The role of positron emission tomography in mediastinal mass

Introduction

The differential diagnosis for mediastinal masses is broad and ranges from benign entities to aggressive malignancies and everything in between. When working them up, a multi-faceted approach is taken in order to narrow the differential and help delineate the type of mass and the stage, which is imperative for decision making. Chest imaging plays a significant part in the assessment of mediastinal masses and often helps determine subsequent steps in diagnosis and management. Positron emission tomography (PET) scans are commonly used in clinically staging malignant tumors. The role of PET scans in the work up and management of mediastinal masses has been controversial and inconsistently utilized with little consensus in the literature about how best to apply it. In this paper, we address the use of PET scans in mediastinal masses and how it influences diagnostic work up and management.

Clinical review

Patients presenting with mediastinal masses can present a diagnostic challenge to thoracic surgeons. They can be found due to work up for symptoms but are often found incidentally on imaging. The location of the mass often helps to narrow the differential diagnosis. The mediastinum is bordered by the pleura laterally on both sides and the thoracic inlet and diaphragm superiorly and inferiorly, respectively. It is further divided into anterior, middle and posterior compartments. About half of all mediastinal masses are anterior, and are comprised of thymic masses, lymphomas, germ cell tumors, or thyroid disease (1). Middle mediastinal masses are typically benign cystic lesions and posterior ones are neurogenic tumors. The initial study is often a computed tomography (CT) scan of the chest, which can give some indication of the etiology, but often more detailed imaging is needed. PET scans are most useful in evaluating anterior masses (2), with some use in posterior masses (3), and less often used for middle mediastinal masses, which tend to be benign cystic lesions.

When evaluating a patient with an anterior mediastinal mass, determining its etiology is critical prior to treatment since the treatment algorithms are different depending on the diagnosis. For example, thymomas and thymic carcinomas are treated with resection, lymphoma with definitive chemotherapy, and germ cell tumors with chemotherapy followed by resection for residual disease. In the initial diagnostic work up, patient demographics, tumor characteristics, symptoms, lab work and imaging are used. Characteristic findings on lab work, such as elevated alpha fetal protein and beta human chorionic gonadotropin (HCG), especially in a man, can confirm a suspected non-seminomatous germ cell tumor. Certain characteristics on imaging can also help elucidate the etiology of the mass (4). Adjunctive imaging, such as magnetic resonance imaging (MRI) or PET, is often performed, with PET being used to help differentiate between benign and malignant disease and to monitor response to treatment (5). In a study looking at lymphoma patients, PET was found to be more accurate in assessing post-treatment response and excluding residual nodal disease (6).

Determining the difference between lymphoma and thymoma is not always clear, but it is crucial to planning treatment. PET scans have been shown to be useful in these settings. In a retrospective study, Byrd et al. evaluated patients with a diagnosis of lymphoma and thymoma and associated PET findings. They found a significant difference in the standardized uptake value (SUV) between lymphoma and thymoma, 18 vs. 4.35, respectively (P<0.001). In this study, an SUV less than 12.85 was associated with thymoma with a sensitivity of 100% and a positive predictive value of 89%. Furthermore, an SUV less than 7 had a 100% positive predictive value for diagnosing thymoma. The utility of differentiating between thymoma and lymphoma is significant given the risk of seeding the tract and upstaging thymoma with percutaneous biopsy and so is discouraged by the National Comprehensive Cancer Network (NCCN) when possible. Based on these findings, a mass deemed resectable should be removed surgically without a biopsy if the SUV is less than 7. If it is above 12.85, then lymphoma is a much more probable diagnosis, and a biopsy should be performed. For masses with SUV between 7 and 12.85, a biopsy should be performed in most cases, but with some consideration based on the appearance of the mass and where on the spectrum the SUV falls (7). If imaging largely favors lymphoma based on clinical presentation and imaging, such as bulky lymphadenopathy with a higher SUV, then we would pursue a biopsy, using the PET as a guide for where to biopsy in order to most efficiently yield a diagnosis.

In addition to aiding in narrowing down the differential, PET scans are key in clinical staging once a diagnosis of cancer is made, especially in lymphoma, thymic carcinoma, and germ cell tumors. In lymphoma, PET scans are much more accurate in determining lymphogenic spread to distant nodes than CT scan, with a sensitivity of 94% and a specificity of 100%. The PET is also key in providing targets of active disease for biopsy, essentially serving as a “map”, especially when patients with suspected lymphoma have bulky heterogenous lymphadenopathy (8).

