Meningiomas are primary benign tumors that occur in the intracranial and intraspinal regions. Although most meningiomas are benign, in rare cases, they could be malignant with aggressive metastases¹²⁾. The types of meningiomas that can metastasize are the atypical (World Health Organization [WHO] grade II) and anaplastic (WHO grade III) types²⁾, which account for less than 5% of all meningiomas⁹⁾. In particular, extracranial metastasis is rarer, with an estimated incidence of 1 to 5 cases per 1000, and spinal metastasis has been reported only in a few studies^1,3). We present a unique case of a patient diagnosed with anaplastic meningioma in 2011 with spinal metastasis, confirmed during examination for the second revision surgery due to the recurrence of the primary tumor.

A 56-year-old female patient at the time of diagnosis in January 2011 suffered from dull headaches, mild dysarthria, and sudden-onset blurred vision. On examination, she was lethargic with mild weakness (Medical Research Council [MRC] scale 4) in the left upper limbs. Contrast-enhanced computed tomography (CT) revealed a mass with peripheral vasogenic edema and a dense area in the right temporal lobe (Fig. 1A). Magnetic resonance imaging (MRI) showed a homogeneously enhanced mass (approximately 5.5 × 2.8 × 3.6-cm in size) (Fig. 1B). In June 2011, the patient underwent right craniotomy and gross total resection. After the first surgery, there was no improvement in left motor weakness, but consciousness and speech were restored. Histological examination revealed anaplastic meningioma (WHO grade III). Gamma knife radiosurgery was performed 4 times at post-operative 2-, 4-, and 6-years to remove the remnant tumors after the initial surgery. Subsequently, an increase in the size of the remnant tumor in the primary site was confirmed in a follow-up MRI 7 years post-operatively (Fig. 2). A revision surgery was conducted, and the patient received radiotherapy of 60 Gy over 6 weeks.

Spinal metastasis of the primary tumor was confirmed when the second revision surgery was to be performed. During the outpatient follow-up after the second revision surgery and radiotherapy, the patient complained of radiating back pain and weakness in the upper and lower extremities (MRC scale 3) which were absent before. A recurrence of the lesion was suspected, and MRI was performed. A mass, mimicking an en-plaque meningioma with an irregular margin (3.3 x 2.0 x 1.2-cm), and perilesional edema were confirmed (Fig. 3). The peculiarity here is that, unlike before, the patient rarely complained of headaches. There was back pain, and the weakness in the upper and lower extremities worsened and was accompanied by leg numbness, predominantly on the right. After a physical examination of the patient, a contrast-enhanced spinal MRI was utilized to evaluate the presence of metastasis to the spine. Although with some degree of expectation, an MRI of the spine revealed a lesion that appeared to be a contrast-enhancing metastatic tumor. Two contrast-enhancing lesions were identified, two intradural extramedullary tumors at the C2-3 level approximately 2.0 cm in size (Fig. 4A, B), and at the L4-5 level approximately 3.6 cm in size (Fig. 4C, D). Including radiating back pain, and weakness in the right upper, lower limbs and left lower limbs that were not previously present had been assumed to be related to spinal metastasis. We performed three surgeries on the patient. First, we decided to operate on the recurring tumor in the brain. For the spinal tumors, we planned to operate on the lumbar region first, followed by the cervical region. Craniotomy was achieved using a previous incision. Gross total resection was performed, and this included the lateral walls of the superior sagittal sinus and falx, which were invaded by the tumor. In the lumbar region, subtotal laminectomy was conducted for the L3 lamina, and the tumor was removed by total laminectomy for the L4 lamina. Facetectomy was conducted to ensure complete tumor resection because it was difficult to remove the tumor while preserving the right facet. To prevent spinal instability, pedicle screw fixation and posterolateral fusion were performed on the L4 and L5 lamina. The tumor in the cervical area was removed by total laminectomy of the C2 lamina; however, the tumor in the left neural foramen area surrounded the vertebral artery and could not be completely removed. Biopsies and immunohistochemical staining were performed during each of the surgeries. Brain tumors showed the proliferation of atypical cells with positivity for epithelial membrane antigen, confirming the diagnosis of meningioma. The tumor was classified as an anaplastic meningioma (WHO grade III) because the tumor cells had nuclear atypia, indicating malignancy. The tumor also showed extensive necrosis, high mitotic activity (19 mitoses/10 high-power fields [HPFs]), and a high Ki-67 proliferation index (approximately 30%). Although tumors in the lumbar and cervical lesions had low mitotic activity (2 mitoses/10 HPFs versus 1 mitoses/10 HPFs), both tumors also showed the same nuclear atypia as tumors in the brain and were diagnosed as anaplastic meningioma. Necrosis and a high Ki-67 proliferation index were also identified in the cervical and lumbar tumors. Glial fibrillary acidic protein (GFAP) and S-100 proteins were absent in all three tumors (Fig. 5). The patient provided informed consent and this case report was approved by the Institutional Review Board (IRB) of Pusan National University Yang-san Hospital (IRB No. 2023-10-020).

Meningioma originates from the intracranial meninges, consists of meningeal epithelial cells, and is one of the most common tumors that affect the central nervous system⁶⁾. Although meningiomas are often benign, their clinical characteristics are variable. In certain histologically distinct subsets, they may recur after complete resection¹⁴⁾. Malignancy and extracranial metastasis are rare in meningioma^1,3). According to WHO criteria, meningiomas are histopathologically subdivided into three grades⁸⁾ (Table 1). A high probability of grade II and III extracranial metastasis has been reported in the literature^5,16). The most frequent sites of metastasis for malignant meningioma are the lungs (60%), abdomen and liver (34%), cervical lymph nodes (18%), iliac, pelvic, and cranial cavity (11%), pleural (9%), central nervous system (7%), and mediastinum (5%), Only 7% occur in the vertebrae⁷⁾. Cases of spinal metastases are rare. A few cases of spinal metastases have been published to date^13,17,18). Immunohistochemical analysis of Ki-67 proliferation index or CDKN2A deletion, associated with 9p21 deletion, is also useful in assessing meningioma recurrence and/or metastasis¹⁵⁾.

Surgical resection may also increase the risk of iatrogenic metastasis of meningiomas with atypical histology, which is believed to be the case in this patient. The primary tumor was located around the Sylvian fissure, and it is presumed that the Sylvian fissure was exposed during the initial and revision surgeries. This iatrogenic cause created a passage between the tumor and the subarachnoid space, which eventually provided an opportunity for the tumor to spread freely along the pathway of cerebrospinal fluid^1,11). In addition, the primary tumor was an anaplastic meningioma, and its multiple recurrences and short interval suggest that extracranial metastasis may have occurred^9,10). Therefore, based on experience in our case, although the incidence of intracranial anaplastic meningioma is low, spinal metastases can occur even with small tumors.

Currently, there are no consensus guidelines for the treatment of metastatic meningioma⁴⁾. The treatment methods for spinal metastases include medical therapy, surgery, and radiation therapy. Based on the extension of life expectancy of patients with tumors due to the development of modern medicine and experience in our case, it is thought that surgical intervention is necessary when pain control, nerve function recovery, and spinal stabilization are to be achieved.

Although uncommon, metastasis of primary malignant meningioma should always be included in the differential diagnosis once there is evidence of pathology and immunohistochemical analysis suggesting metastasis. In addition, if a patient is diagnosed with malignant meningioma, evaluation for spinal metastases is necessary.