Primary central nervous system lymphoma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Overview

On the basis of seizure, visual disturbance, and constitutional symptoms, astrocytoma must be differentiated from oligodendroglioma, meningioma, hemangioblastoma, pituitary adenoma, schwannoma, primary CNS lymphoma, medulloblastoma, ependymoma, craniopharyngioma, pinealoma, AV malformation, brain aneurysm, bacterial brain abscess, tuberculosis, toxoplasmosis, hydatid cyst, CNS cryptococcosis, CNS aspergillosis, and brain metastasis.

Differentiating astrocytoma from other Diseases

Differentiating astrocytoma from other diseases on the basis of seizure, visual disturbance, and constitutional symptoms

On the basis of seizure, visual disturbance, and constitutional symptoms, astrocytoma must be differentiated from oligodendroglioma, meningioma, hemangioblastoma, pituitary adenoma, schwannoma, primary CNS lymphoma, medulloblastoma, ependymoma, craniopharyngioma, pinealoma, AV malformation, brain aneurysm, bacterial brain abscess, tuberculosis, toxoplasmosis, hydatid cyst, CNS cryptococcosis, CNS aspergillosis, and brain metastasis.

	Symptoms				Physical examination	Lab Findings	MRI	Immunohistopathology
Diseases	Clinical manifestations					Para-clinical findings			Gold standard	Additional findings
	Symptoms				Physical examination	Para-clinical findings
	Head- ache	Seizure	Visual disturbance	Constitutional	Focal neurological deficit	Lab Findings	MRI	Immunohistopathology
Adult primary brain tumors
Glioblastoma multiforme ^[1]^[2]^[3]	+	+/−	+/−	−	+	−	Supratentorial Irregular ring-nodular enhancing lesions Central necrosis Surrounding vasogenic edema Cross corpus callosum (butterfly glioma)	Astrocyte origin Pleomorphic cell Pseudopalisading appearance GFAP + Necrosis + Hemorrhage + Vascular prolifration +	Biopsy	Highest incidence in fifth and sixth decades of life Most of the time, focal neurological deficit is the presenting sign.
Oligodendroglioma ^[4]^[5]^[6]	+	+	+/−	−	+	−	Almost always in cerebral hemisphers (frontal lobes) Hypointense on T1 Hyperintense on T2 Calcification Chicken wire capillary pattern	Oligodendrocyte origin Calcification + Fried egg cell appearance	Biopsy	Highest incidence is between 40 and 50 years of age. Most of the time, epileptic seizure is the presenting sign.
Meningioma ^[7]^[8]^[9]	+	+/−	+/−	−	+	−	Well circumscribed Extra-axial mass Dural attachment CSF vascular cleft sign Sunburst appearance of the vessels	Arachnoid origin Psammoma bodies Whorled spindle cell pattern	Biopsy	Highest incidence is between 40 and 50 years of age. Most of the time, focal neurological deficit and epileptic seizure are the presenting signs. May be associated with NF-2
Hemangioblastoma ^[10]^[11]^[12]^[13]	+	+/−	+/−	−	+	−	Infratentorial Cystic lesion with a solid enhancing mural nodule	Blood vessel origin Capillaries with thin walls	Biopsy	Might secret erythropoietin and cause polycythemia May be associated with von hippel-lindau syndrome
Pituitary adenoma ^[14]^[15]^[3]	−	−	+ Bitemporal hemianopia	−	−	Endocrine abnormalities as a result of functional adenomas or pressure effect of non-functional adenomas	Isointense to normal pituitary gland in T1	Endocrine cell hyperplasia	Biopsy	It is associated with MEN1 disease. Initialy presents with upper bitemporal quadrantanopsia followed by bitemporal hemianopsia (pressure on optic chiasma from below)
Schwannoma ^[16]^[17]^[18]^[19]	−	−	−	−	+	−	Split-fat sign Fascicular sign Often have areas of hemosiderin	Schwann cell origin S100+	Biopsy	It causes hearing loss and tinnitus May be associated with NF-2 (bilateral schwannomas)
Primary CNS lymphoma ^[20]^[21]	+	+/−	+/−	−	+	−	Usually deep in the white matter Single mass with ring enhancement	B cell origin Similar to non hodgkin lymphoma (diffuse large B cell)	Biopsy	Usually in young immunocompromised patients (HIV) or old immunocompetent person.
Childhood primary brain tumors
Pilocytic astrocytoma ^[22]^[23]^[24]	+	+/−	+/−	−	+	−	Infratentorial Solid and cystic component Mostly in posterior fossa Usually in cerebellar hemisphers and vermis	Glial cell origin Solid and cystic component GFAP +	Biopsy	Most of the time, cerebellar dysfunction is the presenting signs.
Medulloblastoma ^[25]^[26]^[27]	+	+/−	+/−	−	+	−	Infratentorial Mostly in cerebellum Non communicating hydrocephalus	Neuroectoderm origin Homer wright rosettes	Biopsy	Drop metastasis (metastasis through CSF)
Ependymoma ^[28]^[3]	+	+/−	+/−	−	+	−	Infratentorial Usually found in 4th ventricle Mixed cystic/solid lesion Hydrocephalus	Ependymal cell origin Perivascular pseudorosette	Biopsy	Causes an unusually persistent, continuous headache in children.
