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Brain Tumor Education Resource*
Brain tumor series #3: METASTASIS
This series covers:
- Speech center esophageal cancer metastasis
- Bifrontal supplementary motor area lung cancer metastasis
- Frontal and cerebellar breast cancer metastases
- Metastatic melanoma
For each of these cases, the following format is used:
- Brain tumor background: An introduction to the type of brain tumor being case-presented.
- Brain tumor clinical presentation: What were the brain tumor 's symptoms and signs?
- Brain tumor diagnostic workup: What investigations were used to diagnose the brain tumor?
- Brain tumor treatment paradigm: What were the options and proposed treatment for the brain tumor?
- Brain tumor operative procedure and approach: What specific approach did the surgeon use for the brain tumor?
- Brain tumor technical nuances and potential surgical pitfalls: What were important considerations for the brain tumor surgery?
- Where available, brain tumor pre- and post- and/or intra-operative radiological images will be shown for the following brain tumor case examples.
Introduction to metastases
Metastases (plural of metastasis) are "secondary" tumors that grow at a separate location from the cancer (the "primary" tumor) from which they detached. A metastasis arises from a cancer cell that seeded away or detached from the original cancer. The metastatic cell typically deposits itself in some other organ, usually quite remote from the primary tumor, but sometimes in the same organ but at an anatomically separate location. One or more metastatic cells can break away from the primary tumor, and can deposit and grow in one or more organs, leading to "multiple metastases" or "diffuse metastastic disease". For example, a primary lung cancer can cause metastases to arise in the brain, liver, and bone. Alternatively, brain and spinal metastases can arise from primary tumors in the lung, breast, kidney, gut and other sites. Further, some types of primary brain tumors can cause metastatic deposits to form in other parts of the central nervous system (CNS; brain and spinal cord); these primary brain tumors with "metastatic potential" include the glioma (such as high-grade astrocytoma, but sometimes also lower grade gliomas such as pilocytic astrocytoma, ependymoma and oligodendroglioma), germ cell tumor, pineal gland tumor, hemangioblastoma, medulloblastoma, and (in rare instances) meningioma. Metastases can spread either via the blood stream or via the cerebrospinal fluid.
Metastases represent the most common brain tumor seen by neurosurgeons, and many patients presenting with brain metastatic disease have more than one metastasis at the time of diagnosis. Most CNS metastases occur in adults rather than children. In adults, the most common site of the primary tumor is lung, followed by breast, kidney, bowel, and melanoma. In about 10% of adults, the primary tumor is never found. In children, neuroblastoma, medulloblastoma, rhabdomyosarcoma, and renal cell cancer (Wilm's tumor) are the most frequent primary tumors causing CNS metastases.
Metastatic deposits in the CNS usually lodge at the gray-white junction of the cerebral hemispheres, and less commonly in the cerebellum and dura. They can cause a variety of symptoms and signs depending on their size and location, including slowly progressive mental status changes, or headaches, seizures, and progressive disturbances of movement or sensation. Sometimes, if there is significant hemorrhage into a metastasis, the neurological deterioration can be profound and sudden. Melanoma, lung, choriocarcinoma and renal cancer metastases are particularly disposed to bleeding.
Investigation of patients presenting with suspected metastatic disease include brain CT and MRI studies, with and without contrast, and more advanced imaging in order to define the site of the primary tumor. Advanced imaging include CT of the chest, abdomen and pelvis, and whole-body Positron Emmission Tomography (PET) scanning. Other studies may include spinal MRI, (breast) mammography, lumbar puncture, and stool fecal occult blood testing. Treatment modalities for CNS metastatic disease include open surgery (to remove one or more metastatic deposits), medical therapy (dexamethasone for brain swelling, and chemotherapy), and radiation [whole-brain radiation therapy or stereotactic (focused) radiosurgery using GammaKnife, Linac, CyberKnife, or Novalis]. The type(s) of treatment(s) offered are tailored according to the patient's age and medical condition, and the type of tumor being treated (some tumor-types are more sensitive to radiation and chemotherapy than others). The size and number of metastatic deposits can also affect the type of treatment offered. Larger metastatic deposits (i.e., greater than 2.5-3 cm in diameter) should be considered first for surgical resection, particularly if there are one or a few deposits, and if any of the deposits are associated with significant brain swelling or edema. For adults with metastatic disease in the CNS, a better prognosis is expected for those in good medical condition, age < 60 years, and with one metastatic deposit (as opposed to multiple metastases), and for patients who are able to undergo surgery and postoperative radiation therapy (where appropriate). The length of survival is quite variable from patient to patient, but frequently is somewhere between 0.5 - 1.5 years following diagnosis and treatment of a CNS metastasis. These numbers are afterall statistics, and patients can certainly live beyond these statistics.
