Pulmonary necrotizing granulomas of unknown cause: clinical and pathologic analysis of 131 patients with completely resected nodules.

BACKGROUND: The cause of pulmonary necrotizing granulomas is often unclear, even after histologic examination. Our aim was to determine the clinical significance of histologically unexplained necrotizing granulomas. METHODS: Pulmonary necrotizing granulomas surgically resected at the Mayo Clinic (1994-2004) were retrieved and reviewed retrospectively. Cases in which a cause was evident at the time of initial histologic examination were excluded. The analysis cohort comprised 131 completely resected histologically unexplained pulmonary necrotizing granulomas. Clinical and laboratory information was abstracted from medical records, chest CT scans were reviewed, histologic slides were reexamined, and additional ancillary studies were performed in selected cases. RESULTS: A cause was determined on review in more than one-half of the histologically unexplained necrotizing granulomas (79 of 131, 60%) by reexamining histologic slides (47), incorporating the results of cultures (26), fungal serologies (14), and other laboratory studies (eight), and correlating histologic findings with clinical and radiologic information (13). Infections accounted for the majority (64 of 79), the most common being histoplasmosis (37) and nontuberculous mycobacterial infections (18). Noninfectious diagnoses (15 of 79) were rheumatoid nodule (five), granulomatosis with polyangiitis (Wegener) (five), sarcoidosis (four), and chronic granulomatous disease (one). Many cases remained unexplained even after extensive review (52 of 131, 40%). Most of these patients received no medical therapy and did not progress clinically or develop new nodules (median follow-up, 84 months). CONCLUSIONS: A cause, the most common being infection, can be established in many surgically resected pulmonary necrotizing granulomas that appear unexplained at the time of initial histologic diagnosis. Patients whose granulomas remain unexplained after a rigorous review have a favorable outcome. Most do not develop new nodules or progress clinically, even without medical therapy.

Pneumothorax and bullae in Marfan syndrome.

BACKGROUND: Increased risk of spontaneous pneumothorax has been described in patients with Marfan syndrome and has been attributed, in part, to the presence of apical blebs and bullae. OBJECTIVES: We assess the risk of pneumothorax and its relationship to the presence of apical blebs and bullae in patients with Marfan syndrome in the era of CT imaging. METHODS: A retrospective cohort study was performed of all patients 13 years or older with Marfan syndrome evaluated at the Mayo Clinic, Rochester, Minn., USA, from 1998 through 2008. One hundred and sixty-six patients met the current diagnostic criteria for Marfan syndrome and had chest imaging studies available for review. RESULTS: The median age was 40 years (range 14-71); 37% had a smoking history. Eight of 166 patients (4.8%) had experienced 1 or more episodes of spontaneous pneumothorax, and 2 of these 8 patients had 2 or more episodes. Apical blebs or bullae were identified on radiologic imaging in 16 patients (9.6%). Four of 16 (25%) patients with apical blebs or bullae had a history of spontaneous pneumothorax compared to 4 of 150 patients (2.7%) without blebs or bullae (p = 0.003). CONCLUSIONS: The frequency of blebs is relatively low in patients with Marfan syndrome but the risk of pneumothorax is significantly higher in those with radiologically detectable blebs or bullae. Chest CT scanning to identify blebs and bullae may allow risk stratification for pneumothorax in patients with Marfan syndrome.

