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TRANSTHORACIC HILAR AND MEDIASTINAL BIOPSY
INTERVENTIONAL CHEST RADIOLOGY
0033-8389100 $15.00
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TRANSTHORACIC HILAR AND MEDIASTINAL BIOPSY Zenon Protopapas, MD, and Jack L. Westcott, MD
Transthoracic needle biopsy (TNB) for the diagnosis of pneumonia and lung carcinoma was first described over a century ago, long before radiographic techniques were avail30 Modern fluoroscopy, the use of 18to 22-gauge biopsy needles, and advances in cytopathology revolutionized TNB." The use of fine needles and improved radiologic guidance contributed to the low morbidity and negligible mortality of TNB.69,74 These advances have resulted in a high accuracy of TNB (sensitivity of 90% to 98%) in diagnosing cancer.17, 23. 24. 61. 72. 73 The introduction of CT as guidance for TNB has made the routine retrieval of material from small pulmonary lesions and most hilar and mediastinal masses possible.2,6, 14, 15, 43, 58, 64* 65, 75 Surgical techniques of mediastinal biopsy (mediastinoscopy, mediastinotomy, thoracotomy, or thoracoscopy) have a high diagnostic accuracy but are more invasive and are associated with the morbidity of a surgical procedure. TNB can be performed successfully as an outpatient procedure under local anesthesia, and is particularly useful in the diagnosis of carcinoma where it may obviate the need for a surgical diagnostic procedure. PREBIOPSY PROCEDURES
Prebiopsy laboratory studies that are routinely obtained include prothrombin time and
partial thromboplastin time. In addition, patients are questioned for a history of bleeding diathesis and the use of any antiplateletcontaining medications, such as aspirin. IMAGE GUIDANCE AND TECHNIQUE OF HILAR AND MEDIASTINAL BIOPSY
The size and location of the mass and its relationship to adjacent vascular structures determine the optimal biopsy approach to a hilar or mediastinal mass. A prebiopsy CT scan, preferably contrast-enhanced, is needed to determine the optimal approach to the lesion. CT is the preferred method of guiding mediastinal and hilar biopsies@because most lesions are either poorly seen fluoroscopically or are adjacent to major cardiovascular structures.2,7, 15, 64, 74 As opposed to fluoroscopy, the exact position of the needle tip can be documented with CT, although the actual needle pass is blind. The recent introduction of continuous CT imaging (also referred to as CT j7uoroscopy) permits real-time monitoring during needle placemenP3 and provides significant time savings. Sonographic guidance for mediastinal biopsies has been described by several aut h o r ~ .71,~ 77 ~ ,This technique allows for realtime cross-sectional monitoring during the biopsy. Sonography requires an adequate sonographic window, however, and it has been
From the Department of Radiology, Hospital of Saint Raphael, New Haven, Connecticut
RADIOLOGIC CLINICS OF NORTH AMERICA VOLUME 38 * NUMBER 2 * MARCH 2000
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used mainly for biopsy of mediastinal masses that extend to the chest wall.78Using the prebiopsy CT scan, Rubens et a147defined an adequate sonographic window as 1 cm in diameter space along the chest wall that allowed visualization of the mass without intervening bone cartilage or bone. This allowed for the simultaneous placement of the transducer and needle and allowed real-time imaging during the biopsy. Using this criterion they were able to identify 27 patients as possible candidates for sonographic-guided mediastinal biopsy and were able to perform the biopsy on 25 of these patients (diagnostic biopsies in 24 patients). These authors concluded that this triage criterion is useful in identifying possible candidates for ultrasound-guided mediastinal bi0psy.4~ An anterior parasternal approach is preferred for most anterior mediastinal masses, whereas a posterior paravertebral approach is used for posterior mediastinal masses. The optimal approach for anterior and middle mediastinal masses superior to the heart reflects the anatomic differences between the 74 Right-sided right and left side of the masses located anterior to the superior vena cava can undergo biopsy using an anterior approach, whereas right paratracheal and retrotracheal masses usually undergo biopsy by a right posterior paravertebral approach (Fig. 1).Despite the greater depth of a juxtatracheal lesion from a posterior approach, this approach avoids puncture of the superior vena cava. We have on occasion used an anterior approach (traversing the superior vena cava) for biopsy of paratracheal and pretracheal lymphadenopathy without complication^.^^, 73 Midline (substernal) masses can undergo biopsy from a transternal approach if they are not easily accessible parasternally (Fig. 2). Aortopulmonary lymph nodes are accessed using a left anterior parasternal approach (Fig. 3). TNB of subcarinal masses is usually performed using a right posterior paravertebra1 approach (Fig. 4). Subcarinal biopsy is occasionally performed using a left parasternal approach by entering the mediastinum via the connective tissue space between the descending aorta and spine. Hilar masses may undergo biopsy using an anterior, posterior, or lateral approach depending on the relationship of the mass to the hilar vessels (Fig. 5). Whenever possible, a direct mediastinal approach is preferable to a transpulmonary approach, because the risk of pneumothorax
Figure 1. A 75-year-old patient with right upper lobe opacity and right paratracheal lymphadenopathy. Posterior paravertebral approach was used to biopsy enlarged right paratracheal lymph nodes. A benign transthoracic needle biopsy diagnosis was confirmed with mediastinoscopy and a bronchoscopy. Follow-up CT scan revealed resolution of the adenopathy and right upper lobe density. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
when avoiding pleural puncture is eliminated. Changing the patient’s position is frequently useful. For example, when anterior mediastinal masses do not extend to the chest wall with the patient supine, placing the patient in the lateral decubitus or oblique position may move the mass sufficiently so that it contacts the parasternal chest wall, thereby allowing a direct mediastinal approach.6 The injection of normal saline solution into the paravertebral or substernal extrapleural space is frequently useful to create or expand an extrapleural window for a direct mediastinal approach (Fig. 6).33 A pleural space approach to mediastinal TNB has also been described. With this technique, the pleural space leading to the lesion is widened by an existing effusion or expanded by creation of an iatrogenic pneumo-
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Figure 2. A 47-year-old patient with histoty of thyroid carcinoma and anterior mediastinal lymphadenopathy (arrows). Biopsy of the lymph nodes was performed by transternal approach and revealed metastatic thyroid carcinoma. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
Figure 3. A 65-year-old patient with left upper lobe mass. Paraaortic lymph node transthoracic needle biopsy (TNB) was performed by an anterior parasternal approach. Both TNB of the lung mass and paraaortic adenopathy showed squamous cell carcinoma. Both lesions could be biopsied during the same procedure because both lesions were on the same side. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
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Figure 4. A 72-year-old patient with history of breast carcinoma and subcarinal lymphadenopathy. Transthoracic needle biopsy (TNB) was performed using a right posterior paravertebral approach. TNB revealed metastatic breast carcinoma. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
thorax to avoid puncture of the visceral pleura.6 Following positional maneuvers, a pleural effusion ipsilateral to the mediastinal mass may be interposed between the skin entry site and lesion, providing a pleural window that avoids traversing lung parenchyma.6 Bressler and Kirkham6 described a suprasternal approach for large anterior and right
paratracheal masses under CT guidance. The patient is imaged in a semicoronal position allowing for direct visualization of the needle path. More recently, Belfiore et a14 described a suprasternal approach for CT-guided biopsy of the middle mediastinum. In this study, patients underwent biopsy in the supine position with the neck hyperextended. Using a triangulation method, the anteropos-
Figure 5. A, Chest radiograph of an asymptomatic 58-year-old woman with history of breast carcinoma shows a questionable left hilar mass, confirmed on CT. B, Scan from CT-guided needle biopsy by means of a left lateral approach with the patient on her right side reveals metastatic breast carcinoma. (From Westcott JL: Needle biopsy of chest lesions. In Taveras JM, Ferrucci JT (eds): Radiology. Philadelphia,JB Lippincott, 1992, pp 1-1 4; with permission.)
