Neoplastic Diseases

NEOPLASTIC DISEASES



 


 


 







4.1


Glioblastoma


Case History


A 56-year-old man presented to the hospital with a seizure. He had been complaining of headaches for the past several months and becoming “slow” as per family. He also noticed that he was “bumping into things” for the past few months.


Diagnosis: Glioblastoma Multiforme


Images


Images 4.1A–4.1C: Axial and sagittal postcontrast T1-weighted and axial FLAIR images demonstrate an enhancing mass spanning the splenium of the corpus callosum with mass effect and edema. The symmetrical appearance creates the characteristic “butterfly” appearance of high-grade gliomas. Image 4.1D: Gross pathology of a glioma (image credit The Armed Forces Institute of Pathology).


Introduction


Images  Grade IV astrocytomas, glioblastomas, are the most common and most lethal type of astrocytoma, with a median survival of less than 1 year. They occur most often in people over the age of 50 and are slightly more common in men. They almost always arise in the cerebral hemispheres. Even though the tumor may appear as a discrete mass, neoplastic cells spread along white matter pathways and are invariably spread throughout the brain at the time of diagnosis. There are no known risk factors other than exposure to radiation or rare genetic traits such as Li–Fraumeni syndrome.


Images  Grades I/II constitute about 15% to 20% of tumors, grade III accounts for 30% to 35%, and the highest grade, IV, accounts for about 40% to 50% of tumors. Table 4.1.1 details the WHO grading of central nervous system (CNS) tumors.


Table 4.1.1 WHO Grading of Glial Tumors




























WHO Grade


Tumor Type


Average Life Span


I


Juvenile pilocytic astrocytomas, subependymal giant cell astrocytomas (most commonly associated with tuberous sclerosis), pleomorphic xanthoastrocytoma


These can be cured with complete resection and most often occur in children.


II


Diffuse or fibrillary astrocytomas, oligodendroglioma


7–8 years


III


Anaplastic astrocytoma, anaplastic oligodendroglioma


2–3 years


IV


Glioblastoma multiforme


9–12 months


Clinical Presentation


Images  Tumors of the CNS present with essentially four different symptoms:


       1.  Progressive, focal neurological deficits


       2.  Headaches that are characteristically worse in recumbency and are often associated with nausea, vomiting, and other symptoms of increased intracranial pressure (ICP)


       3.  Seizures, if there is irritation of the cerebral cortex


       4.  Gradual cognitive slowing and personality changes


Images  The symptoms experienced by each patient depend on the location of the tumor and its rate of growth (Table 4.1.2). Slowly growing tumors can grow quite large and have significant mass effect despite causing few symptoms. Occasionally, patients can present with the sudden onset of neurological symptoms. This is common if there is hemorrhage into the tumor, but it sometimes occurs without such a hemorrhage for unclear reasons. Patients with a CNS neoplasm who have symptoms of systemic disease, such as fever and weight loss, are more likely to have metastatic disease rather than a primary CNS neoplasm.


Table 4.1.2 Clinical Presentation of Glioblastomas































Tumor Location


Clinical Presentation


Anterior Frontal Lobe


Images Weakness, primarily of the contralateral leg


Images Personality changes including disinhibition, poor judgment, cognitive slowing, and aphasia for left-sided lesions


Images Urinary incontinence due to disruption of the micturition inhibition center


Images Gaze preference if there is involvement of the frontal eye fields


Images Primitive reflexes such as grasp, suck, and snout reflex


Images Seizures


Posterior Frontal Lobe


Images Contralateral weakness


Images Expressive aphasia for left-sided lesions, neglect for right-sided lesions


Images Seizures


Temporal Lobe


Images Memory impairment


Images Wernicke-type aphasia for left-sided lesions


Images Contralateral superior quadrantanopia, neglect for right-sided lesions


Images Seizures


Occipital Lobe


Images Contralateral homonymous hemianopia, visual hallucinations


Images Alexia without agraphia for left-sided tumors involving the corpus callosum


Images Seizures


Thalamus


Images Contralateral sensory loss


Images Aphasias for left-sided lesions


Brainstem


Images Headache and hydrocephalus if there is obstruction of the ventricular system


Images Cranial nerve deficits


Images Sensory and motor deficits


Cerebellum


Images Ipsilateral limb ataxia for lateral tumors, truncal ataxia for midline tumors


Images Nausea and vomiting


Images Dizziness and vertigo


Images Headaches, often worse in the morning


Images Hydrocephalus if there is occlusion of the fourth ventricle


  


Images  Primary glioblastomas tend to arise de novo from glial cells, while secondary glioblastomas arise from lower grade tumors. The differentiating features are listed in Table 4.1.3.


Images  Mutations of isocitrate dehydrogenase (IDH1) are frequent in secondary glioblastomas (80%) and rare in primary glioblastomas (10%). Thus, IDH1 mutations are strong predictors of more favorable prognosis, and are highly selective molecular markers of secondary glioblastomas that complements clinical criteria for distinguishing it from primary glioblastomas. Additionally, O6-methylguanine-DNA methyltransferase (MGMT) is an important DNA repair enzyme that contributes to glioblastoma resistance to temozolomide. Methylation of MGMT has been reported to be a good prognostic factor for patients with glioblastomas.


Table 4.1.3 Characteristics of Primary and Secondary Glioblastomas



















Primary Glioblastoma


Secondary Glioblastomas


Accounts for >90% of biopsied or resected cases


Comprises <5% of glioblastoma multiforme cases


Occurs in older patients (median age: 60 years)


Occurs in younger patients (median age: 45 years)


Develops de novo from glial cells ~5% can be multifocal


Develops from low-grade or anaplastic astrocytoma


~70% of lower grade gliomas develop into advanced disease within 5–10 years of diagnosis


Radiographic Appearance and Diagnosis


Images  Glioblastomas generally appear as heterogeneously enhancing masses, with the nonenhancing areas representing areas of necrosis. There is mass effect and edema, best seen on T2-weighted images. As shown in Images 4.1A–4.1C, the tumor often crosses the corpus callosum creating a “butterfly” appearance. Ring-like enhancement, with a necrotic center, is common as well.


Images


Images 4.1E–4.1H: Histological features of a glioblastoma are shown (image credit Kia Newman, MD).


Images  A biopsy is required to make the diagnosis. The typical pathology features include necrosis, vascular hyperplasia with plump endothelial cells, pseudopalisading cells around necrosis, and atypical mitotic figures as seen in Images 4.1E–4.1H.


Special Cases


Gliomatosis Cerebri and Multicentric Glioma


Images  Gliomatosis cerebri refers to a type of malignant glioma that is characterized by extensive tumor infiltration without a discrete mass or areas of necrosis. Small areas of enhancement may be seen. There is no pathognomonic clinical presentation, but may present with headaches, seizures, personality change or dementia, or progressive weakness. This type of tumor commonly presents in people younger than 40. These tumors are treated with whole brain radiation and chemotherapy. With such treatment, there is a nearly 3-year life span. Gliomas may be multicentric in up to 5% of cases. These lesions may be very difficult to distinguish from metastatic disease or demyelination.


Images


Images 4.1I–4.1K: Axial FLAIR images demonstrate numerous areas of hyperintensity in the bilateral cerebral hemispheres. On biopsy this was found to be gliomatosis cerebri. Images 4.1L–4.1N: Postcontrast axial T1-weighted images from a different patient demonstrate numerous areas of irregular contrast enhancement (red arrows) in the bilateral cerebral hemispheres. On biopsy, these were found to be a glioblastoma.


Brainstem Glioma


Images  Tumors of the brainstem present with:


        Images  Headache and hydrocephalus if there is obstruction of the ventricular system


        Images  Cranial nerve deficits ipsilateral to the lesion


        Images  Sensory and motor deficits contralateral to the lesion


Images  These tumors are not amenable to surgical resection.


Treatment


Images  Surgery aims to reduce the tumor burden (debulking/cytoreductive), thereby reducing symptoms and extending survival times. A cohort of 1,229 patients demonstrated that survival time is directly correlated with the degree of tumor removed. Patients who had surgical excision of abnormalities on fluid-attenuated inversion recovery (FLAIR) imaging tended to fair better than those in whom surgical excision was limited to total resection of the T1 contrast-enhancing tumor volume. However, complete removal is not possible, as tumor cells are widespread throughout the brain at the time of diagnosis, even in areas that are radiographically unremarkable. Additionally, tumors in the brainstem are not amenable to surgical resection.


Images  Most high-grade glioblastomas will eventually become resistant to treatment, but clinical picture can be confused with pseudoprogression, which is especially seen after chemoradiation when there is a slight increase in enhancement without tumor progression. There are techniques such as magnetic resonance spectroscopy (MRS), PET, and single photon emission computed tomography (SPECT) scans, which can help distinguish pseudoprogression from true recurrence.


Images


Images 4.1O–4.1R: Axial and sagittal FLAIR and postcontrast T1-weighted images demonstrate an enhancing, necrotic mass (red arrow) expanding the pons, mostly on the left.


Images


Images 4.1S and 4.1T: Gross pathology demonstrates a brainstem glioma (image 4.1S credit The Armed Forces Institute of Pathology. Image 4.1T credit www.wikidoc.org via Professor Peter Anderson, DVM, PhD, and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology).


Images


Images 4.1U and 4.1V: Axial FLAIR image and postcontrast axial T1-weighted images demonstrate a T2-hyperintense mass in the right temporal lobe without contrast enhancement. Images 4.1W and 4.1X: Axial FLAIR image and postcontrast T1-weighted images demonstrate postsurgical changes after resection of the mass, found to be an anaplastic glioma on histology. Images 4.1Y and 4.1Z: Axial FLAIR image and postcontrast T1-weighted images 2 years after the surgery demonstrate tumor recurrence with extensive FLAIR hyperintensity and contrast enhancement.


Images  Radiation therapy has short-term side effects (hair loss, skin irritation, nausea, vomiting, fatigue, etc) and long-term sequelae (eg, neurological compromise and radiation-induced necrosis and vasculitis).


Images  Chemotherapy:


        – Temozolomide is an oral alkylating agent indicated for glioblastomas or recurrent anaplastic astrocytomas. In a trial of this medication in patients also treated with radiotherapy, 26.5% of patients treated with temozolomide were alive at 2 years, compared with 10.4% treated with radiotherapy alone.


        Bevacizumab: Tumors release the vascular endothelial growth factor (VEGF) protein, causing nearby blood vessels to sprout new vessels, a process called angiogenesis. These blood vessels feed the growth of the tumor. Bevacizumab is a therapeutic antibody that specifically binds to the VEGF protein, theoretically interfering blood supply of tumor, hence stopping the growth of cancer cells.


        – Other second-line chemotherapy agents include procarbazine, carboplatin, and BCNU/CCNU.


Images  Despite recent treatment advances, the prognosis for glioblastomas remains grim, as few patients survive beyond 2 years.


Images  Symptomatic therapy includes the use of steroids to reduce vasogenic edema, antiemetics, antibiotics, and anticoagulants, as the incidence of venous thromboembolism is 20% to 30%. Despite advances in therapeutic anticoagulation, inferior vena cava filters continue to remain an important part of the therapeutic armamentarium. Anticonvulsants are used in patients who have had seizures, but there is no role for prophylactic treatment.


References


1.  Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. November 2013;310(17):1842–1850.


2.  Mukundan S, Holder C, Olson JJ. Neuroradiological assessment of newly diagnosed glioblastoma. J Neurooncol. September 2008;89(3):259–269.


3.  Minniti G, Scaringi C, Baldoni A, et al. Health-related quality of life in elderly patients with newly diagnosed glioblastoma treated with short-course radiation therapy plus concomitant and adjuvant temozolomide. Int J Radiat Oncol Biol Phys. 2013;86:285.


4.  Barnholtz-Sloan JS, Williams VL, Maldonado JL, et al. Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma. J Neurosurg. 2008;108:642.


5.  Malmstrom A, Gronberg BH, Marosi C, et al. Nordic clinical brain tumour study group (NCBTSG). Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. September 2012;13(9):916–926.


6.  Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. May 2009;10(5):459–466.


7.  Stupp R, Mason WP, van den Bent MJ, et al. European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. March2005;352(10):987–996.


