Neuro Onc Flashcards
Medulloblastoma
Most common childhood brain tumor (25%).
80% arise in the midline vermis with necrosis (arrow) presenting with truncal ataxia and hydrocephalus
Sheets of monotonous small blue cells
– Arranged in a circle with the center filled with cytoplasmic processes (Homer Wright rosettes) (circle).
Retinoblastoma
Located in the retina (arrow).
Sheets of monotonous small blue cells
– Arranged in a circle forming a true lumen (Flexner-Wintersteiner rosettes) (circle).
Most common intraocular neoplasm found in childhood
Heterogeneous retinal mass with calcifications, necrotic components and increased vascularization on Doppler ultrasound/enhancement on CT/MRI.
Retinoblastomas may be sporadic or secondary to a germline mutation of the retinoblastoma protein tumor suppressor gene (RB), which is usually inherited. Loss of Rb gene on 13q
Bilateral (30-40% of cases) essentially always have a germline mutation; unilateral tumors (60-70% of cases) are caused by a germline mutation in approximately 15% of cases, whereas 85% are sporadic. Thus, ~55% of cases are due to a germline mutation. This mutation is inherited in an autosomal dominant fashion with ~90% penetrance
Presentation is most frequently with leukocoria or loss of red-eye reflex.
Flexer-Wintersteiner rosettes: central lumen that contains small cytoplasmic extensions of the encircling cells; however, unlike the center of the Homer Wright rosette, the central lumen does not contain the fiber-rich neuropil
Conservative treatment - external-beam radiation therapy, cryotherapy, laser photocoagulation
radioactive plaque therapy, thermochemotherapy, tumor reduction chemotherapy
Surgical treatment - enucleation, en bloc resection
Pilocytic astrocytoma
Circumscribed cystic lesion with a mural nodule (circle).
– Predilection for posterior fossa
– Also frequently occur in hypothalamus, brainstem and optic nerve
– 20% of childhood tumors
Spindled astrocytes (stain with GFAP) with intracytoplasmic eosinophilic corkscrew inclusions (Rosenthal fibers) (arrow).
Low-grade astrocytoma
Diffuse astrocytoma involving the thalamus (circle).
There is increased cellularity of astrocytes, which stain for GFAP
– Necrosis and vascular proliferation are absent.
Astrocytomas
Adult - supratentorial
IDH mutant (no 1p/19q deletion like oligodendroglioma) vs wild type, which is poor prognosis
Includes GBM
Astrocytoma - imaging
Adult - supratentorial
Diffuse/Low-grade: T2 hyperintense that suppresses on FLAIR (T2-FLAIR mismatch), non-enhancing, no vasogenic edema
Anaplastic: like low grade but enhance and can have some mass effect, no necrosis
GBM: nodular, ring-like enhancing mass that may cross the corpus callosum, vasogenic edema
GBM has heterogeneity, mass effect, vasogenic edema
Classic butterfly lesion of GBM crossing the corpus callosum (circle).
***Lymphoma also involves the CC
May arise de novo or progress from a lower grade astrocytoma.
GBM
Pseudopalisading necrosis (circle).
– areas of ischemia and necrosis occur as the tumor outgrows its blood supply, pleomorphic tumor cells border central areas of necrosis and hemorrhage
Endovascular proliferation (arrow).
– Immature thickened capillaries develop secondary to angiogenic factors produced by the tumor
Grossly, it is a heterogeneous mass with necrosis and hemorrhage. Microscopically, it is very hypercellular, with nuclear atypia and abundant mitoses. Endothelial hyperplasia, necrosis, and perinecrotic pseudopalisading differentiate glioblastoma from other neoplasms, and from astrocytomas of lower grades.
