References for this review were identified by searches of PubMed from 1996 until June, 2006, with the terms “multiple sclerosis”, “demyelinating diseases”, “neurosarcoidosis”, “Behçet disease”, “pyogenic abscess”, “toxoplasmosis”, “tuberculoma”, “neurocysticercosis”, “fungal infections”, “syphilis”, “subacute ischemic stroke”, “haemorrhagic stroke”, “vascular malformation”, and “brain neoplasm”. Articles were also identified through searches of the authors' own files. Articles in English,
ReviewPitfalls in the diagnosis of brain tumours
Introduction
An accurate and timely diagnosis is a key principle in neuro-oncology.1, 2 Cancer treatments are frequently toxic, but the risk of toxic effects is justified by the potential gains in survival seen when the appropriate treatment is assigned to the right patient. Thus, there is little room for presumptive diagnoses and empirical treatments. Conversely, establishing the diagnosis of a brain tumour might not always be a straightforward process. The terms brain tumour and brain neoplasm are frequently used as synonyms and immediately evoke the necessity of a diagnostic surgical procedure. However, many non-neoplastic diseases can present as space-occupying lesions, mimicking brain neoplasms.3, 4 Some of these diseases have a benign character and can be managed without histological confirmation. As such, diagnoses are commonly missed in the preoperative setting and many patients are unnecessarily exposed to the risks of a surgical procedure.5, 6 Additionally, several brain neoplasms can present in the absence of typical space-occupying lesions, simulating other diseases. In this setting, the pitfall is misinterpretation of the real nature of the lesion leading to a delay in histological confirmation.7, 8 Furthermore, even when tissue is obtained an accurate diagnosis might not be attained because sampling errors and misinterpretation of histological findings can still occur.9, 10 The purpose of this Review is to raise awareness to common diagnostic problems in the management of brain tumours, with emphasis on pitfalls in the interpretation of clinical, neuroimaging, and histological findings, as well as in the indication or non-indication for surgical procedures.
Section snippets
Initial approach
When the diagnosis of a brain tumour is raised, a thorough assessment of history, a physical examination, and a minimal workup can provide important clues on the nature of the lesion (ie, neoplastic versus vascular, inflammatory, or infectious lesions) and will avoid missing obvious diagnoses. The panel shows a list of clinical elements that raise the possibility of a non-neoplastic diagnosis. We personally advocate obtaining a body CT scan and anti-HIV and syphilis serology for all patients.
Neuroimaging methods
A first step to avoid diagnostic pitfalls is attentively reviewing all MRI sequences in a standard examination, including the frequently neglected sequence of T1 precontrast, diffusion-weighted sequences (DWI), and apparent diffusion coefficient (ADC) maps. Such thorough review could avoid missing useful diagnostic clues (table 1). As needed, assessment might be complemented by alternative MRI techniques, such as perfusion-weighted MRI (PWI) and proton magnetic resonance spectroscopy (MRS).
Interpretation of pathology findings
Obtaining tissue is not always a guarantee that a final diagnosis will be attained because sampling errors or misinterpretation of findings could still occur. Table 2 summarises the pitfalls commonly encountered in pathology interpretation. Stereotactic biopsies provide exiguous material and, commonly, only normal tissue or unspecific abnormalities such as gliosis or necrosis are seen on histology analysis. The use of spectroscopy, PET, and SPECT for guiding biopsies has decreased sampling
Non-neoplastic diseases presenting as tumefactive enhancing brain lesions
A solid knowledge of how neoplastic and non-neoplastic diseases behave is a key step to avoid missing the correct diagnosis, either in the preoperative or postoperative setting. Here, we review each of the non-neoplastic neurological diseases that might present as brain tumours, focusing on the elements most useful in the differentiation with neoplastic lesions (table 1).
Non-tumoral presentations of neoplastic lesions
Several neoplastic lesions may present without mass effect, especially when they are in the early stages of development or when they diffusely infiltrate normal brain tissue. Low-grade gliomas may present as small FLAIR hypersignal lesions often difficult to distinguish from focal cortical dysplasias and postictal transient neuroimaging abnormalities. MRS has been shown to be useful in such differentiation.95 Of note, transient postictal abnormalities have been reported in locations that are
Conclusion
Technological advances in neuroimaging and histological analysis methods have improved recognition of non-neoplastic diseases presenting as brain tumours, have facilitated interpretation of biopsy material, and have provided clues for recognising non-tumoral presentations of neoplastic diseases. However, no isolated technique achieves 100% specificity and sensitivity, and interpretation of results still relies on sound clinical judgment. Discordance among different assessments and clinical
Search strategy and selection criteria
References (100)
- et al.
Primary brain tumours in adults
Lancet
(2003) Perfusion MR imaging: basic principles and clinical applications
Magn Reson Imaging Clin N Am
(2003)- et al.
Positron emission tomography imaging of brain tumors
Neuroimaging Clin N Am
(2003) - et al.
Astrocytoma-like multiple sclerosis
Clin Neurol Neurosurg
(2005) - et al.
Anaplastic oligodendroglioma and gliomatosis type 2 in interferon-beta treated multiple sclerosis patients. Report of two cases
Clin Neurol Neurosurg
(2006) - et al.
