Cerebrospinal fluid-disseminated meningioma


  • Marc C. Chamberlain M.D.,

    Corresponding author
    1. Department of Neurology, University of Southern California Norris Cancer Center, Lost Angeles, California
    • Department of Neurology, University of Southern California, Norris Comprehensive Cancer Center and Hospital, 1441 Eastlake Avenue, Suite 3459, Los Angeles, CA 90033-0804
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    • Fax (323) 865-0061

  • Michael J. Glantz M.D.

    1. Department of Neurology, University of Massachusetts, Worchester, Massachusetts.
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Intracranial meningiomas are common and comprise 20% of all primary brain tumors. Meningiomas infrequently metastasize; however, to the authors' knowledge there are limited data regarding the spread of disease through cerebrospinal fluid (CSF).


Eight of 200 consecutive patients (4%) with meningiomas manifested CSF dissemination. CSF cytology was positive in all patients, and neuroradiographic studies were consistent with CSF dissemination in eight patients. The patients (6 women and 2 men) ranged in age from 24–87 years (mean age, 52 years). All patients had undergone prior surgery (range, one to five surgeries; median, two surgeries), radiotherapy (involved-field radiotherapy in seven patients and stereotactic radiotherapy in six patients), and chemotherapy (hydroxyurea in eight patients). Multiple sites of metastases were seen in all patients and were both within the nervous system (subarachnoid or ventricular tumor: intracranial in eight patients, spinal cord in four patients) and extraneural (subcutaneous, cervical lymph nodes, orbit, or pulmonary in five patients). Treatment utilized both systemic chemotherapy (temozolomide in four patients, irinotecan in three patients, hydroxyurea in three patients, interferon-α in two patients, and doxorubicin plus ifosfamide in one patient) and intraventricular chemotherapy (liposomal cytosine arabinoside in seven patients, thiotepa in one patient, and busulfan in one patient).


Treatment-related toxicity was seen in eight patients, including chemical meningitis in eight patients (Grade 2), neutropenia in five patients (Grade 2 in four patients and Grade 3 in one patient), fatigue in one patient (Grade 2), and gastrointestinal toxicity in one patient (Grade 2). The best response was stable disease in seven patients and progressive disease in one patient. The response duration ranged from 2–31 months (median, 3.5 months). The median survival was 5.5 months, and 3 patients were alive with disease at the time of last follow-up.


The treatment of CSF-disseminated meningioma, although feasible and comparatively nontoxic, was associated with modest outcomes despite combined systemic and intraventricular chemotherapy. Cancer 2005. © 2005 American Cancer Society.

Meningiomas are extraaxial brain tumors occurring during middle to late adult life and have a female predominance. Overall, 90% of meningiomas are benign, 6% are atypical, and 2% are malignant.1–7 Most patients who are diagnosed with a meningioma decide to have it removed surgically and are advised to do so based on their neurologic symptoms.1–7 Complete surgical resection usually is curative. For patients who have incompletely resected or recurrent tumors that were not irradiated before surgery, radiotherapy is administered.1–7 Radiotherapy may be administered as either conventional external beam irradiation or stereotactically. Stereotactic radiotherapy either as linear accelerator radiotherapy or γ-knife radiosurgery is being utilized increasingly. When the meningioma is unresectable or when all other treatments (e.g., surgery, radiotherapy) have failed, immunochemotherapy may be considered.7 Rarely, meningiomas metastasize and, when seen, most often to extraneural sites (cervical lymph nodes, pulmonary sites).8–13 Herein, we report on eight patients with positive cerebrospinal fluid (CSF) cytology and CSF-disseminated, metastatic, World Health Organization (WHO) Grade 1 meningioma.


