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Biopsy of the Main Carina
Biopsy of the Main Carina· Staging Lung Cancer with the Fiberoptic Bronchoscope Howard M. Robbins, M.D.;o. Douglass A. Morrison, M.D.;t Michael E. Sweet, M.D.;t David A. Solomon, M.D., F.C.C.P.;§ and Allan L. Goldman, M.D., F.C.C.P.II
The efficacy of main carinal biopsy through the fiberoptic bronchoscope for evaluating resedabWty has Dot been determined. Forty-eight patients with carcinoma, but without gross neoplastic involvement of the main carina, underwent biopsy. Five (10 percent) had abnormal results on biopsy of the main carina. Three of the five patients
I t is important to accurately, safely, and econom-
ically stage carcinoma of the lung for .possible surgical resection. The usefulness of main carinal biopsy through the rigid bronchoscope, even when no visible abnormality of the main carina is seen, is well established as a staging procedure. l -3 H staging in certain patients could be accomplished by main carinal biopsy during fiberoptic bronchoscopic examination, additional procedures with higher morbidity, higher mortality, and greater expense could be avoided. The present study assesses the usefulness of main carina! biopsy through the fiberoptic bronchoscope in staging carcinoma of the lung. MATERIALS AND METHODS
AD patients undergoing a fiberoptic bronchoscopic procedure for suspected carcinoma of the lung were initial candidates for this study, which was conducted at the Veterans Administration Hospital, Tampa, Fla, and Tampa General Hospital from March 31, 1977 to March 31, 1978. The fiberoptic bronchoscope (Olympus BF 5B2) and accompanying forceps were used. The procedures were done transnasally with local anesthesia. All visible endobronchial lesions that were suspected of being malignant were biopsied for histologic examination and brushed for cytologic study. In each patient, at least two
°From the
Pulmonary Disease Section, Department of Internal Medicine, University of South Florida College of Medicine and the Veterans Administration Hospital, Tampa, Fla. o °Instructor in Medicine. tFellowi Pulmonary Disease Section. Currently Fellow, Cardio ogy Section, Deparbnent of Internal Medicine, University of Washington, Seattle. iFellow, Pulmonary Disease Section. §Assistant Professor of Medicine. IIAssociate Professor of Medicine and Chief, Pulmonary Disease Section. Manuscript received August 16; revision accepted September
28.
Reprint requests: Dr. Goldman, 13000 North 30th Street, Tampa 33612
484 ROBBINS ET AL
were initially considered candidates for surgery. There were no compUcatioDS from the procedure. Biopsy of the main carina through the 8heroptic bronchoscope Is a valuable staging procedure in selected patients because of its simp6city and yield and the significance of abnol'llUl1 findings.
biopsies of the main carina were obtained with a separate forceps. Tissue was obtained from the posterior tip of the main carina. Specimens were considered abnormal only if evidence of invasion of tissue by carcinoma was present microscopically. Patients were excluded from the study if the main carina was involved with an obvious endobronchial tumor. Since a well-done study with the rigid bronchoscope has demonstrated the lack of efficacy of main carinal biopsies when all bronchi appeared to be normal, l we did not perform main carina! biopsies on patients with totally normal findings on fiberoptic bronchoscopic examination. REsULTS
Seventy-four patients with suspected carcinoma were examined with the fiberoptic bronchoscope. Fifteen patients were excluded because they did not have a biopsy of the main carina, due to technical problems. These problems included the length of the procedure (with waning anesthesia), bleeding from other sites of biopsy, and the lack of a sufficient number of sterilized biopsy forceps. Fifty-nine patients were evaluated. Five had benign disease. Six others probably had tumor, but no histologic diagnosis was made, either because of the patient's refusal of further procedures or because of the patient's inability to tolerate more invasive studies. The remaining 48 patients had histologic confirmation of carcinoma. The histologic types are noted in Table 1. The preponderance of squamous cell, undifferentiated, and oat cell types reflects the relatively central origin of the endoscopically visualized tumors. Abnormal findings on biopsy of the main carina were obtained in five (10 percent) of the 48 patients. A biopsy adequate to evaluate submucosal involvement was obtained in 54 (92 percent) of the 59 patients. Four of the five main carina! biopsies with abnormal results had histologic evidence of sub-
CHEST, 75: 4, APRIL, 1979
Table I-Hi"olopc TyllU 0/ Carcinoma
-:1,
Histologic Type Squamous cell
No. of Patients
No. with Abnormal Findings on Main Carinal Biopsy
30
2
Undifferentiated
8
Oat cell
7
Adenocarcinoma
,
,.
