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Cytology in Fiberoptic Bronchoscopy: Comparison of Bronchial Brushing, Washing and Post-Bronchoscopy Sputum
Cytology in Fiberoptic Bronchoscopy Comparison of Bronchial Brushing, Washing and Post-Bronchoscopy Sputum* D . A. Solomon, M . D N . H. Solliday, D. R. Gracey, M.D., F . C . C . P . J
M.D.,f
and
Fiberoptic bronchoscopy was used to study 103 patients with suspected pulmonary neoplasm. Material for cytologic examination was obtained from bronchial brushing, bronchial washing and post-bronchoscopy sputum. In 87 patients, a definite diagnosis was made. The bronchial brush material was positive in 41 of the 46 patients with carcinoma. Bronchial washing plus post-bronchoscopy
sputum examination identified only one additional neoplasm. Of the 17 patients with hemoptysis and a normal chest roentgenogram a diagnosis was achieved in 14, but no carcinomas were found. It may be preferable to repeat the bronchial brushing rather than rely on bronchial washing or post-bronchoscopy sputum when the initial brushing is not diagnostic.
¥ ^ or over a century, it has b e e n k n o w n t h a t malign a n t cells can b e f o u n d in t h e b r o n c h i a l secretions of patients w i t h l u n g cancer. Cytology has b e c o m e an i m p o r t a n t a d j u n c t to histology a n d is f r e q u e n t l y t h e best m e t h o d of diagnosis. If t h e cytology of e x p e c t o r a t e d s p u t u m is normal, a diagnosis of m a l i g n a n c y m a y still b e possible f r o m material o b t a i n e d d u r i n g fiberoptic b r o n c h o s c o p y b y bronchial b r u s h i n g , bronchial washing, or t h e post-bronchoscopy s p u t u m ( P B S ) specimen.
tients with central lesions plus severe diffuse lung disease; when there was evidence of inoperability or other factors precluding surgery; and in patients with hemoptysis and a normal chest x-ray film. A total of 103 patients met these criteria—74 from a Veterans Administration Hospital and 29 from the private practice of D.G. Cytologic examination of spontaneously produced sputum was negative on at least three specimens in all patients.
It has b e e n o u r p r a c t i c e to o b t a i n all t h r e e types of specimens, b u t this imposes some h a z a r d s a n d disa d v a n t a g e s t h a t could b e eliminated if o n e or m o r e of these p r o c e d u r e s could b e discontinued. F o r example, b r o n c h i a l w a s h i n g has b e e n associated w i t h a c u t e lowering of arterial P021"3 w h i c h m a y b e physiologically undesirable. Post-bronchoscopy sput u m ( P B S ) collection requires a d e q u a t e p a t i e n t coo p e r a t i o n plus additional time b y n u r s i n g a n d laboratory personnel. W e h a v e r e v i e w e d o u r experience to d e t e r m i n e if t h e diagnosis of l u n g c a n c e r is imp r o v e d by t h e a d d i t i o n of t h e latter t w o m e t h o d s over a n d a b o v e results f r o m bronchial b r u s h i n g alone. METHODS
Sotirce of Patients All patients referred during a 15-month period for pulmonary consultation because of suspected lung cancer were considered for fiberoptic bronchoscopy.4 The procedure was performed in all patients with peripheral lung lesions; pa•From Northwestern University Medical School, Chicago. ••Trainee, NIH Graduate Training Grant. tAttending Physician, Northwestern Memorial Hospital; Associate in Medicine. •Director, Pulmonary Medicine Section, Wesley Pavillion, Northwestern Memorial Hospital; Assistant Professor of Medicine. Supported in part by NIH Training Grant HE 05694 and the Ernest S. Bazley Foundation. Manuscript received and accepted February 14. Reprint requests: Dr. David Cugell, 303 East Chicago Avenue, Chicago 60611 616
SOLOMON, SOLLIDAY, GRACEY
Technique of Bronchoscopy Patients were premedicated with intramuscular meperidine (25 to 75 mg) and atropine (0.4 to 0.8 mg) prior to the procedure. An aerosol topical anesthetic (Cetacaine) was applied to the posterior pharynx followed by 2-6 ml of 4 percent lidocaine applied to the vocal cords and trachea. One to 10 mg of diazepam were administered intravenously immediately prior to the procedure in most patients. A minimum dose was chosen so that the patient was drowsy but responsive to commands. Oxygen at 2-5 L/min was given continuously through nasal prongs. A soft rubber endotracheal tube without a cuff was guided into position via the mouth by the bronchoscope. The tube facilitated repeated passages of the bronchoscope for subsequent procedures such as brushing and