GBM
Adult - supratentorial
Most common adult primary brain tumor
CT: irregular thick margins, necrosis, mass effect, edema
T1: hypo/isointense, central heterogeneous necrosis
T2/FLAIR: hyperintense with vasogenic edema; can have low-intensity rim from blood product
C+: variable, irregular enhancement
Gross appearance: These tumors may be firm or gelatinous. Considerable regional variation in appearance is characteristic. Some areas are firm and white, some are soft and yellow (secondary to necrosis), and still others are cystic with local hemorrhage
Poor prognosis. Tx: maximal surgical resection, if possible, focal radiation and temozolamide (Temodar): DNA alkylating agent + tumor treating fields. Dexamethasone if vasogenic edema causing mass effect. AEDs only if seizures
In a patient with a high-grade glioma, improved survival is predicted by methylation of the MGMT (O6-methylguanine-DNA methyltransferase) gene promotor and treatment with temozolomide
Primary CNS lymphoma
Seen in immunocompromised states (e.g. AIDS)
B-cell lymphoma (85%)
B-cells surrounding blood vessels (perivascular cuffing) (circle).
The lymphoma cells have nuclear pleomorphism (arrows).
Oligodendroglioma - Adult supratentorial, usually arising superficially and with cortical involvement
Uniform small round dark nuclei surrounded by a perinuclear halo (fixation artifact) (“fried egg”) (circle).
Delicately branching vessels (chicken wire) (arrow).
Defined as diffusely infiltrating glioma with IDH1 or IDH2 mutation and codeletion of chromosome arms 1p and 19q (CNS WHO grade 2 or 3)
Imaging
involve cortex or subcortical white matter
CT: mixed density (hypodense to isodense). High-attenuation areas within the tumor are likely from calcification
MRI: hypointense on T1 and hyperintense on T2 ((except calcified areas), ~50% enhance, typically no diffusion restriction
Treatment: surgical, with adjuvant radiotherapy and chemotherapy
Loss of heterozygosity for 1p and 19q is a favorable prognostic factor to respond to chemotherapy.
Treatment of oligodendrogliomas involves surgical resection, chemotherapy, and radiation therapy. The chemotherapy used includes temozolomide, or PCV (procarbazine, lomustine, and vincristine).
Ependymoma (pediatric>adult ventricular tumor)
Located in the 4th ventricle (without necrosis)
– Also occur in the filum terminale
Perivascular psuedorosettes
– Ependymal cells that stain positive for vimentin surround a blood vessel (common) (arrow).
Ependymal rosettes (circle)
– Ependymal cells arranged in a circle forming a true lumen (uncommon)
Ependymal cells line the ventricles and create CSF
Located at 4th ventricle in children and can cause hydrocephalous
MRI:
T1 iso to hypointense
T2 hyperintense
C+: heterogeneous enhancement,
Can have cystic areas (typically seen in supratentorial tumors)
Pathology: perivascular pseudorosettes = tumor cells arranged radially around a central vessel. The modifier “pseudo” differentiates this pattern from the Homer Wright (medulloblatoma) and Flexner-Wintersteiner rosettes (retinoblastoma), perhaps because the central structure is not actually formed by the tumor itself, but instead represents a native, non-neoplastic element. Also, some early investigators argued about the definition of a central lumen, choosing “pseudo” to indicate that the hub was not a true lumen but contained structures.
+ GFAP, Vimentin
Macroscopically tend to compress rather than infiltrate
Poor prognosis
Pituitary adenoma
Adult - sellar
Hypercellularity
Single cell type
Destruction of the fibrovascular septa with resulting loss of the acinar structure (circle).
Presentation: Headache, bitemporal hemianopsia, endocrine dysfunction
>10mm = macroadenoma
secretory: ~65%
prolactin: ~50% - tx w bromocriptine or cabergoline
growth hormone (GH): 10%
adrenocorticotropin (ACTH): 6%
thyrotropin (TSH): 1%
mixed non-secretory: ~35%; most tend to be macroadenomas
In Adults, associated with MEN 1 (pituitary adenoma, pancreatic tumors, parathyroid hyperplasia)
Craniopharygioma
Pediatric - sellar
Solid and cystic components
– A viscous dark brown fluid fills the cyst
Islands of peripheral columnar pallisading epithelial cells embedded in a collagenous matrix (arrow).
Nodules of plump pale keratin (circle)
Enhancing calcified cystic mass on CT head
Adamantinomatous – “wet” keratin nodules, and epithelial component, gross resembles motor oil (RITE 2020)
Radical surgery + XRT, risk of chemical meningitis with resection
Pineal Germinoma
Most common tumor of the pineal gland
Two cell populations
– small dark reactive lymphocytes (arrow).
