Beruflich Dokumente
Kultur Dokumente
and P M PRETORIUS,
MSc, FRCR
Department of Neuroradiology, West Wing, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
Summary N Clinical and demographic information should be combined with imaging findings to arrive at a specific diagnosis or a short differential diagnosis. N The age of the patient and anatomical location of the lesion(s) are the most useful discriminating factors. N Intravenous administration of contrast material is indicated when an intracranial mass lesion is detected on CT or MRI. N MRI is the preferred imaging modality for the evaluation of intracranial mass lesions, but CT is often performed at the initial presentation for practical reasons.
Abstract. Intracranial mass lesions are an important cause of neurological morbidity and a common indication for cranial imaging. Given the wide range of pathological processes that can present as intracranial mass lesions, the radiologist has an important role in limiting the differential diagnosis in an individual case in order to inform the clinical decision-making process. This review illustrates the use of cranial CT and MRI, including diffusion weighted imaging (DWI), in the characterization of intracranial mass lesions. A detailed description of the imaging appearances of all mass lesions is beyond the scope of this review, but we hope to provide the reader with a rational approach to the complex task of producing a short differential diagnosis. The management of intracranial mass lesions was revolutionized by the development of CT and MRI. The pivotal role of the radiologist in the diagnostic workup of these patients is summarized in Box 1. The prognosis and management of different intracranial mass lesions vary widely and the radiologist should therefore always strive to provide the referring clinician with as short a differential diagnosis as possible. Being able to exclude certain possibilities with confidence from the differential diagnosis is also very helpful. Some radiologists remain reluctant to offer a short differential diagnosis, reasoning that the pathologist will have the final say in any case. This is an out-dated and unnecessarily defeatist view for three reasons. (1) Several brain masses have pathognomonic or virtually pathognomonic appearances (e.g. cerebral aneurysms [1, 2], lipoma of the corpus callosum [3], dermoid and epidermoid tumours [47], Lhermitte-Duclos disease (Figure 1) [8], most vestibular schwannomas [911] and most meningiomas [12, 13]), rendering biopsy obsolete or even contraindicated unless surgery is indicated for clinical reasons. (2) To minimize surgical morbidity, most brain biopsies are performed through a small burr-hole using a biopsy needle yielding a tiny fragment of tissue. This approach is obviously prone to sampling errors. In a large glioma, for
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instance, the biopsy may only yield tissue corresponding to a World Health Organization (WHO) grade II lesion while the imaging may show contrast enhancement and necrosis indicating a grade IV lesion. (3) Certain histological features are ambiguous and should be interpreted in the light of the imaging findings, e.g. Rosenthal fibres are typically found in pilocytic astrocytomas, but can also be seen in reactive gliosis [14]. CT and MRI can be used to obtain information about several features of a mass lesion, including the location,
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size and extent, tissue composition and state of the bloodbrain barrier. Chemical and pathophysiological information obtained from advanced imaging techniques, such as 1H MR spectroscopy and perfusion imaging, also has a role to play in certain cases but, since these techniques are not currently widely available, we have decided to concentrate on modalities and techniques available in most district general hospitals.
cases while the patients sex is usually irrelevant except in the very specific instances mentioned below. Radiology trainees in particular may find our proposed checklist of eight questions (Box 2) useful when trying to come up with a short differential diagnosis of an intracranial mass. The fact that four of the eight questions refer to clinical and demographic information reflects the importance of this information. The reader should also keep in mind that the relevance of the answer to one question may depend on the answer to another question. For example, the anatomical location of a mass has different implications in different age groups. We shall now briefly discuss the relevance of each of the eight questions using examples. This discussion is far from comprehensive, but hopefully serves to illustrate the usefulness of this approach.
Figure 2. The relevance of patient age in tumours in a particular location. Axial gadolinium enhanced T1 weighted images
through the posterior fossa in (a) a 6-year-old boy and (b) a 62-year-old man, both presenting with recent onset of cerebellar symptoms and signs. Based on the ages of the patients, a primary tumour was considered most likely in the child, whereas a metastasis was suspected in the older patient. Histology confirmed a medulloblastoma in the child (a) and a non small-cell lung cancer metastasis in the man (b).
typically present with a sudden onset of dramatic motor and/or sensory deficits. Infarcts and demyelination only rarely present with seizures [19].
