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Trucut needle biopsy in sarcoidosis. Relationship between histology of the biopsy specimens and radiographic features and pulmonary function
Br. J. Dir.
Chest
(1983)
77,
243
TRUCUT NEEDLE BIOPSY IN SARCOIDOSIS. RELATIONSHIP BETWEEN HISTOLOGY OF THE BIOPSY SPECIMENS AND RADIOGRAPHIC FEATURES AND PULMONARY FUNCTION P. TUKIAINEN”,
E. TASKINENT,
0. KORHOLA$,
of Pulmonary Diseases, fTransplantation Laboratory, Department Diagnostic Radiology, *Department
of
Helsinki University Helsinki
M. VALLE$
AND
P. MAASILTA”
University Central Hospital, Finland; of Helsinki, Finland; and University Central Hospital, Finland
Summary
Ninety-nine TruCut needle biopsies were performed on 92 patients with sarcoidosis. Non-caseating granulomas were found in 77 of 92 patients (84%) and in 78 of 99 biopsies (79%). Granulomas were found in 67% of patients showing only slight radiographic opacity (IL0 classification grades O/O-l/l) and in 90% of patients with higher radiographic grades (IL0 l/2-3/3). Th ere was also a positive relationship between the size of the biopsy specimen and the presence of granulomas. Granulomas were found in 68% of small biopsy specimens and in 90% of moderate or large specimens.
Introduction Sarcoidosis is a multisystemic disease of unknown origin characterized by the presence of non-caseating granulomas in many organs. Although the cause is not understood and the morphological features non- specific, the combination of clinical, radiographic, histological and physiological findings are so characteristic that in clinical practice a diagnosis of sarcoidosis is usually unambiguous. Sarcoidosis has been described in most organs, but in general lung involvement has the most serious consequences (Mitchell & Scadding 1974). At least 90% of all patients with sarcoidosis have pulmonary manifestations (James et al. 1976). Histological confirmation of the diagnosis is frequently desired in patients with suspected sarcoidosis. Less invasive biopsy procedures are preferred in the case of cutaneous lesions, subcutaneous nodules or palpable lymph nodes but such lesions are, however, comparatively uncommon. Open lung biopsy is the most reliable diagnostic procedure and will reveal noncaseating granulomas in practically all cases of sarcoidosis, even in the absence of radiographic pulmonary opacities (Bacharach 1961). In recent years, transbronchial lung biopsy through the fibreoptic bronchoscope has proved to be a safe procedure 23
244
P. Tukiainen,
E. Taskinen,
0. Korhola,
M. Valle and P. Maasilta
with low morbidity and relatively high diagnostic yield, especially if several biopsy specimens are obtained (Mitchell et al. 1980; Roethe et al. 1980). Since 1972 we have performed over 400 TruCut needle biopsies in patients with diffuse lung disease. We have thus had the opportunity to examine a relatively large series of consecutive cases of sarcoidosis. The aim of this study was to analyse the diagnostic yield of this biopsy method and the factors influencing it. The 39 patients published previously are included (Tukiainen 1975).
Materials
and Methods
The series consists of 45 females and 47 males. The mean age of the patients was 41 years (1975 years). Sarcoidosis was diagnosed on the basis of clinical and radiographic findings. In 25 cases there was a positive biopsy finding (other than lung) and/or a positive Kveim test. Forced vital capacity (FVC) and forced expiratory volume in one set (FEVr ) were recorded with a spirometer (Bernstein Spirometer, Kifa) before 1975, and subsequently with a dry rolling seal 12 litre spirometer (CPI Model 220). The values were expressed as a percentage of the reference values of Berglund et al. (1963). Pulmonary diffusing capacity (DLCO) was measured using the single breath method for carbon monoxide (Ogilvie et al. 1957) and the reference values of Cotes (1975). All chest radiographs were assessed and graded by two radiologists (0.K and M.V.) in conformity with the standard film of the IL0 U/C International Classification (197 1). All lung biopsies were performed with a TruCut needle (Travenol Laboratories Inc.). Specimens were taken from a peripheral area of the lung about l-3 cm below the visceral pleura in the posterior region of the right lower lobe (Tukiainen 1975). The size of the specimen was graded on the basis of length. Specimens under 2.5 mm were graded as small, those of 2.5-5.0 mm as moderate and those over 5.0 mm in length as large. Thickening of the alveolar wall was compared with the diameter of the alveolar lumen and estimated as mild, moderate or marked by a method described in detail elsewhere (Tukiainen 1975). The degree of alveolar wall fibrosis was estimated on the basis of thickening of the alveolar wall and the relative proportion of fibroblasts and collagen fibres in it. The granulomatous inflammation in the biopsy specimen was graded on the basis of density of the granulomas: slight, less than half the slide area; moderate, about half the slide area; marked, more than half the slide area. Statistical analysis between biopsy finding and pulmonary function was performed using t-test for correlated means and chi square test.
