Fig. 2.1
Division of the mediastinum into prevascular, visceral, and paravertebral compartments, based on cross-sectional imaging as defined by the International Thymic Malignancy Interest Group. Panel A prevascular compartment. Panel B visceral compartment. Panel C paravertebral compartment. The white outline depicts the referenced compartment in all panels
Fig. 2.2
Lateral view of the thorax indicating the boundaries of the mediastinal compartments as defined by the International Thymic Malignancy Interest Group
The significance of these anatomic subdivisions is twofold. First, since certain tumors/lesions have a predilection for specific compartments, it allows clinicians to organize the mediastinum conceptually, with each compartment having a different differential diagnosis (Table 2.1). As an example, when a patient presents with an anterior mediastinal mass, the most likely diagnosis is a thymic neoplasm or lymphoma. Conversely, a patient with a paravertebral mediastinal mass is most likely to have a neurogenic tumor. This classification then helps dictate further workup because the clinician will tailor the diagnostic maneuvers to the most likely diagnoses. Second, each of the mediastinal compartments has anatomic boundaries that make it accessible to different approaches for biopsies and surgical resection. A lesion in the prevascular compartment is approached in a markedly different manner than in the visceral and paravertebral compartments when it comes to obtaining a tissue diagnosis or performing surgical resection (Table 2.1).
Table 2.1
Impact of compartment location on differential diagnosis and biopsy approaches for mediastinal lesions
Compartment | Commonly encountered lesionsa | Common biopsy approachesb |
|---|---|---|
Prevascular | Thymic neoplasms and cysts Lymphoma Germ cell tumors | Image-guided percutaneous biopsy Anterior mediastinotomy VATSc Extended cervical mediastinoscopy |
Visceral | Cystic lesions Metastatic lymphadenopathy Benign lymphoproliferative disease Lymphoma Esophageal tumors | Endobronchial/endoscopic ultrasound Cervical mediastinoscopy VATS Image-guided percutaneous biopsy |
Paravertebral | Neurogenic tumors Cystic lesions | Image-guided percutaneous biopsy VATS |
Lesions in the prevascular compartment are best approached percutaneously for biopsies. The most commonly diagnosed lesions in this region are thymic neoplasms, lymphoma, and germ cell tumors, although a variety of other very rare tumors may arise here as well, including sarcomas. This compartment is isolated from the tracheobronchial tree and esophagus by the great vessels and pericardial contents, limiting access using transtracheal or transesophageal technologies. In addition, the prevascular compartment lies directly posterior to the sternum and anterior chest wall, with no other intervening structures or lung. Percutaneous approaches include image-guided needle core biopsies and aspirations, or surgical procedures through the anterior chest wall, the most common being the anterior mediastinotomy (AM) (Chamberlain procedure). The prevascular compartment is not accessible to standard cervical mediastinoscopy, since this approach follows the airway down into the visceral compartment. A variation of cervical mediastinoscopy, termed extended cervical mediastinoscopy, allows access to certain limited prevascular areas, but is uncommonly performed given the ease of percutaneous biopsy. Finally, the prevascular compartment can be accessed through either pleural space, typically with video-assisted thoracic surgical (VATS) technology. However, the transpleural approach is less popular because of potential postoperative pain issues, the potential need for a chest tube, and the fear of pleural space seeding when performing biopsy of a malignant tumor.
The visceral mediastinal compartment is less accessible to percutaneous biopsy approaches because it lies in the center of the mediastinum, although percutaneous needle biopsies can still be performed. The most common malignant lesions that are situated in this region are lymphoma and metastatic lymph node disease from other sites, most notable lung cancer. In addition, several benign processes also occur here, including benign lymphoproliferative disorders and mediastinal cysts. Historically, the most commonly utilized approach to obtain tissue samples from the visceral compartment has been cervical mediastinoscopy. However, since the central tracheobronchial tree and esophagus traverse this compartment, approaches that utilize endoscopic and endobronchial technologies are extremely useful when working in the visceral compartment, and have replaced cervical mediastinoscopy in most circumstances. Similar to the prevascular compartment, the visceral area can be approached transpleurally, but this is less desirable for the aforementioned reasons.
Given that the paravertebral compartment once again lies in close proximity to the chest wall, percutaneous, image-guided needle biopsy techniques are once again utilized commonly to obtain a tissue sample. The most common lesions in this compartment are neurogenic tumors and cysts, however, other more rare tumors such as sarcomas can also arise here. Although VATS can also be utilized to obtain a tissue diagnosis from this compartment, it is not commonly used unless an excisional biopsy is intended.