Brain Tumor section; Case 12 - Speech center esophageal cancer metastasis
Background: CNS metastases arising from primary tumors of the bowel are uncommon overall, accounting for approximately 5% of CNS metastases in adults. The colon and rectum are the usual sites from which a "bowel" tumour metastasizes; rarerly, from the esophagus and small intestine.
Clinical presentation: This 52 year old man presented with speech difficulty (aphasia). His neurological exam was normal except for expressive greater than receptive aphasia (i.e., more difficulty with speaking words as opposed to hearing and understanding words).
Diagnostic workup: A brain CT with and without contrast showed a large mass in the left posterior temporal lobe, surrounded by edema. An MRI of the brain with and without contrast showed that the lesion enhanced with contrast in a "ring-like" manner of a mestastasis. A CT of the chest, abdomen and pelvis lead to the discovery of a mass consistent with a cancer of the esophagus.
Treatment paradigm: Since the mass was solitary (single) and located in a critical (eloquent) area with significant edema, and because the patient was relatively young and in good medical condition overall, despite the new diagnosis of esophageal cancer, surgery was offered to the patient as a means of extending his survival. Prior to surgery, a functional MRI (fMRI) study of the brain was carried out with the patient reading and talking to define the areas of the brain cortex which controlled such functions, and their relationship of these critical areas to the metastatic tumor. This was done in order to plan the safest brain-surface entry point and surgical trajectory for the removal of the tumor. It was discussed with the patient that the goal of surgery was gross-total resection of the tumor mass, but because the surgery could not remove every cell of tumor from the brain, postoperative radiation therapy would be recommended. Medical and Radiation Oncology Services were consulted, in addition to GI Surgery, to plan for appropriate treatment of the esophageal mass.
Operative procedure/operative approach: Using stereotactic MRI-guidance, a left temporoparietal craniotomy was carried out, followed by gross-total resection of the tumor. Preoperative functional MRI images were used intraoperatively to plan the best area to enter the brain surface (corticotomy) remote from any language-related areas. The patient's preoperative language dysfunction resolved soon after surgery. Pathology studies confirmed metastasis from an esophageal primary.
Technical nuances and potential surgical pitfalls: In cases of metastatic deposits in eloquent areas of cortex such as the sensory or motor strips or language areas, preoperative fMRI represents an excellent means of defining the relationship between the tumor and functional cortex prior to surgery. These images should be used intraoperatively as part of the overall stereotactic procedure. In order to avoid brain-traction/manipulation injury that is more likely to be detected when operating on metastases located in eloquent brain, gradual central debulking of such lesions via progressive aspiration using suction-cautery or an ultrasonic aspirator may be preferable to the usual manner of defining the brain-metastasis interface and circumferentially "shelling" the metastasis out in toto. Careful examination of the post-resection tumor bed should be carried out to avoid leaving nodular deposits behind. Some metastases are quite vascular, and their vascular pedicle (if any) should be identified and cauterized early in the procedure. Patients can be protected against seizures by administration of a short course of anti-convulsant medications.
