Ultrasound-Guided Core Biopsy of Thoracic 'lumors':'
PAN-CHYR YANG, DUN-BING CHANG, CHONG-JEN YU, YUNG-CHIE LEE, HUEY·DONG WU, SOW-HSONG KUO, and KWEN-TAY LUH
Introduction
Percutaneous transthoracic needle biopsy under fluoroscopic or computed tomographic (CT) guidance is a wellestablished procedure to obtain tissue for histologic diagnosis of a thoracic tumor (1, 2). Recently, ultrasound has also been found useful for guiding a percutaneous needle to biopsy for peripheral pulmonary nodules (3) and for mediastinal tumors (4, 5). The thoracic tumor suitable for ultrasound-guided needle biopsy is not restricted only to those lesions that abut on the pleura. An air-containing lung is a poor transmitting medium for ultrasound. However, an atelectatic or nonaerated lung becomes a good "ultrasound window" that may allow underlying tumors to be visualized (6). Moreover, improved ultrasound resolution and real-time image monitoring of biopsy procedures also allows an approach to thoracic tumors with a greater margin of safety and accuracy (7). Even a 14-18-gauge cutting needle can be used in ultrasound-guided core biopsy of thoracic tumor with acceptable risk of complications (6, 8, 9). Most of the percutaneous guided needle biopsies are done by fine needle (21 gauge or smaller). The materials aspirated are generally suitable only for cytologic examination. Although a welltrained cytopathologist is able to make a diagnosis from these small specimens with high sensitivity and accuracy, the overall sensitivity is around 80% (1, 2, 10).Given that fine-needle aspiration biopsy is a safe procedure with acceptable accuracy for thoracic tumor diagnosis, the very small specimen obtained for cytologic examination often fails to provide precise information about cell type and tumor origin. False-negative results are frequently encountered, and a largebore needle biopsy or thoracotomy is always necessary to confirm the diagnosis. For those patients with mediastinal tumors, a definite histologic diagnosis is essential for subsequent patient management. Fine-needle aspiration biopsy is not always adequate for a histologic di-
SUMMARY 'TWo hundred and eighteen patients, with thoracic tumors larger than 3 cm in size, underwent ultrasound-guided percutaneous transthoracic core biopsy with a large-bore Tru-Cut needle. Fifty-five tumors were In the mediastinum, and 122 tumors were located at subpleural area, and 42 tumors were within the lungs. In 122 subpleural tumors, the sensitivity of ultrasound-guided core biopsy for the diagnosis of malignancy was 96.8%, and accuracy was 97.5%. Sensitivity for the diagnosis of malignant tumors located within the lungs was 94.6%, and accuracy was 95.2%. In 54 patients with mediastinal tumors, definite histologic diagnosis could be obtained in 48 patients (88.9%). The sensitivity of ultrasound-guided biopsy for the diagnosis of malignancy In these 48 mediastinal tumors was 97.1%, with an accuracy of 97.9%. Three patients had complications with minimal pneumothorax and one with mild hemoptysis. Weconclude that percutaneous transthoracic core biopsy with Tru-Cut needle under ultrasound guidance is a safe and sensitive way to obtain specimens for accurate histologic diagnosis of thoracic tumors. The diagnostic yield Is high, and the technique, relatively simple, can also be used for outpatients. AM REV RESPIR DIS 1992; 146:763-767
agnosis of a mediastinal tumor. Low sensitivity of 20 to 71% could only be obtained for lymphoma, Hodgkin's diseases and thymoma by fine needle aspiration biopsy (11). This study assessesthe safety, diagnostic sensitivity, and accuracy of ultrasound-guided core biopsy for 218tumors located in the mediastinum and lung parenchyma, using a large-bore Tru-Cut needle. Methods From January 1985 to December 1990, 302 patients with radiographic evidence of thoracic tumors, suspected of malignancy, were seen at National Taiwan University Hospital. Patients wereselectedfor chest ultrasound examination and ultrasound-guided percutaneous transthoracic biopsy with a TruCut needle according to the following criteria: (1)mediastinal tumors, anterior or posterior in location, which had contact with the chest wall; (2) peripheral pulmonary tumors that abutted on the pleura, or pulmonary tumors with an accessibleultrasound window; (3) for safety, only tumors larger than 3 em in diameter are biopsied by Tru-Cut needle; (4) the patient has platelet count in excess of 100,000/1JL and normal prothrombin time; and (5) patients are cooperative. Eighty-four patients with thoracic tumors wereexcluded: six patients with tumors in the medmediastinum, 26 patients with lung tumors without accessible ultrasound window,31patients with lung tumors smaller than 3 em in diameter, three persons with coagulation ab-
normality, 13 patients who refused transthoracic biopsy, and five uncooperative patients. Thus, a total of 218 patients actually underwent ultrasound-guided biopsy for their thoracic tumors. All patients wereexamined with real-time, linear, convex, and sector ultrasonic units with 3.5 MHz, 5.0 MHz, and 7.5 MHz transducer (Aloka SSD 630; Aloka, Japan; Toshiba 100A; Tokyo, Japan). The sector ultrasound units werealso equipped with Doppler ultrasound, which could be used to detect great vessels and blood flow. The patients were scanned in supine or prone position by means of an intercostal approach. The sonographic images were recorded on polaroid film (Polaroid, Cambridge, MA) for analysis of tumor location and the relationship of the tumor to surrounding vessels and vital structures. After assessment of the tumor location and demarcation of tumor margins, an informed consent was obtained, and the tumor was subjected to percutaneous transthoracic cutting biopsy with a large bore (16 gauge)
(Received in original form October 14, 1991 and in revised form February 28, 1992) 1 From the Departments of Internal Medicine, Surgery, and Clinical Pathology, National Taiwan University Hospital, and Institute of Biomedical Sciences, Academica Sinica, Taipei, Taiwan, Republic of China. 2 Correspondence and requests for reprints should be addressed to Pan-Chyr Yang, M.D., Ph.D., Department of Internal Medicine, National Taiwan University Hospital, No.1, Chang-Te Street, Taipei, Taiwan 100, Republic of China.