Figure 3. Combining clinical and imaging information to reach the correct diagnosis. This 35-year-old man has a 12year history of temporal lobe epilepsy. The coronal gadolinium enhanced T1 weighted image shows an intra-axial, cortically based, partially cystic mass with eccentric rim enhancement. The long history of seizures attributable to this lesion points towards an indolent neoplasm rather than a more aggressive rim enhancing lesion, such as a metastasis, glioblastoma multiforme (GBM) or abscess. In this location, ganglioglioma and dysembryoplastic neuroepithelial tumour (DNET) are the most likely candidates. The enhancement characteristics strongly favour a ganglioglioma and this was confirmed histologically. Imaging, Volume 19 (2007) Number 2
Figure 4. Combining clinical and imaging information to reach the correct diagnosis. Coronal T2 weighted image of a 7-year-old child with precocious puberty and a long history of gelastic seizures shows a small, well defined hyperintense mass arising from the inferior aspect of the hypothalamus. The location and clinical features enable the diagnosis of hypothalamic hamartoma to be made, obviating the need for histological diagnosis. 175
There are two rare exceptions to this rule and both involve lesions of midline structures. First, lymphocytic hypophysitis is a rare non-neoplastic cause of an enlarged enhancing pituitary gland and or pituitary stalk and is at least eight times more common in women than men [31]. We have to stress that the other causes of this appearances, such as pituitary adenoma, Langerhans cell histiocytosis, sarcoidosis and germinoma, are more common in both sexes. Second, germinomas in boys and men tend to occur in the pineal gland while the same tumours in women and girls are more common in the suprasellar region [16]. It goes without saying that the great (more than one hundredfold) gender difference in the incidence of breast carcinoma has an influence on how we search for the primary tumour in cases of cerebral metastases from an unknown primary.
Even a solitary intra-axial enhancing mass in such a patient should be considered a metastasis until proven otherwise. On the other hand, similar appearances in a patient with AIDS would raise the suspicion of primary CNS lymphoma or toxoplasmosis [21]. Neurocutaneous syndromes (particularly von HippelLindau (VHL) [22], neurofibromatosis types 1 and 2 [11, 23] and tuberous sclerosis [2426]) predispose to particular tumours. Knowledge about these conditions allows the radiologist to make a confident diagnosis of a specific histological tumour type in many cases (Figures 5 and 6). At the time of the patients first presentation with an intracranial tumour, the diagnosis of the neurocutaneous syndrome may not yet have been made but additional imaging features often give clues to the underlying genetic condition. Examples of conditions predisposing to non-neoplastic mass lesions include cyanotic heart lesions and pulmonary arteriovenous malformations, which predispose to brain abscesses [27, 28], and adult polycystic kidney disease and coarctation of the aorta, which predispose to cerebral aneurysms [29, 30].