. FIGURE 1. Specimen from main carinal biOpsy, showing nests of adenocarcinoma in lymphatic vessels of submucosa.
mucosal tumor (Fig 1). The biopsy yielded abnormal findings in three of32 patients when tumor was visualized elsewhere in the bronchial tree and in two of 16 patients when an abnormality was noted but no lesion was seen. These abnormalities included extrinsic compression of the bronchus in five patients and erythema or widened edematous segmental carinae (or both) in 11 patients. The five biopsies with abnormal results were obtained from main carinae that either appeared normal (two of 33), were widened with a normal appearing surface (one of ten), or were erythematous without widening (two of five). Most biopsies from widened or erythematous (or both) main carinae were normal, so that the gross appearance of the main carina was not a reliable indicator of malignant involvement. The location of the primary abnormality may influence who will have abnormal findings on main carinal biopsy (Table 2). The diagnostic yield with main-stem lesions (three of five) was higher than with more distal lesions. The procedure was unrewarding when the tumor was located on the left side beyond the main-stem bronchus. Three of the five patients were candidates for surgery by all other usual criteria, and their tumor was considered restaged as unresectable as a result of the carinal biopsy. One patient had small cell carcinoma that was considered inoperable because of histologic type, as well as location. Main carinal biopsy was performed through the rigid bronchoscope in nine patients who had normal results on a main carinal biopsy with the fiberoptic bronchoscope. The rigid bronchoscope yielded larger specimens for biopsy, but in no instance was tumor detected by this technique either. Twenty-six of the 43 patients with normal findings on main carinal biopsy were subsequently shown to have an inoperable tumor because of metastases,
CHEST, 75: 4, APRIL, 1979
Adenosquamous
0
Large cell
0
Total
48
5
poor pulmonary function, severe angina, etc. Seventeen of the patients went on to mediastinoscopic examination, and five of these had tumors that were staged as unresectable by this procedure. Of the 12 patients whose tumors were not staged by mediastinoscopic examination, four either had tumors that were deemed inoperable or refused thoracotomy. Eight patients underwent thoracotomy, and seven had tumors that were found to be unresectable at that time. Therefore, normal findings on main carinal biopsy do not imply resectability, which may need to be determined by other methods; however, the patients with abnormal results 01). main carinal biopsy who were otherwise candidates for surgery would have had to undergo a fruitless mediastinoscopic examination or thoracotomy (or both) and were saved the morbidity, expense, and possibly even the mortality of these additional procedures. DISCUSSION
Studies by Rabin4 and by Rabin and Neuhof5 previously demonstrated that bronchogenic tumors may spread by way of the submucosal lymphatic vessels. These investigators4•5 found that isolated Table 2-Localion 0/ Primary Endobronchial Tumor
No. of Patients
No. with Abnormal Findings on Main Carinal Biopsy
Right main stem
5
1
Right upper lobe
6
Right middle and lower lobes
6
o
Left main stem
5
2
Left upper lobe
18
o o
7
1
48
5
Primary Tumor
Left lower lobe Diffuse erythema; no primary site Total
BIOPSY OF THE MAIN CARINA 485
nests of tumor were present along the submucosal lymphatic vessels beneath the bronchi, often at considerable distances from the site of the primary lesion and in the presence of normal appearing bronchial mucosa. Rabin et all subsequently showed the efficacy of biopsy during rigid bronchoscopic examination in evaluating for this type of proximal extension. In their series, 20 percent of 152 patients with bronchogenic carcinoma had abnormal results on paracarinal biopsy (within 1 em of the main carina), 11.5 percent of whom had no endobronchial lesion at the main carina. Significantly, 16 percent of the patients who had a normal appearing carina and who were otherwise candidates for surgery had tumors that were restaged as unresectable by this procedure. Conversely, the biopsies "restaged" what appeared to be unresectable extension in certain cases. Thirty-one patients appeared to have extension of tumor to the main carina because of the appearance of edema, erythema, or widening of the main carina (or some combination of the