When managing a patient with an anterior mediastinal mass, it is helpful to ascertain which imaging studies will help in decision making, whether it be further diagnostic procedures or proceeding with surgical resection versus systemic therapy. PET scans are not routine “reflex tests” when working up anterior mediastinal tumors so it is important to know when they will contribute to management. Thymic neoplasms are best treated with surgical resection, but their size, location and staging are all determinants of how they are approached and if neoadjuvant treatment should be considered. Thymomas and thymic carcinomas have different features on imaging, with thymic carcinomas often being larger with irregular borders. PET scans can assist further in differentiating the two. Several studies have demonstrated that SUV cutoffs ranging between 4.6 and 5.6 can often reliably differentiate between thymoma and thymic carcinoma (9,10). In a prospective single series study, Terzi et al. evaluated patients with thymic neoplasms and used PET scans for each of them. They found a significant correlation between SUV and staging based on Masaoka staging system and the World Health Organization (WHO) classification, therefore suggesting that a PET scan can be used as a “liquid biopsy” in determining how advanced the malignancy is. This is useful since higher risk thymic neoplasms have a higher rate of local invasion and may benefit from neoadjuvant treatment (11). When thymomas recur, there is a higher risk of metastasis, known as “drop thymomas”. When evaluating a patient with a possible recurrence, a PET should be obtained to assess if any other abnormalities in the chest are drop thymomas by comparing their metabolic activity to the primary lesion on PET scan. Similarly, in thymic carcinomas, which have a higher rate of distant metastasis, a PET should be performed to ascertain this information, which guides treatment algorithms (12).

In addition to location and stage, the size of the suspected thymoma also helps determine what work up is appropriate, which may not include a PET scan. PET scans have little to no utility in isolated, small thymic masses that are consistent with early stage thymomas. In lesions ≤5 cm, a minimally invasive resection should be performed in good surgical candidates for both diagnostic and therapeutic intent. In larger lesions or ones that may involve adjacent structures, a sternotomy may be required for resection. In these cases, a PET should be done to elucidate the stage, identify targets for possible biopsy, assess for drop lesions and distant metastasis, and to help determine if neoadjuvant therapy should be given prior to considering resection.

The management of germ cell tumors is often a multi-pronged approach with a combination of chemotherapy and surgery depending on the response. PET scans are used not only to help in differentiating between benign and malignant germ cell tumors, but also in assessing response. This is especially helpful in seminomatous and non-seminomatous tumors, which are treated with up front chemotherapy, followed by surgery in certain cases. Non-seminomatous germ cell tumors are often diagnosed with elevated tumor markers, and these had been monitored to assess if surgical management was indicated after treatment. There has been a shift in this management, and now nonseminomatous germ cell tumors (NSGCTs) are often resected after chemotherapy when there is residual disease on post-treatment imaging, regardless of tumor marker levels (13). Therefore, PET scans should be obtained on initial diagnosis and be used to assess the response, the location and extent of residual disease after chemotherapy. This information aids in surgical planning and can determine if there is progression with distant metastasis, which would often deem the cancer unresectable or mandate further systemic therapy and reassessment. Seminomatous germ cell tumors had traditionally been managed non-operatively, but there has been a shift in treating them in a similar fashion to NSGCT, with systemic therapy, followed by surgery for residual resectable disease, so PET scans have become useful in this treatment algorithm as well (14). Therefore, once the patient has completed the systemic treatment, a PET scan should be performed to guide next steps and surgical planning.

When assessing a patient with an anterior mediastinal mass, there are numerous options for radiological technique. Most are first discovered with a CT scan. At this point, the surgeon needs to decide which additional imaging is most useful in determining the appropriate management. For small thymic lesions, an MRI is generally preferred over a PET because MRI can help distinguish between a cystic and solid mass as well as thymic hyperplasia. A PET in this situation would likely not contribute to the management. If the MRI shows a cystic lesion or thymic hyperplasia, then surveillance is a reasonable plan. If the MRI is consistent with a small thymoma, then we would recommend surgical resection without biopsy or PET. If, however, there is bulky lymphadenopathy, a large solid-appearing mass on CT, especially if it is involving nearby structures, or the workup is consistent with a germ cell tumor, then a PET is superior to MRI for clinical staging, planning biopsies and monitoring response to treatment (15). Figure 1 illustrates an algorithm for how to approach the diagnostic work-up of mediastinal masses using imaging, biopsies and surgery.

Figure 1 Algorithm for anterior mediastinal mass work up and management. MRI, magnetic resonance imaging; PET, positron emission tomography.

There are few disadvantages to PET scans, the main one being their cost and, previously, their unavailability at many centers. As they have become more ubiquitous, they are now considered standard of care in many oncological workups, as seen in lung cancer. As such, their cost has decreased and in certain situations has been shown to be cost-effective when compared to other modes of imaging (16). Given its utility in guiding treatment algorithms and optimizing targets for biopsies, when used in the appropriate setting, the benefits outweigh the costs.

Conclusions

Given the broad differential of mediastinal masses and the significant variety in management depending on the pathology, the detailed imaging that PET scans can provide aids in embarking on the appropriate treatment in certain patients. Additionally, given the associated morbidity of biopsies in certain settings, using PET scans to better delineate these tumors can help clinicians avoid the morbidity associated with biopsies in some cases. In the case of germ cell tumors, with the increasing use of surgical resection after systemic therapy, PET scans have become essential in the management of these patients. While the utility of PET scans in mediastinal masses has not been standardized in all cases and the data are somewhat limited, there is increasing work in the last decade to better guide how best to use them in the care of these patients.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-24-44/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-24-44/coif). Both authors have no conflicts of interest to declare.

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