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Figure 6. Subcarinal biopsy using artificial widening of the right posterior mediastinum. A, Injection of 10 cc of normal saline caused displacement of the pleura (arrows). Widening of the paravertebral space enabled an extrapulmonary approach to the subcarinal lymph nodes (arrowheads). Curved arrow, left main stem bronchus. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biospy. J Thorac Imaging 12:250-258, 1997; with permission.)
terior and mediolateral inclination of the needle was estimated, and the needle advanced under CT guidance. With this suprasternal approach, Belfiore et a14 were able to obtain adequate biopsy material in 25 (83%) of 30 patients without any major complications. Four patients developed a transient episode of hypotension requiring no pharmacologic treatment. NEEDLE CHARACTERISTICS
Fine aspirating needles (19-gauge or smaller) reliably provide samples for cytollogic and cell block examination, and occasionally provide tissue for histologic examination. Small-gauge cutting needles are designed to provide material for both histologic and cytologic examination. Several investigators have described the use of larger cutting needles for mediastinal TNB in selected patients.25,32, 34, 49, 51, 71 These larger cutting needles provide tissue for histology that may be helpful in the diagnosis of noncarcinomatous neoplasms and nonneoplastic conditions. High diagnostic accuracy for aspiration biopsy of the mediastinum for metastatic carci-
noma has been consistently reported; sensitivity for cancer ranges between 84% and and is comparable to needle biopsy results for pulmonary lesions. The diagnostic accuracy of aspiration biopsy with routine cytology for lymphoma, thymoma, germ cell tumors, and neurogenic tumors, however, is considerably lower.2, Several investigators have reported improved accuracy for core biopsies. Moulton and Moore,34in a study comparing aspiration with core biopsy, reported an increase in sensitivity (68% versus for the diagnosis of lymphoma. Sawhney and c o l l e a g ~ e s using , ~ ~ a 14-gauge core-biopsy needle, were able to obtain adequate tissue for histopathologic diagnosis in all 25 of their patients with mediastinal masses. Several investigators now recommend the use of automated cutting needles for the diagnosis of mediastinal masses. In our practice, we now use 18- or 20-gauge core-biopsy needles but do so selectively and under the following circumstances: (1) in patients in whom metastatic carcinoma is not the most likely diagnosis (lymphoma or other primary neoplasm); and (2) when the initial aspirate is nondiagnostic or suggests either a benign lesion or a noncarcinomatous malignancy.
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Complications
Serious complications resulting from TNB of the mediastinum are extremely rare. Pneumothorax and minimal bleeding are the most common minor complications. The incidence of pneumothorax in several large series of mediastinal and hilar biopsies ranges from 0% to 34%,2, 18, 21. 22. 28, 31, 32, 43, 60, 70, 73, 79 and is comparable with the rate of pneumothorax reported for TNB of pulmonary lesions. In mediastinal biopsies the risk factors for pneumothorax include traversing lung, presence of emphysema, depth of the lesion, and num74 ber of leural surfaces tran~versed.~~, The emoptysis rate from mediastinal and hilar TNB ranges from 0% to 10%. Sawhney and c01leagues~~ and Wernecke and coll e a g u e ~reported ~~ their experience with sonographically guided core biopsy of mediastinal masses extending to the chest wall using a 14-gauge cutting needle. The only reported complication in their 39 combined patients was one case of self-limited mediastinal bleeding. Similarly, Moulton and Moore,%using 18- and 20-gauge core-biopsy needles, reported only one case of biopsy-induced hemothorax requiring hospitalization and medical treatment among 17 mediastinal TNBs.
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DIAGNOSTIC VALUE OF TNB FOR MEDIASTINAL AND HlLAR BIOPSY
The treatment of a mediastinal mass depends on the histology of the lesion. A reliable, accurate, and safe nonsurgical technique for obtaining a tissue diagnosis is highly desirable, particularly for lesions that do not require sur ical management. Metastatic carcinoma to ilar or mediastinal lymph nodes accounts for 49% to 72% of lesions undergoing biopsy in most series.2,28, 73, 79 The other most frequently encountered lesions are lymphoma, thymoma, germ cell tumors, neurogenic tumors, cysts, and benign lymphadenopathy. Because the incidence and diagnostic accuracy of TNB for each of these lesions varies significantly, the use of TNB and alternative diagnostic procedures is discussed separately.
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METASTATIC CARCINOMA
Several investigators report a high sensitivity and specificity of TNB for the diagnosis of
metastatic cancer to the hilum and mediastit~~ a sensinum.2,32, 58, 70,n,79 W e ~ t c o treported tivity of 94% in a series of 72 patients with metastatic carcinoma to the hilum or mediastinum. Morrissey and colleagues32reported a sensitivity of 90% for metastatic carcinoma to the mediastinum using fine-needle aspiration and a slightly higher sensitivity (96%) using core biopsy. Sider and Davis58reported a 95% sensitivity for TNB of hilar carcinomatous masses in patients with negative results from bronchoscopy. Protopapas and W e ~ t c o t t ~ ~ evaluated the use of TNB of slightly to moderately enlarged lymph nodes (defined as discrete, well-defined nodes with a short axis > 10 mm and long axis < 30 mm) in patients with suspected metastatic disease. The sensitivity of TNB for the diagnosis of metastatic carcinoma to these lymph nodes was 98% (40 of 41 patients). Based on its high sensitivity for the diagnosis of metastatic carcinoma to the mediastinum, several investigators*,32, 43, 58, 70, 73, 79 have recommended TNB as the preferred initial method for obtaining tissue from enlarged mediastinal lymph nodes and areas of suspected mediastinal invasion in patients with known or suspected carcinoma. TNB does have advantages over mediastinoscopy for mediastinal evaluation. As compared with mediastinoscopy, TNB is faster, better tolerated, and can be performed under local anesthesia. A disadvantage of standard mediastinoscopy is that anterior mediastinal, paraaortic, aortopulmonary, and some subcarinal lymph nodes are inaccessible to the mediastinoscope. Sampling of these nodes may necessitate an additional procedure, such as mediastinotomy or thoracoscopy. In contrast, all regions of the mediastinum are potentially accessible with TNB. TNB is also substantially less expensive than mediastinoscopy. The combined professional and technical charges for CT-guided TNB at our institution, including the postprocedure chest radiograph, is $1150. In comparison, the combined technical and professional charges for outpatient mediastinoscopy, including general anesthesia, is $3600. (The actual reimbursement for TNB and mediastinoscopy is approximately one third to two thirds of these charges.43)The cost effectiveness of TNB for the evaluation of intrathoracic masses has been demonstrated by Gobien and c o l l e a g ~ e sZafar . ~ ~ and M ~ i n u d d i n ~ ~ recently reported cost savings with mediastinal TNB as opposed to surgical biopsy; the
TRANSTHORACIC HILAR AND MEDIASTINAL BIOPSY
amount of savings varied based on the type of lesion. In 71 of 75 patients with lung cancer diagnosed by TNB, no additional diagnostic procedures were required before institution of definitive therapy (chemotherapy, radiotherapy, or An additional surgical diagnostic procedure was performed in only four cases before definitive therapy was administered. Conversely, all patients with a TNB diagnosis of thymoma required surgery, whether a preoperative diagnosis was established or not, to determine the extent of local invasion and to attempt resection. These results suggest that TNB of the mediastinum is an accurate, less expensive, and less invasive alternative to mediastinoscopy, at least when metastatic carcinoma is the primary diagnostic consideration. Despite these advantages, there are definite limitations of TNB in the nodal staging of malignancy. The main limitation is that a negative TNB does not mean that the mediastinum is benign. In addition, the TNB sampling process is much less complete than surgical sampling techniques. A negative TNB result may require a surgical procedure for confirmation or further evaluation. Transbronchial needle aspiration, performed during fiberoptic bronchoscopy, has been used for sampling enlarged mediastinal lymph nodes." 20, 52, 53, 57, This technique is useful only for lymph nodes immediately adjacent to the trachea and central bronchi and has been used primarily in the evaluation of enlarged paratracheal and subcarinal lymph nodes. The reported incidence of pneumothorax is extremely Occasional false-positives caused by sampling of adjacent cancer-containing lung have been r e p ~ r t e d . ' ~52, Wang and colleagues66 and Schenck and report sensitivities of 76% (19 of 25) and 50% (17 of 34), respectively, in patients with proved carcinomatous involvement of accessible mediastinal lymph nodes. In patients with enlarged lymph nodes by chest radiographs, a yield of 61% has been reported.20Because most of the reported series to date do not include analysis of the size of the sampled lymph nodes, it is not known whether the technique has any use for patients with only slightly or moderately enlarged lymph nodes.20,52, 66 In contrast to CT- or ultrasound-guided mediastinal TNB, transbronchial needle aspiration is blind because it does not allow visual confirmation of the biopsy needle tip position. This may account for the lower sen197