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Tru-Cut needle (Top surgical, Tokyo, Japan) through a sterile puncture transducer (Aloka UST-507 BP). The puncture transducer provided a preset puncture area that could be displayed on the monitor screen. The biopsy route could be adjusted at a fixed angle from - 5° to 25°. The biopsy route was preselected to avoid penetrating great vessels. The ultrasound guided biopsy technique has also been detailed in previous studies (3, 4, 6, 9). The patient was asked to hold his/her breath, and the biopsy procedure was carried out within 10to 15s. The Tru-Cut biopsy specimen was sent for pathologic examination. A specimen obtained by Tru-Cut biopsy was observed grossly, and arbitrarily designated as inadequate if the specimen wassmaller than 2 x 4 mm in size. A Tru-Cut biopsy was repeated immediately before the histologic examination was performed. If a lymphoma or Hodgkin's disease was suspected, multiple biopsies were conducted to obtain at least two adequate specimens for both routine histological examination as well as immunohistologic studies to confirm the cell type. A chest radiograph was performed routinely 24 h after the Tru-Cut biopsy to assess any possible complication. A false-negative result was considered to have occurred if the tumor was confirmed at surgery, by biopsy from other metastatic sites, or if there was evidence of disease progress at follow-up examination. A true negative result was considered if the disease turns out to be benign at follow-up by chest radiographs, CT scan, and fiberoptic bronchoscopy with or without biopsy. A sensitivity was percent of patients with malignant tumor correctly diagnosed as malignant by ultrasoundguided biopsy. A specificity was percent of patients with benign tumor correctly diagnosed as benign. An accuracy was percent of patients with thoracic tumor correctly diagnosed as malignant or benign. A chi-square test was used to compare the sensitivity of ultrasound-guided biopsy between different groups of thoracic tumors.
Fig. 1. (a) Chest radiograph of a 56-yrold man, showing an anterior mediastinal tumor (arrowhead). (b) Chest ultrasound revealing a hypoechoic tumor with smooth margin just anterior to the ascending aorta. The histologic diagnosis from the ultrasound-guided core biopsy is thymoma. A = aorta.
Results
TABLE 1
A total of 218 patients were included in this study. There were 146 men and 72 women, whose ages ranged from 7 to 85 years with a mean of 53 years. One hundred and sixty-five patients were inpatients, and 53 were outpatients. There were 54 tumors in the mediastinum and 164 tumors in the lung parenchyma. Forty-eight mediastinal tumors were located in the anterior mediastinum (figure 1) and eight in the posterior mediastinum. Among the 164pulmonary tumors, 122 tumors were located at subpleural area (figure 2) whereas 42 tumors were located within the lungs (figure 3). The size of tumor varied from 3 to 10 em in diameter with a mean of 5.2 em. One hundred and thirty-two patients underwent only one Tru-Cut biopsy, 66
METHODS OF HISTOLOGIC CONFIRMATION IN 218 THORACIC TUMORS SUSPECTED OF HAVING MALIGNANCY
Methods of Confirmation Transthoracic biopsy only (n = 123) Transthoracic biopsy + bronchoscopic biopsy (n = 42) Transthoracic biopsy + bronchoscopic biopsy + surgery (n = 3) Transthoracic biopsy + surgery (n = 36) Transthoracic biopsy + lymph node biopsy (n = 3) Surgery only (n = 7) Lymph node biopsy only (n = 4)
Lung Tumor (n = 164)
Mediastinal Tumor (n = 54)
Subpleural (n = 122)
Within the Lungs (n = 42)
23
79
21
5
24
13
0
2
18
14
'2
0 2
4 2
4
765
ULTRASOUND-GUIDED CORE BIOPSY OF THORACIC TUMORS
Fig. 2. (a) Chest radiograph of a 65year-old man showing a tumor at right middle lung field; (b) Chest ultrasound showing a hypoechoic tumor (arrowheads). The histologic diagnosis of ultrasound-guided core biopsy is squamous cell carcinoma. The patient received thoracotomy, and the path910gy showed the same results.
