Neuro Onc Flashcards

Question

WHO Grade III

Answer 1

Grade III: “Anaplastic”, hypercellular with increased nuclear atypia, mitotic activity

Answer 2

Grade IV: At least 3 of the following features: - nuclear atypia - mitotic activity - endovascular proliferation - necrosis

Answer 3

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

Answer 4

Oligodendroglioma Astrocytomas Glioblastomas

Answer 5

Pleomorphic xanthoastrocytoma Diffuse midline gliomas Gangliocytoma/ganglioglioma/DNET

Answer 6

Ependymoma Subdependymoma

Answer 7

Ependymoma Central neurocytoma Choroid plexus papilloma Medulloblastoma SEGA

Answer 8

Hemangioma

Answer 9

Pilocytic astrocytoma

Answer 10

Pituitary adenoma

Answer 11

Pituitary adenoma

Answer 12

Craniopharyngioma Hypothalamic hamartoma Rathke's cleft cyst

Answer 13

Ependyoma - both Chordoma - adult\>pediatric

Answer 14

Schwannoma Neurofibroma Malignant peripheral nerve sheath tumor

Answer 15

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. ```

Answer 16

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

Answer 17

Pediatric - supratentorial

Answer 18

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

Answer 19

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

Answer 20

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._

Answer 21

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._

Answer 22

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.

Answer 23

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.

Answer 24

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.

Answer 25

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.

Answer 26

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

Answer 27

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

Answer 28

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)

Answer 29

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.

Answer 30

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)

Answer 31

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

Answer 32

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.

Answer 33

Bevacizumab – PRES, increased incidence of stroke, intracranial hemorrhage and optic neuropathy Cytarabine – acute cerebellar toxicity, worse with renal failure L-arginine – hypercoagulability (specifically CVST)

Answer 34

Associated with ovarian teratomas

Answer 35

Anti-Purkinje cell antibody, associated with gynecological cancer, ovarian or breast 90% of the time Anti-Yo are typically associated with paraneoplastic cerebellar degeneration, usually in the setting of breast or ovarian cancer.

Answer 36

Observe if no visual field deficit; enlarging optic gliomas may be treated with chemotherapy (carboplatin and vincristine); Radiotherapy as they can cause secondary peripheral nerve sheath tumors in the treatment field.

Answer 37

Reacts with nearly all neurons and is commonly associated with sensory neuropathy and encephalomyeloneuropathy. Paraneoplastic subacute sensory neuropathy and neuronopathy are associated with anti-Hu (ANNA-1) antibodies and linked to small cell lung cancer In paraneoplastic limbic encephalitis, anti-Hu is the antibody most commonly detected, and strongly associated with small cell lung cancer.

Answer 38

AEDs prophylaxis is NOT recommended in newly diagnosed brain tumors

Answer 39

This syndrome can present in adults with breast, ovarian, and small cell lung cancer, as well as in children with neuroblastoma (not medulloblastoma). Clinically, these patients have spontaneous rapid, irregular, and high-amplitude conjugate eye movements that occur in any direction, as well as diffuse myoclonic jerks, and ataxia. Adults - anti-Ri (ANNA-2), especially with breast cancer but can also be seen in a percentage of patient with small cell lung cancer Children - neuroblastoma, no associated antibody Characteristically, children with neuroblastoma respond to treatment with ACTH, and may have resolution of the neurologic manifestations when the neuroblastoma is resected. The prognosis tends to be worse in adults.

