First description of cervical intradural thymoma metastasis

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Figure5 : Cervical magnetic resonance imaging after radiation treatment showing (A) almost total disappearance of the mass and (B) axial view (red arrow).

Thymoma and thymic carcinoma are rare epithelial tumors, which originate from the thymus gland.

(Nicola Marotta, Cristina Mancarella, Davide Colistra, Alessandro Landi, Demo Eugenio Dugoni, and Roberto Delfini)

According to the World Health Organization there are “organotypic” (types A, AB, B1, B2, and B3) and “non-organotypic” (thymic carcinomas) thymomas. Type B3 thymomas are aggressive tumors, which can metastasize. Due to the rarity of these lesions, only 7 cases of extradural metastasis are described in the literature. We report the first and unique case of a man with cervical intradural B3 thymoma metastasis. A 46-year-old man underwent thymoma surgical removal. The year after the procedure he was treated for a parietal pleura metastasis. In 2006 he underwent cervical-dorsal extradural metastasis removal and C5-Th1 stabilization. Seven years after he came to our observation complaining left cervicobrachialgia and a reduction of strength of the left arm. He underwent a cervical spine magnetic resonance imaging, which showed a new lesion at the C5-C7 level. The patient underwent a surgery for the intradural B3 thymoma metastasis. Neurological symptoms improved although the removal was subtotal. He went through postoperative radiation therapy with further mass reduction. Spinal metastases are extremely rare. To date, only 7 cases of spinal extradural metastasis have been described in the literature. This is the first case of spinal intradural metastasis. Early individuation of these tumors and surgical treatment improve neurological outcome in patients with spinal cord compression. A multimodal treatment including neoadjuvant chemotherapy, surgery and postoperative radiation therapy seems to improve survival in patients with metastatic thymoma.

Core tip:
To date, only 7 cases of spinal extradural thymoma metastasis have been described in the literature. We report the first case of spinal intradural thymoma metastasis. Early individuation of these tumors and surgical treatment improve neurological outcome in patients with spinal cord compression. A multimodal treatment including neoadjuvant chemotherapy, surgery and postoperative radiation therapy seems to improve survival in patients with metastatic thymoma.

Introduction:
Thymoma and thymic carcinoma are uncommon epithelial lesions, which originate from the thymus gland. To date, the true incidence is not known, but it is estimated to be 0-15 cases/100000 people. Between the fifth and sixth decades of life, this pathology represents 0.2%-1.5% of all malignancies. According to the World Health Organization there are “organotypic” (types A, AB, B1, B2, and B3) and “non-organotypic” (thymic carcinomas) thymomas. Types A, AB, B1 and B2 thymomas are benign tumors. Type B3 thymomas are aggressive tumors of intermediate malignancy. Spinal metastases are very uncommon. In the literature, only 7 patients with spinal extradural metastasis have been described. We report the first and unique case of a man with cervical intradural B3 thymoma metastasis.

Maximum intensity projection reconstruction from computed tomography images shows C5-Th1 stabilization after the first intervention.
Figure1 : Maximum intensity projection reconstruction from computed tomography images shows C5-Th1 stabilization after the first intervention.

Case Report:
A thymoma was resected in a 46-year-old male in 1989. He did not submit himself to adjuvant therapy. A year after the procedure he underwent parietal pleura metastasis resection. The patient remained disease-free until 2006, when he complained a reduction of strength of the left arm, for the presence of a cervico-dorsal extradural metastasis. He underwent resection of the lesion and C5-Th1 stabilization (Figure 1). The lesion was totally removed (R0) and the dura mater appeared intact.

In 2013, the patient came to our observation complaining left cervicobrachialgia and a reduction of strength of the left arm. A cervical spine magnetic resonance imaging (MRI) showed a new lesion at the C5-C7 level (Figure 2). The lesion showed a homogeneous enhancement after gadolinium administration in the T1-weighted sequences, and enclosed the spinal cord, especially on the left side. From the imaging, it was not clear if the lesion was extradural or intradural. Intraoperatively, there was not pathological tissue in the epidural space; it appeared only after opening the dura mater. The patient underwent a sub-total resection, in order to preserve the spinal cord from the surgical manipulation. The lesion was intradural-extramedullary. It was adherent to the spinal cord surface in its lateral and anterior portions.

Cervical spine magnetic resonance imaging. A: A C5-C7 lesion with homogeneous enhancement after gadolinium administration in the T1-weighted sequences; B: T2 weighted sequences showing the enclosed spinal cord; C: Especially on the left side (red arrow). ...
Figure 2 : Cervical spine magnetic resonance imaging. A: A C5-C7 lesion with homogeneous enhancement after gadolinium administration in the T1-weighted sequences; B: T2 weighted sequences showing the enclosed spinal cord; C: Especially on the left side (red arrow). …

A spinal metastasis of the type B3 thymoma according to the World Health Organization 2004 was diagnosed (well-differentiated thymic carcinoma according to Marino and Muller-Hermelick). The immunohistochemical examination demonstrated positivity of neoplastic cells for CK19 and p63 and CD1a positive T-cells (Figure 3). Even if the resection was not total, no postoperative neurological deficits were observed. After 3 mo, the cervico-thoracic spine MRI showed a small residual tumor, especially anteriorly to the cervical spinal cord (Figure 4). Subsequently, focal radiotherapy (25.5 grays) was given. Cervical MRI after radiation treatment showed almost total disappearance of the mass (Figure 5). The patient is free of symptoms.