Imaging:
Image 12.1 (above). Left posterior temporal esophageal metastasis. The preoperative MRI images (T1 with contrast; multiplanar) show a large metastasis (red dashed-circle) situated in arcuate fibers between Wernicke's and Broca's language areas. Edema is noted around the lesion (yellow lines). Note the "ring-enhancement" pattern of metastases.
Image 12.2 (above). Left posterior temporal esophageal metastasis. The preoperative functional MRI images (axial T1 with contrast) show the relationship of the tumor to critical cortical and subcortical language fibers (orange superimposed fMRI regions) identified during reading. The brain cortex entry (corticotomy) point and trajectory (green arrow) could therefore be better planned with this information available intraoperatively via stereotaxis.
Image 12.3 (above). Left posterior temporal esophageal metastasis. The postoperative MRI images (T1 with contrast; multiplanar) show a cavity (arrow heads) following gross-total resection of the metastasis.
Brain Tumor section; Case 13 - Bifrontal supplementary motor area lung cancer metastasis
Background: Nearly one-half of all brain metastases in adults arise from lung cancers. Of these, there are two major types, namely, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Even though SCLC occurs less frequently than NSCLC as a primary lung cancer, SCLC is in fact more likely to give rise to brain metastases than NSCLC. Further, SCLC are more sensitive to chemotherapy and radiation (which is better from a prognosis standpoint) than NSCLC. One or more lung cancer metastases can be treated by surgical resection or by stereotactic radiosurgery, or a combination of surgery followed by some form of radiation therapy.
Clinical presentation: A 60 year old female smoker presented with gradual and significant personality change, followed by impairment of cognitive function (thought processing). Her physical examination was normal, but she had significant impairment of her mental status/cognition.
Diagnostic workup: An MRI of the brain with and without contrast revealed a large mass located in the area between the frontal lobes. The mass enhanced with contrast and appeared to be attached to the "interhemispheric" dura (falx cerebri). Part of the mass invaded or compressed the corpus callosum, an important white matter tract enabling communication between the two hemispheres of the brain. There was considerable brain edema associated with the mass. CT of the chest, abdomen and pelvis revealed a lung "primary".
Treatment paradigm: Owing to the size of the mass and its accessibility, surgery was offered, and postoperative radiation therapy was expected. The potential for a transient supplementary motor area (SMA) syndrome was discussed preoperatively owing to the location and invasive appearance of the mass, as well as the need for surgical manipulation in this region.
Operative procedure/operative approach: A right frontoparietal craniotomy was carried out using MRI stereotaxis intraoperatively. The resection involved an interhemispheric transfalcine corridoor, with the patient's head turned to a true lateral position and elevated 45 degrees from the horizontal. Incision was a partial bicoronal. The epicenter of the tumor was the falx. The tumor was debulked centrally using an ultrasonic aspirator, and the falx from which the tumor arose was incised and resected along with the tumor mass. A near-total resection of the tumor was carried out. A small nodule found to be embedded deep in the corpus callosum, which appeared to be invading this structure, was left behind for postoperative stereotactic radiosurgical (SRS) treatment. The patient experienced a transient SMA syndrome from which she fully recovered.
Technical nuances and potential surgical pitfalls: The frontoparietal interhemispheric approach requires careful exposure and only minimal (nonocclusive) reflection of the superior sagittal sinus (SSS), with preservation of its cortical tributory veins, and the usual precautions for bleeding from associated venous lakes and the SSS itself. An elevated/upward flexed "true-AP" or an elevated/laterally flexed "lateral" head position can be used for this exposure according to surgeon preference. Stereotaxis aids well in maintaining orientation. All brain-tumor interfaces should be sought and followed although at times, even for metastases, these interfaces may be obscured by an increased degree of local "invasion". For large lesions taking origin from the frontal falx and potentially invading or compressing the SMA region, the possibility of a postoperative SMA syndrome and seizures should be discussed preoperatively. Parenchymal invasion should not prevent resection. When incising and resecting the falx, careful attention should be paid to maintaining the integrity of the contralateral mesial cortex and its blood vessels. The inferior sagittal sinus can be sacrificed during a falcine tumor resection; the SSS should be preserved (only the anterior-most end of the SSS can be taken with relatively impunity). Identification and preservation of the corpus callosum and pericallosal arteries is of course important.
