An Official publication of The Asian Congress of Neurological Surgeons (AsianCNS)

Search Article
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Advertise Subscribe Contacts Login  Facebook Tweeter
  Users Online: 64 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size  

   Table of Contents      
Year : 2020  |  Volume : 15  |  Issue : 1  |  Page : 70-75

Intramedullary metastasis to the cervical spinal cord from malignant pleural mesothelioma: Review of the literature and case reports

1 Department of Neurological Surgery, Galliera Hospitals, Genova, Italy
2 Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy

Date of Submission10-Oct-2018
Date of Acceptance20-Aug-2019
Date of Web Publication25-Feb-2020

Correspondence Address:
Claudia Scudieri
Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina, 60 20132, Milan
Dr. Fotios Kalfas
Department of Neurological Surgery, Galliera Hospitals, Via delle Cappuccine, 16128, Genova
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajns.AJNS_234_18

Rights and Permissions

Context: Malignant mesothelioma is an aggressive tumor; median survival of patients following diagnosis is 12 months. Aims: Pleural malignant mesothelioma tends to spread along preexisting tissue planes and has the rare ability to spread along the nerve root into the spinal cord. In our case, there is an evidence of exceptional direct hematogenous spread to the spinal cord by the spinal branch of the intercostal arteries or the veins of Batson's plexus. Settings and Design: The authors report a case of intramedullary hematogenous metastasis to the cervical spinal cord from malignant mesothelioma, with a review of the literature. Materials and Methods: A 68-year-old male was admitted to our department because of a slowly progressive mild weakness of both low extremities, more pronounced on the left side. The patient has been treated for a malignant mesothelioma with left thoracotomy and subsequently underwent radiotherapy. Magnetic resonance imaging of the cervical-thoracic spine revealed a contrast-enhancing intramedullary expansive lesion of the left half of the spinal cord at the C6–C7 level. Results: The patient underwent surgical treatment through a C6–C7 laminectomy. Through a median posterior spinal cord incision, an intramedullary grayish lesion was completely removed. The paraparesis progressively improved and 20 days after surgery, the patient had regained normal lower extremity function. Conclusions: Malignant mesothelioma can spread to the spinal canal by the direct extension through the intervertebral foramina, by hematogenous spread to the spinal meninges, and by perineural growth along a single nerve root. The cleavage plane of the tissue may determine whether a successful gross total resection can be achieved with a good outcome for the patient.

Keywords: Cervical spinal cord, intramedullary metastasis, malignant mesothelioma, surgery

How to cite this article:
Kalfas F, Scudieri C. Intramedullary metastasis to the cervical spinal cord from malignant pleural mesothelioma: Review of the literature and case reports. Asian J Neurosurg 2020;15:70-5

How to cite this URL:
Kalfas F, Scudieri C. Intramedullary metastasis to the cervical spinal cord from malignant pleural mesothelioma: Review of the literature and case reports. Asian J Neurosurg [serial online] 2020 [cited 2021 Nov 27];15:70-5. Available from:

  Introduction Top

Malignant mesothelioma is aggressive cancer arising from the mesothelial surfaces of the pleural in 80% of all cases.[1] The prognosis of pleural malignant mesothelioma (PMM) is dismal even with multimodal therapy; median survival is 12 months after symptom onset.[1],[2],[3],[4],[5] PMM has an increasing incidence due to environmental factors and has been strongly related to inhalational exposure to asbestos[1],[4],[6],[7],[8] but also inhalation of other mineral fibers, such as erionite, a fibrous crystal found in Turkey, has also been identified as a risk factor.[3] Although malignant mesothelioma is a rare disease, the lack of effectiveness in treatment and the increasing incidence through the world have led to improve the clinical research in this field.[1],[9]

Mesothelioma has a predilection for local spread into adjacent tissues.[10] Sites of spread are most thoracic lymph nodes, the contralateral pleura, the abdominal cavity, and distant organs through hematogenous dissemination in the later stages of the disease.[2],[11],[12],[13],[14]