Answer 40

Diffuse astrocytomas : WHO grade II Can be classified according to the histopathologic cell type into fibrillary (prototypical: elongated hyperchromatic nuclei, scant cytoplasm, and the presence of a fibrillary background), gemistocytic (rounded cells with prominent eosinophilic cytoplasm), protoplasmic (oval-shaped nuclei and wispy cobweb-like processes), small cell, giant cell, epithelioid and granular cell, and glioblastoma with oligodendroglioma component. Diffuse astrocytomas -\> infiltrating neoplasms and account for 40% of primary brain tumors. Astrocytomas (WHO grade II) are slow- growing tumors that may evolve into an anaplastic astrocytoma (WHO grade III) or glioblastoma (WHO grade IV). In astrocytomas (WHO II) the MRI shows a T2-hyperintense lesion with no enhancement with gadolinium. Does not include pilocytic astrocytoma, pleiomorophic astrocytoma, or SEGA

Answer 41

(Seen with breast, prostate - via Batson's plexus: network of valveless veins that connect pelvic veins with internal vertebral veins, GI; lung cancer and melanoma) The treatment is radiation therapy to symptomatic areas, often requiring whole-brain radiation. Some cases are treated with intrathecal chemotherapy and, preferably, intraventricular chemotherapy with methotrexate via an Ommaya reservoir. Patients with meningeal carcinomatosis have a poor prognosis, usually with survivals of less than 6 months. In general, best response occurs in lymphomas, breast cancer, and small cell lung cancers. Worse prognosis is seen with other types of lung cancer and melanoma

Answer 42

The diagnosis can be established with CSF studies using cytologic evaluation and flow cytometry. CSF also will show a pleocytosis with increased protein and sometimes reduced glucose. However, CSF cytologic analysis is not sensitive, and many times repeated testing is needed. In some cases, leptomeningeal biopsy may be required.

Answer 43

- Age, radiation exposure Radiation exposure is a well-established risk factor known to be associated with the development of gliomas. Radiation for previous neoplasia of the CNS may increase the risk of developing a glioma. Gliomas are the most common primary brain tumor, and incidence increases with age. There are no other clearly associated risk factors. There is no clear link between these tumors and cell phone use. Immunosuppression and tobacco use have not been associated with these neoplasms.

Answer 44

Glioma, 50% of gliomas = GBM

Answer 45

Rosenthal fibers can be seen in Alexander’s disease, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and chronic reactive gliosis.

Answer 46

This patient with a glioblastoma most likely has a survival time of about 15 months or less. Patients with astrocytomas will have different prognoses depending on the histologic grade, being approximately 5 to 10 years for grade II, 2 to 3 years for grade III, and 1 year or less for grade IV. In a study comparing treatments in patients with glioblastoma, the median survival was 14.6 months with radiotherapy plus temozolomide, and 12.1 months with radiotherapy alone. The prognosis depends on other factors as well. Age is a very important factor, and younger patients do better than older ones. Performance status is also very important, and patients with poor baseline condition and significant neurologic deficits have a worse prognosis.

Answer 47

This type of tumor is the third most common CNS tumor in children, and 90% occur intracranially, most commonly in the infratentorial region, typically in the fourth ventricle. Ependymomas in the supratentorial region occur in the periventricular region, but they may uncommonly be more superficial. Ependymomas can also occur in the spinal cord, more commonly in adults.

Answer 48

Ganglioglioma, dysembryoplastic neuroepithelial tumors, oligodendrogliomas, and astrocytomas frequently present with seizures.

Answer 49

It has a prominent association with ovarian and breast carcinoma, but can also be seen in Hodgkin’s lymphoma, small cell carcinoma of the lung, and other visceral tumors. Associated antibodies Anti-Yo antibodies (also known as anti–Purkinje cell antibodies) are seen in the serum of about 50% of patients with this syndrome, especially in those with ovarian cancer, but in smaller percentages of patients with breast carcinoma. They are less commonly seen in small cell lung cancer and Hodgkin’s lymphoma. Some patients may have anti-Hu antibody (also known as ANNA-1), especially in the setting of small cell carcinoma of the lung. Anti-Tr antibody is associated with _lymphomas_, and seen more commonly in young men.

Answer 50

O-6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that can antagonize the effects of alkylating agents such as temozolomide. Tumors with MGMT methylation have reduced expression of MGMT, with less DNA repair enzyme, and improved survival in patients receiving alkylating agents.