Utility of integrated computed tomography-positron emission tomography for selection of operable malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a primary malignancy characterized by local invasion of the pleura and metastasis. Despite advances in computed tomography (CT) and magnetic resonance imaging (MRI), accurately staging patients remains challenging. Recent studies have examined the use of integrated CT-positron emission tomography (PET) for staging patients. MATERIALS AND METHODS: Mayo Clinic databases were queried to identify cases with a histologic diagnosis of MPM from 2000 to 2006. Inclusion criteria were a diagnosis of MPM, an available CT scan, and an initial staging integrated CT-PET scan. A total of 35 patients were identified who met the inclusion criteria. Computed tomography and integrated CT-PET scans were reviewed by experienced radiologists. Laboratory parameters were reviewed. The Mayo Clinic tumor registry and Social Security database were queried for survival data in patients in which no follow-up was available. RESULTS: Findings on integrated CT-PET excluded 14 of 35 patients from surgical intervention. Extrapleural pneumonectomies (EPPs) were performed in 8 patients, and partial pleurectomies were performed in 2 patients. Upstaging from integrated CT-PET occurred in 70% of the patients when surgical pathology was available, 2 cases to an inoperable stage. Although not statistically significant, median survival was 20 months for patients undergoing an EPP and 12 months for patients excluded from surgical intervention by integrated CT-PET. CONCLUSION: Malignant pleural mesothelioma is a difficult disease to accurately stage. The most common reason for upstaging in our series was an increase in T (tumor; tumor-node-metastasis staging system) disease. Our data suggest that integrated CT-PET is excellent for detecting nodal and distant metastases. However, the ability of this imaging modality to correctly stage locoregional disease is not superior to the combination of CT and MRI as reported in the literature.

Cystic lung disease in Birt-Hogg-Dube syndrome.

BACKGROUND: To describe the clinical, radiologic, and histopathologic aspects of cystic lung disease occurring in patients with Birt-Hogg-Dubé (BHD) syndrome, a rare, inheritable, multisystem disorder. METHODS: We retrospectively reviewed five patients with BHD syndrome evaluated at the Mayo Clinic Rochester from 1998 through 2005. RESULTS: Mean age (+/- SD) at the time of pulmonary evaluation was 56.4 +/- 4.8 years; four patients were men. Three patients had not received a diagnosis of BHD syndrome at the time of initial CT of the chest. Three patients had a smoking history, and two were nonsmokers. Two patients had a history of recurrent pneumothoraces. Pulmonary function tests available in four patients revealed normal results in one patient and mild airflow obstruction or nonspecific pattern of abnormalities in three patients. CT of the chest revealed cystic lung disease in all five patients; cysts were round to oval in shape, ranged widely in size, and were randomly distributed throughout the lungs, except for a predilection to involve the lung bases more extensively. Three patients with a smoking history had more severe cystic changes compared to nonsmokers and included both patients with recurrent pneumothoraces. Surgical lung biopsy available in one patient revealed emphysema-like changes. Follow-up CT scans available in four patients revealed relative stability over a median interval of 20 months (range, 3 to 66 months). CONCLUSION: We conclude that cystic lung disease in BHD syndrome varies widely in severity, mimics pulmonary lymphangioleiomyomatosis, and may be worsened by smoking.

Saddle pulmonary embolism diagnosed by CT angiography: frequency, clinical features and outcome.

OBJECTIVE: To assess the frequency, clinical presentation and outcome associated with saddle pulmonary embolism (PE) diagnosed by computed tomographic angiography (CTA). PATIENTS: Retrospective review of 546 consecutive patients diagnosed to have acute PE by CTA from 1 September 2002 to 31 December 2003. RESULTS: Fourteen of 546 patients (2.6%) had saddle PE; 10 were men (71%). None of these patients had pre-existing cardiopulmonary disease. Most common presenting symptoms included dyspnea (72%) and syncope (43%). Hypotension was documented in 2 patients (14%). The most common risk factor for PE was obesity (64%). CTA revealed saddle PE and additional filling defects in the main pulmonary arteries in all patients. Echocardiography was performed within 48 h of the PE diagnosis in 10 patients and revealed right ventricular dysfunction in 8 (80%). All patients were initially managed in the hospital, median length of stay of 4 days (range, 1-45 days). Standard anticoagulant therapy with heparin and warfarin was administered to all patients. Five patients (36%) received additional therapy; thrombolytic therapy was administered to 1 patient (7%) and 4 patients (29%) received an inferior vena cava filter. None of the patients died during their hospitalization. Four patients (29%) died following their hospitalization after intervals of 1, 5, 6, and 12 months, respectively. Causes of death were known in 3 patients, all of whom died from progressive malignancy. CONCLUSION: Saddle PE in patients without pre-existing cardiopulmonary disease is associated with a relatively low in-hospital mortality rate and may not necessitate aggressive medical management.

