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(Chest. 2000;117:1186-1190.)
© 2000 American College of Chest Physicians

Utility of On-Site Cytopathology Assessment for Bronchoscopic Evaluation of Lung Masses and Adenopathy*

Gregory B. Diette, MD; Peter White, Jr, MD; Peter Terry, MD; Mollie Jenckes, MHS; Dorothy Rosenthal, MD and Haya R. Rubin, MD

* From the Departments of Medicine (Drs. Diette, Terry, Jenckes, and Rubin) and Pathology (Dr. Rosenthal), The Johns Hopkins University School of Medicine, Baltimore, MD, and the Department of Medicine (Dr. White), the University of Arkansas for Medical Sciences, Little Rock, AK.

Correspondence to: Gregory B. Diette, MD, MHS, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, 1830 E. Monument St., Room 301, Baltimore, MD 21205; e-mail: gdiette{at}jhmi.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To determine the extent to which on-site cytopathology assessment improves diagnostic yield when sampling lung nodules or masses and/or hilar or mediastinal lymphadenopathy by fiberoptic bronchoscopy (FOB).

Design: Prospective cohort study.

Setting: Two teaching hospitals in Baltimore, MD.

Patients: Consecutive adult patients (>= 18 years) undergoing FOB for evaluation of lung nodules or masses and/or hilar or mediastinal lymphadenopathy.

Intervention: Prospective collection of data on patient factors and details of the procedure on standardized report forms.

Measurements and results: The primary outcome measure was a new diagnosis obtained by FOB. On-site assessment was used in 81 of 204 cases (40%), and overall diagnostic yield was 62%. Yield was greater when on-site cytopathology assessment was used, in unadjusted analysis (81% vs 50%, p < 0.001) and in a multivariate model (odds ratio, 4.5; 95% confidence interval, 2.1 to 10.0). Other significant predictors of a new diagnosis included older patient age, higher dose of narcotic used during FOB, and shorter procedure time.

Conclusions: We conclude that diagnostic yield was greater when on-site cytopathology was used to assist FOB evaluation of intrathoracic adenopathy and/or lung nodules or masses. Increasing the use of on-site cytopathology assessment may improve the quality of FOB services.

Key Words: cytopathology • fiberoptic bronchoscopy • lung cancer • quality of care


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Sampling of lung masses and hilar and mediastinal adenopathy by transbronchial needle aspiration is an effective means of diagnosing thoracic disease.1 2 3 4 5 6 7 Diagnostic yield of malignant neoplasms can be improved by on-site assessment by cytopathologists of specimens obtained via bronchoscopy. Davenport8 , in an observational study, showed that on-site assessment of specimens by a cytopathologist led to malignant cells being recovered twice as often and "inadequate" specimens one third as often, compared with routine processing. As nondiagnostic procedures often lead to repeat bronchoscopy, transthoracic needle aspiration, or invasive surgical procedures, obtaining a diagnosis the first time can reduce future risks, costs, morbidity, and anxiety for patients, as well as reduce the time to definitive treatments. Despite initial observations of on-site assessment, there have been no confirmatory studies. At our hospitals, we have cytopathologists available to attend bronchoscopy cases, but we do not routinely use these services.

As part of an ongoing bronchoscopy quality improvement project (BRONCHQI) to gather information to support a change in practice policy, we sought to determine the rate at which we use on-site cytopathology assessment services in fiberoptic bronchoscopy (FOB) cases to evaluate lung masses and/or adenopathy and to estimate the impact on diagnostic yield in our population. The purpose of this study was to confirm the findings of Davenport in a population with a high proportion of patients undergoing evaluation of adenopathy, as well as to evaluate the extent to which patient and other care factors alter the association between on-site assessment and diagnostic success.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
We conducted a prospective cohort study of consecutive adult patients undergoing FOB at the Johns Hopkins Medical Institutions (Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center) in Baltimore between July 1996 and June 1997. Our study is part of an ongoing project (BRONCHQI) that has multiple aims, including identifying predictors of outcomes of FOB to reduce adverse events, and to improve diagnostic success, comfort, and satisfaction in patients undergoing FOB.9 10

All patients eligible for this study of on-site cytopathology assessment were adults (>= 18 years) undergoing FOB to evaluate lung mass(es) and/or hilar or mediastinal adenopathy. FOBs were performed by Pulmonary and Critical Care Medicine fellows with faculty supervision or performed alone by full-time faculty members. Data were collected concurrently with performance of bronchoscopy. Standardized reporting instruments were developed for BRONCHQI to report information on patients (including demographics, comorbid conditions, immune status, bleeding factors), process of care factors (medication use, sampling methods, cytopathology on-site assessment), and outcomes (final diagnosis, adverse events). Our study was approved by the Johns Hopkins institutional review board, the Joint Commission on Clinical Investigation.