Answer 51

For recurrent glioblastomas, treatment includes Bevacizumab, which is a monoclonal antibody that binds vascular endothelial growth factor (VGEF) acting as an anti-angiogenic agent. This medication may decrease edema and reduce the need for steroids.

Answer 52

The presence of gadolinium enhancement on MRI represents a disruption of the blood–brain barrier and correlates with the WHO grade. Usually grade II and III tumors have no or minimal enhancement, and grade IV tumors characteristically demonstrate ring enhancement, therefore correlating with a poorer prognosis. However, contrast enhancement is not always an absolute parameter, since lower grade tumors may enhance and higher grade tumors may heterogeneously enhance and rarely minimally enhance.

Answer 53

Certain genetic mutations have been associated with prognosis. IDH1 is a gene that encodes for isocitrate dehydrogenase. Mutations of the IDH1 gene are seen in low-grade gliomas. In a glioblastoma, the presence of IDH1 mutation suggests that it developed from a lower-grade tumor (secondary glioblastoma) and it is not likely to be a primary glioblastoma. IDH1 mutation is associated with improved prognosis. O-6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that can antagonize the effects of alkylating agents such as temozolomide. Tumors with MGMT methylation have reduced expression of MGMT, with less DNA repair enzyme, and improved survival in patients receiving alkylating agents.

Answer 54

The predominant antibody in paraneoplastic optic neuropathy is anti-CRMP-5, which is associated with lung cancer. These patients present with vision loss.

Answer 55

The predominant antibody in paraneoplastic retinal degeneration is anti-recoverin or anti-CAR, and is associated with small cell lung cancer, thymoma, renal cell carcinoma, and melanoma. These patients present with scotomas, vision loss, predominantly nocturnal, and disc swelling.

Answer 56

Lambert–Eaton myasthenic syndrome is a paraneoplastic syndrome presenting in the setting of small cell lung carcinoma and associated with anti–voltage-gated calcium channels of the P/Q type (see Chapter 10).

Answer 57

Presenting with bilateral choreoathetosis and in the setting of lung cancer, is associated with anti-Hu and anti-CRMP-5 antibodies.

Answer 58

Meningiomas are dural-based tumors originating from meningothelial or arachnoid cap cells

Answer 59

With anaplastic astrocytomas, p53 mutations may be seen in nearly half of these tumors. Anaplastic astrocytoma is a WHO grade III tumor, characterized by the presence of nuclear atypia, significant cellular proliferation, and mitotic activity, but without necrosis, perinecrotic pseudopalisading, or endothelial hyperplasia. These tumors are highly infiltrating. Genetic mutations are seen in these tumors, such as p53 mutation in almost half, and loss of p16 and other genes of the retinoblastoma regulatory pathway.

Answer 60

Cerebellar hemangioblastoma are prominently vascular tumors with abundant capillaries and stromal vacuolated cells. Hemangioblastomas are benign, vascular tumors, and the most common primary cerebellar neoplasm in adults. They can occur at any age, with a peak incidence between 25 and 40 years, being slightly more common in males. Macroscopically, they are well demarcated and cystic. Histopathologically, there are abundant capillaries and stromal vacuolated cells. They may present with mass effect and CSF obstruction, leading to increased intracranial pressure. _About 10% of these tumors secrete an erythropoietin-like substance leading to secondary polycythemia_. MRI demonstrates a cyst with an enhancing mural nodule. _This tumor is WHO grade I, and can be resected surgically. Hemangioblastomas are associated with von Hippel–Lindau (VHL) in about 25% of the cases, related to mutations in the VHL gene on chromosome 3p25–26._

Answer 61

Most ependymomas are WHO grade II. Anaplastic ependymomas are graded as WHO III, and are characterized by the presence of increased mitotic activity, hypercellularity, and microvascular proliferation. WHO grade II ependymomas may be surgically curable with a good prognosis, being the extent of resection an important prognostic factor. Radiation therapy may be used for residual disease. Prognosis is worse in patients younger than 3 years of age at presentation. Ependymomas in contact with the CSF may produce drop metastases conferring a worse prognosis

Answer 62

Myxopapillary ependymoma is a WHO grade I variant that occurs almost exclusively in the filum terminale. It is more common in adults, has a red appearance grossly, and a thin collagenous capsule. These tumors have a better prognosis.