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sitivity of transbronchial needle aspiration as compared with TNB in the sampling of mediastinal nodes. As with TNB, a negative or nondiagnostic transbronchial needle aspiration cannot be considered definitive and should be followed by TNB or mediastinoscopy. More recently, the introduction of realtime CT fluoroscopy has allowed real-time guidance of the biopsy needle during TNB.76 Rong and Cui4'jrecently reported an increase in sensitivity of transbronchial aspiration from 20% to 60% by using CT guidance to confirm the needle position, but published experience with this technique is limited. Although transbronchial needle aspiration was described more than a decade ago,66it has not gained widespread popularity among bronchoscopists and the number of reported cases is relatively sma1L3In a survey of bronchoscopists, the routine use of transbronchial needle aspiration for the diagnosis of malignant disease was performed by only 11.8% of the respondents, and "poor results were noted by a significant number."41 In those institutions with the required technical expertise, transbronchial needle aspiration may be a reasonable approach in patients who have radiographic or CT evidence of an endobronchial lesion accompanied by enlarged mediastinal lymph nodes adjacent to the airways. In such patients, both the endobronchial lesion and the lymphadenopathy can undergo biopsy during the same procedure. In patients with peripheral lung nodules and enlarged mediastinal lymph nodes, we believe that TNB is the procedure of choice for both diagnosis and staging given its greater accuracy as compared with fiberoptic bronchoscopy for pulmonary nodules.&10,12,17,24.35,4O,45,48,61.62, 72 In such patients, TNB can be used to sample both the lung lesion and the enlarged mediastinal lymph nodes, usually during a single procedure. According to Shields,55only 20% to 25% of patients with non-small cell carcinoma and 10% to 20% of patients with N2 (ipsilateral mediastinal) nodal disease are surgically resectable. In patients with non-small cell carcinoma and N2 disease, the criteria for establishing unresectability vary widely among different institution^.^, 29, 36, 38, 55, 67 Several findings are commonly used to indicate unresectability. Bulky lymphadenopathy (lymph node enlargement visible on chest radiographs), involvement of two or more lymph node stations, high paratracheal (2R or 2L) disease, and superior vena caval obstruction are
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widely considered to represent unresectable N2 disease?,29, 36, 38, 55, 67 Patients with N3 (contralateral hilar or mediastinal nodal) disease have stage lllb lung cancer and are likewise considered unresectable. The greatest use of any staging procedure is the detection of mediastinal lymph node metastases that prevents an unnecessary thoracotomy in unresectable lung cancer patients, particularly those with enlarged ipsilateral (N2) lymphadenopathy or contralateral (N3) lymphadenopathy or direct mediastinal invasion. In such patients, definitive staging and documentation of unresectability can usually be obtained by mediastinal TNB, with or without sampling of the primary lung lesion. TNB can also be used in conjunction with mediastinoscopy or fiberoptic bronchoscopy and transbronchial needle aspiration to complete or extend the mediastinal sampling process. For example, if transcervical mediastinoscopy or fiberoptic bronchoscopy is used to sample paratracheal or subcarinal lymph nodes, TNB can be used to stage the patient further by sampling enlarged lymph nodes inaccessible to these other staging procedures. LYMPHOMA
Fine-needle aspiration biopsy has a lower diagnostic accuracy for lymphoma than for carcinoma.2,21, 31, 70, 73, 79 Although the reported sensitivity of TNB for lymphoma using fine needles ranges from 42% to 82%,*, 31, 70, 73, 79 the combined number of patients in these studies is relatively small. The sensitivity of TNB depends in part on the specific type of lymphoma. Several authors have reported a higher sensitivity of TNB for non-Hodgkin’s lymphoma than for Hodgkin’s 70, 73, 79 The lower sensitivity of fine-needle TNB for Hodgkin’s lymphoma is often caused by the paucity of diagnostic Reed-Sternberg cells in the aspirated specimen.21The nodular sclerosing subtype of Hodgkin’s lymphoma is particularly difficult to diagnose with fineneedle TNB. Although the accuracy of TNB is considerably higher for non-Hodgkin’s lymphoma, subclassification into low and intermediate grades can be difficult or impossible with cytologic techniques because definitive classification frequently requires histology to characterize tissue architecture. Herman and colleaguesz1reported the results of fine-needle aspiration of 126 patients with anterior mediastinal masses. In 26 pa-
tients with lymphoma, the overall sensitivity was 42%, with a sensitivity for Hodgkin’s lymphoma of 20Y0.2~In addition, five cases of lymphoma were misdiagnosed as thymoma and two patients with thymoma (lymphocytic type) were misdiagnosed as lymphoma. The low accuracy was attributed in part to the use of cytologic methods alone without immunocytochemical studies, making the distinction of lymphoma from thymoma difficult.z1 More recently, Silverman and colleagues59 reported the results of image-guided needle biopsy (both fine needle and core biopsy) in 102 patients with lymphoma (93 with nonHodgkin’s lymphoma and 9 with Hodgkin’s lymphoma). Supradiaphragmatic and infradiaphragmatic biopsies were included in this study. Seventy-two percent of all patients in this study were treated on the basis of results of image-guided needle biopsy alone; for patients with a prior diagnosis of lymphoma this figure increased to 91%. They found immunocytochemical tests helpful in reaching a definitive diagnosis, whereas the size of the needle used for biopsy was not a factor.59 Several recent reports detail the use of core biopsy for the diagnosis of lymphoma. BenYehuda and colleagues5reported their experience using core-needle biopsy in 100 patients with lymphoma (71 with non-Hodgkin’s lymphoma and 29 with Hodgkin’s lymphoma). Eighty-six percent of patients in this study were treated solely on the basis of the results obtained from needle biopsy. Pappa and coll e a g u e reported ~~~ similar results for core-needle biopsy of lymphoma. Moulton and Moore34compared the use of aspiration and core-needle biopsy in 22 patients with lymphoma (21 non-Hodgkin’s lymphoma and 1 Hodgkin’s lymphoma). Aspiration biopsy was positive for lymphoma in 68% (15 of 22) of patients, although information sufficient to determine treatment was obtained in only 53% (8 of 15) of patients with positive cytologic diagnosis for malignant lymphoma. In comparison, core-needle biopsy correctly diagnosed 91% (20 of 22) of lymphomas, and all of these patients were treated based on the results of core-needle biopsy alone.34 In conclusion, it is clear from a review of the published literature that the use of immunocytochemical studies and core-needle biopsy have substantially improved the diagnostic accuracy of TNB for lymphoma, with success rates approaching those reported for carcinoma.
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REPEAT BIOPSY Numerous investigators have emphasized the importance of performing repeat TNB when the results of the initial biopsy are negative or nondiagnostic.l6.43, 50, 69, 7z, 74 Incomplete neoplastic replacement of the node sampled may result in a false-negative lymph node biopsy. Repeat biopsy following a negative TNB is important, particularly when metastatic carcinoma is suspected. In a recent study of 48 patients who underwent mediastinal TNB of enlarged lymph nodes, 8 required a repeat biopsy.43Five of the eight repeat lymph node biopsies were positive for carcinoma on the second attempt. If a repeat TNB had not been performed, there would have been six false-negative biopsies rather than one. Significantly, the single false-negative biopsy in this series did not have repeat TNB performed. Whenever possible, we perform a core biopsy (in addition to fine-needle aspiration) at the time of repeat biopsy. ANTERIOR MEDIASTINAL MASSES The accurate distinction between thymoma, lymphoma, and germ cell tumors has important therapeutic implications. Patients with lymphoma are treated with radiotherapy or chemotherapy depending on the type and stage of disease. Thymoma is primarily treated surgically, with radiotherapy reserved for patients with local invasion. Treatment of germ cell tumors is based on whether they are seminomatous or nonseminomatous. In a series of 29 patients, Weisbrod68reported only a 61% sensitivity of fine-needle aspiration biopsy for the diagnosis of thymoma. In addition, three thymomas were misdiagnosed by TNB, two as lymphoma and one as a cystic teratoma. Extensive fibrosis and cystic degeneration likely accounted for some of the false-negative biopsies. Herman and colleagues,21 also using fine-needle biopsy, reported a sensitivity of 71% in a series of 28 patients with thymoma. They also reported difficulty in differentiating thymoma from lymphoma. Immunohistochemical studies were not performed on the aspirated specimens in either study. Published results of core biopsy for thymomas are limited. Morrissey and colleagues32suggest that core biopsy can be helpful in distinguishing thymoma from lymphoma. Even core biopsy of thymoma, however, cannot reliably distin-
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guish between benign and locally invasive thymomas. Histologic examination of the excised specimen or radiologic evidence of local mediastinal invasion or metastases is necessary to diagnosis a malignant t h y m ~ m a . ~ ~ Based on results to date, we believe that the current potential role of TNB for patients with suspected thymoma is mainly to exclude other types of nonsurgical lesions because definitive evaluation and treatment of thymomas is surgical. Most published series of TNB for mediastinal germ cell tumors comprise only a small number of patients. Herman and colleaguesz1 reported a 91% sensitivity for germ cell tumors in a series of 11 patients using fineneedle TNB. In contrast, Weisbrod68in a series of 10 patients with germ cell tumors reported a sensitivity of only 57% for TNB.