– large atypical cells with prominent nucleoli (circle).
Stains positive for placental alkaline phosphatase
Meningioma
Arise from meningothelial cells of the arachnoid.
Located
– Over the convexities (top)
– At the skull base – interventricular
Sheets of nuclei within distinct cell borders with
– menigothelial whorls (circle).
– psammoma bodies (calcified whorls) (arrow).
Stain with epithelial membrane antigen
Schwannoma
Arise from Schwann cells of any peripheral nerve
Adjacent low cellular areas (Antoni B) (open arrow) and densely cellular areas (Antoni A) (closed arrow).
The nuclei may appear pallisading (Vercoray body) (circle).
Metastases
Most common intracranial tumor (up to 10 times more common than primary brain tumors)
Circumscribed masses at the gray-white junction (arrow). 1⁄2 present with multiple metastases
Common primary tumors
– Lung
– Breast
– Melanoma
– Renal
– GI
Metastatic lesions are more common than primary brain tumors. Eighty percent of brain metastases are supratentorial and 20% intratentorial. Intracranial metastatic lesion can affect the skull, dura and/or brain parenchyma, or produce meningeal carcinomatosis.
The most common source of metastasis to the brain is the lung, followed by breast and then melanoma. _Other tumors that may produce brain metastasis include gastrointestinal tumors (especially from the colon and rectum), kidney cance_r, and tumors originating from the gallbladder, liver, thyroid, testicle, uterus, ovary, and pancreas. It is very rare to have parenchymal brain metastases originating from the prostate, esophagus, oropharynx, and skin (other than melanoma). Colon and pelvic cancers have a tendency to spread to the posterior fossa.
Metastatic lesions can be multiple or single. Multiple metastases are seen with small cell carcinomas and melanomas. _Those that are frequently found as single metastasis originate from the kidney, breast, thyroid, or adenocarcinoma of the lun_g. Hemorrhagic metastases are seen with melanoma, choriocarcinomas, non–small cell carcinomas, thyroid carcinomas, and renal cell carcinomas.
Patients harboring metastasis typically present with seizure, focal neurologic findings, headaches, and sometimes with increased intracranial pressure. Symptom onset is typically relatively rapid and abrupt rather than gradual.
The treatment of brain metastasis includes brain irradiation, surgical intervention for solitary metastasis in some cases, and chemotherapy. Steroids play a significant role in the treatment of surrounding edema from metastatic lesions.
Most common intracranial tumors in adults
Mets
Glioblastoma
Meningioma
Schwanomas
Oligodendromas
MGM StudiOs
Most likely primary to metastasize to the brain
From most to least common
Lung
Breast
Skin (melanoma)
- - -
Kidney
GI
Lots of Bad Stuff Kill Glia
Most likely primary to metastasize to the leptomeninges
Adenocarcinomas (breast, prostate, GI)
NHL
Leukemia
Most common mets to bleed
Melanoma
Renal cell carcinoma
Choriocarcinoma
WHO Grade I
Grade I: Well-circumscribed, cured by resection
WHO Grade II
Grade II: “Diffuse”, generally hypercellular, with mild nuclear atypia but no mitotic activity
WHO Grade III
Grade III: “Anaplastic”, hypercellular with increased nuclear atypia, mitotic activity
Grade IV:
At least 3 of the following features:
- nuclear atypia
- mitotic activity
- endovascular proliferation
- necrosis
WHO Grading system 2016 vs 2021
Separates pediatric and adult tumors
Major emphasis in molecular alterations:
isocitrate dehydrogenase (IDH) mutations
chromosome 1p/19q loss
H3K27M mutation
New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling
Now Arabic numerals
Brain tumors by location
Adult supratentorial tumors
Oligodendroglioma
Astrocytomas
Glioblastomas
Pediatric supratentorial tumors
Pleomorphic xanthoastrocytoma
Diffuse midline gliomas
Gangliocytoma/ganglioglioma/DNET
Adult ventricular tumors
Ependymoma
Subdependymoma
Pediatric ventricular tumors
Ependymoma
Central neurocytoma
Choroid plexus papilloma
Medulloblastoma
SEGA
Adult cerebellar
Hemangioma
Pediatric cerebellar
Pilocytic astrocytoma
Pineal tumors - adult vs children
Adult sellar
Pituitary adenoma
Adult sellar
Pituitary adenoma
Pediatric sellar
Craniopharyngioma
Hypothalamic hamartoma
Rathke’s cleft cyst
Adult and pediatric spinal tumors
Ependyoma - both
Chordoma - adult>pediatric
Peripheral tumors
Schwannoma
Neurofibroma
Malignant peripheral nerve sheath tumor
Pleiomorphic xantoastrocytoma
Pediatric - supratentorial
Rare (1% of primary brain tumors)
BRAF or TSC1/TSC2 mutations
Cortical tumors with a cystic component and vivid contrast enhancement, most commonly in the temporal lobe where they present with temporal lobe epilepsy.