Answer 63

Genetically, ependymomas may be associated with chromosome 22q deletions, and spinal ependymomas may be related to NF2 mutations (not NF1).

Answer 64

Ganglioglioma is a CNS tumor with glial and neuronal components. These tumors occur most commonly in children and young adults, arising from the temporal lobe, extending superficially, and presenting with seizures. Radiologically, the MRI may show a cyst with an enhancing mural nodule. These tumors are usually well circumscribed. Macroscopically, gangliogliomas are partially cystic,with solid components that may be calcified. Microscopically, there is a fibrillary background with dysmorphic ganglion cells showing nuclear pleomorphism, multinucleation, or cytoplasmic vacuolation. Other features include the presence of eosinophilic granular bodies, perivascular lymphocytic cuffing, microcystic spaces, and collagen deposition. The glial component shows glial fibrillary acidic protein (GFAP) positivity, whereas the neuronal component reacts with synaptophysin, chromogranin, and neurofilament.

Answer 65

Neurocytomas are encountered more frequently between the third and fifth decades of life. The location is intraventricular, more commonly in the lateral ventricles and in the third ventricle near the foramen of Monro. Macroscopically, they are well demarcated, soft, and friable. Microscopically, this neoplasm has round cells in a fibrillary background with prominent capillary vasculature, and sometimes with calcification. This tumor resembles oligodendroglioma; however, neurocytomas are immunoreactive for neuronal differentiation, but not for glial markers, being positive for _synaptophysin_ but negative for glial fibrillary acidic protein (GFAP). Ultrastructurally (on electron microscopy), neurocytoma shows neurotubules, neurofilaments, and neurosecretory granules. These tumors are WHO grade II, with good prognosis. The treatment is surgical resection.

Answer 66

Pineocytomas and pineoblastomas are tumors arising from the pineal gland parenchyma, presenting with various manifestations, including ophthalmologic findings such as Parinaud syndrome, brain stem and cerebellar manifestations, features of increased intracranial pressure, and hypothalamic dysfunction. Pineocytomas are more frequent in young adults. These tumors are well demarcated and homogeneous. Histopathologically, this tumor is composed of small uniform cells that resemble pineocytes, with low mitotic activity. There may be rosette formations. Pineoblastomas are more frequent in the first two decades of life, and macroscopically are soft and poorly demarcated, with areas of necrosis and hemorrhage. The cells may resemble those of other embryonal tumors, such as medulloblastomas, and there is significant proliferation of small round cells with high nuclear-to- cytoplasmic ratio, and prominent mitotic activity. These cells lack differentiation and resemble primitive neuroectodermal tumors, and not mature pineocytes. _Pineoblastomas are associated with a deletion on chromosome 11q, and may spread via the craniospinal axis or may metastasize. The prognosis of pineocytomas is better than that of pineoblastomas._

Answer 67

Epidermoid and dermoid cysts arise from _ectopic ectodermal tissue_. Epidermoid cysts occur in young adults and arise from the cerebellopontine angle. On MRI, epidermoid cysts have CSF intensity on T2, being slightly hyperintense to CSF fluid on FLAIR. They have a characteristic restricted diffusion appearance on DWI, which helps to distinguish these cysts from arachnoid cysts. Epidermoid cysts are microscopically lined by _squamous-type epithelium filled with keratinaceous material_. Dermoid cysts arise in children, and tend to occur in the cerebellar vermis, parasellar, or parapontine region and in the lumbosacral region in the spinal canal. They are a “pearly” white structure, with a content similar to epidermoid cysts, and lined by _squamous epithelium_; however, dermoid cysts _also contain hair follicles, sebaceous glands, and sweat glands_. Dermoid cysts can rupture, and the content can incite chemical meningitis characterized by granulomatous inflammation.

