Primitive neuroectodermal tumor of the myocardium: a case report, review of the literature, immunohistochemical, and ultrastructural study.

We report the case of a primitive neuroectodermal tumor (PNET) arising in the heart of a 63-year-old man. The neuroectodermal nature of this tumor was confirmed by the immunohistochemical positivity for O13 (CD99) (the P30/32MIC2 gene product) neuron specific enolase (monoclonal and polyclonal), synaptophysin and vimentin. Other markers, such as actin, desmin, myoglobin, chromogranin, keratin, and leukocyte common antigen were negative. The diagnosis was made on an endomyocardial biopsy and was confirmed in sections from the myocardial tumor found within the heart excised during cardiac transplant. Primitive neuroectodermal tumors have been reported in a variety of sites, most commonly in the extremities. No case has ever been reported within the myocardium, although one has been reported in the pericardium. In addition to morphological similarities, PNET and extraskeletal Ewing's sarcoma have been shown to possess the same chromosomal translocation, t11;22, and the same cell surface antigen, P 30/32. Separation of this case from extraskeletal Ewing's sarcoma was possible because of the absence of PAS positivity, as well as the immunohistochemical positivity for at least two neural markers, as extraskeletal Ewing's sarcoma is only positive for neuron specific enolase.

Parathyroid surgery: the role of chief cell intracellular fat staining with osmium carmine in the intraoperative management of patients with primary hyperparathyroidism.

The surgeon's gross evaluation, the hematoxylin and eosin stain, which assesses extracellular fat, and a new intracellular fat stain, osmium carmine, were comparatively evaluated in 30 consecutive patients who underwent surgery for primary hyperparathyroidism. The surgeon's gross judgment of enlarged and normal parathyroid tissue resulted in the correct functional assessment in 98% and 97% of the glands, respectively. The surgeon's functional assessment was correct in seven of 10 parathyroid glands that were considered by gross examination to be slightly enlarged (50 to 80 mg). The osmium carmine intracellular fat stain provided a correct functional assessment in all 10 of these glands. The osmium carmine stain also appears to have a role in providing scientific quantitative data to limit operations in patients who have a parathyroid adenoma to removal of the adenoma and biopsy of a grossly normal gland that demonstrates normal intracellular fat. Only one side of the neck was explored in 11 patients who fulfilled these criteria. There has been no persistent or recurrent hypercalcemia in these patients.

Electrolyte versus blood cardioplegia: randomized clinical and myocardial ultrastructural study.

In 40 consecutive patients undergoing coronary artery bypass, one of two solutions for cardioplegia, each containing 30 mEq/L of K+ was used randomly. The groups were comparable except for intramyocardial temperature. With electrolyte solution (Group A), it was 16.5 degrees +/- 0.34 degrees C, while with blood from the pump-oxygenator (Group B) it was 20.3 degrees +/- 0.41 degrees C (p less than 0.001). After bypass left atrial pressure (LAP) was 11.9 +/- 0.67 torr in Group A and 8.1 +/- 0.49 torr in Group B (p less than 0.001). CPK-MB was elevated in 45% of Group A patients versus 15% in Group B (p less than 0.05). No patient died. Two myocardial infarctions occurred in Group A and one in Group B. Stereological morphometric electron microscopy was performed on biopsy specimens taken from the left ventricle (1) before perfusion, (2) after cardioplegia, and (3) 30 minutes after reperfusion. Group A showed marked intracellular edema, mitochondrial swelling, pronounced depletion of glycogen stores, and focal myofibrillary disorganization. Group B showed near normal myocardial ultrastructure with increased glycogen stores and minimal mitochondrial swelling. Morphometric analysis revealed a statistically significant increase in the degree of mitochondrial swelling (51%) in Group A compared with Group B after reperfusion (p less than 0.001). Thus, blood K+ cardioplegia resulted in better preservation of myocardial ultrastructure, lower ventricular filling pressure, and lesser CPK-MB release compared with this particular electrolyte cardioplegia.

Effects of antiplatelet drugs on pulmonary responses to thrombin in anesthetized rabbits.

