What is the appropriate management for a patient misdiagnosed with glioblastoma multiforme (GBM) when the actual condition is a lesion caused by neurosarcoidosis?

Management of Neurosarcoidosis Misdiagnosed as Glioblastoma Multiforme

For patients misdiagnosed with glioblastoma multiforme (GBM) when the actual condition is neurosarcoidosis, immediate treatment with glucocorticoids is strongly recommended as first-line therapy, followed by methotrexate if disease persists, and infliximab as third-line therapy if needed. 1

Diagnostic Reassessment

When a patient initially diagnosed with GBM is suspected of having neurosarcoidosis instead:

1. Confirm diagnosis through tissue re-examination:

   • Review previous biopsy material for non-caseating granulomas characteristic of sarcoidosis
   • Consider rebiopsy if initial pathology was inconclusive or showed only gliosis 2
   • Look for sequential involvement of other neurological structures (e.g., optic nerves) that would suggest sarcoidosis 2

2. Additional diagnostic workup:

   • MRI with contrast to evaluate enhancement patterns
   • FDG-PET to differentiate between neoplastic and inflammatory lesions
   • Evaluate for systemic sarcoidosis (chest imaging, serum ACE levels)

Treatment Algorithm for Confirmed Neurosarcoidosis

First-Line Therapy

• Glucocorticoids (Strong recommendation, very low quality of evidence) 1
  • Begin with IV pulse methylprednisolone (1000 mg daily for 3-5 days)
  • Follow with oral prednisone 1 mg/kg/day (maximum 60-80 mg/day)
  • Gradually taper over 6-12 months based on clinical response

Second-Line Therapy

• For patients with persistent disease despite glucocorticoids (Conditional recommendation, very low quality of evidence) 1
  • Add methotrexate 10-25 mg weekly
  • Monitor for hepatotoxicity and myelosuppression
  • Continue glucocorticoids at lowest effective dose

Third-Line Therapy

• For patients with continued disease despite glucocorticoids and methotrexate (Conditional recommendation, very low quality of evidence) 1
  • Add infliximab (5 mg/kg at weeks 0,2,6, then every 4-8 weeks)
  • Alternative second-line agents include azathioprine or mycophenolate mofetil
  • Consider combination therapy for severe or refractory cases

Discontinuing Previous GBM Treatment

1. Immediately discontinue temozolomide or other chemotherapy agents used for GBM
2. Reassess radiation therapy plans:
   • If radiation has not started, hold until neurosarcoidosis treatment response is assessed
   • If radiation is in progress, discuss risks/benefits of continuing versus stopping

Monitoring and Follow-up

• Neurological assessment and neuroimaging every 3 months 1
• Monitor for:
  • Clinical improvement (neurological symptoms, visual function)
  • Radiographic improvement (reduction in lesion size and enhancement)
  • Treatment-related adverse effects

Special Considerations

• Steroid-sparing strategies are important for long-term management to minimize adverse effects
• Double-positive patients (those with features of both neurosarcoidosis and another condition) may require more complex management
• Fatigue management may include pulmonary rehabilitation and/or inspiratory muscle strength training for 6-12 weeks 1

Prognosis

The prognosis for neurosarcoidosis is significantly better than for GBM when appropriate immunosuppressive therapy is initiated promptly. Early recognition and treatment of neurosarcoidosis is crucial to prevent permanent neurological damage and improve quality of life.

Pitfalls to Avoid

• Diagnostic delay: Neurosarcoidosis can mimic CNS tumors radiographically; maintain high index of suspicion in atypical cases 2
• Inadequate immunosuppression: Undertreating neurosarcoidosis can lead to permanent neurological damage
• Overreliance on initial diagnosis: Be willing to reconsider diagnosis when clinical course is atypical for GBM
• Missing systemic sarcoidosis: Always evaluate for extra-neurological manifestations of sarcoidosis