8.  Li YM, Suki D, Hess K, Sawaya R. The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection? J Neurosurg. October 2015;124(4):977–988.



 


 


 







4.2


Juvenile Pilocytic Astrocytoma


Case History


A 7-year-old child developed progressive headaches and ataxia.


Diagnosis: Juvenile Pilocytic Astrocytoma


Images


Images 4.2A–4.2D: Postcontrast axial and sagittal T1-weighted and axial T2-weighted images demonstrate predominantly cystic mass with a peripherally enhancing mural nodule in the right cerebellum. There is mass effect on the fourth ventricle and obstructive hydrocephalus (red arrows).


Introduction


Images  Astrocytomas are the most common type of intracranial neoplasms in children and young adults, comprising approximately half of such tumors. Of these, 75% are juvenile pilocytic astrocytomas (JPAs), which are benign, WHO grade I tumors.


Clinical Presentation


Images  JPAs typically occur in a cerebellar hemisphere where they present with symptoms of increased ICP and ataxia. In very rare cases, they may hemorrhage. They are second only to medulloblastomas in frequency in this location. Although they occur in a cerebellar hemisphere over half of the time, they may occur anywhere in the CNS. Tumors outside of the cerebellum are more common in adults.


Images


Images 4.2E–4.2H: Postcontrast axial, coronal, and sagittal T1-weighted and axial T2-weighted images demonstrate a complex cystic mass arising from the corpus callosum. There is both a ring-enhancing component and a solid-enhancing portion. There is mass effect on the right frontal lobe and hydrocephalus.


Images  JPAs of the optic nerve, chiasm, and tract are common in neurofibromatosis type I.


Images  JPAs may also occur in the spinal cord. They are most commonly found in the cervical cord where they present with central cord or hemicord syndromes and pain in the extremities.


Radiographic Appearance and Diagnosis


Images  On MRI, JPAs are well-circumscribed lesions that commonly have a large cystic component with an enhancing mural nodule. The cyst is typically isodense to cerebrospinal fluid (CSF) on all sequences, though cysts with a high protein content may by hyperintense to CSF on certain sequences. About 30% of cases have a more solid component or are completely solid. The major differential diagnostic consideration in such cases is hemangioblastomas.


Images  On histology, intracytoplasmic inclusions known as Rosenthal fibers are characteristic for JPAs. They are beaded, elongated, or corkscrew-shaped.


Treatment


Images  JPAs are usually amenable to surgical resection and have an excellent clinical outcome. The use of chemotherapy or radiation in the setting of incomplete tumor resection is controversial, given the young age of most patients. Spinal gliomas are not amenable to complete surgical resection, but surgery is needed to establish a diagnosis, and debulking of the tumor may delay progression of symptoms.


Images


Images 4.2I–4.2K: Postcontrast axial, coronal, and sagittal T1-weighted images demonstrate a complex cystic mass arising from the optic chiasm in a patient with neurofibromatosis type I. Image 4.2L: Gross pathology of pilocytic astrocytoma of the hypothalamic region (image credit The Armed Forces Institute of Pathology).


Images


Images 4.2M and 4.2N: Sagittal T2-weighted and postcontrast T1-weighted images demonstrate a heterogeneously enhancing mass (red arrow) in the lower cervical spinal cord with a syrinx below. This was found to be a juvenile pilocytic astrocytoma.


Images


Image 4.2O: Hematoxylin and eosin (H&E) stain demonstrates Rosenthal fibers in a JPA (image credit The Armed Forces Institute of Pathology).


References


1.  Bonfield CM, Steinbok P. Pediatric cerebellar astrocytoma: a review. Childs Nerv Syst. October 2015;31(10):1677–1685.


2.  Chourmouzi D, Papadopoulou E, Konstantinidis M, et al. Manifestations of pilocytic astrocytoma: a pictorial review. Insights Imaging. June 2014;5(3):387–402.



 


 


 







4.3


Oligodendroglioma


Case History


A 47-year-old man presented after a seizure. He was previously healthy and had slight left-sided weakness on neurological examination.


Diagnosis: Oligodendroglioma


Images


Images 4.3A–4.3D: Axial CT, postcontrast T-weighted, and FLAIR images demonstrate a mass in the right frontal lobe with areas of calcification. It demonstrates patchy enhancement and FLAIR hyperintensity, along with mass effect and compression of the lateral ventricle.


Introduction


Images  Oligodendrocytes form the myelin sheath around axons in the CNS, allowing for a rapid increase in the speed of the action potential generated by neurons. A single oligodendrocyte can myelinate up to 50 axons.


Images  Oligodendrogliomas are tumors that arise from oligodendrocytes. They account for 5% to 10% of primary CNS tumors in adults and occur more commonly in women. Patients usually present in their 40s and 50s.


Images  WHO classification:


        Images  Oligodendroglioma (WHO grade II; low grade): well differentiated, diffusely infiltrating, composed of cells resembling oligodendrocytes


        Images  Anaplastic oligodendroglioma (WHO grade III; high grade): malignant features such as the presence or absence of necrosis, vascular proliferation, increased number of mitoses, and increased nuclear atypia


Clinical Presentation


Images  Patients present with seizures, headache, cognitive dysfunction, or focal neurological abnormalities depending on the location of the tumor.


Radiographic Appearance and Diagnosis


Images  There is no radiographic feature that allows them to be reliably differentiated from other glial tumors. They are hypointense on T1-weighted images and hyperintense on T2-weighted images with mass effect. However, they are more likely to show calcification on CT scans and have less avid enhancement with the administration of contrast compared to glioblastomas. Only about 50% of them enhance, most commonly, heterogeneously.


Images  85% are supratentorial, most commonly in the frontal lobes.


Images  Histologically, the cells are characterized by a “fried egg” appearance. Some have features of an astrocytoma as well, and are referred to as oligoastrocytomas. Tumors with a high astrocytic component have a worse prognosis.


Images  The most common molecular genetic abnormality is co-deletion of chromosomal arms 1p and 19q, with about 70% of cases showing this deletion. The high frequency of co-deletion is a “genetic signature” of oligodendrogliomas, and tumors with this co-deletion have a better prognosis and improved responsiveness to chemotherapy.


Treatment


Images  They are treated with a combination of surgical resection, adjuvant chemotherapy (Procarbazine, CCNU, vicristine [PCV] regimen or temozolomide), and radiation.


Images


Image 4.3E: Histological specimen demonstrates the “fried egg” appearance of an oligodendroglioma. Image 4.3F: Gross appearance of an oligodendroglioma (image credit www.wikidoc.org via Professor Peter Anderson, DVM, PhD, and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology).


Images  The natural history is a gradual progression from low-grade tumors to high-grade lesions with anaplastic features. Oligodendrogliomas have an improved clinical response compared to astrocytomas with a 5-year survival rate of 50% to 75%. Many patients may survive 10 years or longer. Predictors of poor outcome include older age, poor functional status, tumor size greater than 4 to 5 cm, tumor outside of frontal lobes, and lack of co-deletion of chromosomal arms 1p and 19q.


References


1.  Roth P, Wick W, Weller M. Anaplastic oligodendroglioma: a new treatment paradigm and current controversies. Curr Treat Options Oncol. December 2013;14(4):505–513.


2.  Jiang H, Zhang Z, Ren X, et al. 1p/19q-driven prognostic molecular classification for high-grade oligodendroglial tumors. J Neurooncol. 2014 Dec;120(3):607–614.


3.  Bromberg JE, van den Bent MJ. Oligodendrogliomas: molecular biology and treatment. Oncologist. February 2009;14(2):155–163.


4.  van den Bent MJ. Diagnosis and management of oligodendroglioma. Semin Oncol. October 2004;31(5):645–652.



 


 


 







4.4


Primary Central Nervous System Lymphoma


Case History


A 45-year-old man presented with progressive right-sided numbness and weakness.


Diagnosis: Primary CNS Lymphoma


Images


Images 4.4A–4.4D: Postcontrast axial T1-weighted, FLAIR, diffusion-weighted, and apparent diffusion coefficient images demonstrate an enhancing mass in the right thalamus with FLAIR hyperintensity and restricted diffusion.


Introduction


Images  Primary CNS lymphoma (PCNSL) is the most common intracranial neoplasm in HIV-positive patients. About 5% of patients with AIDS will develop PCNSL, and the average CD4+ count at the time of diagnosis is 50/uL. In immunocompetent patients, it comprises 2% to 3% of all intracranial neoplasms, and the incidence has risen in the past several decades for unknown reasons.


Images  Most are derived from B cells. The CNS contains no lymphoid tissue, and as such the cellular origin of these tumors is not clear, though lymphoid channels have been found in mice, running parallel to the venous sinuses.


Images  It is highly associated with Epstein-Barr virus (EBV) in immunocompromised patients.


Clinical Presentation


Images  They present with cognitive decline and focal neurological deficits. Headaches and seizures are also possible presentations. It may spread via the CSF as well as to the eyes and bones.


Radiographic Appearance and Diagnosis


Images  They are usually subcortical in location, adjacent to the ependymal or subarachnoid surfaces. They are hypointense on T1-weighted images and have a variable appearance on T2-weighted images and they can be isointense, hypointense, and hyperintense to white matter. They enhance avidly and homogeneously with the administration of contrast. Higher grade tumors have more enhancement. A characteristic finding is avid restricted diffusion. There is less mass effect and edema than with other intracerebral tumors. They are usually hyperdense on T1-weighted images due to increased cellularity.


Images  Intraventricular disease is possible, though uncommon, occurring in less than 10% of patients on presentation.


Images  In contrast to immunocompetent patients, in immunosuppressed patients or those with AIDS, PCNSL typically presents as a ring-enhancing mass. Multiple lesions are common as well. It may be indistinguishable from toxoplasmosis, and patients should be treated empirically for toxoplasmosis. A biopsy should be performed only if there is no clinical or radiographic response.


Images


Images 4.4E and 4.4F: Postcontrast axial and sagittal T1-weighted images demonstrate an enhancing, lobulated tissue surrounding the ventricular system.


Images


Images 4.4G and 4.4H: Postcontrast axial T1-weighted and FLAIR images demonstrate two hyperintense, ring-enhancing lesions in the left frontal lobe due to lymphoma in an HIV-positive patient.


Treatment


Images  In immunocompetent patients there is often a positive response to chemotherapy (primarily with methotrexate) and radiation, but survival time is still only 3 to 4 years. In patients with HIV, the prognosis is dim with a survival time of only several months. There is no role for surgical resection.


Images  Treatment with glucocorticoids has a drastic effect on the radiographic appearance of the tumor as the tumor may shrink significantly and enhancement may disappear.


References


1.  Patrick LB, Mohile NA. Advances in primary central nervous system lymphoma. Curr Oncol Rep. December 2015;17(12):60.


2.  Hoang-Xuan K, Bessell E, Bromberg J, et al. Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol. July 2015;16(7):e322–e332.



 


 


 







4.5


Dysembryoplastic Neuroepithelial Tumor


Case History


A 12-year-old girl presented with intractable partial seizures.


Diagnosis: Dysembryoplastic Neuroepithelial Tumor


Images


Images 4.5A–4.5D: Axial FLAIR, postcontrast axial T1-weighted, and axial and coronal T2-weighted images demonstrate a large mass, of mixed signal with “soap bubble” appearance in the R frontal lobe. On postcontrast images, there is slight enhancement of a mural nodule (red arrow).


Introduction


Images  Dysembryoplastic neuroepithelial tumors (DNETs) are benign (WHO grade I) slow-growing tumors that arise most commonly from the cortex in the temporal lobe.


Images  They are rare tumors and account for less than 1% of intracranial neoplasms.


Clinical Presentation


Images  DNETs present in children and teenagers with intractable partial epilepsy. Patients do not generally have progressive neurological deficits.


Radiographic Appearance and Diagnosis


Images  DNETs are hypointense on T1-weighted images and are hyperintense on T2-weighted images with a “soap bubble” appearance and up to 80% of cases present with cortical dysplasia. Enhancement, often a mural nodule, is seen in about 30% of cases. There is no edema and minimal mass effect associated with DNETs.


Treatment


Images  Surgical removal is indicated in patients with intractable seizures and is usually curative.


