Editing Brain tumor (section)

==Diagnosis==
[[File:Postermass.png|thumb|A posterior fossa tumor leading to mass effect and midline shift]]

There are no specific signs or symptoms for brain cancer, but the presence of a combination of symptoms and the lack of alternative causes may indicate a brain tumor.<ref name="Herholz" /> A [[medical history]] aids in the diagnosis. Clinical and laboratory investigations will serve to exclude infections as the cause of the symptoms.

Brain tumors, when compared to tumors in other areas of the body, pose a challenge for diagnosis. Commonly, [[radioactive tracer]]s are uptaken in large volumes in tumors due to the high activity of tumor cells, allowing for radioactive imaging of the tumor. However, most of the brain is separated from the blood by the [[blood–brain barrier]] (BBB), a membrane that exerts a strict control over what substances are allowed to pass into the brain. Therefore, many tracers that may reach tumors in other areas of the body easily would be unable to reach brain tumors until there was a disruption of the BBB by the tumor. Disruption of the BBB is well imaged via MRI or CT scan, and is therefore regarded as the main diagnostic indicator for malignant gliomas, meningiomas, and brain metastases.<ref name="Herholz">{{cite journal | vauthors = Herholz K, Langen KJ, Schiepers C, Mountz JM | title = Brain tumors | journal = Seminars in Nuclear Medicine | volume = 42 | issue = 6 | pages = 356–70 | date = November 2012 | pmid = 23026359 | pmc = 3925448 | doi = 10.1053/j.semnuclmed.2012.06.001 }}</ref>

===Imaging===
[[File:CT brain tumor.jpg|thumb|[[CT scan]] of a brain tumor, with its diameters marked as an X. There is hypoattenuating (dark) ''peritumoral edema'' in the surrounding white matter, with a "finger-like" spread.|216x216px]]
[[Medical imaging]] plays a central role in the diagnosis of brain tumors. Early imaging methods&nbsp;– invasive and sometimes dangerous&nbsp;– such as [[pneumoencephalography]] and cerebral [[angiography]] have been replaced by non-invasive, high-resolution techniques, especially [[magnetic resonance imaging]] (MRI) and [[computed tomography]] (CT) scans.<ref name="cancer.gov">{{cite web |title=Adult Central Nervous System Tumors Treatment (PDQ®)–Patient Version – National Cancer Institute |url=https://www.cancer.gov/types/brain/patient/adult-brain-treatment-pdq |website=cancer.gov |access-date=29 January 2021 |language=en |date=11 May 2020}}</ref> MRI with contrast enhancement is the preferred imaging test in the diagnosis of brain tumors.<ref name="Schaff 2023" /><ref name=":4">{{cite journal | vauthors = Iv M, Yoon BC, Heit JJ, Fischbein N, Wintermark M | title = Current Clinical State of Advanced Magnetic Resonance Imaging for Brain Tumor Diagnosis and Follow Up | journal = Seminars in Roentgenology | volume = 53 | issue = 1 | pages = 45–61 | date = January 2018 | pmid = 29405955 | doi = 10.1053/j.ro.2017.11.005 }}</ref> Glioblastomas usually enhance with contrast on T1 MRI weighted MRI imaging, and on [[T2*-weighted imaging|T2]] with FLAIR imaging showing hyperintense cerebral edema.<ref name="Schaff 2023" /> Low grade gliomas are usually hypointense on T1 MRI, and hyperintense with T2 with FLAIR MRI. Meningiomas are usually homogenously enhanced with dural thickening on MRI.<ref name="Schaff 2023" />

Treatment with radiation can lead to treatment induced changes in the brain, including radiation necrosis (death of brain tissue due to radiation treatments) visible on brain imaging and which can be difficult to differentiate from tumor recurrence.<ref>{{cite journal |last1=Lee |first1=Dennis |last2=Riestenberg |first2=Robert A. |last3=Haskell-Mendoza |first3=Aden |last4=Bloch |first4=Orin |title=Brain Metastasis Recurrence Versus Radiation Necrosis |journal=Neurosurgery Clinics of North America |date=October 2020 |volume=31 |issue=4 |pages=575–587 |doi=10.1016/j.nec.2020.06.007 |pmid=32921353 |s2cid=221674217 }}</ref>

