Key Points
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Criteria exist to differentiate benign from malignant mediastinal lymph nodes, but used alone these criteria are not sufficiently accurate. Endoscopic ultrasonography-guided fine-needle aspiration (EUS FNA) is required to make sound clinical decisions.
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The overall accuracy for the diagnosis of posterior mediastinal malignancies with transesophageal EUS FNA is greater than 90%.
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The diagnosis of lymphoma in the posterior mediastinum is made by cytology and flow cytometry studies on EUS FNA and core biopsy specimens.
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EUS FNA can be valuable in helping to establish a diagnosis of granulomatous disease involving the mediastinum (sarcoidosis, histoplasmosis, tuberculosis).
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Most mediastinal cysts are benign, and because the risk of infection is high, EUS FNA should not be performed. If a high suspicion of malignancy exists, the cyst should undergo one puncture and be fully drained, and antibiotics should be administered.
Transesophageal endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) offers minimally invasive access for the evaluation and biopsy of posterior mediastinal lesions. Usually these lesions are first detected with computed tomography (CT), but occasionally lesions are incidentally detected during passage of the echoendoscope through the esophagus on the way to image gastrointestinal or pancreatic disease. Transesophageal EUS is well suited to image the posterior mediastinum but is unable to access or visualize much of the anterior mediastinum. The cardiac structures in the middle mediastinum are well visualized and there are a few reports of EUS FNA of atrial and pericardial lesions. This chapter focuses on EUS diagnosis of posterior mediastinal masses, lymph nodes, and cysts. The role of EUS FNA in lung cancer staging is discussed in Chapter 7 .
Endoscopic Ultrasonography Evaluation of Enlarged Posterior Mediastinal Lymph Nodes
Endoscopic Ultrasonography Appearance of Benign Posterior Mediastinal Lymph Nodes
Mediastinal lymph nodes are commonly encountered during EUS for nonthoracic indications. The most common EUS feature of these benign lymph nodes is a triangular or crescent shape, with possibly an echogenic center ( Fig. 9.1 ). The echogenic center represents the hilum of the lymph node. Intranodal blood vessels also suggest benign lymph nodes.
The prevalence of posterior mediastinal adenopathy varies with geographic region of the world, depending on the risk of endemic pulmonary infections. A prospective study from England and Sweden revealed that 62% of patients had posterior mediastinal lymph nodes, with a mean of 1.4 lymph nodes per patient. Nearly all of these lymph nodes had a short-axis diameter of 5 mm or less.
Endoscopic Ultrasonography Appearance of Malignant Posterior Mediastinal Lymph Nodes
EUS findings associated with malignant lymph nodes include round shape, short-axis diameter greater than 10 mm, hypoechoic echotexture, and well-demarcated borders ( Fig. 9.2 , Video 9.1 ). If all four features are present in a lymph node, the chance of malignancy may be as low as 50% with a 60% accurracy. For this reason, tissue sampling is important to obtain diagnostic cytopathologic material of enlarged mediastinal lymph nodes.
Endosonographic Features of a Malignant Lymph Node in the Posterior Mediastinum
Elastography has been reported in the evaluation of mediastinal lymph nodes and masses. However, the sensitivity and specificity (in the range of 80% to 90%) of this technique are lower than those of transesophageal or transbronchial EUS-guided FNA (>90% range). Therefore elastography needs further assessment and improvement before widespread use of this method can be recommended.
Transesophageal Endoscopic Ultrasonography Fine-Needle Aspiration of Mediastinal Lymph Nodes
Table 9.1 shows the types of pathologic lesions that can be diagnosed with transesophageal EUS FNA cytology.
