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Year : 2012  |  Volume : 22  |  Issue : 1  |  Page : 58-62
Multifocal intracranial astrocytoma in a pediatric patient with Ollier disease

1 Department of Diagnostic Imaging, National University Hospital, Singapore
2 Department of Pathology, National University Hospital, Singapore

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Date of Web Publication26-Apr-2012


Ollier disease (OD) is a subtype of enchondromatosis. Historically, it has been distinguished from Maffucci syndrome (MS) by the presence of vascular malformations and nonskeletal neoplasms (NSN) in the latter. However, there is an increasing number of reports of NSN in OD, and this categorization is now being questioned. We report a case of OD complicated by multifocal astrocytoma in a young patient, once again pointing to a possible association between OD and NSN. We also review the available literature and examine the similarities between the reported cases.

Keywords: Astrocytoma; IDH1 mutation; multifocal; Ollier disease

How to cite this article:
Bathla G, Gupta S, Ong CK. Multifocal intracranial astrocytoma in a pediatric patient with Ollier disease. Indian J Radiol Imaging 2012;22:58-62

How to cite this URL:
Bathla G, Gupta S, Ong CK. Multifocal intracranial astrocytoma in a pediatric patient with Ollier disease. Indian J Radiol Imaging [serial online] 2012 [cited 2020 Dec 4];22:58-62. Available from:

   Introduction Top

Enchondromatosis refers to multifocal hamartomatous proliferation of chondrocytes within the metaphyses of bones. [1],[2] These cartilaginous masses cause thinning of the overlying cortices, with associated shortening and deformity of the bone. Limb length discrepancies and pathological fractures can also occur. [1],[3],[4],[5] Enchondromatosis is a rare, nonhereditary condition that was first described by Maffucci in 1881 in association with venous angiomas. [1],[2],[3],[5],[6] In 1899, Ollier described enchondromatosis in a patient with no evidence of vascular anomalies, known as Ollier disease (OD). [1],[2]

Historically, these entities have been distinguished based on the presence of vascular malformations and nonskeletal neoplasms (NSN) in Maffucci syndrome (MS). [2],[7] With advances in medicine and imaging, more and more cases of OD associated with nonskeletal malignancies are now being discovered. This, coupled with the late discovery of vascular malformations in some of the earlier cases of OD, has led many authors to speculate that these entities are just different manifestations of a common disease process. [1],[4],[6]

Our case, together with the previously reported cases, supports the association between OD and NSN and once again questions the existence of OD and MS as distinct identities.

   Case Report Top

A 16-year-old male presented to the clinic with a 2-week history of intermittent headaches. There were no localizing signs or motor or sensory symptoms. The past history was significant only for known multiple enchondromatosis, which had been diagnosed at 15 years of age after a pathological fracture of the proximal phalanx of his right index finger. The lesions had been localized to the index and middle fingers of right hand in a ray distribution [Figure 1].
Figure 1: Anteroposterior radiograph of the right hand shows multiple expansile, osteolytic lesions involving the metacarpals, proximal and middle phalanges of the right index and middle fingers. There is a pathological fracture (white arrow) involving the proximal phalanx of the right index finger

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We obtained a noncontrast computed tomography (CT) scan [Figure 2], which showed a nonspecific hypodense lesion in the right insular cortex. There was no hemorrhage, calcification, or significant perilesional edema. The patient was subsequently lost to follow-up and no further investigations could be performed at that point. Three years later, however, the patient was admitted following a road traffic accident. Noncontrast CT scan [Figure 3] was done and showed a subdural hematoma (SDH) over the left cerebral convexity. The previously identified lesion in the right insular cortex had increased in size. In addition, there were similar hypodense lesions in the left basifrontal region and the left precentral gyrus.
Figure 2: Initial noncontrast CT scan shows an ill-defined lesion (black arrow) in the right frontal lobe. There is no hemorrhage, calcification, perilesional edema, or significant mass effect

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Figure 3: Noncontrast CT scan obtained 3 years later shows subdural hemorrhage (white arrowheads) along the left cerebral convexity, with associated mass effect. The hypodense lesion involving the right frontal lobe (black arrow) has increased in size

