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Glioblastoma multiforme differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Overview

Glioblastoma multiforme must be differentiated from cerebral metastasis, primary CNS lymphoma, cerebral abscess, anaplastic astrocytoma, tumefactive demyelination, stroke, cerebral toxoplasmosis, radiation necrosis, encephalitis, oligodendroglioma, and seizure disorder.[1]

Differentiating Glioblastoma multiforme from other Diseases

Glioblastoma multiforme must be differentiated from the following:[1]

Diseases Clinical manifestations Para-clinical findings Gold
standard 		Additional findings
Symptoms Physical examination
Lab Findings MRI Immunohistopathology
Head-
ache 		Seizure Visual disturbance Constitutional Focal neurological deficit
Adult primary brain tumors
Glioblastoma multiforme
[2][3][4] 		+ +/− +/− − + −
  • Pseudopalisading appearance
Oligodendroglioma
[5][6][7] 		+ + +/− − + −
  • Chicken wire capillary pattern
  • Fried egg cell appearance
Meningioma
[8][9][10] 		+ +/− +/− − + −
  • Well circumscribed
  • Extra-axial mass
  • Whorled spindle cell pattern
  • May be associated with NF-2
Hemangioblastoma
[11][12][13][14] 		+ +/− +/− − + −
Pituitary adenoma
[15][16][4] 		− − + Bitemporal hemianopia − −
  • It is associated with MEN1 disease.
      Schwannoma
      [17][18][19][20]       		− − − − + −
      • Split-fat sign
      • Fascicular sign
      • Often have areas of hemosiderin
      • S100+
      Primary CNS lymphoma
      [21][22]       		+ +/− +/− − + −
      • Single mass with ring enhancement
        Childhood primary brain tumors
        Pilocytic astrocytoma
        [23][24][25]         		+ +/− +/− − + −
        Medulloblastoma
        [26][27][28]         		+ +/− +/− − + −
        • Homer wright rosettes
        Ependymoma
        [29][4]         		+ +/− +/− − + −
        • Hydrocephalus
        • Causes an unusually persistent, continuous headache in children.
        Craniopharyngioma
        [30][31][32][4]         		+ +/− + Bitemporal hemianopia − +
        Pinealoma
        [33][34][35]         		+ +/− +/− − + vertical gaze palsy
        • May cause prinaud syndrome (vertical gaze palsy, pupillary light-near dissociation, lid retraction and convergence-retraction nystagmus
        Vascular
        AV malformation
        [36][37][4]         		+ + +/− − +/− −
        Brain aneurysm
        [38][39][40][41][42]         		+ +/− +/− − +/− −
        • MRA and CTA
        Infectious
        Bacterial brain abscess
        [43][44]         		+ +/− +/− + +
        • Central hypodense signal and surrounding ring-enhancement in T1
        • Central hyperintense area surrounded by a well-defined hypointense capsule with surrounding edema in T2
        • History/ imaging
        Tuberculosis
        [45][4][46]         		+ +/− +/− + +
        • Lab data/ Imaging
        Toxoplasmosis
        [47][48]         		+ +/− +/− − +
        • History/ imaging
        Hydatid cyst
        [49][4]         		+ +/− +/− +/− +
        • Imaging
        CNS cryptococcosis
        [50]         		+ +/− +/− + +
        • We may see numerous acutely branching septate hyphae
        • Lab data/ Imaging
        CNS aspergillosis
        [51]         		+ +/− +/− + +
        • Multiple abscesses
        • Ring enhancement
        • Peripheral low signal intensity on T2
        • We may see numerous acutely branching septate hyphae
        • Lab data/ Imaging
        Other
        Brain metastasis
        [52][4]         		+ +/− +/− + + −
        • Based on the primary cancer type we may have different immunohistopathology findings.
        • History/ imaging