Intra-axial vs extra-axial The term intra-axial implies that a mass arises within the neuraxis, i.e. within the substance of the CNS (brain or spinal cord). Extra-axial lesions can arise within the skull, meninges, cranial nerves or blood vessels. Extra-axial lesions are easier to classify accurately than intra-axial lesions and often have a pathognomonic appearance [913] (Figure 5). The ability to distinguish intra-axial from extra-axial masses is arguably the single most discriminating imaging feature that can be elicited. It can also be a surprisingly difficult distinction to make in some cases. Intra-axial masses are completely surrounded by brain tissue except for rare instances of tumours with an exophytic component. Lesions within the cerebral or cerebellar white-matter or the deep greymatter structures can easily be classified as intra-axial. However, when a lesion involves the cortex it should be carefully evaluated to decide whether it is protruding into the cortex from outside (extra-axial) or arising within the cortex or subcortical white-matter (intraaxial). Imaging features strongly suggestive of an extraaxial origin include trapped cerebrospinal fluid (CSF) and or pial blood vessels between the lesion and the cortex, and a buckled or concertina appearance of the underlying cortex (Figure 7). The presence of oedema is not particularly useful in distinguishing between intraaxial and extra-axial lesions as it can be present or absent in either [13, 32, 33]. Supra-tentorial vs infra-tentorial This is an easy distinction to make and, in combination with the patients age, it is particularly useful in distinguishing between different types of intra-axial tumours. For example, GBMs and metastases together
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Figure 6. Diagnosing specific histological tumour types as features of a predisposing genetic syndrome. (a) Axial T2 weighted and (b)
gadolinium-enhanced T1 weighted MR images in an 8-year-old boy with learning difficulties, epilepsy and a 2-month history of headaches. There is a well circumscribed, avidly enhancing mass in a subependymal location associated with the frontal horn of the right lateral ventricle. In addition, there are bilateral small subependymal nodules in the trigones of the lateral ventricles as well as a cortical/subcortical area of high signal on T2 in the left frontal lobe. These features, particularly given the clinical history, are pathognomonic of tuberous sclerosis (TS). The enhancing mass therefore represents a subependymal giant cell astrocytoma.
account for more than half of all intrinsic neoplasms in adults. While both these tumour types occur more frequently in the supratentorial compartment, only approximately 1% of GBMs are infratentorial vs approximately 15% of brain metastases. An enhancing cerebellar mass lesion in an adult is therefore much more likely to represent a metastasis than a GBM [16]. A cystic lesion with an enhancing mural nodule in the cerebellum of a child suggests a pilocytic astrocytoma while the same appearance in an adult or a patient with VHL syndrome suggests a haemangioblastoma [16, 17, 22, 34]. In the supratentorial compartment, particularly in the temporal lobe of a child or adult with epilepsy the same appearance is suggestive of a ganglioglioma (Figure 3) [17, 35].
Specific sites Certain lesions are specific to or at least more common in certain intracranial locations (Figures 16, 8 and 9); for example, pituitary adenomas are limited to the anterior pituitary gland. Similarly, certain sites give rise to a limited number of lesions; for example, a mass lesion in the jugular foramen is likely to represent a glomus tumour, schwannoma, meningioma or metastasis [36]. Short differential diagnoses for mass lesions in the following locations can be found in standard textbooks of neuroradiology: pituitary/suprasellar region, cerebello-pontine angle, brain stem, pineal, intraventricular, jugular foramen, cavernous sinus.
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Figure 8. Axial T2 weighted MR images in two different patients demonstrating the importance of location vs signal
characteristics. (a) Colloid cyst of the third ventricle. The shape (well defined and round) and location anteriorly in the third ventricle establishes the diagnosis in this case. Colloid cysts are typically non-enhancing and can be hypointense, isointense or hyperintense on T2 weighted images; therefore the signal characteristics are less helpful than the location in making the diagnosis. (b) Cavernoma of the mid-brain. An intra-axial lesion anywhere in the central nervous system with these signal characteristics is most likely to represent a cavernoma. The peripheral low signal is due to haemosiderin staining while the central high signal denotes the presence of extra-cellular methaemoglobin, indicating a more recent episode of haemorrhage. In this case, the signal characteristics are more useful than the location of the lesion, as cavernomata occur throughout the neuraxis and look the same in any location.
multiple sclerosis or acute disseminated encephalomyelitis (ADEM). Primary intra-axial brain tumours are usually solitary although satellite nodules are occasionally seen distant from the main tumour bulk in high-grade lesions such as GBMs [37].
Metastatic spread of primary CNS neoplasms is very uncommon with the exception of metastatic seeding of the CSF spaces. For example, an intra-axial tumour, such as a cerebellar medulloblastoma, could give rise to one or more metastatic deposits in the intracranial or spinal subarachnoid space or within the ventricular system.