| Malignant | Benign |
|---|---|
| Lung cancer | Reactive |
| Primary or metastatic | Granulomatous disease |
| NSCLC | Histoplasmosis |
| Small-cell | Sarcoid |
| Mesothelioma | Tuberculosis |
| Lymphoma | Duplication cyst |
| Metastatic from nonlung primary | Leiomyoma |
| GIST | Mediastinitis/abscess |
| Spindle cell neoplasm | Pleural effusion |
Technique for Endoscopic Ultrasonography Fine-Needle Aspiration of Posterior Mediastinal Lesions
Cross-sectional imaging studies including CT, magnetic resonance imaging (MRI), and positron emission tomography (PET) exams of the chest and abdomen should be reviewed to identify the location of the lesion of interest and its relative location to surrounding structures. This will determine whether a lesion is accessible by transesophageal EUS FNA and assist in locating the lesion with the linear array echoendoscope. If the EUS is performed to evaluate enlarged mediastinal or periesophageal lymph nodes, it is advisable to perform an esophagogastroduodenoscopy (EGD) with a forward-viewing scope first to assess for any esophageal or gastric pathology that may explain the lymphadenopathy. Identification of a luminal mass amenable to biopsy may preclude the need for EUS FNA. The linear echoendoscope is passed into the esophagus and stomach, and then ultrasound imaging is performed as the scope is withdrawn with sweeping motions in a clockwise and counterclockwise fashion to obtain a 360-degree view with the linear echoendoscope. The liver, celiac axis, left adrenal gland, and posterior mediastinum are evaluated for other lymphadenopathy in other lymph node regions, ascites, liver masses, and for other clues as to an advanced malignancy or lymphoma.
During the EUS evaluation of enlarged mediastinal lymph nodes, there are usually several identified. These may be discrete, separate lymph nodes, which is often the case in malignancy, or a conglomeration of matted lymph nodes which can be seen in granulomatous disease. The location of each lesion is documented in terms of the distance in centimeters of the transducer tip from the incisors and the anatomic site (e.g., subcarinal, left paraesophageal, right paratracheal, aortopulmonary window) to assist in future identification and comparison on future examinations. For each lesion, the short-axis and long-axis dimensions are measured, and the degree of demarcation is described (well demarcated or poorly demarcated). The shape is described in terms of round, oval, triangular, draping, or matted. The echogenicity is described in terms of hypoechoic, hyperechoic, heterogeneous, or anechoic.
Transesophageal EUS FNA is generally performed using a linear array echoendoscope and usually a 22- or 25-gauge aspiration or core biopsy needle. Given the esophageal location of mediastinal FNA, the scope is generally straight which allows for easier movement and maneuverability of the needle compared to transduodenal FNA where the scope is more angulated. If there is more than one possible lesion to sample for biopsy, the lesion that is most likely to be malignant (i.e., rounder, larger, more hypoechoic, more demarcated; Fig. 9.3 ) is chosen as the target. However, the presence of intervening blood vessels and distance from the esophagus should also be taken into account as this may make FNA of certain lymph nodes easier and safer. The Doppler imaging function should be utilized to examine the FNA needle trajectory to ensure there are no significant vessels that may complicate FNA. Needle passage through an adjacent blood vessel can usually be avoided by displacing the esophagus with the scope tip to create a different needle path. However, there have been case reports where transaortic EUS FNA puncture with 22- and 25-gauge needles was successfully and safely used for biopsy of mediastinal lesions where the aorta was between the lesion and the esophagus. Once the lesion has been brought into view, the needle is passed through the esophageal wall and into the lymph node under constant ultrasound visualization. The internal stylet (optional) is then removed, intermittent suction may be applied, and the needle is moved back and forth within the lesion to sample the edges as well as the center of the lesion ( Video 9.2 ).
Technique of Transesophageal Endoscopic Ultrasonography-Guided Fine-Needle Aspiration
The needle is then pulled out of the scope, the stylet is slowly reintroduced into the needle, and the aspirated material is slowly expressed either onto a microscope slide and/or into medium for cell block pathology or flow cytometry. The availability of immediate cytologic evaluation may increase the diagnostic yield and allow for fewer passes. If immediate cytologic evaluation raises the possibility of lymphoma or lymphoma is suspected based on clinical history, additional passes should be obtained for flow cytometry and fine-needle core biopsies should be considered. Several core needles are now available which are capable of obtaining larger samples of tissue for histopathology; these can provide tissue architecture which is usually necessary to differentiate the various subtypes of lymphoma. If immediate cytologic evaluation suggests infection, additional passes may be made for microbiologic studies. A final diagnosis is provided only after the cytopathologist has evaluated all processed specimen slides and cell block material. In general, diagnostic material from posterior mediastinal lesions can be obtained within two to five EUS FNA cytology passes, and one to two core biopsy passes.