        References

        1. ↑ 1.0 1.1 DDx of glioblastoma multiforme. Dr Dylan Kurda and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/glioblastoma
        2. ↑ Sathornsumetee S, Rich JN, Reardon DA (November 2007). “Diagnosis and treatment of high-grade astrocytoma”. Neurol Clin. 25 (4): 1111–39, x. doi:10.1016/j.ncl.2007.07.004. PMID 17964028.
        3. ↑ Pedersen CL, Romner B (January 2013). “Current treatment of low grade astrocytoma: a review”. Clin Neurol Neurosurg. 115 (1): 1–8. doi:10.1016/j.clineuro.2012.07.002. PMID 22819718.
        4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.
        5. ↑ Smits M (2016). “Imaging of oligodendroglioma”. Br J Radiol. 89 (1060): 20150857. doi:10.1259/bjr.20150857. PMC 4846213. PMID 26849038.
        6. ↑ Wesseling P, van den Bent M, Perry A (June 2015). “Oligodendroglioma: pathology, molecular mechanisms and markers”. Acta Neuropathol. 129 (6): 809–27. doi:10.1007/s00401-015-1424-1. PMC 4436696. PMID 25943885.
        7. ↑ Kerkhof M, Benit C, Duran-Pena A, Vecht CJ (2015). “Seizures in oligodendroglial tumors”. CNS Oncol. 4 (5): 347–56. doi:10.2217/cns.15.29. PMC 6082346. PMID 26478444.
        8. ↑ Zee CS, Chin T, Segall HD, Destian S, Ahmadi J (June 1992). “Magnetic resonance imaging of meningiomas”. Semin. Ultrasound CT MR. 13 (3): 154–69. PMID 1642904.
        9. ↑ Shibuya M (2015). “Pathology and molecular genetics of meningioma: recent advances”. Neurol. Med. Chir. (Tokyo). 55 (1): 14–27. doi:10.2176/nmc.ra.2014-0233. PMID 25744347.
        10. ↑ Begnami MD, Palau M, Rushing EJ, Santi M, Quezado M (September 2007). “Evaluation of NF2 gene deletion in sporadic schwannomas, meningiomas, and ependymomas by chromogenic in situ hybridization”. Hum. Pathol. 38 (9): 1345–50. doi:10.1016/j.humpath.2007.01.027. PMC 2094208. PMID 17509660.
        11. ↑ Lonser RR, Butman JA, Huntoon K, Asthagiri AR, Wu T, Bakhtian KD, Chew EY, Zhuang Z, Linehan WM, Oldfield EH (May 2014). “Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease”. J. Neurosurg. 120 (5): 1055–62. doi:10.3171/2014.1.JNS131431. PMC 4762041. PMID 24579662.
        12. ↑ Hussein MR (October 2007). “Central nervous system capillary haemangioblastoma: the pathologist’s viewpoint”. Int J Exp Pathol. 88 (5): 311–24. doi:10.1111/j.1365-2613.2007.00535.x. PMC 2517334. PMID 17877533.
        13. ↑ Lee SR, Sanches J, Mark AS, Dillon WP, Norman D, Newton TH (May 1989). “Posterior fossa hemangioblastomas: MR imaging”. Radiology. 171 (2): 463–8. doi:10.1148/radiology.171.2.2704812. PMID 2704812.
        14. ↑ Perks WH, Cross JN, Sivapragasam S, Johnson P (March 1976). “Supratentorial haemangioblastoma with polycythaemia”. J. Neurol. Neurosurg. Psychiatry. 39 (3): 218–20. PMID 945331.
        15. ↑ Kucharczyk W, Davis DO, Kelly WM, Sze G, Norman D, Newton TH (December 1986). “Pituitary adenomas: high-resolution MR imaging at 1.5 T”. Radiology. 161 (3): 761–5. doi:10.1148/radiology.161.3.3786729. PMID 3786729.
        16. ↑ Syro LV, Scheithauer BW, Kovacs K, Toledo RA, Londoño FJ, Ortiz LD, Rotondo F, Horvath E, Uribe H (2012). “Pituitary tumors in patients with MEN1 syndrome”. Clinics (Sao Paulo). 67 Suppl 1: 43–8. PMC 3328811. PMID 22584705.
        17. ↑ Donnelly, Martin J.; Daly, Carmel A.; Briggs, Robert J. S. (2007). “MR imaging features of an intracochlear acoustic schwannoma”. The Journal of Laryngology & Otology. 108 (12). doi:10.1017/S0022215100129056. ISSN 0022-2151.
        18. ↑ Feany MB, Anthony DC, Fletcher CD (May 1998). “Nerve sheath tumours with hybrid features of neurofibroma and schwannoma: a conceptual challenge”. Histopathology. 32 (5): 405–10. PMID 9639114.