Features of slow growth may be present, such as no surrounding edema and scalloping of the overlying bone. A reactive dural involvement expressed by a dural tail sign can be found.
Pathology: pleomorphic – different types of cells (spindle cells, polygonal cells, multinucleated cells, foamy cells) and variable nuclear size. Rosenthal fibers.
Pleomorphic xanthoastrocytoma is not a diffuse astrocytoma and is rather a different type of astrocytoma, which is localized superficially, more commonly in the temporal lobe, with well- demarcated borders, and frequently associated with seizures.
Pleomorphic xanthoastrocytoma (PXA) is a well-demarcated tumor, typically superficial and affecting the cortex, and most commonly encountered in the temporal lobes. It is more common in children and young adults, and manifests clinically as focal epilepsy. On MRI, it is seen as a cyst with an enhancing mural nodule. Macroscopically, it is cystic, sometimes with calcifications. Microscopically, it is composed of pleomorphic astrocytes arranged in fascicles, with intercellular reticulin deposition, mesenchymal- like cells, and multinucleated giant cells. There are lipidized astrocytes in about 25% of the cases. Eosinophilic granular bodies are typically seen, and Rosenthal fibers may be seen in the periphery of the lesion. These tumors are often surgically resectable, and the prognosis is favorable. In about 15% to 20% of the cases PXA undergoes malignant transformation. PXA is classified as WHO grade II, unless there are foci of anaplasia, in which case it is considered grade III.
Diffuse midline gliomas
Pediatrics - supratentorial
Midline = thalamus, brainstem, mesencephalic, pontine
Most common medullary spinal cord
Imaging: Mass effect and hydrocephalus. Can cause CN palsies bc of location
CT: Typically hypodense with little, if any, enhancement.
MRI: T1: decreased intensity
T2: heterogeneously increased
T1 C+ (Gd): usually minimal (can enhance post-radiotherapy)
DWI/ADC: usually normal, occasionally mildly restricted
Extensive spread is relatively frequent, both craniocaudally to involve the cerebral hemispheres and spinal cord, as well as leptomeningeal spread
Due to the high rate of severe complications with biopsy, treatment has historically been commenced without histological confirmation, although due to the recent identification of distinct mutations (K27M mutations in the histone H3 gene H3F3A and related HIST1H3B genes) stereotactic biopsy is being performed in some centers, and may become routine when therapies specifically targeted to these mutations become available .
Prognosis remains poor, with a 2-year survival of less than 10% 3
Gangliocytoma/ganglioglioma/DNET
Pediatric - supratentorial
Subependymoma
Adult - ventricular
Grade I
Typically patients are asymptomatic and small lesions are discovered incidentally
Location: lateral or 4th ventricle
Imaging: T2 hyperintense, sharply demarcated, non-enhancing nodule
Pathology: tumor arising from subependymal glial layer with low cellularity and no high-grade features
Prognosis: good
Central Neurocytoma
Pediatric - ventricular
Grade II
Young adults
Lateral ventricle around the foramen of Monro, often attaches to the septum pellucidum
MRI: isodense, cystic or bubbly appearing
Pathology: small round cells, form neurocytic rosettes, synaptophysin + & neuronal specific enolase + (purely neuronal origin), central lumen or hub filled with fiber-like processes
Rosettes - little round grouping of cells, spoke-wheel or halo arrangement surrounding a central acellular region
Choroid Plexus Papilloma
Pediatric - ventricular
Age: children
Remember: choroid plexus has a lining of specialized epithelial tissue known as ependyma. So like ependymomas, these arise in the ventricles
- originate in the choroid plexus, and thus, children present with obstructive hydrocephalus with vomiting and macrocephaly
Location: lateral or 4th ventricle (more common in adults)
Imaging: hyperdense with calcifications on CT, flow voids on MRI, marked homogenous enhancement
Pathology: highly pleomorphic cells, no necrosis, papillary structure which expresses pancytokeratin & transthyretin
Prognosis: good
Choroid plexus papillomas are tumors of childhood, and most commonly arise from the lateral ventricles, followed by the fourth ventricle and then the third ventricle. Clinically, they may be asymptomatic, or present with hydrocephalus and manifestations of increased intracranial pressure, due to a combination of obstructed flow and increased CSF production.