Imaging:
Image 13.1 (above). Bifrontal/falcine metastasis. The preoperative MRI images (T1 with contrast; multiplanar) show a large metastasis (red dashed-circle) situated in the frontal interhemispheric region. It appears to arise from the falx cerebri. A nodule of tumor invades the corpus collosum (yellow line shown) connecting the two hemispheres. Note the nodular "ring-enhancement" pattern of this metastasis.
Image 13.2 (above). Bifrontal/falcine metastasis. The preoperative MRI images (axial FLAIR) shows the large metastasis (red dashed-circle) surrounded by edema (yellow arrow heads).
Image 13.3 (above). Bifrontal/falcine metastasis. The postoperative MRI images (axial and coronal T1 post-contrast; and axial T2 at bottom right) show a fluid-filled cavity (red dashed-circle) following near-total resection of the metastasis. A nodule of tumor invading the corpus collosum (yellow arrow head) was left behind for postoperative SRS.
Brain Tumor section; Case 14 - Frontal and cerebellar breast cancer metastases
Background: Approximately 10% of metastatic brain tumors arise from "breast cancer primaries". Chemotherapeutic efficacy (the likelihood of certain chemotherapy agents working to destroy the tumor) can vary according to the tumor's pattern of estrogen receptor expression, which can be determined by assaying the operative specimen.
Clinical presentation: A 67 year old female presented with mild sleepiness ("somnolence") and mental status decline, with unexplained "mutism". Physical examination showed a debilitated patient, with some weakness along the right side of her body, and significant cognitive dysfunction, in addition to paucity of speech.
Diagnostic workup: Brain MRI with and without contrast showed a large contrast-enhancing left frontal mass with a second significant mass located in the left cerebellar hemisphere including the left cerebellar tonsil region. There was mild vasogenic edema associated with both masses, and significant mass effect on the ventricular system, with some hydrocephalus. A chest/abdomen/pelvis CT revealed a breast cancer. The mutism was explained in part by the compression of the dominant (left) SMA area by the tumor.
Treatment paradigm: Owing to the size of the lesions and their associated edema and mass effect, surgery was offered as a primary treatment modality, mainly as a life-preserving procedure and at the family's reasonable insistence that everything rationally possible be done for the patient initially. A two-staged operation was proposed because of the patient's age and somewhat debilitated condition (less likely to tolerate a one-stage operation involving two separate craniotomy sites). Postoperative radiation and chemotherapy was anticipated, and the possibility of ventriculoperitoneal shunt placement was discussed given the hydrocephalus from the tumor-mass effect on the ventricular system.
Operative procedure/operative approach: Stage I surgery involved a left suboccipital craniotomy (prone position) with gross-total resection of the left cerebellar tumor. Intraoperative frozen-section pathology returned as tumor consistent with breast primary. The patient tolerated the procedure well. Seventy-two hours later, Stage II surgery was carried out, involving a left frontal craniotomy (supine position) and gross-total resection of the left frontal mass. Both surgeries were carried out using stereotaxy and were uneventful, but the patient did not improve in terms of her mental status impairment, mutism and persistent hydrocephalus. The patient's family declined placement of a ventriculperitoneal shunt, and also declined postoperative chemotherapy and radiation therapy, opting instead for palliative care.
Technical nuances and potential surgical pitfalls: Multi-staged surgery for metastatic disease may be warranted for certain patients. Brain-tumor interfaces are usually readily apparent for breast cancer metasases. Again, operative risks are particularly location-dependent. Frontal/parafalcine lesion resection has been discussed in Case 13. Cerebellar hemisphere and tonsillar resections should involve due caution around the obex region of the floor of the IVth ventricle, as well as careful preservation of local posterior-inferior cerebellar artery (PICA) loops. Durotomy should take into consideration sometimes significant bleeding from an elarged occipital venous sinus (the size of which can be anticipated from preoperative contrast MRI images). Control of such sinuses with one or more of Ligaclips, through-and-through suturing and/or generous cautery may be needed.