Results Non-c&eating granulomas were found in 77 of 92 patients (84%) and in 77 of 90 adequate lung specimens (86%). In seven cases two biopsies were performed because an inadequate specimen was obtained in four and normal lung tissue in two cases. In one case both biopsies showed granulomas, but the second specimen was collected 2 years after the first procedure because of a poor response to corticosteroid treatment. Adequate specimens were obtained in 93% of 99 biopsies and the overall diagnostic yield was 78 of 99 biopsies (79%). There was no clear correlation between the diffusing capacity or vital capacity values and the density of granulomas in the biopsy specimens (Table I). Alveolitis, i.e. diffuse inflammatory cell infiltration in alveolar septa, was observed in 12 (13%) biopsies but was not a prominent feature in any. Fibrosis of
TruCut
Needle Biopsy
in Sarcoidosis
245
the internal framework (interstitial) of the alveolar walls was found in 22 biopsies (24%), and was diffuse in 15 and patchy or perivascular in seven. Diffusing capacity values were slightly lower in the patients with interstitial fibrosis than in those without fibrosis (Table 1, P< 0.05). Vital capacity was the same in the Table I. The relationship between the histological function in patients with sarcoidosis*
and radiographic
features
and pulmonary
No. of cases
DLCO% of predicted mean * SD
Correlation coefficient
F VC% of predicted mean + SD
Correlation coefficient
Alveolar wall thickening no thickening
18 74
66.0 + 16.9 81.8 + 15.2
3.86 P-c 0.001
80.8 31 18.5 88.6 + 15.1
1.85 NS
Alveolar wall fibrosis no fibrosis
24 68
73.0 + 19.1 80.9 + 15.5
2.02 P< 0.05
84.0 + 18.0 88.1 + 15.4
1.05 NS
Density of granulomas moderate marked no granul. mild
45 47
77.8 * 18.8 79.9 + 14.9
0.59 NS
84.0 f 15.5 90.0 f. 16.4
1.78 NS
Radiographic of opacities Z/3-3/3 l/O-2/2
24 68
77.8 + 17.3 78.2 f 17.1
0.15 NS
86.5 f 19.3 87.5 If: 14.6
0.26 NS
grades
*Includes Table II.
90 patients
with adequate
biopsy
specimen.
Relationship between the density of granulomas in 93 adequate biopsy specimens the radiographic opacities (IL0 classification) in patients with sarcoidosis
Degree of radiographic opacities
Density
of granulomas
Marked
Moderate
Mild
No granulomas
Total no. of adequate specimens
o/1-1/1* l/2-2/2 213-313
5 5
7 18 9
5 20 9
6 7 2
18 50 25
Total
10
34
34
15
93
*Includes preponderance.
four
patients
with
l/2-2/2
radiographic
grades
and
marked
and
upper
lobe
patients with and without interstitial fibrosis. The alveolar walls were thickened in 18 biopsies, mostly due to interstitial fibrosis. The values for diffusing capacity were lower in the patients showing alveolar wall thickening than in those not showing this feature (Table I, P< 0.001). There was, however, no statistically significant difference between vital capacity of patients with alveolar wall thickening and without it.
