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|Year : 2020 | Volume
| Issue : 3 | Page : 657-659
A Case of Ollier's Disease with P53 Mutation Positive and IDH1 (R132H) Negative Multicentric Gliomas
Y Nishtha1, B Maya1, Safal S Shetty2, VH Ganaraj2, P Nupur3, TC Yasha4, M Netravathi2
1 Department of Neuroimaging and Interventional Neuroradiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
2 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
3 Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
4 Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
|Date of Web Publication||6-Jul-2020|
Dr. M Netravathi
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka - 560 029
Source of Support: None, Conflict of Interest: None
Ollier disease is a rare nonhereditary disorder characterized by multiple enchondromas (enchondromatosis). To report a rare case of Ollier disease with gliomas and its mutation analysis. We hereby report a young lady who presented with seizures. She had a past history of multiple bony swellings in the right foot (operated) and swelling over the anterior chest wall for the past 15 years. MRI brain revealed multiple expansile T2/FLAIR hyperintense lesions in right superior and middle frontal gyri, left basifrontal lobe, and left precuneus in the cortical–subcortical location suggestive of glioma. She underwent biopsy which revealed left basifrontal anaplastic astrocytoma, not otherwise specified, WHO grade III, IDH1 (R132H) negative, P53 mutation positive, and ATRX loss of expression. We hereby report a rare case of Ollier disease with multicentric intracranial glioma—IDH1 (R132H) negative, P53 mutation positive, and ATRX loss of expression.
Keywords: Astrocytoma, enchondromas, glioma, Ollier disease
Key Messages: We report a rare case of Ollier disease with multicentric intracranial gliomas, with less than 10 cases having molecular diagnosis and mutation analysis.
|How to cite this article:|
Nishtha Y, Maya B, Shetty SS, Ganaraj V H, Nupur P, Yasha T C, Netravathi M. A Case of Ollier's Disease with P53 Mutation Positive and IDH1 (R132H) Negative Multicentric Gliomas. Neurol India 2020;68:657-9
|How to cite this URL:|
Nishtha Y, Maya B, Shetty SS, Ganaraj V H, Nupur P, Yasha T C, Netravathi M. A Case of Ollier's Disease with P53 Mutation Positive and IDH1 (R132H) Negative Multicentric Gliomas. Neurol India [serial online] 2020 [cited 2020 Aug 10];68:657-9. Available from: http://www.neurologyindia.com/text.asp?2020/68/3/657/288998
Ollier disease is a rare (1:100,000) disorder, characterized by multiple enchondromatosis and dysplastic cartilage. Enchondromatosis has been known to have an association with malignancy, including angiosarcomas, osteosarcomas, various central nervous system tumors, ovarian tumors, and leukemias. The association of Ollier disease with intracranial gliomas is very rare, with less than 30 cases reported so far. We report a case of Ollier disease with multicentric intracranial gliomas, with mutation analysis showing IDH1 (R132H) negative, P53 mutation positive, and ATRX loss of expression.
| » Case Report|| |
A 27-year-old woman presented with a history of four episodes of generalized tonic-clonic seizures in eight months. She had a history of multiple bony swellings in the right foot (for which she was operated 15 years back). The histopathology of the operated bony lesions were not available. MRI brain revealed multiple expansile T2/FLAIR hyperintense lesions in the right superior and middle frontal gyri, left basifrontal lobe, and left precuneus in the cortical–subcortical location [Figure 1]. The T2 hyperintense lesion was noted in manubrium sterni, with multiple similar small T2 hyperintense lesions noted in the right coracoid process and left acromion process. Hand X-ray revealed a geographic lytic lesion with well-defined transitional zone in the distal metaphysis of the right radius. Therefore, a possibility of Ollier disease with multicentric gliomas was considered and biopsy from the right superior-middle frontal gyrus lesion was suggested.
