Cytokeratin immunophenotyping of an unusual cervical vertebral chordoma with extensive chondroid foci and perilaryngeal recurrence: a case report with review of the literature.

Chordomas are midline, slowly growing, and locally destructive tumors derived from vestigial remnants of the notochord. We present an unusual case of a cervical vertebral chordoma with extensive chondroid change that aggressively recurred in the anterior larynx and surrounding neck structures, and subsequently in the mediastinum, resulting in the death of the patient. Recent literature has investigated and debated the significance of chondroid elements in chordomas as a differential diagnostic and a prognostic indicator. In particular, the use of immunohistochemical stains for cytokeratin and mesenchymal markers in these areas as a means of distinguishing true from pseudocartilage has received much attention. In this study, we used a spectrum of cytokeratin subtypes (CK 7, 20, 5/6, AE1/3) to further characterize these chondroid areas, and observed that they were positive for the majority of the cytokeratin subtypes, suggesting pseudo, rather than true, cartilaginous change. Clinicopathologic features of this lesion and the recent literature are reviewed.

An approach to dissecting the congenitally malformed heart in the forensic autopsy: the value of sequential segmental analysis.

The demonstration of congenital heart disease at autopsy necessitates the careful preservation and examination of the heart, the vessels, and their connections. Techniques preserving these connections and using a reproducible and systematic approach are preferred. The Rokitansky method of organ block dissection, in combination with a system of heart examination termed sequential segmental analysis, provides such an approach. This study is based on the examination of heart specimens accessioned into the Frank E. Sherman, M.D., and Cora C. Lenox, M.D., Heart Museum (containing approximately 2400 specimens) of the Pathology Department, Children's Hospital of Pittsburgh. Specimens received in consultation during a 25-year period from hospitals and coroners'/medical examiners' offices were examined, and the corresponding reports were reviewed. Of 46 total heart specimens examined (1975-1999), 29 (63%) were dissected properly or left intact for dissection at Children's Hospital of Pittsburgh, and 17 (37%) were incorrectly dissected for the demonstration of congenital heart disease. Of these 17 cases, 11 (24%) displayed dissection errors, which did not hinder a complete diagnosis, 3 cases (6.5%) had errors that enabled only an incomplete diagnosis, and in 3 cases (6.5%), no diagnosis of congenital heart disease could be made. Dissection mistakes and means of avoiding them are discussed. Review of medical and family history, external and internal examination, and a reproducible and sequential method of examining the heart and its connections enables documentation of even the most complex cardiovascular anomalies.

Biomarkers of liver regeneration allow early prediction of hepatic recovery after acute necrosis.

Acute toxic hepatic necrosis is common and may be fatal. Predicting clinical outcome may be aided by following serum markers that could indicate recovery or may signify massive (substantial) destruction of functional liver mass. Previously, in a published case of chloroform poisoning, we serially assayed serum biomarkers of hepatocellular necrosis (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) and markers of hepatocellular regeneration (alpha-fetoprotein, retinol-binding protein, gamma-glutamyl transferase, and des-gamma-carboxyprothrombin). We noted a decline in necrotic markers and a synchronous elevation in regenerative markers, which could be suggestive of a favorable outcome in similar cases. We now report 6 Amanita mushroom poisonings with favorable outcome and 2 fatal acetaminophen poisonings in which the same markers were observed. Our results further support our hypothesis that a sustained decline in serum markers of hepatocyte necrosis with a concurrent elevation in regenerative markers could aid in prediction of favorable outcome in patients with acute liver injury.

The classification, recognition and significance of polyagglutination in transfusion medicine.

Polyagglutination, although an uncommon phenomenon in transfusion medicine, is becoming increasingly recognized as a potential pitfall in correct ABO typing and can hinder the rapid allocation of accurately crossmatched blood products. Polyagglutination refers to erythrocytes which demonstrate agglutination with the majority of adult sera upon initial ABO crossmatch testing. Most types of polyagglutination involve alteration of red cell surface antigens through microbial enzymatic activity in patients with sepsis, and subsequent interaction of these newly exposed 'cryptantigens' with naturally occuring IgM antibody which is present in most adult sera. Less common variants include essential inborn variations in red cell development, and have been associated with myelodysplastic syndromes, congenital anemias, and various leukemias; it has been suggested that patients shown to possess these types of polyagglutination may benefit from increased hematologic surveillance. Recognition of polyagglutination in these settings is important to allow successful resolution of ABO typing discrepancies and permit efficient administration of appropriate blood products to these patients, who are often quite ill. The classification and method of laboratory recognition of polyagglutination is reviewed.

Chylous pleural effusions simulating leukemic infiltrate associated with thoracoabdominal disease and surgery in infants.