Platelet aggregation and fibrin deposition in the pulmonary circulation may contribute to the pathogenesis of lung injury in the adult respiratory distress syndrome (ARDS). We evaluated the effect of two antiplatelet drugs (forskolin & dipyridamole) on pulmonary responses to intravenous infusion of 100 NIH units of thrombin per kg bw in anesthetized, and ventilated rabbits treated with fibrinolysis inhibitor. Thrombin infusion resulted in pulmonary hypertension and increased arterial CO2 tension (PaCO2) and dead space ventilation (VD/VT). Arterial oxygen tension (PaO2) and numbers of circulating leukocytes and platelets dropped after thrombin infusion. These early hemodynamic changes correlated with histological evidence of entrapped leukocytes in the pulmonary microcirculation and transient alveolar edema. Microthrombi were rarely observed in animals that received thrombin. There was little evidence for endothelial damage or progressive lung water accumulation. Treatment with forskolin or dipyridamole reversed thrombin-induced changes in pulmonary artery pressure, PaCO2, VD/VT and systemic oxygenation. Moreover, forskolin and dipyridamole blunted the drop in circulating leukocytes and prevented the development of alveolar edema following thrombin. The beneficial actions of these agents may be due to interference with the release of mediators from leukocytes or platelets.

The core pathobiology and integrated medical science of adult acute respiratory insufficiency.

The straightforward core pathobiologic facts needed for the clinician's basic understanding of the clinical course and pathophysiology of progressive acute respiratory insufficiency (ARI) seen in surgical practice are summarized in the opening paragraphs. The remainder of the article provides the detailed evidence for elucidating the morphogenesis, i.e., the sequence of pathologic events, which determines the natural and the therapeutically altered clinicopathophysiologic courses of ARI. The attempt is to integrate observations concerning altered structure, cell biology, pathophysiology, physiologic function test data, bioengineering principles, clinical course, therapeutic management, and historical aspects of the disease process, into a detailed multidisciplinary but comprehensive explanation of this very complex, difficult disease process.

Automated Speech-recognition Anatomic Pathology (ASAP) reporting.

Artificial intelligence speech-recognizers integrated with Laboratory information and Telefaxcommunication Systems have allowed for totally automated surgical pathology reporting. Automated Speech-Recognition Anatomic Pathology (ASAP) reporting improves the speed, text accuracy, comprehensiveness, and workflow management of diagnostic reports while eliminating support personnel. Healthcare reform goals of increased productivity and economy are furthered. Reports are rendered "as soon as possible" (ASAP) expediting appropriate clinical management and decreased length of stay and hospital costs.

Cervical smears prepared by an automated device versus the conventional method. A comparative analysis.

An automated, fluid-based method for the preparation of cervical Papanicolaou smears/slides was compared to the conventional Papanicolaou smear (CPS) method used for the screening of neoplasia. We determined diagnostic agreement and sources of error for diagnostic disagreement. For 665 patients, one cervical sample was collected to make one CPS. The collection devices, a wooden Ayre spatula and endocervical brush, were rinsed into a vial with fluid medium to be processed in the automated device. All slides were distributed among five cytotechnologists in a blind fashion. Exact diagnostic agreement was 94.6%. The results were not statistically significant (P > or = .70, McNemar's test) but were clinically important, as evidenced by the detection of low grade lesions (LGL), during initial screening, on three slides prepared by the automated device but not on their matched-pair CPSs (0.5% of all specimens). After reevaluation, the three matched CPSs demonstrated LGL. Sources of diagnostic error on the CPSs were: air-drying artifact, obscuring blood/inflammation, crowding/overlapping of cells and/or absence of diagnostic cells. The only source of error in the automated-method smears was absence of diagnostic cells.

Occupational lung disease.

Occupational lung diseases can be conveniently classified into disorders of the airways, the alveoli, and the lung interstitium. Diseases of each category have a distinct clinical and pathologic presentation despite diverse causes.

A comparative study of DNA ploidy in 115 fresh-frozen breast carcinomas by image analysis versus flow cytometry.

BACKGROUND: Qualitative and quantitative analysis of cellular DNA content may be clinically useful in the prognostic evaluation of certain types of malignant tumors, including breast carcinoma. Flow cytometric (FCM) analysis has been the most frequently used procedure for DNA analysis, but it requires a reasonably large tissue sample. Computer-based image analysis (IA) now allows imprint, cytospin, and needle aspiration smear preparations and other small tissue samples to be used. METHODS: To resolve concern about the diagnostic efficacy of small tissue samples in the use of IA, the authors performed a comparative study of FCM analysis and IA using 115 fresh-frozen breast carcinomas. Feulgen-stained imprint preparations for IA and single-cell suspensions from the same fresh-frozen tissue for FCM analysis were used, and the respective histograms were compared. RESULTS: The results were concordant in 90.4% (104 of 115) of the cases, but 11 specimens yielded discordant data. IA provided histograms with a somewhat lower resolution and a relatively high coefficient of variation for the G0/G1 peak, thus rendering occasional tumors, which were near-diploid aneuploid by FCM analysis (four cases), not amenable to diagnosis by aneuploid characterization. In three additional cases, FCM analysis showed aneuploid hyperdiploid (two cases) and multiploid (one case) histograms, but IA only demonstrated a diploid peak. Conversely, in four other cases, aneuploid peaks were recognized only by IA. CONCLUSIONS: Computerized IA has significant advantages over FCM analysis, including lower cost, the ability to analyze very small specimens, the capability of detecting rare high ploidy cells, the capacity to classify cellular populations according to specific morphologic type, and the fact that no destructive enzyme or chemical digestion is required for specimen preparation, thereby preserving the integrity of fragile cells.

