The last decades have witnessed a huge revolution of interventional pulmonology’s role in diagnostic work-up and management of thoracic diseases. The advent of transbronchial aspiration techniques represents one of the most important advances in this context, as it has extended pulmonologists’ perspective beyond the airways, leading to obtain both diagnosis and staging of cancers during the same procedure, avoiding additional or more invasive interventions [1].

Conventional transbronchial needle aspiration (c-TBNA) came first into light in 1949 [2], but the first prototype needle for flexible bronchoscope was designed by Ko-Pen Wang in the early 1980s [3]. Since then, several studies, worldwide, have confirmed the valuable cost-effectiveness and safety profile of TBNA in different clinical scenarios. This procedure, indeed, is currently included in the diagnostic work-up of central and peripheral lesions as well as of hilar/mediastinal lymphadenopathies and masses [4].

More recently, advances in technology have led to development of imaging-assisted TBNA by using reflecting sound waves, named as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) [5]. Echoendoscope offers the operator a real-time visualization of lesions and surrounding structures, enabling to direct the tip of the needle to the target area. Although a superiority of the imaging-guided over the conventional procedure could be reasonable supposed by indirect comparisons of pooled estimates from literature [6, 7], the lack of evidence-based data from randomized studies does not yet allow to definitely assess the best diagnostic strategy in different clinical settings. To date, indeed, only two randomized investigations, limited on sarcoidosis patients, have been actually performed [8, 9]. Moreover, in daily practice, because of the higher costs, timing and specific skills related to more advanced technology, TBNA is still the only available diagnostic tool in several institutions.

The main purpose of the present chapter is to review the current evidence on diagnostic role of c-TBNA for hilar/mediastinal as well as for peripheral lesions, nowadays, in the context of “endobronchial ultrasound era”.

The role of c-TBNA for the diagnosis and staging of hilar/mediastinal lesions is well established. It is a safe, low-cost, minimally invasive sampling technique that allows to both diagnose and stage mediastinal diseases while avoiding additional procedures and unnecessary surgical approaches. Some authors referred to this technique as “blind TBNA”, as it is not possible to directly visualize the target, but we consider more suitable to use the term “conventional” or “standard”, since a deep evaluation of computed tomography (CT) scans and a thorough knowledge of intraluminal landmarks and mediastinal anatomy actually allow an indirect, but accurate, localization of the lesions. In order to guide operators to the correct puncture site, in 1994, Wang et al. proposed a map of 11 lymph node stations accessible from the airways, describing well-defined endobronchial landmarks that correlate with specific CT features [10]. The first step towards performing c-TBNA is, indeed, to properly choose the exact puncture site after a careful CT scans evaluation, in order to assess the location of mediastinal lesions and its relationship with trachea or bronchi.

The subsequent steps deal with the technique in itself and can be summarized as follows: (a) insert the needle into the working channel of the bronchoscope while keeping the instrument as straight as possible and after having verified that the tip of the needle is completely retracted into the sheath in order to avoid any damage to the instrument; (b) extract the tip of the needle from the sheath only when the tip of the catheter is visible outside the bronchoscope (Fig. 27.1a); (c) keep only the needle and the distal metal hub of the catheter outside the bronchoscope, in order to facilitate the movement of the instrument inside the airways (Fig. 27.1b); (d) anchor the tip of the needle in the intercartilaginous space corresponding to the puncture site and bend the bronchoscope in the same direction where the needle should penetrate (Fig. 27.1c); and (e) insert the needle as perpendicularly as possible through the tracheobronchial wall (Figs. 27.1d and 27.2). Three main techniques have been described to insert the needle. The first one, named “jabbing method”, consists in applying a firm and quick jab to the catheter while the scope remains fixed. The second technique is called “pushing” or “piggyback” method, according to which the operator fixes the catheter to the scope at the insertion port of the working channel with his/her little finger or with the other hand (Fig. 27.3). The bronchoscope and the needle are, then, pushed forward together by the operator himself/herself using the other hand or by an assistant. The last method is the “hub against wall” technique, according to which the needle is initially kept in, the catheter hub is pushed against the wall, and the needle, then, is brought out and penetrates into the target [11]. No evidence-based data on a direct comparison between these methods are available, but, overall, the piggyback technique is considered the preferred option by the experts, as it allows a better perpendicular penetration of the needle [11]. To our experience, the “hub against wall” technique may be useful in case of c-TBNA at smaller airways level, as it could be difficult in this context to bend the scope with the needle outside the sheath.

