Diagnosis and typing of lung carcinomas by cytopathologic methods. A review of 108 cases

A correlative review was made of the type of cytology specimens (sputum, bronchial washing and bronchial brushing) together with the corresponding histopathologic specimens of 108 patients. One hundred patients had primary pulmonary carcinomas diagnosed histopathologically (84) or clinically (16); 5 had carcinomas metastatic to the lungs and 3 had apparently false-positive cytologic results for lung cancer. The correlative review was used to determine the diagnostic reliability of pulmonary cytopathologic techniques in the detection and classification of lung carcinomas (i.e., the sensitivity and accuracy). The overall sensitivities of sputum, bronchial washing and bronchial brushing cytology were 60%, 66% and 77%, respectively (p less than 0.05). Bronchial brushing had a higher sensitivity (80%) for peripheral and metastatic lesions than did sputum (37%) or bronchial washing (60%). The overall accuracies of sputum, bronchial washing and bronchial brushing cytology were 79%, 75% and 76%, respectively, which is not statistically different. Regardless of the sampling methods, cytologic typing of squamous-cell and small-cell carcinomas was highly accurate but was less satisfactory for the other types of lung carcinomas. In the 16 cases in which endoscopic biopsies were either not attempted or gave negative results, one or more pulmonary cytologic specimens showed malignant cells. It is concluded that: (1) pulmonary cytopathologic techniques have excellent sensitivity and accuracy in the diagnosis of lung carcinomas; (2) they may establish the diagnosis of pulmonary carcinomas when endoscopic biopsies give negative results; and (3) they are particularly helpful in cases in which endoscopic biopsies suffer from a low yield (peripheral lesions) or create a considerable danger to the patients (iatrogenic hemorrhage).     

Diagnosis of bronchial carcinoma on sections of paraffin-embedded sputum. Sensitivity and specificity of an alternative to routine cytology.

The diagnostic accuracy of sputum cytology for the diagnosis of bronchial carcinoma using paraffin-embedded, serially sectioned and hematoxylin and eosin-stained specimens was tested in 4,297 sputum samples from 1,889 patients, 219 of whom had bronchial carcinoma. The diagnostic sensitivity depended mainly on the number of investigated samples and was 85.4% with three sufficient sputa. The sensitivity was not influenced by the histologic types, location or TNM stage of the tumor. The specificity of the method was 99.5%. In three cases localization of sputum cytologically diagnosed bronchial carcinomas was not possible immediately (occult carcinomas, pTx); in two of these cases the bronchial carcinomas were located during follow-up. The third patient died without verification of the cytologic diagnosis. According to our results, sputum cytology on serial sections is a valuable instrument for mass screening of high-risk groups for the early detection of bronchial carcinoma. Lower sensitivities of sputum cytology in mass screening programs for the early diagnosis of lung cancer are discussed critically.     

Abrasive bronchial brushing cytology. A preliminary study of 200 specimens for the diagnosis of neoplastic and nonneoplastic bronchopulmonary lesions

Two hundred subjects with chronic respiratory symptoms with a suspicion of malignancy were selected for bronchial brushing cytology. Prior sputum examination had shown malignant squamous cells in two cases only. The cytologic appearances of the brushing smears were divided into five categories: 41 (20.5%) smears with positively malignant cells; 20 (10%) smears predominantly showing chronic inflammatory features; 31 (15.5%) smears with mainly acute inflammatory changes; 60 (30%) smears with normal cytologic features; and 48 (24%) smears unsatisfactory for cytologic interpretation. Thirteen patients with a positive cytology had a positive tissue biopsy for malignancy. Among the group with chronic inflammatory changes, acid-fast bacilli were identified in nine cases, and one smear showed frank tuberculous granuloma. In the unsatisfactory group, two cases showed malignant cells in the postbrushing sputum. There was one false-negative report for malignancy in the entire study. This study confirms the sensitivity and accuracy of bronchial brushing cytology in the diagnosis of various bronchopulmonary lesions, especially malignancy and pulmonary tuberculosis, in India.     