The Lewis X antigen. A new paraffin section marker for Reed-Sternberg cells.

Using a monoclonal antibody specific to the Lewis X antigen (anti-Lex), the authors studied 103 cases of Hodgkin's disease (HD) in comparison with 57 cases of non-Hodgkin's lymphoma (NHL); three cases of granulocytic sarcoma (GS); two cases of malignant histiocytosis (MH); one case of monoblastic leukemia (ML); one case of interdigitating reticulum cell sarcoma (IRCS); six cases of histiocytosis X (HX); one case of reticulohistiocytoma (RH); 44 various reactive conditions of the lymph node (LN). Reed-Sternberg and related (R-S) cells stained selectively in 80 of 92 cases of HD (87.0%), excluding 11 cases of lymphocyte predominance type. The stain was better in B-5-fixed specimens than in formalin-fixed specimens, showing a dense deposit of reaction products at a paranuclear site and on the cell surface. The staining results were compared with those of Leu-M1 and found to be superior both qualitatively and quantitatively (detection rate of R-S cells: 87.0% versus 68.5% of Leu-M1). Granulocytes, rare epithelioid histiocytes, and some endothelial and/or erythrocytes also stained with anti-Lex. The stain had positive results in three cases of GS showing a diffuse cytoplasmic staining pattern. Of NHL, two of 29 peripheral T-cell lymphomas stained to show rare paranuclear deposits without cell surface staining. The stain had negative results in MH, ML, IRCS, HX, and RH. Of 45 reactive LN, minute subcapsular collections of Lewis X+, altered-appearing Langerhans'-like cells, were observed in all ten LN from human immunodeficiency virus (HIV)-associated persistent generalized lymphadenopathy (PGL). The stain had negative results in all other various reactive conditions of LN. In conclusion, Lewis X staining is useful as a marker for R-S cells in paraffin sections with staining results superior to those of Leu-M1. Lewis X staining also detects subcapsular clustering of altered-appearing Langerhans'-like cells in PGL, which has not been described previously and warrants additional study.

Individual human tumors in short-term micro-organ cultures: chemosensitivity testing by fluorescent cytoprinting.

Using innovative approaches, we addressed several problems often associated with in vitro chemosensitivity testing of individual human tumors: 1) obtaining a high rate of evaluability; 2) excluding participation of nonmalignant stromal and vascular components usually present in tumor specimens; 3) preserving cell-to-cell interactions present in the original tumor; 4) assessing drug-induced cytotoxicity without sacrificing the tumor culture. To circumvent these problems, tumor specimens were processed as follows: i) tissue (fresh or cryopreserved) was mechanically or enzymatically dissociated under mild conditions into cellular clusters (termed micro-organs); ii) large micro-organs were separated by a brief decantation, resuspended, and then exposed to fluorescein acetate to visualize (under naked eye) viable micro-organs; iii) fluorescent (i.e., viable) micro-organs were collected using a Pasteur pipette, and then planted on a solid support made of cellulose fibers impregnated with collagen. Since tumor micro-organs have been previously shown to consist solely of malignant cells, the procedure described here not only preserves a critical portion of the tumor architecture but eliminates at the onset necrotic tissue and nonmalignant cellular components that could interfere with the chemosensitivity testing. Drug-induced cytotoxicity was measured by "fluorescent cytoprinting", a novel, nondestructive procedure for assessing micro-organ viability in situ. The key feature of fluorescent cytoprinting is that cytotoxic effects are not measured against control cultures but against a baseline provided by a cytoprint of the same culture before drug addition. Using three experimental designs, we tested the potential of the method for clinical applications. The results using 469 human malignant tumors showed that the micro-organ culture assay can distinguish individual tumor chemosensitivity profiles with an overall success rate of 96%. For three commonly used chemotherapeutic drugs, the observed frequency of responding tumors was found to be comparable to previously reported clinical results using single agents.