Eight patients from a cohort of 200 patients who were seen consecutively and were followed prospectively with intracranial meningiomas demonstrated evidence of CSF spread of disease (Table 1; Fig. 1 ). Patients were seen (representing both clinic referrals and institutional patients) between January 1990 and January 2004 in one of two neurooncology clinics (the University of Southern California or the University of Massachusetts). Patients (6 women and 2 men) ranged in age from 24–87 years (median, 52 years). All patients had received extensive prior therapy, including surgery in 8 patients (median, 2 surgeries; range, 1–5 surgeries), external beam fractionated radiotherapy in 7 patients (median dose, 54 grays [Gy]), stereotactic radiotherapy in 5 patient (median dose, 18 Gy), and chemotherapy in 8 patients (hydroxyurea administered for 3–9 months [median, 6 months]). All patients had WHO Grade 1 meningiomas confirmed by histopathology (six patients confirmed by repeat craniotomy; five patients confirmed by biopsy of extraneural metastatic sites). In all patients, cranial magnetic resonance imaging demonstrated disease progression by an increase > 25% in tumor volume.

Table 1. Patient Characteristics
Patient no.GenderAge (yrs)KPSPrior therapySites of metastatic disease
Surgery (no.)EBRTSRTChemotherapyIntracranialSpineCSFRetroorbitalCervical LNsSubcutaneousPulmonary
  1. KPS: Karnofsky performance status; ERBT: external beam radiotherapy; SRT: stereotactic radiotherapy; CSF: cerebrospinal fluid; LNs: lymph nodes; +: present; − : absent; HU: hydroxyurea; R: right; L: left.

1Male54703++HUBihemispheric +++ +
2Female48702++HUBihemispheric +   +
3Female50802++HUBihemispheric++ + +
4Female63602++HUBihemispheric + +  
5Female24705++HUR cerebral, hemisphere, both cerebral peduncles++    
7Female87801HUL frontal convexity++ ++ 
8Male44704++HUBihemispheric + +  


Figure 1.

Contrast-enhanced, T1-weighted axial magnetic resonance image demonstrating intraventricular nodules from cerebrospinal fluid-disseminated meningioma.

The median time to presentation from original surgery was 6.75 years (range, 1.25–14 years) (Table 2). Neurologic examination revealed hemispheric dysfunction in eight patients (hemiparesis in six patients, seizures in five patients, and aphasia in two patients), cranial neuropathy in five patients, and spinal cord disorders in four patients (radiculopathy in two patients and cauda equina in two patients). At the time of presentation, the median Karnofsky performance score was 70 (range, 60–80).

Table 2. Treatment
Patient no.Time to CSF disease presentation (yrs)Leptomeningeal disease presentationCNS pretreatment imagingChemotherapy treatmentHighest grade of of toxicityBest responseResponse duration (mos)Survival (mos)
CerebralCranial nerveSpinal cordBrainSpinal cordCSF flowRegionalSystemic
  • CSF: cerebrospinal fluid; CNS: central nervous system; G2: Grade 2; G3: Grade 3; Ara-C: cytosine arabinoside; TMZ; temozolomide; +: present; IFN-α: interferon-α; CPT-11: irinotecan; SD: stable disease; PD: progressive disease; N/A: not applicable; GI: gastrointestinal; AI: doxorubicin and ifosfamide; Heme: hematologic toxicity.

  • a

    Magnetic resonance image compatible with leptomeningeal metastases.

  • b

    Active treatment.

  • c


16.5++ +a +Liposomal Ara-CTMZ, IFN-α, CPT-11G2 neutropeniaSD48
25.5+++  +Liposomal Ara-CTMZG3 neutropeniaPDN/A4
38.5++++a+a+Liposomal Ara-CTMZ, CPT-11G2 neutropeniaSD36
47.5++ +a +Liposomal Ara-CTMZG2 neutropeniaSD35
51.25+ ++a+a+Liposomal Ara-CHigh-dose AIG2 G1; G3 HemeSD2b2c
66.5+ ++a+a+BusulfanTMZ (low dose, prolonged)NoneSD1011
714.0+ ++a+a+Thiotepa; liposomal Ara-CCytoxan (low, dose, prolonged), IFN-α; bevacizumabG2 fatigueSD3739c
89.0++ +a +Liposomal Ara-CCPT-11G2 neutropeniaSD2b2c