Figure 9. Using age and location to achieve the correct diagnosis: a 4-year-old mute child with cranial nerve palsies. (a) Sagittal
midline fluid attenuated inversion recovery (FLAIR) image shows a uniform high signal mass expanding the pons, characteristic of a pontine astrocytoma. Pontine astrocytomas are usually of the diffuse fibrillary type and are at least World Health Organization (WHO) grade II, whereas astrocytomas in the midbrain and medulla are usually pilocytic astrocytomas (WHO grade I). (b) Axial post-gadolinium T1 weighted image demonstrates patchy contrast enhancement which suggests a WHO grade III lesion.
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Figure 10. Utilizing specific imaging characteristics to reach the correct diagnosis. This 30-year-old man has a history of periodic
headaches and now presents with acute meningeal signs. (a) Sagittal midline unenhanced T1 weighted image showing a large hyperintense and heterogeneous mass with several, similarly strongly hyperintense foci scattered within the sub-arachnoid space. (b) Axial CT image confirms multiple, midline low attenuation foci associated with the falx, confirming these to be fat droplets of a ruptured dermoid cyst. Intracranial dermoids usually contain a varying combination of lipid, liquid cholesterol, whorls of hair, calcifications and decomposed epithelial cells producing typical appearances, as illustrated in this case.
Other tumours associated with this pattern of dissemination include ependymomas, germinomas, pilocytic astrocytomas and glioblastomas [38, 39].
lesions. Two circumstances where DWI is particularly useful are in the evaluation of ring enhancing intra-axial mass lesions and CSF signal extra-axial mass lesions. The differential diagnosis of ring enhancing intracranial mass lesions include metastases, GBM, acute inflammatory demyelination, bacterial abscess and a number of other infectious conditions, such as toxoplasmosis, tuberculoma and cysticercosis. In clinical practice, it is often important to distinguish between a bacterial brain abscess on the one hand and a tumour on the other hand since the former requires urgent surgical aspiration and intravenous antibiotics while the latter can often be managed with oral corticosteroids and elective surgical biopsy (Figure 11). DWI can be used to help distinguish between these two entities since pus in bacterial abscesses demonstrates markedly restricted diffusion (bright on b51000 s mm2 images and dark on apparent diffusion coefficient (ADC) map) while necrotic tumour material demonstrates facilitated diffusion (dark on b51000 s mm2 images and bright on ADC map), except in rare instances where haemorrhage has occurred into the necrotic tumour centre [4547]. An extra-axial mass lesion returning signal isointense or nearly isointense to CSF on T1 and T2 weighted imaging is likely to be either an arachnoid cyst or an epidermoid tumour. Diffusion is facilitated in arachnoid cysts while epidermoid tumours demonstrate restricted diffusion (Figure 12) [48, 49].
Figure 11. The use of diffusion-weighted imagine (DWI) in intra-axial ring enhancing lesions. (a) A contrast-enhanced CT scan of the brain in an elderly woman with headache and a right-sided visual field defect shows a ring enhancing lesion with surrounding vasogenic oedema. (b) A DWI (b51000) image of the same patient shows restricted diffusion (high signal) within the fluid content of the lesion. Surgical aspiration confirmed an abscess. (c) An axial contrast enhanced T1 weighted MR image in an elderly lady with a left sided visual field defect demonstrates an intra-axial ring enhancing lesion. (d) The DWI (b51000) image shows free diffusion (low signal) of the fluid content. Histology confirmed a GBM with a necrotic centre.
implies angioneogenesis with increased endothelial permeability of the abnormal tumour capillaries [50]. Different morphological patterns of contrast enhancement are recognized. Descriptive terms, such as nonenhancement, uniform enhancement, patchy enhancement, gyriform enhancement and ring enhancement (also called rim or peripheral enhancement) are in common use and give useful information about the nature of the lesion. As a general rule, most intracranial tumours whether primary or metastatic show some form of contrast enhancement. The notable exceptions are WHO grade II astrocytomas and oligodendrogliomas (Figures 9 and 13) [16, 51, 52], and gliomatosis cerebri a rare, diffusely infiltrating glial tumour that is usually grade III.
