Bronchoscopic Diagnosis of Solitary Pulmonary Nodules and Lung Masses in the Absence of Endobronchial Abnormality

Bronchoscopic Diagnosis of Solitary Pulmonary Nodules and Lung Masses in the Absence of Endobronchial Abnormality* Vijay Chechani, MD, FCCP To evaluate the individual and additive diagnostic yield(s) of several bronchoscopic sampling techniques for the diagnosis oflung lesions with no corresponding airway abnormalities, consecutive patients with lung nodules or masses were prospectively evaluated between December 1989 and November 1994. ACT of the chest was done in all patients before flexible bronchoscopy (FB). Size, location, and character of the border of the lesion were determined. During FB, using biplane fluoroscopic guidance, the lesion was localized and following sampling techniques were done: brushing, transbronchiallung biopsy (TBLB), and Sofcor transbronchial needle aspiration (STBNA). Bronchial washings (BWs) were collected throughout the procedure. Problems associated with each sampling technique were noted. Forty-nine patients underwent 51 FB. A diagnosis was established by FB in 36 (73% ). After a nondiagnostic FB, histologic diagnosis was established in 9 of 13 patients by other methods. A benign or malignant nature of lesion was established in other four patients by clinical follow-up. FB was diagnostic in 32 of 40 (80%) patients with primary lung cancer, in 3 of6 (50%) patients with benign disease, and in I of 3 (33%) patients with metastatic disease to lung. All sampling procedures could be done in 33 of 51 (65%) FBs. Overall diagnostic yields were as follows: BW, 18 of 51 (35%); brush, 25 of 48 (52%); TBLB, 23 of 40 (57%); and STBNA, 19 of 37 (51%). In 12 of 51 (24%) FBs, only one sample was diagnostic. Lesions with sharp borders had a lower combined diagnostic yield, 13 of 24 (54%) compared to lesions with fuzzy borders, 20 of 24 (83%) (p=0.03). Yield ofTBLB in lesions with fuzzy borders, 14 of 18 (78%), was higher than the yield for lesions with sharp borders, 6 of 19 (32%) (p=0.005). Size of the lesion in centimeters

in patients with a positive FB (4.55±2.35; mean±SD) was significantly larger than in patients with a nondiagnostic FB (3.14±1.31; mean±SD) (p=0.009, t test). Diagnostic yield was directly related to the size of the lesion. For lesions less than 2 em, yield was 6 of II (54%) (p=0.19); for lesions less than 3 em, yield was 12 of 21 (57%) (p=0.07); and for lesions greater than 3 em, yield was 24 of 30 (80% ). Yield from lesions located in the lower lobe basal segments or the apical segment of upper lobes was lower (ll/19, 58%) than that from lesions in other parts of the lung (25/30, 83%) (p=0.05). FB was terminated prior to collecting all samples because of severe bleeding after brushing (n=3) or instability of the patient (n=4). None of the patients required intubation. There were no pneumothoraces. Diagnostic yield of FB depends on the location, size, character of the border of the lesion, and the ability to perfonn all sampling methods. Brushing, TBLB, and STBNA should be perfonned in all patients to give the best diagnostic yield. Routine cytologic examination of BW is unnecessary. Methods other than FB should be considered for lesions 2 em or less in size, especially when they have a sharp border and/or are located in the basal segment of a lower lobe/apical segment of an upper lobe. (CHEST 1996; 109:620-25)

lung lesion may be classified as a nodule A discrete (0.2 to 3.0 em) or a mass (>3.0 cm). Flexible

may be responsible for the wide variability (18 to 75%) in reported diagnostic yield of FB performed to establish the diagnosis of solitary lung lesions in the absence of endobronchial abnormalities. 3-9 These include the following: retrospective study design; exclusion of patients because of lesion size; exclusion of benign lesions in analysis of FB yield; performance of CT prior to FB; utilization of biplane fluoroscopy during FB; variability in the experience of the bronchoscopist; and types of biopsy procedures performed during FB. Transbronchial needle aspiration of a peripheral lung nodule during FB has become possible only recently and has not been evaluated in relation to its advantages in addition to other biopsy techniques.