patients underwent two biopsies, and 20 patients had three. A total of 324 biopsy procedures was conducted. Specimens adequate for histologic diagnosis were obtained in 318biopsies (98.1 070); in a further 6 biopsies (1.9%), necrotic tissues were obtained that were not adequate to make a histologic diagnosis. There were 46 patients who had histologic diagnoses confirmed by surgery, 45 patients by bronchoscopic biopsy, and seven patients by lymph node biopsy. Table 1 shows the additional diagnostic procedures for histologic confirmation in different groups of these 218 patients. The yield of ultrasound-guided transthoracic core biopsy for diagnosis of thoracic malignancy in these 218 patients is shown in table 2. There were 54 patients with mediastinal tumors who underwent Tru-Cut biopsy. The final diagnosis of these 54 mediastinal tumors included seven patients with small cell carcinoma, seven with metastatic carcinoma, six with
lymphoma, four with Hodgkin's disease, fivewith thymic carcinoma, four with unclassified carcinoma, three with thymic carcinoid tumor, one with germ cell tumor, one with embryonal cell carcinoma, 13 with thymoma, one with gan-
glioneuroma, one with neurofibroma, and one with tuberculous lymphadenitis. For the six mediastinal tumors, although grossly adequate specimens were obtained, definite histologic diagnosis still could not be made based simply on the core biopsy specimens. Final diagnosis for these six was confirmed by surgery in four patients and biopsy from metastatic lymph nodes in two patients. There were two patients with thymoma, one with lymphoma, one with Hodgkin's disease, one with thymic carcinoma, and one with unclassified carcinoma. In 48 patients with mediastinal tumors who had definite histologic diagnoses made by Tru-Cut core biopsy, 33 biopsies showed true-positive results for malignancy, 14 showed true negative, one showed false negative, and none showed false positive. The false-negative patient was a patient with unclassified carcinoma. The transthoracic biopsy of this patient revealed chronic inflammation with fibrosis. This patient was diagnosed to have unclassified carcinoma by supraclavicular lymph node biopsy. If the six patients with adequate specimens but without definite histologic diagnoses were to be excluded, the sensitivity of transthoracic core biopsy in the diagnosis of mediastinal malignancy was 97.1 %, and accuracy was 97.9070. One hundred and sixty-four lung tumors underwent ultrasound-guided transthoracic biopsy. One hundred and twenty-six tumors were malignant, and 34 were benign. The overall sensitivity of diagnosing malignancy by ultrasoundguided transthoracic biopsy was 96.2% with an accuracy of 97.0%. The final diagnoses of these 126 patients with malignant lung tumors were 48 with adenocarcinoma, 10with bronchoalveolar carcinoma, 32 with squamous cell carcinoma, six with large cell carcinoma, six with
TABLE 2 RESULTS OF ULTRASOUND-GUIDED CORE BIOPSY FOR THORACIC TUMORS SUSPECTED OF MALIGNANCY Mediastinal Tumor· (n = 48) True positive True negative False negative False positive Sensitivity (%) Specificity (%) Accuracy (%)
33 14 1
Lung Tumor (n = 164) Subpleural (n = 122)
Within the Lungs (n = 42)
90 29 3
35 5 2
o
o
o
97.1
96.8
94.6
100 97.9
100 97.5
100 95.2
• Six patients with indeterminant histologic diagnoses of biopsy specimens were excluded: two thymomas, one lymphoma, one Hodgkin's disease, one thymic carcinoma, and one unclassified carcinoma.
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YANG, CHANG, YU, LEE, WU, KUO, AND WH
one had harmatoma, and one had adenoma. Four patients (1.8%) developed complications after the Tru-Cut biopsy. Three developed minimal pneumothorax that did not require chest tube insertion, and another had mild hemoptysis. Discussion
Fig. 3. (a) Chest radiograph of an 82yr-old man showing an obstructive pneumonitis in the right upper lobe. (b) Chest ultrasound showing a hyperechoic tumor (arrowheads) in the consolidated lung with involvement of pulmonary artery. Histologic examination of the specimen obtained from ultrasound-guided percutaneous core biopsy shows squamous cell carcinoma. The fluid-filled bronchogram is seen within the consolidated lung. L = consolidated lung.
small cell carcinoma, 10 with unclassified carcinoma, and 14 with metastatic carcinoma. There were five patients with false-negative results. Histologic examination of the biopsy specimens showed chronic inflammation, fibrosis, and necrosis. These five patients were proved by surgery or lymph node biopsy to have adenocarcinoma in three, unclassified carcinoma in one, and small cell carcinoma in another. In 122 subpleural tumors, 90 transthoracic core biopsies showed true-positive results for malignancy, 29 showed true negative, three showed false negative, and there were no false positive. The sensitivity for diagnosis of malignant subpleural tumors was 96.8070, and accuracy was 97.5070. In 42 patients with tumors located within the lungs, 35 Tru-Cut biopsies showed truepositive results for malignancy, five
showed true negative, two showed false negative, and none showed false positive. The sensitivity for diagnosis of malignancy for tumor located within the lungs was 94.6%, and accuracy was 95.2070. There was no significant difference in the diagnostic yields of ultrasound-guided core biopsy for the subpleural tumors and tumors located within the lungs (p > 0.10, by test). There were 34 patients with lung tumors who did not have malignancy. Eight patients were proved to have tuberculous granuloma, three had granuloma without definite pathogens identified, six had fungal infections (four aspergillosis and two cryptococcal infection), 11 had chronic inflammation with fibrosis probably from end-stage pneumonia, three had fibroma, one had progressive massive fibrosis caused by pneumoconiosis,
'1:
Since the first report of successful ultrasound-guided percutaneous transthoracic needle biopsy of peripheral pulmonary masses by Chandrasekhar and coworkers (12) in 1976,this technique has gradually been accepted as an alternative approach for diagnosis of thoracic tumors (3-8). However, the application of ultrasound in guiding a percutaneous biopsy for thoracic lesions is limited; most of the percutaneous transthoracic needle biopsy is still guided by CT scan or fluoroscopy (7). The improvement of current real-time ultrasound equipment, particularly electronically-focused, phasedarray transducer designs, has made ultrasound competitive with the CT scan in some situations (13). Ultrasound is not only useful in guiding a percutaneous biopsy of peripheral pulmonary nodules and mediastinal tumors (3-5), but also helpful in guiding a percutaneous aspiration biopsy for etiologic diagnosis of a consolidation or lung abscess (14). Most of the previous studies of ultrasoundguided percutaneous transthoracic needle biopsy have been restricted to lesions adjacent to the chest wall. If one uses the "ultrasound window" created by the consolidated lung, a lung tumor observed as obstructive pneumonitis can also possibly be approached by ultrasound-guided biopsy (figure 2). This study demonstrated that ultrasound can be useful in guiding a percutaneous transthoracic core biopsy with a large bore Tru-Cut needle. The diagnostic sensitivity in malignant thoracic tumors was up to 96.2070 and accuracy 97.0070. The procedure is also very safe. Only 1.8% of the patients developed mild complications of pneumothorax and hemoptysis. Most of the percutaneous transthoracic needle biopsies reported in the literature (1-3, 5, 8, 11) are carried out with a fine needle (21 gauge or smaller). Percutaneous biopsy with a cutting needle has a higher complication rate and is generally not recommended for biopsy of mediastinal tumors or tumors deeply seated in the lung parenchyma (15). Severallarge series studies have claimed that percutaneous transthoracic fine-needle aspiration is safe and can achieve a high