References


1.  Zhang JG, Hu WZ, Zhao RJ, Kong LF. Dysembryoplastic neuroepithelial tumor: a clinical, neuroradiological, and pathological study of 15 cases. J Child Neurol. November 2014;29(11):1441–1447.


2.  Shinoda J, Yokoyama K, Miwa K, et al. Epilepsy surgery of dysembryoplastic neuroepithelial tumors using advanced multitechnologies with combined neuroimaging and electrophysiological examinations. Epilepsy Behav Case Rep. July 2013;1:97–105.


3.  Lee DY, Chung CK, Hwang YS, et al. Dysembryoplastic neuroepithelial tumor: radiological findings (including PET, SPECT, and MRS) and surgical strategy. J Neurooncol. April 2000;47(2):167–174.



 


 


 







4.6


Ependymoma


Case History


A 4-year-old presented with a severe headache, nausea, vomiting, and blurry vision for the past several months. He had decreased visual acuity and papilledema on examination.


Diagnosis: Ependymoma


Images


Images 4.6A–4.6C: Postcontrast axial, coronal, and sagittal T1-weighted images demonstrate a hyperintense, homogeneously enhancing mass arising from the floor of the fourth ventricle causing obstructive hydrocephalus. Image 4.6D: Gross pathology of an ependymoma (image credit The Armed Forces Institute of Pathology).


Introduction


Images  Ependymal cells line the walls of the ventricles in the CNS. The choroid plexus is formed by a network of ependymal cells and capillaries. Ependymal cells secrete and help circulate CSF throughout the ventricular system. Ependymomas are tumors that arise from the ependymal cells.


Images  These account for 2% to 9% of all intracranial tumors and about 12% of pediatric brain tumors. There is a bimodal age of distribution with ependymomas. Peaks occur in children aged 1 to 5 and adults aged 20 to 30.


Images  About 70% of these tumors occur infratentorially, usually from the fourth ventricle. They are the third most common posterior fossa tumor in children, behind juvenile pilocytic astrocytomas and medulloblastomas. Slightly less than half are supratentorial in location.


Images  The WHO assigns a grade to ependymomas based on the pleomorphism, mitotic count, cellularity, vascular proliferation and invasion and divides them into three different subtypes:


       1.  WHO grade I: myxopapillary ependymoma, subependymoma


       2.  WHO grade II: ependymoma (with cellular, papillary, and clear cell, tanycytic)


       3.  WHO grade III: anaplastic ependymoma is a more aggressive, faster growing tumor


Images  In adults, they occur in the spinal canal. Spinal cord ependymomas are the most common intramedullary neoplasm, most often occurring in the cervical cord followed by the thoracic cord. Spinal myxopapillary ependymomas occur in the conus medullaris and filum terminale.


Images  The key histological features are perivascular pseudorosettes and ependymal rosettes. Electron microscopy is necessary to differentiate ependymoma from glioma if rosettes are not present.


Images  The gain of 1q25 and endothelial growth factor receptor (EGFR) overexpression in these tumors is associated with poor prognosis. In contrast, a better prognosis has been associated with the loss of the region 6q25.3 in patients with anaplastic ependymomas. The underexpression of nucleolin carries a favorable prognosis. They may be associated with neurofibromatosis type II.


Clinical Presentation


Images  Intracranial ependymomas: In children, they present primarily with enlarging head circumference and signs of increased ICP and hydrocephalus due to obstruction of the ventricular system. Additionally, the tumors often spread from the fourth ventricle to the spinal canal via the CSF, a pattern of metastasis termed drop metastases. Supratentorial ependymomas present with seizures, headaches, and focal neurological deficits related to their location. Infratentorial lesions can cause nausea, vomiting, ataxia, and nystagmus.


Images  Spinal cord ependymomas: These present with back pain, neck pain, and slowly progressive myelopathy.


Images  Myxopapillary ependymomas: These present with leg and/or back pain as well as cauda equina syndrome. They present in patients between the ages of 30 and 40 years.


Radiographic Appearance and Diagnosis


Images  Intracranial ependymomas: As seen in Images 4.6A–4.6C, ependymomas tend to fill the fourth ventricle and expand through the foramen of Luschka, Magendie, and the foramen magnum. They are heterogeneous, hyperintense on T2-weighted images and enhance avidly, but homogeneously with the administration of contrast. They can be difficult to distinguish from medulloblastomas, but calcification is present in nearly half of the ependymomas, making CTs a key part of the evaluation. Hemorrhage and cystic areas are more common as well.


Images  Spinal cord ependymomas: They are intramedullary tumors that expand the spinal cord. They are hyperintense on T2-weighted images with edema present in over 50% of the cases. About 25% of tumors are surrounded by a hypointense hemosiderin rim on T2-weighted images (the “cap” sign), though this is not entirely specific for ependymomas. There is avid enhancement with the administration of contrast. Histologically, most of these are clear-cell tumors.


Images  Myxopapillary ependymomas: They are intradural and extramedullary tumors. Larger tumors displace the nerve roots of the cauda equina, while smaller tumors engulf them. They are typically hyperintense on T2-weighted image, though may have surrounding hypointensity due to hemorrhage. There is avid and homogeneous enhancement with the addition of contrast.


Treatment


Images  Medical management includes steroids for treatment of peritumoral edema and anticonvulsants in patients with supratentorial ependymoma. Adjuvant therapy includes conventional radiation therapy, radiosurgery, or limited field fractionated external beam radiotherapy (LFFEBRT) and chemotherapy after gross total resection (GTR) of an intracranial WHO grade II ependymoma.


Images  Postoperative LFFEBRT is recommended for WHO grade II ependymomas, when subtotal resection is noted on postoperative MRI, and for grade III anaplastic ependymomas regardless of extent of resection. Craniospinal radiation therapy is indicated regardless of grade or extent of resection if postoperative spinal MRI or lumbar puncture (LP) findings are positive.


Images


Images 4.6E–4.6G: Sagittal T2-weighted and postcontrast sagittal and axial T1-weighted images of the cervical spine demonstrate multiple homogeneously enhancing, intramedullary masses in the cervical spine in a patient with neurofibromatosis type II. The red arrow points to a dominant mass, which was found to be an ependymoma.


Images


Images 4.6H–4.6J: Sagittal T2-weighted and postcontrast sagittal and axial T1-weighted images of the lumbar spine demonstrate a homogeneously enhancing mass (red arrows) in the lumbar spine compressing the cauda equina. Image 4.6K: Gross pathology of ependymoma (image credit The Armed Forces Institute of Pathology; Dr. E. Michael Scott).


Images  Children with posterior fossa lesions can be surgically accessed by a midline suboccipital approach; hydrocephalus can be managed with a perioperative external ventricular drain, ventriculoperitoneal shunt, or, more rarely, third ventriculostomy.


Images  Filum terminale ependymoma should have gross total en bloc resection whenever possible.


Images  Intracranial ependymomas: Tumors that can be totally excised have an excellent prognosis, but due to their location this is often not possible. In these cases, adjuvant radiation therapy is given. The 5-year survival rate is up to 75%. Anaplastic ependymomas have a worse prognosis.


Images


Image 4.6L: Myxopapillary ependymoma: H&E low power microscopic view shows relatively monomorphic cells arranged in perivascular pseudorosettes and abundant blue mucin. It is a slow-growing neoplasm (most commonly encountered at cauda equina) with a low MIB-1 proliferative index (top right). The glial tumor cells are immunoreactive for glial fibrillary acidic protein (GFAP) and sometimes CD99 (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Images  Spinal cord ependymomas: They are generally benign tumors that grow slowly and do not infiltrate the cord, though they can rarely metastasize outside of the spinal cord. Complete surgical resection is possible in about 50% of cases and the 5-year survival rate approaches 90% and recurrence is uncommon. In cases of incomplete resection, the 5-year survival rate drops to 60%.


Images  Myxopapillary ependymomas: They can usually be excised completely with an excellent prognosis. Rarely, they may be spread throughout the CSF.


References


1.  Cage TA, Clark AJ, Aranda D, et al. A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas. J Neurosurg Pediatr. June 2013;11(6):673–681.


2.  Joaquim AF, Ghizoni E, Tedeschi H. Myxopapillary ependymomas. J Neurosurg Spine. May 2014;20(5):598–599.


3.  Benesch M, Weber-Mzell D, Gerber NU, et al. Ependymoma of the spinal cord in children and adolescents: a retrospective series from the HIT database. J Neurosurg Pediatr. August 2010;6(2):137–144.


4.  Monoranu CM, Huang B, Zangen IL, et al. Correlation between 6q25.3 deletion status and survival in pediatric intracranial ependymomas. Cancer Genet Cytogenet. 2008;182:18–26.


5.  Modena P, Lualdi E, Facchinetti F, et al. Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J Clin Oncol. 2006;24:5223–5233.



 


 


 







4.7


Subependymoma


Case History


A 45-year-old man developed headaches. The following lesion was seen and was stable for many years.


Diagnosis: Subependymoma


Images


Images 4.7A and 4.7B: Axial and sagittal FLAIR images demonstrate a lesion consistent with low-grade neoplasm likely arising from the dorsal aspect of the medulla at the level of the pontomedullary junction. Image 4.7C: Postcontrast axial T1-weighted image demonstrates that the lesions do not enhance. Image 4.7D: Gross pathology of subependymoma (image credit The Armed Forces Institute of Pathology).


Introduction


Images  Subependymomas are benign, WHO grade I, slow-growing ependymal tumors.


Images  They are most commonly found in the fourth ventricle and do not invade the brain or cerebellum. They can also arise in the lateral ventricles.


Clinical Presentation


Images  They are often incidental findings, but can present in middle-aged patients with symptoms of increased ICP if they obstruct the ventricular system.


Radiographic Appearance and Diagnosis


Images  MRI is the imaging modality of choice for visualizing these tumors. On T2-weighted images, they are hyperdense. Larger tumors may have a heterogeneous appearance. On T1-weighted images, they are hypointense or isointense to white matter. They rarely enhance with the administration of contrast.


Treatment


Images  Surgery is curative, but should be reserved only for symptomatic patients with hydrocephalus or in lesions that grow over time.


References


1.  Bi Z, Ren X, Zhang J, Jia W. Clinical, radiological, and pathological features in 43 cases of intracranial subependymoma. J Neurosurg. January 2015;122(1):49–60.


2.  Jain A, Amin AG, Jain P, et al. Subependymoma: clinical features and surgical outcomes. Neurol Res. September 2012;34(7):677–684.



 


 


 







4.8


Medulloblastoma


Case History


A 9-year-old boy presented with severe headaches, gait unsteadiness, and blurry vision.


Diagnosis: Medulloblastoma


Images


Images 4.8A–4.8C: Axial CT, FLAIR, and postcontrast T1-weighted images demonstrate a hyperintense and hyperdense midline cerebellar mass. It is growing within and expanding the fourth ventricle. There is evidence of secondary hydrocephalus. There is avid ring enhancement with central necrosis. Image 4.8D: Pathological demonstration of a medulloblastoma (image credit The Armed Forces Institute of Pathology).


Introduction


Images  Medulloblastomas are pediatric tumors that arise from the primitive neuroectoderm of the cerebellar vermis in the fourth ventricle.


Images  They comprise about 20% of all childhood brain tumors and 50% of cerebellar tumors. They occur more commonly in boys than girls with average age of diagnosis of 9 years. They account for less than 1% of tumors in adults.


Clinical Presentation


Images  They present with symptoms of increased ICP due to obstruction of the fourth ventricle or ataxia due to compression of the cerebellum. Symptoms emerge over the course of several weeks.


Radiographic Appearance and Diagnosis


Images  Medulloblastomas arise from the cerebellar vermis and project into the fourth ventricle. They are hyperdense on CT and 50% of cases have cystic necrosis. They are hyperintense on T2-weighted images and almost all have heterogeneous enhancement with contrast administration.


Images  They are most often confused with ependymomas. However, in contrast to ependymomas, which tend to grow within and enlarge the fourth ventricle, medulloblastomas compress the fourth ventricle, leading to hydrocephalus. Calcifications are present in about 10% of medulloblastomas, and in 50% of ependymomas. Occasionally, JPAs may arise from the midline of the cerebellum, but they more commonly arise from the cerebellar hemispheres.