CSF cytology was positive in all patients. Neuroradiography demonstrated bihemispheric intracranial disease in seven patients and spinal subarachnoid disease in four patients. In addition, extraneural metastases were seen in five patients (cervical lymph nodes in four patients, pulmonary in two patients, retroorbital in one patient, and subcutaneous in one patient). Three patients underwent biopsy of an extraneural site of metastases with histopathologic confirmation of metastatic WHO Grade 1 meningioma. All patients underwent the placement of an Ommaya reservoir and intraventricular catheter to facilitate the administration of intra-CSF chemotherapy.


All patients received concurrent systemic and regional chemotherapy (Table 2). Systemic chemotherapy included temozolomide in four patients, irinotecan in three patients, interferon-α in two patients, cyclophosphamide in one patient, doxorubicin plus ifosfamide in one patient, and bevacizumab in one patient. Seven patients received intraventricular liposomal cytosine arabinoside, and one patient each received busulfan or thiotepa by intraventricular administration. Three patients received dexamethasone (median dose of 4 mg per day; range, 2–10 mg per day).

Treatment-related toxicity was noted in eight patients, including chemical meningitis in all eight patients (Grade 2 according to the National Cancer Institute Common Toxicity Criteria), neutropenia in five patients (Grade 2 in four patients and Grade 3 in one patient), fatigue in one patient (Grade 2), and gastrointestinal toxicity in one patient (Grade 2). Chemical meningitis was defined as a transient (< 5 days after intra-CSF drug administration), sterile, inflammatory CSF associated with headache, nausea, emesis, photophobia, or low-grade fever.

The best response was comprised of stable disease in seven patients and progressive disease in one patient. No patient manifested a neuroradiographic complete or partial response. The duration of response ranged from 2–31 months (median, 3.5 months). The median survival was 5.5 months, and 3 patients were alive with disease at the time of last follow-up.


Metastatic meningioma is associated most often with either aggressive meningioma (WHO Grade 2) or malignant meningioma (WHO Grade 3) with a range of occurrence of 10–25%. Not clear from the literature, however, is the risk of CSF dissemination.8–13 In the current, small series, which arguably was biased by referral to a neurooncology clinic, 8 of 200 consecutive patients with meningioma manifested CSF spread of disease defined both radiographically and cytologically. In addition to CSF spread of disease, the majority of these patients (5 of 8 patients; 63%) also had evidence of extraneural metastasis. Furthermore, all patients had received extensive prior therapy, including surgery (often multiple), radiotherapy (often both external beam and stereotactic), and chemotherapy (all patients had received prior hydroxyurea and developed disease progression).

Aside from hydroxyurea, to our knowledge there is a paucity of chemotherapy agents with demonstrated activity against recurrent meningiomas, complicating the management of these already complicated patients.14 Similar to patients with meningeal gliomatosis, the current study patients were treated in a multimodal manner, including both systemic and regional (intraventricular) chemotherapy and involved-field radiotherapy to sites of symptomatic spinal disease (three patients). Despite this aggressive approach, the median survival was only 5.5 months, with all but 3 patients dying of progressive disease. In a previous publication, investigators believed that progression-free survival of > 6 months represented a meaningful response to therapy in patients with recurrent meningioma who were treated previously with maximal surgery and radiotherapy.7

Of the three patients alive at the time of last follow-up, all three patients had residual disease and two patients continued to receive therapy. Furthermore, no patient demonstrated a treatment response (the best response was stable disease) as assessed by neuroradiography. Based on the results of the current study, two conclusions appear to be justified. First, meningiomas do metastasize both hematologically and by CSF dissemination and, second, there is a need for more effective chemotherapy for patients with recurrent meningiomas that are refractory to both surgery and radiotherapy.