three); however, biopsies demonstrated that in 15 of the 31, the appearance was misleading, and no tumor was found in the carina. In 1945, Griess et al 6 demonstrated that the proximal spread of a bronchogenic carcinoma can be more extensive than is visibly appreciated by the bronchoscopist. Usually, the extension of the tumor was in the outer fibrous layer or in the submucosa, rather than in the mucosa, thereby perhaps explaining the findings at bronchoscopic examination. Waltner found a spread of the primary bronchogenic carcinoma to the paracarinal area in five of 12 consecutive cases. In all five of these cases, the spread was to the submucosal lymphatic vessels, with the overlying mucosa pathologically uninvolved. In 1963, Versteegh and Swierenga2 used the rigid bronchoscope and found a 13 percent yield with paracarinal biopsies from normal appearing main carinae in patients with bronchogenic carcinoma." This percentage was more than double that of routine scalene node biopsies in the same patients. The ten patients in this series who had abnormal results on main carinal biopsies but otherwise were considered candidates for surgery had attempted resection. Only one q.Imor was found to be resectable at the time of surgery, and no follow-up on that patient was presented. Versteegh and Swierenga2 concluded that abnormal findings on main carina! (or paracarinal) biopsy preclude a curative resection. While the evidence of tumor within 2 em of the main carina still indicates inoperability,7 newer surgical approaches may change this grim outlook. Our series again demonstrates the occurrence of
•
ROBBINS ET AL
mucosal, submucosal, and lymphatic spread of primary bronchogenic carcinoma to the main carina without endoscopic evidence of neoplastic involvement of the overlying mucosa. The incidence of abnormal results on biopsies with the fiberoptic bronchoscope seems to be comparable to that obtained in previous series using the rigid bronchoscope (10 percent [5/48] in our series; 11.5 percent and 13 percent in other series) .1,2 Furthermore, we found no false-negative results of biopsies in patients who had both fiberoptic and rigid bronchoscopic examinations (nine patients) . We confirmed the findings of Rabin et all that the chances of obtaining abnormal results on main carinal biopsies were much higher when the lesion was in the main-stem bronchus. The lower diagnostic yield of the procedure with lesions in the left segmental bronchi was noted previously and may be attributable either to the different lymphatic drainage of the two lungs or to the longer length of the left main-stem bronchus. 1 Although we did not obtain any abnorm~ results from main carinal biopsies in patients who had the primary abnormality in the left segment bronchi, another series performed with the rigid bronchoscope did. I The very high benefitcost ratio for each biopsy with abnormal results may still justify the procedure in these cases. We conclude that biopsy of the main carina should be obtained in all patients with suspected carcinoma of the lung whenever an abnormality is noted at fiberoptic bronchoscopic examination. An adequate amount of tissue to evaluate the submucosa will be obtained in almost every instance. H tumor cells are seen in the specimen from main carinal biopsy, the tumor is unresectable, and further staging procedures are unnecessary. REFERENCES
1 Rabin CB, Selikoff II, Kramer R: Paracarinal biopsy in evaluation of operability of carcinoma of the lung. Arch Surg 65:822-830, 1952 2 Versteegh RM, Swierenga J: Bronchoscopic evaluation of the operability of pulmonary carcinoma. Acta OtolaryngoI 56:603-611, 1963 3 Waltner JG: Inoperability of carcinoma of the lung established by carinal biopsy. Ann Otolaryngol 70:1165-1171, 1961 4 Rabin CG: Relation of roentgenography of chest to the laryngologist: Atelectasis and neoplasms of lung. Laryngoscope 42:923-930,1932 5 Rabin CB, Neuhof H: Topographic classification of primary cancer of the lung: Its application to the operative indication and treatment. J Thorac Surg 4:147-164, 1934 6 Griess DF, McDonald JR, Clagett OT: Proximal extension of carcinoma of the lung in the bronchial wall. J Thorae Cardiovasc Surg 14:362-368, 1945 7 American Joint Committee for Cancer Staging and EndResults Reporting: Manual for Staging of Cancer 1977. Chicago, 1977, pp 59-61
CHEST, 75: 4, APRil, 1979