Endobronchial Ultrasound
Endobronchial ultrasound (EBUS)-guided FNA has become increasingly available, especially as performed by interventional pulmonologists and thoracic surgeons. EBUS provides unique access to lymph nodes and masses adjacent to the trachea, as well as the subcarinal and perihilar areas. The combination of transesophageal and transbronchial EUS provides nearly complete mediastinal evaluation and avoids risks of mediastinoscopy or other more invasive surgeries to obtain a tissue diagnosis.
Accuracy of Endoscopic Ultrasonography Fine-Needle Aspiration for Diagnosing Posterior Mediastinal Lesions
The overall accuracy rate for diagnosing posterior mediastinal malignancy with transesophageal EUS FNA cytology is approximately 93%. A meta-analysis of 76 studies ( n = 9310 patients) found a pooled sensitivity of 88% and specificity of 96%. Table 9.2 shows a summary of the accuracy rates for EUS FNA for diagnosing malignancy in posterior mediastinal lesions. Several studies showed that the diagnostic accuracy of malignant posterior mediastinal lymph nodes increases with the use of EUS FNA cytology over simple EUS appearance alone.
| Authors (Year) | n | Sensitivity (%) | Specificity (%) | Accuracy (%) | PPV (%) | NPV (%) |
|---|---|---|---|---|---|---|
| Giovannini and coworkers (1995) | 24 | 81 | 100 | 83 | — | — |
| Silvestri and coworkers (1996) | 27 | 89 | 100 | — | — | — |
| Gress and coworkers (1997) | 52 | 95 | 81 | 96 | — | — |
| Hünerbein and coworkers (1998) | 23 | 89 | 83 | 87 | — | — |
| Serna and coworkers (1998) | 21 | 86 | 100 | — | — | — |
| Vazquez-Sequeiros and coworkers (2001) | 82 | 96 | 100 | 98 | 94 | 100 |
| Fritscher-Ravens and coworkers (2000) | 153 | 92 | 100 | 95 | — | — |
| Wallace and coworkers (2001) | 121 | 87 | 100 | — | — | — |
| Devereaux and coworkers (2002) | 49 | — | — | 94 | — | — |
| Larsen and coworkers (2002) | 79 | 92 | 100 | 94 | 100 | 80 |
| Hernandez and coworkers (2004) | 59 | — | — | 84 | — | — |
| Savides and coworkers (2004) | 59 | 96% | 100 | 98 | 100 | 97 |
| Eloubeidi and coworkers (2005) | 104 | 93% | 100 | 97 | 100 | 97 |
| Overall | 91 | 97 | 100 | 97 | 99 | 94 |
Risks of Endoscopic Ultrasonography Fine-Needle Aspiration of Posterior Mediastinal Lesions
EUS FNA of posterior mediastinal lesions is safe, with few complications reported in the thousands of patients described in retrospective and prospective trials. A pooled review of prospective studies revealed a 0.43% risk of complications with mediastinal EUS FNA, mostly pain, bleeding, and perforation. However, several cases of mediastinitis have also been reported after transesophageal EUS FNA. A case of mediastinitis with osteomyelitis has also been reported in the setting of FNA. Although most of these cases have involved mediastinal cysts, some patients with solid lesions (nodes or masses) have also developed post-EUS FNA mediastinitis.
There is a single case of esophageal wall seeding with tumor after EUS FNA of a posterior mediastinal malignant node from a primary gastric cancer. This occurred in the setting of several passes using a large 19-G needle, which may have contributed to the seeding. A case of esophagomediastinal fistula formation after EUS FNA of a posterior mediastinal lymph node resulting from tuberculosis has also been reported. Two cases of esophageal wall rupture in the setting of FNA requiring thoracotomy have been reported. Despite rare reports of severe complications, EUS FNA and EBUS FNA of mediastinal lesions appear to be very safe. Two large, retrospective studies with 16,181 and 16,750 EUS and EBUS procedures with mediastinal FNA demonstrated a mortality of 0 to 0.04% and an adverse event rate of 0.22%.