==== Different Types of MRI Scans ====
'''Magnetic Resonance Angiography (MRA)'''{{snd}} looks at the blood vessels in the brain. In the diagnosis of brain tumor, MRAs are typically carried out before surgery to help surgeons get a better understanding of the tumor vasculature. For example, a study was done where surgeons were able to separate benign brain tumors from malignant ones by analyzing the shapes of the blood vessels that were extracted from MRA.<ref>{{cite conference | vauthors = Bullitt E, Jung I, Muller K, Gerig G, Aylward S, Joshi S, Smith K, Lin W, Ewend M |title=Determining Malignancy of Brain Tumors by Analysis of Vessel Shape |date=2004 | doi = 10.1007/978-3-540-30136-3_79 | conference = Medical Image Computing and Computer-Assisted Intervention – MICCAI 2004 |pages=645–653 |place=Berlin, Heidelberg |publisher=Springer Berlin Heidelberg |isbn=978-3-540-22977-3 |doi-access=free }}</ref> Although not required, some MRA may inject contrast agent, gadolinium, into the patient to get an enhanced image

'''Magnetic Resonance Spectroscopy (MRS)'''{{snd}} measures the metabolic changes or chemical changes inside the tumor. The most common MRS is proton spectroscopy with its frequency measured in parts per million (ppm). Gliomas or malignant brain tumors have different spectra from normal brain tissue in that they have greater choline levels and lower N-acetyl aspartate (NAA) signals.<ref>{{cite journal | vauthors = Horská A, Barker PB | title = Imaging of brain tumors: MR spectroscopy and metabolic imaging | journal = Neuroimaging Clinics of North America | volume = 20 | issue = 3 | pages = 293–310 | date = August 2010 | pmid = 20708548 | doi = 10.1016/j.nic.2010.04.003 | pmc = 2927327 }}</ref> Using MRS in brain tumor diagnosis can help doctors identify the type of tumor and its aggressiveness. For example, benign brain tumors or meningioma have increased alanine levels. It can also help to distinguish brain tumors from scar tissues or dead tissues caused by previous radiation treatment, which does not have increased choline levels<ref>{{Cite web |title=MRI (magnetic resonance imaging) |url=https://mayfieldclinic.com/pe-mrspectroscopy.htm |access-date=2022-11-28 |website=mayfieldclinic.com |language=EN}}</ref> that brain tumors have, and from tumor-mimicking lesions such as abscesses or infarcts.

'''Perfusion Magnetic Resonance Imaging (pMRI)'''{{snd}} assess the blood volume and blood flow of different parts of the brain and brain tumors. pMRI requires the injection of contrast agent, usually gadopentetate dimeglumine (Gd-DTPA) into the veins in order to enhance the contrast. pMRI provides a cerebral blood volume map that shows the tumor vascularity and angiogenesis. Brain tumors would require a larger blood supply and thus, would show a high cerebral blood volume on the pMRI map. The vascular morphology and degree of angiogenesis from pMRI help to determine the grade and malignancy of brain tumors. For brain tumor diagnosis, pMRI is useful in determining the best site to perform biopsy and to help reduce sampling error. pMRI is also valuable for after treatment to determine if the abnormal area is a remaining tumor or a scar tissue. For patients that are undergoing anti-angiogenesis cancer therapy, pMRI can give the doctors a better sense of efficacy of the treatment by monitoring tumor cerebral blood volume.<ref>{{cite journal | vauthors = Cha S | title = Perfusion MR imaging of brain tumors | journal = Topics in Magnetic Resonance Imaging | volume = 15 | issue = 5 | pages = 279–289 | date = October 2004 | pmid = 15627003 | doi = 10.1097/00002142-200410000-00002 | s2cid = 25773559 | doi-access = free }}</ref>

