Metastasis of pulmonary adenocarcinoma to right occipital parafalcine meningioma

Abstract Rationale: Tumor-to-tumor metastasis is a rare clinical phenomenon. Although meningioma is the most common intracranial recipient of cancer metastasis, only a few cases have been reported. We present a case of metastasis of lung adenocarcinoma into intracranial meningioma and review the published literature. Patient concerns: A 70-year-old woman was admitted to our hospital for a 1-month history of headache and pain in her lower extremities. Diagnosis: Brain and lumbar vertebral magnetic resonance imaging showed an intracranial space-occupying lesion in the right occipital region and spinal canal stenosis. Pulmonary computed tomography showed an irregular mass in the right upper lobe of the lung. The postoperative histological examination demonstrated adenocarcinoma metastasis to meningioma. Intervention: The patient underwent right occipital craniotomy for tumor removal and lumbar spinal canal decompression. Outcomes: There were no initial abnormal conditions after the operation. However, the patient died suddenly 7 days after surgery. Lessons: Tumor-to-meningioma metastasis is a rare but important phenomenon. According to previous reports, it is associated with rapid onset of symptoms and a poor prognosis. Histological examination is of great importance in diagnosis. The history and process of malignant carcinoma should be closely monitored.


Introduction
Metastasis from one tumor to another is known as tumor-totumor metastasis (TTM), which is a rare phenomenon. [1] Meningioma, which constitutes 20% of intracranial tumors, is the most common intracranial recipient of systemic metastases. [2] Breast and lung carcinomas are the most common origins of TTM. [2,3] Because there have been few reported cases of metastasis to meningioma, the clinical characteristics of such patients are still unclear. According to previous reports, patients suffering from TTM have an extremely poor prognosis. Therefore, the accumulation of such cases is clinically relevant. Here, we report a case of lung adenocarcinoma metastasizing to meningioma.

Case report
This study was approved by the institutional review board at The First Hospital of China Medical University. Written consent was obtained from the family of the patient for publication of this case report and any accompanying images.
A 70-year-old woman was admitted to our institution with headache and pain in her lower extremities for 1 month, with the left side being more severe. Brain and lumbar vertebral magnetic resonance imaging (MRI) at the local hospital suggested an intracranial space-occupying lesion and spinal canal stenosis. Recently, she had suffered from pain in her waist and both hips and experienced laborious defecation. The patient had no history of smoking or drinking. She had grade 1 hypertension but no diabetes. We performed brain contrast-enhanced MRI and lumbar vertebral (L1-S1) 3-dimensional computed tomography (3D-CT). Brain MRI showed a well-circumscribed mass (4.5 Â 3.6 Â 4.7 cm) that had isointense signals on T1-weighted images and isointense signals with heterogeneity on T2-weighted image in the right occipital parafalcine region (Fig. 1A). Lumbar vertebral 3D-CT showed L3-S1 intervertebral disc bulge, ligamentum flavum thickening, and spinal canal stenosis. Lung CT showed an irregular mass in the upper lobe of the right lung (3.6 Â 3.3 cm), bone destruction in the bilateral ribs, inflammation in the lower field of both lungs, and pleural effusion, which suggested a malignant lesion derived from the lung (Fig. 1B). Comprehensive analysis of pulmonary function showed mixed ventilation dysfunction, small airway dysfunction, and a ventilation reserve of 89%. Following the advice of a respiratory physician, the patient underwent atomization inhalation treatment with ipratropium bromide aerosol, budesonide suspension, and ambroxol hydrochloride for inhalation during the perioperative period. According to the imaging examination, the preoperative diagnosis of the patient was lung cancer, lumbar spinal stenosis, and right occipital meningioma or metastatic tumor. Although lung biopsy was recommended, the patient refused.
Subsequently, the patient underwent right occipital craniotomy for tumor removal (Simpson grade II resection) and lumbar spinal canal decompression. Postoperative brain CT revealed normal postoperative changes, and the tumor was totally removed ( Fig. 2A). There were no initial abnormal conditions after the operation. However, the patient died suddenly of a cardiopulmonary accident 7 days after surgery. Due to the rapid deterioration of the patient, treatment for the lung lesion was not performed.
Immunohistochemically, the brain tumor stained positive for epithelial membrane antigen (EMA), progesterone receptor (PR), vimentin, and E-cadherin (Fig. 2B) and negative for glial fibrillary acidic protein (GFAP), S-100, p53, and oligodendrocyte transcription factor 2 (Olig2), which was consistent with WHO grade I meningioma. The focus within the meningioma stained positive for cytokeratin 7 (CK7) and thyroid transcription factor 1 (TTF-1; Fig. 2B) and negative for CK5/6, p63, CD56, and synaptophysin. TTF-1 and CK7 are markers expressed in adenocarcinoma of lung. Histologically, the brain tumor was psammomatous meningioma characterized by including numerous psammoma bodies (Fig. 2C, yellow arrow). Furthermore, there were hyperchromatic nuclei and prominent nucleoli cancer cells (Fig. 2C, red arrow) among meningioma cells (Fig. 2C, white arrow), which was consistent with metastatic carcinoma. The adenocarcinoma cells showed dense papillary hyperplasia with nuclear atypia (Fig. 2C, red arrow). Therefore, histopathological examination demonstrated adenocarcinoma metastasis to meningioma (Fig. 2C). Immunohistochemical and histopathological examinations were performed and reported by the Department of Pathology at China Medical University.