Endoscopic Ultrasonography Fine-Needle Aspiration Compared With Other Modalities for Evaluation and Biopsy of Posterior Mediastinal Lymph Nodes or Masses
The noninvasive imaging modalities commonly used to evaluate enlarged mediastinal lymph nodes are CT scan and PET scan. These modalities have mostly been compared with EUS FNA in the setting of suspected lung cancer. Both EUS alone and EUS FNA have been shown to be more accurate than CT alone (using short-axis lymph node diameter >10 mm) for diagnosing malignant posterior mediastinal lymph nodes.
PET scanning detects increased uptake of the glucose analog 18 F-2-deoxy- d -glucose. Increased uptake can occur both in malignancy and in inflammatory conditions. A meta-analysis comparing CT with PET scan for evaluation of mediastinal adenopathy in patients with lung cancer revealed that when the CT scan showed enlarged lymph nodes, the sensitivity of PET was 100%, but the specificity was only 78%, in contrast to no CT findings of lymph node enlargement (sensitivity of 82% and specificity of 93%). The low specificity of PET scan implies that 22% of patients with PET-positive enlarged mediastinal lymph nodes actually do not have malignancy (false-positive PET scan). Therefore these PET-positive lymph nodes should undergo tissue biopsy if it is critical to be certain about the diagnosis of malignancy in the nodes. Several studies confirmed the poor specificity of PET compared with transesophageal EUS FNA. One large study found that the EUS FNA positive predictive value of malignancy was 100% compared with 40% for PET. A recent study comparing EUS FNA to PET CT demonstrated superior performance of EUS FNA in the evaluation of mediastinal and upper abdominal lymphadenopathy. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of EUS FNA were 91.3%, 100%, 100%, 92.5%, and 95.8%, respectively. The same values for PET CT were 75%, 25%, 50%, 50%, and 50%, respectively. The combination of PET and EUS FNA improves the specificity and overall accuracy as compared with PET alone.
The other modalities for obtaining tissue samples from posterior mediastinal lesions are percutaneous CT-guided transthoracic FNA, bronchoscopy with transbronchial biopsy, EBUS with transbronchial FNA, and mediastinoscopy with biopsy. Percutaneous transthoracic FNA is generally not used for biopsy of posterior mediastinal lesions because of the risk of pneumothorax or puncture of a major vessel. The diagnostic yield of transbronchial FNA without EBUS is lower than that of EUS FNA, whereas EBUS has a similar diagnostic yield in the biopsying of adenopathy locations visualized by both transesophageal EUS and EBUS. Mediastinoscopy is associated with greater difficulty (and potentially increased risk) in accessing the lymph nodes in stations that are the most easily visualized and biopsied with transesophageal EUS FNA (subcarina, posterior aortopulmonic window, and periesophageal stations). Therefore the less invasive EUS FNA and EBUS FNA are increasingly replacing mediastinoscopy at most referral centers.
Differential Diagnosis of Enlarged Posterior Mediastinal Lymph Nodes
Enlarged mediastinal lymph nodes are usually defined by CT findings of lymph nodes 10 mm diameter or larger. In the setting of a peripheral lung mass and mediastinal lymph nodes, the main concern is primary lung cancer with metastatic disease. The finding of numerous posterior mediastinal and hilar lymph nodes raises the question of whether the diagnosis is benign (sarcoid, histoplasmosis, tuberculosis, reactive) or malignant (especially lymphoma). Often the clinical history suggests the origin.
Malignant Posterior Mediastinal Lymph Nodes
The rate of diagnosis of malignancy with EUS FNA of posterior mediastinal nodes in patients without a known diagnosis of cancer varies depending on prior pulmonary evaluation and local referral patterns; however, it is approximately 50%, and most cancers are of pulmonary origin. Table 9.2 shows the reported operating characteristics of EUS FNA for diagnosing malignancy in posterior mediastinal adenopathy. The overall sensitivity, specificity, and accuracy are greater than 90%.
Metastatic Disease From Thoracic Tumors
Lung Cancer
Most thoracic tumors originate as primary lung cancer. This disease is generally divided into small-cell and non–small-cell lung cancer (NSCLC) pathologic types, and 80% of lung cancer is NSCLC. EUS FNA cytology can diagnose and stage metastatic lung cancer to mediastinal lymph nodes from both small-cell carcinoma and NSCLC. In addition to lymph nodes, lung cancer can present as a mediastinal mass due to metastatic spread. Further discussion of EUS FNA for lung cancer staging is discussed in detail in Chapter 7 .