'''Functional MRI (fMRI)'''{{snd}} measures blood flow changes in active parts of the brain while the patient is performing tasks and provides specific locations of the brain that are responsible for certain functions. Before performing a brain tumor surgery on patients, neurosurgeons would use fMRI to avoid damage to structures of the brain that correspond with important brain functions while resecting the tumor at the same time. Preoperative fMRI is important because it is often difficult to distinguish the anatomy near the tumor as it distorts its surrounding regions. Neurosurgeons would use fMRI to plan whether to perform a resection where tumor is surgically removed as much as possible, a biopsy where they take a surgical sampling amount to provide a diagnosis, or to not undergo surgery at all. For example, a neurosurgeon may be opposed to resecting a tumor near the motor cortex as that would affect the patient's movements. Without preoperative fMRI, the neurosurgeon would have to perform an awake-craniotomy where the patient would have to interact during open surgery to see if tumor removal would affect important brain functions.<ref>{{cite journal | vauthors = Bogomolny DL, Petrovich NM, Hou BL, Peck KK, Kim MJ, Holodny AI | title = Functional MRI in the brain tumor patient | journal = Topics in Magnetic Resonance Imaging | volume = 15 | issue = 5 | pages = 325–335 | date = October 2004 | pmid = 15627006 | doi = 10.1097/00002142-200410000-00005 | s2cid = 45995537 }}</ref>

'''Diffusion Weighted Imaging (DWI)'''{{snd}} a form of MRI that measures random Brownian motion of water molecules along a magnetic field gradient. For brain tumor diagnosis, measurement of apparent diffusion coefficient (ADC) in brain tumors allow doctors to categorize tumor type. Most brain tumors have higher ADC than normal brain tissues and doctors can match the observed ADC of the patient's brain tumor with a list of accepted ADC to identify tumor type. DWI is also useful for treatment and therapy purposes where changes in diffusion can be analyzed in response to drug, radiation, or gene therapy. Successful response results in apoptosis and increase in diffusion while failed treatment results in unchanged diffusion values.<ref>{{cite journal | vauthors = Maier SE, Sun Y, Mulkern RV | title = Diffusion imaging of brain tumors | journal = NMR in Biomedicine | volume = 23 | issue = 7 | pages = 849–864 | date = August 2010 | pmid = 20886568 | pmc = 3000221 | doi = 10.1002/nbm.1544 }}</ref>

==== Other Types of Imaging Techniques ====
'''Computed Tomography (CT) Scan'''{{snd}} uses x-rays to take pictures from different angles and computer processing to combine the pictures into a 3D image. A CT scan usually serves as an alternative to MRI in cases where the patient cannot have an MRI due to claustrophobia or pacemaker. Compared to MRI, a CT scan shows a more detailed image of the bone structures near the tumor and can be used to measure the tumor's size.<ref name=":8">{{Cite web |title=Tests for Brain and Spinal Cord Tumors in Adults |url=https://www.cancer.org/cancer/brain-spinal-cord-tumors-adults/detection-diagnosis-staging/how-diagnosed.html |access-date=2022-11-28 |website=cancer.org |language=en}}</ref> Like an MRI, a contrast dye may also be injected into the veins or ingested by mouth before a CT scan to better outline any tumors that may be present. CT scans use contrast materials that are iodine-based and barium sulfate compounds. The downside of using CT scans as opposed to MRI is that some brain tumors do not show up well on CT scans because some intra-axial masses are faint and resemble normal brain tissue. In some scenarios, brain tumors in CT scans may be mistaken for infarction, infection, and demyelination. To suspect that an intra-axial mass is a brain tumor instead of other possibilities, there must be unexplained calcifications in the brain, preservation of the cortex, and disproportionate mass effect.<ref>{{Cite web |title=Recognizing intra-axial tumors on brain computed tomography (CT) {{!}} Medmastery |url=https://public-nuxt.frontend.prod.medmastery.io/guides/brain-ct-clinical-guide/recognizing-intra-axial-tumors-brain-computed-tomography-ct-and |access-date=2022-11-28 |website=public-nuxt.frontend.prod.medmastery.io |language=en}}</ref>

'''CT Angiography (CTA)'''{{snd}} provides information about the blood vessels in the brain using X-rays. A contrast agent is always required to be injected into the patient in the CT scanner. CTA serves as an alternative to MRA.