1

bronchoscopy (FB) is frequently done in patients with such lung lesions to establish a diagnosis. The diag-

For editorial comment see page 593 nostic yield of FB and biopsy of an endobronchially visible carcinoma is above 90%. 2·3 A variety of factors *Pulmonary Disease, Critical Care Medicine, and Internal Medicine, Roswell, New Mexico. Manuscript received March 31, 1995; revision accepted August 2. Reprint requests: Dr. Chechani, 1600 SE Main St, Suite C, Roswell,

NM 88201

620

BW=bronchial washing; FB=flexible bronchoscopy; STBNA=Sofcor transbronchial needle aspiration; TBLB=transbronchiallung biopsy; TTNA=transthoracic needle aspiration

Key words: bronchial brushing; bronchial washing; flexible fiberoptic bronchoscopy; lung cancer; trans bronchial needle aspiration

Clinical Investigations

Table !-Etiology of Lung Lesions in 49 Patients Diagnosis

No.

2 3

4

5

Diagnostic FB

Lung cancer Squamous cell Large cell Adenocarcinoma Poorly differentiated non-small cell Small cell Bronchoalveolar Presumed lung cancer Benign Coccidioidomycosis Histoplasmosis Granuloma Inflammatory pseudotumor Presumed benign Metastasis to lung Colon cancer Melanoma Prostate Total (%)

The aim of this study was to prospectively evaluate the role of sequential utilization of a series of FB sampling modalities in the diagnosis of well-defined lung lesions that could be classified as either nodules or masses (when no endobronchial abnormality was detected). METHODS

Subjects The study was designed to prospectively evaluate the role of FB in evaluation of patients with a solitary pulmonary nodule or mass detected on the chest radiograph. Forty-nine patients with welldefined lung lesions who underwent bronchoscopy between December 1989 and November 1994 were eligible for the study. These patients were sequentially enrolled at University Hospitai!Harry S. Truman Veterans Administration Hospital, Columbia, Mo, and Eastern New Mexico Medical Center, Roswell, NM. Informed consent was obtained in all patients prior to the procedure. Prior nondiagnostic transthoracic needle aspiration was not an exclusion criterion. Only patients who had a normal endobronchial anatomy at FB were included in the study. Evaluation Prior to FB

Posteroanterior and lateral chest radiograph CT of chest were done in all patients before FB. Liver and adrenal glands were also visualized by the CT at the same time. Location of the lesion was determined from the radiographs and the CT. The size and the character of the border of the lesion were determined from the CT. The largest dimensions of the lesion in anteroposterior and mediolateral directions were measured. The largest of these dimensions was used to define the size of the nodule when calculating the effect of size on the diagnostic yield. Border of the nodule was classified as sharp or fuzzy. FB and Sampling

Continuous pulse oximetry and ECG monitoring were done during FB. BP was measured every 5 min. Patients inhaled albuterol sulfate (0.5 mL of0.5% solution in 2.5 mL of sterile saline solution) mixed with lidocaine (2.5 mL of 2% solution) by ahand-held nebulizer. The throat was anesthetized by two to six sprays of Cetacaine.® Viscous lidocaine was sniffed by the patient in each

Nondiagnostic FB 06 01 01 02 01 00 01 02 02 00 01 01 00 01 02

32 ll ll

04 05 01 00 00

03 02 00 00 01 00

01 01 00

Total Patients (%) 38 (77.5) 12 (31.5) 12 (31.5) 06 (15.7) 06 (15.7) 01 (2.6) 01 (2.6) 02 (4) 05 (10)

01 (2) 03 (6)

00

00

36 (73)

01 01 13 (27)