Answer 68

Arachnoid cysts are basically a cystic space bound by arachnoid membranes, with a location associated with the meninges, predominantly in the temporal lobe region. They are lined by _arachnoid cap cells_.

Answer 69

Rathke’s cleft cysts occur in between the anterior and posterior hypophysis. They have a thin-walled lining containing a cloudy fluid, and are lined by _columnar epithelium with ciliated and goblet cells._

Answer 70

DNET is a benign superficial tumor that is an important cause of refractory seizures inchildren. These tumors are located in the cortical or juxtacortical region, most commonly in the temporal lobe. The MRI shows a nodular or cystic lesion that is hyperintense on T2-weighted images and does not enhance with contrast. It grows very slowly. Macroscopically, it has a multinodular architecture, with mucinous cysts. _Histologically, it is seen as multiple areas in which ganglion cells appear to float within mucin- filled spaces (“floating neurons”)_. In between these nodules, there is a component with more glial characteristics, sometimes resembling an oligodendroglioma. At the edges of these lesions, there may be cortical dysplasia. DNET is a WHO grade I tumor, and surgical resection is helpful for the cure or control of the seizures.

Answer 71

PCNSL occurs predominantly in immunocompromised patients, such as patients with AIDS and posttransplant patients. In these cases they are frequently associated with Epstein–Barr virus (EBV). PCNSL can also occur in immunocompetent hosts; however, this is rare, and there is a lower association with EBV. PCNSL is usually a diffuse, large B-cell lymphoma, and rarely caused by T-cell proliferation. In contrast to secondary invasion by lymphomas from other primary sites, PCNSL invades the parenchyma more than the leptomeninges, and histologically, it is characterized by proliferation and diffuse infiltration of atypical lymphocytes with an angiocentric pattern as seen in Figure 8.12. These neoplasms can be single or multicentric, and can involve the corpus callosum. PCNSL can also involve the eye, and therefore, an ophthalmology evaluation is warranted to examine the vitreous for lymphoma cells. Clinically, the presentation is variable, manifesting with headaches, signs of increased intracranial pressure, seizures, focal neurologic deficits, or alteration in the mental status. MRI shows a lesion with T2 hyperintensity, edema, and contrast enhancement. The prognosis is poor, with 5-year survival rates of 25% to 45%, being much worse in immunocompromised patients. This neoplasm is steroid responsive, and steroids should be avoided before biopsy because they may reduce the yield of this diagnostic test. However in cases of emergency, especially in the presence of significant mass effect and herniation, steroid use may be required. Surgery is not indicated because this neoplasm is often deep and multicentric. The treatment includes radiation therapy and chemotherapy, with agents such as c_ytosine arabinoside and intrathecal methotrexate._ This combination prolongs survival; however, it is associated with leukoencephalopathy and systemic side effects. In patients with HIV-related PCNSL, highly active antiretroviral therapy is the treatment of choice.

Answer 72

This is craniopharyngioma, which is most common in children, but has a bimodal age distribution and is also seen in adults. Craniopharyngiomas are benign epithelioid tumors that originate from remnants of Rathke’s pouch and arise in the sellar region, where they grow to produce manifestations from mass effect on adjacent structures, such as the optic chiasm, pituitary, hypothalamus, bony structures, and ventricular system, even to the point of being able to obstruct CSF flow. Common manifestations are therefore visual disturbances, endocrine deficiencies, diabetes insipidus, and findings of increased intracranial pressure. Macroscopically, these tumors are partially solid with a cystic component, frequently filled with lipid- and cholesterol- rich brown fluid, also called “machine-oil–like fluid,” which if spilled, may cause a xanthogranulomatous inflammation. Microscopic calcifications, keratin, and xanthogranulomatous inflammation are seen more commonly in the adamantinomatous variant. In the papillary variant, the sheets of cells form pseudopapillae. Histology shows a tumor with **_multicystic_** _components, characterized by proliferation of cords of epithelial-appearing cells, with a palisade of basaloid cells toward the lumen of the cysts._ _These tumors are in general surgically resectable. They have a benign behavior, but may recur if there is incomplete resection._

Answer 73

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.