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Relatively uniform enhancement is seen in most solid tumours including meningiomas, schwannomas, pituitary adenomas and pineal tumours, such as germinomas. CNS lymphomas typically show uniform enhancement in immunocompetent patients while ring-enhancing lesions have been described in immunodeficient patients [42]. Ring enhancement also occurs in aggressive tumours such as GBMs and metastases (around areas of necrosis) as well as in abscesses and some inflammatory demyelinating lesions (Figure 11). Other infectious lesions, such as toxoplasmosis, cysticercosis and tuberculomas, can also demonstrate ring enhancement. Inflammatory demyelinating lesions only enhance during the active phase of demyelination [5355]. In multiple sclerosis, this phase usually lasts less than 3 months for individual lesions. All the patterns of
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Figure 12. The use of diffusion-weighted imaging (DWI) in cerebrospinal fluid (CSF) signal extra-axial masses. (a) Axial T2
weighted MR image demonstrates a CSF signal mass lesion in the cisterna magna displacing the medulla posteriorly. (b) The lesion is bright on a b51000 DWI image indicating restricted diffusion. The lesion therefore represents an epidermoid rather than an arachnoid cyst.
enhancement (including no enhancement) listed in Box 2 have been described in demyelinating lesions. Incomplete ring enhancement (also referred to as a broken ring) is an unusual pattern of enhancement and is strongly associated with inflammatory demyelination (Figure 14) including multiple sclerosis although it has been described in infectious and neoplastic conditions [56, 57]. Gyriform enhancement within the cerebral cortex occurs in infarcts and certain encephalitic conditions that affect the cortex [58, 59].
Conclusions
One of the most important roles of the radiologist in the diagnostic pathway of a patient with an intracranial mass is to provide the clinicians with a short differential diagnosis. The radiologist should integrate all the relevant information available on the images as well as the request card to achieve this. Certain bits of information have a higher discriminating value than others and the radiologist should give greater weight to such information when formulating the differential diagnosis.
Figure 13. Contrast enhancement gives information about tumour grade. (a) Axial T1 weighted image in a patient with a
longstanding grade II astrocytoma shows an intra-axial mass with relatively uniform hypointense signal compared with whitematter. (b) Following gadolinium administration, there is a focal area of enhancement anteromedially (arrow) within the mass indicating anaplastic transformation to a grade III astrocytoma.
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Figure 14. Tumefactive demyelination. This 61-year-old man with no history of multiple sclerosis presented with progressive
right sided hemiparesis and left sided facial numbness. The left-sided pontine mass lesion returns high signal on (a) T2 and low signal on (b) T1 weighted imaging. There is incomplete ring enhancement seen on (c) the axial and (d) sagittal gadolinium enhanced T1 weighted images. Given the patients age, a tumour was suspected despite the enhancement pattern. Stereotactic biopsy demonstrated demyelination with no evidence of a tumour.
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References
1. Biondi A, Scialfa G, Scotti G. Intracranial aneurysms: MR imaging. J Neuroradiol 1988;30:2148. 2. Donovan JL, Nesbit GM. Distinction of masses involving the sella and suprasellar space: specificity of imaging features. AJR Am J Roentgenol 1996;167:597603. 3. Ichikawa T, Kumazaki T, Mizumara S, Kijima T, Motohashi S, Gocho G. Intracranial lipomas. J Nippon Med Sch 2000;67:38891. 4. Wilms G, Casselman J, Demaerel Ph, Plets C, Haene I De, Baert AL. CT and MRI of ruptured intracranial dermoids. J Neuroradiol 1991;33:14951. 5. Kallmes DF, Provenzale JM, Cloft HJ, McClendon RE. Typical and atypical MR imaging features of intracranial epidermoid tumors. AJR Am J Roentgenol 1997;169:8837. 