Diagnostic sensitivity and specificity of pulmonary cytology: comparison of techniques used in conjunction with flexible fiber optic bronchoscopy

We examined the accuracy of pulmonary cytology in 224 consecutive patients being evaluated for lung cancer. The diagnostic yeild of specimens obtained by various methods, including flexible fiber optic bronchoscopy (FFB), was compared. Among 69 patients with lung cancer, a cytologic diagnosis was made in 87%, including 73% with peripheral tumors. Prebronchoscopy sputa were positive in 50%, bronchial washings in 63%, postbronchoscopy sputa in 82% and bronchial brushings in 59% of the patients. In only one patient was the bronchial brush specimen the only positive cytologic specimen. Normal FFB and small cell undifferentiated cancer were found with increased frequency (P less than 0.05) among the nine patients (13%) with false-negative cytology. Among 155 patients with nonmalignant lung disease, 16 (10%) had false-positive specimens; this finding was significantly related (P less than 0.05) to necrotizing pneumonia in 13 of the 16 patients (81%). The overall diagnostic accuracy of cytology showed 87% sensitivity and 90% specificity, and the predictive value of a positive specimen was 79%. In the absence of necrotizing pneumonia these values exceeded 95%.     

Diagnosis of adenoid cystic carcinoma of the lung by bronchial brushing: a case report

BACKGROUND: A diagnosis of pulmonary adenoid cystic carcinoma on exfoliative cytology specimen is very uncommon. The diagnostic cytologic material typically is obtained following a tissue biopsy. No previous report of the diagnosis has been made on bronchial brushing cytologic material when the procedure preceded a tissue biopsy. CASE: A 44-year-old man who used to smoke cigarettes and was otherwise well complained of persistent cough for the past 6 months. A chest radiograph revealed a mass lesion in the left hilum. Computed tomography of the chest disclosed an irregular and spiculated soft tissue mass in the left apical anterior segment. Bronchial brushing via bronchoscope was performed, revealing carcinoma cells consistent with an adenoid cystic carcinoma on cytology. A bronchial biopsy and subsequent left upper lobectomy were performed, confirming the diagnosis of adenoid cystic carcinoma of the lung associated with tumor extension to the epithelial surface. CONCLUSION: A diagnosis of bronchial adenoid cystic carcinoma is possible on bronchial brushing. However, as a method in exfoliative cytology, the usefulness of bronchial brushing in diagnosing this tumor is limited by the neoplasm's proximity to the mucosal surface and whether the mucosa has been breached.     

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

Sputum cytology for the diagnosis of lung cancer. Comparison of smear and modified cell block methods

OBJECTIVE: To compare the sputum smear cytology and cell block methods for specimen adequacy, cytology quality and diagnostic accuracy in the diagnosis of lung cancer. STUDY DESIGN: We assessed 2,524 sputum specimens from 768 patients. The specimens were prepared as smears and cell blocks for cytopathologic examination between March 1, 1992, and December 31, 1998. The smear and cell block slides were evaluated both separately and together, and the results were compared with radiologic and histopathologic diagnoses. RESULTS: The sensitivity of the smear method was 69.4% and specificity was 99.5%. The sensitivity of the cell block method was 84.4% and specificity, 100%. The sensitivity of the smear and cell block together was 87.6% and specificity, 99.5%. CONCLUSION: The cell block method increases the sensitivity and specificity of sputum cytology, and when smear and cell block slides are evaluated together, sensitivity reaches its highest value. Therefore, application of smear and cell block methods together seems most useful in the diagnosis of lung cancer.     

Bronchial brushing cytology features of primary malignant fibrous histiocytoma of the lung. A case report

BACKGROUND: Malignant fibrous histiocytoma (MFH) of the lung is rare. Early diagnosis is very important because of its poor prognosis. Long-term survivors of pulmonary MFH are patients who had surgical resection. When the patient can undergo surgery after a prompt diagnosis, the prognosis improves more than with other therapy. However, it is not easy to establish the diagnosis of thoracic MFH. In general, the small fragments from bronchial or percutaneous transthoracic fine needle aspiration (FNA) biopsies are inadequate for cytologic or pathologic analysis. Bronchial brushing cytology is greatly superior to FNA cytology because one can obtain a large amount of cells. Therefore, bronchial brushing cytology may play a useful role in diagnosis when endobronchial involvement is found. CASE: A 65-year-old female was admitted with a cough, yellow sputum and exertional dyspnea. A chest roentgenogram showed a 12 x 12-cm mass in the left lung field. Bronchial brushing cytology revealed many fibroblastlike, histiocytelike, bizarre and multinucleated giant cells in a background of necrosis. Atypical mitotic figures were also found. The cytologic findings strongly suggested MFH. Although the pathologic findings from FNA biopsy showed storiform clusters structured by pleomorphic, fibroblastlike cells with bizarre nuclei and mitotic figures, the material was too small to diagnose it definitively. Six months later the patient died. An autopsy confirmed the diagnosis of MFH: the typical storiform clusters were composed of many fibroblastlike and histiocytelike cells that were positive for CD68 (PGM1) antibody. CONCLUSION: Bronchial brushing cytology may be a useful method for early, definitive diagnosis of MFH. The presence of pleomorphic, spindle-shaped fibroblastlike and histiocytelike cells with the clusters showing a storiform pattern may permit the diagnosis of MFH.     