Neurosarcoidosis presenting with simple partial seizures and solitary enhancing mass: case reports and review of the literature
Epilepsy Behav
(2005) - et al.
Primary cerebral sarcoid granuloma: the importance of definitive diagnosis in the high-risk patient population
Clin Neurol Neurosurg
(2002) - et al.
Discrimination of brain abscess from necrotic or cystic tumors by diffusion-weighted echo planar imaging
Magn Reson Imaging
(1996) - et al.
Differential MRI diagnosis between brain abscesses and necrotic or cystic brain tumors using the apparent diffusion coefficient and normalized diffusion-weighted images
Magn Reson Imaging
(2003) - et al.
Brain abscess: clinical aspects of 100 patients
Int J Infect Dis
(2006)
Quantitative MR spectroscopic imaging of brain lesions in patients with AIDS: correlation with [11C-methyl]thymidine PET and thallium-201 SPECT
Acad Radiol
Role of diffusion weighted imaging in differentiation of intracranial tuberculoma and tuberculous abscess from cysticercus granulomas-a report of more than 100 lesions
Eur J Radiol
Central nervous system histoplasmosis mimicking a brain tumor: difficulties in diagnosis and treatment
Mayo Clin Proc
Intracerebral mass lesions in patients with human immunodeficiency virus infection and cryptococcal meningitis
Diagn Microbiol Infect Dis
Intracranial fungal granuloma: analysis of 40 patients and review of the literature
Surg Neurol
Small cortical infarcts mimicking metastatic tumors
Clin Imaging
PET imaging for differentiating recurrent brain tumor from radiation necrosis
Radiol Clin North Am
Magnetic resonance spectroscopy: a noninvasive diagnosis of gliomatosis cerebri
Magn Reson Imaging
Brain tumors
N Engl J Med
Mimics of brain tumor on neuroimaging: part I
Radiat Med
Mimics of brain tumor on neuroimaging: part II
Radiat Med
Debulking or biopsy of malignant glioma in elderly people: a randomised study
Acta Neurochir (Wien)
Stereotactic biopsy in the era of advanced neuroimaging. Does the minimal therapeutic gain justify its current wide use?
Minim Invasive Neurosurg
Spontaneous intracranial haematomas caused by neoplasms
Acta Neurochir (Wien)
Diagnostic delay in primary central nervous system lymphoma
Acta Oncol
Demyelinating disease versus tumor in surgical neuropathology: clues to a correct pathological diagnosis
Am J Surg Pathol
Stereotactic biopsy for brain tumors: is it always necessary?
Surg Neurol
Multivoxel magnetic resonance spectroscopy of brain tumors
Mol Cancer Ther
Evaluation of malignancy in ring enhancing brain lesions on CT by thallium-201 SPECT
J Neurol Neurosurg Psychiatry
Clinical evaluation of thallium-201 single photon emission computed tomography in equivocal neuroradiological supratentorial lesions
J Neurosurg Sci
Monophasic, solitary tumefactive demyelinating lesion: neuroimaging features and neuropathological diagnosis
Br J Radiol
Open-ring imaging sign: highly specific for atypical brain demyelination
Neurology
Pathognomonic MR imaging findings in Balo Concentric Sclerosis
AJNR Am J Neuroradiol
In vivo differentiation of astrocytic brain tumors and isolated demyelinating lesions of the type seen in multiple sclerosis using 1H magnetic resonance spectroscopic imaging
Ann Neurol
Proton MR spectroscopy of tumefactive demyelinating lesions
AJNR Am J Neuroradiol
Spectroscopic magnetic resonance imaging of a tumefactive demyelinating lesion
Neuroradiology
Dynamic contrast-enhanced T2*-weighted MR imaging of tumefactive demyelinating lesions
AJNR Am J Neuroradiol
TI-201 SPECT in pseudotumoral multiple sclerosis
Clin Nucl Med
Tumefactive demyelinating lesions: conventional and advanced magnetic resonance imaging
Mult Scler
Acute focal demyelinating disease simulating brain tumors: histopathologic guidelines for an accurate diagnosis
Neuropathology
Effect of brain irradiation on demyelinating lesions
Neurology
Microdissection-based genotyping assists discrimination of reactive gliosis from glioma
Am J Clin Pathol
Differentiation between reactive gliosis and diffuse astrocytoma by in situ hybridization
Neurology
Glioblastoma associated with multiple sclerosis: coincidence or induction?
Eur Neurol
Use of serial proton magnetic resonance spectroscopy to differentiate low grade glioma from tumefactive plaque in a patient with multiple sclerosis
Br J Radiol
Neurosarcoidosis: clinical description of 7 cases with a proposal for a new diagnostic strategy
J Neurol
Neuro-Behcet's syndrome in a patient not fulfilling criteria for Behcet's disease: clinical features and value of brain imaging
Clin Rheumatol
Sequential PET studies in neuro-Behcet's syndrome
J Neurol
Proton MRS in Behcet's disease with and without neurological findings
Neuroradiology
Magnetic resonance imaging and proton magnetic resonance spectroscopy in neuro-Behcet's disease
Clin Exp Rheumatol
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