767
ULTRASOUND-GUIDED CORE BIOPSY OF THORACIC TUMORS
diagnostic yield (80070 to 90% sensitivity), especially for the diagnosis of lung cancer (1,2). Although small tissue fragments may sometimes be obtained for histologic examination by fine-needle aspiration (16), such tiny specimens are generally suitable only for cytologic examination. A detailed histologic diagnosis to define the tumor origin and the differentiation grade of malignancy is not possible. A fine-needle aspiration can only achieve a very low sensitivity for diagnosis of mediastinal tumor, especially for lymphoma and thymoma (11), and this may subsequently affect the management of the patient. Present results show that a specimen obtained by core biopsy with a Tru-Cut needle is adequate to make a definite histologic diagnosis. Accurate histologic diagnosis can be obtained in 88.9% of mediastinal tumors, a rate far superior to that achieved by fine-needle aspiration biopsy. Ultrasound-guided transthoracic needle aspiration biopsy has several advantages that other image guiding systems cannot offer. It is relativelyfast, inexpensive, portable, produces no ionizing radiation, and can provide guidance in multiple axial, longitudinal, and oblique planes of section. The ultrasound can depict the vascular structure without need for contrast media. Most important, it provides continuous real-time needle localization. The biopsy route can be preselected to avoid penetrating the aerated lung, bronchi, and great vessels, thus minimizing the complications. Because the diagnostic yield of ultrasound-guided transthoracic biopsy is high, and the procedure is safe, this diagnostic procedure can also be performed for outpatients. It has become the first line of diagnostic approach in this Institute for patients with thoracic tumors. This technique is also particularly helpful for mediastinal tumor and peripheral lung tumor, which
cannot be reached by other conventional diagnostic approaches such as bronchoscopic biopsy. There are three types of ultrasound equipment available for guiding a percutaneous biopsy. These include (l) sonographic transducers with built-in needle slots within the central or side portion of the transducer that directs the needle into a predetermined angle within the plane of view of the transducers (3, 5, 6); (2) an attachable stretcher guide can be fitted to existing transducers, thus directing the needle to various depths from the transducer, depending on the angle of the guide that is set by the operator (9, 13); (3) a "freehand" approach, in which the needle is inserted through the skin directly into the plane of view of the transducer without a guide (10, 13). For guiding a percutaneous transthoracic needle biopsy, the transducer with built-in needle slots and adjustable needleguiding channel was preferred here. This system can precisely guide the needle to the target. A small lesion and a deeply seated lung tumor can possibly be reached by this technique without difficulty (17). The attachable stretcher guides and the freehand approach are only suitable for superficial and large thoracic masses. In a small tumor with only a small "ultrasound window" available, the needle may have to go through the normal aerated lung while conducting the biopsy. The needle tips are not possibly seen by ultrasound. The rate of complication may therefore increase. In conclusion, ultrasound-guided core biopsy is a safe and sensitive diagnostic approach for thoracic tumors. Accurate histologic diagnosis can be obtained in most patients. The technique is particularly useful for histologic diagnosis of mediastinal tumors and peripheral pulmonary malignancy.
References 1. Westcott JL. Percutaneous transthoracic needle biopsy. Radiology 1988; 169:593-601.
2. Weisbrod GL. Transthoracic percutaneous lung biopsy. Rad Clin North Am 1990; 28:647-55. 3. YangPC, Luh KT, Sheu JC, Kuo SH, YangSP. Peripheral pulmonary lesions: ultrasonography and ultrasonically guided aspiration biopsy. Radiology 1985; 155:451-6. 4. Yu CJ, Yang PC, Chang DB, et al. Evaluation of ultrasound-guided biopsies of mediastinal masses. Chest 1991; 100:399-405. 5. Wernecke K, Vassallo P, Peters PE, von Bassewitz DB. Mediastinal tumors: biopsy under US guidance. Radiology 1989; 172:473-6. 6. YangPC, Luh KT, Wu HD, et al. Lung tumors associated with obstructive pneumonitis: US studies. Radiology 1990; 174:717-20. 7. Charboneau JW, Reading CC, Welch TJ. CT and sonographically guided needle biopsy: current techniques and new innovations. AJR 1990; 154:1-10.
8. Ikezoe J, Morimoto S, Arisawa J, Takashima S, Kozuka T, Nakahara K. Percutaneous biopsy of thoracic lesions: value of sonography for needle guidance. AJR 1990; 154:1181-5. 9. Yang PC, Lee LN, Luh KT, Kuo SH, Yang SP. Ultrasonography of Pancoast tumor. Chest 1988; 94:124-8. 10. Jennings PE, Donald 11, Coral A, Rode J,
Lees WR. Ultrasound-guided core biopsy. Lancet 1989; 1:1369-71. 11. Herman SJ, Holub RV, Weisbrod GL, Cham-
berlain DW. Anterior mediastinal masses: utility of transthoracic needle biopsy. Radiology 1991; 180:167-70. 12. Chandrasekhar AJ, Reynes CJ, Churchill RJ.
Ultrasonically guided percutaneous biopsy of peripheral pulmonary masses. Chest 1976; 70:627-30. 13. Matalon TAS, Silver B. US guidance of interventional procedures. Radiology 1990; 174:43-7. 14. Yang PC, Luh KT, Lee YC, et al. Lung abscesses: US examination and US-guided transthoracic aspiration. Radiology 1991; 180:171-5. 15. Sokolowski JW Jr, Burgher LW,Jones FL Jr, Patterson JR, SeleckyPA. Guidelines for percutaneous transthoracic needle biopsy. Am Rev Respir Dis 1989; 140:255-6. 16. Weisbrod GL, Herman SJ, Liang-Che T. Preliminary experience with a dual cutting edge needle in thoracic percutaneous fine-needle aspiration biopsy. Radiology 1987; 163:75-8. 17. Yuan A, Yang PC, Chang DB, et al. Ultrasound-guided aspiration biopsy of small peripheral pulmonary nodules. Chest 1992; 101:926-30.