'''Positron Emission Tomography (PET) Scan'''{{snd}} uses radiolabelled substances, such as [[Fluorodeoxyglucose|FDG]] which taken up by cells that are actively dividing. Tumor cells are more actively dividing so they would absorb more of the radioactive substance. After injection, a scanner would be used to create an image of the radioactive areas in the brain. PET scans are used more often for high-grade tumors than for low-grade tumors. It is useful after treatment to help doctors determine if the abnormal area on an MRI image is a remaining tumor or a scar tissue. Scar tissues will not show up on PET scans while tumors would.<ref name=":8" />

===Pathology===
[[File:Oligodendroglioma1 high mag.jpg|thumb|[[Micrograph]] of an [[oligodendroglioma]], a type of brain cancer. Brain [[biopsy]]. [[H&E stain]].]]
Maximal safe surgical resection (to preserve as much neurological function as possible) and histologic examination of the tumor is also required to aid in the diagnosis.<ref name="Schaff 2023" /> Cancer cells may have specific characteristics.

[[Atypia]]: an indication of abnormality of a cell (which may be indicative of malignancy). Significance of the abnormality is highly dependent on context.<ref>{{Cite journal | vauthors = Watson AN |date=2007-01-01 |title=Significance of "Atypia" Found on Needle Biopsy of the Breast: Correlation with Surgical Outcome |url=https://elischolar.library.yale.edu/ymtdl/384 |journal=Yale Medicine Thesis Digital Library}}</ref>

[[Neoplasia]]: the (uncontrolled) division of cells that is characteristic of cancer.<ref>{{cite web |title=Neoplasia |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neoplasm |website=www.cancer.gov |publisher=National Cancer Institute |language=en |date=2 February 2011}}</ref>

[[Necrosis]]: the (premature) death of cells, caused by external factors such as infection, toxin or trauma. Necrotic cells send the wrong chemical signals which prevent [[phagocyte]]s from disposing of the dead cells, leading to a buildup of dead tissue, cell debris and toxins at or near the site of the necrotic cells<ref name=necrs>{{MedlinePlus|002266|Necrosis}}</ref>

Local [[hypoxia (medical)|hypoxia]], or the deprivation of adequate oxygen supply to certain areas of the brain, including within the tumor, as the tumor grows and recruits local blood vessels.<ref>{{cite journal | vauthors = Emami Nejad A, Najafgholian S, Rostami A, Sistani A, Shojaeifar S, Esparvarinha M, Nedaeinia R, Haghjooy Javanmard S, Taherian M, Ahmadlou M, Salehi R, Sadeghi B, Manian M | title = The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment | journal = Cancer Cell International | volume = 21 | issue = 1 | pages = 62 | date = January 2021 | pmid = 33472628 | pmc = 7816485 | doi = 10.1186/s12935-020-01719-5 | doi-access = free }}</ref>

===Classification===
Tumors can be [[benign]] or [[malignant]], can occur in different parts of the brain, and may be classified as primary or secondary. A primary tumor is one that has started in the brain, as opposed to a [[metastasis|metastatic]] tumor, which is one that has spread to the brain from another area of the body.<ref>{{cite web|url=http://www.cancer.gov/cancertopics/wyntk/brain/page1|title=What you need to know about brain tumors|publisher=National Cancer Institute|archive-url=https://web.archive.org/web/20120127124137/http://www.cancer.gov/cancertopics/wyntk/brain/page1|archive-date=27 January 2012|url-status=live|access-date=25 February 2012}}</ref> The incidence of metastatic tumors is approximately four times greater than primary tumors.<ref name=Mer2012/> Tumors may or may not be [[symptomatic]]: some tumors are discovered because the patient has symptoms, others show up incidentally on an imaging scan, or at an autopsy.{{citation needed|date=December 2020}}