The efficacy of main carinal biopsy through the fiberoptic bronchoscope for evaluating resedabWty has Dot been determined. Forty-eight patients with carcinoma, but without gross neoplastic involvement of the main carina, underwent biopsy. Five (10 percent) had abnormal results on biopsy of the main carina. Three of the five patients
I t is important to accurately, safely, and econom-
ically stage carcinoma of the lung for .possible surgical resection. The usefulness of main carinal biopsy through the rigid bronchoscope, even when no visible abnormality of the main carina is seen, is well established as a staging procedure. l -3 H staging in certain patients could be accomplished by main carinal biopsy during fiberoptic bronchoscopic examination, additional procedures with higher morbidity, higher mortality, and greater expense could be avoided. The present study assesses the usefulness of main carina! biopsy through the fiberoptic bronchoscope in staging carcinoma of the lung. MATERIALS AND METHODS
AD patients undergoing a fiberoptic bronchoscopic procedure for suspected carcinoma of the lung were initial candidates for this study, which was conducted at the Veterans Administration Hospital, Tampa, Fla, and Tampa General Hospital from March 31, 1977 to March 31, 1978. The fiberoptic bronchoscope (Olympus BF 5B2) and accompanying forceps were used. The procedures were done transnasally with local anesthesia. All visible endobronchial lesions that were suspected of being malignant were biopsied for histologic examination and brushed for cytologic study. In each patient, at least two
°From the
Pulmonary Disease Section, Department of Internal Medicine, University of South Florida College of Medicine and the Veterans Administration Hospital, Tampa, Fla. o °Instructor in Medicine. tFellowi Pulmonary Disease Section. Currently Fellow, Cardio ogy Section, Deparbnent of Internal Medicine, University of Washington, Seattle. iFellow, Pulmonary Disease Section. §Assistant Professor of Medicine. IIAssociate Professor of Medicine and Chief, Pulmonary Disease Section. Manuscript received August 16; revision accepted September
28.
Reprint requests: Dr. Goldman, 13000 North 30th Street, Tampa 33612
484 ROBBINS ET AL
were initially considered candidates for surgery. There were no compUcatioDS from the procedure. Biopsy of the main carina through the 8heroptic bronchoscope Is a valuable staging procedure in selected patients because of its simp6city and yield and the significance of abnol'llUl1 findings.
biopsies of the main carina were obtained with a separate forceps. Tissue was obtained from the posterior tip of the main carina. Specimens were considered abnormal only if evidence of invasion of tissue by carcinoma was present microscopically. Patients were excluded from the study if the main carina was involved with an obvious endobronchial tumor. Since a well-done study with the rigid bronchoscope has demonstrated the lack of efficacy of main carinal biopsies when all bronchi appeared to be normal, l we did not perform main carina! biopsies on patients with totally normal findings on fiberoptic bronchoscopic examination. REsULTS
Seventy-four patients with suspected carcinoma were examined with the fiberoptic bronchoscope. Fifteen patients were excluded because they did not have a biopsy of the main carina, due to technical problems. These problems included the length of the procedure (with waning anesthesia), bleeding from other sites of biopsy, and the lack of a sufficient number of sterilized biopsy forceps. Fifty-nine patients were evaluated. Five had benign disease. Six others probably had tumor, but no histologic diagnosis was made, either because of the patient's refusal of further procedures or because of the patient's inability to tolerate more invasive studies. The remaining 48 patients had histologic confirmation of carcinoma. The histologic types are noted in Table 1. The preponderance of squamous cell, undifferentiated, and oat cell types reflects the relatively central origin of the endoscopically visualized tumors. Abnormal findings on biopsy of the main carina were obtained in five (10 percent) of the 48 patients. A biopsy adequate to evaluate submucosal involvement was obtained in 54 (92 percent) of the 59 patients. Four of the five main carina! biopsies with abnormal results had histologic evidence of sub-
CHEST, 75: 4, APRIL, 1979
Table I-Hi"olopc TyllU 0/ Carcinoma
-:1,
Histologic Type Squamous cell
No. of Patients
No. with Abnormal Findings on Main Carinal Biopsy
30
2
Undifferentiated
8
Oat cell
7
Adenocarcinoma
,
,.