Treatment


Images  Surgical resection is the mainstay of treatment, along with radiation and chemotherapy in select patients. They have the potential to spread through the CSF to other locations in the CNS. Imaging of the entire neuroaxis is important for this reason.


Images  In patients without metastases, favorable tumor markers, and in whom complete surgical resection is possible, the 5-year survival rate is about 80%. Survival drops to 20% in patients with metastases and incomplete surgical resection. Children younger than 3 years of age have a worse prognosis.


References


1.  Gerber NU, Mynarek M, von Hoff K, Friedrich C, Resch A, Rutkowski S. Recent developments and current concepts in medulloblastoma. Cancer Treat Rev. April 2014;40(3):356–365.


2.  Dhall G. Medulloblastoma. J Child Neurol. November 2009;24(11):1418–1430.


3.  Martin AM, Raabe E, Eberhart C, Cohen KJ. Management of pediatric and adult patients with medulloblastoma. Curr Treat Options Oncol. December 2014;15(4):581–594.


4.  Fruehwald-Pallamar J, Puchner SB, Rossi A, et al. Magnetic resonance imaging spectrum of medulloblastoma. Neuroradiology. June 2011;53(6):387–396.



 


 


 







4.9


Ganglioglioma


Case History


A 12-year-old child presented with seizures.


Diagnosis: Ganglioglioma


Images


Images 4.9A–4.9D: Axial T2-weighted and postcontrast T1-weighted and coronal FLAIR images demonstrate a cystic mass in the right temporal lobe with a small enhancing nodule.


Introduction


Images  Gangliogliomas are slow-growing tumors that most commonly occur in children and young adults. They are composed of a mixture of glial and neural elements. They are WHO grade I or II tumors, though they may undergo malignant transformation in rare cases. When the neural elements predominate, they are termed ganglioneuromas.


Images  They account for 10% of primary CNS neoplasms in children.


Images


Images 4.9E and 4.9F: Axial T2-weighted and postcontrast T1-weighted images demonstrate a mass with a large cystic component in the right frontal lobe with minimal enhancement of the tumor wall (red arrow).


Clinical Presentation


Images  They present with refractory seizures in children and young adults.


Radiographic Appearance and Diagnosis


Images  They are generally cystic tumors with or without a solid component. They are isodense or hypointense on T1-weighted images and hyperintense on T2-weighted images. There is usually no peritumoral edema. There is a variable degree of enhancement with the administration of contrast and is present in about 50% of tumors. CT will reveal calcifications about 40% of the time, which helps differentiate these tumors from juvenile pilocytic astrocytomas and pleomorphic xanthoastrocytomas.


Images  They are most commonly found in the temporal lobes, followed by the frontal, parietal, and occipital lobes. They may also be found near the hypothalamus and infratentorially.


Treatment


Images  They are treated with surgery, and total resection is curative. Radiation and chemotherapy can be added in cases where the location of the tumor renders complete resection impossible or those with malignant histological features.


References


1.  Karremann M, Pietsch T, Janssen G, Kramm CM, Wolff JE. Anaplastic ganglioglioma in children. J Neurooncol. April 2009;92(2):157–163.


2.  Ogiwara H, Nordli DR, DiPatri AJ, Alden TD, Bowman RM, Tomita T. Pediatric epileptogenic gangliogliomas: seizure outcome and surgical results. J Neurosurg Pediatr. March 2010;5(3):271–276.


3.  Hu WH, Ge M, Zhang K, Meng FG, Zhang JG. Seizure outcome with surgical management of epileptogenic ganglioglioma: a study of 55 patients. Acta Neurochir (Wien). May 2012;154(5):855–861.



 


 


 







4.10


Hemangiopericytoma


Case History


A 45-year-old man presented with a seizure.


Diagnosis: Hemangiopericytoma


Images


Images 4.10A–4.10D: Axial T2-weighted, FLAIR, and postcontrast T1-weighted images demonstrate an extraaxial mass in the right frontal lobe with mass effect. There are multiple flow voids (red arrows) due to blood vessels. There is prominent, but heterogeneous enhancement.


Introduction


Images  A hemangiopericytoma is an aggressive, extraaxial, meningeal WHO grade II tumor. They are highly vascularized mesenchymal neoplasms. More aggressive tumors, called anaplastic hemangiopericytomas, can metastasize outside the CNS and are WHO grade III.


Images  They are uncommon, accounting for less than 1% of all intracranial neoplasms.


Clinical Presentation


Images  They present with headaches, seizures, and focal neurological deficits depending on the location of the tumor. They can be seen at any age, but are most common in patients aged 30 to 40 years.


Radiographic Appearance and Diagnosis


Images  They are isointense to gray matter on T1-weighted images and isointense or hyperintense on T2-weighted images. Flow voids due to prominent vessels are commonly seen on T2-weighted images. There is avid, though heterogeneous enhancement with contrast administration. This contrasts with more homogeneous enhancement of meningiomas. Like meningiomas, hemangiopericytomas are adherent to the dura and a dural tail is often present.


Images  In contrast to meningiomas, there is no calcification on CT, and though they may invade and erode the bone, there is no hyperostosis.


Treatment


Images  They are treated with surgical resection, but commonly recur even with complete resection of the visible tumor mass. Chemotherapy and radiation are usually added for this reason. The median survival rate is 8 to 16 years and correlates with the degree of tumor resection.


References


1.  Rutkowski MJ, Sughrue ME, Kane AJ, et al. Predictors of mortality following treatment of intracranial hemangiopericytoma. J Neurosurg. August 2010;113(2):333–339.


2.  Rutkowski MJ, Jian BJ, Bloch O, et al. Intracranial hemangiopericytoma: clinical experience and treatment considerations in a modern series of 40 adult patients. Cancer. March 2012;118(6):1628–1636.


3.  Melone AG, D’Elia A, Santoro F, et al. Intracranial hemangiopericytoma–our experience in 30 years: a series of 43 cases and review of the literature. World Neurosurg. March–April 2014;81(3–4):556–562.



 


 


 







4.11


Pineoblastoma


Case History


An 11-year-old girl developed headaches and restricted upgaze.


Diagnosis: Pineoblastoma


Images


Images 4.11A–4.11D: Axial CT scan, axial T2-weighted, and postcontrast axial and sagittal T1-weighted images demonstrate a heterogeneously enhancing pineal mass with peripheral calcification.


Introduction


Images  Primary tumors of the pineal gland are known as pinealomas. The two forms are pineocytomas and pineoblastoma. Pineoblastomas are WHO grade IV tumors. They present before the age of 20, most commonly in children younger than 10. Pineocytomas are less malignant tumors that do not occur in children.


Images  They comprise 15% to 20% of pineal region tumors. They occur equally in males and females, in contrast to germinomas, which are more common in males.


Clinical Presentation


Images  Tumors of the pineal region present with the dorsal midbrain syndrome, disturbances in circadian rhythms, hydrocephalus, and headaches due to increased ICP.


Images  Pineocytomas are often clinically silent until they affect the midbrain and cause visual symptoms (primarily paralysis of upgaze), though they can cause disruptions of circadian rhythms as well. Large tumors may directly invade surrounding brain tissue.


Radiographic Appearance and Diagnosis


Images  Calcification around the periphery of the tumor is common. With germinomas, the calcification is more in the center of the tumor. On both T1-weighted and T2-weighted images, the tumor is isodense to the adjacent brain. Cystic areas are common. There is homogeneous enhancement with the addition of contrast. A biopsy is required to make the diagnosis.


Images  Imaging of the entire neuroaxis to screen for metastases is required as they are found in nearly 50% of patients.


Treatment


Images  Pineoblastomas are treated with surgical resection and radiation treatment to the entire brain and spinal cord to treat potential metastases. These tumors can spread throughout the subarachnoid space. The 5-year survival rate is only around 50%. Pineocytomas are treated with surgery alone. The 5-year survival rate is nearly 90%.


References


1.  Farnia B, Allen PK, Brown PD, et al. Clinical outcomes and patterns of failure in pineoblastoma: a 30-year, single-institution retrospective review. World Neurosurg. December 2014;82(6):1232–1241.


2.  Tate M, Sughrue ME, Rutkowski MJ, et al. The long-term postsurgical prognosis of patients with pineoblastoma. Cancer. January 2012;118(1):173–179.


3.  Lee JY, Wakabayashi T, Yoshida J. Management and survival of pineoblastoma: an analysis of 34 adults from the brain tumor registry of Japan. Neurol Med Chir (Tokyo). March 2005;45(3):132–141.



 


 


 







4.12


Germinoma of Pineal Gland


Case History


An 11-year-old boy developed headaches and “blurry vision” over the course of several months. On exam, the patient had difficulty looking upwards and his pupils did not react to accommodation, though they reacted to light.


Diagnosis: Pineal Germinoma


Images


Images 4.12A–4.12D: Axial CT, sagittal T2-weighted, axial FLAIR, and postcontrast axial T1-weighted images demonstrate a partially, centrally calcified, homogeneously enhancing pineal mass. It has mixed signal intensity on T2-weighted image.


Introduction


Images  The pineal gland is a midline endocrine gland that secretes melatonin, a hormone that regulates the sleep–wake cycle. It is stimulated by darkness and inhibited by light.


Images  Pineal region neoplasms account for 1% of all CNS tumors. They can be subdivided into those that arise from the pineal gland itself (pineoblastomas and pineocytomas), and those of germ cell origin (germinomas, teratomas, embryonal carcinomas, and choriocarcinomas).


Images  The majority of pineal tumors are of germ cell origin. Of these, germinomas comprise about 60% of all germ cell tumors and 40% of pineal regions masses overall. Germinomas are also frequently found in the suprasellar region and in the floor of the third ventricle.


Images  Other germ cell tumors include teratomas, embryonal carcinomas, and choriocarcinomas. These are collectively referred to as nongerminous germ cell tumors. Teratomas are the next most frequent germ cell tumor.


Clinical Presentation


Images  Tumors of the pineal region present with vertical gaze palsy, disturbances in circadian rhythms, hydrocephalus, and headaches due to increased ICP, if there is obstruction of the cerebral aqueduct, and occasionally thrombosis of the vein of Galen, which courses over the pineal gland.


Images  The dorsal midbrain syndrome (Parinaud’s syndrome) is a combination of eye movement and pupil dysfunction. It is commonly seen due to pineal tumors. Its core features are:


        Images  Severe restriction of upgaze with preservation of downward gaze. In the primary position, the eyes are often deviated downward and inward, due to an inability to abduct the eyes (the sun-setting sign).


        Images  Accommodative paresis, where patients’ pupils do not react to light, but constrict during accommodation. This is also termed pupillary light-near dissociation and when due to neurosyphilis, is referred to as Argyll Robertson pupils.


Images


Images 4.12E–4.12H: Axial FLAIR, and axial and postcontrast sagittal and axial T1-weighted images demonstrate multifocal enhancing masses of the pituitary stalk (red arrows), pineal gland (yellow arrows), and within the ventricular system in a patient with a germinoma.


        Images  Convergence–retraction nystagmus.


        Images  Eyelid retraction (Collier’s sign).


Images  Involvement of the pituitary stalk leads most commonly to diabetes insipidus, hypopituitarism, and visual disturbances due to involvement of the optic chiasm.


Images  Germinomas of the pineal region are more common in males and in people of Asian descent. They present in children between the ages of 10 and 13, with only 10% of patients presenting after the age of 20.


Radiographic Appearance and Diagnosis


Images  On CT, germinomas are hyperdense due to increased cellularity. The center of the tumor frequently calcifies, which is always pathological in children under 6 and a normal finding in only 10% of children under the age of 12. On both T1-weighted and T2-weighted images, they are either isointense or hyperintense compared to the brain. Cystic components are seen in 50% of cases. They enhance avidly and homogeneously with the addition of contrast. Germinomas frequently occur in the pineal region and within the ventricular system as well.


Images  In addition to its imaging characteristics, germinomas may have serum markers such as elevated human chorionic gonadotropin (HCG) and placental alkaline phosphatase. A biopsy is required to make the diagnosis.


Images  Teratomas frequently contain bone, fat, calcium, and sebaceum leading to a pattern of irregular enhancement, with a cystic component, in contrast to germinomas, which enhance homogeneously. The serum commonly contains β-human chorionic gonadotropin (β-hCG) and alpha-fetoprotein.


