Anterior Mediastinal Tumors: Biopsy—When, Why, How?

Mediastinal masses are relatively rare and encompass a wide variety of diseases from the purely benign to the extremely malignant. The three anatomic mediastinal compartments are clinically notable because specific lesions characteristically arise in certain locations, making the compartment of origin integral to the differential diagnosis. Greater than half of mediastinal masses occur in the anterior/superior compartment. Thymic neoplasms, lymphomas, thyroid masses, and germ cell tumors make up the classic differential. Management strategies for these tumors are diverse and depend strongly on the histologic diagnosis and extent of disease. The rarity of these masses has led to an unstructured approach to their workup, with a diversity of choices and indications for histologic diagnosis.

CT scan, MRI, and fluorodeoxyglucose positron emission tomography (FDG-PET) are the main imaging modalities used to evaluate anterior mediastinal masses. CT scanning provides a reliable evaluation of mediastinal anatomy and relationship of the lesion to adjacent structures. CT scan findings that help differentiate tumor histologic state are the presence of fat, cysts, and calcifications; contrast enhancement; invasion of adjacent structures; and associated mediastinal lymphadenopathy. Of these criteria, the presence of fat and associated mediastinal lymphadenopathy are the most useful. Presence of fat density on CT scan has a 57% sensitivity, 97% specificity, and 90% positive predictive value (PPV) for the diagnosis of a germ cell tumor, while associated mediastinal lymphadenopathy has a 75% sensitivity, 93% specificity, and 67% PPV for lymphoma (Totanarungroj et al. J Med Assoc Thai. 2010;93[4]:489).

While a definitive diagnosis can never be made by CT scan alone, there are constellations of CT findings that assist with diagnosis. Lymphomas are heterogeneous but rarely cystic. They may invade contiguous structures and have associated pleural or pericardial effusions. Only 5% of lymphomas occur solely in the mediastinum; therefore, extrathoracic lymphadenopathy is typically present. Teratomas can be smooth or lobulated but with smooth margins. Most are very heterogeneous with fluid, soft tissue, fat, and calcium. Seminomas are typically bulky, projecting out both sides of the mediastinum but rarely invade contiguous structures. They are homogeneous and have mild enhancement. Nonseminomatous germ cell tumors are large and inhomogeneous with areas of necrosis and hemorrhage, frequently invading or compressing adjacent structures, with resultant signs of obstruction. Substernal thyroid goiters can be traced in continuity to the cervical thyroid and have prolonged contrast enhancement. They can be definitively diagnosed by CT scan. Thymomas are typically well-defined and asymmetric, draping along one side of the heart. They can be homogeneous or heterogeneous based upon presence of hemorrhage, necrosis, and cyst formation, which are soft indicators for more invasive histologic status. Thymic carcinomas are similar in appearance to thymomas but have more irregular contour, necrotic or cystic components, heterogeneous enhancement, and evidence of great vessel invasion. They may also present with findings suggestive for metastatic spread.

MRI can provide additional information with regard to separation from bronchial and vascular structures. MRI is more accurate than CT scanning in assessing invasion into vessels and adjacent structures. T1- weighted images are best for anatomic assessment, while T2-weighted images are preferred for tissue characterization. FDG-PET can be useful in predicting grade of malignancy in thymic epithelial tumors and serves as a useful adjunct for assessment of extrathoracic lymphadenopathy in lymphomas.

The precise histologic state of an anterior mediastinal mass cannot be determined without tissue, but a reasonable diagnosis can frequently be made considering the radiographic findings, age of the patient, the presence or absence of symptoms, associated systemic disease, and biochemical markers. Thymoma accounts for 70% of anterior mediastinal masses in patients over 50 when one excludes the easily recognizable substernal goiters (Detterbeck et al. Thorac Surg Clin. 2011;21[1]:59). In this age group, one can be comfortable that a mass with the typical appearance of a thymoma is a thymoma. Conversely, thymomas are relatively uncommon in those younger than 20; clinical features are generally sufficient to guide treatment in this age group, but tissue is almost always required if the mass does not have the appearance of a mature teratoma. In the 20- to 40-year age group, the precise workup can be less clear. Thymomas in this age group are usually associated with myasthenia gravis or an indolent presentation. Lymphomas, on the other hand, typically present with B symptoms and a rapid progression of chest symptoms.

