With sputum cytology a diagnosis of lung cancer can be established with a high specificity (99%) and without aggravating investigations for the patient. The
sensitivity however is low (pooled sensitivity of 66%) and depends highly on tumor location, sputum collection and processing logistics[22] In general it only has a limited role in diagnosing central endobronchial tumors.
Invasive diagnostics Evaluation of local disease
Almost all thoracic masses require tissue sampling for a definitive diagnosis and only a few diagnoses are made on radiologic appearance alone like bronchogenic or cardiac cysts and hydatid cysts.
Distinguishing benign disease from malignant disease is difficult on CT alone. PET is helpful in determining the need for further diagnostic interventions. When masses are
radiographies, 88% of benign diagnoses was based on integrated FDG-PET-CT without pathologic confirmation but with follow up [23].
To analyze a thoracic lesion without evidence of mediastinal or distant metastasis, several techniques are available to obtain tissue specimen for a pathological diagnosis.
For central lesions, bronchoscopy is preferred by many pulmonologists for its diagnostic sensitivity of 89% but for peripheral lesions the sensitivity decreases to 69% and even 33% for lesions smaller than 2 cm.[24]. The performance of
bronchoscopy can be increased for these small lesions when sampling is guided by a radial ultrasound (US) probe [25]. Another technique to improve results for sampling peripheral lung lesions is electromagnetic navigation but the impact on diagnostic results still has to be established and weighed against the costs[26].
Centrally located tumors invading or originating from the mediastinum or hilus or situated in close contact with the mediastinum can be diagnosed with bronchoscopy, endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS) depending on site and preference of the endoscopist. For EUS and EBUS both a diagnostic accuracy of 94% was reported for mediastinal masses of unknown origin and without central endobronchial involvement[27, 28].
Transthoracic needle aspiration (TTNA) or core tissue biopsies (CTB) performed under CT or ultrasound (US) guidance is very helpful to diagnose peripheral and pleural lesions. The sensitivity of CT guided percutaneous biopsies is 92% but the sensitivity depends obviously on size[22].
US guided transthoracic sampling has practical advantages over CT guidance because it is widely available, easy to learn and cheap. The real-time characteristic of US facilitates the biopsy procedure and increases safety. Lesions however must lie in contact with the pleura or originate from the pleura. If these criteria are fulfilled, high diagnostic success rates are possible[29-31].
For mesothelioma, image-guided sampling with either CT or US has a good diagnostic performance (sensitivity of 88%) [32]. Since mesothelioma presents in most cases with pleural effusion, thoracoscopic evaluation is preferred because immediate pleurodesis after evacuation of the effusion is possible. When
mesothelioma presents without pleural effusion or with loculated effusions, US guided CTB is a very useful and safe diagnostic alternative as was recently demonstrated in our own series[33].
Evaluation of nodal disease
The analysis of primary thoracic malignancies requires special attention for hilar, mediastinal and supraclavicular regions because lymphogenic spread of primary pulmonary tumors evolve to these nodes and determine the N-stage of disease. Hilar regions are easily accessible with ultrasound guided transbronchial needle aspiration (EBUS-TBNA). The excellent diagnostic characteristics of EBUS provide a diagnosis in most benign or malignant hilar disease sites[34, 35]. Although the finding of hilar metastasis in lung cancer does not preclude surgery, the extend of resection may depend on hilar involvement. Confirmation of hilar involvement during the
preoperative analysis is also important to determine the need for further assessment of upstream lymphogenic mediastinal spread.
The sensitivity of aspirations of hilar lymph nodes (stations 10 and 11) is not different from the sensitivity of aspiring mediastinal lymph nodes as was demonstrated in a large multicenter study[36].
Before US guided devices were developed, blind CT guided transbronchial needle aspiration (TBNA) was used to sample suspected mediastinal lymph nodes. Despite reasonably high accuracy rates in experienced hands and a high range of variation in yield described in reviews, a head to head comparison showed superiority of
EBUS[37].
Nowadays the preferred first step in the approach of suspected mediastinal metastatic disease is EBUS-TBNA, endoscopic ultrasound guided fine-needle
aspirations (EUS-FNA) or combinations of both. The diagnostic performance of these minimally invasive staging devices is outstanding and pushed surgical staging
(mediastinoscopy) to the background in the last decade [38]. In a recent study, mediastinal staging with EUS and EBUS followed by mediastinoscopy (in case of negative endoscopy results) had higher sensitivity than surgical staging alone[39]. Even in patients without visible mediastinal nodes on CT, EUS was able to detect metastasis in 25% of patients with lung cancer[40]. A report on EBUS in patients with a negative mediastinum on PET and CT, demonstrated in 9% of patients with stage I disease mediastinal metastasis[40][41]. The combination of both EBUS and EUS in a CT negative mediastinum was better than EBUS alone and almost significantly better than EUS alone[42].
Supraclavicular lymph nodes are frequently involved in thoracic malignancies and are important for prognosis and therapeutic decisions.
After visualization with PET-CT, adequate pathologic sampling by fine needle aspirations (FNA) is possible under US guidance with a diagnostic accuracy of 85%[31].
Evaluation of distant metastatic disease
If imaging shows abnormalities suspect for metastatic disease of a primary thoracic tumor the most efficient way to make a diagnosis and confirm disease stage is to perform needle biopsies. Pleural effusion, soft tissue, destructed bone, axillary, retromandibular, retroauricular, intercostal and skin metastasis can be sampled after palpation, under CT-guidance or under real-time US guidance with high success rates if not surrounded by air or covered by bone[31].
Deeper located lesions eg. in the left adrenal gland, the celiac region, the spleen, the pancreas or left liver lobe can be reached by EUS-FNA effectively[43, 44].
When imaging obviously demonstrates metastatic disease that is hard to reach for pathologic sampling, it is recommended in guidelines to approach easier accessible lesions like the primary tumor or a lymph node to obtain tissue specimen[22].
Nevertheless, clinical situations exist that require surgical procedures such as