Once the needle has been properly inserted, a suction is applied through the syringe attached to the proximal end of the needle, and the catheter should be quickly moved up and down for no longer than 10 s overall, in order to avoid coagulation of blood. Another crucial step is represented by a proper handling of the material obtained, blown by an air-filled syringe onto a slide. It is, then, smeared using another slide and immediately fixed in alcohol 95%. If tissue cores are present on the slide, these should be gently removed with a small forceps and put in formalin. If histological needle are employed, the material can be directly put into a formalin test tube. Different types of needle are, indeed, available on the market, with sizes ranging from 19 to 22 gauge (G). 21-G and 22-G needles are intended for cytological evaluation, while the 19-G allows to provide tissue core for histological assessment [4]. There is not yet a definite consensus on the number of specimens needed to optimize the diagnostic yield of TBNA, although it is reasonable to propose a minimum of three needle passes or two “adequate” samples [1]. In this context, the rapid on-site evaluation (ROSE) of cytologic smears has been suggested to play an important role, as it allows to assess the adequacy of specimens obtained, providing relevant information to the operator, who can modify the technique or the target site in case of inconclusive results [12]. Furthermore, the operator can determine whether additional material needs to be collected to further characterize the lesions in ancillary studies, as, in the era of targeting lung cancer therapy, a sample should be considered as diagnostic only if it provides an amount of cells suitable for both immunocytochemical and molecular studies [13].

The whole procedure is performed under local anaesthesia with conscious sedation in the endoscopy suite. Overall, c-TBNA is a safe procedure with no additional risks to a standard bronchoscopy, as complications rarely occur and include pneumothorax, haemomediastinum and major bleeding [14].

Against a very high specificity (96–100%), the sensitivity of TBNA varies greatly in the published literature. To date, two meta-analyses of data on c-TBNA accuracy for lung cancer staging have been performed: one reported an average pooled sensitivity of 76%, ranging from 14% to 100% [15], while the other, restricted to studies including patients with non-small lung cancer (NSCLC), provided two separate estimates according to low or high prevalence of mediastinal disease, 39% and 78%, respectively [16]. The range of c-TBNA sensitivity was even larger in the diagnostic work-up of suspected sarcoidosis (6–90%), with a pooled value of 62%, as reported in a meta-analysis conducted by Agarwal et al. [17].

Besides the underlying clinical setting, the reasons for variability in TBNA accuracy appear to be related to baseline clinical characteristics, as well as to procedural aspects, evaluated as potential predictors of a successful aspirate in several investigations, reporting, however, conflicting results. In order to provide an extensive description and synthesis of available evidence in this context, we performed a systematic review of literature, and 53 studies, involving more than 8000 patients and evaluating 23 potential predictive factors, were identified [1]. Major predictors of c-TBNA yield for the diagnosis of mediastinal lymphadenopathies/masses included an increasing lymph node size, the presence of abnormal endoscopic findings, underlying malignant conditions, station 4R and 7 as site of samples and the use of histological needle by an “experienced” bronchoscopist, although the type and duration of educational interventions evaluated varied widely among studies. In the subgroup of patients with suspected/known lung cancer, other predictors were selected features of primary tumour, as the presence of SCLC subtype rather than NSCLC, most likely due to higher biological aggressiveness and lower adhesion of small cells, and right-side location [1].