Our primary endpoint was to determine the etiology and prevalence of malignancy for hypermetabolic and enlarged hilar/mediastinal LNs in patients with a previously diagnosed extrapulmonary malignancy during the oncologic follow-up period and the diagnostic yield of EBUS-TBNA in these LNs. We determined that in patients with a proven extrapulmonary malignancy, only 37.5% had malignancy in recently arising mediastinal or hilar pathologic LNs. Also, the sensitivity, specificity, and negative predictive value of EBUS-TBNA for malignancy were found to be 83.3%, 100%, and 90.9%, respectively. When all malignant and nonmalignant diseases were taken into consideration, the sensitivity, specificity, and negative predictive value were 89.2%, 100%, and 86.9%, respectively. The diagnostic accuracy of EBUS-TBNA was found to be 93.7%.
TBNA is a safe, minimally invasive, and repeatable technique for mediastinal LN sampling. However, since it is a blind method, it has a moderate diagnostic yield. Its utility can be improved with guidance by endoscopic or endobronchial ultrasonography.[4
] Yasufuku et al
. reported the sensitivity, specificity, and negative predictive value of EBUS-TBNA as 94.6%, 100%, and 89.5%, respectively. The accuracy was 96.3%.[7
] In a more recent study, EBUS-TBNA was found to have better diagnostic yield, with 95% sensitivity, 100% specificity, 93% negative predictive value, and 97% accuracy.[8
Endoscopic ultrasound (EUS) is another potential minimally invasive and inexpensive alternative for mediastinal LN sampling. To date, studies have shown that EBUS-TBNA has higher diagnostic yield in comparison to EUS-guided fine needle aspiration (EUS-FNA).[9
] One possible explanation for this is that EBUS allows access to a higher number of LNs.
Mediastinoscopy is the gold standard for mediastinal LN sampling, with 80 to 85% sensitivity, 89% negative predictive value, and 100% positive predictive value. However, it is an invasive procedure necessitating general anesthesia, hospital admission, and higher cost. Although generally safe, it still has the potential risks of major morbidity and mortality. Moreover, it is limited in accessing the aortopulmonary window and posterior subcarinal and hilar regions. EBUS, on the other hand, allows access to posterior the subcarinal and hilar regions. It can safely be done as an outpatient procedure, carries much lower morbidity, and can easily be repeated if necessary.[4
In a prior report about the role of EBUS-TBNA in diagnosing mediastinal or hilar LNs in cases with extrapulmonary malignancies, EBUS-TBNA was found to have a sensitivity, accuracy, and negative predictive value of 88%, 93%, and 85%, respectively.[11
] A relatively high (38.6%) number of cases were confirmed to have benign diagnoses.
Park et al
. evaluated mediastinal LNs in 39 patients with extrathoracic malignancy and 20 patients with no known primary malignancy. The most common sites of primary malignancies in their study population were colon, liver, kidney, and breast. They included cases who underwent EBUS-TBNA for suspected mediastinal LN metastases according to CT findings (short axis larger than 1 cm) or PET-CT results. They found that 40 of the 59 patients were found to have mediastinal metastases using any diagnostic tool. EBUS-TBNA findings indicated that 34 of the 59 patients were positive for malignancy. They reported that the EBUS-TBNA sensitivity and specificity for the detection of mediastinal malignancy in patients with a previous extrathoracic malignancy were 96.3% and 100%, respectively, and 61.5% and 100% in patients without a previously diagnosed malignancy. The overall sensitivity and specificity were 81.0% and 100%, respectively.[12
Tournoy et al
. analyzed 92 patients with extrathoracic malignancy with a suspicion of mediastinal or hilar spread, who underwent EBUS-TBNA. The majority of the study population (nearly 70%) had head and neck carcinomas, colorectal carcinomas, and renal cell carcinomas; 73% had PET-CT scans and 97% of these showed positive FDG uptake. As a final diagnosis, 29 cases had benign conditions (reactive adenopathy, sarcoidosis, silicosis, and hamartoma). They reported the sensitivity and negative predictive value of EBUS in detecting mediastinal spread of extrathoracic malignancies as 85% and 76%, respectively.[13
] In a multicenter study, intrathoracic LN metastases from an extrathoracic malignancy were evaluated by EBUS-TBNA. EBUS-TBNA was found to have 87% sensitivity, 73% negative predictive value for malignancy, and 88% overall accuracy. This analysis concluded that EBUS-TBNA diagnosed mediastinal or hilar metastases in 44% of the patients, new lung cancer in 12% of the patients, and sarcoidosis in 9% of the patients.[14
] In our study, we diagnosed mediastinal or hilar LN metastasis in 31.2% of the patients but we did not detect any new lung cancer.
In our study, the most common previously diagnosed primary malignancies were breast carcinoma, followed by gastrointestinal malignancies and genitourinary malignancies. Park et al
. reported that the most common sites of primary malignancies in their study population were colon, liver, kidney, and breast, respectively.[12
] In the study of Tournoy et al
., head and neck carcinomas were the most common primary malignancies followed by colorectal carcinomas and renal cell carcinomas.[13
] In our study, all EBUS-TBNA performed LNs were hypermetabolic at PET-CT. In the study of Tournoy et al
., PET scan was available only in 73% of cases (positive in 97%), while in the other patients the size of the LN or just the presence of the lung lesion explained the clinical suspicion for metastasis.[13
Consistent with previous reports, our findings demonstrate similar diagnostic accuracy of EBUS-TBNA for detection of malignant LNs. The sensitivity and specificity for detecting malignancy in our study was 83.3% and 100%, respectively. Another important finding in our study is the high prevalence of benign conditions involving mediastinal or hilar LNs in patients with confirmed malignancies and the diagnostic value of EBUS-TBNA in these diseases. For granulomatous diseases (six tuberculosis and four sarcoidosis), the diagnostic accuracy and sensitivity were 100%. In a patient with a confirmed malignancy, a recent onset of a LN is often thought to be metastasis; however, granulomatous inflammation or other benign conditions are ultimately diagnosed in many cases. Tuberculosis accounts for an important number of cases in areas where the prevalence of tuberculosis is high (i.e., 30/100 000 in Turkey).[15
] Without definitive histopathological confirmation, many LNs in cancer patients may be falsely attributed to recurrence of malignancy and unnecessary toxic treatments may be administered. Therefore, definitive tissue diagnosis is mandatory to consider a LN metastatic.
We conclude that it must be kept in mind that not all newly occurring LNs in cancer patients are malignant. Benign conditions constitute to a relatively high percentage of the final diagnoses of these lymphadenopathies. EBUS is a safe, minimally invasive, and accurate procedure for diagnosing mediastinal or hilar lymphadenopathy in patients with known extrathoracic malignancy. Nevertheless, due to the possibility of underdiagnosis, an invasive technique is indicated when the results are negative.