The presence or absence of lymph node metastasis in lung carcinoma has a significant effect on the treatment policy and prognosis. Recent advances in medical technology has helped establish several new methods for diagnosis—fluorodeoxyglucose positron emission tomography (FDG-PET), PET-computed tomography (CT), transbronchial needle aspiration (TBNA), endobronchial ultrasound-guided TBNA (EBUS-TBNA), convex type EBUS-TBNA, endoscopic ultrasound-guided needle aspiration (EUS-NA), mediastinoscopy (MED), video-assisted MED (VAM), and video-assisted thoracoscopic surgery (VATS). The combined use of non-invasive and invasive methods for the diagnosis of lymph node metastasis is challenging and the features of each method must be carefully considered before choosing them (Table 1).
Non-invasive methods (diagnostic imaging)
Non-invasive diagnostic imaging such as CT, FDG-PET, and PET-CT, can detect all lymph nodes in the chest, however positive predictive values (PPVs) are not high in spite of a relatively high negative predictive value. Presently, there is no substitute for histological examination, and invasive methods are required only for the final diagnosis
Various criteria for the diagnosis of mediastinal lymph node metastasis by CT have been proposed such as the product of the major and minor axis, size of the transition by station, and change of the standard by tissue type (1). Since there is presently no consensus, lymph nodes measuring more than 1 cm at the minor axis are considered as metastatic. Several reports have used this method to confirm metastasis in case of a surgical adaptation; mean sensitivity and specificity are 44% and 89% (Table 2).
FDG-PET use has been ubiquitous due to the development of the delivery system. It was initially considered as a substitute for cytology or tissue sampling for the diagnosis of cancer, but it should be used with care as false positives and false negatives are seen occasionally (Table 3), and careful evaluation is necessary for the diagnosis of mediastinal lymph nodes. However, a good quality image, and fusion PET-CT provides accurate information for diagnosis (Table 4). An FDG is known to accumulate in lymph nodes in non-malignant conditions such as inflammation and the results can be pseudo positive as the specificity or negative predictive values are relatively low. The Z0050 trial (7) which analyzed the use of PET for staging in 303 cases of non-small cell lung carcinoma with surgical adaptation revealed an N1 detection rate of 13% vs. 42%, N2 and N3 detection of 32% vs. 58%, and sensitivity of 37% vs. 61%, by CT and PET scans respectively. This makes it possible to prevent unnecessary thoracotomies; however, a definite diagnosis is still necessary for confirmatory findings.
Invasive methods (cytological-pathological diagnosis)
It is necessary to perform an invasive procedure such as MED, VAM, VATS, TBNA, EBUS-TBNA, or EUS-NA (sensitivity of the needle biopsy is lower in the case of N0) even after PET scans show positive or negative lymph nodes. The most appropriate method is chosen according to the surgeon’s skill, experience, and lymph node position (Figure 1).
MED and VATS
Traditionally, lymph nodes sampling is carried under direct visualization, but currently it is done by viewing an image on the video monitor and is performed with more safety. Additionally, the accuracy of MED is similar to MED and VAM (Table 5). A report on MED in 202 cases after a PET scan (11) revealed that only 29 cases were PET-positive, while 65 cases were positive in MED; N2 and N3 stages were observed in 16 out of 137 PET negative cases. MED is considered to be a standard procedure by some for the diagnosis of mediastinal lymph nodes. VATS has been used to assess aorto-pulmonary window lymph nodes (level 5) and paraaortic lymph nodes (level 6). The overall results of this technique are summarized in Table 6. Specific results for stations 5 and 6 have not been reported but are likely to be better because these are easier to access than other mediastinal node stations. In specific cases, a combination of VAM and VATS is performed for the management of lung cancer (39).
Although TBNA has been used for some time, the rate of diagnosis is greatly affected by the experience of the examiner and is no longer used as a standard diagnostic tool. The results of studies on TBNA containing more than 100 cases is shown in Table 7, and reveals that mean specificity, sensitivity, PPV, and negative predictive values were 72%, 100%, 100%, and 63%, respectively.
The method of identifying the position of lymph nodes using ultrasound to increase the accuracy of the lymph node metastasis has progressed. The combined results of lymph node metastasis by EBUS-TBNA from various studies are summarized in Table 8.
The convex-operated ultrasonic bronchoscopic needle biopsy method (Convex probe EBUS-TBNA) has recently emerged as a popular technique. Yasufuku et al. was the first to perform an EBUS-TBNA using a convex type model (64). A total of 70 patients with a confirmed or suspected malignant tumor, with lymph nodes of more than 1 cm on CT (mediastinal lymph nodes 58 cases, hilar lymph nodes 12 cases) were analyzed in real-time. According to the report, 68 positive cases were identified from the patients with lymph nodes, and two cases were found to be negative. Forty-five cases were found to be malignant and 25 were benign. The test results showed that sensitivity, specificity, and accuracy were 95.7%, 100%, and 97.1%, respectively. The patients had good results, and no complications were reported. In another study, Yasufuku et al. compared CT, PET, and EBUS-TBNA in patients with lung cancer or suspected surgical adaptation in published reports and reported that their respective sensitivities were 76.9%, 80.0%, 92.3%; specificities were 55.3%, 70.1%, 100%; and accuracies were 60.8%, 72.5%, 98.0%. EBUS-TBNA was found to have excellent results (65).
The CT is inaccurate and so is the PET, although it increased the possibility of different diagnoses. The TBNA is a blind procedure, and the CT-guided cytology is more restrictive than the conventional ultrasound guided cytology, and the standard MED is also restricted and invasive. Although a TBNA cannot reach levels 5, 6, 8, 9 of lymph nodes, it is possible to access levels 10 and 11, and the total mediastinum can be reached when combined with EUS-NA. In addition, if the MED and EBUS-TBNA are compared, the EBUS-TBNA may reduce the necessity of a MED without complications; however, it is necessary to assess the possibility of micro metastases by EBUS-TBNA.
An EUS-NA is a transesophageal ultrasound endoscope, which can access parts unreachable by mediastinoscope and is more accurate than a PET or CT; its PPV is particularly good (Table 9). An EUS-NA and an EBUS-TBNA are complementary technologies and can be adapted to be used together (Table 10).
Although techniques for mediastinal lymph node diagnosis should be chosen depending on the experience and skill of the surgeon, the relatively minimally invasive EBUS-TBNA is preferred to obtain a histological diagnosis. However, more advanced technologies to match the pathological diagnosis by PET imaging are expected in the future.
We would like to thank Editage (www.editage.com) for English language editing.
Conflicts of Interest: The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Cite this article as: Sawabata N. Mediastinal lymph node staging for lung cancer. Mediastinum 2019;3:33.