A Highly Efficient Gene Expression Programming (GEP) Model for Auxiliary Diagnosis of Small Cell Lung Cancer

Background

Lung cancer is an important and common cancer that constitutes a major public health problem, but early detection of small cell lung cancer can significantly improve the survival rate of cancer patients. A number of serum biomarkers have been used in the diagnosis of lung cancers; however, they exhibit low sensitivity and specificity.

Methods

We used biochemical methods to measure blood levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), Na⁺, Cl^-, carcino-embryonic antigen (CEA), and neuron specific enolase (NSE) in 145 small cell lung cancer (SCLC) patients and 155 non-small cell lung cancer and 155 normal controls. A gene expression programming (GEP) model and Receiver Operating Characteristic (ROC) curves incorporating these biomarkers was developed for the auxiliary diagnosis of SCLC.

Results

After appropriate modification of the parameters, the GEP model was initially set up based on a training set of 115 SCLC patients and 125 normal controls for GEP model generation. Then the GEP was applied to the remaining 60 subjects (the test set) for model validation. GEP successfully discriminated 281 out of 300 cases, showing a correct classification rate for lung cancer patients of 93.75% (225/240) and 93.33% (56/60) for the training and test sets, respectively. Another GEP model incorporating four biomarkers, including CEA, NSE, LDH, and CRP, exhibited slightly lower detection sensitivity than the GEP model, including six biomarkers. We repeat the models on artificial neural network (ANN), and our results showed that the accuracy of GEP models were higher than that in ANN. GEP model incorporating six serum biomarkers performed by NSCLC patients and normal controls showed low accuracy than SCLC patients and was enough to prove that the GEP model is suitable for the SCLC patients.

Conclusion

We have developed a GEP model with high sensitivity and specificity for the auxiliary diagnosis of SCLC. This GEP model has the potential for the wide use for detection of SCLC in less developed regions.     

Neuron-specific enolase in the diagnosis and therapy monitoring of lung cancer: a comparison with CEA, TPA, ferritin and calcitonin

The significance of neuron-specific enolase (NSE) in the diagnosis and treatment monitoring of lung cancer was investigated in comparison with such established tumour markers as carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin and calcitonin. We determined the serum concentrations of these tumour markers in 25 patients with small cell lung cancer (SCLC), 30 patients with non small cell lung cancer (NSCLC), and 38 patients with benign pulmonary diseases (BPD). In 14 patients with lung cancer, it was possible to follow up the behaviour of the tumour markers under treatment for up to 16 months. Calcitonin proved to have a surprisingly low sensitivity for SCLC. The utility of TPA and of ferritin was restricted, although the sensitivity was comparably high, by the high rate of false positive results. For NSCLC, CEA proved to be the best tumour marker. At present, NSE appears to be the tumour marker with the greatest specificity and sensitivity for SCLC. Its determination in the diagnosis, treatment and follow-up of SCLC makes good sense.     

Increase of sensitivity of sputum cytology using high-resolution image cytometry: field study results

Lung cancer remains the leading cause of cancer deaths in the developed world. There is no widely accepted method to screen for this cancer. The most commonly used method remains conventional sputum cytology, but this method is hampered by low sensitivity. We tested the hypothesis that sensitivity of sputum cytology for early lung cancer can be greatly improved by using image analysis of sputum cells, at a modest reduction of specificity.The study was double-blinded and used sputum samples from subjects with well-characterized clinical diagnoses. There were 177 cancers, 98 dysplasias, and 558 normals. The study samples were separated into two independent sets: training set and test set. Sputum samples were collected prospectively from subjects with a high probability of having lung cancer. Seven institutions from five countries participated in the study. All subjects had complete clinical diagnoses which included, as a minimum, negative chest x-rays for all negative cancers, while all cancers had confirmed tissue pathology. Samples were prepared according to the Saccomanno method. For conventional cytology, slides were stained using Papanicolaou stain. For image analysis, slides were stained using a DNA-specific (Feulgen-Thionin) stain. An automated, high-resolution image cytometer was used for measurements.At 90% specificity, sensitivity of 60% can be achieved for adenocarcinoma, compared to only 14% sensitivity of conventional cytology (at 99% specificity). Similarly, 45% sensitivity at 90% specificity can be reached for stages 0 and I lung cancer, compared to only 14% (at 99% specificity) using conventional cytology.Cytometry combined with conventional cytology shows an increase in sensitivity to early-stage cancer and to adenocarcinomas compared to conventional cytology alone. While the results are encouraging, the sensitivity to detect early lung cancer should be further improved to 70-80% at 90-95% specificity before this test can be considered for screening of high-risk individuals for lung cancer. Cytometry (Clin. Cytometry) 50:168-176, 2002.     

