Recurrent Thymoma with Lung, Pleural, and Splenic Metastases Demonstrated on F-18 FDG PET/CT ()
1. Introduction
Thymomas are uncommon, indolent tumors of epithelial origin affecting mostly Asians, African Americans, and Pacific islanders aged 40 - 70 years old. The etiology is unknown and is said to be of genetic predisposition. Thymomas spread locally and are less invasive than thymic carcinoma. [1] [2] Complete tumor resection is the mainstay of treatment with a 5-year survival rate of approximately 90% for grossly and microscopically encapsulated thymomas. [2]
The lung is its most common metastatic site. [3] Since extra-thoracic metastasis is low at 3% - 6%, chest CT-scan has been the imaging modality of choice for initial staging and follow-up. [2] [3] [4] However, there are some cases of distant metastases to the brain, liver, pancreas, kidneys, and intraperitoneum. [5] - [10] In the literature search, there were only a handful of cases of thymoma with splenic metastasis. Patients reported in the 1990s, both had liver and spleen metastases discovered only during autopsy. But with active disease surveillance through diagnostic imaging, early intervention halted disease progression in recent years. Here we present the FDG avidity of pulmonary, pleural and spleen metastases in a patient with recurrent thymoma.
2. Case Presentation
This is a case of a 60-year-old, female presenting with a benign right thyroid nodule. Her chest x-ray had an incidental finding of anterior mediastinal mass. Chest CT and F-18 FDG PET/CT scans were performed for disease staging that showed a 4.8 cm hypermetabolic soft tissue mass in the anterior mediastinum with SUVmax of 5 (Figure 1(a)). There was no other abnormal hypermetabolic lesion, suggesting metastasis. The patient underwent total thymectomy with adjuvant radiation therapy. Biopsy revealed a 7.3 × 5 × 4 cm thymoma type B3 with invasion to soft tissue, had infiltrative border but with a clear margin of resection. Post-operative PET/CT showed no residual tumor (Figure 1(b)).
Two years from the time of diagnosis, the patient developed a 6 mm subpleural nodule in the posterior basal segment of the left lung on a CT-scan. The nodule was indeterminate for metastasis, thus close chest x-ray and CT-scan monitoring were done. With the significant increase from 6 mm to 9 mm in the next eight months, F-18 FDG PET/CT was requested for further evaluation. Hypermetabolic lesions were noted in the left pleura SUVmax 3.0 (Figure 1(c)) and left lower lung SUVmax 1.9 (Figure 1(d)). These were resected and a biopsy reported metastatic thymoma. After surgical intervention, there were no residual FDG-avid lesions seen (Figure 1(e)). The patient was disease-free for the next two years. Then, there was a recurrence of the mediastinal mass on the CT-scan. The resected mass measured 2.3 × 0.9 × 0.6 cm; consistent with thymoma type B3, clinically recurred.
Two years from the time of primary tumor recurrence, there was pleural seeding in the left mid to upper hemithorax on chest CT-scan. On F-18 FDG PET/CT, there were metabolically active lesions seen in the left pleura SUVmax 4.9 and in the capsular area of the spleen SUVmax 2.9 (Figure 1(f)). Resection and biopsy of the above findings showed metastatic thymoma in the left pleura and its adjacent 8th-11th ribs and in the 2.3 × 2.1 × 0.7 cm splenic mass.
3. Discussion
Thymomas, previously are divided into three types: benign encapsulated, type 1 malignant (invasive thymoma) and type 2 malignant (thymic carcinomas) thymomas.
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Figure 1. Transaxial F18-FDG PET/CT images of a 60-year old female with a hypermetabolic mass in the anterior mediastinum (SUVmax 5), consistent with Type B3 thymoma. (b) Post-total thymectomy with adjuvant radiation therapy scan showed interval resolution of FDG uptake in the surgical site. However, thymoma clinically recurred with metastases to the pleura (c), lung (d), and spleen (f) with low-grade FDG uptake. Post-resection of left lower lung hypermetabolic lesion (e).
The recent classification by WHO is based on five histological subtypes (A, AB, B1, B2, and B3) and can be further divided according to the presence of spindled (A, AB) or epithelioid neoplastic epithelial cells (B1-B3). Thymic carcinoma, on the other hand, exhibits a definite cytologic atypia similar to those histologic features observed in carcinomas of other organs. [11]
In particular, Type B3 thymoma is mainly composed of epithelial cells exhibiting mild or no atypia. [11] Despite features of low-grade neoplasm, about 5% of invasive thymomas have distant metastasis, occurring on an average of 3.6 months from the time of diagnosis to development of extra-thoracic metastasis. [4] Meanwhile, recurrent cases were mostly intrathoracic and pleural with a median time from operation to progression of 20 months. [12] About 1.8% of thymomas metastasized to the lymph nodes and 1.2% had hematogenous spread. [4] Frequent metastatic sites for thymic epithelial tumors were the lung followed by bone and liver. One hypothesis for the rare splenic metastasis by epithelial cancers is the exposure of the transiting granulocyte and cancer cells to pro-apoptotic signals as they undergo pooling within the spleen. [13]
The 5-year overall and progression-free survivals of thymoma patients were 89% and 75%, respectively. [4] Significant factors for survival are the clinical stage of Masaoka (based on the degree of local invasion) and the completeness of resection. [4] The time to progression from relapse was shorter for those with incomplete resections (8 mos vs 29 mos for complete resection). [12] Thus, assessment of surgical resectability of the primary tumor and the tumor spread is key to a patient’s disease-free survival.
The advantage of PET/CT lies in its ability to physiologically and anatomically image the entire body in one session. Glucose transporter and hexokinase mediate the cellular uptake of F-18 FDG in epithelial cells. Findings of thymic hypermetabolism may represent normal physiologic uptake (in the first two decades of life), hyperplasia (post-chemotherapy rebound), lymphomatous infiltration, primary thymic neoplasm or metastatic disease. [14] The intensity of FDG uptake reflects metabolic activity and correlates with tumor growth rate. Low-grade thymomas (type A and B1) have low, heterogeneous uptake as compared with high-risk thymoma (type B2, B3) and thymic carcinoma, which are more likely to have high and homogenous activity. [15] Using an SUV cutoff of 5 in differentiating thymic carcinoma from thymoma; sensitivity, specificity, and accuracy were 84.6%, 92.3%, and 88.5%, respectively. [14]
Other case reports likewise presented low FDG avidity with lung [16] , pleura [6] , or spleen [17] metastasis. For splenic metastasis, Metser et al. [18] reported that F-18 FDG PET could reliably discriminate between benign and malignant solid splenic masses in patients with known 18F-FDG?avid malignancy (SUV of benign 1.87 ± 0.32 vs malignant lesions 7.86 ± 5.57; p < 0.01). This borderline metabolic activity warrants the PET reader to look closely in the spleen and not totally rule out metastasis despite mild FDG uptake, which still harbors malignancy.
4. Conclusion
A growing body of diagnostic evidence has shed light on the use of whole-body imaging to detect distance metastasis, particularly for aggressive pathologies. Here we presented the case of invasive thymoma with disease recurrence and a rare metastasis to the spleen. The use of F18-FDG PET/CT was valuable for staging and restaging, especially since patients can be asymptomatic even in advanced cases. Despite low FDG avidity of thymoma metastases PET/CT scan was still able to facilitate early detection that led to timely intervention.