49

nostril. Oxygen was administered by either a nasal cannula or a Hudson catheter and flows were adjusted upward from 2 Umin to keep Sp0 2 above 90%. Meperidine and midazolam were used in minimum amounts when necessary to achieve adequate cough suppression and sedation. Flexible fiberoptic bronchoscopes with similar specifications (Pentax FB-19H; Orangeburg, NY; or Olympus BF-20D; Melville, NY) were used for all procedures. Once the fiberoptic bronchoscope was advanced beyond the vocal cords, all secretions from the suction channel were collected in a trap. All collections were labeled as bronchial washings (BWs). All segments of the bronchial tree were visualized. Absence of endobronchial abnormality (intraluminal growth/submucosal abnomlality/extrinsic compression from a mass lesion ) was essential for patients to be included in the study. The bronchoscope was then advanced to the lobe and segment known to be the location of the lesion. Biplane fluoroscopic guidance was provided by a C-arm or a fixed fluoroscopy unit. A cytology brush (1.73 mm outer diameter; Microvasive Corp; Watertown, Mass) was then advanced into the bronchus under fluoroscopic guidance. If the brush appeared to reach the outer edge of the lesion, the C-arm was rotated in two perpendicular directions. If the brush and the lesion stayed together during these movements of the C-arm, localization of the nodule was considered good. The brush was then advanced into the lesion and a few vigorous back-and-forth movements were made to collect the sample on the brush. The brush was then withdrawn, cut, and sent for cytologic examination. If tuberculosis or a fungal infection were suspected, brushing was repeated and the material was smeared on slides, air dried, and sent for acid-fast and Gomori-methenamine silver staining. Once adequate hemostasis was accomplished, a biopsy specimen of the lesion was then taken by standard-size forceps (Olympus FB20C). The forceps was advanced to the outer border of the lesion. The cup of the forceps was then opened and the forceps was advanced into the lesion by a centimeter and the forceps cup was then closed. Barring complications, at least four good-sized biopsy pieces were obtained and placed in formalin. After this, transbronchial needle aspiration was done by using Sofcor transbronchial needle aspiration (STBNA) (Microvasive; Watertown, Mass). Under fluoroscopy the needle was advanced to the periphery of the nodule. The needle was then advanced to pierce the lesion. A10-mL syringe was used to provide suction while the lesion was stabbed rapidly multiple times. Suction was then released and the needle was CHEST I 109 I 3 I MARCH, 1996

621

Table 2-Diagnostic Yields of Different Sampling Metlwds and Problems Encountered in 51 FBs* Procedure Done Not done: reasons Lesion not seen under fluoroscopy Unable to localize accurately Severe bleeding with same sample at previous FB Severe bleeding from brushing Patient in unstable condition Lesion localized but instruments slide along the lesion Cavitary lesion Positive sample

Exclusively diagnostic test 12/51 (24%) Brushing, TBLB, STBNA all positive ll/33 (33%)

Washing

Brushing

TBLB

STBNA

51

48 03 01 01 01

40 11 01 03

37 14 01 03

00

00

03 02 02

03 03 01

00

18 (35%) (17 CA and l Cocci culture) None

25 (52%) (25CA) 3/48 (6%)

23(57%) (21 CA and 2 Cocci) 6/40(15%)

03 19 (51%) (18 CA and l pseudotumor) 3/37 (8%)

*CA=cancer; Cocci=Coccidioides immitis. withdrawn from the suction channel. The contents of the needle were then pushed out by air on slides. If a core of tissue was seen, this was picked up by a needle and placed in formalin and sent for histologic examination. The remainder of the aspirate was smeared on slides and quickly Hxed in 70% alcohol and sent for cytologic examination. Long needle core of tissue was considered a good sample. If a long needle core of tissue was not obtained, STBNA was repeated. STBNA was not performed when the lesion was a hollow cavity. All washings were pooled and sent for cytologic examination, Gram stain and bacterial culture, acid-fast smear and culture, and potassium hydroxide smear and fungal culture. Difficulties With Fluoroscopy

If the lung lesion could not be visualized under fluoroscopy, brushing, transbronchiallung biopsy (TBLB) and STBNA were not performed. The involved lobar segment was lavaged with two 60-mL aliquots of sterile saline solution and additional washings were obtained from the other segments of the lobe. BAL and BW were submitted separately for examinations. Difficulties With Localization