collection of washings. Additional small quantities of lidocaine were instilled through the bronchoscope as needed to control coughing. This was especially common on entering the upper lobe bronchi. Collection of Specimens Lesions and suspicious areas visible through the fiberscope were biopsied with the biopsy forceps made for the BF5B2 Olympus bronchoscope. The cytology brush was positioned with the fiberscope. When a peripheral lesion was present, fluoroscopic guidance was also used. Material on the brush was spread over the surface of several slides which were immersed immediately in 95 percent alcohol. Two or more brushings were made from each lesion. One or two washings with 20-30 ml of normal saline solution were also performed in the appropriate area of the bronchial tree. The aspirate was collected in a Luken's trap to which 95 percent alcohol was added. The precipitated aspirate was prepared for histologic examination of the cell block and for cytologic study. All sputa expectorated during the 24 hours subsequent to bronchoscopy was collected. All specimens were read by the same cytotechnologist and pathologist. Specimens which did not contain carbon-laden histiocytes CHEST, 65: 6, JUNE, 1974
Table 1—Results of Fiberoptic Primary lung tumor Cell Type
Bronchoscopy
Table 3—Cytologic Findings in 11 Central Tumors 47
Central
squamous cell large cell undiff •small cell undiff adenocarcinoma malignant-cell type not classified hamartoma "Tuberculosis Bronchitis Pneumonia Bronchiectasis Abscess (bacterial) Sjogren's syndrome with lung Reticulum cell sarcoma Mitral stenosis Pulmonary emboli Unknown
Peripheral
6 1 0 1
14 8 5 3
2 1
6 0
involvement
•Total Patients
6 11 11 4 5 1 1 1 1 16 103
"Includes one patient who had both TB and small cell carcinoma were judged inadequate and called class O. The five other classifications are: (1) absence of atypical cells; (2) apparently benign changes; (3) changes suggestive of malignancy; (4) changes highly suggestive of malignancy; (5) changes conclusive of malignancy. In class 5, cell type was identifiable. RESULTS
Table 1 lists the final diagnosis of each patient, plus the cell type and location of all identified neoplasms. There were 47 patients with proved tumors among the 103 patients we examined. Twenty patients had squamous cell carcinoma, of which six were central in location, ie, visible with the bronchoscope. In the other 27 patients with a neoplasm, a central location was found in: one of nine, one of four, and none of five large cell undifferentiated, adenocarcinoma, and small cell undifferentiated carcinomas respectively. Eight tumors were definitely malignant, but the cell type could not be classified. Two of these eight tumors were central in location (Table 1). In 16 patients, the cytology and culture results of the specimens were negative. These individuals had a resolving infiltrate of presumed viral or bacterial origin. They have been followed from 5 to 13 months without recurrence of illness. Table 2—Location of Lesions on Chest X-Ray Film Right upper lobe Right middle lobe Right lower lobe Left upper lobe Lingula Left lower lobe Normal
27 7 12 25 6 9 17 TOTAL
CHEST, 65: 6, JUNE, 1974
103
Brush
Cell Type squamous cell squamous cell squamous cell squamous cell squamous cell squamous cell large cell adenocarcinoma unclassified unclassified hamartoma
5 5 5 5 5 4 5 4 4 4 1
Cytologic Class Wash PBS* 3 3 0 2 1 4 1 1 1 2 1
2 2 1 2 1 2 1 1 2 1 1
*Post-bronchoscopy sputum
The anatomic location of the lesions seen on the chest x-ray films is given in Table 2. The apparent preference for the upper lobes (58/103) is an artifact resulting from the relative unsuitability of the rigid bronchoscope for studying these areas and the preferential use of the fiberoptic bronchoscope in these patients. The final three tables compare the cytologic findings from material obtained by bronchial brushing, washing and the post-bronchoscopy sputum in 11 patients with central tumors (Table 3), 36 with peripheral tumors (Table 4) and 17 with normal chest roentgenograms who were suspected of neoplasm because of hemoptysis (Table 5). The brush specimen was diagnostic of malignancy (class 4 or 5) in 10 of 11 patients with central tumors (Table 3). In six patients, the cell type was recognizable on the cytologic specimen. In the remaining four, cell type was determined by histologic examination of material obtained with the biopsy forceps via the fiberoptic bronchoscope. The one patient with a benign tumor, a hamartoma, had negative cytology from every source. In no instance did