Choroid plexus papillomas are circumscribed masses composed of epithelium lining fibrovascular cores, resembling normal choroid plexus. I_n contrast to papillomas, choroid plexus carcinomas are invasive, with nuclear pleomorphism, demonstrating atypia, mitosis, and necrosis._
Choroid plexus papillomas are surgically resectable and considered low grade or WHO grade I. Choroid plexus carcinomas are higher grade (WHO grade III), and after surgical resection, radiotherapy and chemotherapy may be needed.
Medulloblastoma
Pediatric - ventricular
Grade IV
Primitive neuroectodermal tumor (PNET)
Most common malignant CNS tumor of childhood
Age: children > adults
Location: 4th ventricle, cerebellar vermis
Imaging:
CT hyperdense, heterogeneous enhancement
T1 hypointense to grey matter
T1 C+ (Gd) overall 90% enhance, often heterogeneously, group 4 tumors tend to enhance less
T2/FLAIR overall are iso to hyperintense to grey matter, heterogeneous due to calcification, necrosis and cyst formation, surrounding edema is common 10
DWI/ADC high DWI signal (“restricted diffusion”)
Pathology: synaptophysin+ Homer-Wright rosettes
Genetics: c-myc, n-myc (poor prognosis), Li-Fraumeni, nevoid basal cell carcinoma syndrome
Can result in drop metastases (CNS neoplasm metastasizing in the spine/CSF) (RITE 2020) and leptomeningeal disease
True rosettes. Fibrin layer. Described by Homer-Wright.
Homer-Wright pseudorosettes, even though not appreciated in this picture, are seen in about a third of cases. Macroscopically, medulloblastomas are soft tumors, with necrosis and hemorrhage.
Medulloblastoma is a rapidly growing and invasive tumor, which arises from the cerebellum. It is seen in children, and accounts for 20% of childhood brain tumors.
Medulloblastomas are embryonal tumors that arise from pluripotential cells and are encountered in children, more commonly in males. These tumors are located in the posterior fossa, more specifically in the cerebellum. The clinical presentation includes manifestations of increased intracranial pressure, hydrocephalus, and cerebellar findings. The most common genetic defect is on chromosome 17.
Treatment involves maximal surgical resection, in addition to chemotherapy and radiation therapy, with survival rates up to 80% at 5 years.
A desmoplastic variant confers a better prognosis. Features of poor prognosis include early age at the onset (younger than 3 years of age), incomplete resection, presence of brain stem invasion, metastasis, large cell variants, glial differentiation, and N-myc transcription factor amplification.
SEGA
Pediatric - ventricular
Age: children with tuberous sclerosis
Location: lateral or 3rd ventricle
Imaging: heterogenous, marked enhancement
Pathology: giant cells, multiple nuclei
Genetics: TSC1 or TSC2 mutation (causes increased activity of tumor suppressor gene mTOR)
Treatment: surveillance + everolimus (mTOR inhibitor) or resection
A benign hamartomatous tumor, WHO grade I, located in the intraventricular region, commonly in the third or lateral ventricles. It is seen in tuberous sclerosis almost exclusively, and it occurs in children and young adults, but not in elderly patients. Macroscopically, it is solid, well demarcated, noninfiltrative, and frequently has calcifications. SEGA is surgically resectable. Microscopically, there is a glioneuronal appearance, and the cells are packed in fascicles and around blood vessels, giving the appearance of perivascular pseudorosettes. “Candle gutterings” are masses along the ventricular surface, similar histologically to SEGA, and seen in this condition.
