Brain tumor differential diagnosis

	Brain tumor Microchapters
Patient Information
Overview
Classification Adult brain tumors Glioblastoma multiforme Oligodendroglioma Meningioma Hemangioblastoma Pituitary adenoma Schwannoma Primary CNS lymphoma Childhood brain tumors Pilocytic astrocytoma Medulloblastoma Ependymoma Craniopharyngioma Pinealoma Metastasis Lung cancer Breast cancer Melanoma Gastrointestinal tract cancer Renal cell carcinoma Osteoblastoma Head and neck cancer Neuroblastoma Lymphoma Prostate cancer
Causes
Differentiating Brain Tumor from other Diseases

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

Overview[edit | edit source]

Brain tumors should be differentiated from essential tremors, stroke, chronic subdural hematoma, meningitis, orbital optic neuritis, arteriovenous malformation, intraocular optic neuritis, brain abscess, and neurosyphilis.

Differentiating brain tumor from other diseases[edit | edit source]

Essential tremor
Seizures
Stroke
Chronic subdural hematoma
Meningitis
Orbital optic neuritis
Intraocular optic neuritis
Arteriovenous malformation
Brain abscess
Neurosyphilis

Diseases	Diagnostic tests				Physical Examination					Symptoms			Past medical history	Other Findings
Diseases	Na+, K+, Ca2+	CT /MRI	CSF Findings	Gold standard test	Neck stiffness	Motor or Sensory deficit	Papilledema	Bulging fontanelle	Cranial nerves	Headache	Fever	Altered mental status	Past medical history	Other Findings
Brain tumour^[1]^[2]		✔	Cancer cells^[3]	MRI		✔	✔	✔	✔	✔		✔		Cachexia, gradual progression of symptoms
Delirium tremens		✔		Clinical diagnosis		✔	✔		✔	✔	✔	✔	Alcohol intake, sudden witdrawl or reduction in consumption	Tachycardia, diaphoresis, hypertension, tremors, mydriasis, positional nystagmus,
Subarachnoid hemorrhage^[4]		✔	Xanthochromia^[5]	CT scan without contrast^[6]^[7]	✔	✔	✔	✔	✔	✔	✔	✔	Trauma/fall	Confusion, dizziness, nausea, vomiting
Stroke		✔	Normal	CT scan without contrast		✔	✔		✔	✔		✔	TIAs, hypertension, diabetes mellitus	Speech difficulty, gait abnormality
Neurosyphilis^[8]^[9]		✔	↑ Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive^[10]	✔	✔	✔	✔		✔		✔	Unprotected sexual intercourse, STIs	Blindness, confusion, depression, Abnormal gait
Viral encephalitis		✔	Increased RBCS or xanthochromia, mononuclear lymphocytosis, high protein content, normal glucose	Clinical assesment	✔	✔	✔		✔	✔	✔	✔	Tick bite/mosquito bite/ viral prodome for several days	Extreme lethargy, rash hepatosplenomegaly, lymphadenopathy, behavioural changes
Herpes simplex encephalitis		✔		Clinical assesment			✔	✔	✔	✔	✔		History of hypertension	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy			Normal				✔	✔			✔		History of alcohal abuse	Ophthalmoplegia, confusion
CNS abscess		✔	↑ leukocytes >100,000/ul, ↓ glucose and ↑ protien, ↑ red blood cells, lactic acid >500mg	Contrast enhanced MRI is more sensitive and specific, Histopathological examination of brain tissue	✔	✔	✔		✔	✔	✔	✔	History of drug abuse, endocarditis, ↓ immune status	High grade fever, fatigue,nausea, vomiting
Drug toxicity											✔	✔		Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder				Diagnosis of exclusion		✔		✔		✔	✔	✔		Tremors, blindness, difficulty swallowing
Electrolyte disturbance	↓ or ↑			Depends on the cause						✔		✔		Confusion, seizures
Febrile convulsion			Not performed in first simple febrile seizures	Clinical diagnosis and EEG					✔	✔	✔	✔	Family history of febrile seizures, viral illness or gastroenteritis	Age > 1 month,
Subdural empyema		✔		Clinical assesment and MRI	✔	✔	✔	✔	✔			✔	History of relapses and remissions	Blurry vision, urinary incontinence, fatigue
Hypoglycemia	↓ or ↑			Serum blood glucose HbA1c		✔				✔		✔	History of diabetes	Palpitations, sweating, dizziness, low serum, glucose