        19. ↑ Chen H, Xue L, Wang H, Wang Z, Wu H (July 2017). “Differential NF2 Gene Status in Sporadic Vestibular Schwannomas and its Prognostic Impact on Tumour Growth Patterns”. Sci Rep. 7 (1): 5470. doi:10.1038/s41598-017-05769-0. PMID 28710469.
        20. ↑ Hardell, Lennart; Hansson Mild, Kjell; Sandström, Monica; Carlberg, Michael; Hallquist, Arne; Påhlson, Anneli (2003). “Vestibular Schwannoma, Tinnitus and Cellular Telephones”. Neuroepidemiology. 22 (2): 124–129. doi:10.1159/000068745. ISSN 0251-5350.
        21. ↑ Chinn RJ, Wilkinson ID, Hall-Craggs MA, Paley MN, Miller RF, Kendall BE, Newman SP, Harrison MJ (December 1995). “Toxoplasmosis and primary central nervous system lymphoma in HIV infection: diagnosis with MR spectroscopy”. Radiology. 197 (3): 649–54. doi:10.1148/radiology.197.3.7480733. PMID 7480733.
        22. ↑ Paulus, Werner (1999). “Classification, Pathogenesis and Molecular Pathology of Primary CNS Lymphomas”. Journal of Neuro-Oncology. 43 (3): 203–208. doi:10.1023/A:1006242116122. ISSN 0167-594X.
        23. ↑ Sathornsumetee S, Rich JN, Reardon DA (November 2007). “Diagnosis and treatment of high-grade astrocytoma”. Neurol Clin. 25 (4): 1111–39, x. doi:10.1016/j.ncl.2007.07.004. PMID 17964028.
        24. ↑ Pedersen CL, Romner B (January 2013). “Current treatment of low grade astrocytoma: a review”. Clin Neurol Neurosurg. 115 (1): 1–8. doi:10.1016/j.clineuro.2012.07.002. PMID 22819718.
        25. ↑ Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.
        26. ↑ Dorwart, R H; Wara, W M; Norman, D; Levin, V A (1981). “Complete myelographic evaluation of spinal metastases from medulloblastoma”. Radiology. 139 (2): 403–408. doi:10.1148/radiology.139.2.7220886. ISSN 0033-8419.
        27. ↑ Fruehwald-Pallamar, Julia; Puchner, Stefan B.; Rossi, Andrea; Garre, Maria L.; Cama, Armando; Koelblinger, Claus; Osborn, Anne G.; Thurnher, Majda M. (2011). “Magnetic resonance imaging spectrum of medulloblastoma”. Neuroradiology. 53 (6): 387–396. doi:10.1007/s00234-010-0829-8. ISSN 0028-3940.
        28. ↑ Burger, P. C.; Grahmann, F. C.; Bliestle, A.; Kleihues, P. (1987). “Differentiation in the medulloblastoma”. Acta Neuropathologica. 73 (2): 115–123. doi:10.1007/BF00693776. ISSN 0001-6322.
        29. ↑ Yuh, E. L.; Barkovich, A. J.; Gupta, N. (2009). “Imaging of ependymomas: MRI and CT”. Child’s Nervous System. 25 (10): 1203–1213. doi:10.1007/s00381-009-0878-7. ISSN 0256-7040.
        30. ↑ Brunel H, Raybaud C, Peretti-Viton P, Lena G, Girard N, Paz-Paredes A, Levrier O, Farnarier P, Manera L, Choux M (September 2002). “[Craniopharyngioma in children: MRI study of 43 cases]”. Neurochirurgie (in French). 48 (4): 309–18. PMID 12407316.
        31. ↑ Prabhu, Vikram C.; Brown, Henry G. (2005). “The pathogenesis of craniopharyngiomas”. Child’s Nervous System. 21 (8–9): 622–627. doi:10.1007/s00381-005-1190-9. ISSN 0256-7040.
        32. ↑ Kennedy HB, Smith RJ (December 1975). “Eye signs in craniopharyngioma”. Br J Ophthalmol. 59 (12): 689–95. PMC 1017436. PMID 766825.
        33. ↑ Ahmed SR, Shalet SM, Price DA, Pearson D (September 1983). “Human chorionic gonadotrophin secreting pineal germinoma and precocious puberty”. Arch. Dis. Child. 58 (9): 743–5. PMID 6625640.
        34. ↑ Sano, Keiji (1976). “Pinealoma in Children”. Pediatric Neurosurgery. 2 (1): 67–72. doi:10.1159/000119602. ISSN 1016-2291.
        35. ↑ Baggenstoss, Archie H. (1939). “PINEALOMAS”. Archives of Neurology And Psychiatry. 41 (6): 1187. doi:10.1001/archneurpsyc.1939.02270180115011. ISSN 0096-6754.
        36. ↑ Kucharczyk, W; Lemme-Pleghos, L; Uske, A; Brant-Zawadzki, M; Dooms, G; Norman, D (1985). “Intracranial vascular malformations: MR and CT imaging”. Radiology. 156 (2): 383–389. doi:10.1148/radiology.156.2.4011900. ISSN 0033-8419.