246
P. Tukiainen,
E. Taskinen,
0. Korhola,
M.
Valle
and P. Maasilta
Granulomas were found in 12 of 18 (67%) patients with only slight radiographic opacities, or none (IL0 O/O-l/l) (Table II). This percentage includes patients with upper lobe preponderance of pulmonary opacities (IL0 grades 2/2 in two and 2/3 in two) and normal or nearly normal radiographic appearances at the site of biopsy. On the other hand, granulomas were found in 66 of 75 biopsies (90%) from those patients who had higher radiographic grades (IL0 l/2-3/3), Table II. The density of granulomas in the biopsy specimen had a loose relationship with the radiographic grade of opacity (Table II, PC 0.10). A clear relationship was found between the size of the biopsy specimens and the biopsy findings (Table III). Including all adequate biopsy specimens granulomas were found in 17 of 25 (68%) small biopsy specimens and in 61 of 68 (90%) moderate or large specimens (P < 0.05). Pneumothorax was observed in 17 of 91 biopsies, one of them requiring chest tube aspiration. Minimal haemoptysis occurred after 10 biopsies and in one patient was of 150 ml. There were no fatal complications. Table ZZZ. Relationship
between
the
size
of
the
biopsy
specimen
and
the
finding
of
granulomas
Size of the specimen Large Moderate Small Total
Biopsy finding Granulomas 30 (91%) 31 (89%) 17 (68%) 78
(%)
No
granulomas
Total no. of adequate specimens
3 4 8
33 35 25
15
93
Discussion Our series consists of consecutive patients with sarcoidosis and with diffuse radiographic opacities in all cases except one (in which the chest radiograph was normal and a gas transfer defect was the indication for lung biopsy). It therefore represents a selected group of patients. The radiographs were read using the IL0 classification system ( 19 7 1) j which was originally devised for epidemiological use in pneumoconiosis. It has been also used in non-occupational lung diseases in which the radiographic features have many similarities to fibrosing alveolitis (Carrington et al. 1978, Turner-Warwick et al. 1980). On the basis of our experience the system seems to be suitable also for evaluation of radiographs in patients with sarcoidosis. The chance of finding granulomas in a lung biopsy specimen depends on their density in the lung tissue. In our series there was a positive relationship between the presence of granulomas in the biopsy specimen and the profusion of radiographic changes. On the other hand, there was no clear correlation between the presence of granulomas in the biopsy specimen and pulmonary function, which is in contrast to the findings of Koontz et al. (1976). This lack of a relationship is probably explained by the absence of diffuse alveolitis, as seen for example in
TruCut Needle Biopsy in Sarcoidosis
247
allergic alveolitis. On the other hand, diffusing capacity correlated with the degree of alveolar wall thickening, which in our material was due mainly to interstitial fibrosis. Alveolitis was observed only in 13% of the patients, which is less than the figure given by Rosen et al. (1978), who found that alveolitis was a predominant or conspicuous feature in 62% of their 128 cases showing granulomas. The cause of this discrepancy is obscure. The material of Rosen et al. was perhaps obtained from patients with more advanced disease or with a more severe clinical course. Moreover, some patients showing diffuse alveolitis but no granulomas may have been misdiagnosed as having conditions other than sarcoidosis, such as fibrosing alveolitis. This does not however account for the difference, because in our series of sarcoidosis patients there were no patients with prominent alveolitis. In our material there was a clear relationship between the size of the biopsy specimen and the occurrence of granulomas in the biopsy specimen. The diagnostic value of biopsy techniques depends on the size of the specimen and the safety of the procedure. We have performed TruCut needle biopsy on over 400 patients. In one-third some complication occurred, mostly a minimal pneumothorax or slight haemoptysis but there have been no fatal complications. In 3% of patients a pneumothorax required