MEDIASTINAL CYSTS Congenital mediastinal cysts include a variety of bronchopulmonary malformations, such as bronchogenic, esophageal duplication, and neuroenteric cysts. The CT appearance and location of such cysts usually suggest the diagnosis. Aspiration of mediastinal cysts has been described in patients to confirm the diagnosis.z6In symptomatic patients, aspiration of a bronchogenic cyst may be used for diagnosis and treatment in adults.', 54
SUMMARY TNB of the mediastinum is an accurate, safe, and cost-effective diagnostic tool for the evaluation of mediastinal masses and lymphadenopathy. The technique is most useful in the staging of carcinoma, where it serves as a less expensive and minimally invasive alternative to mediastinoscopy for establishing unresectability. With recent advances in immunohistochemical and core biopsy techniques, TNB has become more accurate for establishing the initial diagnosis of lymphoma and for confirming recurrent disease. Core-needle biopsy has improved the accuracy of TNB and is particularly useful when fine-needle aspiration fails to yield a specific diagnosis, or when lymphoma or a noncarcinomatous lesion is suspected.
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References 1. Adam A, MacSweeney JE, Whyte MK, et al: CTguided extrapleural drainage of bronchogenic cyst. J Comput Assist Tomogr 13:1065-1068, 1989 2. Adler OB, Rosenberger A, Peleg H Fine-needle aspiration biopsy of mediastinal masses: Evaluation of 136 experiences. AJR Am J Roentgenol 140:893-896, 1983 3. Arroliga AC, Matthay RA: The role of bronchoscopy in lung cancer. Clin Chest Med 14237-98, 1993 4. Belfiore G, Camera L, Moggio G, et al: Middle mediastinum lesions: Preliminary experience with CTguided fine-needle aspiration biopsy with a suprasternal approach. Radiology 202870-873, 1997 5. Ben-Yehuda D, Polliack A, Okon E, et al: Imageguided core-needle biopsy in malignant lymphoma: Experience with 100 patients that suggests the techniaue is reliable. 1 Clin Oncol 142431-2434, 1996 6. Brissler EL, Kirkham JA Mediastinal masses: Alternative approaches to CT-guided needle biopsy. Radi010w191:391-396, 1994 7. Cohan RH, Newman GE, Braun SD, et al: CT assistance for fluoroscopicallyguided transthoracic needle aspiration biopsy. J Comput Assist Tomogr 810931098, 1984 8. Collins CD, Breatnach E, Nath PH: Percutaneous needle biopsy of lung nodules following failed bronchoscopic biopsy. Eur J Radiol 15:49-53, 1992 9. Cooper JD,Ginsberg RJ: The use of mediastinoscopy in lung cancer: Preoperative evaluation. In Kittle CF (ed): Current Controversies in Thoracic Surgery. Philadelphia, WB Saunders, 1986, pp 162-168 10. Cortese DA, McDougall J C Biopsy and brushing of peripheral lung cancer with fluoroscopic guidance. Chest 75141-145,1979 11. Dahlgren S, Nordenstrom B: Transthoracic Needle Biopsy. Chicago, Mosby Year Book, 1966 12. Gaeta M, Russi EG, La Spada F, et al: Small bronchogenic carcinomas presenting as solitary pulmonary nodules. Bioptic approach guided by CT-positive bronchus sign. Chest 1021167-1170,1992 13. Gobien RF, Bouchard EA, Gobien BS, et al: Thin needle aspiration biopsy of thoracic lesions: Impact on hospital charges and patterns of patient care. Radiology 1486M7, 1983 14. Gobien RF, Skucas J, Paris BS: CT-assisted fluoroscopically guided aspiration biopsy of central hilar and mediastinal masses. Radiology 141443-447, 1981 15. Gobien RP, Stanley JH, Vujic I, et al: Thoracic biopsy: CT guidance of thin-needle aspiration. AJR Am J Roentgenol 142S27-830, 1984 16. Gobien RP, Valicenti JF, Paris BS, et al: Thin-needle aspiration biopsy: Methods of increasing the accuracy of a negative prediction. Radiology 145:60> 605, 1982 17. Greene R Transthoracic needle aspiration biopsy. In Athanasoulis CA, Greene R, Pfister RC, et a1 (eds): Interventional Radiology. Philadelphia, WB Saunders, 1982, pp 587434 18. Gunther RW Percutaneous interventions in the thorax. Seventh annual Charles Dotter memorial lecture. J Vasc Interv Radiol 3:379-390, 1992 19. Harrow E, Halber M, Hardy S, et al: Bronchoscopic and roentgenographic correlates of a positive transbronchial needle asuiration in the s t a h e ; of lung v cancer. Chest 100:1562-1596, 1991 20. Harrow EM, Oldenburg FA, Smith AM: Transbron"
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chial needle aspiration in clinical practice. Thorax 40:75&759, 1985 21. Herman SJ, Holub RV, Weisbrod GL, et al: Anterior mediastinal masses: Utility of transthoracic needle biopsy. Radiology 180167-170, 1991 22. Jereb M, Us-Krasovec M Transthoracic needle biopsy of mediastinal and hilar lesions. Cancer 40:13541357, 1977 23. Khouri NF, Meziane MA: Transthoracic needle aspiration biopsy: Optimizing the yield. J Thorac Ima&g 2:18-26, 1987 24. Khouri.NF, Stitik FP, Erozan YS, et al: Transthoracic needle aspiration biopsy of benign and malignant lung lesions. AJR Am J Roentgenol 1M281-288, 1985 25. Klein JS, Salomon G, Stewart E A Transthoracic needle biopsy with a coaxially placed 20-gauge automated cutting needle: Results in 122 patients. Radiology 198:715-720, 1996 26. Kuhlman JE, Fishman EK, Wang KP, et al: Mediastinal cysts: Diagnosis by CT and needle aspiration. AJR Am J Roentgenol 150:75-78, 1988 27. Leyden H Ueber infektiose pneumonie. Dtsch Med Wochenschr 9352-54, 1883 28. Linder J, Olsen GA, Johnston WW: Fine-needle aspiration biopsy of the mediastinum. Am J Med 81:1005-1008, 1986 29. Martini N, Flehinger BJ: The role of surgery in N2 lung cancer. Surg Clin North Am 671037-1049, 1987 30. Menetrier P: Cancer primitif du poumon. Bul SOC Anat (Paris) 61:643-647, 1886 31. Moinuddin SM, Lee LH, Montgomery JH: Mediastinal needle biopsy. AJR Am J Roentgenol 143:531532, 1984 32. Morrissey B, Adams H, Gibbs AR, et al: Percutaneous needle biopsy of the mediastinum: Review of 94 procedures. Thorax 48:632-637, 1993 33. Moulton J S Artificial extrapleural window for mediastinal biopsy. J Vasc Intern Radiol 4825829, 1993 34. Moulton JS, Moore PT Coaxial percutaneous biopsy technique with automated biopsy devices: Value in improving accuracy and negative predictive value. Radiology 186:515-522, 1993 35. Naidich DP, Sussman R, Kutcher WL, et al: Solitary pulmonary nodules. CT-bronchoscopic correlation. Chest 93:595-598, 1988 36. Naruke T, Goya T, Tsuchiya R, et al: The importance of surgery to non-small cell carcinoma of lung with mediastinal lymph node metastasis. Ann Thorac Surg 46:60?-610, 1988 37. Pappa VI, Hussain HK, Reznek RH, et al: Role of image-guided core-needle biopsy in the management of patients with lymphoma. J Clin Oncol 1424272430, 1996 38. Pearson FG, DeLarue NC, Ilves R, et al: Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg 83:l-11, 1982 39. Poe RH, Kallay MC, Wicks CM, et al: Predicting risk of pneumothorax in needle biopsy of the lung. Chest 85:232-235, 1984 40. Poe RH, Ortiz C, Israel RH, et al: Sensitivity, specificity, and predictive values of bronchoscopy in neoplasm metastatic to lung. Chest 88:84-88, 1985 41. Prakash UB, Offord KP, Stubbs SE: Bronchoscopy in North America: The ACCP survey. Chest 10016681675, 1991 42. Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997
