Elsevier

The Lancet Neurology

Volume 5, Issue 11, November 2006, Pages 937-948
The Lancet Neurology

Review
Pitfalls in the diagnosis of brain tumours

https://doi.org/10.1016/S1474-4422(06)70597-XGet rights and content

Summary

Establishing the diagnosis of a brain tumour is not always a straightforward process. Many non-neoplastic neurological diseases can mimic brain neoplasms on neuroimaging or on histological examination, including multiple sclerosis, stroke, pyogenic abscess, toxoplasmosis, tuberculosis, cysticercosis, fungal infections, syphilis, sarcoidosis, Behçet disease, radiation necrosis, venous thrombosis, and others. Conversely, several types of brain neoplasms, such as glioblastomas, low-grade gliomas, CNS lymphomas, and brain metastases, can present in the absence of typical tumefactive lesions, posing significant diagnostic challenges. In this Review, we discuss the process of accurately establishing the diagnosis of brain tumours, focusing on pitfalls commonly encountered in clinical practice. We also discuss the rational use and limitations of new diagnostic techniques, such as diffusion-weighted MRI, perfusion-weighted MRI, magnetic resonance spectroscopy, single-photon emission tomography, and positron emission tomography, as well as new tools for histological examination, such as immunohistochemistry and molecular genetics analysis.

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 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,

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