Since the introduction of video-assisted thoracoscopic surgery (VATS), the threshold for resection of mediastinal lesions without precise histologic diagnosis has been lowered. In patients who present with typical radiographic signs of mature teratomas, or in an older patient with a typical radiographic appearance for a thymoma, one can be confident in the diagnosis. In a recent survey of current practices among members of the European Society of Thoracic Surgeons, 91% of centers reported that they did not routinely look for a histologic diagnosis when presented with a small, resectable, encapsulated lesion, where the clinical presentation and CT scan characteristics are not suggestive of lymphoma (Ruffini et al. J Thoracic Oncol. 2011;6[3]:614). The presence of myasthenia gravis also helps in securing the diagnosis. Frozen section confirmation at the time of resection is difficult and not recommended unless unexpected intraoperative findings are encountered. There is no harm in performing a needle or incision biopsy of a small thymoma, if needed. The fear of tumor spread as a result of biopsy is not supported in the literature.

Making a precise diagnosis without tissue for poorly demarcated tumors of the anterior mediastinum is more difficult since large thymomas, thymic carcinomas, seminomas, nonseminomatous germ cell tumors, and lymphomas can have a similar radiographic appearance. Tissue diagnosis is particularly important if there is a high index of suspicion for a lymphoma or germ cell tumor, as these are not treated surgically. A variety of anterior mediastinum biopsy techniques are available, including CT-guided percutaneous needle biopsy, parasternal anterior mediastinotomy (Chamberlain procedure), VATS, and open surgical approaches. None of these procedures are universally accepted, either because of low diagnostic yield or associated morbidity. Core needle biopsy is preferred by some due to its ease, patient comfort, and low morbidity. Unfortunately, an accurate diagnosis by core biopsy is dependent upon good tissue retrieval without extensive necrosis, on-site cytologic examination, and an experienced pathologist. Immunohistochemistry enhances the diagnostic accuracy because of its utility in identifying and classifying lymphomas. In a recent comparison of core needle biopsy to mini-mediastinotomy in a series of 40 large unresectable anterior mediastinal masses, the diagnostic yield of mini-mediastinotomy was 85.7%, significantly higher than that of core needle biopsy at 41.7% (Fang et al. Chin Med J (Engl). 2007;120[8]:675). Extensive necrosis was cited as most frequent reason for inability to make a diagnosis. Throughout the literature, sensitivity of needle biopsy is approximately 60%, while that of surgical biopsy is 90%. The perceived fear of pleural seeding during transthoracic core needle biopsy is also not substantiated in the literature. Many surgeons recommend surgical biopsy when histologic status is needed. In the recent European Society of Thoracic Surgeons survey, most respondents stated that they preferred surgical biopsy by VATS or anterior mediastinotomy when histologic status is required. During anterior mediastinotomy, efforts should be made to avoid the internal mammary artery and to stay out of the pleural space. These biopsies are typically done under general anesthesia but have been reported in awake patients. VATS approaches are preferred by many, and awake biopsy by this approach has also been reported (Pompeo et al. Thorac Surg Clin. 2010;20[2]:225). There are rare occasions when minimally invasive approaches are insufficient to obtain adequate tissue, and sternotomy or thoracotomy is indicated. This is most common with nodular sclerosing Hodgkin’s disease, due to its dense fibrotic capsule.

Tumors of the anterior mediastinum generate substantial interest, typically due to their large size and the diversity of the diagnosis and associated treatment plans. The threshold for biopsy prior to definitive resection is based on numerous factors, including size, encapsulation, respectability, patient age, and associated clinical scenario. Since resectability is an important component of this decision, appropriate diagnostic workup is best determined by a team that includes a thoracic surgeon. Mode of biopsy is highly dependent on institutional expertise, but surgical biopsy provides the greatest chance for adequate diagnosis with minimal associated morbidity and mortality.

Dr. Jessica S. Donington, MSCR
Assistant Professor
Department of Cardiothoracic Surgery
NYU School of Medicine
New York, NY