Physical Examination, Complementary Tests, and Functional Status Assessment

Chest computed tomography (CT) showed a large* 2.5 cm subcarinal lymph node with no associated pulmonary nodules, masses, or infiltrates. Although variations in normal node size are significant, depending on the location of the node, by convention, the upper limit of normal for mediastinal lymph nodes is considered to be 1 cm in the short axis, except in the subcarinal region, where an upper limit of 1.5 cm is generally used.¹ Micrometastasis can be present, however, in the absence of lymph node enlargement in patients with known or suspected lung cancer or other malignancy. Conversely, enlarged lymph nodes may just be post inflammatory or hyperplastic, especially in a patient without cancer risk factors. Very large lymph nodes (short axis >2 cm) in the middle mediastinum, including the subcarinal region, often reflect metastatic primary lung carcinoma, metastatic extrapulmonary carcinoma,^† lymphoma, tuberculosis, fungal disease (e.g., histoplasmosis, coccidioidomycosis), or sarcoidosis. A careful review of the chest CT is always warranted to avoid confusion with a bronchogenic cyst,^‡ a dilated azygos vein, esophageal varices, or a hiatal hernia.

This patient does not have a high pretest probability for sarcoidosis or another granulomatous disorder. In sarcoidosis, lymph node enlargement is seen in more than 80% to 95% of cases but predominates in the right paratracheal, aorto-pulmonary window, and hilar regions. CT scans show enlarged subcarinal lymph nodes in approximately 65% of patients.²

Although enlargement of lymph nodes in a single station can be seen in patients with Hodgkin’s disease, this most often occurs in the anterior mediastinum. Non-Hodgkin’s lymphoma, on the other hand, may show involvement of only one node group in 40% of cases, most commonly involving the superior mediastinum. Another lymphoproliferative disorder, the hyaline vascular type of Castleman’s disease, is often asymptomatic, presents as a hilar or localized mediastinal mass in any mediastinal compartment, and could be responsible for this patient’s large subcarinal lymph node.² The lack of multiple enlarged lymph nodes, constitutional symptoms, and normal laboratory markers makes rare lymphoproliferative disorders or leukemia less likely to explain this patient’s isolated subcarinal lymphadenopathy.

In active tuberculosis, right-side lymphadenopathy predominates (i.e., right paratracheal), but subcarinal nodes are abnormal in 50% of patients. Histoplasmosis and coccidioidomycosis are well-known causes of hilar and mediastinal lymphadenopathy. In view of the lack of pulmonary or systemic symptoms; chest radiograph or CT parenchymal abnormalities such as infiltrates, masses, or nodules; immunosuppression; or travel history to endemic regions, infectious causes are unlikely. This could, of course, represent primary lung carcinoma or metastatic adenocarcinoma, given the patient’s age, medical history, and smoking history. This could also be recurrent melanoma with mediastinal metastasis. Indeed, settings in which biopsy remains mandatory, even if imaging findings may suggest an alternative diagnosis (e.g., sarcoidosis), are represented by human immunodeficiency virus (HIV)-positive patients or patients presenting with lung infiltrates and/or enlarged hilar mediastinal positron emission tomography (PET)-positive lymph nodes with a clinical history of neoplasm. From this patient’s history and physical examination, review of imaging studies, and laboratory workup, no diagnosis could be made, thus warranting tissue diagnosis.

Comorbidities

Chronic obstructive pulmonary disease (COPD) is reportedly associated with an increased complication rate after bronchoscopy compared with that seen in patients with normal lung function. Concern for bronchospasm is increased, but premedication with inhaled short-acting agonists is not routinely recommended.³

Support System

This patient lived alone and had very few acquaintances. Given that our main differential diagnoses were cancer and sarcoidosis, we wondered whether he might eventually benefit from participation in support groups. For people with sarcoidosis, many of these groups are available online, and they may become necessary when physical and emotional problems associated with this disease arise. In self-help groups, patients might better cope with problems and concerns related to their disease and feelings of isolation.⁴ Similarly, for cancer, support groups focus on behavioral issues and symptoms, or on the expression of emotions. Most of these support programs are structured to ensure delivery of information and to provide emotional and social support, stress management strategies based on cognitive-behavioral approaches, and relaxation techniques. Group therapy helps patients gain emotional support from others with similar experiences and learn to use these experiences to reduce their fear of dying and uncertainty.⁵

Patient Preferences and Expectations

Our patient was anxious about his potential diagnosis and had many questions regarding his health. In such circumstances, effective communication skills improve a patient’s understanding of the condition and promote adherence to potential treatment regimens. Having good communication skills helps health care providers use time efficiently, avoid burnout, and enhance feelings of professional fulfillment. Blocking,* lecturing, depending on a routine, collusion,^† coercion, and premature reassurance are usually ill advised. One well-recognized and effective communication skill is the “ask-tell-ask technique,” which is based on the notion that providing patient education requires knowing what the patient already knows and building on that knowledge. Of course, building a relationship with a patient requires that the physician listen to the patient, understand and empathize with his perspectives, show compassion, and respect the patient’s agenda, even if it is not quite in line at all times with the way the physician might want to do things.⁶