Surgical procedures and diseases in childhood involving damage to or obstruction of the thoracic duct and related lymphatic channels can cause pleural effusions that are often chylous and can be massive. The morphology of fluid cytology in these cases can prompt a mistaken diagnosis of a hematolymphoid malignancy. We describe 6 infants, aged 3 days to 5 months, in whom thoracoabdominal disease and/or surgical procedures interfered with lymphatic drainage of the thorax and pleural space. In 5 cases, the clinically significant chylous pleural effusion was postoperative; in 1 case, it was related to congenital abnormalities. After chest tube drainage, the effusion resolved in all cases. Fluid cytology revealed a predominant population of small to medium immature-appearing cells with moderate amounts of basophilic cytoplasm without granules. The nuclei were often irregular or slightly lobulated, with evenly dispersed chromatin and occasionally prominent nucleoli. Flow cytometry performed on these cases revealed a heterogeneous population of lymphoid cells, most of which showed phenotypic markers typical for mature T cells. A complete patient history and ancillary studies in such cases can correctly characterize the cells to reach an accurate diagnosis.

Evolving strategies in the treatment of sepsis and systemic inflammatory response syndrome (SIRS).

In recent years, much basic science research has investigated the predisposing factors, initiation, propagation, and resolution of Gram-negative sepsis, endotoxaemic shock, and the newly defined entity of systemic inflammatory response syndrome (SIRS). A major cause of morbidity and mortality in the post-surgical, neonatal, and geriatric hospital population, sepsis has proven itself notoriously resistant to classical modes of therapy, including antibiotics, fluid/pressor and respiratory support. Recently, the widespread nosocomial isolation of new antibiotic-resistant strains of endotoxin-producing bacteria has further complicated management. For these reasons, there is much interest in alternative treatment modalities which focus upon the endotoxin molecule itself and the systemic inflammatory response it provokes via the cytokine, complement, and coagulation cascades. In this review, recent experimental approaches to the therapy of sepsis and SIRS are discussed in light of each step in the complex inflammatory cascade and in comparison to traditional approaches to prevention and therapy of Gram-negative bacteraemia and septic shock.

Left atrial myxoma with embolization presenting as an acute infrarenal aortic occlusion.

We present the case of a 42-year-old woman who had acute total infrarenal aortic occlusion resulting from embolic implantation from a left atrial myxoma. We propose that the small aortic aneurysm that was discovered and repaired in this case may be a direct result of invasion and destruction of the aortic elastic laminae by implanted myxomatous tissue originating in the primary atrial tumor. This behavior has been noted in small vessels of the cerebrum and upper extremities with this lesion, but no prior reports of this occurrence in the aorta has been noted after extensive review of the literature.

Continuing medical education on the World Wide Web (WWW). Interactive pathology case studies on the Internet.

OBJECTIVE: To present interactive online continuing medical education (CME) over the World Wide Web as a more efficient alternative to traditional modes of CME delivery. DESIGN: A departmental Web site available to those with access to the Internet. SETTING: A tertiary-care teaching hospital in the United States. RESULTS: Comprehensive case studies have been developed and are complete with images, text, and questions, including explanations for correct and incorrect responses. The images are linked to pertinent text to maximize their educational value. The cases are easily accessible, user friendly, and fully referenced. The system became operational in January 1996, and the first CME certificate was awarded to a participant shortly thereafter. CONCLUSIONS: Continuing medical education over the World Wide Web is an efficient means of delivering CME to the community at large; it allows participating physicians the latitude to obtain convenient CME credit at their leisure, in contrast to the regimented experience of formal CME conferences or symposiums. The interactive format of the CME cases allows the participant to submit immediate comments or criticism to case authors and receive instant feedback on their own performance, features unavailable in comparable educational software packages. The dynamic environment of the World Wide Web lends itself to the production and dissemination of such flexible forms of CME for the physician and will continue to expand in this capacity into the foreseeable future.

Hemocytic rickettsia-like organisms in ticks: serologic reactivity with antisera to Ehrlichiae and detection of DNA of agent of human granulocytic ehrlichiosis by PCR.

Ixodid ticks were collected from Connecticut, Massachusetts, Missouri, Pennsylvania, Rhode Island, and British Columbia (Canada) during 1991 to 1994 to determine the prevalence of infection with hemocytic (blood cell), rickettsia-like organisms. Hemolymph obtained from these ticks was analyzed by direct and indirect fluorescent antibody (FA) staining methods with dog, horse, or human sera containing antibodies to Ehrlichia canis, Ehrlichia equi, or Rickettsia rickettsii. Of the 693 nymphal and adult Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, and Ixodes pacificus ticks tested with dog anti-E. canis antiserum, 209 (32.5%) contained hemocytic bacteria. The prevalence of infected ticks varied greatly with species and locale. In parallel tests of duplicate hemolymph preparations from adult I. scapularis ticks, the hemocytic organisms reacted positively with E. canis and/or E. equi antisera, including sera from persons who had granulocytic ehrlichiosis. In separate PCR analyses, DNA of the agent of human granulocytic ehrlichiosis was detected in 59 (50.0%) of 118 adult and in 1 of 2 nymphal I. scapularis ticks tested from Connecticut. There was no evidence of Ehrlichia chaffeensis DNA in these ticks. In indirect FA tests of hemolymph for spotted fever group rickettsiae, the overall prevalence of infection was less than 4%. Specificity tests of antigens and antisera used in these studies revealed no cross-reactivity between E. canis and E. equi or between any of the ehrlichial reagents and those of R. rickettsii. The geographic distribution of hemocytic microorganisms with shared antigens to Ehrlichia species or spotted fever group rickettsiae is widespread.