PAN-CHYR YANG, DUN-BING CHANG, CHONG-JEN YU, YUNG-CHIE LEE, HUEY·DONG WU, SOW-HSONG KUO, and KWEN-TAY LUH
Introduction
Percutaneous transthoracic needle biopsy under fluoroscopic or computed tomographic (CT) guidance is a wellestablished procedure to obtain tissue for histologic diagnosis of a thoracic tumor (1, 2). Recently, ultrasound has also been found useful for guiding a percutaneous needle to biopsy for peripheral pulmonary nodules (3) and for mediastinal tumors (4, 5). The thoracic tumor suitable for ultrasound-guided needle biopsy is not restricted only to those lesions that abut on the pleura. An air-containing lung is a poor transmitting medium for ultrasound. However, an atelectatic or nonaerated lung becomes a good "ultrasound window" that may allow underlying tumors to be visualized (6). Moreover, improved ultrasound resolution and real-time image monitoring of biopsy procedures also allows an approach to thoracic tumors with a greater margin of safety and accuracy (7). Even a 14-18-gauge cutting needle can be used in ultrasound-guided core biopsy of thoracic tumor with acceptable risk of complications (6, 8, 9). Most of the percutaneous guided needle biopsies are done by fine needle (21 gauge or smaller). The materials aspirated are generally suitable only for cytologic examination. Although a welltrained cytopathologist is able to make a diagnosis from these small specimens with high sensitivity and accuracy, the overall sensitivity is around 80% (1, 2, 10).Given that fine-needle aspiration biopsy is a safe procedure with acceptable accuracy for thoracic tumor diagnosis, the very small specimen obtained for cytologic examination often fails to provide precise information about cell type and tumor origin. False-negative results are frequently encountered, and a largebore needle biopsy or thoracotomy is always necessary to confirm the diagnosis. For those patients with mediastinal tumors, a definite histologic diagnosis is essential for subsequent patient management. Fine-needle aspiration biopsy is not always adequate for a histologic di-
SUMMARY 'TWo hundred and eighteen patients, with thoracic tumors larger than 3 cm in size, underwent ultrasound-guided percutaneous transthoracic core biopsy with a large-bore Tru-Cut needle. Fifty-five tumors were In the mediastinum, and 122 tumors were located at subpleural area, and 42 tumors were within the lungs. In 122 subpleural tumors, the sensitivity of ultrasound-guided core biopsy for the diagnosis of malignancy was 96.8%, and accuracy was 97.5%. Sensitivity for the diagnosis of malignant tumors located within the lungs was 94.6%, and accuracy was 95.2%. In 54 patients with mediastinal tumors, definite histologic diagnosis could be obtained in 48 patients (88.9%). The sensitivity of ultrasound-guided biopsy for the diagnosis of malignancy In these 48 mediastinal tumors was 97.1%, with an accuracy of 97.9%. Three patients had complications with minimal pneumothorax and one with mild hemoptysis. Weconclude that percutaneous transthoracic core biopsy with Tru-Cut needle under ultrasound guidance is a safe and sensitive way to obtain specimens for accurate histologic diagnosis of thoracic tumors. The diagnostic yield Is high, and the technique, relatively simple, can also be used for outpatients. AM REV RESPIR DIS 1992; 146:763-767
agnosis of a mediastinal tumor. Low sensitivity of 20 to 71% could only be obtained for lymphoma, Hodgkin's diseases and thymoma by fine needle aspiration biopsy (11). This study assessesthe safety, diagnostic sensitivity, and accuracy of ultrasound-guided core biopsy for 218tumors located in the mediastinum and lung parenchyma, using a large-bore Tru-Cut needle. Methods From January 1985 to December 1990, 302 patients with radiographic evidence of thoracic tumors, suspected of malignancy, were seen at National Taiwan University Hospital. Patients wereselectedfor chest ultrasound examination and ultrasound-guided percutaneous transthoracic biopsy with a TruCut needle according to the following criteria: (1)mediastinal tumors, anterior or posterior in location, which had contact with the chest wall; (2) peripheral pulmonary tumors that abutted on the pleura, or pulmonary tumors with an accessibleultrasound window; (3) for safety, only tumors larger than 3 em in diameter are biopsied by Tru-Cut needle; (4) the patient has platelet count in excess of 100,000/1JL and normal prothrombin time; and (5) patients are cooperative. Eighty-four patients with thoracic tumors wereexcluded: six patients with tumors in the medmediastinum, 26 patients with lung tumors without accessible ultrasound window,31patients with lung tumors smaller than 3 em in diameter, three persons with coagulation ab-
normality, 13 patients who refused transthoracic biopsy, and five uncooperative patients. Thus, a total of 218 patients actually underwent ultrasound-guided biopsy for their thoracic tumors. All patients wereexamined with real-time, linear, convex, and sector ultrasonic units with 3.5 MHz, 5.0 MHz, and 7.5 MHz transducer (Aloka SSD 630; Aloka, Japan; Toshiba 100A; Tokyo, Japan). The sector ultrasound units werealso equipped with Doppler ultrasound, which could be used to detect great vessels and blood flow. The patients were scanned in supine or prone position by means of an intercostal approach. The sonographic images were recorded on polaroid film (Polaroid, Cambridge, MA) for analysis of tumor location and the relationship of the tumor to surrounding vessels and vital structures. After assessment of the tumor location and demarcation of tumor margins, an informed consent was obtained, and the tumor was subjected to percutaneous transthoracic cutting biopsy with a large bore (16 gauge)
(Received in original form October 14, 1991 and in revised form February 28, 1992) 1 From the Departments of Internal Medicine, Surgery, and Clinical Pathology, National Taiwan University Hospital, and Institute of Biomedical Sciences, Academica Sinica, Taipei, Taiwan, Republic of China. 2 Correspondence and requests for reprints should be addressed to Pan-Chyr Yang, M.D., Ph.D., Department of Internal Medicine, National Taiwan University Hospital, No.1, Chang-Te Street, Taipei, Taiwan 100, Republic of China.