Images


Images 4.12I–4.12L: Axial CT image and postcontrast sagittal and axial T1-weighted images demonstrate a hyperdense, centrally calcified (red arrow) and hemorrhagic (yellow arrow), homogeneously enhancing mass in the pineal region. This was found to be a choriocarcinoma on biopsy.


Images  Choriocarcinomas are commonly hemorrhagic, and the serum contains β-hCG and placental lactogen.


Treatment


Images  Germinomas respond well to chemotherapy and radiotherapy, with surgery playing a secondary role. Up to 90% of tumors can be cured using radiotherapy. Spreading of tumor cells throughout the CSF is a frequent occurrence, though this does not influence the long-term prognosis.


Images  Teratomas and choriocarcinomas have a worse prognosis compared to germinomas.


References


1.  Salzman KL, Rojiani AM, Buatti J, et al. Primary intracranial germ cell tumors: clinicopathologic review of 32 cases. Pediatr Pathol Lab Med. September–October 1997;17(5):713–727.


2.  Westphal M, Emami P. Pineal lesions: a multidisciplinary challenge. Adv Tech Stand Neurosurg. 2015;42:79–102.


3.  Dufour C, Guerrini-Rousseau L, Grill J. Central nervous system germ cell tumors: an update. Curr Opin Oncol. November 2014;26(6):622–626.


4.  Echevarría ME, Fangusaro J, Goldman S. Pediatric central nervous system germ cell tumors: a review. Oncologist. June 2008;13(6):690–699.



 


 


 







4.13


Central Neurocytoma


Case History


A 34-year-old woman presented with severe headaches for the past several months. They are accompanied by blurry vision and are much worse during mornings.


Diagnosis: Central Neurocytoma


Images


Images 4.13A–4.13D: Axial FLAIR, T2-weighted, and postcontrast T1-weighted images demonstrate a hyperintense, though cystic, moderately enhancing mass in the right frontal horn.


Introduction


Images  Central neurocytomas typically develop in the lateral ventricles, next to the septum pellucidum in the region of the foramen of Monro.


Images  They are generally benign, although aggressive variants do exist. For this reason, they are WHO grade II tumors.


Images  They are rare and represent less than 0.5% of intracranial tumors.


Clinical Presentation


Images  Patients present with signs of increased ICP, namely headache, nausea, vomiting, and blurry vision, especially when there is obstruction of the foramen of Monro.


Images  Symptoms usually develop over the course of several months. Tumors extending outside the ventricular system may present with seizures. In rare cases, they may present with hemorrhage.


Images  Patients typically present between the ages of 20 and 40. These tumors are more common in people of Asian descent.


Radiographic Appearance and Diagnosis


Images  Tumors usually have both solid and cystic components. The solid component is typically isointense or hyperintense to gray matter on T2-weighted images. Flow voids may be seen. There is a variable degree of enhancement with the addition of contrast, ranging from intense enhancement to none at all. Punctate calcification is common and is best visualized on CT scan.


Images  Table 4.13.1 enlists other intraventricular tumors, which can be mistaken for central neurocytomas.


Images  On histological examination, central neurocytomas have neuronal features characterized by monotonous bland cells with minimal cytoplasm, often an empty-appearing “halo” resembling oligodendroglioma, salt and pepper fine chromatin, embedded in eosinophilic fibrillar matrix with rare Homer Wright rosettes and ganglion cells. These tumors typically lack necrosis, infiltrating margin, endothelial proliferation, and mitotic figures but rarely may show necrosis and mitotic figures. The cells are positive for synaptophysin, Neu-N, and neuron specific enolase immunostains.


Table 4.13.1 Differential Diagnosis of Central Neurocytomas


















Ependymoma


Subependymoma


Choroid plexus papilloma


Intraventricular meningioma


Intraventricular metastasis


Oligodendroglioma


Treatment


Images  Surgical resection is usually curative and a 5-year survival rate is over 80%. They recur 20% of the time and can be treated with adjuvant chemotherapy and radiotherapy.


References


1.  Donoho D, Zada G. Imaging of central neurocytomas. Neurosurg Clin N Am. January 2015;26(1):11–19.


2.  Patel DM, Schmidt RF, Liu JK. Update on the diagnosis, pathogenesis, and treatment strategies for central neurocytoma. J Clin Neurosci. September 2013;20(9):1193–1199.


3.  Monaco EA 3rd, Niranjan A, Lunsford LD. The management of central neurocytoma: radiosurgery. Neurosurg Clin N Am. January 2015;26(1):37–44.


4.  Garcia RM, Ivan ME, Oh T, Barani I, Parsa AT. Intraventricular neurocytomas: a systematic review of stereotactic radiosurgery and fractionated conventional radiotherapy for residual or recurrent tumors. Clin Neurol Neurosurg. February 2014;117:55–64.



 


 


 







4.14


Hypothalamic Hamartoma


Case History


A 5-year-old boy presented with gelastic seizures and behavioral problems.


Diagnosis: Hypothalamic Hamartoma


Images


Image 4.14A: Axial T2-weighted image demonstrates a round, heterogeneous mass of the hypothalamus that is isointense to the gray matter. The optic tracts are splayed and the optic chiasm is anteriorly displaced. The floor of the third ventricle is elevated. The interpeduncular fossa shows displacement of the cerebral peduncles laterally without edema. Images 4.14B–4.14D: Sagittal and axial T1-weighted images with and without contrast demonstrate the mass elevating the floor of the third ventricle. The lesion does not enhance with the administration of contrast.


Introduction


Images  Hypothalamic hamartomas (HH) are rare, benign lesions that are likely congenital in nature. They are composed of ganglion cells arranged singly and in clusters against a neurofibrillary background.


Images  They arise from the tuber cinereum, which consists of neuronal tissue in an ectopic location. Most of these lesions occur in the hypothalamus. Other locations may be the subcortical cerebral cortex and periventricular region.


Clinical Presentation


Images  The age of clinical presentation can vary from neonates to early childhood, though occasionally patients do not present until adulthood. There are two types of HH, sessile and pedunculated.


Images  Sessile tumors have a broad-based attachment to the hypothalamus and are typically associated with gelastic seizures. Gelastic seizures are characterized by fits of uncontrolled laughter. They last less than 30 seconds, though they are often only a few seconds long, and consciousness may not be impaired. Note that gelastic seizures can also originate from temporal and mesial frontal regions. Other seizure types such as atonic, tonic, generalized tonic–clonic seizures, or focal onset seizures may also occur.


Images  The pedunculated tumors are associated with precocious puberty, which results from the capacity of ganglion cells to secrete hypothalamic hormones in an aberrant fashion. They can also present with visual loss due to mass effect on the optic chiasm. Patients may have depression, behavioral abnormalities, and cognitive impairment.


Radiographic Appearance and Diagnosis


Images  MRI is the imaging modality of choice to evaluate suspected HHs. On all imaging modalities, they are isodense to the cortex and do not enhance with the administration of contrast. They do not grow on serial imaging. These lesions may be quite large at presentation and may be associated with other congenital or neuronal migration abnormalities.


Treatment


Images  Patients with precocious puberty can be treated with hormonal suppression therapy, such as leuprolide, a luteinizing hormone receptor agonist. This may also help control the seizures.


Images  There are various surgical options: endoscopy, microsurgery, stereotactic radiosurgery (SRS), and stereotactic laser ablation. Many patients have been treated with multimodality staged strategy as there are pros and cons of different surgical techniques.


References


1.  Pati S, Sollman M, Fife TD, Ng YT. Diagnosis and management of epilepsy associated with hypothalamic hamartoma: an evidence-based systematic review. J Child Neurol. July 2013;28(7):909–916.


2.  Mittal S, Mittal M, Montes JL, Farmer JP, Andermann F. Hypothalamic hamartomas. Part 1. Clinical, neuroimaging, and neurophysiological characteristics. Neurosurg Focus. June 2013;34(6):E6.


3.  Striano S, Santulli L, Ianniciello M, Ferretti M, Romanelli P, Striano P. The gelastic seizures-hypothalamic hamartoma syndrome: facts, hypotheses, and perspectives. Epilepsy Behav. May 2012;24(1):7–13.


4.  Fenoglio KA, Wu J, Kim do Y, et al. Hypothalamic hamartoma: basic mechanisms of intrinsic epileptogenesis. Semin Pediatr Neurol. 2007;14(2):51–59.


5.  Kameyama S, Shirozu H, Masuda H, Ito Y, Sonoda M, Akazawa K. MRI-guided stereotactic radiofrequency thermocoagulation for 100 hypothalamic hamartomas. J Neurosurg. May 2016;124(5):1503–1512.



 


 


 







4.15


Clivus Chordoma


Case History


A 21-year-old female presented with dizziness and dysphagia over the course of several months. On exam, she had dysarthria and brisk reflexes in all four extremities.


Diagnosis: Clivus Chordoma


Images


Images 4.15A–4.15D: Postcontrast sagittal and coronal T1-weighted and axial FLAIR images demonstrate an enormous, hyperintense mass arising from the clivus with significant mass effect on the medulla.


Introduction


Images  Chordomas are tumors that arise from remnants of the notochord, an embryologic structure that eventually forms part of the spinal column that did not appropriately form bone.


Images  They are considered benign tumors, though they are often locally invasive causing bone destruction. They can metastasize in about 10% of patients and are then called chondrosarcomas.


Images  Chordomas are slow-growing tumors that most commonly involve the midline of the axial skeleton. About 30% to 40% involve the base of the skull (clivus in the region of the spheno-occipital synchondrosis), approximately 49% involve the sacrum, and ~15% involve the vertebral column, usually the cervical spine.


Images  They arise from the bone and are extraaxial tumors and represent less than 1% of intracranial tumors.


Images  Chordomas: This neoplasm is composed of hepatoid trabeculae of epithelioid cells with eosinophilic and bubbly cytoplasm in a myxoid matrix. The bubbly cells are called physaliphorous cells.


Images  Ecchordosis physaliphora are small, well-circumscribed gelatinous masses/lesions adherent to the brainstem, which behave like benign developmental remnants of notochord and histologically resembles a chordoma.


Images  The other two chondroid CNS tumors are chordoid glioma of the third ventricle and chordoid meningioma.


Images  There are three types of chordomas, which can be differentiated based on histological markers. These are:


       1.  Conventional: There is absence of cartilaginous or additional mesenchymal components. These are keratin positive, epithelial membrane antigen (EMA) positive, S100 positive, and carcinoembryonic antigen (CEA) negative.


       2.  Chondroid: They have chordomatous and chondromatous features, have a predilection for the spheno-occipital region, and account for 5% to 15% of all chordomas. Chondrosarcoma would be S100 positive, keratin negative, and EMA negative.


       3.  Dedifferentiated: Sarcomatous transformation can occur in 2% to 8% of chordomas and are typically keratin positive, EMA positive, CEA positive, and usually S100 negative.


Clinical Presentation


Images  Clival chordomas usually present in young adults (ages 20–40) with pain from bone destruction, cranial neuropathies (especially if there is involvement of the cavernous sinuses), and mass effect on the brainstem.


Images  Sacrococcygeal chordomas present in older patients with back pain that is worse when seated. They may also present with cauda equina syndrome, which includes saddle anesthesia, and bladder and/or bowel dysfunction.


Radiographic Appearance and Diagnosis


Images  Clivus chordomas are very hyperintense on T2-weighted images and isointense on T1-weighted images. They enhance heterogeneously with the administration of contrast. A classic finding is an indentation of the pons, called the thumb sign.”


Images  Local bone destruction is best appreciated on CT. The tumor is typically isodense or slightly hyperdense. Areas of hemorrhage or calcification may be seen.


Images


Images 4.15E and 4.15F: Postcontrast sagittal and axial T1-weighted images demonstrate a heterogeneously enhancing mass indenting the pons, the “thumb sign.”


Images


Image 4.15G: Reformatted sagittal CT image demonstrates destruction of the clivus (red arrow) in a patient with a clivus chordoma.


Treatment


Images  The best results in the treatment of chordomas of the skull base are reported when using surgery and adjuvant high-dose proton therapy. The surgical techniques for margin-free, en bloc tumor resection have been proven to be effective in terms of local control and long-term prognosis for chordomas occurring in the thoracic and lumbar spine. They have a very high recurrence rate with slightly less than half of the patients surviving 10 years.