Colloid cysts
Not tumors
Age: adults
Location: anterior roof of the 3rd ventricle at the foramen of Monro
Imaging: hyperdense on CT, no enhancement, variable appearance on MR due to variations in protein, mucin and water content in the cystic fluid
Presents with intermittent or persistent increased ICP headaches from “ball-valve” obstruction of the third ventricle
Vignette of positional headache
A 36-year-old man presents after a sudden loss of consciousness. His brain MRI scan prompts transfer to a tertiary care facility, where he is now alert and oriented, with intact cranial nerve function, intact reflexes, no sensory deficits, and a normal motor exam. 2021 RITE | 78 Given the MRI and biopsy images shown, which of the following is the most likely diagnosis? A. choroid plexus papilloma B. colloid cyst C. craniopharyngioma D. neurocysticercosis E. Rathke cleft cyst
Patients with colloid cysts tend to present with headaches from obstructive hydrocephalus, but they may have syncope and sometimes sudden death occurs. The cysts are bright on noncontrast T1 studies and do not enhance with contrast. The cyst contents are proteinaceous and do not suppress on T2 FLAIR sequence images. The epithelium is pseudostratified, ciliated, and has goblet cells but may be flattened and unrecognizable. The lining seen here is not consistent with the epithelium in a papilloma or craniopharyngioma. A Rathke cleft cyst may have a similar lining but would be in the pituitary, not the third ventricle.
Radiologically, these cysts may have increased signal on T1, with no significant enhancement, or with a small enhancing rim. C_olloid cysts have a thin-walled lining and contain thick and cloudy gelatinous fluid. Microscopically, there is a single layer of columnar ciliated or goblet cells._ The treatment is surgical resection, and sometimes shunt placement is required for management of hydrocephalus.
Hemangioma
Adult - cerebellar
Location: posterior fossa/spine
Imaging: sharply demarcated masses composed of cyst with non-enhancing walls and vividly enhancing mural nodule (RITE 2020)
Pathology: capillary rich and stromal tumor cells with vacuolated foamy cytoplasm (RITE 2019)
Genetics: von Hippel Landau (vHL=chromsome 3).
Treatment: radical surgery or limited resection + XRT; risk of chemical meningitis during resection
Patients may have polycythemia due to erythropoeitin production by stromal cells
From RITE 2019: Histopathologic examination w vascular channels and numerous capillaries, as well as stromal tumor cells that have vacuolated (“foamy”) cytoplasm
A 65-year-old woman has had worsening occipital headache, nausea, and vomiting for the past week. Examination reveals a wide-based gait and ataxia. Her pre- and post-gadolinium sagittal T1-weighted and post-gadolinium coronal images are shown. Which of the following is the most likely diagnosis? A. glioblastoma multiforme B. arteriovenous malformation C. cerebellar abscess D. cerebellar hemangioblastoma E. resolving hematoma Rationale: The lesions shown have a typical intensely enhancing nodule with a nonenhancing cyst-like fluid collection surrounding it, suggesting cerebellar hemangioblastoma. Resolving hematoma would not have the intense focus of enhancement and would have differing signal intensity. Cerebellar abscess would have prominent vasogenic edema, which is absent. Anaplastic astrocytoma would have a more infiltrative appearance than this lesion.
Pilocytic astrocytoma
Pediatric - cerebellar
Age: Children
Location: midline posterior fossa, hypothalamus/thalamus, optic nerve (in NF)
Imaging: cyst with hyperintense, enhancing mural nodule (RITE 2020)
Pathology: GFAP+, eosinophilic Rosenthal fibers (distinguish it from oligodendroglioma)
Genetics: N_F1 The association between NF1 and pilocytic astrocytomas is so strong that up to 20% of all patients with NF1 will develop these tumors_
Prognosis: good
Rosenthal fibers are astrocytic cytoplasmic inclusions, typically found in areas of longstanding gliosis. These elongated or “corkscrew” structures occur within astrocytic processes and are brightly eosinophilic (stain bright pink on the H&E stain) 1-3.
