Well-differentiated papillary mesothelioma.

Well-differentiated papillary mesothelioma is an unusual variant of epithelial mesothelioma considered to be of low malignant potential. The majority of previously reported cases developed in the peritoneum of young women without a history of asbestos exposure. The authors report 14 cases of well-differentiated papillary mesothelioma, seven of which originated in the pleura, six in the peritoneum, and one in the tunica vaginalis. Eleven of the patients were male and three were female, with an average age at presentation of 58 years (range 32-82 years). Six of the patients had a quantifiable history of asbestos exposure. Of the nine cases with complete follow-up, six had clinically indolent disease, one showed resolution after adjuvant chemotherapy, one pursued an aggressive course, and one died of other causes. These findings indicate that well-differentiated papillary mesothelioma is a rare variant of mesothelioma with a variable clinical prognosis that is etiologically related to asbestos exposure in some cases.

Fine needle aspiration cytology of mucinous cystadenocarcinoma of the lung: report of a case with radiographic and histologic correlation.

BACKGROUND: Mucinous cystadenocarcinoma of the lung is an uncommon tumor. Because it contains relatively few neoplastic cells relative to the amount of mucin produced, diagnosis of this entity, particularly on small specimens, is exceedingly difficult. CASE: The diagnosis of adenocarcinoma was made on transthoracic fine needle aspiration from a patient with a right upper lobe lung mass. Abundant mucoid material suggested a mucin-producing neoplasm. Histopathology revealed a mucinous cystadenocarcinoma with focal mucinous bronchoalveolar carcinoma. CONCLUSION: The presence of copious extracellular mucin in fine needle aspirates from the lung otherwise diagnostic of adenocarcinoma should raise the possibility of a mucinous tumor. In particular, the diagnosis of mucinous cystadenocarcinoma may be suggested in cases that have a cystic appearance on imaging studies.

Amiodarone and cyclophosphamide: potential for enhanced lung toxicity.

Antineoplastic therapy can be associated with drug-induced lung toxicity. With the increasing use of amiodarone for cardiac dysrhythmias there is an increasing possibility of its combined use with chemotherapies for various malignancies. We report a patient on long-term amiodarone who developed biopsy-proven drug-induced lung toxicity after receiving high-dose cyclophosphamide, at a time-frame much shorter than would have been predicted with cyclophosphamide alone. The potential for enhanced lung toxicity secondary to combination of amiodarone and cyclophosphamide is discussed.

The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer.

The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response (P < 0.001). High-level expression of GST-pi, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation.

Loss of heterozygosity at the mannose 6-phosphate insulin-like growth factor 2 receptor (M6P/IGF2R) locus predisposes patients to radiation-induced lung injury.

PURPOSE: To investigate the relationship between loss of heterozygosity (LOH) at the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) gene locus and the development of radiation-induced lung injury. MATERIAL AND METHODS: Thirty-five lung cancer patients with both stored plasma for Transforming Growth Factor beta1 (TGFbeta1) analysis and sufficient quantities of archival pathology tissue to screen for LOH were studied. All patients had been treated with thoracic radiotherapy for their malignancy and had radiographically detectable tumor present before beginning radiotherapy. Tumor and normal cells were microdissected from archival lung cancer pathology specimens. Two polymorphisms in the 3' untranslated region of the M6P/IGF2R were used to screen for LOH. Plasma TGFbeta1 levels were measured using acid-ethanol extraction and an ELISA. TGFbeta1 and M6P/IGF2R protein expression was estimated by immunofluorescence and immunohistochemical staining. Symptomatic radiation pneumonitis was scored according to National Cancer Institute Common Toxicity Criteria without knowledge of the results of TGFbeta or LOH analyses. RESULTS: Of the 35 patients, 10 were homozygous for this polymorphism (noninformative) and were excluded. Of the 25 informative patients, 13 had LOH. Twelve of 13 patients with LOH had increased pretreatment plasma TGFbeta1 levels, vs. 3/12 patients without LOH (p < 0.01). A decrease or loss of M6P/IGF2R protein in the malignant cell accompanied by increased latent TGFbeta1 protein in extracellular matrix and tumor stroma was found in tumors with LOH, suggesting that this mutation resulted in loss of function of the receptor. Seven of 13 (54%) LOH patients developed symptomatic radiation-induced lung injury vs. 1/12 (8%) of patients without LOH (p = 0.05). CONCLUSION: Loss of the M6P/IGF2R gene strongly correlates with the development of radiation pneumonitis after thoracic radiotherapy (RT). Furthermore, patients with LOH (in the setting of measurable tumor) are much more likely to have elevated plasma TGFbeta, suggesting an inability to normally process this cytokine. Thus, loss of the M6P/IGF2R gene may predispose patients to the development of radiation-induced lung injury.

Epithelioid hemangioendothelioma of the pleura: clinical and radiologic features.

OBJECTIVE: The purpose of our study was to describe the clinical and radiologic features of epithelioid hemangioendothelioma of the pleura. CONCLUSION: Pleural epithelioid hemangioendothelioma is an uncommon malignancy that typically affects older men, who present with chest pain and dyspnea. This lesion manifests on chest radiographs and CT scans with unilateral pleural fluid and nodular pleural thickening and appears similar to diffuse pleural carcinomatosis or mesothelioma.