Mesothelioma
Mesothelioma is a much rarer pleura-based tumor of the thoracic cavity associated with asbestos exposure and can present with pleural-based tumors and effusions ( Fig. 9.4 ). EUS FNA can diagnose mesothelioma metastases in posterior mediastinal lymph nodes. The combination of transbronchial EBUS FNA and transesophageal EUS FNA may increase the sensitivity of diagnosed metastatic mesothelioma, especially because mesothelioma can also metastasize or directly extend below the diaphragm into the abdominal cavity, where EUS FNA can detect metastases.
Metastatic Disease From Extrathoracic Malignancy
Various tumors result in metastases to the posterior mediastinum, and they appear as either a lymph node or a mass ( Fig. 9.5 ). Metastatic lymph nodes from breast, colon, renal, testicular, laryngeal, pancreas, and esophageal cancers have been diagnosed by transthoracic EUS FNA.
Lymphoma
EUS FNA and fine-needle biopsy (FNB) can diagnose lymphoma in posterior mediastinal lymph nodes by obtaining material that can be evaluated with cytology, histopathology, flow cytometry, and immunohistochemistry. In one study, the sensitivity of lymphoma diagnosis increased from 44% to 86% with the addition of flow cytometry and immunocytochemistry. Nodal architecture is often necessary to distinguish lymphoma subtypes and it is therefore recommended that a core biopsy needle be utilized when lymphoma is suspected, either based on initial cytology results or clinical picture to avoid a repeat EUS procedure for tissue diagnosis.
Benign Posterior Mediastinal Lymph Nodes
Reactive Lymph Nodes
Reactive lymph nodes are usually the result of previous pulmonary infections. Cytologically, they appear as a mixture of lymphoid elements, with reactive and hyperplastic features.
Granulomatous Lymph Nodes
EUS FNA cytology is able to demonstrate granulomatous disease in lymph nodes. The cytologic appearance is that of histiocytes in a swirling pattern. The differential diagnosis usually includes sarcoid, histoplasmosis, tuberculosis, and coccidiomycosis. The presence or absence of caseating granulomas does not necessarily help with the diagnosis because caseation can be seen in all of these disorders. Sending EUS FNA cytology material for fungal stains and culture, acid-fast bacillus stain, and mycobacterial culture can help to determine whether the cause is infectious. Lymphoma is also rarely associated with granulomas.
Sarcoid
Sarcoid is a multisystemic granulomatous disease of unknown origin. It typically involves mediastinal lymph nodes. The final diagnosis is made by using clinical criteria and by excluding other causes of granulomatous disease. No pathognomonic laboratory or pathologic finding exists for this disease. Elevated serum angiotensin-converting enzyme levels may suggest this diagnosis. The diagnosis of noncaseating granulomas in a mediastinal lymph node supports the diagnosis of sarcoid.
The usual endosonographic appearance of posterior mediastinal sarcoid is the presence of numerous enlarged lymph nodes ( Fig. 9.6 ). EUS FNA can obtain granulomatous material to support the diagnosis of sarcoid with a high degree of accuracy ( Table 9.3 ). One retrospective study found the sensitivity and specificity of EUS FNA for diagnosing granulomas in suspected sarcoid to be 89% and 96%, respectively. Another study found that EUS FNA demonstrated noncaseating granulomas in 41 of 50 patients (82%) with a final clinical diagnosis of sarcoidosis. A study of patients with bilateral hilar lymphadenopathy, in whom EUS FNA was performed with a 19-G needle and whose material was sent for both cytologic and histopathologic examination, found that 94% of the histopathology specimens had noncaseating granulomas, compared with 79% of the cytology specimens ( P = .04). Studies suggest that sarcoid lymph nodes aspirated via the transesophageal route may be at increased risk for mediastinitis (albeit rare) compared to EBUS FNA. EBUS FNA has been shown to be superior to blind transbronchial FNA in the diagnosis of sarcoid.
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