TRANSTHORACIC HILAR AND MEDIASTINAL BIOPSY 43. Protopapas Z, Westcott JL: Transthoracic needle biopsy of mediastinal lymph nodes for staging lung and other cancers. Radiology 199489496,1996 44. Protopapas Z, White CS, Miller BH, et al: Transthoracic needle biopsy practices: Results of a nationwide survey. In Radiological Society of North America Annual Meeting. Chicago, 1996 45. Radke JR, Conway WA, Eyler WR, et al: Diagnostic accuracy in peripheral lung lesions. Factors predicting success with flexible fiberoptic bronchoscopy. Chest 76:176-179, 1979 46. Rong F, Cui 8 : CT scan directed transbronchial needle aspiration biopsy for mediastinal nodes. Chest 114:36-39, 1998 47. Rubens DJ, Strang JG, Fultz PJ, et al: Sonographic guidance of mediastinal biopsy: An effective alternative to CT guidance. AJR Am J Roentgenol 169:16051610, 1997 48. Sage1 SS, Ferguson TB, Forrest JV, et al: Percutaneous transthoracic aspiration needle biopsy. Ann Thorac Surg 26:399405,1978 49. Saito T, Kobayashi H, Sugama Y, et al: Ultrasonically guided needle biopsy in the diagnosis of mediastinal masses. Am Rev Respir Dis 138679-684, 1988 50. Sargent EN, Turner AF, Gordonson J, et al: Percutaneous pulmonary needle biopsy. Report of 350 patients. AJR Am J Roentgenol 122:758-768, 1974 51. Sawhney S, Jain R, Berry M Tru-Cut biopsy of mediastinal masses guided by real-time sonography. Clin Radiol 44:16-19,1991 52. Schenk DA, Bower JH, Bryan CL, et al: Transbronchial needle aspiration staging of bronchogenic carcinoma. Am Rev Respir Dis 134146148, 1986 53. Schenk DA, Bryan CL, Bower JH, et al: Transbronchial needle aspiration in the diagnosis of bronchogenic carcinoma. Chest 92:8%35, 1987 54. Schwartz AR, Fishman EK, Wang KP: Diagnosis and treatment of a bronchogenic cyst using transbronchial needle aspiration. Thorax 41:326-327, 1986 55. Shields TW: Surgical therapy for carcinoma of the lung. Clin Chest Med 14:121-147, 1993 56. Shure D: Is transbronchial needle aspiration worthwhile? Pulmonary Perspectives 8:l-3, 1991 57. Shure D, Fedullo PF: The role of transcarinal needle aspiration in the staging of bronchogenic carcinoma. Chest 86:693-696, 1984 58. Sider L, Davis TM Jr: Hilar masses: Evaluation with CT-guided biopsy after negative bronchoscopic examination. Radiology 164:107-109, 1987 59. Silverman SG, Lee BY, Mueller PR, et al: Impact of positive findings at image-guided biopsy of lymphoma on patient care: Evaluation of clinical history, needle size, and pathologic findings on biopsy performance. Radiology 190:759-764, 1994 60. Sinner WN: Directed fine needle biopsy of anterior and middle mediastinal masses. Oncology 42:92-96, 1985
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61. Sinner WN: Pulmonary neoplasms diagnosed with transthoracic needle biopsy. Cancer 43:1533-1540, 1979 62. Stringfield JT, Markowitz DJ, Bentz RR, et al: The effect of tumor size and location on diagnosis by fiberoptic bronchoscopy. Chest 723474476, 1977 63. Templeton PA, White CS, Protopapas Z, et al: Realtime continuous imaging CT guidance for lung biopsy. In Radiological Society of North America Annual Meeting. Chicago, 1996 64. vansonnenberg E, Casola G, Ho M, et al: Difficult thoracic lesions: CT-guided biopsy experience in 150 cases. Radiology 167457461, 1988 65. vansonnenberg E, Lin AS, Deutsch AL, et al: Percutaneous biopsy of difficult mediastinal, hilar, and pulmonary lesions by computed tomographic guidance and a modified coaxial technique. Radiology 148:300302, 1983 66. Wang KP, Brower R, Haponik EF, et al: Flexible transbronchial needle aspiration for staging of bronchogenic carcinoma. Chest 84:571-576, 1983 67. Watanabe Y, Shimizu J, Oda M, et al: Aggressive surgical intervention in N2 non-small cell cancer of the lung. AM Thorac Surg 51:253-261, 1991 68. Weisbrod GL: Percutaneous fine-needle aspiration biopsy of the mediastinum. Clin Chest Med 8:2741, 1987 69. Weisbrod GL: Transthoracic percutaneous lung biopsy. Radiol Clin North Am 28:647-655, 1990 70. Weisbrod GL, Lyons DJ, Tao LC, et al: Percutaneous fine-needle aspiration biopsy of mediastinal lesions. AJR Am J Roentgenol 143:525-529, 1984 71. Wernecke K, Vassallo P, Peters PE, et al: Mediastinal tumors: Biopsy under US guidance. Radiology 172473-476, 1989 72. Westcott JL: Direct percutaneous needle aspiration of localized pulmonary lesions: Results in 422 patients. Radiology 13731-35, 1980 73. Westcott JL: Percutaneous needle aspiration of hilar and mediastinal masses. Radiology 141:323-329,1981 74. Westcott JL: Percutaneous transthoracic needle biopsy. Radiology 169:593401, 1988 75. Westcott JL, Rao N, Colley DP: Transthoracic needle biopsy of small pulmonary nodules. Radiology 202~97-103, 1997 76. White CS, Templeton PA, Hasday JD: CT-assisted transbronchial needle aspiration: Usefulness of CT fluroscopy. AJR Am J Roentgenol 169:393-394, 1997 77. Yang PC, Chang DB, Lee YC, et al: Mediastinal malignancy: Ultrasound guided biopsy through the supraclavicular approach. Thorax 47377-380, 1992 78. Yu CJ, Yang PC, Chang DB, et al: Evaluation of ultrasonically guided biopsies of mediastinal masses. Chest 100:399405, 1991 79. Zafar N, Moinuddin S: Mediastinal needle biopsy. A 15-year experience with 139 cases. Cancer 76:10651068, 1995
Address reprint requests to Zenon Protopapas, MD Department of Radiology Hospital of Saint Raphael 1450 Chapel Street New Haven, CT 06511 e-mail: [email protected]
0033-8389100 $15.00
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TRANSTHORACIC HILAR AND MEDIASTINAL BIOPSY Zenon Protopapas, MD, and Jack L. Westcott, MD
Transthoracic needle biopsy (TNB) for the diagnosis of pneumonia and lung carcinoma was first described over a century ago, long before radiographic techniques were avail30 Modern fluoroscopy, the use of 18to 22-gauge biopsy needles, and advances in cytopathology revolutionized TNB." The use of fine needles and improved radiologic guidance contributed to the low morbidity and negligible mortality of TNB.69,74 These advances have resulted in a high accuracy of TNB (sensitivity of 90% to 98%) in diagnosing cancer.17, 23. 24. 61. 72. 73 The introduction of CT as guidance for TNB has made the routine retrieval of material from small pulmonary lesions and most hilar and mediastinal masses possible.2,6, 14, 15, 43, 58, 64* 65, 75 Surgical techniques of mediastinal biopsy (mediastinoscopy, mediastinotomy, thoracotomy, or thoracoscopy) have a high diagnostic accuracy but are more invasive and are associated with the morbidity of a surgical procedure. TNB can be performed successfully as an outpatient procedure under local anesthesia, and is particularly useful in the diagnosis of carcinoma where it may obviate the need for a surgical diagnostic procedure. PREBIOPSY PROCEDURES
Prebiopsy laboratory studies that are routinely obtained include prothrombin time and
partial thromboplastin time. In addition, patients are questioned for a history of bleeding diathesis and the use of any antiplateletcontaining medications, such as aspirin. IMAGE GUIDANCE AND TECHNIQUE OF HILAR AND MEDIASTINAL BIOPSY
The size and location of the mass and its relationship to adjacent vascular structures determine the optimal biopsy approach to a hilar or mediastinal mass. A prebiopsy CT scan, preferably contrast-enhanced, is needed to determine the optimal approach to the lesion. CT is the preferred method of guiding mediastinal and hilar biopsies@because most lesions are either poorly seen fluoroscopically or are adjacent to major cardiovascular structures.2,7, 15, 64, 74 As opposed to fluoroscopy, the exact position of the needle tip can be documented with CT, although the actual needle pass is blind. The recent introduction of continuous CT imaging (also referred to as CT j7uoroscopy) permits real-time monitoring during needle placemenP3 and provides significant time savings. Sonographic guidance for mediastinal biopsies has been described by several aut h o r ~ .71,~ 77 ~ ,This technique allows for realtime cross-sectional monitoring during the biopsy. Sonography requires an adequate sonographic window, however, and it has been
From the Department of Radiology, Hospital of Saint Raphael, New Haven, Connecticut