Images  Chordomas are not sensitive to chemotherapy, similar to many other low-grade malignancies. Accordingly, chemotherapy response has been reported in patients with high-grade dedifferentiated chordomas, which represent less than 5% of all chordomas. Cytotoxic chemotherapy has virtually no role in this disease; however, molecularly targeted therapy is showing significant promise and is an area of great potential.


References


1.  Neelakantan A, Rana AK. Benign and malignant diseases of the clivus. Clin Radiol. December 2014;69(12):1295–1303.


2.  Radner G, Dross PE. Clivus chordoma. Del Med J. September 1997;69(9):467–469.


3.  Géhanne C, Delpierre I, Damry N, Devroede B, Brihaye P, Christophe C. Skull base chordoma: CT and MRI features. JBR-BTR. November–December 2005;88(6):325–327.



 


 


 







4.16


Corpus Callosum Lipoma


Case History


A 23-year-old woman presented with a seizure.


Diagnosis: Pericallosal Lipoma


Images


Images 4.16A and 4.16B: Sagittal and axial CT images demonstrate a hypodense mass consistent with a corpus callosum lipoma. Images 4.16C and 4.16D: Noncontrast sagittal and axial T1-weighted images demonstrate a pericallosal, hyperintense mass consistent with a corpus callosum lipoma.


Introduction


Images  Pericallosal lipomas are congenital, adipose lesions of the interhemispheric fissure that trace the trajectory of the corpus callosum, which is often hypoplastic.


Images  They are rare, accounting for less than 1% of all intracranial neoplasms.


Clinical Presentation


Images  Seizures are the most common clinical manifestation. There is a wide range in their severity. In older adults, they are often incidental findings.


Radiographic Appearance and Diagnosis


Images  The lesion follows fat on all sequences. On CTs, it is hypodense, though there may be some calcifications. On T1-weighted images, they are hyperintense, and there is no enhancement with the administration of contrast.


Images  There are two distinct varieties: tubulonodular and curvilinear. Tubulonodular lipomas are thicker (>2 cm), located more anteriorly, and are round or lobulated. They are more common, and patients may have facial abnormalities. The corpus callosum is markedly dysmorphic. Curvilinear lipomas are thinner (<1 cm), located posteriorly, and follow the corpus callosum rather than replace it.


Treatment


Images  Antiepileptic medication is the mainstay of treatment. There is no role for surgery.


References


1.  Karaka E, Do an MS, Çullu N, Kocatürk M, et al. Intracranial lipomas: clinical and imaging findings. Clin Ter. 2014;165(2):e134–e138.


2.  Loddenkemper T, Morris HH, Diehl B, Lachhwani DK. Intracranial lipomas and epilepsy. J Neurol. 2006;253:590–593.



 


 


 







4.17


Meningioma


Case History


A 65-year-old woman presented with personality changes, paranoia, and confusion over the course of several months. On exam, she had mild bilateral papilledema and weakness of her legs.


Diagnosis: Meningiomas


Images


Images 4.17A–4.17D: Axial CT (4.17A), FLAIR (4.17B), and axial (4.17C) and coronal T1-weighted images (4.17D) post-Gd demonstrate a calcified extraaxial mass in the interhemispheric fissure, which is isointense to gray matter and demonstrates near homogeneous enhancement, consistent with a meningioma.


Introduction


Images  Meningiomas are slow-growing, generally benign tumors that comprise 20% of all primary CNS neoplasms. They are the most common benign, extraaxial, intracranial neoplasm and are second only to gliomas in frequency.


Images  They are believed to arise from cells of the arachnoid and they are firmly adherent to the dura. Only rarely do they invade the brain and surrounding bone.


Images  They occur most commonly in middle-aged women; multiple meningiomas may occur in patients with neurofibromatosis II. Prior irradiation, often for other cancers, is the only known environmental risk factor.


Images  There are a number of histological subtypes of meningiomas, the vast majority of which are WHO grade I tumors. Atypical meningiomas are WHO grade II, while anaplastic or malignant meningiomas are WHO grade III tumors that exhibit a high mitotic index (Table 4.17.1). Anaplastic meningiomas are very rare, accounting for less than 1% of tumors. The major difference between the 2007 and 2000 WHO grading versions is that brain invasion in an otherwise grade I meningioma is a criterion for classification as grade II.


Table 4.17.1 Subtypes and WHO Grading of Meningiomas



















WHO Grading


Types


Grade I


Meningothelial, fibrous, transitional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic


Grade II


Atypical, clear cell, chordoid


Grade III


Anaplastic, papillary, rhabdoid


Clinical Presentation


Images  They are extraaxial tumors that produce symptoms by compressing nervous tissue externally. They can present with headaches, seizures, and focal neurological findings depending on the location of the tumor.


Images  They can arise anywhere along the neuraxis. Over 95% are supratentorial in location. Locations include: the falx cerebri (25%), cerebral convexities (20%), cerebellopontine angle (CPA), the sphenoid wing (20%), the suprasellar region (10%), the planum sphenoidale/olfactory groove (10%), the posterior fossa (CPA tentorium cerebelli 10%), intraventricular (2%), the orbit, and the spinal cord. Meningiomas are slow-growing tumors; these can be asymptomatic or symptomatic; symptoms may vary according to their location (Table 4.17.2).


Table 4.17.2 Common Locations and Symptomatology of Meningiomas








































Location


Symptoms


Parasellar or subfrontal


Foster Kennedy syndrome


Intraventricular


Dizziness, headache or altered sensorium due to


obstructive hydrocephalus


Convexity


Seizures, headache, neurological deficits


Falx and parasagittal


Personality changes, vision, headache, vision changes, arm or leg weakness


Olfactory groove


Anosmia, personality or vision changes


Intraorbital


Loss of vision


Cerebellopontine angle


Sensorineural hearing loss


Petroclival


Trigeminal neuralgia


Foramen magnum


Headache, difficulty walking


Spinal


Back pain, loss of sensation, paraparesis or paralysis of legs


  


Images  Although the vast majority are benign, even grade I meningiomas sometimes invade blood vessels and may metastasize, most commonly to the lungs.


Radiographic Appearance and Diagnosis


Images  On CT, they are hyperdense to the brain. They are highly calcified about 25% of the time. Edema is common and is hypodense on CT.


Images  Meningiomas only very rarely invade the brain, but often invade and remodel the skull. This remodeling or secondary excessive growth of bone is termed hyperostosis. This is best seen with CT scans. Some meningiomas are associated with cyst formation.


Images  On MRI, they are typically isointense to the brain T1-weighted image and isointense or hyperintense on T2-weighted image. They may be associated with significant amounts of edema, and this is sometimes, though not always, an indicator of a more aggressive tumor. They enhance avidly and homogeneously with the administration of contrast. A characteristic enhancement appearance is the “sunburst” or “spoke wheel” pattern of vasculature created by arterial feeders that radiate into the center of the tumor.


Images


Images 4.17E–4.17G: Postcontrast axial, sagittal, and coronal T1-weighted images demonstrate a meningioma arising from the cerebral convexity on the left with mass effect. Image 4.17H: Axial FLAIR image demonstrates peritumoral edema.


Images


Images 4.17I–4.17K: Axial and coronal T2-weighted and postcontrast T1-weighted images demonstrate a large meningioma arising from the sphenoid wing with significant mass effect on the left temporal lobe and lateral ventricle. Image 4.17L: Gross pathology of a sphenoid wing meningioma.


Images


Images 4.17M–4.17O: Postcontrast sagittal, axial, and coronal T1-weighted images demonstrate a homogeneous enhancing mass in the suprasellar region.


Images


Images 4.17P and 4.17Q: Postcontrast axial and sagittal T1-weighted images demonstrate a uniformly enhancing meningioma arising from the planum sphenoidale.


Images


Images 4.17R and 4.17S: Postcontrast axial and sagittal T1-weighted images demonstrate a uniformly enhancing meningioma in the cerebellopontine angle.


Images


Images 4.17T–4.17V: Postcontrast axial, coronal, and sagittal T1-weighted images demonstrate a meningioma arising from the incisure of the tentorium cerebelli with downward mass effect on the cerebellum.


Images


Images 4.17W and 4.17X: Postcontrast axial and sagittal T1-weighted images demonstrate an enhancing mass in the fourth ventricle with significant mass effect on the lower brainstem and cerebellum.


Images


Images 4.17Y and 4.17Z: Postcontrast axial T1-weighted and FLAIR images demonstrate an enhancing mass in the occipital horn of the lateral ventricle and falx cerebri over the occipital lobe. There is mass effect and edema. An additional mass is seen arising from the posteior falx cerebri.


Images


Images 4.17AA and 4.17BB: Postcontrast axial and sagittal T1-weighted images demonstrate a well-circumscribed, extramedullar meningioma (red arrows) with compression of the spinal cord (yellow arrow).


Images


Images 4.17CC and 4.17DD: Postcontrast axial and coronal T1-weighted images demonstrate a well-demarcated enhancing mass superiorly located at the left orbital apex (yellow arrows). The superior rectus muscle is displaced inferiorly and medially as is the optic nerve (red arrow). These tumors may be difficult to differentiate from optic nerve gliomas.


Images


Images 4.17EE–4.17GG: Axial, sagittal, and coronal CT images demonstrate a hyperdense meningioma arising from the planum sphenoidale. Image 4.17HH: Axial CT image from a different patient scan shows a heavily calcified meningioma arising from the left sphenoid wing.


Images


Images 4.17II and 4.17JJ: Axial FLAIR and postcontrast T1-weighted images demonstrate a left subfrontal meningioma with surrounding edema. Images 4.17KK and 4.17LL: Axial and coronal CT images demonstrate hyperostosis (red arrows) of the bone in a patient with a meningioma.


Images


Images 4.17MM–4.17PP: Axial FLAIR, T2-weighted, and pre- and postcontrast T1-weighted images demonstrate the characteristic findings of a meningioma. It is hyperintense on T2-weighted images with edema. It is isointense on T1-weighted images with “sunburst” or “spoke wheel” enhancement on postcontrast images.


Images  A characteristic finding is known as a dural tail. This refers to enhancement of the meninges flanking the bulk of the tumor, though this finding is seen in other neoplasms as well.


Images  In contrast to lower grade meningiomas, more aggressive tumors may display a heterogeneous pattern of enhancement and significant peritumoral edema, though such edema may occur with benign subtypes as well. They may invade the bone and the underlying brain.


Images  Meningiomas are highly vascular tumors and cerebral angiograms are often performed prior to an operation to better define the vasculature surrounding the meningioma. On angiograms the tumor blush is seen in the arterial phase and remains in the venous phase. Since the finding comes early and stays late, this is called the “mother-in-law” sign.


Images  Pathologically, meningiomas occur in several types including meningothelial (meningeal cells with indistinct cell borders arranged in whorls), angiomatous, microcystic, and fibrous. These patterns do not correlate with an aggressive phenotype and are generally seen in WHO grade I meningiomas.


Images


Images 4.17QQ and 4.17RR: Postcontrast axial T1-weighted images demonstrate homogeneously enhancing extraaxial masses in the left cerebellopontine angle and along the right cerebral convexity. In both cases, a characteristic dural tail is seen (red arrows).


Images


Images 4.17SS–4.17VV: Postcontrast axial and sagittal T1-weighted and axial FLAIR images demonstrate a right frontal convexity meningioma with extensive bony invasion and associated calvarial expansion. The margins of the meningioma with the frontal lobe brain tissue are ill-defined suggesting brain invasion.


Images


Images 4.17WW and 4.17XX: Catheter angiography reveals tumor blush (red arrows), in both the arterial and venous phases, the “mother-in-law” sign. Inset, an axial postcontrast T1-weighted image shows a large falx meningioma.


Images


Image 4.17YY: H&E stain showing meningothelial, microcystic, and fibrous meningiomas (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Images


Image 4.17ZZ: Immunostains for epithelial membrane antigen and progesterone receptors (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Images  Meningioma cells are immunoreactive for epithelial membrane antigen and progesterone receptors.


Images  Chordoid and clear-cell meningiomas have a higher rate of recurrence and are classified as WHO grade II. Rhabdoid and papillary meningiomas are aggressive neoplasms that warrant WHO grade III.