Solitary pulmonary metastasis presenting 20 years after primary resection of Wilms tumor.

Wilms tumor is the most common renal malignancy of childhood. Relapse occurs most often within 4 years of initial diagnosis, and the most common site of metastasis is the lung. We describe a 22-year-old man who presented with hemoptysis and a solitary pulmonary lesion 20 years after primary resection of Wilms tumor. Computed tomography of the chest showed an indeterminate pulmonary mass of heterogeneous attenuation with no other intrathoracic abnormalities. Surgical resection revealed a solitary pulmonary metastasis from Wilms tumor. Further evaluation yielded no evidence of extrathoracic metastases. This case shows that late relapse in the form of a solitary pulmonary mass can occur in patients with Wilms tumor.

Lack of evidence for an association between neurofibromatosis and pulmonary fibrosis.

STUDY OBJECTIVES: To reassess the association between neurofibromatosis and pulmonary fibrosis. DESIGN: Retrospective single-center study with analysis of patients' chest radiographs, CT scans, and medical records. SETTING: Tertiary care, referral medical center. PATIENTS: One hundred fifty-six adult patients with neurofibromatosis seen over a 6-year period between 1997 and 2002. RESULTS: A review of chest radiographs revealed abnormal findings in 70 patients (44.9%). The most common radiographic abnormalities were extrapulmonary nodules or masses seen in 22 patients (14.1%), followed by skeletal abnormalities in 16 patients (10.3%). Bilateral interstitial infiltrates were noted in only three patients (1.9%), all of whom had potential causes other than neurofibromatosis for their lung infiltrates, including smoking-related interstitial lung disease, rheumatoid lung disease, recurrent pneumonias, and a history of ARDS. CT scans were available in two of these patients and revealed nonspecific patterns of abnormalities with no honeycombing. Six patients had bullae or cystic airspaces demonstrated on chest radiography or CT scan; all of these findings occurred in the context of smoking-related emphysema. Combined together, bilateral interstitial lung infiltrates or cystic airspaces were demonstrated in five patients (3.2%) by chest radiography, and in eight patients (5.1%) by chest radiography or CT scanning; one patient had both findings on the CT scan. CONCLUSIONS: We found little evidence to support an association between neurofibromatosis and pulmonary fibrosis or any other form of parenchymal lung disease. Interstitial lung disease and bullae described in association with neurofibromatosis in previous reports may have, in part, represented smoking-induced manifestations.

Septic pulmonary embolism: presenting features and clinical course of 14 patients.

BACKGROUND: Septic pulmonary embolism (SPE) is an uncommon disorder with an insidious onset and is difficult to diagnose. STUDY OBJECTIVES: To characterize the presenting features and clinical course of patients with SPE. DESIGN: Retrospective study. SETTING: Tertiary care, referral medical center. PATIENTS: Fourteen subjects with SPE diagnosed during a 6-year period between 1996 and 2002. INTERVENTIONS: None. RESULTS: The median age of these patients was 37.5 years (range, 14 to 81 years) and included five women. Presenting symptoms included fever (93%), dyspnea (36%), pleuritic chest pain (29%), cough (14%), and hemoptysis (7%). The median duration of symptoms before diagnosis was 18 days (range, 5 to 180 days). A potential source or underlying condition that predisposed to SPE was identified in all 14 patients and included Lemierre syndrome (4 patients), central venous catheter infection (3 patients), prosthetic cardiac valve (2 patients), and pacemaker infection (2 patients). Two patients had a focal extrapulmonary infection, and one patient was an IV drug user. Most common pathogens were staphylococcal species (eight patients) and fusobacterium (four patients). Chest radiographic presentation was usually nonspecific, but CT was more helpful and revealed multiple nodular opacities peripherally, often with cavitation. Transesophageal echocardiography was performed in eight patients and demonstrated infectious vegetations in four cases. Aside from antimicrobial therapy and removal of infected devices, the management of these patients included cardiac surgery (two patients), thoracoscopic surgery with decortication (one patient), and tube thoracostomy (one patient). All 14 patients recovered from their illness. CONCLUSIONS: We conclude that SPE presents with variable and often nonspecific clinical and radiographic features. The diagnosis is usually suggested by the presence of a predisposing factor, febrile illness, and CT findings of multiple, nodular lung infiltrates peripherally, with or without cavitation.