. FIGURE 1. Specimen from main carinal biOpsy, showing nests of adenocarcinoma in lymphatic vessels of submucosa.
mucosal tumor (Fig 1). The biopsy yielded abnormal findings in three of32 patients when tumor was visualized elsewhere in the bronchial tree and in two of 16 patients when an abnormality was noted but no lesion was seen. These abnormalities included extrinsic compression of the bronchus in five patients and erythema or widened edematous segmental carinae (or both) in 11 patients. The five biopsies with abnormal results were obtained from main carinae that either appeared normal (two of 33), were widened with a normal appearing surface (one of ten), or were erythematous without widening (two of five). Most biopsies from widened or erythematous (or both) main carinae were normal, so that the gross appearance of the main carina was not a reliable indicator of malignant involvement. The location of the primary abnormality may influence who will have abnormal findings on main carinal biopsy (Table 2). The diagnostic yield with main-stem lesions (three of five) was higher than with more distal lesions. The procedure was unrewarding when the tumor was located on the left side beyond the main-stem bronchus. Three of the five patients were candidates for surgery by all other usual criteria, and their tumor was considered restaged as unresectable as a result of the carinal biopsy. One patient had small cell carcinoma that was considered inoperable because of histologic type, as well as location. Main carinal biopsy was performed through the rigid bronchoscope in nine patients who had normal results on a main carinal biopsy with the fiberoptic bronchoscope. The rigid bronchoscope yielded larger specimens for biopsy, but in no instance was tumor detected by this technique either. Twenty-six of the 43 patients with normal findings on main carinal biopsy were subsequently shown to have an inoperable tumor because of metastases,
CHEST, 75: 4, APRIL, 1979
Adenosquamous
0
Large cell
0
Total
48
5
poor pulmonary function, severe angina, etc. Seventeen of the patients went on to mediastinoscopic examination, and five of these had tumors that were staged as unresectable by this procedure. Of the 12 patients whose tumors were not staged by mediastinoscopic examination, four either had tumors that were deemed inoperable or refused thoracotomy. Eight patients underwent thoracotomy, and seven had tumors that were found to be unresectable at that time. Therefore, normal findings on main carinal biopsy do not imply resectability, which may need to be determined by other methods; however, the patients with abnormal results 01). main carinal biopsy who were otherwise candidates for surgery would have had to undergo a fruitless mediastinoscopic examination or thoracotomy (or both) and were saved the morbidity, expense, and possibly even the mortality of these additional procedures. DISCUSSION
Studies by Rabin4 and by Rabin and Neuhof5 previously demonstrated that bronchogenic tumors may spread by way of the submucosal lymphatic vessels. These investigators4•5 found that isolated Table 2-Localion 0/ Primary Endobronchial Tumor
No. of Patients
No. with Abnormal Findings on Main Carinal Biopsy
Right main stem
5
1
Right upper lobe
6
Right middle and lower lobes
6
o
Left main stem
5
2
Left upper lobe
18
o o
7
1
48
5
Primary Tumor
Left lower lobe Diffuse erythema; no primary site Total
BIOPSY OF THE MAIN CARINA 485
nests of tumor were present along the submucosal lymphatic vessels beneath the bronchi, often at considerable distances from the site of the primary lesion and in the presence of normal appearing bronchial mucosa. Rabin et all subsequently showed the efficacy of biopsy during rigid bronchoscopic examination in evaluating for this type of proximal extension. In their series, 20 percent of 152 patients with bronchogenic carcinoma had abnormal results on paracarinal biopsy (within 1 em of the main carina), 11.5 percent of whom had no endobronchial lesion at the main carina. Significantly, 16 percent of the patients who had a normal appearing carina and who were otherwise candidates for surgery had tumors that were restaged as unresectable by this procedure. Conversely, the biopsies "restaged" what appeared to be unresectable extension in certain cases. Thirty-one patients appeared to have extension of tumor to the main carina because of the appearance of edema, erythema, or widening