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The patient underwent an emergency craniotomy for the SDH. A subsequent magnetic resonance imaging (MRI) done 1 week later [Figure 4] showed an additional smaller lesion in the right cingulate gyrus. None of these lesions showed contrast enhancement. The possibility of multifocal gliomas was raised. The patient subsequently underwent biopsy of the left high frontal lesion. The initial pathology report, based on hematoxylin and eosin (H&E) staining, showed mild focal increase in cellularity within the sampled tissue [Figure 5]. There was no conclusive evidence of a glioma. Immunohistochemical staining for mutant isocitrate dehydrogenase-1 (IDH1) was subsequently performed and came back positive in the areas of increased cellularity. The final diagnosis was diffusely infiltrative low-grade glioma.
Figure 4 (A, B): MRI done 1 week after evacuation of the subdural hemorrhage. Coronal FLAIR MRI (A) shows areas of signal alteration involving the right frontal lobe (short arrow), cingulate gyrus (arrowhead), and left basifrontal region (long arrow). Axial T2W MRI (B) shows another lesion (arrow) in the region of the left precentral gyrus. Note the interval craniotomy

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Figure 5: Medium-power view (H and E, ×20) shows areas of mildly increased cellularity composed of astrocytic and oligodendroglial cells (lower part of the image) as compared to normal brain parenchyma (upper part of the image)

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Follow-up MRI after 6 months did not show any significant change in the lesions. The patient is being planned for radiotherapy.

   Discussion Top

This patient has multifocal low-grade gliomas with associated OD. Together with the previously reported cases, this again points to an association of OD with cerebral glioma [Table 1].
Table 1: Intracranial neoplasms in patients with Ollier disease

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A retrospective analysis of cases of OD with gliomas reveals that the initial age at diagnosis of intracranial gliomas in these patients ranges from 6 to 46 years (cases 9 and 16, respectively), with a mean age of 23.7 years. This is similar to the observation of Hori et al., who reported that the median age of diagnosis of glioma was 26.4 years. [8] Including the present case, there were five patients within the pediatric age-group (i.e. <18 years). More significantly, 14 out of 19 (73%) patients were aged between 10 and 30 years.

The gender of case 1 was not available; analysis of the remaining 18 cases reveals a male predominance, with a male:female ratio of 2:1 (12 males and 6 females).

Tissue diagnosis was not obtained in two cases (cases 11 and 12). Out of the remaining 17 cases, 2 cases were reported as astrocytoma, with no further subdivision into low or high grade (cases 4 and 15). Of the remaining, six each were low- and high-grade astrocytomas, two were oligoastrocytomas, and one was an oligodendroglioma.

A total of 6 out of 19 cases (31.5%) were multifocal, with more than one noncontiguous lesion. Based on our review, we speculate that this high rate of multifocality is unlikely to be a chance finding and may point to a widespread astrocyte mutation, predisposing them toward malignant change. This is further supported by the fact that OD is believed to be due to postzygotic somatic mutation, which results in a mosaic cell population. This also helps explain the random distribution of enchondromas in both OD and MS. [17] Occurrence of gliomas in identical twins again points toward an underlying genetic predisposition in these patients to develop gliomas. [2],[3]

Evaluation based on the site of lesions showed that in 8 of the 16 cases (50%) there was a distinct frontal lobe lesion, followed by 6 out of 16 cases (37.5%) with brainstem lesions. This is different from non-Ollier astrocytomas, which most commonly involve the temporal lobe. Two cases showed involvement of multiple lobes/extensive disease (cases 7 and 18), while no exact site of involvement was specified in case 15; these three cases were not included in this analysis.

Our patient is the first case where a mutation within the glioma has been identified in a patient with known OD. The IDH1 mutation is seen in up to 75% (range: 50-80%) of grade II and grade III diffuse gliomas and secondary glioblastoma multiforme (75%) and is most common in young patients. [18] Very recently, mutations in the IDH1 gene were also detected in conventional cartilaginous tumors of patients having both single and multiple enchondromas. [19] IDH mutations may provide a common link between gliomas and enchondromas in patients with OD, though this remains speculative at this point.

Mutations involving the parathyroid hormone-related peptide (PTHrP) type 1 receptor (PTHR1) have also been described in patients with OD, but are seen in only about 10% of cases. [20] In the central nervous system (CNS), PTHrP overexpression has been described in normal embryonic and human glial tumors. [21] These findings may point to another common link involving enchondromas and gliomas in patients with OD. Considering the multifactorial etiology of enchondromatosis, we speculate that IDH1 mutations may also account for another subset of OD patients. However, further studies on a larger scale are needed to establish the pathophysiology of OD and associated tumors.

   Conclusion Top

This is the first case report of a multifocal glioma in a pediatric patient, where the underlying genetic mutation was identified. The analysis of available literature shows that patients with OD develop gliomas at a relatively younger age and there is a high rate of multifocality. In addition, involvement of the frontal lobe and brainstem is more common.

The relatively asymptomatic presentation in our case may argue in favor of routine screening of these patients for intracranial gliomas.

