The Role of 18F-FDG PET/CT Scan in Predicting Histological Type of Thymic Epithelial Tumors: Indications and Practical Clinical Considerations
28 February 2017
02 June 2017
20 July 2017 (eFirst)
Although not yet universally accepted, TETs may be distinguished in different subgroups—“low-risk” thymomas versus “high-risk” thymomas—with different prognosis  while thymic carcinomas clearly stay as a separate class with poorer prognosis, as remarked in a recent meta-analysis by Marchevsky et al. The distinction between WHO “low-risk” versus “high-risk” TETs is usually achieved by the pathological evaluation of surgical specimens; in terms of therapeutic strategy, there is evidence that in selected thymomas (high-risk or locally advanced tumors) a postsurgical adjuvant therapy (mostly radiotherapy alone or combined with chemotherapy) provides better long-term results.
However, predicting the histological type of TETs (WHO “low-risk” vs. “high-risk”) is extremely important for planning treatment strategies and surgical approach. Indeed, with the advent of minimally invasive surgical techniques, the selection of patients has become pivotal to identify the best candidates who can benefit from this approach, basically those patients with early-stage and histological “low-risk” thymic tumors.
In this framework, recent evidence points at fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography associated with computer tomography (PET/CT) as a potentially useful tool to preoperatively discriminate the WHO malignancy grade of TETs. 
In this setting, Tomita et al analyzed the correlation between 18F-FDG PET/CT findings and WHO histological features in a large monocentric clinical series of 73 patients having undergone surgical resection for TETs, adds very interesting information to the debate. The authors confirmed the results of the previous studies  that the ratio between PET maximum standardized uptake value (SUVmax) and the tumor size (SUVmax/T) is more useful than the SUVmax alone for differentiating low-risk and high-risk thymomas. Moreover, the authors found that both radiometabolic parameters showed higher values in patients with advanced Masaoka stage disease than in those with early-stage disease. From these results, they concluded that FDG-PET might have further use for radiological differential diagnosis of TETs, including the possibility that FDG-PET could replace CT-guided fine-needle biopsy.
Controversial opinions exist concerning the opportunity and usefulness to routinely include preoperative cytohistology in the staging of a mediastinal mass. Indeed, when the clinical scenario and radiological characteristics do not allow to distinguish between a lymphomatous disease and other mediastinal tumors, it seems reasonable to propose a CT-guided fine-needle biopsy because in these cases 18F-FDG PET/CT scan is rarely useful in differential diagnosis. On the contrary, when the clinical scenario does not coincide with a lymphomatous disease and the radiological findings are mostly in favor of a thymic neoplasm, the opportunity of performing a biopsy is almost questionable and debated. Indeed, albeit some authors believe that preoperative histological confirmation of all mediastinal masses is mandatory, even in those cases where little doubt exists after imaging, several others  do not support the usefulness of this procedure when imaging supports the diagnosis of TET. Indeed, the tissue/cell acquisition is often not supportive of a final (and detailed) diagnosis, a small (although not negligible) risk of complications exists and, more rarely, a neoplastic seeding has been reported when the tumor capsule is interrupted. 
In daily clinical practice, this represents probably the best subset of patients where a PET-CT scan could be most useful to achieve information on WHO malignancy grade without performing a (minimally) invasive biopsy. In fact, in such cases, by evaluating the radiometabolic parameters coming from PET/CT scan (SUVmax and SUVmax/T) the physicians could have viable information on the histological malignancy grade for planning treatment strategies and the best surgical approach.
In conclusion, as previously remarked,  and largely supported by Tomita et al's experience, the achievement of a detailed preoperative WHO criteria-based diagnosis could play a crucial role when planning the best strategy of care in patients with mediastinal lesions radiologically suspected to be thymic epithelial tumors. Despite the 18F-FDG PET/CT cannot replace the surgical biopsy in all TET patients (especially when a neoadjuvant therapy is scheduled), this “metabolic biopsy” could integrate the data coming from the biopsy and, in selected cases, avoid this procedure, and help the physicians with the strategy of care.