The immunohistochemical examination demonstrated positivity of neoplastic cells for (A) CK19, (B) p63 and (C) CD1a positive T-cells.
Figure 3 : The immunohistochemical examination demonstrated positivity of neoplastic cells for (A) CK19, (B) p63 and (C) CD1a positive T-cells.
Figure 4 : Magnetic resonance imaging of the cervico-thoracic spine at 3-mo follow-up showing (A) a small residual tumor, especially anteriorly to the cervical spinal cord and (B) axial view (red arrow).
Figure 4 : Magnetic resonance imaging of the cervico-thoracic spine at 3-mo follow-up showing (A) a small residual tumor, especially anteriorly to the cervical spinal cord and (B) axial view (red arrow).

A search was carried out about spinal thymoma metastasis in the English language literature. We excluded one work because it is available only in Japanese language[4] and another because it did not report sufficient data to be included in our series. We used the following key words: “thymoma metastasis”, “thymic carcinoma”, “spinal cord compression”, and “spinal metastasis”. The data were extracted according to these parameters: (1) author and year of publication; (2) age; (3) sex; (4) time to spinal metastasis; (5) site of spinal metastasis; (6) sign and symptoms; (7) surgery; (8) follow-up; (9) radiotherapy; and (10) classification of histological type of the thymoma.

Figure5 : Cervical magnetic resonance imaging after radiation treatment showing (A) almost total disappearance of the mass and (B) axial view (red arrow).
Figure5 : Cervical magnetic resonance imaging after radiation treatment showing (A) almost total disappearance of the mass and (B) axial view (red arrow).

DISCUSSION
We found 6 papers, in which 7 cases were described. We included our case in the review, for a total number of 8 cases of spinal thymoma metastasis. Four patients were male and 3 were female. About the age, the average was 51.4 years old (range, 29-70 years). The median time from thymoma diagnosis to spinal metastasis was 7.9 years (range, 1-17 years); in one case the spinal metastasis was diagnosed before primary tumor; the case with longer time to spinal metastasis was our case. The spinal metastases were localized at the thoracic level in 4 cases, at the cervico-thoracic site in 1 case, cervical level in 2 cases, and lumbar level in 1 case. Patients presented symptoms related to the thymoma in 2 cases (myasthenia gravis); in all cases they had neurological symptoms related to the spinal metastasis (motor deficit, sensitive deficit or pain). All patients underwent surgical treatment. During the follow-up, 3 patients died after 3 mo, 5 mo and 2 years, respectively; 4 patients survived with a time of follow-up from 9 mo to 8 years (our case). Five patients did not receive radiation therapy, and 2 underwent RT. Histological diagnosis was not based on the actual WHO classification in 2 cases; the histological subtype was B2 in 1 case, B3 in 2 cases, and C in 2 cases.

Thymoma and thymic carcinoma are uncommon epithelial lesions, which originate from the thymus gland. Thymoma is a rare tumor, commonly associated with the myasthenia gravis (15%); local dissemination occurs quickly, but distant spinal metastasis may occur up to 16 years after the diagnosis of thymomas. They can metastasize to the pleura regional nodes, liver and lung. Spinal metastases are very uncommon. In the literature, only 7 patients with spinal extradural metastasis have been described. We report a unique case of spinal intradural metastasis. On MRI, the vertebral metastases appear hypointense on T1-weighted images and hyperintense on T2-weighted images. Infiltration of the paravertebral muscles and vertebral elements, evident on axial views, is possible. Imaging after gadolinium administration shows an important enhancement. A computed tomography scan shows infiltration of the vertebral body, with both osteolytic and osteoblastic lesions. The spinal metastasis can cause, in fact, vertebral collapse, spinal instability and neurological deterioration. Early diagnosis and surgery have the goal to control pain and reduce motor deficits. It is fundamental to take in account that an invasive thymoma can metastasize both extradurally and intradurally, because patient’s survival may be extended by an early diagnosis followed by an appropriate treatment.

We report the first case of spinal intradural metastasis. It is not yet known the gold standard of treatment, but a multimodal treatment which includes neoadjuvant chemotherapy, surgery and postoperative radiotherapy seems to improve survival in patients with metastatic thymoma.

References

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3. Marino M, Müller-Hermelink HK. Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus. Virchows Arch A Pathol Anat Histopathol.1985;407:119–149. [PubMed]
4. Akamatsu H, Tsukuura T, Matsunaga H, Suzuki A. [Study of combination therapy for thymoma: a case of stage IV which presented as total spinal block caused by epidural metastasis and which preoperative combination therapy was effective for minimizing the tumor] Kyobu Geka. 1993;46:1156–1160. [PubMed]
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Francesco Marotta
Prof. Marotta is one of the world's leading researchers on probiotics and human health. After his graduation from Catania University with MD (cum Laude) in 1981, he joined University of Chicago as a visiting fellow in gastroenterology. Two years later he was selected by South African Education Ministry to serve as registrar at the University of Cape-Town, Groote Schuur Hospital. He is the first Italian to obtain a PhD from the University of Hirosaki, Japan with entire curriculum in Japanese. He later received a Fellowship from the Japanese Science & Technology Ministry to continue his studies at the National Cancer Center in Tokyo. Upon returning to Italy, he was appointed as chief consultant in Gastroenterology at S. Anna Hospital, Como, Italy and then as Consultant at Hepato-GI Unit, S. Giuseppe Hosp., Milano, Italy. He is also Consulting Professor at WHO-affiliated Center for Biotechnology and Traditional Medicine, Dept. of Anatomy, University of Milano, Consulting Professor of BioGerontology, Urology Dept., University of Pavia and Visiting Professor at many Japanese Institutions. He also acts as international consultant to several Asian and middle-eastern gastroenterological societies, and has chaired several international gastroenterology, bioscience and aging meetings. He has received over 20 national and international awards for research papers and lectures at distinguished universities. He is the leading author of several papers, over 350 scientific communications and lectures and many book sections dealing with experimental and clinical gastroenterology, oxidative stress and aging.

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