Craniopharyngioma ^[29]^[30]^[31]^[3]	+	+/−	+ Bitemporal hemianopia	−	+	Hypopituitarism as a result of pressure effect on pituitary gland	Calcification Lobulated contour Motor-oil like fluid within tumor	Ectodermal origin (Rathkes pouch) Calcification +	Biopsy	Initialy presents with lower bitemporal quadrantanopsia followed by bitemporal hemianopsia (pressure on optic chiasma from above)
Pinealoma ^[32]^[33]^[34]	+	+/−	+/−	−	+ vertical gaze palsy	B-hCG rise leads to precocious puberty in males	Hydrocephalus (compression of cerebral aqueduct)	Similar to testicular seminoma	Biopsy	May cause prinaud syndrome (vertical gaze palsy, pupillary light-near dissociation, lid retraction and convergence-retraction nystagmus
Vascular
AV malformation ^[35]^[36]^[3]	+	+	+/−	−	+/−	−	Supratentorial: ~85% Flow voids on T2 weighted images	We do not perform biopsy for AVM	Angiography	We may see bag of worms appearance in CT angiography
Brain aneurysm ^[37]^[38]^[39]^[40]^[41]	+	+/−	+/−	−	+/−	−	In magnetic resonance angiography, we may see aneurysm mostly in anterior circulation (~85%)	We do not perform biopsy for brain aneurysm	MRA and CTA	It is associated with autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome, pseudoxanthoma elasticum and Bicuspid aortic valve (Angiography is reserved for patients who have negative MRA and CTA)
Infectious
Bacterial brain abscess ^[42]^[43]	+	+/−	+/−	+	+	Leukocytosis Elevated ESR Blood culture may be positive for underlying organism	Central hypodense signal and surrounding ring-enhancement in T1 Central hyperintense area surrounded by a well-defined hypointense capsule with surrounding edema in T2	We do not perform biopsy for brain abscess	History/ imaging	The most common causes of brain abscess are Streptococcus and Staphylococcus.
Tuberculosis ^[44]^[3]^[45]	+	+/−	+/−	+	+	Positive acid-fast bacilli (AFB) smear in CSF specimen Positive CSF nucleic acid amplification testing Hyponatremia (inappropriate secretion of antidiuretic hormone) Mild anemia Leukocytosis	Hydrocephalus combined with marked basilar meningeal enhancement	We do not perform biopsy for brain tuberculosis	Lab data/ Imaging	It is associated with HIV infection
Toxoplasmosis ^[46]^[47]	+	+/−	+/−	−	+	Normal CSF	Multifocal masses with ring enhancement Mostly in basal ganglia, thalami, and corticomedullary junction.	We do not perform biopsy for brain toxoplasmosis	History/ imaging	It is associated with HIV infection
Hydatid cyst ^[48]^[3]	+	+/−	+/−	+/−	+	Positive serology (Antibody detection for E. granulosus)	Honeycomb appearance Necrotic area	We do not perform biopsy for hydatid cysts	Imaging	Brain, eye, and splenic cysts may not produce detectable amount of antibodies
CNS cryptococcosis ^[49]	+	+/−	+/−	+	+	Positive CSF antigen testing (coccidioidomycosis) CSF lymphocytic pleocytosis Elevated CSF proteins and lactate Low CSF glucose	Dilated perivascular spaces Basal ganglia pseudocysts Soap bubble brain lesions (cryptococcus neoformans)	We may see numerous acutely branching septate hyphae	Lab data/ Imaging	It is the most common brain fungal infection It is associated with HIV, immunosuppressive therapies, and organ transplants In may happen in immunocompetent patients undergoing invasive procedures ( neurosurgery) or exposed to contaminated devices or drugs Since brain biopsies are highly invasive and may may cause neurological deficits, we diagnose CNS fungal infections based on laboratory and imaging findings
CNS aspergillosis ^[50]	+	+/−	+/−	+	+	Positive galactomannan antigen testing (aspergillosis) CSF lymphocytic pleocytosis Elevated CSF proteins and lactate Low CSF glucose	Multiple abscesses Ring enhancement Peripheral low signal intensity on T2	We may see numerous acutely branching septate hyphae	Lab data/ Imaging	It is associated with HIV, immunosuppressive therapies, and organ transplants In may happen in immunocompetent patients undergoing invasive procedures ( neurosurgery) or exposed to contaminated devices or drugs Since brain biopsies are highly invasive and may may cause neurological deficits, we diagnose CNS fungal infections based on laboratory and imaging findings
Other
Brain metastasis ^[51]^[3]	+	+/−	+/−	+	+	−	Multiple lesions Vasogenic edema	Based on the primary cancer type we may have different immunohistopathology findings.	History/ imaging	Most common primary tumors that metastasis to brain: Lung cancer Renal cell carcinoma Breast cancer Melanoma Gastrointestinal tract If there is any uncertainty about etiology, biopsy should be performed