Outcome Measurement
The main outcome was whether or not a new diagnosis was made, based on samples obtained from the current FOB (eg, malignancy based on final cytology or surgical pathology report or mycobacterial infection based on cultures). Diagnoses were reported by the bronchoscopists based on their review of all cytopathologic, surgical pathologic, and microbiologic findings from the FOB. Success included new diagnoses made during the FOB, though not always made directly by cytopathologic assessment of specimens obtained by needle or brush biopsy (ie, microbiologic cultures, surgical pathology, cytopathology, direct visualization). We recognized that potential advantages of on-site assessment can be both positive (eg, case can be stopped because malignancy is confirmed) or negative (eg, no malignancy discovered, so bronchoscopist should keep sampling with the same or other methods).

Predictor Variables: Patient and Process of Care
Patient and process-of-care factors were identified by review of the literature and clinician judgment. Patient factors collected included age, sex, race, and immune status (normal vs abnormal). Specific immune deficiencies were also reported, including HIV, post-bone marrow transplantation, immunosuppressive medication use, and others. Process-of-care factors included diagnostic aids (on-site cytopathology assessment and fluoroscopy), sampling methods used (needle aspiration or biopsy, brushing [proximally or peripherally]), medications used and doses (fentanyl, midazolam), and length of the procedure (the length of time the bronchoscope was in the patient’s airways, in minutes).

Statistical Analysis
Patient and process-of-care factors were examined by proportions of categorical values and means (± SD) for continuous variables. Bivariate analyses consisted of comparisons of patient and process-of-care factors associated with a new diagnosis (yes or no). Statistical significance was determined by using the {chi}2 test, with statistically significant results reported as p < 0.05. For ease of interpretation of the bivariate analyses, continuous variables were examined in ordinal categories: time (<= 15, 16 to 30, 31 to 45, > 45 min), medication dose (fentanyl: 0 to 50, 51 to 100, > 100 µg; midazolam: 0 to 2, 2.1 to 4, > 4 mg), and age (18 to 30, 31 to 40, 41 to 65, > 65). As only 4% of patients were neither black nor white, race was examined as white vs nonwhite.

To assess the independence of on-site assessment effect on diagnostic yield, we developed multivariate logistic regression models.11 We considered factors from the bivariate analysis if p < 0.10 or if judged clinically important by the investigators. We retained factors with p < 0.05 in the models.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Between July 1996 and June 1997, 204 FOBs were performed to evaluate lung mass(es) and/or hilar or mediastinal adenopathy. The mean age of patients was 59.1 ± 15.6 years, 59.8% were male, and 62.8% were white. Only 16.2% of patients had a known immune deficiency. A new diagnosis was obtained in 127 cases (62.2%), and most new diagnoses were malignancies (94 cases). Other diagnoses included fungal and mycobacterial infections, sarcoidosis, benign pathology, organizing pneumonia, bronchiolitis obliterans organizing pneumonia, and bronchogenic cyst.

Yield was similar when the indication for FOB was to evaluate only adenopathy (62.5%) or only masses (61.2%). On-site cytopathology assessment was used in 81 cases (39.9%). Sampling methods included needle aspiration or biopsy in 54.7%, brushing of proximal lesion in 15.8%, brushing of peripheral lesion in 30.5%, and transbronchial biopsy in 35.5%. Mean number of needle attempts was slightly greater with on-site assessment (5.2 vs 4.4, not significant). Fentanyl was used in 98.0% of cases with a mean dose of 111.4 µg (range, 24 to 400 µg), and midazolam was used in 97.1% with a mean dose of 3.8 mg (range, 0.5 to 10 mg). Procedure length averaged 35.2 min (range, 4 to 122 min) and was longer with on-site assessment (39.1 vs 32.6 min, p < 0.01).