treatment by chest tube or needle aspiration and in another 3% haemoptysis of over 100 ml occurred. The frequency of complications in patients with sarcoidosis was in fact slightly lower than in the whole series of TruCut biopsies. In needle biopsies massive haemoptysis is a potentially dangerous complication (Yomanas et al. 1970; Boylen et al. 1973). Our biopsies are performed under fluoroscopic guidance in the most peripheral part of the lower lobe, and we believe that dangerous complications have been avoided by this method. In trephine biopsy the size of the lung biopsy specimen and the complication frequency seem to be the same as in TruCut biopsy (Steel & Winstanley 1969). Transbronchial lung biopsy (TBB) seems to be safe, mortality being less than 0.5%. The size of the specimen is only a few millimetres and the diagnostic yield, 74% in a combined series of 198 cases (Roethe et al. 1980), is comparable to our results in patients with small biopsy specimens (68%). Koontz et al. (1976) were able to improve the diagnostic yield to 80% by taking six transbronchial biopsy specimens in one procedure. They detected granulomas in 36 out of 37 patients, and Mitchell et al. (1980) in 32 of 42 patients with sarcoidosis. This increased yield is probably due to sampling a large quantity of pulmonary tissue. In contrast to these observations, Wall et al. (1981) h ave recently reported that among 53 patients with diffuse lung disease TBB was diagnostic in 20 (38%), while the histological appearance in the remaining biopsies was non-specific. Subsequent open lung biopsy gave a specific diagnosis in 92%. In sarcoidosis TBB was diagnostic in 67% of cases. With a few exceptions, transbronchial biopsy seems to be of greater diagnostic value in patients with sarcoidosis (Wall et al. 1981), while a larger specimen is needed in patients with other diffuse lung diseases such as fibrosing alveolitis, allergic alveolitis and asbestosis. In patients with bilateral hilar node enlargement the probability of sarcoidosis is high and transbronchial biopsy might be preferable to needle biopsy if several specimens are collected, and in patients with upper lobe infiltrates (sarcoidosis,
248
P. Tukiainen,
E. Task&en,
0. Korhola,
M. Valle and P. Maasilta
silicosis) TBB is preferred. In all other instances of diffuse lung opacities needle biopsy (TruCut, trephine) might yield more diagnoses than TBB, and in the case of a non-specific needle biopsy finding, operative biopsy is indicated.
Acknowledgement This investigation has been supported by grants-from Finland, and the Finnish Anti-Tuberculosis Association.
the Paul0
Foundation,
References Bacharach, T. (1961) Sarcoidosis: a clinical review of 111 cases. Am. Rev. resp. Dis. 84, 12. Berglund, E., Birath, F., Bjure, J., Grimby, F., Kjellman, I., Sandquist, L. & Soderholm, K. (1963) Spirometric studies in normal subjects. 1. Forced expirograms in subjects between 7 and 70 years of age. Acta med. stand. 173, 185. Boylen, C. T., Johnson, R. R., Richters, V. & Balchum, 0. J. (1973) High speed trephine lung biopsy method and results. Chest 63, 59. Carrington, C. B., Gaensler, E. A., Coutu, R. E., Fitzgerald, M. X. & Gupta, R. G. (1978) Natural history and treated course of usual and desquamative interstitial pneumonia. New Engl. J. Med. 298, 801. Cotes, J. E. (1975) Lung Function. Assessment and Application in Medicine. Oxford: Blackwell Scientific Publications. IL0 U/C (1971) International Classification of Radiographs of Pneumoconiosis. Occupational safety and health series. Geneva: International Labour Office. James, D. G., Neville, E., Silzbach, L. E. et al. (1976) A worldwide survey of sarcoid. In: Seventh International Conference on Sarcoidosis, ed. L. E. Silzbach. Ann. N. Y. Acad. Sci. 278, 321. Koontz, C. H., Joyner, L. R. & Nelson, R. A. (1976) Transbronchial lung biopsy via the fiberoptic bronchoscope in sarcoidosis. Ann. intern. Med. 85, 64. Mitchell, D. M., Emerson, C. J., Collyer, J. & Collins, J. V. (1980) Fibreoptic bronchoscopy: ten years on. Occasional review. Br. med. J. 281, 360. Mitchell, D. N. & Scadding, J. G. (1974) Sarcoidosis. Am. Rev. resp. Dis. 110, 774. Ogilvie, C. M., Forster, R. E., Blakemore, W. S. & Morton, J. W. (1957) A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J. clin. Invest. 