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

|
|
|
|
|

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
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]

1. Episodes of focal seizures
2. Signs of increased intracranial pressure
3. 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]

1. Cranial nerve neuropathies: Facial palsy is the most common presentation.
2. Meningeal involvement: diffuse meningeal inflammation can cause diffuse basilar polyneuropathy in 40% of the patients. with neurosarcoidosis.
3. Inflammatory spinal cord disease: Inflammatory span usually more than 3 spinal cord segments which helps to differentiate it from Multiple Sclerosis.
4. Peripheral neuropathy: Asymmetric polyneuropathy or mononeuritis multiplex. It may also manifest as Guillain-Barré syndrome (GBS) like presentation.
5. 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

|
|
|
|
|

Headache | ↓LOC | Motor weakness | Abnormal sensory | Motor Deficit | Sensory deficit | Speech difficulty | Gait abnormality | Cranial nerves | CT /MRI | CSF Findings | Gold standard test
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]

1. ↑ Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
2. ↑ Invalid `<ref>` tag; no text was provided for refs named `pmid3883130`
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.CS1 maint: Multiple names: authors list (link)
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
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.
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.
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.
12. ↑ "Brain Abscess — NEJM".
13. ↑ 13.0 13.1 "Primary Brain Tumors in Adults - American Family Physician".
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".
15. ↑ 15.0 15.1 "Neurosarcoidosis".
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.
17. ↑ Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
19. ↑ Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.