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Tru-Cut needle (Top surgical, Tokyo, Japan) through a sterile puncture transducer (Aloka UST-507 BP). The puncture transducer provided a preset puncture area that could be displayed on the monitor screen. The biopsy route could be adjusted at a fixed angle from - 5° to 25°. The biopsy route was preselected to avoid penetrating great vessels. The ultrasound guided biopsy technique has also been detailed in previous studies (3, 4, 6, 9). The patient was asked to hold his/her breath, and the biopsy procedure was carried out within 10to 15s. The Tru-Cut biopsy specimen was sent for pathologic examination. A specimen obtained by Tru-Cut biopsy was observed grossly, and arbitrarily designated as inadequate if the specimen wassmaller than 2 x 4 mm in size. A Tru-Cut biopsy was repeated immediately before the histologic examination was performed. If a lymphoma or Hodgkin's disease was suspected, multiple biopsies were conducted to obtain at least two adequate specimens for both routine histological examination as well as immunohistologic studies to confirm the cell type. A chest radiograph was performed routinely 24 h after the Tru-Cut biopsy to assess any possible complication. A false-negative result was considered to have occurred if the tumor was confirmed at surgery, by biopsy from other metastatic sites, or if there was evidence of disease progress at follow-up examination. A true negative result was considered if the disease turns out to be benign at follow-up by chest radiographs, CT scan, and fiberoptic bronchoscopy with or without biopsy. A sensitivity was percent of patients with malignant tumor correctly diagnosed as malignant by ultrasoundguided biopsy. A specificity was percent of patients with benign tumor correctly diagnosed as benign. An accuracy was percent of patients with thoracic tumor correctly diagnosed as malignant or benign. A chi-square test was used to compare the sensitivity of ultrasound-guided biopsy between different groups of thoracic tumors.
Fig. 1. (a) Chest radiograph of a 56-yrold man, showing an anterior mediastinal tumor (arrowhead). (b) Chest ultrasound revealing a hypoechoic tumor with smooth margin just anterior to the ascending aorta. The histologic diagnosis from the ultrasound-guided core biopsy is thymoma. A = aorta.
Results
TABLE 1
A total of 218 patients were included in this study. There were 146 men and 72 women, whose ages ranged from 7 to 85 years with a mean of 53 years. One hundred and sixty-five patients were inpatients, and 53 were outpatients. There were 54 tumors in the mediastinum and 164 tumors in the lung parenchyma. Forty-eight mediastinal tumors were located in the anterior mediastinum (figure 1) and eight in the posterior mediastinum. Among the 164pulmonary tumors, 122 tumors were located at subpleural area (figure 2) whereas 42 tumors were located within the lungs (figure 3). The size of tumor varied from 3 to 10 em in diameter with a mean of 5.2 em. One hundred and thirty-two patients underwent only one Tru-Cut biopsy, 66
METHODS OF HISTOLOGIC CONFIRMATION IN 218 THORACIC TUMORS SUSPECTED OF HAVING MALIGNANCY
Methods of Confirmation Transthoracic biopsy only (n = 123) Transthoracic biopsy + bronchoscopic biopsy (n = 42) Transthoracic biopsy + bronchoscopic biopsy + surgery (n = 3) Transthoracic biopsy + surgery (n = 36) Transthoracic biopsy + lymph node biopsy (n = 3) Surgery only (n = 7) Lymph node biopsy only (n = 4)
Lung Tumor (n = 164)
Mediastinal Tumor (n = 54)
Subpleural (n = 122)
Within the Lungs (n = 42)
23
79
21
5
24
13
0
2
18
14
'2
0 2
4 2
4
765
ULTRASOUND-GUIDED CORE BIOPSY OF THORACIC TUMORS
Fig. 2. (a) Chest radiograph of a 65year-old man showing a tumor at right middle lung field; (b) Chest ultrasound showing a hypoechoic tumor (arrowheads). The histologic diagnosis of ultrasound-guided core biopsy is squamous cell carcinoma. The patient received thoracotomy, and the path910gy showed the same results.
