Abstract
Background: Thymic carcinoma is a rare cancer that often metastasizes to the liver and kidneys but rarely to the brain. Case Report: We present a rare case of an 81-year-old woman with multiple cerebellar metastases of thymic carcinoma. She was initially diagnosed with stage IVb thymic carcinoma based on biopsy examination of a lesion in the anterior mediastinum. The patient refused to undergo treatment at the time. Six months later, she presented with gait disturbance and nausea. Contrast-enhanced magnetic resonance imaging revealed multiple cerebellar metastases. She underwent craniotomy and resection of the left cerebellar metastasis. Postoperative histological examination confirmed metastasis of the original thymic carcinoma. The patient underwent additional stereotactic radiotherapy for the cavity of the cerebellar metastasis and the small cerebellar metastatic lesions. Seven months after radiotherapy, she died due to progression of the thymic carcinoma. Conclusion: We believe that these findings add important information to the literature on this rare entity.
Thymic epithelial tumours (TETs) are very rare tumours that are classified as thymomas or thymic carcinomas based on the histological features of the thymic gland. The annual incidence of TETs is approximately 0.15 per 100,000 individuals (1). TETs often occur in adults who are over 30 years of age, and there is no gender-based difference in their incidence. More than half of all cases are asymptomatic and are often found incidentally during medical check-ups. TETs mainly exhibit local invasion, therefore hematogenous distant metastasis is rare (2). They often metastasize to the liver, kidney, lung, and bone but rarely to the brain (3-5). Compared with thymomas, thymic carcinomas are more likely to metastasize, and these metastases are most common in the pleura, followed by the bone and liver (6). We reviewed the literature from 1984 to the present and found reports on only 26 cases of thymic carcinoma metastasis to the brain (7-20). Here, we report a rare case of thymic carcinoma brain metastasis and review its medical and surgical management.
Case Report
The patient was an 81-year-old woman who had visited our hospital for a medical check-up when she was 72 years old. During the check-up, an abnormal mediastinal shadow was observed in a chest radiograph. Computed tomography (CT) of the chest was indicative of a tumour that resembled TET. She was encouraged to have another medical examination, but she hoped to undergo a radiological follow-up examination. Nine years later, CT of the chest revealed an irregular mass in the anterior mediastinum, and a contrast-enhanced CT revealed lesions that were suspected of being metastases in the right lung, sternum, and left adrenal gland (Figure 1). At the time, magnetic resonance imaging (MRI) of the head revealed that there was no brain metastasis. An open biopsy of the anterior mediastinum was conducted to establish a definitive diagnosis. Immunohistochemical staining of the biopsy sample showed that the lesions were positive for CD5, CD117, and p40. Based on these immunopathological findings, the patient was diagnosed with stage IVb thymic carcinoma (Figure 2).
Imaging findings for the mass of the anterior mediastinum. Chest radiograph (A), plain (B) and contrast-enhanced (C) computed tomography scans depict the irregular mass.
Histopathological findings for the lesions detected in the present case. A: Histopathological findings showing polygonal tumour cells with enlarged nuclei in the fragmented tissue proliferated on the sheet and in the form of alveolar lesions (haematoxylin–eosin staining). B: Immunohistochemistry of tumour cells showing positive staining for CD5. C: Immunohistochemical results showing CD117 positivity in tumour cells. D: Immunohistochemical results showing p40 positivity in tumour cells. Original magnification, A: ×200; B-D: ×200.
She hoped to undergo follow-up without chemotherapy and radiation therapy again. Six months later, she presented with gait disturbance and nausea. MRI was indicative of brain metastasis in the left cerebellum attached to the tentorium (Figure 3).
Pre- and postoperative magnetic resonance imaging (MRI) findings for metastatic masses in the cerebellum. Preoperative contrast-enhanced MRI showing a metastatic mass in the left cerebellum (A and B: axial images, C: sagittal image). Postoperative MRI showing the remnant of the tumour attached to the tentorium and new small metastases in the right cerebellum (D-F: axial images).
The tumour was removed via infratentorial craniotomy. The tumour had partially adhered to the dural matter, therefore dural invasion was suspected. Pathological examination showed that the tumour cells were polygonal in shape, proliferating and had enlarged nuclei. Additionally alveolar lesions accompanied by necrosis were observed in some places. Polygonal tumour cells were observed in all the lesions examined. Based on the findings, the patient was diagnosed with brain metastasis of thymic cancer.