36, 1. Roethe, R. A., Fuller, P. B., Byrd, R. B. & Hafermann, D. R. (1980) Transbronchoscopic lung biopsy in sarcoidosis. Optimal number and sites for diagnosis. Chest 77, 400. Rosen, Y., Athanassiades, T. J., Moon, S. & Lyons, H. A. (1978) Non-granulomatous interstitial pneumonitis in sarcoidosis. Relationship to development of epitheloid granulomas. Chest 74, 122. Steel, S. J. & Winstanley, D. P. (1969) Trephine biopsy of the lung and pleura. Thorax 24, 576. Tukiainen, P. (1975) Needle biopsy in diffuse lung manifestations. An analysis of 145 consecutive cases. Stand. J. resp. Dis. Suppl. 94, 1. Turner-Warwick, M., Burrows, B. &Johnson, A. (1980) Cryptogenic fibrosing alveolitis: clinical features and their influence on survival. Thorax 35, 17 1. Wall, C. P., Gaensler, E. A., Carrington, C. B. & Hayes, J. A. (1981) Comparison of transbronchial and open biopsies in chronic infiltrative lung diseases. Am. Rev. resp. Dis. 123, 280. Yomanas, C. R., De Groot, W. J., Marshall, R., Morettin, L. B. & Derrick, J. R. (1970) Needle biopsy of the lung in diffuse parenchymal disease. Am. J. Med. 120, 637.
Chest
(1983)
77,
243
TRUCUT NEEDLE BIOPSY IN SARCOIDOSIS. RELATIONSHIP BETWEEN HISTOLOGY OF THE BIOPSY SPECIMENS AND RADIOGRAPHIC FEATURES AND PULMONARY FUNCTION P. TUKIAINEN”,
E. TASKINENT,
0. KORHOLA$,
of Pulmonary Diseases, fTransplantation Laboratory, Department Diagnostic Radiology, *Department
of
Helsinki University Helsinki
M. VALLE$
AND
P. MAASILTA”
University Central Hospital, Finland; of Helsinki, Finland; and University Central Hospital, Finland
Summary
Ninety-nine TruCut needle biopsies were performed on 92 patients with sarcoidosis. Non-caseating granulomas were found in 77 of 92 patients (84%) and in 78 of 99 biopsies (79%). Granulomas were found in 67% of patients showing only slight radiographic opacity (IL0 classification grades O/O-l/l) and in 90% of patients with higher radiographic grades (IL0 l/2-3/3). Th ere was also a positive relationship between the size of the biopsy specimen and the presence of granulomas. Granulomas were found in 68% of small biopsy specimens and in 90% of moderate or large specimens.
Introduction Sarcoidosis is a multisystemic disease of unknown origin characterized by the presence of non-caseating granulomas in many organs. Although the cause is not understood and the morphological features non- specific, the combination of clinical, radiographic, histological and physiological findings are so characteristic that in clinical practice a diagnosis of sarcoidosis is usually unambiguous. Sarcoidosis has been described in most organs, but in general lung involvement has the most serious consequences (Mitchell & Scadding 1974). At least 90% of all patients with sarcoidosis have pulmonary manifestations (James et al. 1976). Histological confirmation of the diagnosis is frequently desired in patients with suspected sarcoidosis. Less invasive biopsy procedures are preferred in the case of cutaneous lesions, subcutaneous nodules or palpable lymph nodes but such lesions are, however, comparatively uncommon. Open lung biopsy is the most reliable diagnostic procedure and will reveal noncaseating granulomas in practically all cases of sarcoidosis, even in the absence of radiographic pulmonary opacities (Bacharach 1961). In recent years, transbronchial lung biopsy through the fibreoptic bronchoscope has proved to be a safe procedure 23
244
P. Tukiainen,
E. Taskinen,
0. Korhola,
M. Valle and P. Maasilta
with low morbidity and relatively high diagnostic yield, especially if several biopsy specimens are obtained (Mitchell et al. 1980; Roethe et al. 1980). Since 1972 we have performed over 400 TruCut needle biopsies in patients with diffuse lung disease. We have thus had the opportunity to examine a relatively large series of consecutive cases of sarcoidosis. The aim of this study was to analyse the diagnostic yield of this biopsy method and the factors influencing it. The 39 patients published previously are included (Tukiainen 1975).
