Thymoma with an isolated splenic metastasis eight years after extended thymectomy: a case report

Thymomas are typically slow-growing tumors and type AB thymomas are considered no/low risk tumors with a generally better prognosis. Although recurrence and metastasis of type AB thymoma have been reported, their progression commonly occurs in patients with direct invasion or pleural dissemination, and extra-thoracic metastases are extremely rare. To the best of our knowledge, no patient with an isolated splenic metastasis has been reported in the literature. Here we report a patient who underwent laparoscopic splenectomy for a slow-growing, isolated splenic metastasis, eight years after undergoing extended thymectomy for a thymoma.

Thymomas are anterior mediastinal tumors that usually arise in 40–70 year old patients. Thymomas are also associated with myasthenia gravis, pure red cell aplasia, and hypo-γ-globulinemia. Although thymomas constitute about one half of malignant tumors in the anterior mediastinum, they are rare, with a frequency of 1.5 per 1 million people [1‐5]. The 5-year survival rate is approximately 78%.

Typical progression of thymoma is direct invasion and dissemination into the thoracic cavity, then extra-thoracic distant metastases that arise through hematogenous spread are considered uncommon [6]. Lewis et al. studied 283 patients with thymoma and reported that extra-thoracic distant metastases in only eight patients (3%), all of whom had widespread metastatic disease [7]. Huang et al. discussed 15 patients with recurrence among 97 patients who had undergone resection of thymoma and reported that only two patients had distant metastases to the lung, and no patients had extra-thoracic metastases [8]. Although some patients with extra-thoracic metastases from a thymoma such as a liver, pancreas, ovarian, breast, brain, spine have been reported, but an isolated splenic metastasis has not been reported to date [9‐14]. There are a few previous reports of splenic metastases from thymic carcinomas [15, 16].

Splenic tumors are divided into two major classes, including metastatic and primary tumors. Most metastatic splenic tumors originate from hematological diseases, of which leukemia and malignant lymphoma account for approximately two-thirds. Splenic metastases from non-hematologic malignancies occur as part of widespread systemic disease in the end-stage of the disease usually, and an isolated splenic metastasis is quite rare [17]. Autopsy studies in patients who died of malignancies report metastases of malignant tumors to the spleen in 0.3–7.1% of cases, with malignant melanoma, ovarian cancer, breast cancer, and lung cancer reported most often [18, 19]. Some reports regarding metastases from colorectal cancer, gastric cancer, uterine cancer, ovarian cancer and pancreatic neuroendocrine tumor have been recently documented, with results suggesting that advances in chemotherapy and other systemic treatments have affected the long-term survival of patients with malignant tumors [20‐26]. The reason that splenic metastases are rare in patients with non-hematologic malignancies is unclear, but several hypotheses have been suggested. The spleen has few afferent lymphatic vessels and the acute angle of the splenic artery leaving the celiac artery may prevent large clumps of tumor cells from gaining access to the spleen. Rhythmic contractions of the spleen forcing blood flow from the sinusoids to the splenic veins may prevent tumor fixation. In addition, the spleen includes large numbers of lymphocytes and macrophagocytes which may allow immunologic inhibition of the induction and growth of tumor cells [15]. Marymont et al. demonstrated that splenic metastases result from the splenic artery route, splenic vein route, and lymphatic route, and are seen in the venous sinusoids and /or red pulp, supporting a hematogenous origin [17]. Sakuma et al. suggested that congestion in the splenic vein may result in development of a splenic metastasis [24]. Although we suspect a hematogenous origin for the metastasis in this patient, there were no vascular abnormalities and no invasion in the splenic artery or vein.

There are benign primary tumors of the spleen which include hemangiomas and hamartomas. In addition, primary malignant tumors of the spleen can include sarcomatous lesions, because the spleen is of mesodermal origin. Splenic primary neoplastic lesions include malignant lymphoma, hemangioendothelioma, lymphatic sarcoma, fibrosarcoma, and malignant fibrous histiocytoma. However, tumors other than malignant lymphoma and hemangioendothelioma are extremely rare.

Although differentiation between primary splenic tumor and metastatic splenic tumors is difficult based on imaging studies, recent progress in imaging modalities have rendered MRI and PET-CT findings useful. Thymoma with low-grade malignancy shows characteristic uniformity with a low to intermediate signal strength on T1-weighted images and hyperintense signal strength on T2-weighted images. Despite variability, PET-CT scan have shown low accumulation for low-grade thymoma and high accumulation for malignant cases such as thymic cancer, reflecting the level of malignancy. These findings are similarly observed for metastases and are useful for diagnosis. Malignant lymphoma, which requires differentiation, exhibits an intermediate signal intensity on T1-weighted images, intermediate and uniform signal intensity on T2-weighted images, and high accumulation on PET-CT scan. Metastatic malignant tumors often exhibit low signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and high accumulation on PET-CT scan. For benign tumors such as hemangioma and lymphangioma, the tumor appears non-uniform in T1 and T2-weighted images and exhibits low accumulation on PET-CT scan. Images acquired using these modalities are helpful for diagnosis. In the present patient, the findings were not consistent with any of these patterns, making diagnosis difficult to base on imaging data.

In the present patient, the recurrence occurred eight years postoperatively during long-term follow-up. Furthermore, the metastatic tumor showed slow growth. Therefore, we selected surgical resection as the treatment. In the National Comprehensive Cancer Network Guidelines revised in 2014, staging/histological classification and treatment plans for thymoma are summarized in addition to those for thymus cancer [6]. According to these guidelines, complete removal of the tumor is recommended for resectable thymomas, and radiation therapy, chemotherapy, and/or postoperative adjuvant therapy are selected depending on the stage. Although there are reports of splenectomy for isolated splenic metastases from thymic carcinoma, no standardized treatment plans have been proposed [16]. We considered surgical resection to be reasonable because surgical resection is the first-choice treatment for thymoma. Eligibility for and effectiveness of surgical treatment of splenic metastases of malignant tumors vary depending on the primary lesion, and the long-term prognosis is still an issue that requires further investigation. We suggest that long-term follow up for at least 10 years is desirable after thymectomy even if the lesion is a low-grade thymoma [13].

Thymomas are rare lesions, and extra-thoracic spread of thymomas is extremely uncommon. Isolated splenic metastases from any primary lesion are extremely rare. This is the first report of an isolated splenic metastasis from a thymoma. Further cases are needed to standardize this surgery for such lesions.