Indications for Mediastinal Biopsies
Undiagnosed mediastinal masses and lymphadenopathy. Given that the radiographic appearances of many mediastinal tumors and lesions are similar, in the vast majority of cases tissue sampling is necessary prior to formulating a treatment plan. A notable exception may be hormonally active germ cell tumors, which may arise as primary tumors in the prevascular compartment. Patients with non-seminomatous malignant germ cell tumors in the prevascular compartment may be treated with chemotherapy if their serum tumor markers (α-fetoprotein [AFP], β-human chorionic gonadotropin [β-HCG]) are significantly elevated, in the absence of a biopsy [4, 5]. Primary tumors of the mediastinum are treated differently depending on their histology, with some optimally managed with upfront surgical resection (thymic and neurogenic tumors) and others managed primarily with systemic therapies (germ cell tumors and lymphomas).
In addition to primary mediastinal tumors, the etiology of mediastinal lymphadenopathy is very diverse, with a range of malignant and benign conditions potentially capable of causing enlarged lymph nodes. Benign lymphoproliferative disorders mainly consist of reactive hyperplasia, granulomatous inflammation (infectious and noninfectious), as well as Castleman’s disease. Malignant disorders associated with mediastinal lymphadenopathy are similarly diverse, ranging from primary malignancies (lymphomas) to metastatic lesions. Metastatic lymphadenopathy is frequently associated with primary tumors of the thorax, most commonly lung and esophageal cancer. Additionally, many extrathoracic malignancies may also metastasize to the mediastinal lymph nodes, especially head and neck and colon cancers.
Staging of thoracic cancers. In patients with a known or suspected diagnosis of lung or esophageal cancer, appropriate clinical staging of the tumor often requires biopsy of the mediastinal lymph nodes. In this regard, standardized lymph node staging maps have been proposed and adopted for these and other thoracic cancers, including thymic malignancies [6–8]. For non-small cell lung cancer, it is often necessary to perform biopsies of several lymph node stations, which may require more than a single biopsy approach (Fig. 2.3). In these cases, it is frequently possible to obtain a tissue sample from the primary tumor as well, if deemed necessary.
Fig. 2.3
Lymph node stations commonly biopsied for lung cancer staging. In each panel, the designated lymph nodes are within the white circle. Panel A Right level 4 (paratracheal), most commonly accessed using either cervical mediastinoscopy or endobronchial ultrasound. Panel B Level 6 (preaortic) most commonly accessed using anterior mediastinotomy or video-assisted thoracic surgery. Panel C Level 7 (subcarinal), most commonly accessed using endobronchial ultrasound, endoscopic ultrasound, or cervical mediastinoscopy
Tissue for molecular testing. As molecular and genetic alterations in human malignancies become more clearly defined, the use of therapies targeted toward these alterations becomes more commonplace. This is especially pronounced in non-small cell lung cancer [9]. The most well characterized of these changes is related to the epidermal growth factor receptor (EGFR), where response rates to targeted therapies are profound [10]. Given this revolution in “personalized” cancer therapies, oftentimes it becomes important to obtain additional tissue in patients in whom the diagnosis and stage have already been established.
Although “liquid” biopsies looking for genetic alterations in peripheral blood are under active investigation [11], it is frequently necessary to perform mediastinal biopsies of the malignant lesions themselves to evaluate the tumor for these molecular changes. The biopsy technique utilized for this purpose has to provide enough tissue to perform the analyses desired, but as expertise and technology improves, most of this testing can be performed on needle cores and even aspirates in many circumstances. In the realm of lung cancer, endobronchial ultrasound-guided needle aspirations of mediastinal and hilar lymph nodes have been demonstrated to be sufficient for these purposes [12].
Incisional versus excisional biopsy. When obtaining tissue for analysis from a patient with a mediastinal lesion, a decision must be made regarding not only the biopsy approach and technique, but also the “extent” of biopsy. An “incisional” biopsy implies that only a small portion of the lesion is removed for analysis and is performed using techniques that utilize needles and small biopsy forceps. Although the phenomenon of “needle tract seeding” has been reported, this appears to be a rare event, especially given the large proportion of needle biopsies performed for both lesions in the mediastinum and other body regions [13]. Another approach is to perform an “excisional” biopsy, which implies that the entire lesion is removed. An excisional biopsy is both diagnostic and therapeutic when performed for a mediastinal lesion that would require removal anyway once diagnosed. The decision of whether to perform an incisional or an excisional biopsy needs to take into account several factors, as outlined in Table 2.2. In general, an excisional biopsy is performed for smaller, easily resectable lesions that are likely to represent histologies where surgical resection is the preferred treatment. Examples include small prevascular masses that are likely to be thymomas, cysts in the visceral compartment, and benign neurogenic tumors in the paravertebral compartment (Fig. 2.4).