The diagnostic accuracy of sputum and urine cytology

The diagnostic accuracies of sputum and urinary cytology were examined in series spanning more than 20 years. The sensitivity and respiratory tract cytology in 1,289 patients with subsequently proven lung cancer was 69% while that or urine cytology in 860 patients with urinary tract cancer was 77%. The specificities were 96% for lung cancer and 97% for urinary tract cancer. Neither procedure was widely used for routine screening, but diagnostic cytology played an important part in providing a definite morphologic diagnosis in many of these cases. Urinary cytology was also very effective in the follow-up of patients with treated bladder cancer because of its high sensitivity for detecting carcinoma in situ.     

Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer? – experience at Kuwait University

Objectives:  This prospective study was undertaken to evaluate nuclear matrix protein (NMP22) compared to urine cytology in the detection of bladder cancer and also to determine whether indexing suspicious cytology to NMP22 could enhance the clinical utility of cytology.
Methods:  Cytological findings of voided urine collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in 46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The patients were clinically categorized into newly diagnosed cases of transitional cell carcinoma (TCC), recurrent TCC, TCC in remission and controls.
Results:  Using histological diagnosis as the gold standard the sensitivity and specificity of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology were 30% and 87% respectively. If suspicious and malignant cytology were combined as positive results the sensitivity increased significantly to 87% while the specificity decreased but not significantly to 74%. Suspicious or malignant cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of 87% neither of which was significantly different from cytology alone. There were three false positive cases on cytology and 13 false positive cases on NMP22 assay. There were three false negative cytology and five false negative NMP22 cases but only one was false negative for both, resulting in a high sensitivity (96%) but low specificity (30%) if either positive NMP22 or malignant or suspicious cytology was taken as a positive result.
Conclusion:  Combining NMP22 with malignant or suspicious cytological result improved sensitivity for the detection of bladder cancer but with a major decrease in specificity, suggesting a potential role in screening rather than diagnosis.     

Immunocytologic diagnosis of small-cell lung cancer in imprint smears.

Imprints of histologic or autopsy specimens from 12 small-cell lung cancers (SCLCs), 82 non-SCLCs (50 adenocarcinomas, 25 squamous-cell carcinomas, 1 adenosquamous carcinoma and 6 large-cell carcinomas), 2 carcinoid tumors, 1 malignant lymphoma and 8 metastatic carcinomas were examined immunocytologically for the presence of cluster 1 SCLC antigen (neural-cell adhesion molecule: N-CAM), chromogranin A, Leu-7, neuron-specific enolase (NSE) and gastrin-releasing peptide (GRP). The monoclonal antibodies NCC-LU-243 and NCC-LU-246, which are reactive with cluster 1 SCLC antigen/N-CAM, diffusely stained the cell membranes of all SCLCs and carcinoid tumors (100%) and diffusely and focally stained those of two of the large-cell carcinomas, two of the adenocarcinomas, two of the squamous-cell carcinomas and the one adenosquamous carcinoma. Malignant lymphoma and metastatic carcinoma were negative for this antigen. A few cases of large-cell carcinoma, adenocarcinoma, squamous-cell carcinoma and adenosquamous carcinoma were also stained with these antibodies, which may indicate a neuroendocrine differentiation. However, these tumors were different from SCLCs in that their positive tumor cell population was definitely smaller than that in SCLC, in which almost all tumor cells were positive. This confirmed the usefulness of antibodies against cluster 1 SCLC antigen for the immunocytologic diagnosis of SCLC and carcinoid tumor in imprint smears. Chromogranin A, GRP, NSE and Leu-7 were not useful in immunocytologically differentiating the imprints from these cases since only a few tumor cells were reactive with these antibodies. The antibodies against cluster 1 SCLC antigen/N-CAM can also be applied to cytologic preparations of sputum, pleural fluid and fine needle aspirates stained routinely by the Papanicolaou method since the antigen is preserved in such alcohol-fixed smears.     