Consecutive repair of complex congenital heart disease using hypothermic cardioplegic arrest--its results and ultrastructural study of the myocardium.

Cold potassium cardioplegia was used in 78 consecutive patients undergoing correction of complex congenital heart disease between 1977 and 1982. Ages ranged from 4 weeks to 21 years (mean 6.7 years). The anatomical diagnoses were: tetralogy of Fallot (33), common AV canal (12), pulmonary atresia with ventricular septal defect (VSD) with previous shunts (5), transposition of great arteries (5), total anomalous pulmonary venous return (3), complex VSD (4), and complex anomalies (16). There were 3 deaths (4%). Electron microscopy was performed on biopsy specimens taken from the hypertrophied or volume-loaded cardiac chamber (1) before perfusion, (2) after cardioplegia, and (3) 30 minutes after cardioplegia. It showed near normal myocardial ultrastructure after cardioplegic arrest, however there was minimal mitochondrial and intracellular edema after reperfusion. Post-operatively, 80% of the patients had spontaneous defibrillation and only 10% required brief inotropic support. The operative exposure was excellent. No patient developed heart block during repair.

Interaction of thromboxane A2 and tissue pathology during graded bacteremia.

The purpose of this study was to determine whether or not thromboxane A2 (TXA2) was necessary or sufficient for the development of end-organ pathology during graded bacteremia. Pulmonary artery catheters were placed in 21 adult male pigs under pentobarbital anesthesia and breathing room air. After a control period, animals were studied in four groups: Group 1, anesthesia only; Group 2, infusion of 1 X 10(9) ml Aeromonas hydrophila which was gradually increased from 0.2 ml/kg/hr to 4.0 ml/kg/hr over 4 hours; Group 3, pretreatment with SQ 29,548 (TXA2 antagonist) then Aeromonas h. infusion; Group 4, infusion of U46619 (TXA2 agonist) to pulmonary artery pressures measured in Group 2. Animals were sacrificed after 4 hours and the lungs, liver, spleen, kidneys, and heart were examined under light microscopy by a pathologist unaware of study groups. The results indicated that physiologic thromboxane A2 agonist (Group 4) was sufficient alone to cause pulmonary inflammation. Thromboxane A2 was neither necessary nor sufficient for significant renal, hepatic, pulmonary, or splenic pathology to occur in graded bacteremia, manifested in similar microanatomic abnormalities in these organs in Groups 2 and 3 and in Groups 1 and 4. Pulmonary leukocyte infiltration was significantly increased in Group 3 compared to all other groups, suggesting that TXA2 impairs inflammatory responses.

Lung function and structure after Escherichia coli endotoxin in rabbits: effect of dose and rate of administration.

We evaluated the effect of increasing doses of Escherichia coli endotoxin and its rate of administration on systemic blood pressure, alveolar-arterial oxygen gradient (A- aDO2 1.0), dynamic compliance (Cdyn), circulating platelets and leukocytes, and postmortem bloodless wet to dry ratios in anesthetized rabbits. Infusion of endotoxin resulted in systemic hypotension, diminished Cdyn, thrombocytopenia, and leukopenia, but did not influence venous admixture. These parameters were not affected by the rapidity of administration, but changes in Cdyn and circulating platelets were dose-dependent. High (15 mg/kg), but not low (0.5 mg/kg), doses of endotoxin resulted in an early but transient increase in lung water, but bloodless wet to dry weight ratios were not increased at 4-6 h following endotoxin even when high doses were injected. Ultrastructural studies done in six rabbits showed an early but transient platelet sequestration in pulmonary capillaries, progressive increase in intracapillary leukocytes, interstitial edema, and focal, although minimal, endothelial injury at 4 h after injection. Thus, infusion of E coli endotoxin in rabbits does not result in increased lung water and intrapulmonary shunting acutely; this tolerance to endotoxin is not related to the dose or rates of administration studied.

Nontraumatic fat embolization. A rare cause of new pulmonary infiltrates in an immunocompromised patient.

Diffuse pulmonary infiltrates and hypoxemia are common in immunocompromised patients. We describe a patient with lymphoma who developed hypoxemia and diffuse pulmonary infiltrates during treatment with corticosteroids. Open lung biopsy and postmortem examination indicated that the cause of the infiltrates was nontraumatic fat embolization (NTFE). Most previous cases of NTFE have implicated a fatty liver as the source of emboli; however, this patient had no fatty changes of the liver. The diagnosis of NTFE in an immunocompromised patient is difficult to make because its distinguishing features, such as hypoxemia, petechiae, and altered mental status, are nonspecific in this setting.