There are piloid or hair-like astrocytic processes, which give the name to this tumor. In addition, Rosenthal fibers and a few eosinophilic granular bodies are seen, neither of which are pathognomonic, but are typically seen in these tumors. These demonstrates a biphasic pattern of compact regions along with microcystic components.
This patient has pilocytic astrocytoma, which is a WHO grade I astrocytoma and the most common glioma in children, occurring usually in the first or second decade of life, but can be seen at any age. These tumors are well circumscribed, frequently located in the cerebellum, but can also be seen in the hypothalamus, third ventricle, optic nerve, spinal cord, and dorsal brain stem. In the cerebellum, they are characteristically cystic with a gadolinium- enhancing mural nodule, as depicted in Figure 8.4. In the hypothalamus and optic nerves these tumors are solid.
Most pilocytic astrocytomas are sporadic; however, neurofibromatosis type 1 is associated with these tumors, especially in the optic nerve.
Given the well-demarcated lesion, these tumors tend to be surgically curable with a good prognosis. If the tumor cannot be completely resected, radiation therapy or chemotherapy may be required.
Hypothalamic hamartoma
Pediatric - sellar
Associated clinically with precocious puberty and gelastic epilepsy
Age: children
Location: attaches to the tuber cinereum and projects into the suprasellar cistern or attaches to the mammillary region and can extend into the third ventricle
Imaging: iso on CT, T2 iso- to hyperintense on, no enhancement
Rathke’s cleft cyst
Embryonic rathke’s pouch, a structure of ectodermal origin that folds superiorly from the pharynx during the fourth week of gestation giving rise to the pituitary
Spinal cord ependymoma
Most common spinal tumor in adults, MC cervical
Clinical presentation is similar to that of other intramedullary spinal tumors, with pain, weakness, and sensory changes common.
Imaging: widened spinal cord, well-circumscribed, T2 hyperintense, vivid enhancement, calcification is uncommon (unlikely intracranial ependymomas)
Chordoma
Adult>pediatric spinal chordoma
Comes from notochord
Chordomas: arising from primitive notochordal remnants with a high rate of recurrence. Since chordomas arise in bone, they are usually extradural and result in local bone destruction.
Imaging: skull/bone based along neuroaxis, most often at the clivus or sacrococcygeal region, spanning more than 1 vertebral segment (RITE 2020)
A 37-year-old man presents with progressive vision loss and proptosis of the right eye. His axial CT scan is shown. Which of the following is the most likely diagnosis? A. multiple myeloma B. meningioma C. metastatic prostate cancer D. chordoma E. fibrous dysplasia Rationale: The CT scan, displayed in bone windows, shows abnormal fibrous and osseous tissue replacing normal bone in the sphenoid, temporal, and orbital bones. These findings are characteristic of fibrous dysplasia. Multiple myeloma can have a range of imaging abnormalities, including punched-out lytic lesions, diffuse osteopenia, or a solitary plasmacytoma. Bony metastatic lesions would not be this diffuse. A chordoma stems from remnant of embryonic notochord tissue and is positioned in or near the midline along the vertebral column
Not to be confused with:
Langerhans cell histiocytosis – think (pre)teenager with vertebral fracture
Brown tumor– hypercalcemia.
Chordomas are invasive osseodestructive tumors encountered in adults, more commonly in males, and arise from remnants of the primitive notochord. They are located most commonly in the clivus and sacrococcygeal region. If in the clivus, they may present clinically with headaches, neck pain, and multiple cranial neuropathies due to brain stem compression. If in the sacrococcygeal region, they may present with sphincter dysfunction and pain.
These tumors are locally invasive and tend to destroy the bone, which is appreciated on radiologic studies such as CT and MRI. Grossly, this tumor is infiltrative and lobulated. Microscopically, there is a lobulated pattern with fibrovascular septa and cords of epithelioid cells. There are large vacuolated cells called physaliphorous cells.
The treatment is surgical excision and sometimes radiotherapy for residual disease. There may be recurrences from residual tumor.
