 cases, including 23 of the tongue. We report the first case of a congenital leiomyoma of the tongue presenting with airway obstruction. A 6-day-old female infant, intubated since birth for respiratory distress, was evaluated for an obstructing oropharyngeal mass. The tumor was pedunculated, mucosa-covered, and localized to the posterior tongue. The mass was completely excised using a CO2 laser. There has been no recurrence in 1 year of follow-up.

Nesidiodysplasia and nesidioblastosis of infancy: ultrastructural and immunohistochemical analysis of islet cell alterations with and without associated hyperinsulinaemic hypoglycaemia.

The pancreata of hyperinsulinaemic, hypoglycaemic infants, having the anatomic anomalies characterised as "nesidioblastosis', were compared with age matched control infants by light microscopy, and electron microscopy. While the hyperinsulinaemic infants showed an apparent increase in total endocrine volume compared with control infants, the light microscopic alterations of topographic maldistribution of endocrine cells, irregularly defined islets and intermingling of endocrine with exocrine elements were common to both hypoglycaemic and control groups. In at least one control case, the total endocrine cell volume was comparable to that seen in hypoglycaemic infants and was not associated with endocrine dysfunction. The ratios of insulin: somatostatin: glucagon cells in hypoglycaemic infants were similar to those of control infants. The results of both immunohistochemistry and electron microscopy gave strong indications of endocrine cells containing more than one immunoreactive peptide and heterogenous granule populations respectively. Ultrastructurally, "composite' cells with features of both exocrine and endocrine differentiation were found with some frequency in two hypoglycaemic infants. These findings are discussed in the light of current notions of gastroentero-pancreatic endocrine system development. We conclude that "nesidioblastosis' as currently defined is not the anatomic substratum of infantile hyperinsulaemic hypoglycaemia. We propose the term "nesidiodysplasia' to encompass the apparently increased and possibly maldistributed and/or malregulated endocrine cells associated with the clinical manifestations of hyperinsulinaemia. The precise relationship between the presumed anatomic abnormalities and abnormal insulin secretion remains to be clarified by further investigations.

Congenital posthemorrhagic hydrocephalus: report of a case.

A newborn infant with hydrocephalus was found to have residua of subependymal-intraventricular hemorrhage and associated obliterative arachnoiditis. This process is well known in the postnatal period but not as an in utero event. The present article documents antenatal intraventricular hemorrhage as a cause of hydrocephalus.

Electron microscopy of adipose tissue tumors: comparative features of hibernomas, myxoid and pleomorphic liposarcomas.

Two hibernomas, 16 myxoid, and eight pleomorphic liposarcomas were studied by transmission electron microscopy. Neoplastic cells in hibernomas and the type I cells--adipocytes--in myxoid liposarcomas consistently display abundant lipid droplet populations and prominent basal lamina deposition. Despite some variability in their distribution, these features clearly pertain to the mature and/or maturing characteristics of brown and white adipose cells. On the other hand, the more primitive type II cells of myxoid liposarcomas display highly variable, and occasionally absent, lipid droplet populations and basal lamina deposition. Moreover, the type II cells may also display other features such as prominent cytoplasmic filaments and rough endoplasmic reticulum that, while not characteristic of typical adipose cells, are still consistent with the more primitive mesenchymal cells from which they are assumed to derive. The cells of pleomorphic liposarcomas exhibit a variable lipid droplet population and apparently total absence of basal lamina deposition. Moreover, they often display atypical cell junctions that are neither characteristic for adipose cells nor for the "primitive reticular cells" from which adipocytes presumably derive. These observations would suggest that some "high grade" sarcomas may no be truly "undifferentiated"; rather, they may often display structural characteristics indicative of multiple as well as variable lines of differentiation. Therefore, classifications of such tumors based on quantitatively limited observations may not truly reflect their evident complexities.

Nesidiodysplasia and nesidioblastosis of infancy: structural and functional correlations with the syndrome of hyperinsulinemic hypoglycemia.

Subtotal pancreatectomy specimens of seven infants with persistent hyperinsulinemic hypoglycemia were studied; all showed the characteristic light microscopic picture of nesidioblastosis. Specimens were studied by electron and conventional light microscopy and by light microscopic immunohistochemistry for insulin, glucagon, somatostatin, and HPP (human pancreatic polypeptide); double staining and quantitative methods were also used. Findings were compared with those in age-matched controls. In the hyperinsulinemic hypoglycemic infants, an increase in total endocrine cell volume was found; however, the typical features of nesidioblastosis were also found in the controls. In both groups, immunohistochemistry and electron microscopy suggested that some endocrine cells are capable of producing synchronously more than one hormone. Amphicrine ("composite" or "intermediate") cells with exocrine and endocrine differentiation were found in three hypoglycemic infants. Observations are discussed in relation to current concepts of embryogenesis of the gastroenteropancreative endocrine system. We conclude that nesidioblastosis, as defined anatomically cannot be considered as the morphologic basis of hyperinsulinemic hypoglycemia. The term "nesidiodysplasia" is suggested and includes increased, maldistributed, and malregulated or malprogrammed endocrine and amphicrine cells when associated with endocrine abnormality.