Materials
and Methods
The series consists of 45 females and 47 males. The mean age of the patients was 41 years (1975 years). Sarcoidosis was diagnosed on the basis of clinical and radiographic findings. In 25 cases there was a positive biopsy finding (other than lung) and/or a positive Kveim test. Forced vital capacity (FVC) and forced expiratory volume in one set (FEVr ) were recorded with a spirometer (Bernstein Spirometer, Kifa) before 1975, and subsequently with a dry rolling seal 12 litre spirometer (CPI Model 220). The values were expressed as a percentage of the reference values of Berglund et al. (1963). Pulmonary diffusing capacity (DLCO) was measured using the single breath method for carbon monoxide (Ogilvie et al. 1957) and the reference values of Cotes (1975). All chest radiographs were assessed and graded by two radiologists (0.K and M.V.) in conformity with the standard film of the IL0 U/C International Classification (197 1). All lung biopsies were performed with a TruCut needle (Travenol Laboratories Inc.). Specimens were taken from a peripheral area of the lung about l-3 cm below the visceral pleura in the posterior region of the right lower lobe (Tukiainen 1975). The size of the specimen was graded on the basis of length. Specimens under 2.5 mm were graded as small, those of 2.5-5.0 mm as moderate and those over 5.0 mm in length as large. Thickening of the alveolar wall was compared with the diameter of the alveolar lumen and estimated as mild, moderate or marked by a method described in detail elsewhere (Tukiainen 1975). The degree of alveolar wall fibrosis was estimated on the basis of thickening of the alveolar wall and the relative proportion of fibroblasts and collagen fibres in it. The granulomatous inflammation in the biopsy specimen was graded on the basis of density of the granulomas: slight, less than half the slide area; moderate, about half the slide area; marked, more than half the slide area. Statistical analysis between biopsy finding and pulmonary function was performed using t-test for correlated means and chi square test.
Results Non-c&eating granulomas were found in 77 of 92 patients (84%) and in 77 of 90 adequate lung specimens (86%). In seven cases two biopsies were performed because an inadequate specimen was obtained in four and normal lung tissue in two cases. In one case both biopsies showed granulomas, but the second specimen was collected 2 years after the first procedure because of a poor response to corticosteroid treatment. Adequate specimens were obtained in 93% of 99 biopsies and the overall diagnostic yield was 78 of 99 biopsies (79%). There was no clear correlation between the diffusing capacity or vital capacity values and the density of granulomas in the biopsy specimens (Table I). Alveolitis, i.e. diffuse inflammatory cell infiltration in alveolar septa, was observed in 12 (13%) biopsies but was not a prominent feature in any. Fibrosis of
TruCut
Needle Biopsy
in Sarcoidosis
245
the internal framework (interstitial) of the alveolar walls was found in 22 biopsies (24%), and was diffuse in 15 and patchy or perivascular in seven. Diffusing capacity values were slightly lower in the patients with interstitial fibrosis than in those without fibrosis (Table 1, P< 0.05). Vital capacity was the same in the Table I. The relationship between the histological function in patients with sarcoidosis*
and radiographic
features
and pulmonary
No. of cases
DLCO% of predicted mean * SD
Correlation coefficient
F VC% of predicted mean + SD
Correlation coefficient
Alveolar wall thickening no thickening
18 74
66.0 + 16.9 81.8 + 15.2
3.86 P-c 0.001
80.8 31 18.5 88.6 + 15.1
1.85 NS
Alveolar wall fibrosis no fibrosis
24 68
73.0 + 19.1 80.9 + 15.5
2.02 P< 0.05
84.0 + 18.0 88.1 + 15.4
1.05 NS
Density of granulomas moderate marked no granul. mild
45 47
77.8 * 18.8 79.9 + 14.9
0.59 NS
84.0 f 15.5 90.0 f. 16.4
1.78 NS
Radiographic of opacities Z/3-3/3 l/O-2/2
24 68
77.8 + 17.3 78.2 f 17.1
0.15 NS
86.5 f 19.3 87.5 If: 14.6
0.26 NS
grades
*Includes Table II.
