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Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017
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Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Adult brain tumors constitute about 2% of all cancers in the United States, and about one third of those tumors are malignant. (The image in the slide shows a large cerebral carcinoma.) Brain tumors emerge from various cells of the central nervous system (CNS) or, more commonly, from metastases to the brain.[1] More than one half of intracranial tumors are induced by brain metastases. Increased intracranial pressure (ICP) and stress on neighboring structures give rise to a range of symptoms, including severe headaches, seizures, syncope, and cognitive problems.[2,3] Proper diagnosis entails obtaining a detailed patient history, conducting a thorough neurologic examination, and ordering appropriate neuroradiologic imaging studies.[4] Depending on the severity and origin of the brain tumor, treatment can include surgery, chemotherapy, stereotactic radiosurgery, and whole-brain radiation therapy (WBRT).
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
The image in the slide shows a cancerous formation in the frontal lobe.
Which of the following genetic syndromes is/are associated with an increased risk of developing a CNS tumor?
Von Hippel-Lindau disease
Tuberous sclerosis
Li-Fraumeni syndrome
Turcot syndrome
Neurofibromatosis type 1 and 2
All of the above
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Answer: F. All of the above.
The conditions listed in answers A, B, C, D, and E are all associated with an increased risk of developing brain tumors.[5] The image in the slide is a high-magnification micrograph of metastasis to the brain. Normal brain tissue is on the left, and the tumor is on the right. The distinct separation is typical of brain metastases.
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
It is well known that lung cancer (both small cell and non-small cell types) can spread to the brain (arrow), accounting for approximately half of all brain metastatic tumors.[6,7]
Which of the following cancers does not commonly spread to the brain?
Breast cancer
Kidney cancer
Colon cancer
Melanoma
Gastrointestinal stromal tumor (GIST)
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Answer: E. Gastrointestinal stromal tumor (GIST).
Although a few case reports exist of GIST spreading to the brain, this phenomenon is extremely rare. GISTs are more commonly involved in metastasis of the posterior fossa. The image in the slide shows common areas of cancer metastasis.
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
The image in the slide shows a recurrent meningioma (arrow). Which of the following statements regarding meningiomas is false?
Meningiomas generally grow slowly and commonly form in the olfactory groove, foramen magnum, and sphenoid ridge
Surgery is generally the mainstay of treatment for meningiomas that progress after observation
Chemotherapy has been shown to improve outcomes
Radiation therapy may be employed if surgical treatment is not possible or if tumor recurrence develops
Meningiomas account for approximately one third of all primary brain tumors
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Answer: C. Chemotherapy has been shown to improve outcomes.
Various chemotherapeutic agents (eg, hydroxyurea and temozolomide) have been used in the treatment of meningiomas. However, analysis of the outcomes has not identified any evidence of significant relief stemming from the administration of these agents[8]; this is especially true in the case of hydroxyurea. The image in the slide shows a resected meningioma.
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
The slide depicts coronal contrast-enhanced T1-weighted magnetic resonance imaging (MRI) of a meningioma.
A 76-year-old man presents with nausea, vomiting, syncope, sensory loss, and aphasia. Computed tomography (CT) of the head is performed and shows a 6-cm tumor in the frontal cortex. The patient has a history of stage III melanoma that was resected 20 years ago and treated with adjuvant interferon.
Which of the following would be the least reasonable next step for treating this patient?
Perform a biopsy of the brain tumor
Immediately administer steroids
Obtain MRI of the brain
Order positron emission tomography (PET)/CT to evaluate for hypermetabolic areas within the brain and in the body
Conduct a full physical examination, including a neurologic assessment
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Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Answer: B. Immediately administer steroids.
Although this tumor could be a recurrent metastatic melanoma, one would have to make sure that it is not a primary CNS lymphoma. (The image shows a sagittal MRI T1 scan of a primary CNS lymphoma.) Immediate administration of steroids could shrink the tumor and interfere with a tissue diagnosis in the future.[9] Corticosteroids are lymphocytoxic and should not be used before biopsy or surgery in a patient who has been diagnosed with primary CNS lymphoma. Even a single dose can cause the lymphoma to recede for a short time and thereby create a discrepancy in the treatment course. In this situation, it is vital to avoid giving steroids unless they are absolutely necessary.
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
The image in the slide is a PET scan from a 62-year-old man with a grade III astrocytoma. The scan shows hypermetabolic activity in the tumor region.
Which of the following statements regarding gliomas is/are true?