Localization was considered to be poor if the brush!forcep and the lesion moved away from each other with the rotation of the Carm. Other segments in the same lobe and other lobes were then entered to ascertain the correct location of the lesion. If localization was still considered poor, brushing was done from the nearest location to the lesion, but TBLB and STBNA were not performed. Difficulties During FB

Amount of bleeding that occurred with each procedure, brushing, TBLB, and STBNA was noted. Bleeding was considered severe (approximate volume, 60 mL) if adequacy of the airway was in jeopardy. In the event of severe bleeding, once adequate hemostasis was obtained by instillation of aliquots of epinephrine (3 mL of 1:20,000 solution) and wedging of the bronchoscope, FB was ended without further sampling. Bleeding was considered moderate (approximate volume, 30 mL) when there was no danger to the airway but significant effort was required to achieve hemostasis. In the event of moderate bleeding, the sampling procedure that caused the bleeding was ended and the next sampling procedure was begun. FB was prematurely terminated if the patient appeared unstable (severe tachycardia!desaturation!wheezing). An expiratory portable upright chest radiograph was done in all patients after the FB. 622

Follow-up After FB

Attempt was made to obtain a histologic diagnosis in all patients with a nondiagnostic FB. When a histologic diagnosis could not be made, clinical follow-up was done to establish malignant or benign nature of the lesion. Surgical pathologic diagnosis was compared with the broncho~copic diagnosis in patients who underwent subsequent resection. RESULTS

Forty-nine patients were enrolled. FB was performed twice in two patients and thus 51 FBs were performed. Twenty-five patients were studied at University Hospital/Harry S. Truman Veterans Administration Hospital, Columbia, Mo, and 24 patients were studied at Eastern New Mexico Medical Center, Roswell, NM. Table 1 shows the diagnoses established in the 49 patients by FB thoracotomy, CT-guided transthoracic needle aspiration (TINA), or by clinical follow-up. Definitive diagnosis was established by FB sampling in 36 patients (73%). Of the 13 patients with nondiagnostic FB, a diagnosis was established by TINA in four, by thoracotomy in four, and by liver biopsy (metastatic melanoma) in one. In four patients, a tissue diagnosis could not be established. Two of these patients had primary lung cancers, one patient had benign granuloma from prior tuberculosis, and one patient had metastatic disease from a prostate primary. In two patients, the first FB was nondiagnostic. One had severe bleeding after bronchial brushing and the first FB ended prematurely. ACT-guided TINA was then performed, the results of which were nondiagnostic. FB was then repeated and only STBNA was performed which established the diagnosis oflarge cell carcinoma. Moderate bleeding occurred with STBN A. Another patient underwent a nondiagnostic FB when the tumor size was lx2 em. A tug was noted with each Clinical Investigations

Table 3-Effect of Border on Sample Yields Yield, No.(%) Borde r

Washing

Brushing

TBLB

STBNA

Total

Sharp Fuzzy Cavity

6/24 (25) 10/24 (42) 213 (66)

10/22 (45) 15/23 (65) 1/3 (33)

6/19 (32) 14/18 (78)* 3/3 (100)

11/21 (52) 8/16 (SO) Not done

13/24 (54) 20/24 (83) 1 3/3 (100)

