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Cerebellar Tumors in Adults
The cerebellum serves as the principal site of disease in 2.6% of all primary central nervous system tumors, with a much higher prevalence in children than in adults. The clinical impact of a mass in the cerebellum belies its relatively low incidence, and involvement of contiguous brainstem structures significantly increases the morbidity and mortality of these tumors. A wide spectrum of pathologies is observed among cerebellar tumors. This chapter will focus on intrinsic cerebellar tumors in adults, with considerations for commonly observed extrinsic tumors, such as meningiomas or schwannomas, to be discussed elsewhere.
Clinical Presentation
Cerebellar tumors commonly present as one of several distinct scenarios. Headache, nausea, imbalance, and gait dysfunction are the most frequent complaints, attributable to mass effect and/or hydrocephalus. Involvement of the adjacent brainstem, tectum, and cranial nerves are less common presenting findings.
The cerebellum demonstrates functional localization; cerebellar signs often correlate with the location of the cerebellar lesion. Lesions involving the cerebellar hemispheres are more likely to show limb ataxias and associated dysmetria. Midline lesions, affecting the cerebellar vermis and midline cerebellar nuclei, are more likely to demonstrate truncal instability. The midline fastigial nuclei play a role in postural ataxia, whereas globus, embolliform, and dentate nuclei are important for limb ataxia. Injury to the dentate nuclei can lead to dysarthria and mutism in some patients.
Examination should look for presence of dysmetria in finger-to-nose or heel-to-shin testing, and dysdiadochokinesis on testing of rapid alternating movements. Gait and postural stability are important elements of the physical exam for patients with a cerebellar tumor.
Hydrocephalus and increased intracranial pressure are some of the most feared presentations and complications of cerebellar tumors, given the potential for rapid evolution of symptoms. This may result from compression and primary obstruction of the aqueduct or fourth ventricular outflow by a mass. It may also result from chemical irritation and nonobstructive hydrocephalus such as by leptomeningeal disease in the posterior fossa. Headache and nausea are early harbingers of elevated intracranial pressure, which may be compartmentalized to the posterior fossa. Emesis and lethargy should trigger urgent intervention, either through resection of the offending mass or temporization with an external ventricular drain.
Imaging
Upon presentation with symptoms and signs suggestive of a cerebellar mass, a computed tomography (CT) and/or magnetic resonance imaging (MRI) is typically obtained next. CT scans have the advantage that they can be done rapidly and thus help to determine immediate treatment upon initial presentation of the patient. MRI offers more definitive visualization of the mass in determining differential diagnosis and surgical strategy.
Cerebellar tumors can be solid or cystic. Solid masses are frequently isointense to gray matter on T1- and T2-weighted images; however, tumors such as pilocytic astrocytomas can appear isointense to cerebrospinal fluid (CSF) on T2. , Highly cellular tumors, such as medulloblastoma, frequently demonstrate restricted diffusion with high signal on diffusion-weighted imaging and low apparent diffusion coefficient signal. Tumors that have abnormal vessels, such as in Lhermitte-Duclos, or those with evidence of prior hemorrhage, will benefit from susceptibility-weighted imaging sequences, which are sensitive to blood. Cystic tumors are generally hypointense on T1 and hyperintense on T2 due to the liquid component; fluid-attenuation inversion recovery sequences can be helpful in tumors such as hemangioblastomas where the cystic component is different from CSF. Tumors with a large percentage of fat-containing substance, such as in cerebellar liponeurocytomas, can be identified by hyperintense streaks on T1, and fat suppression sequences can aid in their diagnosis. The pattern of contrast enhancement after the administration of gadolinium is also useful in narrowing the differential diagnosis.
Systemic imaging should be considered for adults with an enhancing cerebellar mass, when clinically appropriate, to evaluate for a primary cancer that metastasized to the cerebellum or drop metastases from the cerebellum to the rest of the neuraxis.
Tumor Subtypes
Hemangioblastomas
Clinical Features
Hemangioblastomas are the most common primary tumors of the cerebellum in adults (76%), accounting for 1.5% to 2.5% of intracranial tumors and 7% to 8% of posterior fossa tumors in adults. They can be divided into sporadic tumors, which accounts for approximately 75% of hemangioblastomas, or those associated with von Hippel-Lindau (VHL) disease (10% to 40%). Hemangioblastomas have a slight male predominance in sporadic patients, and female predominance in VHL patients. In sporadic cases, they are more common in the fifth and sixth decades of life, whereas in VHL, patients are usually diagnosed in the second and third decade of life. The most common locations include cerebellum (>70%), brainstem (>20%), fourth ventricle (2%), cerebellopontine angle (2%), and craniocervical junction (2%). Furthermore, 5% of all spinal cord primary neoplasms are hemangioblastomas.
Hemangioblastomas are benign, well-circumscribed, and highly vascular lesions. MRI features of an enhancing nodule associated with a peritumoral cyst in the cerebellum, with low T1-weighted signal and high-contrast enhancement, with flow voids on T2-weighted imaging, raise suspicion for the diagnosis. Morphologically, tumors can be divided into solid (48%), cystic (26%), cystic with mural nodule (21%), and both solid and cystic (5%), with the solid type dominating across both sporadic and VHL subtypes. Multiple lesions are almost exclusively associated with VHL.
Biology
Histologic examination of hemangioblastomas shows an extensive vascular network with neoplastic stromal cells with abundant cytoplasm and lipid vacuoles with a typical clear cell morphology. Markers for vimentin (100%), vascular endothelial growth factor (VEGF; 100%), CD34 (82%), neuron-specific enolase (93%), S-100 (81%), and glial fibrillary acidic protein (50%) are frequently immunopositive.