of the main carina (or some combination of the three); however, biopsies demonstrated that in 15 of the 31, the appearance was misleading, and no tumor was found in the carina. In 1945, Griess et al 6 demonstrated that the proximal spread of a bronchogenic carcinoma can be more extensive than is visibly appreciated by the bronchoscopist. Usually, the extension of the tumor was in the outer fibrous layer or in the submucosa, rather than in the mucosa, thereby perhaps explaining the findings at bronchoscopic examination. Waltner found a spread of the primary bronchogenic carcinoma to the paracarinal area in five of 12 consecutive cases. In all five of these cases, the spread was to the submucosal lymphatic vessels, with the overlying mucosa pathologically uninvolved. In 1963, Versteegh and Swierenga2 used the rigid bronchoscope and found a 13 percent yield with paracarinal biopsies from normal appearing main carinae in patients with bronchogenic carcinoma." This percentage was more than double that of routine scalene node biopsies in the same patients. The ten patients in this series who had abnormal results on main carinal biopsies but otherwise were considered candidates for surgery had attempted resection. Only one q.Imor was found to be resectable at the time of surgery, and no follow-up on that patient was presented. Versteegh and Swierenga2 concluded that abnormal findings on main carina! (or paracarinal) biopsy preclude a curative resection. While the evidence of tumor within 2 em of the main carina still indicates inoperability,7 newer surgical approaches may change this grim outlook. Our series again demonstrates the occurrence of
•
ROBBINS ET AL
mucosal, submucosal, and lymphatic spread of primary bronchogenic carcinoma to the main carina without endoscopic evidence of neoplastic involvement of the overlying mucosa. The incidence of abnormal results on biopsies with the fiberoptic bronchoscope seems to be comparable to that obtained in previous series using the rigid bronchoscope (10 percent [5/48] in our series; 11.5 percent and 13 percent in other series) .1,2 Furthermore, we found no false-negative results of biopsies in patients who had both fiberoptic and rigid bronchoscopic examinations (nine patients) . We confirmed the findings of Rabin et all that the chances of obtaining abnormal results on main carinal biopsies were much higher when the lesion was in the main-stem bronchus. The lower diagnostic yield of the procedure with lesions in the left segmental bronchi was noted previously and may be attributable either to the different lymphatic drainage of the two lungs or to the longer length of the left main-stem bronchus. 1 Although we did not obtain any abnorm~ results from main carinal biopsies in patients who had the primary abnormality in the left segment bronchi, another series performed with the rigid bronchoscope did. I The very high benefitcost ratio for each biopsy with abnormal results may still justify the procedure in these cases. We conclude that biopsy of the main carina should be obtained in all patients with suspected carcinoma of the lung whenever an abnormality is noted at fiberoptic bronchoscopic examination. An adequate amount of tissue to evaluate the submucosa will be obtained in almost every instance. H tumor cells are seen in the specimen from main carinal biopsy, the tumor is unresectable, and further staging procedures are unnecessary. REFERENCES
1 Rabin CB, Selikoff II, Kramer R: Paracarinal biopsy in evaluation of operability of carcinoma of the lung. Arch Surg 65:822-830, 1952 2 Versteegh RM, Swierenga J: Bronchoscopic evaluation of the operability of pulmonary carcinoma. Acta OtolaryngoI 56:603-611, 1963 3 Waltner JG: Inoperability of carcinoma of the lung established by carinal biopsy. Ann Otolaryngol 70:1165-1171, 1961 4 Rabin CG: Relation of roentgenography of chest to the laryngologist: Atelectasis and neoplasms of lung. Laryngoscope 42:923-930,1932 5 Rabin CB, Neuhof H: Topographic classification of primary cancer of the lung: Its application to the operative indication and treatment. J Thorac Surg 4:147-164, 1934 6 Griess DF, McDonald JR, Clagett OT: Proximal extension of carcinoma of the lung in the bronchial wall. J Thorae Cardiovasc Surg 14:362-368, 1945 7 American Joint Committee for Cancer Staging and EndResults Reporting: Manual for Staging of Cancer 1977. Chicago, 1977, pp 59-61
CHEST, 75: 4, APRil, 1979