*p=O.OOS, x2. 1 p=0.03, x2

TBLB. STBNA was not performed during the first FB because of patient instability. Poor lung function (FEV1 <0.8 L) precluded surgical resection. Location of the tumor in the middle third of the lung fields presented a high risk for development of pneumothorax by TINA. After 6 months, the tumor size had increased to 2.7x3 em and the patient then agreed to a second FB. STBNA was the only diagnostic sample and revealed squamous cell carcinoma. Fifteen 51 (30%) FBs were non diagnostic. In 7 of 15 instances, the procedure was completely satisfactory. The visualization and localization of the lesion under fluoroscopy were good and all sampling methods (brush, TBLB, STBNA,) were performed. In 8 of 15 instances, adequate FB could not be performed because of following reasons: nonvisualization of the lesion under fluoroscopy (n=1), inability to accurately localize the correct bronchial subsegment leading to the lesion (n=3), sliding of the sampling instruments along the sides of the lesion (n=2), early termination of FB because of bleeding (n=1), or patient instability (n=l). Thirty-six of 51 (70%) FBs were diagnostic. All sampling procedures could be performed in 33 of 51 (65%). Table 2 shows the diagnostic yield of each sampling method and reasons why they could not be performed in all patients. Long needle cores of tissues were obtained in 14 of 37 (38%) of STBNA attempts and were diagnostic in 12 (85%). Small core of tissue was obtained in five attempts and was positive in three (60%) . STBNA aspirate was sent for cytologic examination in 27 and was positive in 17 (62%). The yield from needle core (15/19, 78%) was higher than cytologic yield (17/27, 62%) but statistically insignificant (p=0.24, x2 ). Table 3 illustrates the effect of border characteristics on the yield. Lesions with sharp borders had a lower combined diagnostic yield (13/24, 54%) compared the lesions with fuzzy borders (20/24, 83%) (p=0.03, x2 ) . Yield of TBLB for lesions with fuzzy borders (14118, 78%) was higher compared to the yield for lesions with sharp borders (6/19, 32%) (p=0.005, x2 ). Border characteristics did not affect the yield from STBNA, brush, or BW. Table 4 shows the effect of size on the yield from FB.

Diagnostic yield from FB was higher for lesions defined as mass (>3 em size; 24130, 80%) than lesions defined as nodules (:s3 em; 12121, 57%), but it did not achieve statistical significance (p=0.07, x2 ) . Size of the lesion in centimeters in patients with a positive FB (4.55±2.35; mean±SD) was significantly larger than in patients with a nondiagnostic FB (3.14± 1.31; mean±SD) (p=0.009, t test). Once the size of the lesion was more than 6 em, chance of FB being nondiagnostic was zero. Yield was also affected by the location of the lesion. Positive yields from different locations were as follows : upper lobe apical segment (7/11, 63%), upper lobe posterior segment (8/9, 89%), upper lobe anterior segment (415, 80%), lingula (3/4, 75%), right middle lobe (5/6, 83%), lower lobe superior segment (5/6, 83%), and lower lobe basal segments (418, 50%). Combined yield from upper lobe apical segment and lower lobe basal segment (11/19, 58%) was significantly lower than the other parts of the lung (25/30, 83%) (p=0.03, x2 ). Severe bleeding was noted only with brushing and was seen in 3 of 48 (6%) instances. Moderate bleeding was noted with brushing in 3 of 48 (6%), with TBLB in 6 of 40 (15%) and with STBNA in 3 of37 (8%). Severe bleeding was not noted with TBLB or STBNA. FB was terminated early because of patient instability in four and because of severe bleeding after brushing in three instances. None of the patients required intubation. There was no mortality. Pneumothorax did not occur in any patient. Thirty-eight patients were diagnosed as having lung cancer and two patients were presumed to have lung cancer. Lung cancer was diagnosed in 32 of 40 (80%) patients by FB. Only 12 of32 (38%) patients diagnosed as having lung cancer by FB were surgical candidates Table 4--Effect of Size of the Lesion on Yield Lesion Size, em

:52 2.1-3.0 3.1-4.0 4.1-5.0 >5.1

Bronchoscopy Yield, No. (%) 6/ll (54) 6/10 (60) 8/ll (73) 9/ll (82) 7/8 (87)