Spinal involvement of a PMM is exceptional with only a few reported cases.[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33]

The authors report a case of a hematogenous intramedullary metastasis to the cervical spinal cord from malignant mesothelioma. Six articles with cranial or spinal meningeal infiltration of a mesothelioma without intradural tumor were found in literature.[28],[30],[34],[35],[36] Ten reports [Table 1] were retrieved with one case of intradural mesothelioma each,[12],[13],[17],[18],[19],[20],[21],[22],[23],[25] two of which were in intradural extramedullary location,[23],[24] and eight of which showed intramedullary growth[12],[13],[17],[18],[19],[20],[21],[22],[25] [Table 2]. These eight cases were analyzed and together with the current case, serve as the basis for the discussion of intradural intramedullary metastasis from PMM.
Table 1: Intradural spinal cord metastasis from pleural malignant mesothelioma

Click here to view
Table 2: Overall review of intramedullary metastasis from pleural malignant mesothelioma

Click here to view

  Case Report Top

On March 2000, a 68-year-old, right-handed male with a history of malignant mesothelioma was admitted to our department after 3 weeks of progressive mild bilateral low extremity weakness, more pronounced on the left side. The patient had previous occupational exposure to asbestos working at a fiber cement factory for 20 years, and in 1989, he was diagnosed with asbestosis. He had undergone a left thoracotomy for tumor resection and subsequently treated with local radiotherapy 1 year ago.

Neurological examination revealed a paraparesis of lower extremities (4/5 on the right and 3/5 on the left side), decreased light touch, pain, and temperature sensation on the right side below T1, without sphincter disturbance. Increased reflexes in the lower extremities, while the joint position and vibration sense were normal. He had upgoing toes bilaterally (partial Brown–Sèquard syndrome). Cervical X-rays film did not show any bony abnormalities. Magnetic resonance imaging (MRI) of the cervical-thoracic spine revealed a hypointense left intramedullary anterolateral lesion at the level of C6–C7 strongly enhancing after gadolinium administration [Figure 1] and [Figure 2].
Figure 1: Coronal T1-weighted magnetic resonance images of the cervicothoracic spine after gadolinium injection demonstrating a well-shaped enhancing mass in the spinal cord at the C6–C7 level. Images showing no evidence of (a) perimedullary or paravertebral (b) mass (yellow arrowheads)

Click here to view
Figure 2: Axial T1-weighted magnetic resonance images after gadolinium injection, showing intradural enhancing mass, with no evidence of transdural extension or foramina involvement (yellow arrows)

Click here to view

The patient underwent surgery through median posterior short incision and C6–C7 laminectomy. Opening the dura and the arachnoid, the spinal cord appeared bulky on the left side by an intramedullary grayish lesion that was completely removed, even though a clear plane was difficult to identify between the tumor and surrounding spinal cord. No intradural or extradural nerve involvement was seen. Pathological examination of the specimen revealed malignant mesothelioma. The cells exhibited large irregular nuclei with prominent nucleoli, small-to-moderate amounts of pale-staining cell cytoplasm, and mitotic figures [Figure 3]. Immunohistochemical staining was positive for keratin, vimentin, epithelial membrane antigen, and cytokeratin 5/6 and was negative for S100, CD15 (LeuM1), and carcinoembryonic antigen. This staining profile was consistent with sarcomatous-type malignant mesothelioma.
Figure 3: Hematoxylin and eosin staining (a and b) showing mesothelioma cells with large irregular nuclei and prominent nucleoli, pale staining cell cytoplasm, and mitotic figures

Click here to view

The postoperative course was favorable. The patient's neurological condition improved and 20 days after surgery, he had completely regained normal lower extremity function. Eight months after surgery, the patient died due to the progression of the thoracic disease.