patients underwent two biopsies, and 20 patients had three. A total of 324 biopsy procedures was conducted. Specimens adequate for histologic diagnosis were obtained in 318biopsies (98.1 070); in a further 6 biopsies (1.9%), necrotic tissues were obtained that were not adequate to make a histologic diagnosis. There were 46 patients who had histologic diagnoses confirmed by surgery, 45 patients by bronchoscopic biopsy, and seven patients by lymph node biopsy. Table 1 shows the additional diagnostic procedures for histologic confirmation in different groups of these 218 patients. The yield of ultrasound-guided transthoracic core biopsy for diagnosis of thoracic malignancy in these 218 patients is shown in table 2. There were 54 patients with mediastinal tumors who underwent Tru-Cut biopsy. The final diagnosis of these 54 mediastinal tumors included seven patients with small cell carcinoma, seven with metastatic carcinoma, six with
lymphoma, four with Hodgkin's disease, fivewith thymic carcinoma, four with unclassified carcinoma, three with thymic carcinoid tumor, one with germ cell tumor, one with embryonal cell carcinoma, 13 with thymoma, one with gan-
glioneuroma, one with neurofibroma, and one with tuberculous lymphadenitis. For the six mediastinal tumors, although grossly adequate specimens were obtained, definite histologic diagnosis still could not be made based simply on the core biopsy specimens. Final diagnosis for these six was confirmed by surgery in four patients and biopsy from metastatic lymph nodes in two patients. There were two patients with thymoma, one with lymphoma, one with Hodgkin's disease, one with thymic carcinoma, and one with unclassified carcinoma. In 48 patients with mediastinal tumors who had definite histologic diagnoses made by Tru-Cut core biopsy, 33 biopsies showed true-positive results for malignancy, 14 showed true negative, one showed false negative, and none showed false positive. The false-negative patient was a patient with unclassified carcinoma. The transthoracic biopsy of this patient revealed chronic inflammation with fibrosis. This patient was diagnosed to have unclassified carcinoma by supraclavicular lymph node biopsy. If the six patients with adequate specimens but without definite histologic diagnoses were to be excluded, the sensitivity of transthoracic core biopsy in the diagnosis of mediastinal malignancy was 97.1 %, and accuracy was 97.9070. One hundred and sixty-four lung tumors underwent ultrasound-guided transthoracic biopsy. One hundred and twenty-six tumors were malignant, and 34 were benign. The overall sensitivity of diagnosing malignancy by ultrasoundguided transthoracic biopsy was 96.2% with an accuracy of 97.0%. The final diagnoses of these 126 patients with malignant lung tumors were 48 with adenocarcinoma, 10with bronchoalveolar carcinoma, 32 with squamous cell carcinoma, six with large cell carcinoma, six with
TABLE 2 RESULTS OF ULTRASOUND-GUIDED CORE BIOPSY FOR THORACIC TUMORS SUSPECTED OF MALIGNANCY Mediastinal Tumor· (n = 48) True positive True negative False negative False positive Sensitivity (%) Specificity (%) Accuracy (%)
33 14 1
Lung Tumor (n = 164) Subpleural (n = 122)
Within the Lungs (n = 42)
90 29 3
35 5 2
o
o
o
97.1
96.8
94.6
100 97.9
100 97.5
100 95.2
• Six patients with indeterminant histologic diagnoses of biopsy specimens were excluded: two thymomas, one lymphoma, one Hodgkin's disease, one thymic carcinoma, and one unclassified carcinoma.
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YANG, CHANG, YU, LEE, WU, KUO, AND WH
one had harmatoma, and one had adenoma. Four patients (1.8%) developed complications after the Tru-Cut biopsy. Three developed minimal pneumothorax that did not require chest tube insertion, and another had mild hemoptysis. Discussion
Fig. 3. (a) Chest radiograph of an 82yr-old man showing an obstructive pneumonitis in the right upper lobe. (b) Chest ultrasound showing a hyperechoic tumor (arrowheads) in the consolidated lung with involvement of pulmonary artery. Histologic examination of the specimen obtained from ultrasound-guided percutaneous core biopsy shows squamous cell carcinoma. The fluid-filled bronchogram is seen within the consolidated lung. L = consolidated lung.
small cell carcinoma, 10 with unclassified carcinoma, and 14 with metastatic carcinoma. There were five patients with false-negative results. Histologic examination of the biopsy specimens showed chronic inflammation, fibrosis, and necrosis. These five patients were proved by surgery or lymph node biopsy to have adenocarcinoma in three, unclassified carcinoma in one, and small cell carcinoma in another. In 122 subpleural tumors, 90 transthoracic core biopsies showed true-positive results for malignancy, 29 showed true negative, three showed false negative, and there were no false positive. The sensitivity for diagnosis of malignant subpleural tumors was 96.8070, and accuracy was 97.5070. In 42 patients with tumors located within the lungs, 35 Tru-Cut biopsies showed truepositive results for malignancy, five
showed true negative, two showed false negative, and none showed false positive. The sensitivity for diagnosis of malignancy for tumor located within the lungs was 94.6%, and accuracy was 95.2070. There was no significant difference in the diagnostic yields of ultrasound-guided core biopsy for the subpleural tumors and tumors located within the lungs (p > 0.10, by test). There were 34 patients with lung tumors who did not have malignancy. Eight patients were proved to have tuberculous granuloma, three had granuloma without definite pathogens identified, six had fungal infections (four aspergillosis and two cryptococcal infection), 11 had chronic inflammation with fibrosis probably from end-stage pneumonia, three had fibroma, one had progressive massive fibrosis caused by pneumoconiosis,
'1:
Since the first report of successful ultrasound-guided percutaneous transthoracic needle biopsy of peripheral pulmonary masses by Chandrasekhar and coworkers (12) in 1976,this technique has gradually been accepted as an alternative approach for diagnosis of thoracic tumors (3-8). However, the application of ultrasound in guiding a percutaneous biopsy for thoracic lesions is limited; most of the percutaneous transthoracic needle biopsy is still guided by CT scan or fluoroscopy (7). The improvement of current real-time ultrasound equipment, particularly electronically-focused, phasedarray transducer designs, has made ultrasound competitive with the CT scan in some situations (13). Ultrasound is not only useful in guiding a percutaneous biopsy of peripheral pulmonary nodules and mediastinal tumors (3-5), but also helpful in guiding a percutaneous aspiration biopsy for etiologic diagnosis of a consolidation or lung abscess (14). Most of the previous studies of ultrasoundguided percutaneous transthoracic needle biopsy have been restricted to lesions adjacent to the chest wall. If one uses the "ultrasound window" created by the consolidated lung, a lung tumor observed as obstructive pneumonitis can also possibly be approached by ultrasound-guided biopsy (figure 2). This study demonstrated that ultrasound can be useful in guiding a percutaneous transthoracic core biopsy with a large bore Tru-Cut needle. The diagnostic sensitivity in malignant thoracic tumors was up to 96.2070 and accuracy 97.0070. The procedure is also very safe. Only 1.8% of the patients developed mild complications of pneumothorax and hemoptysis. Most of the percutaneous transthoracic needle biopsies reported in the literature (1-3, 5, 8, 11) are carried out with a fine needle (21 gauge or smaller). Percutaneous biopsy with a cutting needle has a higher complication rate and is generally not recommended for biopsy of mediastinal tumors or tumors deeply seated in the lung parenchyma (15). Severallarge series studies have claimed that percutaneous transthoracic fine-needle aspiration is safe and can achieve a high
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ULTRASOUND-GUIDED CORE BIOPSY OF THORACIC TUMORS
diagnostic yield (80070 to 90% sensitivity), especially for the diagnosis of lung cancer (1,2). Although small tissue fragments may sometimes be obtained for histologic examination by fine-needle aspiration (16), such tiny specimens are generally suitable only for cytologic examination. A detailed histologic diagnosis to define the tumor origin and the differentiation grade of malignancy is not possible. A fine-needle aspiration can only achieve a very low sensitivity for diagnosis of mediastinal tumor, especially for lymphoma and thymoma (11), and this may subsequently affect the management of the patient. Present results show that a specimen obtained by core biopsy with a Tru-Cut needle is adequate to make a definite histologic diagnosis. Accurate histologic diagnosis can be obtained in 88.9% of mediastinal tumors, a rate far superior to that achieved by fine-needle aspiration biopsy. Ultrasound-guided transthoracic needle aspiration biopsy has several advantages that other image guiding systems cannot offer. It is relativelyfast, inexpensive, portable, produces no ionizing radiation, and can provide guidance in multiple axial, longitudinal, and oblique planes of section. The ultrasound can depict the vascular structure without need for contrast media. Most important, it provides continuous real-time needle localization. The biopsy route can be preselected to avoid penetrating the aerated lung, bronchi, and great vessels, thus minimizing the complications. Because the diagnostic yield of ultrasound-guided transthoracic biopsy is high, and the procedure is safe, this diagnostic procedure can also be performed for outpatients. It has become the first line of diagnostic approach in this Institute for patients with thoracic tumors. This technique is also particularly helpful for mediastinal tumor and peripheral lung tumor, which
cannot be reached by other conventional diagnostic approaches such as bronchoscopic biopsy. There are three types of ultrasound equipment available for guiding a percutaneous biopsy. These include (l) sonographic transducers with built-in needle slots within the central or side portion of the transducer that directs the needle into a predetermined angle within the plane of view of the transducers (3, 5, 6); (2) an attachable stretcher guide can be fitted to existing transducers, thus directing the needle to various depths from the transducer, depending on the angle of the guide that is set by the operator (9, 13); (3) a "freehand" approach, in which the needle is inserted through the skin directly into the plane of view of the transducer without a guide (10, 13). For guiding a percutaneous transthoracic needle biopsy, the transducer with built-in needle slots and adjustable needleguiding channel was preferred here. This system can precisely guide the needle to the target. A small lesion and a deeply seated lung tumor can possibly be reached by this technique without difficulty (17). The attachable stretcher guides and the freehand approach are only suitable for superficial and large thoracic masses. In a small tumor with only a small "ultrasound window" available, the needle may have to go through the normal aerated lung while conducting the biopsy. The needle tips are not possibly seen by ultrasound. The rate of complication may therefore increase. In conclusion, ultrasound-guided core biopsy is a safe and sensitive diagnostic approach for thoracic tumors. Accurate histologic diagnosis can be obtained in most patients. The technique is particularly useful for histologic diagnosis of mediastinal tumors and peripheral pulmonary malignancy.
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2. Weisbrod GL. Transthoracic percutaneous lung biopsy. Rad Clin North Am 1990; 28:647-55. 3. YangPC, Luh KT, Sheu JC, Kuo SH, YangSP. Peripheral pulmonary lesions: ultrasonography and ultrasonically guided aspiration biopsy. Radiology 1985; 155:451-6. 4. Yu CJ, Yang PC, Chang DB, et al. Evaluation of ultrasound-guided biopsies of mediastinal masses. Chest 1991; 100:399-405. 5. Wernecke K, Vassallo P, Peters PE, von Bassewitz DB. Mediastinal tumors: biopsy under US guidance. Radiology 1989; 172:473-6. 6. YangPC, Luh KT, Wu HD, et al. Lung tumors associated with obstructive pneumonitis: US studies. Radiology 1990; 174:717-20. 7. Charboneau JW, Reading CC, Welch TJ. CT and sonographically guided needle biopsy: current techniques and new innovations. AJR 1990; 154:1-10.
8. Ikezoe J, Morimoto S, Arisawa J, Takashima S, Kozuka T, Nakahara K. Percutaneous biopsy of thoracic lesions: value of sonography for needle guidance. AJR 1990; 154:1181-5. 9. Yang PC, Lee LN, Luh KT, Kuo SH, Yang SP. Ultrasonography of Pancoast tumor. Chest 1988; 94:124-8. 10. Jennings PE, Donald 11, Coral A, Rode J,
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Ultrasonically guided percutaneous biopsy of peripheral pulmonary masses. Chest 1976; 70:627-30. 13. Matalon TAS, Silver B. US guidance of interventional procedures. Radiology 1990; 174:43-7. 14. Yang PC, Luh KT, Lee YC, et al. Lung abscesses: US examination and US-guided transthoracic aspiration. Radiology 1991; 180:171-5. 15. Sokolowski JW Jr, Burgher LW,Jones FL Jr, Patterson JR, SeleckyPA. Guidelines for percutaneous transthoracic needle biopsy. Am Rev Respir Dis 1989; 140:255-6. 16. Weisbrod GL, Herman SJ, Liang-Che T. Preliminary experience with a dual cutting edge needle in thoracic percutaneous fine-needle aspiration biopsy. Radiology 1987; 163:75-8. 17. Yuan A, Yang PC, Chang DB, et al. Ultrasound-guided aspiration biopsy of small peripheral pulmonary nodules. Chest 1992; 101:926-30.