   References Top

1.Ranger A, Szymczak A, Hammond RR, Zelcer S. Pediatric thalamic glioblastoma associated with Ollier disease (multiple enchondromatosis): A rare case of concurrence. J Neurosurg Pediatr 2009;4:363-7.  Back to cited text no. 1
2.Hofman S, Heeg M, Klein JP, Krikke AP. Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease: More evidence for non-mesodermal tumor predisposition in multiple enchondromatosis. Skeletal Radiol 1998;27:688-91.   Back to cited text no. 2
3.Chang S, Prados MD. Identical twins with Ollier's disease and intracranial gliomas: Case report. Neurosurgery 1994;34:903-6.  Back to cited text no. 3
4.Ranger A, Szymczak A. The association between intracranial tumours and multiple dyschondroplasia (Ollier's disease or Maffucci's syndrome): Do children and adults differ? J Neurooncol 2009;95:165-73.   Back to cited text no. 4
5.Frappaz D, Ricci AC, Kohler R, Bret P, Mottolese C. Diffuse brain stem tumor in an adolescent with multiple enchondroma­tosis (Ollier's disease). Childs Nerv Syst 1999;15:222-5.   Back to cited text no. 5
6.Mellon CD, Carter JE, Owen DB. Ollier's disease and Maffucci's syndrome: Distinct entities or a continuum. Case report: Enchondromatosis complicated by an intracranial glioma. J Neurol 1998;235:376-8.   Back to cited text no. 6
7.Balcer LJ, Galetta SL, Cornblath WT, Liu GT. Neuro-ophthalmologic manifestations of Maffucci's syndrome and Ollier's disease. J Neuroophthalmol 1999;19:62-6.  Back to cited text no. 7
8.Hori K, Matsumine A, Niimi R, Maeda M, Uchida K, Nakamura T, et al. Diffuse gliomas in an adolescent with multiple enchondromatosis (Ollier's disease). Oncol Lett 2010;1:595-7.  Back to cited text no. 8
9.Becker W, Thron A. Dyschondroplasie mit gliomatosem hirntumor: Oritter histologisch gesicherter fall. Arch Orthop Trauma Surg 1979;93:141-4.  Back to cited text no. 9
10.Rawlings CE 3rd, Bullard DE, Burger PC, Friedman AH. A case of Ollier's disease associated with two intracranial gliomas. Neurosurgery 1987;21:400-3.   Back to cited text no. 10
11.Schwartz HS, Zimmerman NB, Simon MA, Wroble RR, Millar EA, Bonfiglio M. The malignant potential of enchon­dromatosis. J Bone Joint Surg Am 1987;69:269-74.  Back to cited text no. 11
12.Patt S, Weigel K, Mayer HM. A case of dyschondroplasia associated with brain stem glioma: Diagnosis by stereotactic biopsy. Neurosurgery 1990;27:487-91.  Back to cited text no. 12
13.Bendel CJ, Gelmers HJ. Multiple enchondromatosis (Ollier's disease) complicated by malignant astrocytoma. Eur J Radiol 1991;12:135-7.   Back to cited text no. 13
14.Simsek S, Seckin H, Belin D. Ollier's disease with intracranial glioma. Turk Norosirurji Derg 2002;12:66-9.  Back to cited text no. 14
15.Mahafza WS. Multiple enchondromatosis Ollier's disease with two primary brain tumors. Saudi Med J 2004;25:1261-3.   Back to cited text no. 15
16.Koc F, Koc Z. Ollier disease anaplastic mixed oligoastrocytoma: A rare association with brain tumors. Neurosurg Q 2006;4:195-7.   Back to cited text no. 16
17.Walid MS, Troup EC. Cerebellar anaplastic astrocytoma in a teenager with Ollier Disease. J Neurooncol 2008;89:59-62.   Back to cited text no. 17
18.Kloosterhof NK, Bralten LB, Dubbink HJ, French PJ, Van den Bent MJ. Isocitrate dehydrogenase-1 mutations: A fundamentally new understanding of diffuse glioma? Lancet Oncol 2011;12:83-91.   Back to cited text no. 18
19.Amary MF, Bacsi K, Maggiani F, Damato S, Halai D, Berisha F, et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol 2011;224:334-43.  Back to cited text no. 19
20.Pansuriya TC, Kroon HM, Bovee JV. Enchondromatosis: Insights on the different subtypes. Int J Clin Exp Pathol 2010;3:557-69.  Back to cited text no. 20
21.Evliyaoglu C, Carroll R, Folkerth R, Bello L, Bruns DE, Black PM. Parathyroid hormone-related protein and its receptor in human glial tumors. Acta Neurochir (Wien) 2000;142:871-8.  Back to cited text no. 21

Correspondence Address:
Girish Bathla
Department of Diagnostic Imaging, National University Hospital, 5, Lower Kent Ridge Road, Singapore 119 074

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-3026.95406

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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