J Neurooncol (2016) 128:373–375 DOI 10.1007/s11060-016-2118-9
LETTER TO THE EDITOR
Diffuse astrocytoma arising within a demyelinating plaque David Ryan Ormond1 • B. K. Kleinschmidt-DeMasters2
Received: 10 December 2015 / Accepted: 23 March 2016 / Published online: 31 March 2016 Ó Springer Science+Business Media New York 2016
To the Editor, The co-occurrence of astrocytomas and multiple sclerosis (MS) is an uncommon, but well reported phenomenon [1, 2]. Our group recently reported the genetic features of eight well characterized patients with co-existent glioma and multiple sclerosis and found no unique genetic features in tumors from MS patients [1]. None of those cases showed a definitive relationship between the tumor and a demyelinative lesion. However, since the 1980s, there has been speculation that chronic gliosis in demyelinative plaques may predispose to secondary induction of a glial neoplasm [2]. Malmgren et al. reviewed 25 cases in the literature, specifically looking for features that might link the two disorders: contiguity of glioma and MS plaques, neoplastic transformation of astrocytes within MS plaques, multicentricity of gliomas, increased proportion of an astrocytic type of glioma, temporal sequence of MS and glioma, possible increased rate of gliomas in MS patients, and a biological plausibility of a causal relationship [2]. They concluded that ‘‘there currently is no reason to believe that the lesions of multiple sclerosis promote the development of gliomas’’ [2].
& David Ryan Ormond
[email protected] 1
Brain Tumor Program, Department of Neurosurgery, University of Colorado School of Medicine, 12631 E. 17th Avenue, Mail Stop C307, Academic Office 1, Room 5001, Aurora, CO 80045, USA
2
Department of Pathology, University of Colorado School of Medicine, 12631 E. 17th Avenue, Mail Stop C307, Academic Office 1, Room 5001, Aurora, CO 80045, USA
Herein, we report a case of diffuse low-grade astrocytoma with strong IHC expression for both IDH1 and p53 arising at the edge of a definitive small ovoid demyelinative plaque, fulfilling a major criterion of Malmgren et al., and suggesting that, at least in some cases, chronic gliosis in demyelinative plaques may result in neoplastic astrocytic transformation.
Case description A 30-year-old woman presented with a history of right facial numbness that improved slowly over several months with one relapse involving numbness in her hands and arms. Workup included MRI Brain without and with gadolinium where 13 lesions were found in the brain, including five periventricular lesions, three juxtacortical lesions, two infratentorial lesions and one T1 hypointense lesion. There was also a single enhancing lesion in the left frontal lobe, showing simultaneous asymptomatic enhancing and nonenhancing lesions in a single scan. Later imaging showed resolution of many of these lesions, but the persistence of a nonenhancing juxtacortical lesion that continued to grow and expand the gyrus (Fig. 1a). Spine imaging was not performed. She fulfilled 2010 International Panel criteria for the diagnosis of MS, but had not started therapy since clinical symptoms had resolved spontaneously and the patient had sought a second opinion regarding treatment options. During routine follow-up imaging, it was noted that while other lesions showed exacerbations and remissions, as expected, one lesion in the left parietal lobe continued to increase in size, expanding the gyrus, concerning for glioma. It did not enhance with contrast. She underwent surgical excision of this lesion.
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J Neurooncol (2016) 128:373–375
Fig. 1 Diffuse astrocytoma shown arising within a demyelinating plaque
Surgical resection material demonstrated small ovoid demyelinative lesions with myelin loss on Luxol fast blueperiodic acid Schiff (PAS) stain (Fig. 1b) and myelin basic protein IHC (Fig. 1c), consistent with multiple sclerosis. Hypercellularity throughout the plaque due to macrophage
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influx (Fig. 1b) matched by strong CD68 IHC? and PASpositive macrophage debris indicated active myelin breakdown. Individual diffuse astrocytoma tumor cells appeared to ‘‘spin off’’ the perimeter of the active demyelinating plaque, with tumor definitively identified on
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strong p53 (Fig. 1d) and IDH1 (isocitrate dehydrogenase 1) IHC (Fig. 1e). Macrophages did not appear to contain IDH1 immunoreactive debris. IDH1 IHC unequivocally distinguishes diffuse glioma from gliosis [3]. Moderate numbers of tumor cells individually-infiltrated the adjacent gray matter, likely explaining the abnormal MRI cortical signal (see Fig. 1a). Cytological atypia was minimal, mitotic activity and MIB-1 cell cycle labeling rate were low (2.7 %), nuclear ATRX was retained, and CD3 highlighted non-neoplastic T cell lymphocytes in perivascular and parenchymal areas of active plaque. At least three smaller perivenular chronic, inactive hypocellular plaques were also identified in the same specimen (Fig. 1f), but these showed no increased numbers of IHC? tumor cells at their perimeter. Thus, there was no tropism for the tumor cells to these chronic inactive plaques. Following gross total resection, she has been followed for 14 months with surveillance neuroimaging, is thus far stable, and has not required further surgery or adjuvant treatment. While a single case is never definitive in proving causation for a disease, this case does raise the possibility that
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at least a rare glioma may arise directly from a demyelinative lesion. Of more importance, the case highlights the fact that MS patients who have expanding lesions without the expected fluctuation and remission should be watched carefully and considered for early biopsy to exclude glioma.
References 1. Khalil A, Serracino H, Damek DM, Ney D, Lillehei KO, Kleinschmidt-DeMasters BK (2012) Genetic characterization of gliomas arising in patients with multiple sclerosis. J Neurooncol 109(2):261–272 2. Malmgren RM, Detels R, Verity MA (1984) Co-occurrence of multiple sclerosis and glioma—case report and neuropathologic and epidemiologic review. Clin Neuropathol 3:1–9 3. Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J (2010) Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol 34(8):1199–1204
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