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used mainly for biopsy of mediastinal masses that extend to the chest wall.78Using the prebiopsy CT scan, Rubens et a147defined an adequate sonographic window as 1 cm in diameter space along the chest wall that allowed visualization of the mass without intervening bone cartilage or bone. This allowed for the simultaneous placement of the transducer and needle and allowed real-time imaging during the biopsy. Using this criterion they were able to identify 27 patients as possible candidates for sonographic-guided mediastinal biopsy and were able to perform the biopsy on 25 of these patients (diagnostic biopsies in 24 patients). These authors concluded that this triage criterion is useful in identifying possible candidates for ultrasound-guided mediastinal bi0psy.4~ An anterior parasternal approach is preferred for most anterior mediastinal masses, whereas a posterior paravertebral approach is used for posterior mediastinal masses. The optimal approach for anterior and middle mediastinal masses superior to the heart reflects the anatomic differences between the 74 Right-sided right and left side of the masses located anterior to the superior vena cava can undergo biopsy using an anterior approach, whereas right paratracheal and retrotracheal masses usually undergo biopsy by a right posterior paravertebral approach (Fig. 1).Despite the greater depth of a juxtatracheal lesion from a posterior approach, this approach avoids puncture of the superior vena cava. We have on occasion used an anterior approach (traversing the superior vena cava) for biopsy of paratracheal and pretracheal lymphadenopathy without complication^.^^, 73 Midline (substernal) masses can undergo biopsy from a transternal approach if they are not easily accessible parasternally (Fig. 2). Aortopulmonary lymph nodes are accessed using a left anterior parasternal approach (Fig. 3). TNB of subcarinal masses is usually performed using a right posterior paravertebra1 approach (Fig. 4). Subcarinal biopsy is occasionally performed using a left parasternal approach by entering the mediastinum via the connective tissue space between the descending aorta and spine. Hilar masses may undergo biopsy using an anterior, posterior, or lateral approach depending on the relationship of the mass to the hilar vessels (Fig. 5). Whenever possible, a direct mediastinal approach is preferable to a transpulmonary approach, because the risk of pneumothorax
Figure 1. A 75-year-old patient with right upper lobe opacity and right paratracheal lymphadenopathy. Posterior paravertebral approach was used to biopsy enlarged right paratracheal lymph nodes. A benign transthoracic needle biopsy diagnosis was confirmed with mediastinoscopy and a bronchoscopy. Follow-up CT scan revealed resolution of the adenopathy and right upper lobe density. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
when avoiding pleural puncture is eliminated. Changing the patient’s position is frequently useful. For example, when anterior mediastinal masses do not extend to the chest wall with the patient supine, placing the patient in the lateral decubitus or oblique position may move the mass sufficiently so that it contacts the parasternal chest wall, thereby allowing a direct mediastinal approach.6 The injection of normal saline solution into the paravertebral or substernal extrapleural space is frequently useful to create or expand an extrapleural window for a direct mediastinal approach (Fig. 6).33 A pleural space approach to mediastinal TNB has also been described. With this technique, the pleural space leading to the lesion is widened by an existing effusion or expanded by creation of an iatrogenic pneumo-
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Figure 2. A 47-year-old patient with histoty of thyroid carcinoma and anterior mediastinal lymphadenopathy (arrows). Biopsy of the lymph nodes was performed by transternal approach and revealed metastatic thyroid carcinoma. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
Figure 3. A 65-year-old patient with left upper lobe mass. Paraaortic lymph node transthoracic needle biopsy (TNB) was performed by an anterior parasternal approach. Both TNB of the lung mass and paraaortic adenopathy showed squamous cell carcinoma. Both lesions could be biopsied during the same procedure because both lesions were on the same side. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
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Figure 4. A 72-year-old patient with history of breast carcinoma and subcarinal lymphadenopathy. Transthoracic needle biopsy (TNB) was performed using a right posterior paravertebral approach. TNB revealed metastatic breast carcinoma. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biopsy. J Thorac Imaging 12:250-258, 1997; with permission.)
thorax to avoid puncture of the visceral pleura.6 Following positional maneuvers, a pleural effusion ipsilateral to the mediastinal mass may be interposed between the skin entry site and lesion, providing a pleural window that avoids traversing lung parenchyma.6 Bressler and Kirkham6 described a suprasternal approach for large anterior and right
paratracheal masses under CT guidance. The patient is imaged in a semicoronal position allowing for direct visualization of the needle path. More recently, Belfiore et a14 described a suprasternal approach for CT-guided biopsy of the middle mediastinum. In this study, patients underwent biopsy in the supine position with the neck hyperextended. Using a triangulation method, the anteropos-
Figure 5. A, Chest radiograph of an asymptomatic 58-year-old woman with history of breast carcinoma shows a questionable left hilar mass, confirmed on CT. B, Scan from CT-guided needle biopsy by means of a left lateral approach with the patient on her right side reveals metastatic breast carcinoma. (From Westcott JL: Needle biopsy of chest lesions. In Taveras JM, Ferrucci JT (eds): Radiology. Philadelphia,JB Lippincott, 1992, pp 1-1 4; with permission.)
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Figure 6. Subcarinal biopsy using artificial widening of the right posterior mediastinum. A, Injection of 10 cc of normal saline caused displacement of the pleura (arrows). Widening of the paravertebral space enabled an extrapulmonary approach to the subcarinal lymph nodes (arrowheads). Curved arrow, left main stem bronchus. (From Protopapas Z, Westcott JL: Transthoracic hilar and mediastinal biospy. J Thorac Imaging 12:250-258, 1997; with permission.)
terior and mediolateral inclination of the needle was estimated, and the needle advanced under CT guidance. With this suprasternal approach, Belfiore et a14 were able to obtain adequate biopsy material in 25 (83%) of 30 patients without any major complications. Four patients developed a transient episode of hypotension requiring no pharmacologic treatment. NEEDLE CHARACTERISTICS
Fine aspirating needles (19-gauge or smaller) reliably provide samples for cytollogic and cell block examination, and occasionally provide tissue for histologic examination. Small-gauge cutting needles are designed to provide material for both histologic and cytologic examination. Several investigators have described the use of larger cutting needles for mediastinal TNB in selected patients.25,32, 34, 49, 51, 71 These larger cutting needles provide tissue for histology that may be helpful in the diagnosis of noncarcinomatous neoplasms and nonneoplastic conditions. High diagnostic accuracy for aspiration biopsy of the mediastinum for metastatic carci-
noma has been consistently reported; sensitivity for cancer ranges between 84% and and is comparable to needle biopsy results for pulmonary lesions. The diagnostic accuracy of aspiration biopsy with routine cytology for lymphoma, thymoma, germ cell tumors, and neurogenic tumors, however, is considerably lower.2, Several investigators have reported improved accuracy for core biopsies. Moulton and Moore,34in a study comparing aspiration with core biopsy, reported an increase in sensitivity (68% versus for the diagnosis of lymphoma. Sawhney and c o l l e a g ~ e s using , ~ ~ a 14-gauge core-biopsy needle, were able to obtain adequate tissue for histopathologic diagnosis in all 25 of their patients with mediastinal masses. Several investigators now recommend the use of automated cutting needles for the diagnosis of mediastinal masses. In our practice, we now use 18- or 20-gauge core-biopsy needles but do so selectively and under the following circumstances: (1) in patients in whom metastatic carcinoma is not the most likely diagnosis (lymphoma or other primary neoplasm); and (2) when the initial aspirate is nondiagnostic or suggests either a benign lesion or a noncarcinomatous malignancy.