Immunoradiometric assay of chromogranin A in the diagnosis of small cell lung cancer: comparative evaluation with neuron-specific enolase

The aims of our work were 1) to determine the diagnostic performance of an immunoradiometric assay of chromogranin A (CgA) in small cell lung cancer and 2) to compare its discriminatory power with that of neuron-specific enolase (NSE), the marker currently used for SCLC. We selected 166 cases of small cell (64) and non-small cell (102) lung cancer and 106 cases of non-malignant lung diseases as controls. Both CgA and NSE were assayed by immunoradiometric methods and cutoff values were established on the basis of a pre-fixed specificity of 95% in non-malignant lung diseases. The CgA assay showed better diagnostic sensitivity than NSE in SCLC (61% versus 57%), especially in limited disease, and a low positivity rate in NSCLC with respect to NSE (14% versus 22%). By contrast, NSE reflected disease extent more accurately than CgA (U test: CgA p<0.05, NSE p<0.001). Finally, we found that the CgA assay was not affected by hemolysis whereas NSE serum levels greatly increased in hemolyzed sera. In conclusion, CgA assaying by an IRMA method is a reliable procedure in the diagnosis of SCLC. NSE remains the marker of choice in staging and monitoring of the disease. Further studies are needed to evaluate the prognostic significance of the marker and its role in therapy monitoring and patient follow-up.     

Immunohistochemical analysis and comparison of napsin A,TTF1, SPA and CK7 expression in primary lung adenocarcinoma

We investigated the expression of napsin A, TTF1, SPA and CK7 in primary lung adenocarcinoma (ADC) and compared antibody specificity and sensitivity. We used immunohistochemistry (IHC) using antibodies directed against napsin A, TTF1, SPA, and CK7 on cancer tissue from 454 patients diagnosed with lung cancer. In primary lung ADC, napsin A exhibited a sensitivity of 87.25% and specificity of 95.02%, TTF1 exhibited a sensitivity of 80.72% and specificity of 90.48%, SPA exhibited a sensitivity of 60.46% and specificity of 94.87% and CK7 exhibited a sensitivity of 100% and specificity of 80.31%. The order of sensitivity of the four indicators was CK7 > napsin A > TTF1 > SPA, and the order of specificity was napsin A > SPA > TTF1 > CK7. We can select effective indicators for diagnostic and differential diagnostic purposes based on differences in sensitivity and specificity.     

The role of transbronchial lung biopsy in the diagnosis of solitary pulmonary nodule

Transbronchial lung biopsy (TBLB) is a well-recognized diagnostic technique in diffuse interstitial lung diseases, but it is not considered to be the first choice in investigation of solitary pulmonary nodules (SPN). The main idea of this study was to increase the sensitivity of bronchoscopy using multiple techniques, especially TBLB, thus to avoid more aggressive diagnostic procedures. The objective of this prospective study was to evaluate the efficacy and safety of TBLB in the diagnosis of SPN, in comparison with other bronchoscopic techniques. Fifty patients with chest x-ray finding consistent with SPN underwent bronchoscopy with bronchial washing, brushing, bronchoalveolar lavage (BAL) and TBLB were included in this study. Thirty-one patients suffered from malignant tumors, while 19 patients had nonmalignant lesions. TBLB achieved overall diagnostic sensitivity of 62%, BAL of 29%, bronchial brushing of 16% and washing of 6%. Combining all techniques together, bronchoscopy had overall sensitivity of 86%. Concerning malignant lesions, TBLB had a sensitivity of 65%, specificity of 100%, and accuracy of 82%. TBLB had a significantly better yield for lesions with a diameter > or = 25 mm than for lesions of < 25 mm (sensitivity of 82% and 53% respectively, p < 0.05). Diagnostic yield improved significantly with the increasing number of specimens (less than 3 specimens: sensitivity 59%, 3 or more specimens: sensitivity 87%, p < 0.05). Complications of TBLB occurred in 2 (4%) patients: 1 incomplete pneumothorax and 1 hemorrhage. According to the results, we conclude that TBLB is an accurate and safe technique for the diagnosis of pulmonary solitary nodule with a diameter equal or greater than 25 mm.