Indications

In general, proposed indications for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) include nondiagnostic conventional TBNA, staging of the radiologically normal mediastinum in case of suspected or confirmed lung cancer, mediastinal restaging after induction chemotherapy, and, more commonly, diagnosis of mediastinal or hilar lymphadenopathy.⁷ In patients with a history of cancer, such as ours, the diagnosis of new mediastinal adenopathy suggests recurrence of malignancy; therefore this diagnosis needs to be excluded or confirmed. Because not all cases of PET-positive mediastinal adenopathy are due to cancer recurrence, lymph node sampling is usually warranted. In this patient with a newly discovered large subcarinal lymph node, a tissue diagnosis was going to be obtained using EBUS-guided TBNA with the patient under general anesthesia.

Contraindications

No contraindications to bronchoscopy under general anesthesia were noted.

Expected Results

The yield of EBUS-guided TBNA varies depending on the ultimate diagnosis and usually is higher for malignant than for benign disorders.

Team Experience

A single-institution study suggested that the learning curve for EBUS-TBNA for thoracic surgeons requires 10 procedures to reach the high yields reported in controlled clinical trials.¹⁸ In reality, however, the actual number of any given procedure performed does not account for the different rates at which people learn. With regard to EBUS-TBNA, one study assessed the learning curves of five independent operators by retrospectively applying cusum analysis* to the first 100 cases of each¹⁹; over a wide range of time, EBUS-TBNA competence was attained and the pooled sensitivity of EBUS-TBNA under conscious (moderate) sedation was 67.4%—lower than the high (>90%) rates reported in clinical trials.¹⁹

The usefulness of EBUS-TBNA resides in its clinical significance, accuracy, and reproducibility, which are usually shown to be excellent among pathologists experienced with these types of samples. Pathologists with little experience must climb what appears to be a steep learning curve.²⁰

Diagnostic Alternatives

Figure 19-2 Schematic map of commonly sampled hilar and mediastinal lymph node stations. Anatomic borders are based on the International Association for the Study of Lung Cancer (IASLC) lymph node staging system.

Cost-Effectiveness

It is debatable whether EBUS-TBNA is more cost-effective than mediastinoscopy for evaluation of mediastinal lymphadenopathy in non–small cell lung cancer.²⁸ In patients with a benign disease such as sarcoidosis, this issue has not been studied in a systematic fashion. Mediastinoscopy is usually considered the gold standard approach for undiagnosed mediastinal adenopathy, including sarcoidosis,²⁹ and before the introduction of EBUS in clinical practice, one cost-benefit analysis of mediastinoscopy for patients with suspected stage I sarcoidosis (asymptomatic bilateral hilar adenopathy) showed that benefits of mediastinoscopy would be minimal and likely would be offset by the procedure’s morbidity and mortality.³⁰

Informed Consent

The patient showed understanding of the indications, expected results, and potential complications, as well as alternative procedures, including observation, conventional TBNA, EUS-FNA, and mediastinoscopy. He preferred to proceed with EBUS-guided TBNA under general anesthesia.

Anesthesia and Perioperative Care

We performed the procedure with the patient under general anesthesia, but many operators perform it with the patient under moderate (conscious) sedation. Many studies reporting a high yield for the procedure were conducted with patients under general anesthesia.²⁸

Instrumentation

A dedicated EBUS bronchoscope, which offers direct real-time ultrasound imaging with a curved linear array transducer, was used. The frequency was set to 10 MHz. The associated ultrasound processor has adjustable gain and depth to optimize image quality, along with Doppler capabilities to distinguish vascular structures such as the heart and the inferior pulmonary veins; this is useful in sampling the subcarinal node. The 22 gauge acrogenic needle with an inner stylet allows for dislodgment of bronchial wall debris from the needle. This theoretically enhances the adequacy of the specimen (Figure 19-3). The needle guide system locks to the scope, and precise needle projection up to 4 cm is possible.

Figure 19-3 Images A, B, C, and D are consecutive still images captured from a video showing endobronchial ultrasound–transbronchial needle aspiration (EBUS-TBNA) during needle aspiration. A, The stylet pushed the bronchial wall debris inside the node. B, The needle is retracted, and the debris becomes evidently dislodged from the needle. C, The needle is advanced while aspiration is in process. D, The debris has completely disappeared, having been aspirated into the syringe. This probably explains how bronchial cells were present in the cytology specimen.

Anatomic Dangers and Other Risks

Concern has arisen regarding mediastinal abscess after EBUS-TBNA.³¹ In addition, pericarditis may occur in cases of inadvertent contamination of the pericardial space.³² With full-needle extension, the needle tip can be difficult to visualize, because small changes in the ultrasound angle can cause the needle tip to be out of plane with the ultrasound wave (see video on ExpertConsult.com) (Video IV.19.1). As a result, the pericardium (or vascular structures) may be violated but not visualized.³²