ABBREVIATIONS

CNS=Central nervous system, AV=Arteriovenous, CSF=Cerebrospinal fluid, NF-2=Neurofibromatosis type 2, MEN-1=Multiple endocrine neoplasia, GFAP=Glial fibrillary acidic protein, HIV=Human immunodeficiency virus, BhCG=Human chorionic gonadotropin, ESR=Erythrocyte sedimentation rate, AFB=Acid fast bacilli, MRA=Magnetic resonance angiography, CTA=CT angiography

References

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↑ 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.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.
↑ Smits M (2016). "Imaging of oligodendroglioma". Br J Radiol. 89 (1060): 20150857. doi:10.1259/bjr.20150857. PMC 4846213. PMID 26849038.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ Perks WH, Cross JN, Sivapragasam S, Johnson P (March 1976). "Supratentorial haemangioblastoma with polycythaemia". J. Neurol. Neurosurg. Psychiatry. 39 (3): 218–20. PMID 945331.
↑ 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.
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↑ 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.
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Template:WH Template:WS

[pmid17964028-1] 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.

[pmid22819718-2] 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.

[:0-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.

[pmid26849038-4] Smits M (2016). "Imaging of oligodendroglioma". Br J Radiol. 89 (1060): 20150857. doi:10.1259/bjr.20150857. PMC 4846213. PMID 26849038.

[pmid25943885-5] 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.

[pmid26478444-6] 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.

[pmid1642904-7] 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.

[pmid25744347-8] 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.

[pmid17509660-9] 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.

[pmid24579662-10] 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.

[pmid17877533-11] 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.

[pmid2704812-12] 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.

[pmid945331-13] Perks WH, Cross JN, Sivapragasam S, Johnson P (March 1976). "Supratentorial haemangioblastoma with polycythaemia". J. Neurol. Neurosurg. Psychiatry. 39 (3): 218–20. PMID 945331.

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Primary central nervous system lymphoma differential diagnosis

Overview

Differentiating astrocytoma from other Diseases

Differentiating astrocytoma from other diseases on the basis of seizure, visual disturbance, and constitutional symptoms

References

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