http://neurology.thelancet.com Vol 5 November 2006 937 Review Pitfalls in the diagnosis of brain tumours Antonio M P Omuro, Claudia C Leite, Karima Mokhtari, Jean-Yves Delattre 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. 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. If not contraindicated by mass effect, lumbar puncture might provide useful information or even a definitive diagnosis, such as in patients with infectious diseases and some types of brain neoplasms. To avoid masking a diagnosis of CNS lymphoma and other corticosteroid-responsive diseases, steroids should be avoided until the diagnosis is established, unless severe or life-threatening mass effect is present. Slit-lamp examination and vitreous biopsy might also be helpful, especially if CNS lymphoma is suspected. Other examinations should be done as dictated by findings in the initial workup and on neuroimaging. Neuroimaging methods A first step to avoid diagnostic pitfalls is attentively reviewing all MRI sequences in a standard examination, Lancet Neurol 2006; 5: 937–48 AP-HP Hôpital Pitié-Salpêtrière, Service de Neurologie Mazarin, Universite Paris VI Pierre et Marie Curie, IFR 70, Unite Inserm U711, Paris, France (A M P Omuro MD, J-Y Delattre MD); Departamento de Radiologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil (C C Leite MD); and AP-HP Hôpital Pitié-Salpêtrière, Laboratoire de Neuropathologie Raymond Escourolle, Unité Inserm U711, Paris, France (K Mokhtari MD) Correspondence to: Antonio Omuro, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, 75661 Paris Cedex 13, France antonio.omuro@psl.ap-hop- paris.fr Panel: Elements that may suggest a non-neoplastic diagnosis in patients with brain tumours • Onset in young adults (AIDS and other infectious or inflammatory diseases) • Travel to countries with endemic infectious diseases (cysticercosis, hydatidosis, amobiasis) • Sexual risk behaviour (AIDS, syphilis) • IV drug addiction (AIDS, syphilis, brain abscess) • History of contact with tuberculosis • Personal or family history of autoimmune/inflammatory diseases (multiple sclerosis, Behçet, sarcoidosis) • Chronic fever, recent dental procedures or ears/nose/throat infections (brain abscesses) • Immunosuppression, including diabetes (opportunistic infections) • History of subtle and transient neurological deficits, including transient visual symptoms (multiple sclerosis) • Presence or history of oral and genital ulcers (Behçet, syphilis) and uveites (Behçet) • Dental abscess (brain abscess); oral candidiasis (AIDS, immunosuppression) • Skin rashes (Behçet, sarcoidosis, AIDS) • Abnormalities on body CT scan (sarcoidosis, tuberculosis, fungal infections, cysticercosis) • Good control of systemic cancer and absence of lung metastases (argues against brain metastases in patients with history of cancer)