CT screening for lung cancer: five-year prospective experience.

PURPOSE: To report results of a 5-year prospective low-dose helical chest computed tomographic (CT) study of a cohort at high risk for lung cancer. MATERIALS AND METHODS: After informed written consent was obtained, 1520 individuals were enrolled. Protocol was approved by institutional review board and National Cancer Institute and was compliant with Health Insurance Portability and Accountability Act, or HIPAA. Participants were aged 50 years and older and had smoked for more than 20 pack-years. Participants underwent five annual (one initial and four subsequent) CT examinations. A significant downward shift was evaluated in non-small cell lung cancers detected initially from advanced stage down to stage I by using a one-sided binomial test of proportions. Poisson regression and Fisher exact tests were used for comparisons with Mayo Lung Project. RESULTS: In 788 (52%) men and 732 (48%) women, 61% (927 of 1520) were current smokers, and 39% were former smokers. After five annual CT examinations, 3356 uncalcified lung nodules were identified in 1118 (74%) participants. Sixty-eight lung cancers were diagnosed (31 initial, 34 subsequent, three interval cancers) in 66 participants. Twenty-eight subsequent cases of non-small cell cancers were detected, of which 17 (61%; 95% confidence interval: 41%, 79%) were stage I tumors. Diameter of cancers detected subsequently was 5-50 mm (mean, 14.4 mm; median, 10.0 mm). Analysis for a more than 50% shift in proportion of stage I non-small cell cancer detection did not show statistical significance. Forty-eight participants died of various causes since enrollment. Lung cancer mortality rate for incidence portion of trial was 1.6 per 1000 person-years. There was no significant difference in lung cancer mortality rates of cancers detected in subsequent examinations between this trial and Mayo Lung Project after separation of participants into subsets (2.8 vs 2.0 per 1000 person-years, P = .43). CONCLUSION: CT allows detection of early-stage lung cancers. Benign nodule detection rate is high. Results suggest no stage shift.

Autopsy results after surgery for non-small cell lung cancer.

OBJECTIVE: To determine the percentage of metastatic and unexpected residual lung cancer at autopsy in patients considered for curative resection of non-small cell lung cancer during a time when computed tomography was available as a preoperative staging tool. MATERIAL AND METHODS: Clinical data and surgical and autopsy slides of all patients who underwent curative resection of nonsmall cell lung cancer at the Mayo Clinic in Rochester, Minn, between 1985 and 1999 and who underwent autopsy within 30 days of surgery were reviewed retrospectively for the presence of residual or metastatic disease. RESULTS: The study group consisted of 25 men and 7 women, with a mean age of 70 years. A pulmonary metastasis was identified at surgery in 1 patient (3%). Metastases were found in an additional 5 patients (16%) at autopsy, 1 of whom had 2 sites involved. These sites included the liver in 2 and lung, epicardium, adrenal gland, and kidney in 1 each. The average diameter of metastases was 1.6 cm. No factor studied was found to be significantly associated with the presence of unrecognized metastatic disease at autopsy. CONCLUSION: The advent of computed tomography as a staging tool has decreased the percentage of patients with undiagnosed metastatic disease at surgery; however, preoperative understaging in lung cancer remains a problem.

Pulmonary embolization of 2-octyl cyanoacrylate after endoscopic injection therapy for gastric variceal bleeding.