90 patients
with adequate
biopsy
specimen.
Relationship between the density of granulomas in 93 adequate biopsy specimens the radiographic opacities (IL0 classification) in patients with sarcoidosis
Degree of radiographic opacities
Density
of granulomas
Marked
Moderate
Mild
No granulomas
Total no. of adequate specimens
o/1-1/1* l/2-2/2 213-313
5 5
7 18 9
5 20 9
6 7 2
18 50 25
Total
10
34
34
15
93
*Includes preponderance.
four
patients
with
l/2-2/2
radiographic
grades
and
marked
and
upper
lobe
patients with and without interstitial fibrosis. The alveolar walls were thickened in 18 biopsies, mostly due to interstitial fibrosis. The values for diffusing capacity were lower in the patients showing alveolar wall thickening than in those not showing this feature (Table I, P< 0.001). There was, however, no statistically significant difference between vital capacity of patients with alveolar wall thickening and without it.
246
P. Tukiainen,
E. Taskinen,
0. Korhola,
M.
Valle
and P. Maasilta
Granulomas were found in 12 of 18 (67%) patients with only slight radiographic opacities, or none (IL0 O/O-l/l) (Table II). This percentage includes patients with upper lobe preponderance of pulmonary opacities (IL0 grades 2/2 in two and 2/3 in two) and normal or nearly normal radiographic appearances at the site of biopsy. On the other hand, granulomas were found in 66 of 75 biopsies (90%) from those patients who had higher radiographic grades (IL0 l/2-3/3), Table II. The density of granulomas in the biopsy specimen had a loose relationship with the radiographic grade of opacity (Table II, PC 0.10). A clear relationship was found between the size of the biopsy specimens and the biopsy findings (Table III). Including all adequate biopsy specimens granulomas were found in 17 of 25 (68%) small biopsy specimens and in 61 of 68 (90%) moderate or large specimens (P < 0.05). Pneumothorax was observed in 17 of 91 biopsies, one of them requiring chest tube aspiration. Minimal haemoptysis occurred after 10 biopsies and in one patient was of 150 ml. There were no fatal complications. Table ZZZ. Relationship
between
the
size
of
the
biopsy
specimen
and
the
finding
of
granulomas
Size of the specimen Large Moderate Small Total
Biopsy finding Granulomas 30 (91%) 31 (89%) 17 (68%) 78
(%)
No
granulomas
Total no. of adequate specimens
3 4 8
33 35 25
15
93
Discussion Our series consists of consecutive patients with sarcoidosis and with diffuse radiographic opacities in all cases except one (in which the chest radiograph was normal and a gas transfer defect was the indication for lung biopsy). It therefore represents a selected group of patients. The radiographs were read using the IL0 classification system ( 19 7 1) j which was originally devised for epidemiological use in pneumoconiosis. It has been also used in non-occupational lung diseases in which the radiographic features have many similarities to fibrosing alveolitis (Carrington et al. 1978, Turner-Warwick et al. 1980). On the basis of our experience the system seems to be suitable also for evaluation of radiographs in patients with sarcoidosis. The chance of finding granulomas in a lung biopsy specimen depends on their density in the lung tissue. In our series there was a positive relationship between the presence of granulomas in the biopsy specimen and the profusion of radiographic changes. On the other hand, there was no clear correlation between the presence of granulomas in the biopsy specimen and pulmonary function, which is in contrast to the findings of Koontz et al. (1976). This lack of a relationship is probably explained by the absence of diffuse alveolitis, as seen for example in
TruCut Needle Biopsy in Sarcoidosis
247