[[Grading of the tumors of the central nervous system]] commonly occurs on a 4-point scale (I-IV) created by the World Health Organization in 1993. Grade I tumors are the least severe and commonly associated with long-term survival, with severity and prognosis worsening as the grade increases. Low-grade tumors are often benign, while higher grades are aggressively malignant and/or metastatic. Other grading scales do exist, many based upon the same criteria as the WHO scale and graded from I-IV.<ref>{{cite journal | vauthors = Gupta A, Dwivedi T | title = A Simplified Overview of World Health Organization Classification Update of Central Nervous System Tumors 2016 | journal = Journal of Neurosciences in Rural Practice | volume = 8 | issue = 4 | pages = 629–641 | date = October 2017 | pmid = 29204027 | pmc = 5709890 | doi = 10.4103/jnrp.jnrp_168_17 | doi-access = free }}</ref>

==== Primary ====
[[File:Meningioma of the sagittal sinus isolated.jpg|thumb|Meningioma of the middle third of the sagittal sinus with large [[hyperostosis]]]]
The most common primary brain tumors are:<ref>{{Cite book|title=Meningiomas: Diagnosis, Treatment, and Outcome| vauthors = Park BJ, Kim HK, Sade B, Lee JH |publisher=Springer|year=2009|isbn=978-1-84882-910-7| veditors = Lee JH |page=11|chapter=Epidemiology}}
</ref>
* [[Gliomas]]<ref name=aans>{{cite web |title=Brain Tumors – Classifications, Symptoms, Diagnosis and Treatments |url=https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Brain-Tumors |website=aans.org |access-date=29 January 2021 |language=en}}</ref> (50.4%)
* [[Meningiomas]]<ref name=aans/> (20.8%)
* [[Pituitary adenomas]]<ref name=aans/> (15%)
* [[Nerve sheath tumors]] (10%)

These common tumors can also be organized according to tissue of origin as shown below:<ref name="AANS 41723ct">{{cite web|url=http://www.aans.org/en/Media/Classifications-of-Brain-Tumors|title=Classifications of Brain Tumors|website=AANS|publisher=American Association of Neurological Surgeons|archive-url=https://web.archive.org/web/20170424085734/http://www.aans.org/en/Media/Classifications-of-Brain-Tumors|archive-date=24 April 2017|url-status=live|access-date=23 April 2017}}</ref>
{| class="wikitable"
|-
!
Tissue of origin
! Children !! Adults
|-
|[[Astrocytes]]||[[Pilocytic astrocytoma|Pilocytic Astrocytoma]] (PCA) ||[[Glioblastoma]]
|-
|[[Oligodendrocytes]]||  ||[[Oligodendroglioma]]
|-
|[[Ependyma]]||[[Ependymoma]]||
|-
|[[Neurons]]||[[Medulloblastoma]]||
|-
|[[Meninges]]||  ||[[Meningioma]]
|}

====Secondary====
Secondary tumors of the brain are [[metastasis|metastatic]] and have spread to the brain from [[cancer]]s originating in another organ. Metastatic spread is usually by the blood. The most common types of cancers that spread to the brain are [[lung cancer]] (accounting for over half of all cases), [[breast cancer]], [[melanoma]] skin cancer, [[kidney cancer]] and [[colon cancer]].<ref name="Brenner 2022">{{cite journal |last1=Brenner |first1=Alex W. |last2=Patel |first2=Akash J. |title=Review of Current Principles of the Diagnosis and Management of Brain Metastases |journal=Frontiers in Oncology |date=24 May 2022 |volume=12 |doi=10.3389/fonc.2022.857622|doi-access=free |pmid=35686091 |pmc=9171239 }}</ref>