Images  Meningiomas with a mitotic count greater than 4/10 high power fields are classified as atypical (WHO grade II) and those with more than 20/10 high power fields are classified as anaplastic (WHO grade III).


Images  WHO grade I meningiomas have a pushing border against the brain; however, meningiomas with brain invasion have a higher rate of recurrence, warranting classification as WHO grade II.


Images


Image 4.17AAA: H&E stain demonstrating chordoid and rhabdoid meningiomas (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Images


Image 4.17BBB: H&E staining of a meningioma showing multiple mitotic figures (yellow ovals) (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Images


Image 4.17CCC: H&E staining of a meningioma showing brain invasion (red arrows) (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Treatment


Images  Surgical resection is the mainstay of treatment for meningiomas. Larger tumors may require preoperative embolization of the tumor. Up to 25% recur, and the recurrence rate for more malignant tumors is much higher, up to 80%, and radiation may be used for such tumors. SRS is particularly useful for tumors where surgical removal of the tumor is difficult, such as the cavernous sinus. Atypical and malignant meningiomas are associated with an increased risk of local recurrence and decreased overall survival compared with grade I meningiomas. Asymptomatic meningiomas may be followed with repeat imaging. For patients with atypical meningioma, close surveillance serial MRIs are obtained at 3, 6, and 12 months postoperatively, then every 6 to 12 months for 5 years, and then every 1 to 3 years.


References


1.  Stessin AM, Schwartz A, Judanin G, et al. Does adjuvant external-beam radiotherapy improve outcomes for nonbenign meningiomas? A Surveillance, Epidemiology, and End Results (SEER)-based analysis. J Neurosurg. 2012;117:669.


2.  Perry A, Louis DN, Scheithauer BW, et al. Meningiomas. In: Louis DN, Ohgaki H, Wiestler OD, eds. WHO Classification of Tumours of the Central Nervous System. Lyon: IARC Press; 2007:164.


3.  Longstreth WT, Dennis LK, McGuire VM, et al. Epidemiology of intracranial meningiomas. Cancer. 1993;72:639–648.


4.  Hsu DW, Efird JT, Hedley-Whyte ET. Progesterone and estrogen receptors in meningiomas: prognostic considerations. J Neurosurg. 1997;86:113–120.



Unless otherwise stated, all pathology images in this chapter are from the website medicine.stonybrookmedicine.edu/pathology/neuropathology and are reproduced with permission of the author, Roberta J. Seidman, MD, Associate Professor. Unauthorized reproduction is prohibited.



 


 


 







4.18


Vestibular Schwannoma


Case History


A 45-year-old man presented with gradual hearing loss and tinnitus in his left ear. Weber and Rinne tests confirmed the left sensorineural hearing loss.


Diagnosis: Vestibular Schwannoma


Images


Images 4.18A–4.18C: Postcontrast axial and coronal T1-weighted and coronal T2-weighted images demonstrate an enhancing mass in the left cerebellopontine angle due to a vestibular schwannoma. The lesion arises in the internal auditory meatus and extends into the cerebellopontine angle. The appearance is known as the “ice cream cone” sign. Image 4.18D: Gross pathology of a left vestibular schwannoma (image courtesy of Roberta J. Seidman, MD, Associate Professor, Stony Brook School of Medicine, Department of Pathology).


Introduction


Images  The most common pathological processes in the CPA masses are schwannomas and meningiomas. Schwannomas arise from Schwann cells, which myelinate axons of the peripheral nervous system. The differential diagnosis of CPA masses can be memorized by the mnemonic SAME (Table 4.18.1). Other rare masses, such as lipoma, neurosarcoidosis lesion, cholesterol granuloma, paraganglioma, chordoma, and chondrosarcoma, should also be considered in the differential.


Table 4.18.1 Differential Diagnosis of CPA Masses (Mnemonic SAME)



























 

Lesion Type


Comments


S


Schwannomas: acoustic, vestibular, trigeminal, facial


Low T1, high T2, enhance


A


Arachnoid cyst


Aneurysm


Follows CSF, does not enhance


High T1 signal from thrombosed berry aneurysm with a calcified rim, and hemosiderin staining


M


Meningiomas


Metastasis


Iso/low T1, iso-high T2, enhance


Enhance, usually from breast, lung, malignant melanoma


E


Ependymoma


Epidermoid cyst


Low T1, high T2, enhance


Follows CSF signal, does not enhance


CSF, cerebrospinal fluid.


Images  Schwannomas may arise from any cranial nerve (except the optic and olfactory nerves, which are myelinated by oligodendrocytes) as well as from spinal nerve roots. They most commonly arise from the vestibular portion of the vestibulocochlear nerve and were formerly known as acoustic neuromas. They are almost always benign; however, rare malignant versions have been reported.


Images  They occur with equal frequency on the superior and inferior branches of the vestibular nerve; only rarely are they derived from the cochlear portion of the VIII nerve.


Images  They account for about 10% of all intracranial tumors and 80% of CPA tumors. The median age of diagnosis is 50 years. The majority is unilateral. Bilateral schwannomas are limited to patients with neurofibromatosis II.


Clinical Presentation


Images  Patients present with slowly progressive hearing loss and tinnitus and episodic unsteadiness while walking. True spinning vertigo is uncommon. Patients less commonly develop dizziness or imbalance problems as the lesions grow slowly enough that the brain has time to compensate. Not infrequently, these symptoms go unnoticed and patients present due to mass effect on the brainstem or other cranial neuropathies. Rarely, there may be hemorrhage into the tumor.


Images  The trigeminal nerve is the second most common nerve from which schwannomas arise. These patients present with facial numbness or trigeminal neuralgia. Facial nerve paresis and ataxia are less common.


Images  Jugular foramen schwannomas are rare, and presenting symptoms include dizziness, hearing loss, ear pain, dysphagia, tongue weakness, and dysphonia.


Images


Images 4.18E–4.18H: Postcontrast axial, sagittal, and coronal T1-weighted images demonstrate an enhancing mass entering Meckel’s cave with extension into the left CP angle due to schwannoma growing from the trigeminal nerve.


Images


Images 4.18I and 4.18J: Postcontrast axial and coronal T1-weighted images demonstrate an enhancing mass in the right jugular foramen (red arrow) with significant mass effect on the medulla.


Radiographic Appearance and Diagnosis


Images  They are hypointense on T1-weighted images and hyperintense on T2-weighted images, often with cystic areas. They enhance avidly on postcontrast T1-weighted images. The enhancement is homogeneous with smaller tumors, but often heterogeneous with larger lesions. Other enhancing CPA masses include meningiomas, ependymomas, and other metastasis (Table 4.18.1).


Images  The tumor originates in the internal auditory meatus and extends into the CPA. This is a characteristic finding for vestibular schwannomas. As shown in Images 4.18A and 4.18B, this is known as the “ice cream cone” sign.


Images  Widening of internal auditory meatus is best seen on CT and is called a “trumpeted” internal acoustic meatus. This finding is not found with meningiomas, which can also be found in the CPA and have a similar appearance.


Images


Images 4.18K and 4.18L: Axial CT image demonstrates a “trumpeted internal acoustic meatus” (red arrow). The tumor can be seen within the internal acoustic meatus on postcontrast T1-weighted image as well (blue arrow).


Images


Images 4.18M–4.18P: Axial T2-weighted and noncontrast T1-weighted and postcontrast axial and coronal T1-weighted images demonstrate bilateral vestibular schwannomas in a patient with neurofibromatosis II.


Images


Images 4.18Q and 4.18R: H&E low power view shows alternating Antoni A (cellular and pink) and Antoni B (loose stroma, fewer cells and myxoid changes) areas; image 4.18R shows palisading basophilic nuclei surrounding pink areas referred to as Verocay bodies (images courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Images  Bilateral vestibular schwannomas are associated with neurofibromatosis type II.


Treatment


Images  There are three standard operative approaches for resection of these tumors. These are retromastoid suboccipital (retrosigmoid), translabyrinthine, and middle fossa approaches. The choice of surgical approach depends on the size of the tumor and whether preservation of the cranial nerve function is the goal of the surgery or not. Tumors can be surgically resected to prevent further hearing loss or compression of adjacent brainstem structures. The most common complication is facial nerve damage causing unilateral facial paralysis.


Images  SRS uses multiple convergent beams to deliver a high single dose of radiation to a radiographically discrete treatment volume. Gamma knife (Elekta), linear accelerator (LINAC), or proton beam machines are used to deliver radiation accurately. Cranial nerve toxicities, cystic degeneration, postradiation tumor expansion, malignant transformation, and local tissue scarring are some of the potential complications of SRS.


Images  Serial imaging is needed, and therapeutic intervention is indicated if there is evidence of rapid tumor growth (ie, >2.5 mm/year), regardless of tumor size. In other patients with a slower growth, no intervention may be needed and the tumor can be watched on serial imaging.


References


1.  Maniakas A, Saliba I. Neurofibromatosis type 2 vestibular schwannoma treatment: a review of the literature, trends, and outcomes. Otol Neurotol. January 2014;35(5):889–894.


2.  Maniakas A, Saliba I. Conservative management versus stereotactic radiation for vestibular schwannomas: a meta-analysis of patients with more than 5 years’ follow-up. Otol Neurotol. February 2012;33(2):230–238.


3.  Carlson ML, Link MJ, Wanna GB, Driscoll CL. Management of sporadic vestibular schwannoma. Otolaryngol Clin North Am. June 2015;48(3):407–422.


4.  Vesper, J, Bolke E, Wille C, et al. Current concepts in stereotactic radiosurgery—a neurosurgical and radiooncological point of view. Eur J Med Res. 2009;14(3):93–101.


5.  Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC. Long-term outcomes after radiosurgery for acoustic neuromas. N Engl J Med. 1998;339:1426.



 


 


 







4.19


Glomus Jugulare


Case History


A 70-year-old man presented with dizziness, hoarseness, and hearing loss.


Diagnosis: Glomus Jugulare Tumor


Images


Images 4.19A–4.19C: Postcontrast axial and coronal T1-weighted and axial FLAIR images demonstrate a heterogeneously enhancing mass in the right jugular foramen consistent with a glomus jugulare tumor. This shows the “salt and pepper” appearance of the tumor. Image 4.19D: Photograph showing the high vascular nature of glomus jugulare tumors (image credit Dr. Michael Hawke).


Introduction


Images  Glomus jugulare tumors are a subtype of paraganglioma, an uncommon neuroendocrine neoplasm. They grow within the jugular foramen, which contains the glossopharyngeal, vagus, and accessory nerves. The jugular foramen also contains nerve fibers known as glomus bodies, which respond to changes in blood pressure and temperature.


Clinical Presentation


Images  Glomus jugulare tumors typically occur in patients 60 and older and present with pulsatile tinnitus and hearing loss. Other symptoms occur due to compression of the cranial nerves in the jugular foramen, and may cause dysphagia and dysarthria. Compression of other cranial nerves can lead to tongue and facial weakness. Some patients develop a Horner’s syndrome (ptosis, miosis, and anhydrosis).


Images  They are benign over 90% of the time.


Radiographic Appearance and Diagnosis


Images  They are hyperintense on T2-weighted images and hypointense on unenhanced T1-weighted images. On postcontrast T1-weighted images, they enhance avidly. They are said to have a “salt and pepper” appearance—the “salt” is from hemorrhage, while the “pepper” is from hypervascularity and flow voids.


Images  CT scans are important to visualize the surrounding bones, which are frequently eroded by the tumor, which often extends into the middle ear.


Treatment


Images  They are treated with surgical resection, though cranial nerve deficits commonly persist after surgery. Radiation therapy is useful in incomplete resection. Recurrence occurs in nearly half of the patients.


Images


Images 4.19E and 4.19F: Axial CT images with contrast show a hyperdense mass originating from the jugular foramen, which is eroding the temporal bone on the right.


References


1.  Jayashankar N, Sankhla S. Current perspectives in the management of glomus jugulare tumors. Neurol India. January–February 2015;63(1):83–90.


2.  Ivan ME, Sughrue ME, Clark AJ, et al. A meta-analysis of tumor control rates and treatment-related morbidity for patients with glomus jugulare tumors. J Neurosurg. May 2011;114(5):1299–1305.