VHL disease is transmitted in an autosomal dominant manner with an incidence of 1/36,000. It is caused by a mutation in the VHL gene on chromosome 3p25-26, resulting in loss of function for the VHL tumor suppressor, which serves as a negative regulator of VEGF. Criteria for diagnosis of VHL include positive germline mutation on peripheral blood, family history of VHL disease and VHL-associated tumor, negative family history with two or more central nervous system (CNS) hemangioblastomas, or one hemangioblastoma and a VHL-associated tumor. Additional tumors observed in VHL include retinal angiomas, renal cell carcinomas pheochromocytomas, pancreatic tumors, renal and epididymis cysts, and endolymphatic sac tumors. Neurosurgeons should be aware of these associations to ensure adequate multidisciplinary treatment. The current recommendations for patients with newly suspected hemangioblastomas are to perform imaging of the full neuroaxis, ophthalmoscopy, abdominal ultrasound, testing for metanephrines, vanillylmandelic acid (VMA), and auditory screening. , , ,
Retinal angiomas are found in 60% of VHL patients and can lead to vision loss if untreated. As such, patients should undergo systematic screening and treatment with effective results in 70% of cases. Renal disease occurs in greater than 60% of patients, with a mean onset of 44 years of age, requiring systematic screening and intervention based on the encountered pathology (e.g., surveillance in renal cysts to partial nephrectomy in renal cell carcinoma). Patients with pheochromocytomas can present with a classic pattern of paroxysmal hypertension, headache, sweating, and tachycardia and are found in up to 10% of VHL patients. These patients require adequate preoperative work-up to minimize perioperative mortality. , , ,
Treatment
Surgical resection is the mainstay of treatment for hemangioblastoma, providing potential cure in sporadic cases. Patients have a favorable outcome in more than three-quarters of cases, with no significant differences between VHL and sporadic cases. Nevertheless, VHL patients have significant morbidity due to their systemic disease and disease recurrence with growth of additional hemangioblastomas. Thus the clinical decision-making and timing for intervention for VHL patients should take into account the higher likelihood that lesions will become symptomatic with close observation. Tumor/cyst size greater than 69 mm 3 or growth greater than 112 mm 3 per month are strong predictors of symptomatic progression.
Radiation therapy may play a role in select cases. Studies suggest improved progression-free survivals in smaller, solid tumors and with margin doses of greater than 15 Gy. ,
Follow-up recommendations for sporadic cases are less well developed but include MRI of the neuroaxis at 6 and 12 months postoperatively. Patients with VHL disease are recommended to undergo annual MRI of the neuroaxis with additional examinations including ophthalmoscopy, abdominal ultrasound, audiometry, and studies for pheochromocytoma.
Case Report: Hemangioblastoma
A 25-year-old female presented with positional headaches, associated with nausea, vomiting, and dizziness. Exam revealed dysmetria on finger-to-nose testing. Imaging revealed an enhancing mural nodule near the torcula ( Fig. 10.1A , arrow ) within a large cystic lesion (see Fig. 10.1B ). Imaging of the neuraxis did not reveal any additional lesions. However, chest, abdomen, and pelvis CT scans revealed multiple pancreatic cysts and kidney lesions, suspicious for VHL.
The patient was brought to the operating room for a suboccipital craniotomy. She was positioned prone with the back elevated. A large cystic lesion was encountered and decompressed first to allow for cerebellar relaxation prior to gross total resection of the mural nodule and lesion (see Fig. 10.1C and D ). The pathology was consistent with hemangioblastoma. The patient had resolution of her symptoms following surgery and was referred to genetics for evaluation of VHL.
Pilocytic Astrocytoma
Clinical Features
Pilocytic astrocytoma is a benign astrocytic tumor of the central nervous system classified as World Health Organization (WHO) grade I. The majority of pilocytic astrocytomas appear as a cystic mass with an enhancing mural nodule. However, they can also present as solid tumors or a heterogenous admixture of cystic and solid components. More than a third of pilocytic astrocytomas are found in the cerebellum. Although the tumor is most common in children aged 0 to 4 and 15 to 19 years old, it can occur in the adult population. A population-based study of 865 patients aged 20 and older who were diagnosed with pilocytic astrocytoma reported that survival rates in the population decreased with increasing age. Symptoms at presentation commonly include headache, nausea, vomiting, nystagmus, vertigo, and cerebellar signs. Cerebellar pilocytic astrocytomas have been noted on T2-weighted MRI images to be isointense to CSF.
Biology
On histology, pilocytic astrocytomas have alternating regions of microcystic, loosely organized cells and compact bipolar cells with eosinophilic Rosenthal fibers. Eosinophilic granular bodies are dispersed through both areas. Recent genetic studies have sought to classify the molecular characteristics that distinguish the different grades of astrocytomas. Pilocytic astrocytomas have a duplication at chromosome band 7q34 with a BRAF-KIAA1549 gene fusion in 70% of cases and lack the IDH1/2 mutation. ,
Treatment
Surgery with curative intent by gross total resection is the treatment of choice for pilocytic astroctyomas. Even though pilocytic astrocytomas are classified as WHO grade I, they can exhibit an aggressive nature in adults. Survival rates for pilocytic astrocytoma are correlated with age, with a 96.5% 60-month survival in patients aged 5 to 19 years and a 52.9% survival in patients aged 60 and older. In a study of 44 adult patients with pilocytic astrocytomas, which included all brain locations, disease progression or tumor recurrence was noted in 30% of patients, with mortality in 18% of patients associated with the disease.
Malignant Gliomas
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