bronchial wash specimens have a higher cytologic classification than the bronchial brush specimens. Indeed, if we had relied solely on the washings, a diagnosis of definite malignancy would have been made in only one case. Post-bronchoscopy sputum specimens provided an even lower yield than the washings and were never diagnostic by themselves. Table 4 gives our experience with proved peripheral lung tumors. Using the fluoroscope to check the brush position, diagnostic specimens were obtained in 23 of 25 ( 92 percent) patients. Eleven patients with peripheral tumors were examined during a period when our fluoroscope was out of order. The brush specimen was diagnostic in seven of these 11 patients. In two cases, the washings provided a more diagnostic cytologic classification than the brushing. One of these patients had a squamous cell carcinoma of the right upper lobe. His brushing was class 4, while the washing was class 5; this diagnosis would not CYTOLOGY IN FIBEROPTIC BRONCHOSCOPY
617
Table 4—Cytologic Findings in 36 Proved Peripheral Cell Type
Brush
sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell large cell large cell large cell large cell
5 5 5 5 5 5 5 5 5 4 4 4 4 2 5 5 5 5
Cytologic Class Wash PBS* 2 2 2 2 2 5 4 4 4 1 2 5 4 2 2 3 1 1
3 2 1 4 2 lost lost 3 4 5 1 3 1 2 2 2 1 1
Tumors
Cell Type
Brush
large cell large cell large cell large cell small cell small cell small cell small cell small cell adenoca. adenoca. adenoca. unclass. unclass. unclass. unclass. unclass. unclass.
5 4 2 2 5 5 4 2 1 5 4 4 5 4 4 4 4 2
Cytologic Class Wash PBS* 2 1 2 1 2 3 2 1 1 2 2 2 5 2 1 1 2 4
4 1 2 2 2 5 2 2 1 1 2 2 1 2 1 2 1 4
* Post-bronchoscopy sputum
have been missed if only the brushing were done. The second case was similar with a squamous cell carcinoma of the left upper lobe. The PBS was class 5, but the brushing was class 4. In one unclassified carcinoma of the left lower lobe, both the washings and PBS gave class 4 specimens, but the brushings yielded material of only class 2. Although the fluoroscope was used to check the brush position, in this case the brush may not have come into contact with the tumor or material may have been lost during withdrawal of the brush. Bronchial brushings were diagnostic of malignancy in 30 of 36 proved peripheral tumors, washings were diagnostic in eight of the 36, while the PBS detected cancer in only six. Washings and PBS combined were somewhat better than either one Table 5—Hemoptysis with Normal Chest X-Ray Films (First episode) Diagnosis Bronchitis Asthma with bronchitis Bronchitis Unknown, no recurrence Bronchitis Bronchitis Tuberculosis Bronchitis Tuberculosis Unknown, no recurrence Unknown, no recurrence Bronchiectasis Bronchitis Pulmonary emboli Mitral stenosis Bronchitis Bronchitis
Brush
Cytologic Class Wash PBS*
alone. The PBS was diagnostic of malignancy in four of 28 cases in which the washings failed, and the washings were diagnostic of malignancy in 4 of 28 where the PBS failed. In six proved cases, a diagnostic brushing was not obtained, but in only one of these was there a positive washing or positive PBS (the same case). Thus, the addition of washing and PBS to bronchial brushing resulted in a diagnosis in only one additional case. In 17 patients with their first episode of hemoptysis and a normal chest roentgenogram, a definite diagnosis was obtained in 14 (Table 5). Malignancy was not found in any patient. The three undiagnosed cases had negative cytologic specimens from all sources and were followed for a minimum of seven months without any disease process developing. One patient of the 103 had a significant complication of bronchoscopy. He had subacute bronchitis with recurrent hemoptysis and a negative chest x-ray film. Immediately following bronchoscopy, he had an episode of laryngospasm which was managed conservatively and resolved promptly. DISCUSSION
X 1
* Post-bronchoscopy sputum X Not done 618 SOLOMON, SOLLIDAY, 6RACEY
In his review of the world literature on early detection of lung cancer, Davies5 reported that in various series 23.7 to 79 percent of "well-established peripheral carcinomas" were cytologically positive. Oswald and associates6 found a positive sputum cytology in 48 percent of 2545 patients with primary lung cancer. Positive results increased as more specimens were examined, with up to 85 percent of all malignancies being detected when four or more samples were examined.6 Sputa obtained after bronchoscopy were frequently positive even if previous sputa were negative.7 CHEST, 65: 6, JUNE, 1974