They include a heterogeneous mix of tumors that are classified on the basis of both tissue type and, occasionally, the results of certain molecular tests
Lower-grade gliomas (ie, grades I and II) are slow-growing and have a better prognosis than higher-grade gliomas (ie, grades III and IV)
Maximal surgical removal is the first step in treatment for most gliomas
Molecular testing provides information regarding prognosis and overall survival
Radiation and chemotherapy are postoperative treatment options for low-grade gliomas
All of the above
Image courtesy of Medscape by Sam Shlomo Spaeth.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Answer: F. All of the above.
Certain genetic factors are now being utilized to determine prognosis and likelihood of response to specific chemotherapy and radiation therapy techniques after maximal surgical resection.[10] These include testing for the codeletion of 1p/19q and mutations in the genes encoding the isocitrate dehydrogenase (IDH) isozymes IDH1 and IDH2 (ie, IDH1 and IDH2).
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
The MRI scan in the slide shows an oligoastrocytoma.
In the case of diffuse grade II or III gliomas and oligodendroglial tumors, do tumors characterized by mutations in IDH1 and IDH2 have a better prognosis than IDH wild-type tumors do?
Image courtesy of Medscape.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Yes. The 2016 World Health Organization (WHO) classification of CNS tumors now includes molecular information in addition to the traditional histologic classification.[11] Checking IDH1 and IDH2 status by means of immunohistochemistry, in addition to testing for codeletion of 1p/19q, is key in the classification of astrocytic and oligodendroglial tumors. The image in the slide shows a subdural meningioma.
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
The MRI scans in the slide illustrate the progression of an astrocytoma over a period of 7 years.
A 37-year-old woman enters the emergency department (ED) with a throbbing headache and vision loss. CT is performed and identifies a large 5-cm mass lesion in the occipital cortex. Soon after, a surgical specimen of the lesion shows a high-grade glioma, also known as a glioblastoma or a grade IV astrocytoma.
Which of the following treatment options should not be considered for this patient?
Surgical resection
Radiation therapy
Temozolomide
Bevacizumab, in the case of recurrent disease
None of the above
Image courtesy of Medscape.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Answer: E. None of the above.
Answers A, B, C, and D are all potential treatment options in this scenario[12,13]; however, the prognosis for glioblastomas remains poor and is an area of active research. The fluid-attenuated inversion recovery (FLAIR) MRI scan in the slide shows severe edema in a patient with glioblastoma.
Image courtesy of Medscape.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
The image in the slide is a histologic view of a glioblastoma.
The patient described in slides 14 and 15 undergoes surgical resection of her glioblastoma, with clear margins obtained. Her tumor was found to be O6-methylguanine-DNA methyltransferase (MGMT)-methylated; accordingly, she receives temozolomide as adjuvant therapy, along with radiation therapy, for 6 weeks. After 2 months of treatment, an MRI scan is obtained, which shows slight progression of the disease (10% increase in tumor size).
Which of the following is the best next step in the management of this patient?
Continue treatment with temozolomide
Administer additional doses of radiation
Begin FOLFOX chemotherapy (ie, oxaliplatin with fluorouracil and folinic acid)
Perform surgical re-resection
Obtain another opinion
Image courtesy of Wikimedia Commons.
Adult Brain Tumors: A Spreading Problem
Roman Leonid Kleynberg, MD; Gennadiy Guralnik | April 27, 2017 | Contributor Information
Answer: A. Continue treatment with temozolomide.
Pseudoprogression in glioblastoma is well documented, and early imaging may indicate an increase in tumor size and worsening of symptoms in such cases.[14] It is imperative to follow these patients closely, because often their imaging results and symptoms will improve after the initial swelling subsides. That is, the apparent initial worsening of the patient's condition may not reflect true disease progression—hence the term pseudoprogression. These patients may do well with further treatment.[12] The image in the slide is from a 15-year-old boy with a grade IV glioblastoma.
Pancreatic Cancer: Difficult Diagnosis, Ominous Outlook
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Contributor Information
Authors
Roman Leonid Kleynberg, MD
University of California, Irvine Medical Center
Chao Family Comprehensive Cancer Center
Department of Hematology/ Oncology
Orange, CA
Disclosure: Roman Leonid Kleynberg, MD, has disclosed no relevant financial relationships.
Gennadiy Guralnik
Neuroscience Interdepartmental Program
University of California, Los Angeles
Disclosure: Gennadiy Guralnik has disclosed no relevant financial relationships.
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