CHEST I 109 I 3 I MARCH, 1996

623

and subsequently underwent resection. Nodal disease was not detected in any of these 12 patients. A total of 15 of 40 (38%) patients with lung cancer underwent surgical resection for possible cure. Twenty-five patients were excluded from surgical resection for the following reasons: metastasis to brain (n=3), metastasis to kidneys/adrenal/liver (n=4), metastasis to bone (n=3), N2 disease by mediastinoscopy (n=4), poor lung functions (n=7), small cell carcinoma (n=l), and poor health status from other diseases (n=3). Thus, in 22 of 40 (55%) patients with lung cancers not visible through the endoscope, surgical excision was not feasible. Diagnosis by FB sampling was successful in 4 of 6 (67%) patients with adenocarcinomas and in 28 of 32 (88%) patients with all other cell types. Bronchoscopic diagnosis correlated with the surgical histologic type in 9 of 12 patients with lung cancer. Of the two patients diagnosed as having large cell cancer by FB, one patient was found to have squamous cell cancer and another adenocarcinoma at resection. One patient had poorly differentiated carcinoma that presented as a Pancoast tumor. This patient received 3,000 rad of external radiation therapy before lobectomy. No viable tumor cells, only necrotic tissue was detected in the surgical specimen. DISCUSSION

This study shows that lung lesions not visible through the bronchoscope can be diagnosed with accuracy in most patients by FB. This study shows that stepwise performance of all three sampling methods, brushing, TBLB, and STBNA, increases the diagnostic yield of FB. The lung lesions were primary lung cancer in 82% of the patients. Metastasis to lung from another primary was seen in 6% and benign disease was seen in only 12%. Higher overall diagnostic accuracy of FB (73%) compared with other studies may also reflect this higher percentage of patients with lung cancer. Of the 40 patients with lung cancer, 32 (80%) had conditions diagnosed by FB while only 3 of 6 (50%) of the benign lesions were diagnosed by FB. It is quite apparent that although we planned to perform all procedures (brush, TBLB, STBNA) with each FB, unforeseeable reasons prevented us from doing so. The most important aspect of the procedure is good fluoroscopic localization. Among the 15 nondiagnostic FBs, nonvisualization of the lesion under fluoroscopy (n=l) and inaccurate localization (n=5) accounted for the failure of the procedure in 6 instances. Besides poor visualization and poor fluoroscopic localization, bleeding after brushing and patient instability also precluded performance of TBLB and STBNA in all patients. Thus, all procedures could be done in only 33 of 51 (65%) of the FBs. Fluoroscopic localization is most difficult when lesions are small ( <2 em) and located in the lower lobe 624

basal segments or the upper lobe apical segment. Lower diagnostic yield was noted for lesions in these two segments (58%) when compared with yields from all other locations (83%). Fletcher and Levine7 did study the yield related to the segmental location of the lesion. Their overall diagnostic yield from FB was only 35.6% and thus yields from all segments were poor but the worst yields were from lower lobe basal segments (217, 28%) and superior segment (5/19, 26%). Table 4 shows that the success of FB was directly related to the size of the lesion. Success rate of FB for lesions 2 em or less (6/11, 54%) and lesions 3 em or less (12121, 57%) were lower than that for lesions greater than 3 em (24/30, 80%). Diagnostic yields of FB for lesions less than 2 em in previously published reports have been lower (5 to 28%). Radke et al6 had a yield of28% (6/21) and recommended that FB not be done for such lesions. Stringfield et al 5 had a positive yield in 4 of 15 (27%) for lung cancers less than 2 em in size. Wallace and Deutch 10 had a positive yield in 3 of 65 (5% ). Cortese and McDougall did not diagnose any of the four patients with lung cancers less than 2 em in size. Fletcher and Levin7 had a positive yield in 4 of 32 (12.5%). Shiner et al 8 excluded patients with lesions less than 2 em from their study. Some of these studies have included benign and malignant lesions 6·7J 0 while others have studied only lung cancers. 4·5 In our study, FB was able to diagnose three of four lesions in upper lobes, two of five lesions in lower lobes, zero of one lesion in middle lobe, and one of one lesion in the lingula. The number of patients with lesions less than 2 em was too small to study the effect of segmental location of the lesion on yield. Tsuboi et al 11 found that although all tumors were intraluminal, 62.~% of the lesions less than 3 em were supplied by only one bronchus and the remainder by only two bronchi. However, there were three or more bronchi in 60% of the tumors that were more than 3 em in diameter. This increase in bronchial supply with increase in size of the tumor is probably responsible for the direct relationship between the yield of FB and the lesion size. FB was more successful in diagnosing lesions with fuzzy borders (83%) and cavitating nodules (100%) than lesions with sharp borders (54%). This again may be related to limited bronchial access in lesions with sharp borders. Four of the six benign lesions had sharp borders. Only one of four benign lesions with sharp borders could be diagnosed by FB. In this patient, only STBNA was the positive sample. Both of the benign lesions with fuzzy borders were diagnosed as coccidioidomycosis by TBLB. This suggests that benign lesions with sharp borders may not be intraluminal in origin and therefore FB may not be as successful in diagnosis of such lesions. STBNA may be able to pierce through a bronchus and thus enter the lesion even though that bronchial lumen may not be communiClinical Investigations