These impressive figures were obtained prior to the availability of fiberoptic bronchoscopy and bronchial brushing. With access to a much greater portion of the bronchial tree there has been a higher yield. Zavala et al8 found positivity rates of 72, 82 and 89 percent for non-mobile bronchial brushing catheters, mobile catheters, and brushes guided by bronchofiberscope respectively. A bronchial brush guided by the fiberoptic bronchoscope and the fluoroscope (for peripheral lesions) was very useful since diagnosis was made in 41 of 46 patients with carcinoma and in 87 of the 103 patients in the whole series. In contrast to brushing, the yield obtained by bronchial washing was very small. Washings were positive for cancer in only 7 of 46 patients. In all but one of these the diagnosis was established by bronchial brushing. Post-bronchoscopy sputum specimens were also disappointing in that only six of 44 patients were positive for cancer. Again, all but one of these had a diagnostic bronchial brushing. Thus, the additional yield from combining bronchial washing with PBS after bronchial brushing is very small. Whenever good material is obtained with the bronchial brush, then either washing or PBS can be omitted. Since neither the wash nor PBS is superior to the other, maximum diagnostic yield is obtained by combining brushing with either PBS or washing. Because of the ready acceptance of fiberoptic bronchoscopy by patients repeat bronchoscopy should be considered whenever initial specimens are nondiagnostic. Patients presenting with hemoptysis and a normal chest roentgenogram are a special group. Pulmonary neoplasm is usually suspected and fiberoptic bronchoscopy is potentially very useful. Rath and colleagues9 reported 17 such patients as part of a larger series. A definite diagnosis was achieved in 12, but a malignancy was found in only one. Richardson and
CHEST, 65: 6, JUNE, 1974
coworkers10 found an explanation for nine of their 23 patients with hemoptysis and a normal x-ray film. Only three had neoplasms. We have routinely bronchoscoped every patient with significant hemoptysis and established a diagnosis in 14 of 17 such patients during the period of this study (Table 5). No neoplasms were seen nor has one yet become apparent. Although this series of patients is small, bronchoscopy does not appear to be indicated as a part of the work-up of a patient experiencing his first episode of hemoptysis if the chest x-ray film is negative and good quality sputum specimens for cytology are negative. If fiberoptic bronchoscopy is done in these patients and no lesion is seen, then further search for a carcinoma at this time is futile. REFERENCES
1 Harrell JH, et al: Gas exchange abnormalities induced during fiberoptic bronchoscopy. Am Rev Resp Dis 107: 1091, 1973 (abstract) 2 Dubrowsky C, Arve R, Jenkins D: Effect of fiberoptic bronchoscopy on oxygenation of arterial blood. Chest 64:393, 1973 (abstract) 3 Kleinholz E, Fussell J, McBrayer R: Arterial blood gas studies during fiberoptic bronchoscopy. Am Rev Resp Dis 108:1014, 1973 4 Ikeda S: Flexible bronchofiberscope. Ann Otol Rhinol Laryngol 79:916, 1970 5 Davies DF: A review of detection methods for the early diagnosis of lung cancer. J Chron Dis 19:819-845, 1966 6 Oswald NC, et al: The diagnosis of primary lung cancer with special reference to sputum cytology. Thorax 26:623631, 1971 7 Grunge H: Cytologic diagnosis of tumors of the chest. Acta Cytologica 17:148-159, 1973 8 Zavala DG, et al: Use of bronchofiberscope for bronchial brush biopsy. Chest 63:889-892, 1973 9 Rath GS, Schaff JT, Snider GL: Flexible fiberoptic bronchoscopy. Chest 63:689-693, 1973 10 Richardson RH, et al: The use of fiberoptic bronchoscopy and brush biopsy in the diagnosis of suspected pulmonary malignancy. Am Rev Resp Dis 109:63-66, 1974
CYTOLOGY IN FIBEROPTIC BRONCHOSCOPY
619
M.D.,f
and
Fiberoptic bronchoscopy was used to study 103 patients with suspected pulmonary neoplasm. Material for cytologic examination was obtained from bronchial brushing, bronchial washing and post-bronchoscopy sputum. In 87 patients, a definite diagnosis was made. The bronchial brush material was positive in 41 of the 46 patients with carcinoma. Bronchial washing plus post-bronchoscopy
sputum examination identified only one additional neoplasm. Of the 17 patients with hemoptysis and a normal chest roentgenogram a diagnosis was achieved in 14, but no carcinomas were found. It may be preferable to repeat the bronchial brushing rather than rely on bronchial washing or post-bronchoscopy sputum when the initial brushing is not diagnostic.