Differentiating brain tumors from other brain cystic lesions
Disease	Prominent clinical features	Lab findings	Radiological findings
Neurocysticercosis	Presenting symptoms differ according to the site of the cysticerci. Parenchymal neurocysticercosis causes all the symptoms and signs of space occupying lesions. Extraparenchymal neurocysticercosis causes manifestations of increased intracranial pressure if cysts are present in the subarachnoid space or in the ventricles, manifestations of spinal cord compression if present in the spinal cord or causes eye disease if cysts are present in the orbit.	CDC's immunoblot is based on detection of antibody to one or more of 7 lentil-lectin purified structural glycoprotein antigens from the larval cysts. It is 100% specific and has a sensitivity superior to that of any other test yet evaluated	Computerized tomography (CT) is superior to magnetic resonance imaging (MRI) for demonstrating small calcifications. However, MRI shows cysts in some locations (cerebral convexity, ventricular ependyma) better than CT, is more sensitive than CT to demonstrate surrounding edema, and may show internal changes indicating the death of cysticerci.
Brain abscess	Headaches are the most common symptom. Usually, headaches occur on the same side of the abscess and tend to be severe (not responding to analgesics). Fever is not a reliable sign.^[11]	Lumbar puncture is contraindicated but when done, it was variable between patients. Culture from the CT-guided aspirated lesion helps in identifying the causative agent.	Contrast enhanced CT provides rapid assessment of the size and number of the abscesses. MRI: Diffusion-weighted imaging (DWI) MRI can differentiate brain abscesses from cystic brain lesions with sensitivity and specificity of 96%.^[12]
Brain tumors	Most common presenting symptom is dull aching headache. Usually, it's associated with other symptoms of increased intracranial pressure (ICP) as seizures, visual disturbances, nausea, and vomiting.^[13]		CT may be used in localizing the tumor and getting a rough estimate on the dimensions. MRI: Gadolinium-enhanced MRI is the preferred imaging modality for assessing the extension of the tumor and its exact location.^[13]
Brain tuberculoma	Brain tuberculomas has insidious onset of symptoms as compared to tuberculous meningitis. Presentations are usually due to the pressure effect, not the T.B. bacilli. Presenting symptoms and signs in order of occurrence:^[14] Episodes of focal seizures Signs of increased intracranial pressure Focal neurologic deficits.	T.B. should be investigated everywhere else in the body (e.g. peripheral lymphadenopathy, sputum and blood culture)	CT: Contrast-enhanced CT scan shows a ring enhancing lesion surrounded by an area of hypodensity (cerebritis) and the resulting mass effect. MRI: Better than CT scan in assessing the site and size of the tuberculoma. Gadolinium-enhanced MRI shows a ring enhancing lesion between 1-5 cm in size (In NCC, the wall is thicker, calcifications are eccentric and the diameter is less than 2 cm)
Neurosarcoidosis	70% of the patients present with the neurological symptoms rather than the presentation of systemic disease. Common presentations are:^[15] Cranial nerve neuropathies: Facial palsy is the most common presentation. Meningeal involvement: diffuse meningeal inflammation can cause diffuse basilar polyneuropathy in 40% of the patients. with neurosarcoidosis. Inflammatory spinal cord disease: Inflammatory span usually more than 3 spinal cord segments which helps to differentiate it from Multiple Sclerosis. Peripheral neuropathy: Asymmetric polyneuropathy or mononeuritis multiplex. It may also manifest as Guillain-Barré syndrome (GBS) like presentation. HPO axis involvement: may present as diabetes insipidus. More than 50% of the cases have no radiological signs.	Noninvasive tests have low sensitivity and specificity. Serum ACE levels are elevated in 25% of the cases Lumbar puncture shows elevated CSF proteins together with mild-moderate pleocytosis. It is usually accompanied by oligoclonal bands.^[15]	MRI with contrast shows enhancement of the inflamed areas (i.e. cranial nerves, meninges or HPO axis)

MRI brain showing brain abscess - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/4933"	MRI brain showing Glioblastoma multiforme - Case courtesy of A.Prof Frank Gaillard, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/28272">rID: 28272</a>	MRI brain showing tuberculoma - Case courtesy of Dr G Balachandran, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/5489"	MRI brain showing Neurosarcoidosis - Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org/ From the case https://radiopaedia.org/cases/4364S

Brain tumors must be differentiated from other causes of headache, seizures and loss of consciousness.

