Faculty Bibliography

The distinction between malignant mesothelioma and other neoplastic processes involving the pleura is difficult, partly due to the lack of specific markers expressed on mesothelioma. Because of evidence suggesting that the Wilms' tumor susceptibility gene (WT1), unlike other tumor suppressor genes, is restricted mostly to mesenchymally derived tissues, we hypothesized that the WT1 gene products could serve as a potential marker for mesothelioma. The expression of WT1 mRNA was analyzed in 19 malignant mesothelioma cell lines and 9 tumors and compared with the expression of WT1 in 10 non-small cell lung cancer lines and 9 lung cancer specimens. WT1 mRNA was detectable by Northern analysis in 16 of 19 mesothelioma cell lines and in 5 of 8 malignant mesothelioma tumors. In contrast, WT1 mRNA was not detected by Northern analysis in non-small cell lung cancer lines or carcinomas. Immunoprecipitation with an anti-WT1 monoclonal antibody showed that a 52- to 54-kd protein was present in 4 mesothelioma cell lines. Immunostaining with this antibody localized the WT1 protein to the nucleus in two mesothelioma lines and in 20 of 21 mesothelioma tumors examined. This distinctive pattern of nuclear immunoreactivity was absent in 26 non-mesothelioma tumors involving the lung, including 20 non-small cell lung carcinomas. The detection of WT1 mRNA or protein may thus provide a specific molecular or immunohistochemical marker for differentiation of mesothelioma from other pleural tumors, in particular, adenocarcinoma

A complex interplay of peptides known as the cytokines may have a tremendous influence over a number of inflammatory related conditions. Tumor necrosis factor occupies an early and central role in the initiation of cascades that ultimately influences a number of cell types involved in tissue inflammation, tissue rejection, cancer, and injuries from ischemia reperfusion. Only now are the cascades being defined and therapies being designed to interrupt the toxic effects of these cytokines and to treat malignancy

Previous reports of the association between the debrisoquine metabolic polymorphism and lung cancer risk have been conflicting. We examined the hypothesis that the genetically determined ability to metabolize debrisoquine identifies individuals at increased risk for lung cancer in a study designed to address some of the methodological criticisms of previous studies. A case-control study of 335 incident Caucasian lung cancer patients and 373 controls matched for age, race, sex, and hospital, was conducted at the National Naval Medical Center (Bethesda, MD) and at the Laval Hospital (Sainte-Foy, Quebec, Canada). Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8-h urine collected. Stratified and logistic regression analyses were used to evaluate the association between extensive or intermediate debrisoquine metabolism and lung cancer risk. We found no increased risk among extensive or intermediate metabolizers (odds ratio, 0.6; 95% confidence interval, 0.3-1.2). The lack of an association was not confounded by control diagnoses, medications used within 1 month of debrisoquine administration, smoking, stage, or histology of lung cancer. No relationship was found among either heavy smokers or light and nonsmokers. Our results do not support the role of debrisoquine metabolism as a marker for lung cancer risk. While the concept that polymorphisms of metabolism may account for differential susceptibility to lung cancer is sound, debrisoquine metabolic phenotype was not associated with lung cancer risk in these data

Middle mediastinal pheochromocytomas are exceedingly rare. Because so few cases have been reported, consensus has not been reached regarding the anesthetic management of patients with these tumors. The use of cardiopulmonary bypass (CPB) for the resection of intrapericardial pheochromocytomas has met with varied success. We report the first documented case of successful anesthetic and surgical management of an acute, massive hemorrhage during the dissection of an intrapericardial pheochromocytoma, which was managed without cardiopulmonary bypass. Perioperative anesthetic considerations, including the risks and benefits of CPB, are discussed

The pathologic features in pulmonary specimens are reported from 32 open thoracotomies of 20 patients with chronic granulomatous disease (CGD). The pattern of inflammation present in the resected material varied, but a granulomatous component was present in each case. In 78% of the specimens, a distinctive form of granuloma was found: a neutrophilic microabscess surrounded by palisading histiocytes. In four specimens eosinophils were also found within the microabscesses. This feature was found exclusively in cases of fungal infection. Fungal organisms were found by culture in 18 specimens (56%) and in 17 of these specimens (94%), they also were seen by histopathology. In 9 cases (28%) routine bacterial cultures were positive, and in one case an atypical Mycobacterium was cultured. These organisms were not prospectively identified on special stains of histologic sections in any of the cases. Abscess formation was found more commonly in pure fungal infections (41%) than in pure bacterial infections (14%). In contrast to earlier reports, well-formed granulomas with giant cells were not specific for fungal infections. In this series, they were present in 57% of cases with pure bacterial infections. A subset of the patients received gamma interferon therapy or granulocyte transfusions before the surgical procedures. No differences in the histopathology of the inflammation were associated with granulocyte transfusions, but gamma interferon therapy was associated with a reduction in necrotizing granulomatous inflammation. Additionally, one case of severe cytomegalovirus pneumonitis is described in a CGD patient receiving chronic steroid therapy

We used RNA-RNA in situ hybridization to study expression of the human CC10 gene in morphologically normal and atypical areas of 32 non-neoplastic lung specimens resected from 26 non-small cell lung cancer patients. We scored strong, moderate or weak levels of CC10 mRNA expression in 3 distinct lung compartments. In morphologically normal lungs, strong and moderate levels of CC10 mRNA were observed in bronchioli and bronchi, respectively, but the expression was rarely observed in the alveolar region. Distinct alterations in CC10 mRNA expression were noted in specific histologic abnormalities within bronchi and the alveolar region. CC10 hybridization signal decreased markedly in bronchi containing diffuse goblet cell hyperplasia or squamous metaplasia, while CC10 mRNA expression remained unchanged in bronchi with basal cell hyperplasia or focal goblet cell hyperplasia. Bronchiolar CC10 mRNA levels remained unchanged in sections containing abnormalities elsewhere. Interestingly, in alveoli with bronchiolization of the alveoli, high levels of CC10 mRNA were observed. These regions also contained strongly stained keratin 14-positive cells, which may indicate a concurrent metaplastic process. In lungs with morphologic atypias, no correlation was found between abnormalities detected in bronchi and alveoli from the same lung. A comparison of mRNA expression and clinicopathologic features demonstrated that the amount of histologic abnormalities increased with smoking history (pack years); however, no correlation between CC10 mRNA expression and sex, age or smoking history was found

During the past decade, an increasing spectrum of pathogenic Zygomycetes fungi have caused infections in humans. The preponderance of these deeply invasive infections have been caused by members of the order Mucorales. However, deeply invasive zygomycoses due to genera of the order Entomophthorales (Conidiobolus species and Basidiobolus species) have seldom been reported. We describe a granulocytopenic patient with pulmonary and pericardial zygomycosis due to Conidiobolus incongruus, describe this organism's susceptibility to antifungal agents, characterize its diagnostic microbiological characteristics, and review previously reported cases of deeply invasive zygomycosis due to Conidiobolus species. In immunocompromised patients, C. incongruus is an uncommon but highly invasive fungal pathogen that may be resistant to amphotericin B and can be distinguished from other Zygomycetes fungi by characteristic mycological features