¥ ^ or over a century, it has b e e n k n o w n t h a t malign a n t cells can b e f o u n d in t h e b r o n c h i a l secretions of patients w i t h l u n g cancer. Cytology has b e c o m e an i m p o r t a n t a d j u n c t to histology a n d is f r e q u e n t l y t h e best m e t h o d of diagnosis. If t h e cytology of e x p e c t o r a t e d s p u t u m is normal, a diagnosis of m a l i g n a n c y m a y still b e possible f r o m material o b t a i n e d d u r i n g fiberoptic b r o n c h o s c o p y b y bronchial b r u s h i n g , bronchial washing, or t h e post-bronchoscopy s p u t u m ( P B S ) specimen.
tients with central lesions plus severe diffuse lung disease; when there was evidence of inoperability or other factors precluding surgery; and in patients with hemoptysis and a normal chest x-ray film. A total of 103 patients met these criteria—74 from a Veterans Administration Hospital and 29 from the private practice of D.G. Cytologic examination of spontaneously produced sputum was negative on at least three specimens in all patients.
It has b e e n o u r p r a c t i c e to o b t a i n all t h r e e types of specimens, b u t this imposes some h a z a r d s a n d disa d v a n t a g e s t h a t could b e eliminated if o n e or m o r e of these p r o c e d u r e s could b e discontinued. F o r example, b r o n c h i a l w a s h i n g has b e e n associated w i t h a c u t e lowering of arterial P021"3 w h i c h m a y b e physiologically undesirable. Post-bronchoscopy sput u m ( P B S ) collection requires a d e q u a t e p a t i e n t coo p e r a t i o n plus additional time b y n u r s i n g a n d laboratory personnel. W e h a v e r e v i e w e d o u r experience to d e t e r m i n e if t h e diagnosis of l u n g c a n c e r is imp r o v e d by t h e a d d i t i o n of t h e latter t w o m e t h o d s over a n d a b o v e results f r o m bronchial b r u s h i n g alone. METHODS
Sotirce of Patients All patients referred during a 15-month period for pulmonary consultation because of suspected lung cancer were considered for fiberoptic bronchoscopy.4 The procedure was performed in all patients with peripheral lung lesions; pa•From Northwestern University Medical School, Chicago. ••Trainee, NIH Graduate Training Grant. tAttending Physician, Northwestern Memorial Hospital; Associate in Medicine. •Director, Pulmonary Medicine Section, Wesley Pavillion, Northwestern Memorial Hospital; Assistant Professor of Medicine. Supported in part by NIH Training Grant HE 05694 and the Ernest S. Bazley Foundation. Manuscript received and accepted February 14. Reprint requests: Dr. David Cugell, 303 East Chicago Avenue, Chicago 60611 616
SOLOMON, SOLLIDAY, GRACEY
Technique of Bronchoscopy Patients were premedicated with intramuscular meperidine (25 to 75 mg) and atropine (0.4 to 0.8 mg) prior to the procedure. An aerosol topical anesthetic (Cetacaine) was applied to the posterior pharynx followed by 2-6 ml of 4 percent lidocaine applied to the vocal cords and trachea. One to 10 mg of diazepam were administered intravenously immediately prior to the procedure in most patients. A minimum dose was chosen so that the patient was drowsy but responsive to commands. Oxygen at 2-5 L/min was given continuously through nasal prongs. A soft rubber endotracheal tube without a cuff was guided into position via the mouth by the bronchoscope. The tube facilitated repeated passages of the bronchoscope for subsequent procedures such as brushing and collection of washings. Additional small quantities of lidocaine were instilled through the bronchoscope as needed to control coughing. This was especially common on entering the upper lobe bronchi. Collection of Specimens Lesions and suspicious areas visible through the fiberscope were biopsied with the biopsy forceps made for the BF5B2 Olympus bronchoscope. The cytology brush was positioned with the fiberscope. When a peripheral lesion was present, fluoroscopic guidance was also used. Material on the brush was spread over the surface of several slides which were immersed immediately in 95 percent alcohol. Two or more brushings were made from each lesion. One or two washings with 20-30 ml of normal saline solution were also performed in the appropriate area of the bronchial tree. The aspirate was collected in a Luken's trap to which 95 percent alcohol was added. The precipitated aspirate was prepared for histologic examination of the cell block and for cytologic study. All sputa expectorated during the 24 hours subsequent to bronchoscopy was collected. All specimens were read by the same cytotechnologist and pathologist. Specimens which did not contain carbon-laden histiocytes CHEST, 65: 6, JUNE, 1974