Diseases	Symptoms				Physical Examination					Past medical history	Diagnostic tests			Other Findings
Diseases	Headache	↓LOC	Motor weakness	Abnormal sensory	Motor Deficit	Sensory deficit	Speech difficulty	Gait abnormality	Cranial nerves	Past medical history	CT /MRI	CSF Findings	Gold standard test	Other Findings
Meningitis	+	-	-	-	-	+	+	-	-	History of fever and malaise	-	↑ Leukocytes, ↑ Protein ↓ Glucose	CSF analysis^[16]	Fever, neck rigidity
Encephalitis	+	+	+/-	+/-	-	-	+	+/-	+	History of fever and malaise	+	↑ Leukocytes, ↓ Glucose	CSF PCR	Fever, seizures, focal neurologic abnormalities
Brain tumor^[17]	+	-	-	-	+	+	+	-	+	Weight loss, fatigue	+	Cancer cells^[3]	MRI	Cachexia, gradual progression of symptoms
Hemorrhagic stroke	+	+	+	+	+	+	+	+	-	Hypertension	+	-	CT scan without contrast^[6]^[7]	Neck stiffness
Subdural hemorrhage	+	+	+	+	+	-	-	-	+	Trauma, fall	+	Xanthochromia^[5]	CT scan without contrast^[6]^[7]	Confusion, dizziness, nausea, vomiting
Neurosyphilis^[8]^[9]	+	-	+	+	+	+	-	+	-	STIs	+	↑ Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive^[10]	Blindness, confusion, depression, Abnormal gait
Complex or atypical migraine	+	-	+	+	-	-	+	-	-	Family history of migraine	-	-	Clinical assesment	Presence of aura, nausea, vomiting
Hypertensive encephalopathy	+	+	-	-	-	-	+	+	-	Hypertension	+	-	Clinical assesment	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy	-	+	-	-	-	+	+	+	+	History of alcohal abuse	-	-	Clinical assesment and lab findings	Ophthalmoplegia, confusion
CNS abscess	+	+	-	-	+	+	+	-	-	History of drug abuse, endocarditis, immunosupression	+	↑ leukocytes, ↓ glucose and ↑ protien	MRI is more sensitive and specific	High grade fever, fatigue,nausea, vomiting
Drug toxicity	-	+	-	+	+	+	-	+	-	-	-	-	Drug screen test	Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder	+	+	+	+	+	+	+	+		History of emotional stress	-	-	Diagnosis of exclusion	Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia)	-	+	+	+	+	+	-	-	+	-	-	Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia	Depends on the cause	Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation	-	-	+	+	-	+	+	+	+	History of relapses and remissions	+	↑ CSF IgG levels (monoclonal bands)	Clinical assesment and MRI ^[18]	Blurry vision, urinary incontinence, fatigue
Seizure	+	+	-	-	+	+	-	-	+	Previous history of seizures	-	Mass lesion	Clinical assesment and EEG ^[19]	Confusion, apathy, irritability,

References[edit | edit source]