allergic alveolitis. On the other hand, diffusing capacity correlated with the degree of alveolar wall thickening, which in our material was due mainly to interstitial fibrosis. Alveolitis was observed only in 13% of the patients, which is less than the figure given by Rosen et al. (1978), who found that alveolitis was a predominant or conspicuous feature in 62% of their 128 cases showing granulomas. The cause of this discrepancy is obscure. The material of Rosen et al. was perhaps obtained from patients with more advanced disease or with a more severe clinical course. Moreover, some patients showing diffuse alveolitis but no granulomas may have been misdiagnosed as having conditions other than sarcoidosis, such as fibrosing alveolitis. This does not however account for the difference, because in our series of sarcoidosis patients there were no patients with prominent alveolitis. In our material there was a clear relationship between the size of the biopsy specimen and the occurrence of granulomas in the biopsy specimen. The diagnostic value of biopsy techniques depends on the size of the specimen and the safety of the procedure. We have performed TruCut needle biopsy on over 400 patients. In one-third some complication occurred, mostly a minimal pneumothorax or slight haemoptysis but there have been no fatal complications. In 3% of patients a pneumothorax required treatment by chest tube or needle aspiration and in another 3% haemoptysis of over 100 ml occurred. The frequency of complications in patients with sarcoidosis was in fact slightly lower than in the whole series of TruCut biopsies. In needle biopsies massive haemoptysis is a potentially dangerous complication (Yomanas et al. 1970; Boylen et al. 1973). Our biopsies are performed under fluoroscopic guidance in the most peripheral part of the lower lobe, and we believe that dangerous complications have been avoided by this method. In trephine biopsy the size of the lung biopsy specimen and the complication frequency seem to be the same as in TruCut biopsy (Steel & Winstanley 1969). Transbronchial lung biopsy (TBB) seems to be safe, mortality being less than 0.5%. The size of the specimen is only a few millimetres and the diagnostic yield, 74% in a combined series of 198 cases (Roethe et al. 1980), is comparable to our results in patients with small biopsy specimens (68%). Koontz et al. (1976) were able to improve the diagnostic yield to 80% by taking six transbronchial biopsy specimens in one procedure. They detected granulomas in 36 out of 37 patients, and Mitchell et al. (1980) in 32 of 42 patients with sarcoidosis. This increased yield is probably due to sampling a large quantity of pulmonary tissue. In contrast to these observations, Wall et al. (1981) h ave recently reported that among 53 patients with diffuse lung disease TBB was diagnostic in 20 (38%), while the histological appearance in the remaining biopsies was non-specific. Subsequent open lung biopsy gave a specific diagnosis in 92%. In sarcoidosis TBB was diagnostic in 67% of cases. With a few exceptions, transbronchial biopsy seems to be of greater diagnostic value in patients with sarcoidosis (Wall et al. 1981), while a larger specimen is needed in patients with other diffuse lung diseases such as fibrosing alveolitis, allergic alveolitis and asbestosis. In patients with bilateral hilar node enlargement the probability of sarcoidosis is high and transbronchial biopsy might be preferable to needle biopsy if several specimens are collected, and in patients with upper lobe infiltrates (sarcoidosis,
248
P. Tukiainen,
E. Task&en,
0. Korhola,
M. Valle and P. Maasilta
silicosis) TBB is preferred. In all other instances of diffuse lung opacities needle biopsy (TruCut, trephine) might yield more diagnoses than TBB, and in the case of a non-specific needle biopsy finding, operative biopsy is indicated.
Acknowledgement This investigation has been supported by grants-from Finland, and the Finnish Anti-Tuberculosis Association.
the Paul0
Foundation,
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