Table 1—Results of Fiberoptic Primary lung tumor Cell Type
Bronchoscopy
Table 3—Cytologic Findings in 11 Central Tumors 47
Central
squamous cell large cell undiff •small cell undiff adenocarcinoma malignant-cell type not classified hamartoma "Tuberculosis Bronchitis Pneumonia Bronchiectasis Abscess (bacterial) Sjogren's syndrome with lung Reticulum cell sarcoma Mitral stenosis Pulmonary emboli Unknown
Peripheral
6 1 0 1
14 8 5 3
2 1
6 0
involvement
•Total Patients
6 11 11 4 5 1 1 1 1 16 103
"Includes one patient who had both TB and small cell carcinoma were judged inadequate and called class O. The five other classifications are: (1) absence of atypical cells; (2) apparently benign changes; (3) changes suggestive of malignancy; (4) changes highly suggestive of malignancy; (5) changes conclusive of malignancy. In class 5, cell type was identifiable. RESULTS
Table 1 lists the final diagnosis of each patient, plus the cell type and location of all identified neoplasms. There were 47 patients with proved tumors among the 103 patients we examined. Twenty patients had squamous cell carcinoma, of which six were central in location, ie, visible with the bronchoscope. In the other 27 patients with a neoplasm, a central location was found in: one of nine, one of four, and none of five large cell undifferentiated, adenocarcinoma, and small cell undifferentiated carcinomas respectively. Eight tumors were definitely malignant, but the cell type could not be classified. Two of these eight tumors were central in location (Table 1). In 16 patients, the cytology and culture results of the specimens were negative. These individuals had a resolving infiltrate of presumed viral or bacterial origin. They have been followed from 5 to 13 months without recurrence of illness. Table 2—Location of Lesions on Chest X-Ray Film Right upper lobe Right middle lobe Right lower lobe Left upper lobe Lingula Left lower lobe Normal
27 7 12 25 6 9 17 TOTAL
CHEST, 65: 6, JUNE, 1974
103
Brush
Cell Type squamous cell squamous cell squamous cell squamous cell squamous cell squamous cell large cell adenocarcinoma unclassified unclassified hamartoma
5 5 5 5 5 4 5 4 4 4 1
Cytologic Class Wash PBS* 3 3 0 2 1 4 1 1 1 2 1
2 2 1 2 1 2 1 1 2 1 1
*Post-bronchoscopy sputum
The anatomic location of the lesions seen on the chest x-ray films is given in Table 2. The apparent preference for the upper lobes (58/103) is an artifact resulting from the relative unsuitability of the rigid bronchoscope for studying these areas and the preferential use of the fiberoptic bronchoscope in these patients. The final three tables compare the cytologic findings from material obtained by bronchial brushing, washing and the post-bronchoscopy sputum in 11 patients with central tumors (Table 3), 36 with peripheral tumors (Table 4) and 17 with normal chest roentgenograms who were suspected of neoplasm because of hemoptysis (Table 5). The brush specimen was diagnostic of malignancy (class 4 or 5) in 10 of 11 patients with central tumors (Table 3). In six patients, the cell type was recognizable on the cytologic specimen. In the remaining four, cell type was determined by histologic examination of material obtained with the biopsy forceps via the fiberoptic bronchoscope. The one patient with a benign tumor, a hamartoma, had negative cytology from every source. In no instance did bronchial wash specimens have a higher cytologic classification than the bronchial brush specimens. Indeed, if we had relied solely on the washings, a diagnosis of definite malignancy