Answer 74

Adenomas greater than 1 cm in size are classified as macroadenomas, whereas those less than 1 cm in size are classified as microadenomas. Pituitary adenomas are the most common masses in the sellar region. The lesion is isointense on T1, and enhances almost homogeneously with contrast. Pituitary apoplexy, or hemorrhage into, most commonly, a pituitary macroadenoma, presents with sudden severe headache, ophthalmoparesis, and in some cases evidence of increased intracranial pressure

Answer 75

Metastases are round and demarcated, located in the gray–white junction, and hyperintense on T2-weighted images, with significant enhancement with gadolinium, and prominent surrounding vasogenic edema,

Answer 76

Positive with epithelial intermediate filaments,

Answer 77

Glial fibrillary acidic protein (GFAP) is positive with glial intermediate filaments,

Answer 78

Positive with melanocytic cells

Answer 79

CD45 is a marker of lymphocytes, CD3 for T cells, and CD20 for B cells.

Answer 80

Ki- 67 (or MIB-1) is a marker of nuclear proliferation.

Answer 81

Astrocytomas are classified as at least WHO grade II in the presence of atypia. Anaplastic astrocytomas are classified as WHO grade III on the basis of the presence of atypia and mitotic activity. Glioblastomas are WHO grade IV, having endothelial hyperplasia and necrosis. Astrocytomas can also be classified as diffuse astrocytomas, pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and subependymal giant cell astrocytomas. Diffuse astrocytomas can be subdivided according to the predominant histologic cell type (see questions 2 and 3).

Answer 82

IDH1 is a gene that encodes for isocitrate dehydrogenase. M_utations of the IDH1 gene are seen in low-grade gliomas, however, WHO I tumors are negative for this mutatio_n. Therefore, the presence of IDH1 mutation can help differentiate between WHO I and WHO II gliomas which are sometimes difficult to distinguish histopathologically. _In a glioblastoma, the presence of IDH1 mutation suggests that it developed from a lower-grade tumor (secondary glioblastoma) and it is not likely to be a primary._

Answer 83

This syndrome can present in patients with small cell lung cancer associated with anti-Hu (ANNA-1) antibodies. In young males, it may be associated with testicular germ-cell tumors, in which case the most common antibody encountered is anti-Ma. An autoimmune, nonparaneoplastic limbic encephalitis associated with voltage-gated potassium channel antibodies (anti-VGKC antibodies) may lead to a similar presentation. Treatment involves addressing the primary neoplasm. Some cases are responsive to steroids or other immunomodulatory therapies such as plasmapheresis or intravenous immunoglobulins. A paraneoplastic encephalitis has been reported in patients with ovarian teratomas associated with antibodies to NMDA receptors. This type of encephalitis manifests with psychiatric symptoms, amnesia, seizures, dyskinesias, autonomic dysfunction, and decreased level of consciousness. In these patients, tumor resection and immunotherapy lead to improvement, and in some cases, to full recovery.

Answer 84

_Mutation of p53 is not typically seen in oligodendrogliomas, and its presence suggests the possibility of an astrocytic neoplasm_. Deletion of the chromosomal region _p16 is more commonly seen in anaplastic astrocytomas and glioblastomas, and is associated with progression_.

Answer 85

Stiff-person syndrome is an autoimmune condition that can be either paraneoplastic or nonparaneoplastic. The nonparaneoplastic form is most commonly associated with anti-glutamic acid decarboxylase (anti-GAD) antibodies. _The paraneoplastic form is most commonly associated with anti-amphiphysin antibodies, and typically in the setting of breast cancer._ There are case reports of Stiff-person syndrome associated with _anti-Ri antibodies in the setting of lung cancer, and anti-gephyrin antibodies in mediastinal cancer, however, these are not common._ Treatment of the underlying malignancy and immunomodulatory therapies (intravenous immunoglobulin) have been reported. Benzodiazepines may be helpful for symptomatic treatment.