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Complications
Serious complications resulting from TNB of the mediastinum are extremely rare. Pneumothorax and minimal bleeding are the most common minor complications. The incidence of pneumothorax in several large series of mediastinal and hilar biopsies ranges from 0% to 34%,2, 18, 21. 22. 28, 31, 32, 43, 60, 70, 73, 79 and is comparable with the rate of pneumothorax reported for TNB of pulmonary lesions. In mediastinal biopsies the risk factors for pneumothorax include traversing lung, presence of emphysema, depth of the lesion, and num74 ber of leural surfaces tran~versed.~~, The emoptysis rate from mediastinal and hilar TNB ranges from 0% to 10%. Sawhney and c01leagues~~ and Wernecke and coll e a g u e ~reported ~~ their experience with sonographically guided core biopsy of mediastinal masses extending to the chest wall using a 14-gauge cutting needle. The only reported complication in their 39 combined patients was one case of self-limited mediastinal bleeding. Similarly, Moulton and Moore,%using 18- and 20-gauge core-biopsy needles, reported only one case of biopsy-induced hemothorax requiring hospitalization and medical treatment among 17 mediastinal TNBs.
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DIAGNOSTIC VALUE OF TNB FOR MEDIASTINAL AND HlLAR BIOPSY
The treatment of a mediastinal mass depends on the histology of the lesion. A reliable, accurate, and safe nonsurgical technique for obtaining a tissue diagnosis is highly desirable, particularly for lesions that do not require sur ical management. Metastatic carcinoma to ilar or mediastinal lymph nodes accounts for 49% to 72% of lesions undergoing biopsy in most series.2,28, 73, 79 The other most frequently encountered lesions are lymphoma, thymoma, germ cell tumors, neurogenic tumors, cysts, and benign lymphadenopathy. Because the incidence and diagnostic accuracy of TNB for each of these lesions varies significantly, the use of TNB and alternative diagnostic procedures is discussed separately.
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METASTATIC CARCINOMA
Several investigators report a high sensitivity and specificity of TNB for the diagnosis of
metastatic cancer to the hilum and mediastit~~ a sensinum.2,32, 58, 70,n,79 W e ~ t c o treported tivity of 94% in a series of 72 patients with metastatic carcinoma to the hilum or mediastinum. Morrissey and colleagues32reported a sensitivity of 90% for metastatic carcinoma to the mediastinum using fine-needle aspiration and a slightly higher sensitivity (96%) using core biopsy. Sider and Davis58reported a 95% sensitivity for TNB of hilar carcinomatous masses in patients with negative results from bronchoscopy. Protopapas and W e ~ t c o t t ~ ~ evaluated the use of TNB of slightly to moderately enlarged lymph nodes (defined as discrete, well-defined nodes with a short axis > 10 mm and long axis < 30 mm) in patients with suspected metastatic disease. The sensitivity of TNB for the diagnosis of metastatic carcinoma to these lymph nodes was 98% (40 of 41 patients). Based on its high sensitivity for the diagnosis of metastatic carcinoma to the mediastinum, several investigators*,32, 43, 58, 70, 73, 79 have recommended TNB as the preferred initial method for obtaining tissue from enlarged mediastinal lymph nodes and areas of suspected mediastinal invasion in patients with known or suspected carcinoma. TNB does have advantages over mediastinoscopy for mediastinal evaluation. As compared with mediastinoscopy, TNB is faster, better tolerated, and can be performed under local anesthesia. A disadvantage of standard mediastinoscopy is that anterior mediastinal, paraaortic, aortopulmonary, and some subcarinal lymph nodes are inaccessible to the mediastinoscope. Sampling of these nodes may necessitate an additional procedure, such as mediastinotomy or thoracoscopy. In contrast, all regions of the mediastinum are potentially accessible with TNB. TNB is also substantially less expensive than mediastinoscopy. The combined professional and technical charges for CT-guided TNB at our institution, including the postprocedure chest radiograph, is $1150. In comparison, the combined technical and professional charges for outpatient mediastinoscopy, including general anesthesia, is $3600. (The actual reimbursement for TNB and mediastinoscopy is approximately one third to two thirds of these charges.43)The cost effectiveness of TNB for the evaluation of intrathoracic masses has been demonstrated by Gobien and c o l l e a g ~ e sZafar . ~ ~ and M ~ i n u d d i n ~ ~ recently reported cost savings with mediastinal TNB as opposed to surgical biopsy; the
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amount of savings varied based on the type of lesion. In 71 of 75 patients with lung cancer diagnosed by TNB, no additional diagnostic procedures were required before institution of definitive therapy (chemotherapy, radiotherapy, or An additional surgical diagnostic procedure was performed in only four cases before definitive therapy was administered. Conversely, all patients with a TNB diagnosis of thymoma required surgery, whether a preoperative diagnosis was established or not, to determine the extent of local invasion and to attempt resection. These results suggest that TNB of the mediastinum is an accurate, less expensive, and less invasive alternative to mediastinoscopy, at least when metastatic carcinoma is the primary diagnostic consideration. Despite these advantages, there are definite limitations of TNB in the nodal staging of malignancy. The main limitation is that a negative TNB does not mean that the mediastinum is benign. In addition, the TNB sampling process is much less complete than surgical sampling techniques. A negative TNB result may require a surgical procedure for confirmation or further evaluation. Transbronchial needle aspiration, performed during fiberoptic bronchoscopy, has been used for sampling enlarged mediastinal lymph nodes." 20, 52, 53, 57, This technique is useful only for lymph nodes immediately adjacent to the trachea and central bronchi and has been used primarily in the evaluation of enlarged paratracheal and subcarinal lymph nodes. The reported incidence of pneumothorax is extremely Occasional false-positives caused by sampling of adjacent cancer-containing lung have been r e p ~ r t e d . ' ~52, Wang and colleagues66 and Schenck and report sensitivities of 76% (19 of 25) and 50% (17 of 34), respectively, in patients with proved carcinomatous involvement of accessible mediastinal lymph nodes. In patients with enlarged lymph nodes by chest radiographs, a yield of 61% has been reported.20Because most of the reported series to date do not include analysis of the size of the sampled lymph nodes, it is not known whether the technique has any use for patients with only slightly or moderately enlarged lymph nodes.20,52, 66 In contrast to CT- or ultrasound-guided mediastinal TNB, transbronchial needle aspiration is blind because it does not allow visual confirmation of the biopsy needle tip position. This may account for the lower sen197
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sitivity of transbronchial needle aspiration as compared with TNB in the sampling of mediastinal nodes. As with TNB, a negative or nondiagnostic transbronchial needle aspiration cannot be considered definitive and should be followed by TNB or mediastinoscopy. More recently, the introduction of realtime CT fluoroscopy has allowed real-time guidance of the biopsy needle during TNB.76 Rong and Cui4'jrecently reported an increase in sensitivity of transbronchial aspiration from 20% to 60% by using CT guidance to confirm the needle position, but published experience with this technique is limited. Although transbronchial needle aspiration was described more than a decade ago,66it has not gained widespread popularity among bronchoscopists and the number of reported cases is relatively sma1L3In a survey of bronchoscopists, the routine use of transbronchial needle aspiration for the diagnosis of malignant disease was performed by only 11.8% of the respondents, and "poor results were noted by a significant number."41 In those institutions with the required technical expertise, transbronchial needle aspiration may be a reasonable approach in patients who have radiographic or CT evidence of an endobronchial lesion accompanied by enlarged mediastinal lymph nodes adjacent to the airways. In such patients, both the endobronchial lesion and the lymphadenopathy can undergo biopsy during the same procedure. In patients with peripheral lung nodules and enlarged mediastinal lymph nodes, we believe that TNB is the procedure of choice for both diagnosis and staging given its greater accuracy as compared with fiberoptic bronchoscopy for pulmonary nodules.&10,12,17,24.35,4O,45,48,61.62, 72 In such patients, TNB can be used to sample both the lung lesion and the enlarged mediastinal lymph nodes, usually during a single procedure. According to Shields,55only 20% to 25% of patients with non-small cell carcinoma and 10% to 20% of patients with N2 (ipsilateral mediastinal) nodal disease are surgically resectable. In patients with non-small cell carcinoma and N2 disease, the criteria for establishing unresectability vary widely among different institution^.^, 29, 36, 38, 55, 67 Several findings are commonly used to indicate unresectability. Bulky lymphadenopathy (lymph node enlargement visible on chest radiographs), involvement of two or more lymph node stations, high paratracheal (2R or 2L) disease, and superior vena caval obstruction are