In bivariate analysis, older patients and those with normal immune status were more likely to have a new diagnosis (Table 1 ). FOBs with needle aspiration or biopsy had significantly greater diagnostic success, and those using peripheral brushing had less (Table 2 ). On-site cytopathology assessment was associated with greater diagnostic success (81% vs 50%) as was the use of higher, rather than lower, doses of narcotic.


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  		Table 1. Bivariate Associations of New Diagnosis With Patient Factors

 

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  		Table 2. Bivariate Associations of a New Diagnosis With Process of Care Factors

 
In multivariate analysis, advancing age was strongly associated with diagnostic success (Table 3 ). This finding mirrors the increasing prevalence of malignancy in older adults.12 The presence of on-site assessment was also a strong predictor (odds ratio, 4.5) of diagnostic success, even after controlling for the sampling methods used and patient age. A higher dose of narcotic was associated with success, and longer procedures were less likely to be successful.


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  		Table 3. Logistic Regression Model to Predict Diagnostic Success in Evaluation of Lung Mass(es) or Adenopathy

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study suggests the importance of using on-site cytopathology assessment of bronchoscopically obtained specimens to evaluate lung masses and adenopathy. In unadjusted analysis, the diagnostic yield was 64% greater when cytopathologists were present. After considering patient and process-of-care factors, a significant advantage persisted. For example, a 62-year-old patient undergoing a needle biopsy lasting 20 min and receiving 75 µg of fentanyl would have an 89% chance of a new diagnosis with on-site assessment and a 64% chance without (40% improvement in yield). As we used on-site assessment in only 40% of cases, we believe that increasing our use might have improved diagnostic yield.

Davenport,8 in a bivariate analysis, reported similar improvements in yield with on-site assessment (81% improvement). Reasons for the different rate of improvement in our study could include different mix of patient and process-of-care factors, although different study designs and reported clinical detail preclude direct comparison. Also, Davenport defined success as diagnosis of malignancy, whereas we considered a wide range of new diagnoses, including granulomatous diseases and infections.

To determine whether on-site findings by the cytopathologists were consistent with final reported diagnoses, we retrospectively examined the preliminary diagnoses recorded at one of the study hospitals. There were 45 cases during which on-site assessment was used. In 41 cases, the specimen was judged adequate or diagnostic on-site, and in four cases, it was judged inadequate. In the cases judged to be adequate, 37 (85%) were adequate on final review, whereas 15% were not. Of the four specimens initially judged inadequate, two (50%) ultimately yielded a definitive diagnosis. Thus, overall concordance of preliminary and final diagnoses was 87% (39 of 45 cases). Although the concordance was high, the cases of initial misclassification do show that on-site evaluation is not perfect. The final diagnosis considers the total specimen, processed several ways, including cytocentrifugation and thin-layer preparations, using multiple stains, and ancillary tests, including immunohistochemistry and flow cytometry. The additional testing that occurs between the preliminary and final diagnoses can explain some degree of discordance, but there may still be opportunities to improve on-site methods.

The finding that procedure time length was inversely related to success is not surprising. Longer procedures were likely those that were more difficult technically to perform, with lesions less accessible to the bronchoscopist. Longer procedure length could also be a marker of operator experience and skill, although we have not studied such factors in this study. In a model that did not include time, on-site assessment was still associated with significantly greater yield (odds ratio, 3.52; 95% confidence interval, 1.70 to 7.27). However, we prefer to include time in the multivariate model to partially account for potential confounding by difficulty and operator ability. The longer procedure time found with on-site assessment may have a penalty, as we have previously reported that procedure length is directly related to patient-reported nose pain.10

Finding that higher doses of the narcotic fentanyl were associated with success suggests that patient comfort (minimizing pain and cough) may be a significant contributor to diagnostic yield. Patients who are more comfortable may allow successful completion of the FOB, and if coughing less, they may interfere less with diagnostic sampling attempts.

In this study, patient age was the strongest predictor of obtaining a new diagnosis. The prevalence of many carcinomas, including lung cancer, increases markedly with advancing age.12 13 As the majority of new diagnoses in this study were cancers, the strong age effect was not surprising.

