Abstract
It is of great value by using PET imaging in oncology to recognize any atypical uptake not related to the underlying disease. That helps in avoiding the false positive finding and may contribute in extending the application range of used radiopharmaceuticals in further disorders. It is well known that radiolabeled choline is an essential PET tracer used currently in prostate cancer. The physiological choline distribution was described. Nevertheless there is still a lack of studies, which describe this distribution in young patients; given that the radiolabeled choline is generally being used in the field of prostate cancer. Whether the thymus exhibits normally a positive choline uptake or not is still unknown. In particular, it is known that the lymphocytes express high affinity of choline transporter and enzymes involving its metabolism. Some cases of thymus carcinoma exhibiting a positive choline had been reported in the literature, however, mostly using 11C-choline. We report a rare case of metastatic thymic carcinoma detected incidentally using 18F-choline-PET in a 78-year-old male patient referred with elevation of prostate specific antigen. Moreover we present a comparison pattern with 18F-FDG-PET modality, in which 18F-choline-PET was turned out to be superior in tumor delineation.
1. Introduction
The field of diagnostic nuclear medicine is wide and open for developing new applications. Radiolabeled choline was introduced as a good PET tracer in assessing the prostate cancer.
Either labeled with carbon (11C) or with fluoride (18F), the choline is considered widely as the favorable choice in prostate tumor; primary and recurrent tumor as well.
Owing to the short half-life of 11C, the appliance of 11C-labeled choline is restricted in centers equipped with cyclotron on site. F-18-labeled choline was considered as an alternative to 11C labeled choline nearly in all applications.
Schillaci et al. [1] described the physiological distribution of F-18 fluorethyl choline in 80 patients with prostate cancer. Normal uptake was observed in liver, pancreas, spleen, salivary, and lachrymal glands. Abnormal uptake not owing to PCA was found in 15 patients out of 80 (18.7%).
Using 11C-labeled choline, Fallanca et al. [2] described an unusual case of incidental detection of thymoma in addition to local recurrence in prostate cancer patient referred due to biochemical recurrence. On the other hand, Calabria et al. [3] reported in 2011 the first case of thymus tumor detected incidentally by fluoride labeled choline.
Generally in thymus tumors, it remains a big challenge by using 18F-FDG-PET to detect them among wide range of mediastinal tumors, since nearly all these tumors show a positive FDG uptake. This fact emphasizes the importance of researching for another diagnostic method specific for thymus cancer. In this setting, Shibata et al. [4] described the role of 11C-acetate PET for diagnosing the histological type of thymus tumor.
We describe in this report a rare case of thymus carcinoma with pleura metastases detected incidentally using 18F-FECH-PET. Additionally, we offer a comparison model with 18F-FDG-PET.
This case highlights the potential role of 18F-FECH-PET in identifying the thymus tumor and raises the question about the possibility to nominate it to turn into a standard diagnostic method for thymus cancer besides its main use in prostate cancer diagnosis.
2. Case Presentation
A 78-year-old male patient was referred to our department due to an unexplained PSA elevation. He underwent 18F-FECH-PET to evaluate the prostate gland.
No evidence of prostate cancer was detected. However, F-18 fluoroethy lcholine-PET/CT demonstrated an increased uptake in a mass in the anterior mediastinum, besides two other positive findings corresponding morphologically with pleura thicknesses (Figure 1). This mass was confirmed to be thymic carcinoma with pleural involvement.
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Given that 18F-FDG-PET is a method of value in the mediastinal tumors, further examination using 18F-FDG-PET was done three days later.
No additional data had been reported and the images were similar to that using 18F-FECH-PET, however, with few discrepancies.
Clearly, the uptake of 18F-FDG was more pronounced than choline uptake, that was also confirmed by SUV measurement (4, 08 in 18F-FECH-PET versus. 6, 05 in 18F-FDG-PET). However, by using 18F-FECH-PET the thymic tumor was the sole structure in mediastinum showing a positive uptake, which resulted in a high target to background signal ratio and better tumor delineation.
In contrast, by using 18F-FDG-PET, the mediastinal blood pool activity affects negatively the tumor demarcation.
Of course, the 18F-FECH-PET is not an established diagnostic tool for thymic cancer. Nevertheless such cases pave the way for further extended studies involving the potential benefit of 18F-FECH-PET in thymic cancer.
In conclusion, this report does not only display a rare case of thymic cancer detected incidentally by 18F-FECH-PET but provides an ideal comparison model between 18F-FECH-PET and 18F-FDG-PET in this uncommon tumor.
3. Discussion
3.1. Overview about Thymus and Relation with Cholinergic System
It is well know that the thymus is a specialized organ of the immune system. Its task is production and education of T-lymphocytes. Lymphocytes express most components of the cholinergic system including acetylcholine, muscarinic, and nicotinic acetylcholine receptors, choline acetyltransferase, and acetylcholinesterase [5, 6].
Based on this fact, normal thymus tissue is supposed to be of positive choline uptake.
While a physiologic 18F-FDG uptake in thymus has been reported in children and in sporadic cases in adults after chemotherapy [7], there is no report about physiologic 18F-FECH uptake in thymus. However, the pattern of physiological distribution of radiolabeled choline is not available in children, simply because its application is mostly in adult patients with prostate cancer.
3.2. Types of Thymus Tumors and Diagnostic Methods
Thymomas and thymic carcinomas are the most common tumors of the anterior mediastinum. Thymomas are generally encapsulated and have a mild histologic appearance. By contrast, thymic carcinomas present more likely in an invasive shape.
The complete resection improves survival in locally invasive thymic tumors.
Adjuvant postoperative radiation therapy may improve the outcome in patients with invasive disease [8].
Long term followup is required essentially concerning the incidence of local relapse. At this point in such critical anatomical location (anterior mediastinum), the morphological images are of negligible value in distinction between recurrent disease from postoperative or post-irradiation fibrosis.
Thus, there is a need of new nonanatomical methods able to recognize the residual tissue from surrounding tissue.
El-Bawab et al. [9] explained the importance of 18F-FDG-PET and its superiority over computed tomography during followup after thymoma excision, in the early detection and localization of meditational recurrence.
On the other hand, 18F-FECH-PET was demonstrated as a method of value in tumors with low glucose metabolism. There are enough studies describing its role in the diagnosis of prostate cancer. Thymic carcinoma has been already shown likely to have a positive uptake in 18F-FECH-PET; however, such report of metastatic thymus carcinoma detected using 18F-FECH-PET additionally with a comparison pattern with 18F-FDG-PET imaging was rare reported. In conclusion in the absence of the data describing a physiological 18F-FECH uptake in thymus gland, each uptake in thymus should be suspected in until proven otherwise.