  Materials and Methods Top

Intradural mesothelioma is highly uncommon and has been reported in 11 cases, including the present case, so far[12],[13],[17],[18],[19],[20],[21],[22],[23],[24],[25] [Table 1] and [Table 2]. In two cases,[23],[24] the lesion was extramedullary. In one of those two cases,[23] a thoracic roots invasion by desmoplastic malignant mesothelioma without intramedullary tumor localization were reported.

  Discussion Top

Overhauling our analysis [Table 1] and [Table 2], spinal involvement of a malignant PMM is in general exceptional and occurs most commonly as involvement of the vertebral body or epidural space.[3],[11],[27],[33],[37],[38] Spinal metastasis can be considered as a direct centrifugal extension into the nerve root through the intervertebral foramen, or as a result of hematogenous spread to the meninges through the intercostal arteries or the veins of Batson's plexus.[21],[28],[30] A characteristic way of spreading is perineural or “neurotropic” growth along nerve roots due to primary tumors neurotropism.[11],[24] Extension along the pia matter or arachnoid membrane surrounding the nerve root, known as leptomeningeal spread, can be interpreted as one of the hematogenous metastases. Eight previous case reports document intramedullary spinal cord metastasis due to PMM. Compared to all cases reported above, in only three cases (including our case), intramedullary tumors were considered resulted from hematogenous or leptomeningeal spread, without continuity with the pleural lesion.

Due to the paucity of cases, no prediction can be made for which histological type of mesotheliomas has a tendency for intradural spread. Sarcomatous desmoplastic malignant mesotheliomas constitute approximately 10% of malignant mesotheliomas[1],[9],[33] and have been more frequently associated with metastasis and shorter survival in one series.[1]

In six[17],[18],[19],[22],[25] of the 11 cases reported so far, including the present case, a sarcomatous type malignant mesothelioma was detected in the histological examination suggesting a strong tendency of this type of mesothelioma for intradural spread.

However, it may be hypothesized that a protracted course of disease may leave enough time for a mesothelioma to slowly transgress the dura and infiltrate the spinal cord; concordantly, Lee's case has a 18-month history,[38] Hillard's case a 24-month history,[12] and Payer's case a 28-month history of pleural mesothelioma prior to spinal infiltration.[19] In our case, diagnosis of intradural mesothelioma occurred in a patient with a 14-month history of PMM. The median time from symptom/treatment of PMM to diagnosis of intramedullary mesothelioma is 13.3 months, in the cases reported so far.

In our case, the tumor appeared as an intramedullary localized mass at the C6–C7 level and like in Cooper[15] and Yamamoto et al.[25] reports, there is an evidence of direct hematogenous spread to the spinal cord by the spinal branch of the intercostal arteries or the veins of Batson's plexus. Hence, in our case, no leptomeningeal spread or neoplastic deposits to the arachnoid sheath was found. Furthermore, no epidural spinal canal, no nerve roots, or extramedullary involvement was found.

Intramedullary involvement is extremely rare,[6],[12],[13],[17],[18],[19],[20],[21],[22],[25] with nine cases including the present case. The majority of reports indicate that the thoracic spinal cord is most often involved, followed by one case of the junction cervical/thoracic cord. Our case is the second reported one of intramedullary cervical spine cord metastasis from PMM[6],[12],[13],[17],[18],[19],[20],[21],[22],[23],[24],[25] [Table 2]. No multiple metastases to the spinal cord are reported so far.

Most patients present with rapid onset of symptoms referable to the spinal cord, including pain, weakness, sensory loss, and incontinence. Weakness is the most common presenting symptom and resembles a Brown–Sèquard syndrome. Sensory symptoms are often difficult to characterize but are frequent and may be contralateral to the weak extremity. In one case (Yamamoto et al.[25]), a Brown–Sèquard syndrome was associated to a C5 radiculopathy. Contrast-enhanced spine MRI is the most sensitive and reliable radiographic means to diagnose intramedullary mesothelioma.

