Solitary demyelinating plaques mimicking brain tumors: A tricky similarity

S Bacigaluppi¹, M Bacigaluppi², G Tredici³,  
¹ Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Monza; Department of Neurosurgery, CTO Hospital, Torino, Italy
² Neuroimmunology Unit, San Raffaele Hospital, Milano, Italy
³ Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Monza, Italy

Correspondence Address:
S Bacigaluppi
Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Monza; Department of Neurosurgery, CTO Hospital, Torino
Italy

Full Text

Recognition is application. Only the knowing recognizes. [1] Medical reports have the role of reporting new findings, discoveries or innovative therapeutic strategies available; identification of a disease and even upstreaming the consideration of differential diagnoses implies the knowledge of their broad spectrum of existence.

In the issue of this journal, Sinha et al.[2] present two cases of tumefactive demyelinating plaques that might indeed help the readers to understand better the importance of extensive neuroradiological imaging when dealing with tumor-like lesions.

Although estimated to have a rare occurrence (1-2/1,000 cases of multiple sclerosis [3] ) and a prevalence of about 3/10 6 inhabitants per year, [4] these figures might indeed be an underestimation if one considers the large number of inflammatory lesions that undergo biopsy. [5] Not to mention the heavy risks and sequels of surgery or, even worse, inadequate pharmacological treatments, that might result in the absence of a proper diagnosis.

A variety of terms have been used to define these rare cases of demyelination, including Marburg's disease, Balo's concentric sclerosis, transitional sclerosis, pseudotumoral multiple sclerosis and diffuse myelinoclastic sclerosis. This somehow leads to the lack of uniform nomenclature and definition of the common denominator in terms of clinical and neuroradiological features.

These challenging tumefactive lesions can present with neuroradiological features mimicking brain tumors (subcortical localization, solitary lesions, ring-like or patchy contrast enhancement) and a neurological onset atypical for multiple sclerosis (MS). The atypical clinical pictures can include bilateral optic nerve involvement, signs of intracranial hypertension, psychiatric manifestations, seizures, aphasia, apraxia and less commonly normal cerebral spinal fluid analysis or at least atypical for MS. [6],[7]

In the past years, efforts have been carried out to try to identify these lesions. To cite a remarkable example, Poser listed a series of clinical criteria to identify a well-described variety of these solitary demyelinating tumor-like lesions, known under the eponym of Schilder's disease. [7] Nonetheless, these criteria do not always allow to rule out a brain tumor and need to be complemented. [6]

Going back to the possible diagnostic pitfalls, a first problem is the knowledge of symptoms (mostly atypical for MS) at presentation and neuroradiological findings (some hints are absence of mass effect, presence of one or two subcortical cyst-like lesions with open-ring contrast enhancement), suggestive of tumefactive demyelination and not of brain tumors. Being aware of these aspects in differential diagnostics enables the application of non-invasive clinical and imaging criteria for non-invasive diagnosis of these kinds of lesions. [6]

A good example for this situation is provided by the second case described by Sinha et al., where the presence of mass effect for a brain lesion of 4.8 cm with rim enhancement was initially misleading: the potential presence of a demyelinating lesion was not considered and the path of invasive diagnosis was chosen too early. [2]

Bearing in mind the presence of simulators in front of atypical demylinating features should possibly lead to deeper neuroradiological investigations before considering any surgical decision as brain biopsy for diagnostic purposes or even resection. Furthermore, recently revised data pointed out that even histologic analysis (given the hypercellular nature of the lesion and the common presence of atypical reactive astrocytes, mitotic figures [5] and, often, absence of standard myelination stainings in standard tumor histopathological protocols) [8] is not always explanatory for proper diagnosis. [6]

Are imaging studies capable of helping the clinician in this delicate differential diagnosis? Again, Sinha et al.[2] in the first case presented in this issue exemplify the potentiality of an extensive imaging in clarifying the diagnosis.

In fact, although some neuroradiological features seem reliable identifiers of patients harboring tumefactive demyelinating lesions rather than brain tumors, only a very careful and complete workup allows to rule out other causes. [6],[9]



Increased ADC and increased DWI on MRI can help in ruling out an abscess and an ischemic lesion. [10],[11]The presence of N-acetylaspartic-acid on MRI spectroscopy rules out metastasic lesions. [12]No increase in relative cerebral blood flow excludes a malignant brain tumor. [13]The glutamate/glutamine peak rules out a lymphoma. [12]

The use of a combination of different imaging techniques to pin down a differential diagnostic decisional tree is always helpful and might have been mentioned in the first case described by Sinha et al., [2] where, indeed, neuroradiological features allowed non-invasive diagnosis.

However, it is also worth to remember that advancement of neuroradiological diagnosis relies also on histological correlates: cases where histology was obtained together with a comprehensive neuroradiological study allow to strengthen the reliance on the non-invasive diagnostic path.

Finally, the good clinical and radiological response after corticosteroids further might contribute to confirm the correct diagnosis in the involved patient. [6],[14]

The two cases reported by Sinha et al.[2] not only serve as a very concrete reminder of a rare, often ignored differential diagnosis but also offer an opportunity to discuss on a wider scale the prognosis of these patients.

As little follow-up of patients with tumefactive demyelinating lesions is known and the evolution of the disease is relatively inhomogeneous and wide ranged, a large multicentric, prospective data collection protocol, including also an extensive follow-up time, would be highly desirable to understand more of this challenging demyelinating inflammatory disease of the central nervous system.

References