Pulmonary drug toxicity: radiologic and pathologic manifestations.

Pulmonary drug toxicity is increasingly being diagnosed as a cause of acute and chronic lung disease. Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity. The clinical and radiologic manifestations of these drugs generally reflect the underlying histopathologic processes and include diffuse alveolar damage (DAD), nonspecific interstitial pneumonia (NSIP), bronchiolitis obliterans organizing pneumonia (BOOP), eosinophilic pneumonia, obliterative bronchiolitis, pulmonary hemorrhage, edema, hypertension, or veno-occlusive disease. DAD is a common manifestation of pulmonary drug toxicity and is frequently caused by cytotoxic drugs, especially cyclophosphamide, bleomycin, and carmustine. It manifests radiographically as bilateral hetero- or homogeneous opacities usually in the mid and lower lungs and on high-resolution computed tomographic (CT) scans as scattered or diffuse areas of ground-glass opacity. NSIP occurs most commonly as a manifestation of carmustine toxicity or of toxicity from noncytotoxic drugs such as amidarone. At radiography, it appears as diffuse areas of heterogeneous opacity, whereas early CT scans show diffuse ground-glass opacity and late CT scans show fibrosis in a basal distribution. BOOP, which is commonly caused by bleomycin and cyclophosphamide (as well as gold salts and methotrexate), appears on radiographs as hetero- and homogeneous peripheral opacities in both upper and lower lobes and on CT scans as poorly defined nodular consolidation, centrilobular nodules, and bronchial dilatation. Knowledge of these manifestations and of the drugs most frequently involved can facilitate diagnosis and institution of appropriate treatment.

Cystic fibrosis: usefulness of thoracic CT in the examination of patients before lung transplantation.

PURPOSE: To evaluate the usefulness of thoracic computed tomography (CT) in the pre-lung transplantation examination of patients with cystic fibrosis (CF). MATERIALS AND METHODS: Fifty-six patients (age range, 12-42 years) with CF were evaluated for possible lung transplantation from 1991 to 1997. Twenty-six of these patients underwent bilateral lung transplantation, 19 were awaiting transplantation at the time of the study, seven died before transplantation, and four were excluded for psychosocial concerns. Preoperative chest radiographic and CT findings were reviewed and correlated with clinical, operative, and pathology records. RESULTS: In seven patients, discrete, 1-2-cm pulmonary nodules were detected at CT. Five of these patients underwent transplantation; the nodules were found to be mucous impactions. No malignancy was found in any of the patients who underwent transplantation. Pretransplantation sputum cultures grew Aspergillus fumigatus in seven patients, none of whom had radiologic findings suggestive of Aspergillus infection. Radiographic or CT findings were suggestive of mycetoma in five cases, but no such tumors were found at transplantation. The accuracies of chest radiography and CT for the detection of pleural disease in 48 hemithoraces were 81% (n = 39) and 69% (n = 33), respectively. The radiologic findings of pleural thickening did not influence the surgical approach in any patient. CONCLUSION: Thoracic CT has little utility in the routine pre-lung transplantation examination of patients with CF.

Laparoscopy and mesothelioma.

Malignant mesothelioma is a well-recognized long-term sequela of chronic asbestos exposure. Asbestos use in the United States began in the 1950s and was widespread until the mid-1970s. Although currently only 2.2 cases per million population per year are diagnosed, disease incidence is increasing because of the long latency of this neoplasm. A latency of 15-50 years means that a higher incidence of this neoplasm can be anticipated in the future. The authors report a patient with peritoneal mesothelioma and no known prior exposure to asbestos. The diagnosis was confirmed by exploratory laparoscopy, which entailed biopsies of the diaphragm and of the peritoneal and abdominal walls, and by cytologic evaluation of 700 ml ascitis fluid. At present, exploratory laparoscopy offers the quickest, safest, and least invasive way to confirm the clinical diagnosis of peritoneal malignant mesothelioma.

Pulmonary cholesterol granulomas in patients with pulmonary artery hypertension: chest radiographic and CT findings.

OBJECTIVE: We describe the chest radiographic and CT findings of pulmonary cholesterol granulomas in patients with pulmonary artery hypertension. CONCLUSION: Histopathologic evidence of cholesterol granulomas was found in five (25%) of 20 patients with severe pulmonary hypertension. In three of these five patients, the granulomas manifested on chest radiographs and CT as small centrilobular nodules mimicking the appearance of sarcoidosis, bronchiolitis, hypersensitivity pneumonitis, or aspiration.

Lentil aspiration pneumonia: radiographic and CT findings.

Aspiration of leguminous vegetables can cause a granulomatous pneumonitis know as lentil aspiration pneumonia that manifest on radiologic studies with small, poorly defined nodular opacities. We report two cases of lentil aspiration pneumonia that manifested with nodules up to 1.0 cm in diameter on radiographs and CT, simulating metastases.

Parapneumonic empyema. A pitfall in diagnosis.

Two patients eventually shown to have empyema were encountered in which the initial thoracentesis revealed fluid compatible with either a simple or a complicated parapneumonic effusion. In both cases, the diagnosis of empyema was made by a second thoracentesis done at a close interval of time from a different site. Therefore, the physician should approach parapneumonic effusions systematically, and remember that in some cases, multiple thoracenteses may be required to make the correct diagnosis of an empyema.