Meningioma
Extra-axial tumors and represent the most common tumor of the meninges. They are a non-glial neoplasm that originates from the meningocytes or arachnoid cap cells of the meninge
Age: adults, increased risk with history of radiation or NF2
Location: dural based (cavernous sinus, ON, spine) (RITE 2020 x2)
Imaging: homogenously enhancing +/- dural tail
Pathology: meningeal whorls that calcify into psammoma bodies
Prognosis: Good
Foster Kennedy Syndrome - usually due to an olfactory groove meningioma
Ipsilateral compressive optic atrophy
Ipsilateral anosmia
Contralateral papilledema
These tumors account for 13% to 26% of primary intracranial tumors, and are more common in women, with a peak in the sixth or seventh decades of life. The most common sites include the cerebral convexities, parasagittal region, sphenoid wing, parasellar region, and spinal canal.
Meningiomas are dural-based tumors, often with a dural tail seen on imaging and sometimes with mass effect on the adjacent parenchyma. Calcifications may occur. These tumors are generally benign, slow-growing, firm, rubbery, and well-demarcated, compressing brain tissue rather than infiltrating it (same as ependymoma). However, in malignant meningiomas, there may be tissue infiltration.
Microscopically, these tumors are composed of monomorphic cells with oval nuclei, and the presence of psammoma bodies is common. However, meningiomas are very heterogeneous, with multiple histologic variants ranging in the spectrum of histologic WHO grades I, II, and III. The majority of meningiomas are syncytial, fibrous, or transitional types, which are benign variants.
Radiologically, on MRI meningiomas are isointense to gray matter on T1 and T2, with homogeneous enhancement. A dural tail may be appreciated as mentioned.
More than half of meningiomas are associated with loss of chromosome 22, and there are associations of meningiomas with neurofibromatosis type 2, previous radiation, and breast carcinoma. (Same as ependymoma though 22q in that case)
Primary CNS lymphoma
Primary CNS lymphomas (PCNSL) are relatively uncommon tumors, accounting for 2.5% of all brain tumors. By definition, there is no co-existing systemic disease at the time of diagnosis, distinguishing it from CNS involvement from systemic lymphoma (secondary CNS lymphoma).
The vast majority (>90%) of primary CNS lymphomas are B-cell in origin (RITE = CD20): diffuse large B-cell lymphoma and high-grade Burkitt-like B-cell lymphoma
Primary CNS lymphomas present as solitary (60-70%) or multiple (30-40%) lesions with a predilection for the periventricular white matter, although they can also arise in the cortex or deep grey matter; the latter being more common in low-grade lesions 1,14. They are most frequently found in the supratentorial brain (~70%) 14.
CSF examination demonstrates elevated protein and decreased glucose. Positive cytology is uncommon (~25%). Positive EBV DNA in CSF is helpful for the diagnosis of lymphoma, particularly in immunocompromised individuals.
CT hyperdense enhancing supratentorial mass, with MRI T1 hypointense, T2 iso- to hypointense, vivid homogeneous enhancement and restricted diffusion. Usually, there is relatively little associated vasogenic edema and no central necrosis, although it is important to note that in immunocompromised individuals appearances tend to be more heterogeneous.
Treatment: steroid and methotrexate-based regimens help avoid or defer radiation, RT
Neuroblastoma
MC tumos of the adrenal gland in children, usually <4y/o. from neural crest cells
MC presentation is abdominal distention and firm, irregular mass that can cross midline (vs Wilms tumor that stays Midline)
Can also present with opsoclonus myoclonus
Increased HVA and VMA (catecholamine metabolites)
N-myc oncogene = poor prognosis
Opsoclonus –myoclonus: rapid, multi-directional eye movements (opsoclonus), quick, involuntary muscle jerks (myoclonus), uncoordinated movement (ataxia), irritability, and sleep disturbance.
Up to half of patients have an underlying occult neuroblastoma. The movements are believed to be from autoantibodies that occur either against neuroblastoma or an infection.
Vestibular schwannoma
These are tumors that occur more commonly in the fourth and fifth decades of life, and most commonly arise from the vestibular portion of cranial nerve VIII. They grow in the cerebellopontine angle, and may compress the brain stem and erode into the internal auditory meatus. Clinically, they grow slowly and may be asymptomatic, or present with hearing loss, tinnitus, and in some cases with cerebellar findings given that the cerebellar peduncles are compressed. Radiologically, they are seen as circumscribed isointense tumors with contrast enhancement. It is extra-axial (not within the brain parenchyma) and is not within the ventricular system.