↑ Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
↑
↑ ^3.0 ^3.1 Weston CL, Glantz MJ, Connor JR (2011). "Detection of cancer cells in the cerebrospinal fluid: current methods and future directions". Fluids Barriers CNS. 8 (1): 14. doi:10.1186/2045-8118-8-14. PMC 3059292. PMID 21371327.
↑ Yeh ST, Lee WJ, Lin HJ, Chen CY, Te AL, Lin HJ (2003) Nonaneurysmal subarachnoid hemorrhage secondary to tuberculous meningitis: report of two cases. J Emerg Med 25 (3):265-70. PMID: 14585453
↑ ^5.0 ^5.1 Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
↑ ^6.0 ^6.1 ^6.2 Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
↑ ^7.0 ^7.1 ^7.2 DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease". J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.
↑ ^8.0 ^8.1 Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients". J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.
↑ ^9.0 ^9.1 Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
↑ ^10.0 ^10.1 Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. doi:10.1097/OLQ.0b013e31824ee574. PMC 3746559. PMID 22421697.
↑ Brouwer MC, Tunkel AR, McKhann GM, van de Beek D (2014). "Brain abscess". N. Engl. J. Med. 371 (5): 447–56. doi:10.1056/NEJMra1301635. PMID 25075836.
↑ "Brain Abscess — NEJM".
↑ ^13.0 ^13.1 "Primary Brain Tumors in Adults - American Family Physician".
↑ "The Journal of Association of Chest Physicians - Tuberculoma of the brain - A diagnostic dilemma: Magnetic resonance spectroscopy a new ray of hope : Download PDF".
↑ ^15.0 ^15.1 "Neurosarcoidosis".
↑ Carbonnelle E (2009). "[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent]". Med Mal Infect. 39 (7–8): 581–605. doi:10.1016/j.medmal.2009.02.017. PMID 19398286.
↑ Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.
↑ Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH; et al. (1994). "Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group". Arch Neurol. 51 (1): 61–6. PMID 8274111.
↑ Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.

[pmid1278192-1] Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192

[pmid3883130-2] ↑

[pmid21371327-3] 3.0 ^3.1 Weston CL, Glantz MJ, Connor JR (2011). "Detection of cancer cells in the cerebrospinal fluid: current methods and future directions". Fluids Barriers CNS. 8 (1): 14. doi:10.1186/2045-8118-8-14. PMC 3059292. PMID 21371327.

[pmid14585453-4] Yeh ST, Lee WJ, Lin HJ, Chen CY, Te AL, Lin HJ (2003) Nonaneurysmal subarachnoid hemorrhage secondary to tuberculous meningitis: report of two cases. J Emerg Med 25 (3):265-70. PMID: 14585453

[pmid1198628-5] 5.0 ^5.1 Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.

[pmid21694755-6] 6.0 ^6.1 ^6.2 Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.

[pmid21807345-7] 7.0 ^7.1 ^7.2 DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease". J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.

[pmid22482824-8] 8.0 ^8.1 Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients". J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.

[pmid24365430-9] 9.0 ^9.1 Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.

[pmid22421697-10] 10.0 ^10.1 Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. doi:10.1097/OLQ.0b013e31824ee574. PMC 3746559. PMID 22421697.

[pmid25075836-11] Brouwer MC, Tunkel AR, McKhann GM, van de Beek D (2014). "Brain abscess". N. Engl. J. Med. 371 (5): 447–56. doi:10.1056/NEJMra1301635. PMID 25075836.

[urlBrain_Abscess_—_NEJM-12] "Brain Abscess — NEJM".

[urlPrimary_Brain_Tumors_in_Adults_-_American_Family_Physician-13] 13.0 ^13.1 "Primary Brain Tumors in Adults - American Family Physician".

[urlThe_Journal_of_Association_of_Chest_Physicians_-_Tuberculoma_of_the_brain_-_A_diagnostic_dilemma:_Magnetic_resonance_spectroscopy_a_new_ray_of_hope_:_Download_PDF-14] "The Journal of Association of Chest Physicians - Tuberculoma of the brain - A diagnostic dilemma: Magnetic resonance spectroscopy a new ray of hope : Download PDF".

[urlNeurosarcoidosis-15] 15.0 ^15.1 "Neurosarcoidosis".

[pmid19398286-16] Carbonnelle E (2009). "[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent]". Med Mal Infect. 39 (7–8): 581–605. doi:10.1016/j.medmal.2009.02.017. PMID 19398286.

[pmid10582668-17] Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.

[pmid8274111-18] Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH; et al. (1994). "Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group". Arch Neurol. 51 (1): 61–6. PMID 8274111.

[pmid11385043-19] Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]