There are several limitations to our study. First, as this was an observational study, confounding by propensity to use on-site services could explain the apparent advantage of on-site assessment. If our bronchoscopists systematically invited cytopathologists to less-difficult cases, we could observe an apparent advantage of on-site assessment. On the other hand, if cytopathologists were involved in the more challenging cases, we may have underestimated their benefits. We are not aware of a standardized measure to characterize the difficulty of cases, although in our study, we found that cases that used proximal airway sampling methods (eg, needle or proximal brushing) had higher yield than those that used peripheral airway sampling methods (eg, transbronchial biopsy or peripheral brushing). Because the advantage of cytopathology persisted in multivariate models that accounted for sampling method, we believe that we have accounted for some degree of difficulty, and we have shown that advantages of on-site assessment persisted. Because this study was performed at a single institution, generalizations to other institutions may be limited if there are important differences in patient mix and in the capabilities of bronchoscopists and cytopathologists.

Although the advantages of on-site assessment of bronchoscopy samples by a cytopathologist may seem obvious to some clinicians, some pathologists argue against the practice because of the time involved. Remuneration may be sufficient to compensate for pathologist time, but reimbursement is highly variable, sometimes as low as nothing or a negotiated percentage of the charges, depending on the health-care coverage of the individual patient. At the Johns Hopkins Medical Institutions, the cytopathologist is accompanied by a cytology laboratory technician who prepares the smears and stains them outside the bronchoscopy suite. When the procedure requires multiple passes to harvest adequate material, the technician can be fixing and staining the smears while the pathologist is reviewing the prior slides. The average time spent by the pathologist and the laboratory technician is 45 min, and the standard charge for on-site assessment is $125.00. However, not only is adequacy for diagnosis assessed, but also the need for ancillary tests is appreciated on the spot. Therefore, adequate material is also obtained for cultures, flow cytometry, and immunochemical stains. If the pathologist deems necessary, a biopsy specimen can also be put into glutaraldehyde for electron microscopy. All of these ancillary tests are then started the same day as the procedure, saving at least 24 h in turnaround time for the final diagnosis. The need for repeat procedure or additional invasive tests is thereby saved because all the material for a complete diagnostic workup is obtained in one procedure.

The on-site assessment should be viewed in the same light as the intraoperative frozen section examination. Comparable clinician–pathologist interaction occurs in the two scenarios. However, the reimbursement philosophy has at times been different, with some third-party payers viewing the on-site assessment simply as part of the final diagnosis. This attitude obviously discourages the majority of pathologists from undertaking on-site assessment not only for lack of adequate staff, but also primarily for lack of adequate reimbursement.

With the experience at the Johns Hopkins Hospital, we are now considering performing on-site assessment for every bronchoscopic evaluation of lung masses and mediastinal hilar adenopathy because of the enhanced diagnostic yield and the accelerated patient throughput. We plan to evaluate costs related to on-site assessment and to perform a cost-benefit analysis. Independent of costs, however, we believe that the use of on-site assessment is clearly in the best interests of patients, as it can avert future invasive diagnostic procedures and decrease the time to therapy. We would suggest that guidelines be formulated by pulmonary, bronchology, or cytopathology specialty societies to delineate circumstances in which on-site assessment should be used.

We have again demonstrated the utility of on ongoing quality improvement project (BRONCHQI).9 10 By prospectively and systematically studying patient and process-of-care factors for an invasive diagnostic procedure, we can identify and confirm ways to improve the care that we deliver, and measure the effect of changes in care on outcomes over time. An aim of BRONCHQI was to identify ways to improve diagnostic yield. We have demonstrated the potential utility of a significant diagnostic aid and can use the information to plan additional studies of outcomes related to on-site cytopathology evaluation.


   Acknowledgements
 
The authors thank Debbie Belcastro, David Thompson, and Cara Zbylut for their diligence and hard work on many operational aspects of BRONCHQI. We thank Charles Wiener for many intangible contributions. We also deeply appreciate the assistance with data collection by the endoscopy nurses and technicians at the Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center.


   Footnotes
 
Abbreviations: BRONCHQI = bronchoscopy quality improvement project; FOB = fiberoptic bronchoscopy

Supported by The Johns Hopkins Medical Institutions.

Received for publication April 19, 1999. Accepted for publication October 18, 1999.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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