N-butyl-2-cyanoacrylate, a tissue adhesive that polymerizes on contact with weak bases such as blood, is being used widely outside the United States to obliterate gastric varices. Embolization of this material can occur via portosystemic shunts. We report a case of pulmonary embolization of 2-octyl cyanoacrylate (an analogue of N-butyl-2-cyanoacrylate) that occurred after endoscopic injection therapy for gastric variceal bleeding. Cyanoacrylate embolism is difficult to diagnose with computed tomographic angiography because radiopaque emboli are masked by the contrast material. It is important to distinguish these emboli from conventional thromboemboli because "glue emboli" require only symptomatic treatment. Clinicians should have a high index of suspicion for embolism in the setting of tachycardia, chest pain, or hypoxia after a patient undergoes endoscopic injection therapy with cyanoacrylate glue for gastric variceal bleeding. The radiologist should be alerted so that the appropriate radiographic settings are used to make the diagnosis.

Glomus tumor of the trachea: value of multidetector computed tomographic virtual bronchoscopy.

Glomus tumor of the trachea is extremely rare. We report a case of tracheal glomus tumor in a 39-year-old man who presented with hemoptysis. The diagnosis was made after bronchoscopic biopsy of a tumor involving the posterior wall of the upper trachea. Thin-section multidetector computed tomography of the chest was performed before surgical resection, with multiplanar re-formations and 3-dimensional virtual bronchoscopic reconstruction. Tracheal sleeve resection with reconstruction was successful, and pathological studies confirmed complete resection and the diagnosis of glomus tumor. The patient was disease-free 3 months postoperatively. To our knowledge, this is the first reported case in which additional computed postprocessing was used to help evaluate the extent of such a tumor.

Lung cancer screening with CT: Mayo Clinic experience.

PURPOSE: To evaluate a large cohort of patients at high risk for lung cancer by using screening with low-dose spiral computed tomography (CT) of the chest. MATERIALS AND METHODS: A prospective cohort study was performed with 1,520 individuals aged 50 years or older who had smoked 20 pack-years or more. Participants underwent three annual low-dose CT examinations of the chest and upper abdomen. Characteristics of pulmonary nodules and additional findings were tabulated and analyzed. RESULTS: Two years after baseline CT scanning, 2,832 uncalcified pulmonary nodules were identified in 1,049 participants (69%). Forty cases of lung cancer were diagnosed: 26 at baseline (prevalence) CT examinations and 10 at subsequent annual (incidence) CT examinations. CT alone depicted 36 cases; sputum cytologic examination alone, two. There were two interval cancers. Cell types were as follows: squamous cell tumor, seven; adenocarcinoma or bronchioloalveolar carcinoma, 24; large cell tumor, two; non-small cell tumor, three; small cell tumor, four. The mean size of the non-small cell cancers detected at CT was 15.0 mm. The stages were as follows: IA, 22; IB, three; IIA, four; IIB, one; IIIA, five; IV, one; limited small cell tumor, four. Twenty-one (60%) of the 35 non-small cell cancers detected at CT were stage IA at diagnosis. Six hundred ninety-six additional findings of clinical importance were identified. CONCLUSION: CT can depict early-stage lung cancers. The rate of benign nodule detection is high.

Screening for lung cancer with low-dose spiral computed tomography.

Studies suggest that screening with spiral computed tomography can detect lung cancers at a smaller size and earlier stage than chest radiography can. To evaluate low-radiation-dose spiral computed tomography and sputum cytology in screening for lung cancer, we enrolled 1,520 individuals aged 50 yr or older who had smoked 20 pack-years or more in a prospective cohort study. One year after baseline scanning, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed (22 prevalence, 3 incidence). Computed tomography alone detected 23 cases; sputum cytology alone detected 2 cases. Cell types were: squamous cell, 6; adenocarcinoma or bronchioalveolar, 15; large cell, 1; small cell, 3. Twenty-two patients underwent curative surgical resection. Seven benign nodules were resected. The mean size of the non-small cell cancers detected by computed tomography was 17 mm (median, 13 mm). The postsurgical stage was IA, 13; IB, 1; IIA, 5; IIB, 1; IIIA, 2; limited, 3. Twelve (57%) of the 21 non-small cell cancers detected by computed tomography were stage IA at diagnosis. Computed tomography can detect early-stage lung cancers. The rate of benign nodule detection is high.