Imaging:
Image 14.1 (above). Frontal and cerebellar metastases. The preoperative MRI images (T1 with contrast; multiplanar) show two large metastases (yellow arrow heads) situated in the frontal and cerebellar regions. There are significant mass effect and shift associated with these metastases, in addition to hydrocephalus.
Image 14.2 (above). Frontal and cerebellar metastases. The postoperative MRI images (T1 with contrast; multiplanar) show the expected cavities (arrow heads) following gross-total resection of the two (remotely located) metastases removed in a two-stage procedure.
Brain Tumor section; Case 15 - Metastatic melanoma
Background: Melanoma metastases can arise from abnormal "melanocytes" (cells that produce a pigment called melanin) present outside of the nervous system (i.e., in skin or gastrointestinal mucosa) or those present in the nervous system itself (around the brainstem ventral medulla or in the retina's choroid layer). Unfortunately, melanoma metastatic to the brain is typically an aggressive disease process. Fortunately, brain metastatic melanoma accounts for less than 3% of all brain metastases. Melanoma, like other metastatic processes, can deposit in the brain substance (intraparenchymal) or in its coverings (meninges). In the brain, melanoma metastases are frequently multiple and hemorrhagic (prone to bleeding). They can be operated, but tend to be resistant to chemotherapy and radiation therapy.
Clinical presentation: This 34 year old patient presented with acute headache. Physical examination showed no gross motor or sensory or mental status impairment.
Diagnostic workup: CT head showed an area of hemorrhage at the confluence of the left parietal and occipital lobes. Some edema was present around the area of hemorrhage, as confirmed by brain MRI with and without contrast. Areas within the mass appeared to enhance with contrast. Other areas were consistent with brain hemorrhage cavities. Given the age of the patient and hemorrhagic presentation, the possibility of a small ruptured arteriovenous malformation (AVM) was suspected, and a cerebral angiogram was carried out. The angiogram revealed no AVM, but a small blush in the region was consistent with a solid component of tumor.
Treatment paradigm: A hemorrhagic tumor was suspected and surgery was offered to both remove the mass and obtain a pathologic (tissue) diagnosis. Postoperative treatment would be guided by the pathology.
Operative procedure/operative approach: A left parietal craniotomy was carried out using MRI stereotaxy, and the lesion was uneventfully gross-totally resected. Intraoperative frozen section pathology revealed melanoma, subsequently confirmed by the embedded sections. Oncology services (medical and radiation) were consulted. Surprisingly, no skin or nervous system or other primary was found (i.e., in this patient's case, a "tumor of unknown origin").
Technical nuances and potential surgical pitfalls: Metastatic melanoma deposits tend to be vascular, like renal cell cancer metastases. A vascular pedicle should be sought and coagulated/eliminated early in the resection. In order to minimize blood loss and for optimal surgical efficacy, vascular lesions such as these should be resected in toto by defining and exploiting the tumor-lesion interface. Where possible, circumferential gentle blunt dissection using multiple low-profile patties allows the plane between the tumor and more normal brain to be defined. If brisk bleeding is encountered from the metastasis, the remainder should be rapidly resected (this itself controls the bleeding). Hematoma cavities can be followed to the solid or nodular component of the tumor. As an aside, it should be remembered that in patients presenting with an intraparenchymal hemorrhage but no obvious solid component to the lesion, after an angiogram is carried out to rule out an AVM, if the patient is taken to the OR, multiple biopsy specimens of the wall of the hemorrhagic cavity should be obtained to rule-out occult tumor.
Imaging:
Image 15.1 (above). Melanoma metastasis. The preoperative T2 axial MRI image shows a nodular component to the tumor (dashed-circle), and associated pockets or cavities of hemorrhage (note the dark hemosiderin ring around these areas). Edema is also noted.
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