would have been made in only one case. Post-bronchoscopy sputum specimens provided an even lower yield than the washings and were never diagnostic by themselves. Table 4 gives our experience with proved peripheral lung tumors. Using the fluoroscope to check the brush position, diagnostic specimens were obtained in 23 of 25 ( 92 percent) patients. Eleven patients with peripheral tumors were examined during a period when our fluoroscope was out of order. The brush specimen was diagnostic in seven of these 11 patients. In two cases, the washings provided a more diagnostic cytologic classification than the brushing. One of these patients had a squamous cell carcinoma of the right upper lobe. His brushing was class 4, while the washing was class 5; this diagnosis would not CYTOLOGY IN FIBEROPTIC BRONCHOSCOPY
617
Table 4—Cytologic Findings in 36 Proved Peripheral Cell Type
Brush
sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell sq cell large cell large cell large cell large cell
5 5 5 5 5 5 5 5 5 4 4 4 4 2 5 5 5 5
Cytologic Class Wash PBS* 2 2 2 2 2 5 4 4 4 1 2 5 4 2 2 3 1 1
3 2 1 4 2 lost lost 3 4 5 1 3 1 2 2 2 1 1
Tumors
Cell Type
Brush
large cell large cell large cell large cell small cell small cell small cell small cell small cell adenoca. adenoca. adenoca. unclass. unclass. unclass. unclass. unclass. unclass.
5 4 2 2 5 5 4 2 1 5 4 4 5 4 4 4 4 2
Cytologic Class Wash PBS* 2 1 2 1 2 3 2 1 1 2 2 2 5 2 1 1 2 4
4 1 2 2 2 5 2 2 1 1 2 2 1 2 1 2 1 4
* Post-bronchoscopy sputum
have been missed if only the brushing were done. The second case was similar with a squamous cell carcinoma of the left upper lobe. The PBS was class 5, but the brushing was class 4. In one unclassified carcinoma of the left lower lobe, both the washings and PBS gave class 4 specimens, but the brushings yielded material of only class 2. Although the fluoroscope was used to check the brush position, in this case the brush may not have come into contact with the tumor or material may have been lost during withdrawal of the brush. Bronchial brushings were diagnostic of malignancy in 30 of 36 proved peripheral tumors, washings were diagnostic in eight of the 36, while the PBS detected cancer in only six. Washings and PBS combined were somewhat better than either one Table 5—Hemoptysis with Normal Chest X-Ray Films (First episode) Diagnosis Bronchitis Asthma with bronchitis Bronchitis Unknown, no recurrence Bronchitis Bronchitis Tuberculosis Bronchitis Tuberculosis Unknown, no recurrence Unknown, no recurrence Bronchiectasis Bronchitis Pulmonary emboli Mitral stenosis Bronchitis Bronchitis
Brush
Cytologic Class Wash PBS*
alone. The PBS was diagnostic of malignancy in four of 28 cases in which the washings failed, and the washings were diagnostic of malignancy in 4 of 28 where the PBS failed. In six proved cases, a diagnostic brushing was not obtained, but in only one of these was there a positive washing or positive PBS (the same case). Thus, the addition of washing and PBS to bronchial brushing resulted in a diagnosis in only one additional case. In 17 patients with their first episode of hemoptysis and a normal chest roentgenogram, a definite diagnosis was obtained in 14 (Table 5). Malignancy was not found in any patient. The three undiagnosed cases had negative cytologic specimens from all sources and were followed for a minimum of seven months without any disease process developing. One patient of the 103 had a significant complication of bronchoscopy. He had subacute bronchitis with recurrent hemoptysis and a negative chest x-ray film. Immediately following bronchoscopy, he had an episode of laryngospasm which was managed conservatively and resolved promptly. DISCUSSION
X 1
* Post-bronchoscopy sputum X Not done 618 SOLOMON, SOLLIDAY, 6RACEY
In his review of the world literature on early detection of lung cancer, Davies5 reported that in various series 23.7 to 79 percent of "well-established peripheral carcinomas" were cytologically positive. Oswald and associates6 found a positive sputum cytology in 48 percent of 2545 patients with primary lung cancer. Positive results increased as more specimens were examined, with up to 85 percent of all malignancies being detected when four or more samples were examined.6 Sputa obtained after bronchoscopy were frequently positive even if previous sputa were negative.7 CHEST, 65: 6, JUNE, 1974