Answer 86

Inflammatory myopathies are associated with increased incidence of malignancy. This increased risk is more common with dermatomyositis (27% to 40%), but is also seen in polymyositis (15% to 18%). Inclusion body myositis has also been reported to be associated with malignancy risk, but this association is less well studied. Dermatomyositis is associated with ovarian, lung, gastric, colorectal, and pancreatic cancer, as well as non–Hodgkin lymphoma. Polymyositis has been associated with non–Hodgkin lymphoma, lung and bladder cancer. Anti-Jo antibodies are encountered in patients with inflammatory myopathies, such as polymyositis and less commonly dermatomyositis, but the titer does not correlate with malignancy risk or burden, and they may be less likely detected in cancer- associated myopathy.

Answer 87

In opsoclonus myoclonus syndrome in adults, anti-Ri (ANNA- 2) is the most commonly associated antibody, especially in the setting of breast cancer.

Answer 88

The predominant antibody in paraneoplastic retinal degeneration and is associated with small cell lung cancer, thymoma, renal cell carcinoma, and melanoma.

Answer 89

Paraneoplastic limbic encephalitis is associated with autoantibodies in the majority of the cases, with classic autoantibodies to intracellular antigens associated with paraneoplastic limbic encephalitis being * Anti-Hu, anti-Ma2 (Ta), and anti-CV2/CRMP5. In anti-Hu positive patients, _small cell lung cancer is the most frequent neoplasm_. Anti-Ma2 (Ta) in young males is almost always associated with _testicular germ-cell tumors._ * Anti-CV2/CRMP5 may be seen with _small cell lung cancer or thymoma_. * Autoantibodies to neuronal cell-surface antigens may also be associated with paraneoplastic limbic encephalitis. _These antibodies include anti-VGKC (small cell lung cancer and thymoma), anti- NMDA receptors (ovarian teratoma), anti-AMPA receptor (small cell lung cancer, breast cancer and thymoma), and anti-GABA-B receptor (small cell lung cancer)_ About 10% of patients with paraneoplastic or autoimmune limbic encephalitis have no detected autoantibodies. Treatment of paraneoplastic limbic encephalitis should initially focus on the treatment of the underlying neoplasm. Immunotherapy is frequently required and includes intravenous steroids followed by intravenous immunoglobulin or plasma exchange.

Answer 90

Glioblastoma

Answer 91

Oligodendroglioma

Answer 92

Ependymoma

Answer 93

Ependymoma

Answer 94

Medulloblastoma

Answer 95

Marker of nuclear proliferation

Answer 96

Glial fibrillar acidic protein. Marker of glial intermediate fibers.

Answer 97

Marker of epithelial intermediate filaments

Answer 98

Positive in melanyocytic cells

Answer 99

Positive in melanyocytic cells

Answer 100

Pilocytic astrocytoma, pleomorphic xantoastrocytoma, Alexander's disease, chronic reactive gloss

Answer 101

Pilocytic astrocytoma, pleomorphic xantoastrocytoma, Alexander's disease, chronic reactive gloss

Answer 102

Good prognostic factor in oligodendroglioma

Answer 103

Tuberous sclerosis

Answer 104

Oligodendroglioma, gangliogliomas, DNETs

Answer 105

Cereberallar hemangioblastoma, chromosome 3, AD

Answer 106

Paraganglioma

Answer 107

Lung\>brain\>melanoma

Answer 108

Anti-Yo antibodies

Answer 109

Anto-Hu (ANNA-1)

Answer 110

Anti-Ri (ANNA-2) antibodies

Answer 111

Neuroblastoma

Answer 112

Anti-recoverin antibodies

Answer 113

Anti-voltage gated calcium channel P/Q type antibodies

Answer 114

Anti-Ma antibodies

Answer 115

Anti-NMDA receptor antibodies

Answer 116

Anti-amphiphysin