Discussion
TTM is a rare and well-recognized phenomenon. [4,5] The most common malignant recipient tumor is renal cell carcinoma. [1,2] Meningiomas are the most common benign tumors to harbor systemic metastases, [6] but tumor-to-meningioma metastasis (TMM) has rarely been reported since the first case reported by Fried in 1930. [7][8][9] To the best of our knowledge, there are fewer than 30 reports of lung carcinoma metastasis to meningioma. [3][4][5]7, The epidemiology of TMM is still unknown. From January 2011 to January 2019, there were 2922 consecutive patients diagnosed with meningioma and 540 consecutive patients diagnosed with intracranial metastatic tumor at the Department of Neurosurgery at The First Hospital of China Medical University. There was only 1 TMM patient, accounting for 0.03% of meningioma and 0.19% of intracranial metastasis cases.
For diagnosis of TTM, Campbell et al proposed the following criteria: at least 2 primary tumors must exist, the metastatic focus must show established growth inside the host tumor and not be of contiguous growth, and the host tumor must be a true neoplasm and cannot be a lymph node involved in leukemia or lymphoma. [1,35] Our case fulfilled the inclusion criteria for TTM established by Campbell et al. Previous studies presented different hypotheses related to the reasons why meningioma is the most common intracranial host in TTM. Meningiomas can provide an accessible and favorable environment for growth to receive metastases [19] because they are highly vascular tumors [36] and exhibit slow growth and an indolent nature. [19,37] Furthermore, their high collagen and lipid content may provide a "fertile soil" for the seeding of malignant cells. [6,19,20,38] Some researchers have suggested that cell-cell adhesion molecules, such as E-cadherin, [39,40] may play a role in TMM. [2,26,38,39] Ecadherin expression is downregulated when carcinoma cells escape from the primary tumor. [41] Metastatic cells resume Ecadherin expression upon seeding their destination. [14] It has been demonstrated that meningiomas highly express E-cadherin. [40,42] Moreover, meningiomas harboring metastases are more likely to express E-cadherin than meningiomas in general. [6] Therefore, the above evidence reveals that E-cadherin may play a role in TMM. Consistent with previous reports, in the present case, the tumor also exhibited high expression of E-cadherin, as demonstrated by immunohistochemistry (Fig. 2B). However, the relationship and underlying mechanism between E-cadherin and TMM requires further research. Psammoma bodies are concen-tric whorl calcification structures that exist in 45% of meningiomas. [43] The possible protective role of psammoma bodies in the spread of TMM has been discussed in previous reports, [11,22] and the meningioma in our case was rich in psammoma bodies. We summarize the published lung carcinoma TMM cases in Table 1 and immunohistochemical results in Table 2. The mean age of patients was 65.03 years (range, 39-91 years), and there were 15 women and 14 men among the published cases (female: male = 1.07:1). According to the available immunohistochemical results of published cases, the meningioma components were often positive for EMA, PR, and vimentin (except for 1 case of secretory meningioma), and the pulmonary carcinoma components were frequently positive for TTF-1 and CK7. All the cases were supratentorial lesions. Except for 1 case of atypical meningioma, the others were benign meningiomas. The most common type of lung carcinoma was adenocarcinoma (69.0%). Most of them were discovered by chance at surgery or autopsy and had the feature of a previously existing malignant tumor. However, cases of TMM of occult lung malignant tumors have www.md-journal.com Table 1 Summary of cases of lung carcinoma metastasis to intracranial meningioma. rarely been reported. [5,23,27,31] In our case, there were no preoperative symptoms of lung carcinoma except for an irregular mass on imaging examinations. Many authors have considered it difficult for clinicians to provide a specific preoperative diagnosis of TMM by imaging examination. [2,27,28] There are no conclusive MRI features. [25,27,28] Danisman Specialist et al suggested that perfusion MRI is an advantageous preoperative proposal for differential diagnosis of meningioma. [33] Lung carcinoma is known to commonly metastasize to the brain, with 10% to 36% of all lung carcinomas developing brain metastasis. [44] The average survival of patients with brain metastasis is less than 6 months. [45,46] Whole-brain radiotherapy is the main treatment for brain metastases, but it is limited by long-term side effects. [47] A combination of stereotactic and whole-brain radiotherapy for brain metastases can significantly improve local control. [48] In the previous reports, 7 patients (24.1%) underwent lung lobectomy. Nineteen patients (65.5%) underwent craniotomy. In patients without early positive intervention for malignant carcinoma, the course of the disease often deteriorated quickly, and they had poor prognosis. For intracranial lesions of TMM, surgical indications are usually space-occupying effects and central nervous system symptoms. In the present case, the intracranial tumor had a maximum diameter of 4.7 cm. Based on the preoperative imaging examination, it was considered to be meningioma, although metastatic tumor could not be excluded because of the irregular mass in the lung. Therefore, surgical resection was performed. Owing to incomplete follow-up information in previous case reports and the rarity of the disease, we are unable to summarize the specific survival period. According to the data available to us, the shortest postoperative survival time is 30 hours, and the longest is 9 months. The patient in our case suddenly developed dyspnea and cardiac arrest at 7 days postoperatively. Although rescue was performed, her condition continued to deteriorate. Our patient died shortly after surgery, and since autopsy was not performed, we were unable to determine the exact cause of death. However, we should carefully assess the systemic status of patients and surgical indications, because coexistent malignancy and TMM might significantly affect patients' physical function. Therefore, aggressive surgical treatment should be carefully considered and advised. Due to the poor prognosis, it is necessary to develop an optimal management method for these superimposed malignancies.

Conclusion
TMM is a rare but important phenomenon. The precise mechanisms of this unique event remain undefined, and most patients have an extremely poor prognosis. Histological examination is the only diagnostic approach. The history and clinical process of TMM should be closely monitored.