As the disease progresses, patients often deteriorate and manifest a complete spinal cord transection with paraplegia. In most patients reported with intramedullary metastatic mesothelioma who underwent surgery did not achieve any improvement in their neurological condition. In our case, a favorable surgical outcome was achieved with normal lower extremity function. However, patient's preoperative neurological examination (partial Brown–Sèquard syndrome without sphincter disturbance) and short-time diagnosis to surgical treatment, were crucial for the outcome.

If the patient suffers neurological deterioration with possible preservable function, and preoperative imaging not indicates definitively whether the intraspinal involvement is intradural, surgical decompression with intradural exploration is recommended. Extradural tumor can be removed safely in most cases. Intradural tumor's cleavage plane of the tissue may determine whether successful gross total resection can be achieved. In selected cases, partial spinal decompression may be sufficient to prevent further neurological deterioration.[6]

The treatment of intramedullary metastasis from PMM is poorly defined, as there have been no prospective trials due in large part to the infrequency of occurrence. As a consequence, the literature reflects expert opinion, case series, and review of the literature. Two general approaches have been suggested: resective surgery and CyberKnife stereotactic radiotherapy. In the majority of the cases reported neither of these approaches or improve function. Although not in all cases of intramedullary metastasis due to PMM, a follow-up is available, an average survival period following diagnosis and treatment of intramedullary mesothelioma is settled between 3 and 11 months [Table 2].

New concept management of patients with PMM has used antifolate (pemetrexed or raltitrexed) platinum combinations and new radiotherapy techniques such as intensity-modulated radiation therapy.[39]

There are some reports that radiation therapy only is an effective treatment for intramedullary spinal cord metastasis in terms of clinical symptoms and radiological findings.[17],[22],[40],[41] However, there is no standard treatment for spinal cord metastasis. In case of undiagnosed or limited cases such as radioresistant tumors and rapid neurological deterioration, surgical resection is recommended. In our case, surgical resection was undertaken due to the moderate neurological symptoms, rapidly progressive neurological deterioration, and to confirm the definitive diagnosis.

  Conclusions Top

Spinal metastasis must be considered if a patient with PMM shows neurological worsening, and MRI shows an abnormal lesion in the cervical or more common in the thoracic cord. Sarcomatous-type PMM should be considered propended for intradural metastasis.