Table 2.2
Factors affecting the choice of incisional versus excisional biopsy in the mediastinum
Type of biopsy | Presumptive diagnosis | Size | Likelihood of tumor aggressiveness |
|---|---|---|---|
Incisional | Lymphoma Germ cell tumor Metastatic disease | Large | High |
Excisional | Thymic lesions Cystic lesions Neurogenic tumors | Small | Low |
Fig. 2.4
Benign neurogenic tumor for excisional biopsy. Panel A Computed tomographic image of tumor in the paravertebral compartment. Panel B Image obtained using video-assisted thoracic surgery at the time of excisional biopsy. In both panels, the white arrow indicates the tumor
Mediastinal Biopsy Techniques and Approaches
There are multiple techniques and approaches that can be used to perform biopsies of various mediastinal lesions. Each choice has its advantages and drawbacks, making no single technique ideal for all indications (Table 2.3). Over the past two decades, technology and expertise has become more evolved and sophisticated, with several new, safe options commonly performed at many centers.
Table 2.3
Advantages and disadvantages of mediastinal biopsy techniques
Biopsy technique | Advantages | Disadvantages |
|---|---|---|
Image-guided percutaneous biopsy (IGPB) | Less invasive Local anesthesia Minimal postprocedure pain | Risk of nondiagnostic biopsies Incisional biopsies only |
Cervical mediastinoscopy (CM) | Larger biopsies than IGPB Some excisional biopsies | General anesthesia Visceral compartment only |
Anterior Mediastinotomy (AM) | Larger biopsies than IGPB Some excisional biopsies | General anesthesia Postoperative pain Risk of cosmetic deformity |
Endoscopic ultrasound (EUS) | Less invasive Minimal postprocedure pain | Visceral compartment only Incisional biopsies only |
Endobronchial ultrasound (EBUS) | Less invasive Minimal postprocedure pain | Visceral compartment only Incisional biopsies only |
Video-assisted thoracic surgery (VATS) | Access to all 3 compartments Excisional biopsies Evaluation of lung and pleura | General anesthesia Postoperative pain Potential for chest tube |
Image-guided percutaneous biopsy (IGPB). Percutaneous needle biopsy of mediastinal lesions using imaging modalities as guidance is a commonly utilized mediastinal biopsy approach, especially given advances in technology, imaging, and expertise. Although IGPB can be used to access any lesion in all three mediastinal compartments [14], it is usually utilized to obtain tissue from lesions in the prevascular and paravertebral regions (Fig. 2.5). This is because these two compartments lie just deep to the chest wall, eliminating the need to traverse the pleural space in most circumstances. Although the visceral compartment is accessible percutaneously, this region is farther away from the chest wall, the pleural space may need to be traversed, and newer, endoluminal image-guided technologies are available and are rapidly becoming widely adopted for access to this region.
Fig. 2.5
Mediastinal regions where image-guided percutaneous biopsies are typically performed. The black areas represent the most common regions where image-guided percutaneous biopsy is employed
The most commonly used imaging modality for IGPB is computed tomography (CT) due to its precision in imaging both the target lesion and surrounding vital structures, however, ultrasound (US) is also utilized, especially for larger lesions in the prevascular compartment. US may be used in these latter cases when a patient with a large prevascular mass cannot lie supine for CT imaging. US also allows passage of the biopsy needle under real-time guidance, whereas the needle is advanced in increments sequentially with CT guidance to verify proper targeting. In most circumstances where IGPB is employed, the operator uses the coaxial technique, where a larger guide needle is placed in or adjacent to the target lesion. Once located with the larger guide needle, the lesion is sampled with either fine needles or larger core needles through the channel of the guide needle. The coaxial technique eliminates the need to repeatedly pass needles through the skin and surrounding mediastinal tissues with each sampling [14, 15].
Adverse events resulting from IGPB of the mediastinum are uncommon, and consist mainly of bleeding, pneumothorax, and failure to obtain a definitive diagnosis [15]. Significant bleeding is an extremely unusual event, but may result in mediastinal, chest wall and pulmonary hematomas, hemothorax, and even pericardial tamponade. It is important to avoid inadvertent damage to the internal mammary vessels when performing a biopsy of a prevascular mass. The risk of pneumothorax becomes significant when the pleural space is traversed during the procedure, however, the need to place a chest tube is infrequent [15, 16].
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