6. Davidson HD, Ouchi T, Steiner RE. NMR imaging of congenital intracranial germinal layer neoplasms. J Neuroradiol 1985;27:3013. 7. Tampieri D, Melanson D, Ethier R. MR imaging of epidermoid cysts. AJNR Am J Neuroradiol 1989;10:3516. 8. Ashley DG, Zee CS, Chadrasoma PT, Segall HD. LhermitteDuclos disease: CT and MR findings. J Comput Assist Tomogr 1990;14:9847. 9. Curati WL, Graif M, Kingsley DP, Niendorf HP, Young IR. Acoustic neuromas: Gd-DTPA enhancement in MR imaging. Radiology 1986;158:44751. 10. Eldevik OP, Gabrielsen TO, Jacobsen EA. Imaging findings in schwannomas of the jugular foramen. AJNR Am J Neuroradiol 2000;21:113944. 11. Shu HH, Mirowitz SA, Wippold FJ. Neurofibromatosis: MR imaging findings involving the head and spine. AJR Am J Roentgenol 1993;160:15964. 12. Goldsher D, Litt AW, Pinto RS, Bannon KR, Kricheff II. Dural tail associated with meningiomas on Gd-DTPAenhanced MR images: characteristics, differential diagnostic value, and possible implications for treatment. Radiology 1990;176:44750. 13. Buetow MP, Buetow PC, Smirniotopoulos JG. Typical, atypical, and misleading features in meningioma. Radiographics 1991;11:1087106. 14. Dinda AK, Sarkar C, Roy S. Rosenthal fibres: an immunohistochemical, ultrastructural and immunoelectron microscopic study. Acta Neuropathol 1990;79:45660. 15. Klatzo I. Pathophysiological aspects of brain edema. Acta Neuropathol 1986;72:2369. 16. Chapter 1: Astrocytic Tumours. In: Kleihous P, Cavenee WK, editors. WHO Classification of Tumours. Pathology and genetics. Tumours of the Nervous System. Lyon, France: IARC Press, 2000:17684. 17. Rickert CH, Paulus W. Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification. Childs Nerv Syst 2001;17:50311. 18. Zentner J, Wolf HK, Ostertun B, Hufnagel A, Campos MG, Solymosi L, et al. Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients. J Neurol Neurosurg Psychiatry 1994;57:1497502. 19. Bladin CF, Alexandrov AV, Bellavance A, Bornstein N, Chambers B, Cote R, et al. Seizures after stroke: a prospective multicenter study. Arch Neurol 2000;57:161722. 20. Merchut MP. Brain metastases from undiagnosed systemic neoplasms. Arch Intern Med 1989;149:107680. 21. Levy RM, Pons VG, Rosenblum ML. Central nervous system mass lesions in the acquired immunodeficiency syndrome. J Neurosurg 1984;61:916. 22. Maher ER, Yates JRW, Harries R, Benjamin C, Harris R, Moore T, et al. Clinical features and natural history of von Hippel-Lindau disease. QJM 1990;77:115163.
N N N
N N
Confirm the presence of a mass lesion/lesions Determine whether there are any complications needing urgent attention, e.g. hydrocephalus, tonsillar herniation, compression of the anterior optic pathways Offer a short differential diagnosis: N Try to distinguish neoplastic from non-neoplastic masses N Inform the referring clinicians urgently if the differential diagnosis includes infectious conditions, such as bacterial abscess or tuberculosis Liaise with the neuropathologist in cases where a biopsy is performed, particularly if there are ambiguous histological findings Provide information relevant to the surgical management: N Relationship of tumour to major arteries and venous sinuses and whether those structures are patent N Relationship to eloquent brain areas such as the motor-cortex and other important structures such as cranial nerves N In cases of obstructive hydrocephalus, sagittal high resolution midline T2 weighted sequences are needed to determine whether a third ventriculostomy can be performed safely
Box 2 Eight questions to help limit the differential diagnosis of intracranial masses:
1. How old is the patient? 2. How did the patient present? 3. Does the patient have a disease or syndrome, e.g. a phacomatosis or AIDS or a known malignancy elsewhere? 4. Is the patient male or female? 5. Where is the lesion located? - Intra-axial vs extra-axial - Supra-tentorial vs infra-tentorial - Specific sites: brainstem, pituitary, suprasellar, pineal, intra-ventricular, cerebellopontine angle/ IAM 6. Are the lesions solitary or multiple? 7. What are the imaging characteristics on unenhanced CT/MRI? 8. What are the enhancement characteristics? - None - Solid - Ring - Smooth - Irregular
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