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widely considered to represent unresectable N2 disease?,29, 36, 38, 55, 67 Patients with N3 (contralateral hilar or mediastinal nodal) disease have stage lllb lung cancer and are likewise considered unresectable. The greatest use of any staging procedure is the detection of mediastinal lymph node metastases that prevents an unnecessary thoracotomy in unresectable lung cancer patients, particularly those with enlarged ipsilateral (N2) lymphadenopathy or contralateral (N3) lymphadenopathy or direct mediastinal invasion. In such patients, definitive staging and documentation of unresectability can usually be obtained by mediastinal TNB, with or without sampling of the primary lung lesion. TNB can also be used in conjunction with mediastinoscopy or fiberoptic bronchoscopy and transbronchial needle aspiration to complete or extend the mediastinal sampling process. For example, if transcervical mediastinoscopy or fiberoptic bronchoscopy is used to sample paratracheal or subcarinal lymph nodes, TNB can be used to stage the patient further by sampling enlarged lymph nodes inaccessible to these other staging procedures. LYMPHOMA
Fine-needle aspiration biopsy has a lower diagnostic accuracy for lymphoma than for carcinoma.2,21, 31, 70, 73, 79 Although the reported sensitivity of TNB for lymphoma using fine needles ranges from 42% to 82%,*, 31, 70, 73, 79 the combined number of patients in these studies is relatively small. The sensitivity of TNB depends in part on the specific type of lymphoma. Several authors have reported a higher sensitivity of TNB for non-Hodgkin’s lymphoma than for Hodgkin’s 70, 73, 79 The lower sensitivity of fine-needle TNB for Hodgkin’s lymphoma is often caused by the paucity of diagnostic Reed-Sternberg cells in the aspirated specimen.21The nodular sclerosing subtype of Hodgkin’s lymphoma is particularly difficult to diagnose with fineneedle TNB. Although the accuracy of TNB is considerably higher for non-Hodgkin’s lymphoma, subclassification into low and intermediate grades can be difficult or impossible with cytologic techniques because definitive classification frequently requires histology to characterize tissue architecture. Herman and colleaguesz1reported the results of fine-needle aspiration of 126 patients with anterior mediastinal masses. In 26 pa-
tients with lymphoma, the overall sensitivity was 42%, with a sensitivity for Hodgkin’s lymphoma of 20Y0.2~In addition, five cases of lymphoma were misdiagnosed as thymoma and two patients with thymoma (lymphocytic type) were misdiagnosed as lymphoma. The low accuracy was attributed in part to the use of cytologic methods alone without immunocytochemical studies, making the distinction of lymphoma from thymoma difficult.z1 More recently, Silverman and colleagues59 reported the results of image-guided needle biopsy (both fine needle and core biopsy) in 102 patients with lymphoma (93 with nonHodgkin’s lymphoma and 9 with Hodgkin’s lymphoma). Supradiaphragmatic and infradiaphragmatic biopsies were included in this study. Seventy-two percent of all patients in this study were treated on the basis of results of image-guided needle biopsy alone; for patients with a prior diagnosis of lymphoma this figure increased to 91%. They found immunocytochemical tests helpful in reaching a definitive diagnosis, whereas the size of the needle used for biopsy was not a factor.59 Several recent reports detail the use of core biopsy for the diagnosis of lymphoma. BenYehuda and colleagues5reported their experience using core-needle biopsy in 100 patients with lymphoma (71 with non-Hodgkin’s lymphoma and 29 with Hodgkin’s lymphoma). Eighty-six percent of patients in this study were treated solely on the basis of the results obtained from needle biopsy. Pappa and coll e a g u e reported ~~~ similar results for core-needle biopsy of lymphoma. Moulton and Moore34compared the use of aspiration and core-needle biopsy in 22 patients with lymphoma (21 non-Hodgkin’s lymphoma and 1 Hodgkin’s lymphoma). Aspiration biopsy was positive for lymphoma in 68% (15 of 22) of patients, although information sufficient to determine treatment was obtained in only 53% (8 of 15) of patients with positive cytologic diagnosis for malignant lymphoma. In comparison, core-needle biopsy correctly diagnosed 91% (20 of 22) of lymphomas, and all of these patients were treated based on the results of core-needle biopsy alone.34 In conclusion, it is clear from a review of the published literature that the use of immunocytochemical studies and core-needle biopsy have substantially improved the diagnostic accuracy of TNB for lymphoma, with success rates approaching those reported for carcinoma.
TRANSTHORACIC HILAR AND MEDIASTINAL BIOPSY
REPEAT BIOPSY Numerous investigators have emphasized the importance of performing repeat TNB when the results of the initial biopsy are negative or nondiagnostic.l6.43, 50, 69, 7z, 74 Incomplete neoplastic replacement of the node sampled may result in a false-negative lymph node biopsy. Repeat biopsy following a negative TNB is important, particularly when metastatic carcinoma is suspected. In a recent study of 48 patients who underwent mediastinal TNB of enlarged lymph nodes, 8 required a repeat biopsy.43Five of the eight repeat lymph node biopsies were positive for carcinoma on the second attempt. If a repeat TNB had not been performed, there would have been six false-negative biopsies rather than one. Significantly, the single false-negative biopsy in this series did not have repeat TNB performed. Whenever possible, we perform a core biopsy (in addition to fine-needle aspiration) at the time of repeat biopsy. ANTERIOR MEDIASTINAL MASSES The accurate distinction between thymoma, lymphoma, and germ cell tumors has important therapeutic implications. Patients with lymphoma are treated with radiotherapy or chemotherapy depending on the type and stage of disease. Thymoma is primarily treated surgically, with radiotherapy reserved for patients with local invasion. Treatment of germ cell tumors is based on whether they are seminomatous or nonseminomatous. In a series of 29 patients, Weisbrod68reported only a 61% sensitivity of fine-needle aspiration biopsy for the diagnosis of thymoma. In addition, three thymomas were misdiagnosed by TNB, two as lymphoma and one as a cystic teratoma. Extensive fibrosis and cystic degeneration likely accounted for some of the false-negative biopsies. Herman and colleagues,21 also using fine-needle biopsy, reported a sensitivity of 71% in a series of 28 patients with thymoma. They also reported difficulty in differentiating thymoma from lymphoma. Immunohistochemical studies were not performed on the aspirated specimens in either study. Published results of core biopsy for thymomas are limited. Morrissey and colleagues32suggest that core biopsy can be helpful in distinguishing thymoma from lymphoma. Even core biopsy of thymoma, however, cannot reliably distin-
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guish between benign and locally invasive thymomas. Histologic examination of the excised specimen or radiologic evidence of local mediastinal invasion or metastases is necessary to diagnosis a malignant t h y m ~ m a . ~ ~ Based on results to date, we believe that the current potential role of TNB for patients with suspected thymoma is mainly to exclude other types of nonsurgical lesions because definitive evaluation and treatment of thymomas is surgical. Most published series of TNB for mediastinal germ cell tumors comprise only a small number of patients. Herman and colleaguesz1 reported a 91% sensitivity for germ cell tumors in a series of 11 patients using fineneedle TNB. In contrast, Weisbrod68in a series of 10 patients with germ cell tumors reported a sensitivity of only 57% for TNB.
MEDIASTINAL CYSTS Congenital mediastinal cysts include a variety of bronchopulmonary malformations, such as bronchogenic, esophageal duplication, and neuroenteric cysts. The CT appearance and location of such cysts usually suggest the diagnosis. Aspiration of mediastinal cysts has been described in patients to confirm the diagnosis.z6In symptomatic patients, aspiration of a bronchogenic cyst may be used for diagnosis and treatment in adults.', 54
SUMMARY TNB of the mediastinum is an accurate, safe, and cost-effective diagnostic tool for the evaluation of mediastinal masses and lymphadenopathy. The technique is most useful in the staging of carcinoma, where it serves as a less expensive and minimally invasive alternative to mediastinoscopy for establishing unresectability. With recent advances in immunohistochemical and core biopsy techniques, TNB has become more accurate for establishing the initial diagnosis of lymphoma and for confirming recurrent disease. Core-needle biopsy has improved the accuracy of TNB and is particularly useful when fine-needle aspiration fails to yield a specific diagnosis, or when lymphoma or a noncarcinomatous lesion is suspected.
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Address reprint requests to Zenon Protopapas, MD Department of Radiology Hospital of Saint Raphael 1450 Chapel Street New Haven, CT 06511 e-mail: [email protected]