These impressive figures were obtained prior to the availability of fiberoptic bronchoscopy and bronchial brushing. With access to a much greater portion of the bronchial tree there has been a higher yield. Zavala et al8 found positivity rates of 72, 82 and 89 percent for non-mobile bronchial brushing catheters, mobile catheters, and brushes guided by bronchofiberscope respectively. A bronchial brush guided by the fiberoptic bronchoscope and the fluoroscope (for peripheral lesions) was very useful since diagnosis was made in 41 of 46 patients with carcinoma and in 87 of the 103 patients in the whole series. In contrast to brushing, the yield obtained by bronchial washing was very small. Washings were positive for cancer in only 7 of 46 patients. In all but one of these the diagnosis was established by bronchial brushing. Post-bronchoscopy sputum specimens were also disappointing in that only six of 44 patients were positive for cancer. Again, all but one of these had a diagnostic bronchial brushing. Thus, the additional yield from combining bronchial washing with PBS after bronchial brushing is very small. Whenever good material is obtained with the bronchial brush, then either washing or PBS can be omitted. Since neither the wash nor PBS is superior to the other, maximum diagnostic yield is obtained by combining brushing with either PBS or washing. Because of the ready acceptance of fiberoptic bronchoscopy by patients repeat bronchoscopy should be considered whenever initial specimens are nondiagnostic. Patients presenting with hemoptysis and a normal chest roentgenogram are a special group. Pulmonary neoplasm is usually suspected and fiberoptic bronchoscopy is potentially very useful. Rath and colleagues9 reported 17 such patients as part of a larger series. A definite diagnosis was achieved in 12, but a malignancy was found in only one. Richardson and
CHEST, 65: 6, JUNE, 1974
coworkers10 found an explanation for nine of their 23 patients with hemoptysis and a normal x-ray film. Only three had neoplasms. We have routinely bronchoscoped every patient with significant hemoptysis and established a diagnosis in 14 of 17 such patients during the period of this study (Table 5). No neoplasms were seen nor has one yet become apparent. Although this series of patients is small, bronchoscopy does not appear to be indicated as a part of the work-up of a patient experiencing his first episode of hemoptysis if the chest x-ray film is negative and good quality sputum specimens for cytology are negative. If fiberoptic bronchoscopy is done in these patients and no lesion is seen, then further search for a carcinoma at this time is futile. REFERENCES
1 Harrell JH, et al: Gas exchange abnormalities induced during fiberoptic bronchoscopy. Am Rev Resp Dis 107: 1091, 1973 (abstract) 2 Dubrowsky C, Arve R, Jenkins D: Effect of fiberoptic bronchoscopy on oxygenation of arterial blood. Chest 64:393, 1973 (abstract) 3 Kleinholz E, Fussell J, McBrayer R: Arterial blood gas studies during fiberoptic bronchoscopy. Am Rev Resp Dis 108:1014, 1973 4 Ikeda S: Flexible bronchofiberscope. Ann Otol Rhinol Laryngol 79:916, 1970 5 Davies DF: A review of detection methods for the early diagnosis of lung cancer. J Chron Dis 19:819-845, 1966 6 Oswald NC, et al: The diagnosis of primary lung cancer with special reference to sputum cytology. Thorax 26:623631, 1971 7 Grunge H: Cytologic diagnosis of tumors of the chest. Acta Cytologica 17:148-159, 1973 8 Zavala DG, et al: Use of bronchofiberscope for bronchial brush biopsy. Chest 63:889-892, 1973 9 Rath GS, Schaff JT, Snider GL: Flexible fiberoptic bronchoscopy. Chest 63:689-693, 1973 10 Richardson RH, et al: The use of fiberoptic bronchoscopy and brush biopsy in the diagnosis of suspected pulmonary malignancy. Am Rev Resp Dis 109:63-66, 1974
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