After the craniotomy procedure, the patient’s symptoms improved quickly. Stereotactic radiotherapy with a 35-Gy dose delivered in 7-Gy daily fractions was performed for the cavity of the cerebellar metastasis and small metastases. The patient refused further treatment for thymic carcinoma. Seven months after radiotherapy, she died as a result of progression of the thymic cancer.
Discussion
Here, we discuss the findings and implications of a rare case of brain metastasis of thymic carcinoma that was treated with surgery and radiotherapy.
According to the World Health Organization’s classification system for TETs established in 2004 (3), TETs are classified into type A, AB, B1, B2, B3, and C (thymic carcinoma) based on the degree of malignancy. Type A, AB, B1, B2, and B3 thymomas are characterized by CD99-positive immature T-lymphocytes, while type C (thymic carcinoma) thymoma does not have CD99-positive immature T-lymphocytes (5, 21, 22). In the present case, the patient was diagnosed with thymic carcinoma. In a previous report, 58.6% of TETs with brain metastases were histopathologically diagnosed as thymic carcinoma (19). This may mean that thymic carcinomas have a greater propensity for brain metastasis than other TETs. Thus, patients diagnosed with thymic carcinoma must be regularly followed-up and examined for brain metastasis.
The Masaoka classification system is used to define the extent of TETs as stage I (macroscopic encapsulation with no microscopic capsular invasion), stage II (macroscopic invasion into the fatty tissue surrounding the mediastinal pleura or microscopic invasion into the capsule), stage III (macroscopic invasion into neighbouring organs), stage IVa (pleural or pericardial dissemination), and stage IVb (lymphogenous or hematogenous metastasis). The findings in the present case were indicative of stage IVb TET, due to brain metastasis.
The main treatment for stage I and II tumours is surgery, and stage III and IV tumours are usually treated by chemotherapy combined with surgery (23). Radiation therapy is often used in cases of incomplete resection. Since 1984, the treatment of thymic carcinoma has included surgery and radiation therapy, and the application of chemotherapy is gradually increasing. In the present case, the patient underwent craniotomy and radiation therapy for brain metastasis but refused further treatment for thymic carcinoma.
The 5-year survival rate of patients with type A, AB, B1, and B2 TETs is 100%, and that of type B3 TETs is 65%. Furthermore, the 10-year survival rate of patients with type A, AB, and B1 TETs is 100%; type B1 TETs, 94%; type B2 TETs, 77% (24); and thymic carcinoma (type C), 15-19% (7, 25). With regard to tumours classified under different Masaoka stages, the 5-year rate was 92.6% for those with stage I tumours, 85.7% for stage II tumours, 69.6% for stage III tumours, and 50% for stage IV tumours (4). With regard to brain metastasis of TETs, it has been reported that the overall survival after the detection of a single brain metastasis was 256 days, and it was 64 days after the detection of multiple brain metastases (16). Among the 27 reported patients with brain metastasis of thymic carcinoma including our case, 12 were male, six were female, and nine were unknown in the reports with a median age of 49 years (range=31-81 years). Most patients underwent surgery and additional radiosurgery. The time to brain metastasis from initial diagnosis of thymic carcinoma was within 6 months in eight cases but more than 7 months in 10 cases. Once thymic carcinoma has been diagnosed, a screening test with MRI of the head is recommended. Nine died within 16 months of diagnosis (Table I). These findings indicate that metastases to the brain are associated with poor prognosis.
Summary of the reported cases of brain metastasis of thymic carcinoma.
Conclusion
This case report highlights that metastasis to the brain may occur in patients with thymic carcinoma and is associated with poor prognosis.
Footnotes
Conflicts of Interest
The Authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Authors’ Contributions
TM, KG, and HN performed the surgery. TM, HI and RM analyzed the clinical course and wrote the manuscript. All Authors discussed the clinical results, critically revised the report, commented on drafts of the manuscript and approved the final manuscript. IN and HN supervised the findings of this case.
- Received December 2, 2021.
- Revision received December 14, 2021.
- Accepted January 7, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
References
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.