Despite the natural history of the disease and the management of the intradural mesothelioma both disappointing, we advocate surgical excision for the extradural localization. However, if the patient has neurological deterioration with possible preservable function, with a short time history of neurological sequelae, we recommend a neurologic decompression with intradural exploration. The cleavage plane of the tissue may determine whether a successful gross total resection can be achieved with a good outcome for the patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Sterman DH, Albelda SM. Advances in the diagnosis, evaluation, and management of malignant pleural mesothelioma. Respirology 2005;10:266-83.  Back to cited text no. 1
Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet 2005;366:397-408.  Back to cited text no. 2
Pistolesi M, Rusthoven J. Malignant pleural mesothelioma: Update, current management, and newer therapeutic strategies. Chest 2004;126:1318-29.  Back to cited text no. 3
West SD, Lee YC. Management of malignant pleural mesothelioma. Clin Chest Med 2006;27:335-54.  Back to cited text no. 4
Edwards JG, Abrams KR, Leverment JN, Spyt TJ, Waller DA, O'Byrne KJ. Prognostic factors for malignant mesothelioma in 142 patients: Validation of CALGB and EORTC prognostic scoring systems. Thorax 2000;55:731-5.  Back to cited text no. 5
Bourdès V, Boffetta P, Pisani P. Environmental exposure to asbestos and risk of pleural mesothelioma: Review and meta-analysis. Eur J Epidemiol 2000;16:411-7.  Back to cited text no. 6
Mohr S, Keith G, Rihn B. Asbestos and malignant pleural mesothelioma: Molecular, cellular and physiopathological aspects. Bull Cancer 2005;92:959-76.  Back to cited text no. 7
Pass HI, Lott D, Lonardo F, Harbut M, Liu Z, Tang N, et al. Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med 2005;353:1564-73.  Back to cited text no. 8
Hughes RS. Malignant pleural mesothelioma. Am J Med Sci 2005;329:29-44.  Back to cited text no. 9
Boutin C, Schlesser M, Frenay C, Astoul P. Malignant pleural mesothelioma. Eur Respir J 1998;12:972-81.  Back to cited text no. 10
Gijtenbeek JM, Brouwer HI, Boerman RH, Wiggenraad RG, Vecht CJ, Smitt PA. Extensive epidural cufflike growth of malignant pleural mesothelioma causing spinal cord compression. J Thorac Cardiovasc Surg 2002;124:200-2.  Back to cited text no. 11
Hillard VH, Liu JK, Kwok A, Schmidt MH. Perineural spread of malignant mesothelioma resulting in an intradural spinal cord mass: Case report. J Neurooncol 2007;81:185-9.  Back to cited text no. 12
Lee AW, Nikitins I, Pozza C, Koblar SA. Pleural mesothelioma with extension into the thoracic spinal cord. Intern Med J 2005;35:195-6.  Back to cited text no. 13
Lee YC, Light RW, Musk AW. Management of malignant pleural mesothelioma: A critical review. Curr Opin Pulm Med 2000;6:267-74.  Back to cited text no. 14
Semb G. Diffuse malignant pleural mesothelioma: A clinicopathological study of 10 fatal cases. Acta Chir Scand 1963;126:78-91.  Back to cited text no. 15
Au VW, Thomas M. Radiological manifestations of malignant pleural mesothelioma. Australas Radiol 2003;47:111-6.  Back to cited text no. 16
Chamberlain MC, Eaton KD, Fink JR, Tredway T. Intradural intramedullary spinal cord metastasis due to mesothelioma. J Neurooncol 2010;97:133-6.  Back to cited text no. 17
Okura H, Suga Y, Akiyama O, Kudo K, Tsutsumi S, Abe Y, et al. Pleural malignant mesothelioma causing cord infiltration through the nerve root. Case report. Neurol Med Chir (Tokyo) 2009;49:167-71.  Back to cited text no. 18
Payer M, von Briel T. Intradural pleural malignant mesothelioma. Acta Neurochir (Wien) 2007;149:1053-6.  Back to cited text no. 19
Newlin HE, Morris CG, Amdur RJ, Mendenhall WM. Neurotropic melanoma of the head and neck with clinical perineural invasion. Am J Clin Oncol 2005;28:399-402.  Back to cited text no. 20
Cooper D. Malignant mesothelioma invading the spinal canal. Postgrad Med J 1974;50:718-23.  Back to cited text no. 21
Dewas S, Le Rhun E, Duhem R, Dansin E, Prevost B, Lartigau E. Solitary intramedullary metastasis from malignant pleural mesothelioma treated with cyberKnife®: A case report. Rev Neurol (Paris) 2011;167:185-6.  Back to cited text no. 22