eating with the tumor. This was the case in one patient with inflammatory pseudotumor in whom only the core of tissue obtained by STBNA was positive. In lesions with sharp borders, yield of brushing and TBLB is lower than that of STBNA. Although the difference in these yields did not achieve statistical significance, STBNA was the only positive sample in some of these patients. Thus, bronchoscopic sampling of a lesion with sharp borders is incomplete without STBNA. We did not utilize STBNA in patients with cavitating nodules, although this is not a contraindication for STBNA. Popovich et al3 theorized that as many as ten TBLBs may need to be performed to maximize diagnostic yield for peripheral carcinomas. In their study, the diagnostic accuracy increased from 60% for four biopsy specimens to 75% with six biopsy specimens. Our aim in the current study was to obtain at least four good-sized pieces by TBLB whenever possible. Since STBNA had to be performed following the TBLB, time would not have allowed more TBLB. Brushing, TBLB, and STBNA are all important in the diagnosis of a lung lesion because in 24%, only one sample was diagnostic. BWs were never positive as a sole specimen in any patient. Severe bleeding leading to a premature end of the procedure was associated only with brushing. It is possible that if brushing had been performed after TBLB and STBNA in these patients, complete sampling could have been accomplished in more patients. Under fluoroscopy, image of the STBNA is not as sharp as that of the biopsy forceps and the brush. I, therefore prefer the brush or the forceps for initial localization under fluoroscopy. Thus, the best sequence of specimen sampling would be TBLB, STBNA, and then brushing. Cytologic examination of BWs for the diagnosis of malignancy is aredundant test and should not be done. Lung lesion was invisible under fluoroscopy in one patient and BAL in this patient was also nondiagnostic. Gracia et al 12 evaluated the role of BAL in the diagnosis of peripheral lung cancer when fluoroscopic guidance was not available. BAL established a diagnosis in 10 of35 (28%) patients with nodules. The size, location, and the character of the border of the lesion were not mentioned in the study. Bellmunt et al 13 evaluated 26 patients with peripheral lung cancer presenting as lung nodules or masses. BAL was diagnostic in 5 of 26 (19%) patients. In their study, BAL did not significantly increase the diagnostic sensitivity obtained with the use of BW plus postbronchoscopy sputum. Role of BAL in the diagnosis of peripheral lung lesions is limited. It may be useful when fluoroscopic-guided brushing, TBLB, and STBNA cannot be performed. Only 38% of the patients with a peripheral lung cancer underwent surgical resection. Others were not surgical candidates. Thus, bronchoscopic diagnosis could be correlated to the surgical histologic type in

only 12 patients. Differences between the two specimens were noted in two (16%) patients. Chuanget al 14 found that 41 of 107 (38%) surgically removed specimens differed in cell type from their corresponding bronchoscopic specimens, although they did not specifY how many of their patients had peripheral lesions. In summary, FB sampling is safe with a high rate of accuracy in diagnosis oflung lesions not visible through the bronchoscope. Diagnostic yield depends on the location, size, character of the border of the lesion, and the ability to perform all sampling methods. Brushing, TBLB, and STBNA should be performed in all patients to give the best diagnostic yield. Routine cytologic examination of BWs is unnecessary. Methods other than FB should be considered for lesions 2 em or less in size, especially when they have a sharp border and/or are located in the basal segment of a lower lobe/apical segment of an upper lobe. ACKNOWLEDGMENT: I thank Stephan L. Kamholz, MD, for his critical review of the manuscript.

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