Pulmonary blastoma with neuroendocrine differentiation in cell morules resembling neuroepithelial bodies.

Pulmonary blastoma is an infrequent malignant neoplasm, so called because of its resemblance to fetal lung. The original description outlined the components as variable mixtures of epithelial and stromal elements. More recently, a variant displaying almost exclusively epithelial differentiation has been described. We report our findings in a case of pulmonary blastoma with predominance of epithelial cells, forming tubular structures and large morules. The architectural arrangement of the morules was remarkably similar to normal bronchial neuroepithelial bodies. Moreover, their immunohistochemical profiles were also very similar, including the expression of cytokeratins, chromogranin, neuron-specific enolase, synaptophysin, gastrin, calcitonin, bombesin, somatostatin and serotonin.

Differential distribution of tenascin in the normal, hyperplastic, and neoplastic breast.

We studied by immunohistochemistry the distribution of tenascin with the monoclonal antibody 100EB2, and compared it with that of laminin in breast tissue samples from fetal, adult resting, lactating, and aging parenchyma, variants of fibrocystic disease, fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies were applied to cryosections by the avidin-biotin-complex method; selected samples were studied by double immunofluorescence, and by Western blot analysis. In adult resting and aging breasts, tenascin immunoreactivity was noted in the periductal and periacinar stromal regions as thin irregular bands; in the lactating breast, broader periductal bands were observed. In these samples, laminin immunoreactivity was a single continuous line around ducts, acini, and vessels. In fetal breasts, tenascin appeared as thick periductal bands, whereas laminin remained as a delicate single line. In FCD, tenascin increased around ducts showing hyperplasia, papillomas and apocrine metaplasia, whereas laminin retained its delicate linear pattern. Similar patterns were seen in fibroadenomas and cystosarcoma phylloides with variable tenascin reactivity in the stroma beyond the ducts. Tenascin immunoreactivity was markedly increased around ducts containing in situ carcinoma appearing as broad bands, whereas that of laminin showed a linear, frequently discontinuous appearance. Prominent stromal tenascin immunoreactivity was seen in infiltrating ductal and lobular carcinomas, whereas laminin was virtually absent save for scattered lines. The abundance of tenascin in the carcinomatous stroma contrasted with its scarcity in the non-neoplastic stromal regions. By Western blotting, both chains of tenascin with molecular weights 250,000 and 180,000 were shown in ductal and lobular carcinomas as well as in normal breast. Tenascin immunoreactivity was noted in the periepithelial stromal regions of adult resting and aging breast ducts and acini. The amount of tenascin was moderately enhanced in certain physiologic conditions (fetal growth, gestation), as well as hyperplasias, dysplasias (fibrocystic disease) and benign tumors, whereas it was markedly enhanced in intraductal and infiltrating carcinomas. During fetal mammary development, adult physiologic and pathologic hyperplasias, and in carcinomas, the increasing tenascin reactivity contrasted with the stable or decreasing laminin reactivity.

Cystic fibrosis associated islet changes may provide a basis for diabetes. An immunocytochemical and morphometrical study.

The pancreases of 23 patients (mean age 10.5 years, range 5-22) years dying of cystic fibrosis (CF) were evaluated at autopsy by routine histology and immunostaining for changes in their endocrine cell compartment. The severely altered pancreatic tissues showed end stage CF, with either a fibrotic pattern (CF-FIB, n = 14) or a lipoatrophic pattern (CF-LIP, n = 9) prevailing. In all specimens, irrespective of the dominating pattern, the islet system was affected by marked periinsular and intrainsular sclerosis. Quantitatively, the volume densities (relative tissue components) of the parenchymal, fibrotic, fatty and total endocrine compartments as well as the four islet cell types (B, A, D, PP) were determined by point counting. Compared with controls, the CF patients (including two patients with overt diabetes and glucose intolerance, respectively) had a significantly decreased insulin (B)-cell ratio (from 64.4 to 34%) with a concomitant rise in non-B-cells (A-cells: 23.2 to 35%; D-cells: 10.4 to 22%; PP-cells; 2 to 9%). Comparison of endocrine cell ratios in CF-FIB pancreases with CF-LIP pancreases revealed no significant differences. The reduction of approximately 50% of insulin cells in CF patients with advanced disease supports the concept that destruction of exocrine tissue with concomitant fibrous disorganization of islets gradually changes the proportional distribution of the endocrine cells in favor of the noninsulin cells. This slowly ongoing process probably provides the basis for islet dysfunction, i.e. diabetes, increasingly observed in final stage CF.

Ovarian cancer metastatic to the brain: what is the optimal management?

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.