3.  Sheehan JP, Tanaka S, Link MJ, et al. Gamma Knife surgery for the management of glomus tumors: a multicenter study. J Neurosurg. August 2012;117(2):246–254.


4.  Semaan MT, Megerian CA. Current assessment and management of glomus tumors. Curr Opin Otolaryngol Head Neck Surg. October 2008;16(5):420–426.



 


 


 







4.20


Esthesioneuroblastoma


Case History


A 53-year-old man presented with frequent nosebleeds and nasal congestion over the course of 6 months. His wife also said that he had become more irritable and had a “shorter fuse” compared to his baseline. On exam, he had a marked decrease in his sense of smell (hyposmia).


Diagnosis: Esthesioneuroblastoma


Images


Images 4.20A–4.20D: Postcontrast sagittal and coronal T1-weighted and axial T1-weighted FLAIR images demonstrate a homogeneously enhancing lesion arising from the sinuses, which involves the right medial frontal lobe with significant mass effect, vasogenic edema, and right-to-left midline shift.


Introduction


Images  Esthesioneuroblastomas, also known as olfactory neuroblastomas, are rare tumors, believed to originate from olfactory neuroepithelium in the cribriform region of the nasal septum and spread into the nasal and cranial cavities.


Clinical Presentation


Images  They usually present with nasal congestion, anosmia, and epistaxis. Approximately 30% extend into the frontal lobes where they can present with seizures, personality changes, or focal neurological deficits.


Images  Patients usually present between the ages of 50 and 60.


Radiographic Appearance and Diagnosis


Images  On both T1-weighted and T2-weighted images, they have variable signals and can be hyperintense or hypointense. There is usually avid enhancement on postcontrast T1-weighted images. They are slow-growing tumors and there is often significant tumor burden at the time of presentation. The surrounding bone is often remodeled and destroyed. This is best seen on CT scans.


Images  A biopsy is required to make a definitive diagnosis, as imaging alone cannot distinguish them from olfactory groove meningiomas or sinonasal carcinomas. They are characterized by small, round, monomorphic cells, which are arranged in sheets or lobules. Immunoreactivity for cytokeratins is exceptional, but these lack immunoreactivity with epithelial membrane antigen.


Treatment


Images  They are treated with a combination of chemotherapy and radiation. In patients with localized disease, over 60% of patients are alive at 5 years and slightly less than 50% alive at 10 years. Patients with distant metastases have a much worse prognosis.


References


1.  Jethanamest D, Morris LG, Sikora AG, Kutler DI. Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg. March 2007;133(3):276–280.


2.  Kumar R. Esthesioneuroblastoma: multimodal management and review of literature. World J Clin Cases. September 2015;3(9):774–778.


3.  Bak M, Wein RO. Esthesioneuroblastoma: a contemporary review of diagnosis and management. Hematol Oncol Clin North Am. December 2012;26(6):1185–1207.



 


 


 







4.21


Spinal Epidural Metastases


Case History


A 65-year-old man with a history of prostate cancer presented with lower back pain for the past week. He also said that going up the stairs in his house had been more difficult than usual. On exam, he had severe tenderness to palpation of his thoracic and lumbar spine. He had weakness of his legs and a sensory level at T4. He was diffusely hyperreflexic with upgoing toes bilaterally. His gait was labored and spastic.


Diagnosis: Spinal Epidural Metastases


Images


Images 4.21A and 4.21B: Sagittal T2-weighted and postcontrast sagittal T1-weighted images demonstrate multiple spinal epidural metastases with significant cord compression. Image 4.21C: Axial T2-weighted image demonstrates the spinal cord (blue arrow) being compressed and displaced to the right by a tumor (red arrow).


Introduction


Images  The vertebral column is a highly vascular structure and as such it is a common location for metastases to the epidural location. Epidural metastases to the spinal canal arise most commonly from breast, lung, or prostate cancers. Other frequent primary cancers include: thyroid, renal, melanoma, and blood dyscrasias such as lymphoma and multiple myeloma. Spinal cord compression occurs most frequently at the thoracic level.


Clinical Presentation


Images  Patients present with pain, weakness, sensory loss, and bowel/bladder incontinence.


Images  Neurological exam will reveal a varying degree of myelopathic signs below the level of lesion. These include spastic paraparesis or quadriparesis, sensory loss, hyperreflexia and pathological reflexes, and loss of rectal sphincter tone.


Radiographic Appearance and Diagnosis


Images  MRI with contrast is the imaging modality of choice. The lesions typically enhance with the administration of contrast. They compress the spinal cord, distorting its normal architecture. Hyperintensity within the cord is common on T2-weighted images.


Images  CSF analysis may show a marked elevated protein if there is blockage of CSF flow within the spinal canal.


Images  In patients with an unknown primary, biopsy of the lesion should be undertaken.


Treatment


Images  Spinal cord compression is a neurological emergency. Once myelopathic symptoms develop, they may progress rapidly leading to permanent injury. Patients who have motor deficits that persist beyond 24 hours usually do not recover. The immediate administration of high-dose intravenous (IV) corticosteroids is required in all patients with spinal cord compression from metastases.


Images  Radiotherapy is useful even in patients whose tumors are classically resistant to this treatment. Decompressive surgery should be used in patients with rapidly progressive neurological deficits or in patients whose symptoms progress despite the use of radiotherapy.


Reference


1.  Shah LM, Salzman KL. Imaging of spinal metastatic disease. Int J Surg Oncol. 2011;2011:769753.



 


 


 







4.22


Cerebral Metastases


Case History


A 67-year-old man presented with a partial seizure with secondary generalization. His daughter said that he had been increasingly confused over the past few weeks.


Diagnosis: Cerebral Metastases


Images


Images 4.22A–4.22D: Postcontrast axial T1-weighted and FLAIR images demonstrate extensive metastases, both intraparenchymal and leptomeningeal with mass effect and edema.


Introduction


Images  Up to 20% of patients with cancer will develop a metastatic lesion to the brain, making brain metastases much more common than primary brain tumors. There are nearly 100,000 such cases annually in the United States.


Images  Lung cancers account for 50% of all brain metastases followed by breast cancer, melanoma, renal cell carcinomas, and gastrointestinal malignancies.


Images  The tumors with the highest propensity to hemorrhage are melanoma, renal cell carcinoma, choriocarcinoma, and papillary thyroid cancer. At times, breast/lung or hepatocellular carcinoma can present with hemorrhagic intracranial metastases.


Clinical Presentation


Images  Patients present with headaches, seizures, cognitive slowing, personality change, or focal neurological deficits depending on the number, size, and location of the tumors.


Radiographic Appearance and Diagnosis


Images  There is a variable appearance on both CT and MRI. On CT, the tumor may be hypodense, isodense, or hyperdense to the brain. On T1-weighted images, metastases are hypointense unless there is hemorrhage. On T2-weighted images, they may be hyperintense or hypointense. There is often peritumoral edema and mass effect. With the addition of contrast, there is avid enhancement, which may be solid, ring-shaped, or punctate.


Images  Hemorrhage is the presenting symptom in about half of these tumors.


Images


Images 4.22E–4.22G: Axial CT images and postcontrast T1-weighted images demonstrate hemorrhagic metastatic lesions in a patient with melanoma. There is both solid and ring-enhancing with the addition of contrast. Image 4.22H: Gross pathology of hemorrhagic metastatic melanoma (image courtesy Roberta J. Seidman, MD, Associate Professor, Stony Brook School of Medicine, Department of Pathology).


Images  Metastases to the brain occur when tumor cells spread via the bloodstream, and they are most commonly found at the gray–white junction, where there is relatively slow blood flow. In cases with an unknown primary, a biopsy is needed to confirm the diagnosis.


Images  Immunohistochemistry for breast cancer can be estrogen receptor, progesterone receptor, and HER2/neu positive. The BRST-2 immunohistochemistry labeling for GCDFP is a relatively specific marker of tumors of breast origin (refer to Image 4.22O). Immunohistochemistry (IHC) markers are used for metastatic brain tumors without unknown primary. The immunoreactivity for cytokeratin (CK)-7 and thyroid transcription factor-1 (TTF-1) favor a lung primary whereas immunoreactivity for CK20 and CDX-2 favors lower gastrointestinal malignancies (Image 4.22P). Carcinomas immunoreactive for CK7 and CDX-2 are compatible with metastases from an upper gastrointestinal primary, most commonly the stomach.


Images  Tumors in the cerebellum are very likely to be metastatic disease in adults.


Images  Nearly half of metastases are single lesions, and these may be indistinguishable from primary brain tumors. About 33% of patients with a metastatic brain lesion do not have a known primary, and a search for the primary tumor is mandatory. In about 30% to 40% of cases, these studies do not reveal the primary tumor.


Images


Image 4.22I: Gross pathology of a metastatic carcinoma at the gray–white junction (image courtesy Roberta J. Seidman, MD, Associate Professor, Stony Brook School of Medicine, Department of Pathology). Image 4.22J: H&E stain demonstrates an adenocarcinoma infiltrating the brain (image credit Jensflorian).


Images


Images 4.22K–4.22N: Axial, sagittal, and coronal postcontrast T1-weighted images and sagittal FLAIR MRI demonstrate multiple enhancing masses in the cerebellum with edema and significant mass effect on the fourth ventricle. Metastatic lesions are also visible in the brain.


Images


Image 4.22O: Immunohistochemistry for breast cancer showing metastases from a triple positive (estrogen receptor, progesterone receptor, and Her2-Neu) with breast carcinoma as primary. The BRST-2 immunohistochemistry labeling for GCDFP is a relatively specific marker of tumors of breast origin (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Treatment


Images  As with primary brain tumors, glucocorticoids are used to reduce edema and improve symptoms, often dramatically over the course of a day or two. The treatment strategies for brain metastases are listed in Table 4.22.1 and range from IV/oral steroids, chemotherapy, surgery, whole brain radiation therapy (WBRT), or more localized radiation, or a combination of these.


Images  Single brain lesions can be surgically excised, though this does not improve the overall survival. There is some evidence that resection of up to three lesions can be beneficial. When numerous lesions are present, treatment with whole brain radiation is indicated.


Images


Image 4.22P: Most commonly used initial IHCs for metastatic brain tumors include CK7 and TTF-1, which favor a lung primary, whereas carcinomas immunoreactive for CK7 and CDX-2, as shown are compatible with metastases from an upper gastrointestinal primary, most commonly the stomach (image courtesy of Dr. Seema Shroff, Fellow, Neuropathology, NYULMC).


Table 4.22.1 Treatment Approaches for Intracranial Metastases






















Corticosteroids


WBRT


Surgery +/- WBRT


Surgery +/- localized radiation


WBRT + radiation sensitizers


WBRT + chemotherapy


SRS +/-WBRT


Chemotherapy


WBRT, whole brain radiation therapy, SRS, stereotactic radiosurgery.


Images  SRS can be considered when metastatic lesion is radiographically distinct on neuroimaging, pseudospherical in shape, and displacing the normal brain tissue with minimal invasion of normal brain. The ideal size of metastatic lesion at presentation should be 3 cm or less for SRS.


Images  Chemotherapy is indicated if the primary tumor is sensitive.


Images  The use of prophylactic anticonvulsant therapy is not recommended, though seizures occur in about 30% of patients with cerebral metastases.


References


1.  Posner JB. Management of brain metastases. Rev Neurol (Paris). 1992;148(6–7):477–487.


2.  Wen PY, Loeffler JS. Management of brain metastases. Oncology (Huntingt). July 1999;13(7):941–954, 957–961; discussion 961–962, 9.


3.  Sze G, Milano E, Johnson C. Detection of brain metastases: comparison of contrast-enhanced MR with unenhanced MR and enhanced CT. AJNR Am J Neuroradiol. July–August 1990;11(4):785–791.


4.  Barajas RF Jr, Cha S. Imaging diagnosis of brain metastasis. Prog Neurol Surg. 2012;25:55–73.


5.  Ozawa Y, Omae M, Fujii M, et al. Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer. BMC Cancer. August 2015;15:589.


6.  Fink KR, Fink JR. Imaging of brain metastases. Surg Neurol Int. 2013;4(Suppl. 4):S209–S219.

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Apr 19, 2018 | Posted by in NEUROLOGY | Comments Off on Neoplastic Diseases
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