        37. ↑ Fleetwood, Ian G; Steinberg, Gary K (2002). “Arteriovenous malformations”. The Lancet. 359 (9309): 863–873. doi:10.1016/S0140-6736(02)07946-1. ISSN 0140-6736.
        38. ↑ Chapman, Arlene B.; Rubinstein, David; Hughes, Richard; Stears, John C.; Earnest, Michael P.; Johnson, Ann M.; Gabow, Patricia A.; Kaehny, William D. (1992). “Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease”. New England Journal of Medicine. 327 (13): 916–920. doi:10.1056/NEJM199209243271303. ISSN 0028-4793.
        39. ↑ Castori M, Voermans NC (October 2014). “Neurological manifestations of Ehlers-Danlos syndrome(s): A review”. Iran J Neurol. 13 (4): 190–208. PMC 4300794. PMID 25632331.
        40. ↑ Schievink, W. I.; Raissi, S. S.; Maya, M. M.; Velebir, A. (2010). “Screening for intracranial aneurysms in patients with bicuspid aortic valve”. Neurology. 74 (18): 1430–1433. doi:10.1212/WNL.0b013e3181dc1acf. ISSN 0028-3878.
        41. ↑ Germain DP (May 2017). “Pseudoxanthoma elasticum”. Orphanet J Rare Dis. 12 (1): 85. doi:10.1186/s13023-017-0639-8. PMC 5424392. PMID 28486967.
        42. ↑ Farahmand M, Farahangiz S, Yadollahi M (October 2013). “Diagnostic Accuracy of Magnetic Resonance Angiography for Detection of Intracranial Aneurysms in Patients with Acute Subarachnoid Hemorrhage; A Comparison to Digital Subtraction Angiography”. Bull Emerg Trauma. 1 (4): 147–51. PMC 4789449. PMID 27162847.
        43. ↑ Haimes, AB; Zimmerman, RD; Morgello, S; Weingarten, K; Becker, RD; Jennis, R; Deck, MD (1989). “MR imaging of brain abscesses”. American Journal of Roentgenology. 152 (5): 1073–1085. doi:10.2214/ajr.152.5.1073. ISSN 0361-803X.
        44. ↑ Brouwer, Matthijs C.; Tunkel, Allan R.; McKhann, Guy M.; van de Beek, Diederik (2014). “Brain Abscess”. New England Journal of Medicine. 371 (5): 447–456. doi:10.1056/NEJMra1301635. ISSN 0028-4793.
        45. ↑ Morgado, Carlos; Ruivo, Nuno (2005). “Imaging meningo-encephalic tuberculosis”. European Journal of Radiology. 55 (2): 188–192. doi:10.1016/j.ejrad.2005.04.017. ISSN 0720-048X.
        46. ↑ Be NA, Kim KS, Bishai WR, Jain SK (March 2009). “Pathogenesis of central nervous system tuberculosis”. Curr. Mol. Med. 9 (2): 94–9. PMC 4486069. PMID 19275620.
        47. ↑ Chinn RJ, Wilkinson ID, Hall-Craggs MA, Paley MN, Miller RF, Kendall BE, Newman SP, Harrison MJ (December 1995). “Toxoplasmosis and primary central nervous system lymphoma in HIV infection: diagnosis with MR spectroscopy”. Radiology. 197 (3): 649–54. doi:10.1148/radiology.197.3.7480733. PMID 7480733.
        48. ↑ Helton KJ, Maron G, Mamcarz E, Leventaki V, Patay Z, Sadighi Z (November 2016). “Unusual magnetic resonance imaging presentation of post-BMT cerebral toxoplasmosis masquerading as meningoencephalitis and ventriculitis”. Bone Marrow Transplant. 51 (11): 1533–1536. doi:10.1038/bmt.2016.168. PMID 27348541.
        49. ↑ Taslakian B, Darwish H (September 2016). “Intracranial hydatid cyst: imaging findings of a rare disease”. BMJ Case Rep. 2016. doi:10.1136/bcr-2016-216570. PMC 5030532. PMID 27620198.
        50. ↑ McCarthy M, Rosengart A, Schuetz AN, Kontoyiannis DP, Walsh TJ (July 2014). “Mold infections of the central nervous system”. N. Engl. J. Med. 371 (2): 150–60. doi:10.1056/NEJMra1216008. PMC 4840461. PMID 25006721.
        51. ↑ McCarthy M, Rosengart A, Schuetz AN, Kontoyiannis DP, Walsh TJ (July 2014). “Mold infections of the central nervous system”. N. Engl. J. Med. 371 (2): 150–60. doi:10.1056/NEJMra1216008. PMC 4840461. PMID 25006721.
        52. ↑ Pope WB (2018). “Brain metastases: neuroimaging”. Handb Clin Neurol. 149: 89–112. doi:10.1016/B978-0-12-811161-1.00007-4. PMC 6118134. PMID 29307364.


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