=====By behavior=====
Brain tumors can be [[cancerous]] (malignant) or non-cancerous (benign). However, the definitions of malignant or benign neoplasms differ from those commonly used in other types of cancerous or non-cancerous neoplasms in the body.
In cancers elsewhere in the body, three malignant properties differentiate benign tumors from malignant forms of cancer: benign tumors are self-limited and do not invade or metastasize. Characteristics of malignant tumors include:<ref>{{cite journal | vauthors = Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW | title = The 2021 WHO Classification of Tumors of the Central Nervous System: a summary | journal = Neuro-Oncology | volume = 23 | issue = 8 | pages = 1231–1251 | date = August 2021 | pmid = 34185076 | pmc = 8328013 | doi = 10.1093/neuonc/noab106 }}</ref>
* uncontrolled mitosis (growth by division beyond the normal limits)
* [[anaplasia]]: the cells in the neoplasm have an obviously different form (in size and shape). Anaplastic cells display marked [[pleomorphism (cytology)|pleomorphism]]. The [[cell nuclei]] are characteristically extremely hyperchromatic (darkly stained) and enlarged; the nucleus might have the same size as the [[cytoplasm]] of the cell (nuclear-cytoplasmic ratio may approach 1:1, instead of the normal 1:4 or 1:6 ratio). [[Giant cells]] – considerably larger than their neighbors – may form and possess either one enormous nucleus or several nuclei ([[syncytium|syncytia]]). Anaplastic nuclei are variable and bizarre in size and shape.
* invasion or infiltration:
** Invasion or invasiveness is the spatial expansion of the tumor through uncontrolled mitosis, in the sense that the neoplasm invades the space occupied by adjacent tissue, thereby pushing the other tissue aside and eventually compressing the tissue. Often these tumors are associated with clearly outlined tumors in imaging.
** Infiltration is the behavior of the tumor either to grow (microscopic) tentacles that push into the surrounding tissue (often making the outline of the tumor undefined or diffuse) or to have tumor cells "seeded" into the tissue beyond the circumference of the tumorous mass.
* [[metastasis]] (spread to other locations in the body via lymph or blood).

==== By genetics ====
In 2016, the WHO restructured their classifications of some categories of [[glioma]]s to include distinct [[genetic mutations]] that have been useful in differentiating tumor types, prognoses, and treatment responses. Genetic mutations are typically detected via [[immunohistochemistry]], a technique that visualizes the presence or absence of a targeted protein via [[staining]].<ref name=":4" />
* Mutations in [[IDH1]] and [[IDH2]] genes are commonly found in low-grade gliomas
* Loss of both IDH genes combined with loss of [[chromosome]] arms 1p and 19q indicates the tumor is an [[oligodendroglioma]]<ref>{{cite web |url= https://www.lecturio.com/concepts/oligodendroglioma/| title= Oligodendroglioma|website=The Lecturio Medical Concept Library |access-date= 21 August 2021}}</ref>
* Loss of [[P53|TP53]] and [[ATRX]] characterizes [[astrocytoma]]s
* Genes [[Epidermal growth factor receptor|EGFR]], [[Telomerase reverse transcriptase|TERT]], and [[PTEN (gene)|PTEN]], are commonly altered in gliomas and are useful in differentiating tumor grade and biology<ref name=":4" />

====Specific types====
{{main|WHO classification of the tumors of the central nervous system}}
[[Anaplastic astrocytoma]], [[Anaplastic oligodendroglioma]], [[Astrocytoma]], [[Central neurocytoma]], [[Choroid plexus carcinoma]], [[Choroid plexus papilloma]], [[Choroid plexus tumor]], [[Colloid cyst]], [[Dysembryoplastic neuroepithelial tumour]], [[Ependymal tumor]], [[Fibrillary astrocytoma]], [[Giant-cell glioblastoma]], [[Glioblastoma]], [[Gliomatosis cerebri]], [[Gliosarcoma]], [[Hemangiopericytoma]], [[Medulloblastoma]], [[Medulloepithelioma]], [[Meningeal carcinomatosis]], [[Neuroblastoma]], [[Neurocytoma]], [[Oligoastrocytoma]], [[Oligodendroglioma]], [[Optic nerve sheath meningioma]], [[Pediatric ependymoma]], [[Pilocytic astrocytoma]], [[Pinealoblastoma]], [[Pineocytoma]], [[Pleomorphic anaplastic neuroblastoma]], [[Pleomorphic xanthoastrocytoma]], [[Primary central nervous system lymphoma]], [[Sphenoid wing meningioma]], [[Subependymal giant cell astrocytoma]], [[Subependymoma]], [[Trilateral retinoblastoma]].