Richter H, Hildebrandt G, Heilbronner R. Intradural perineural spread of mesothelioma causing myelopathy by tethering of the spinal cord. J Neurol Surg A Cent Eur Neurosurg 2012;73:111-5.  Back to cited text no. 23
Steel TR, Allibone J, Revesz T, D'Arrigo C, Crockard HA. Intradural neurotropic spread of malignant mesothelioma. Case report and review of the literature. J Neurosurg 1998;88:122-5.  Back to cited text no. 24
Yamamoto J, Ueta K, Takenaka M, Takahashi M, Nishizawa S. Sarcomatoid malignant mesothelioma presenting with intramedullary spinal cord metastasis: A case report and literature review. Global Spine J 2014;4:115-20.  Back to cited text no. 25
Margery J, Grassin F, Le Moulec S, Ruffié P. Spinal cord compression from a malignant pleural mesothelioma. Rev Pneumol Clin 2005;61:112-4.  Back to cited text no. 26
Mikhael MA, Paige ML, Thayer C. Computerized tomography of malignant pleural mesothelioma with spinal canal invasion. Comput Radiol 1982;6:11-5.  Back to cited text no. 27
Murray JB, Neilly JB, Hadley D, Moran F, McKean M. Diffuse meningeal thickening associated with pleural mesothelioma. Thorax 1990;45:70-1.  Back to cited text no. 28
Nixon PF, Wolfenden WH, Hirst E. Paraplegia and destruction of ribs. Med J Aust 1964;1:207-12.  Back to cited text no. 29
de Pangher Manzini V, Chizzola A, Brollo A, Bianchi C. Diffuse neoplastic infiltration of leptomeninges by malignant pleural mesothelioma. Recenti Prog Med 1989;80:16-7.  Back to cited text no. 30
Rojas JL, Alfageme I, De la Cruz I, Reyes N, Muñoz J. Radicular involvement and medullary invasion from a malignant mesothelioma. Respiration 2001;68:106-8.  Back to cited text no. 31
Taryle DA, Lakshminarayan S, Sahn SA. Pleural mesotheliomas – An analysis of 18 cases and review of the literature. Medicine (Baltimore) 1976;55:153-62.  Back to cited text no. 32
Hirano H, Maeda H, Sawabata N, Okumura Y, Takeda S, Maekura R, et al. Desmoplastic malignant mesothelioma: Two cases and a literature review. Med Electron Microsc 2003;36:173-8.  Back to cited text no. 33
Oksüzoǧlu B, Yalçin S, Erman M, Daǧdelen S. Leptomeningeal infiltration of malignant mesothelioma. Med Oncol 2002;19:167-9.  Back to cited text no. 34
Petit BM, Ruffie P, Varlet P, Ciolocca C. Meningeal metastasis of pleural mesothelioma. Rev Mal Respir 2001;18:661-3.  Back to cited text no. 35
Petrovic BD, Kozic DB, Semnic RR, Prvulovic M, Djilas-Ivanovic D, Sener RN, et al. Leptomeningeal metastasis from malignant pleural mesothelioma. AJNR Am J Neuroradiol 2004;25:1223-4.  Back to cited text no. 36
Cheng WF, Berkman AW. Malignant mesothelioma with bone metastases. Med Pediatr Oncol 1990;18:165-8.  Back to cited text no. 37
Ishikawa R, Kikuchi E, Jin M, Fujita M, Itoh T, Sawa H, et al. Desmoplastic malignant mesothelioma of the pleura: Autopsy reveals asbestos exposure. Pathol Int 2003;53:401-6.  Back to cited text no. 38
Ceresoli GL, Gridelli C, Santoro A. Multidisciplinary treatment of malignant pleural mesothelioma. Oncologist 2007;12:850-63.  Back to cited text no. 39
Endo S, Hida K, Yano S, Ito M, Yamaguchi S, Kashiwazaki D, et al. Intramedullary spinal cord metastasis treated with radiation therapy: Report of 3 cases. No Shinkei Geka 2008;36:345-9.  Back to cited text no. 40
Villegas AE, Guthrie TH. Intramedullary spinal cord metastasis in breast cancer: Clinical features, diagnosis, and therapeutic consideration. Breast J 2004;10:532-5.  Back to cited text no. 41


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]

This article has been cited by
1 Perineural spread to the brachial plexus: a focused review of proposed mechanisms and described pathologies
Nikhil K. Murthy,Kimberly K. Amrami,Robert J. Spinner
Acta Neurochirurgica. 2020;
[Pubmed] | [DOI]
2 Brown-Séquard syndrome in a desmoplastic malignant mesothelioma patient: A rare complication
Mike Ralki,Anouk Serrien,Julie Lambert,Mathias Leys,Kristiaan Nackaerts
Clinical Lung Cancer. 2020;
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)  

  In this article
  Case Report
   Materials and Me...
   Article Figures
   Article Tables

 Article Access Statistics
    PDF Downloaded170    
    Comments [Add]    
    Cited by others 2    

Recommend this journal