|Figure 1: Images showing lesion in the right frontal lobe that was biopsied. T2W axial image (a) shows the presence of T2 hyperintense lesion with ill-defined margins and surrounding edema. On T1W image, (b) the lesion is hypointense and shows the areas of suppression on FLAIR (c). No area of blooming noted on susceptibility weighted imaging (d). No diffusion restriction noted as shown on trace image (e) and ADC map (f). No contrast enhancement was noted (g). No area of raised perfusion was seen (h). Multiple well-defined expansile bony lesions were identified upon spine screening, involving manubrium sterni (i), right coracoid process (j), and left acromion process (k). The lesions are hyperintense on T2, with areas of hypointensity within, suggestive of chondroid matrix. Hand radiograph (l) revealed geographic lytic lesion involving distal radius with narrow zone of transition|
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Biopsy revealed infiltrating glial neoplasm composed of pleomorphic gemistocytic astrocytes and protoplasmic astrocytes dispersed over a glial fibrillary stroma [Figure 2]. These cells showed nuclear atypia, hyperchromasia, multinucleation and brisk mitosis. Immunohistochemistry revealed negative IDH1 (R132H), loss of expression of ATRX, positive P53, and an MIB labelling index of 10%. It was diagnosed as anaplastic astrocytoma of WHO grade III, IDH1 (R132H) negative, and ATRX loss of expression.
|Figure 2: Anaplastic astrocytoma. (a) Moderately cellular glial tumor with fibrillated, pleomorphic, and gemistocytic cells in a fibrillary stroma. (b) The loss of normal nuclear expression of ATRX in the tumor cells, indicating ATRX gene mutation. (c) Tumor cells are negative for IDH1-R132H, a proxy marker for IDH1 R132H mutation. (d) Positive staining for p53. (e) High Ki67 (MiB1) proliferation index. (a: HE; b-e: Immunohistochemistry; Original magnification: a-d X200; e: X100)|
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| » Discussion|| |
Enchondromatosis primarily affects the long bones and cartilage of the joints of the arms and legs, specifically at the metaphysis and is divided into six types. Type I (Ollier disease) consists of multiple enchondromas of tubular and flat bones. Type II (Mafucci syndrome) is defined by multiple enchondromatosis associated with the soft tissue hemangiomas, typically sparing the spine. Type III (metachondromatosis) is characterized by enchondromas and digital osteochondromas. Type IV (spondyloenchondrodysplasia) consists of enchondromas of the bones and spinal dysplasia. Type V is defined by bone and vertebral body lesions with minimal hand involvement, and Type VI has severe hand and foot lesions and erosion of the iliac crests.
A retrospective analysis of 19 cases of Ollier disease with gliomas by Bathla et al. revealed that the clinical manifestations often appear in the first decade of life and usually start with local pain, bone swelling, and palpable bony masses, which is often associated with the bone deformity. They noted that in 50% cases there was a distinct frontal lobe lesion, followed by brainstem lesions in 37.5%. This was different from non-Ollier astrocytomas that most commonly involve the temporal lobe. Our patient also was found to have frontal predominant distribution with multicentric glioma. Charlotte Bonnet et al. summarized clinical, histological, and molecular characteristics of patients of Ollier's disease and Maffucci syndrome. They found that including the previous studies, 32% had multicentric gliomas. IDH mutations were assessed in eight cases and detected in seven patients (IDH1 R132H in five patients; IDH2 R172S in two patients). In the negative case, no expression of IDH1 R132H was detected on immunohistochemistry, which was also the case with our patient. P53 expression was noted in our patient and previously it was studied in six patients and found to be present in five patients.
Ollier disease and Maffucci syndrome have been shown to have a mutation in IDH1 or IDH. In animal models, IDH mutations have been shown to be sufficient to induce enchondromas and chondrosarcomas. IDH mutations are considered to be the earliest oncogenic events in the majority of low-grade gliomas. The occurrence of gliomas in enchondromatosis patients, in whom IDH mutations are thought to occur as an early post-zygotic event suggests that IDH mutations can initiate glioma genesis. In contrast to enchondromas, IDH mutation alone is probably not sufficient to induce gliomas and additional alterations such as ATRX and P53 mutations are necessary. This could explain why enchondromas appear much earlier than gliomas in patients with enchondromatosis.
Only a few reported cases are available with the molecular analysis of gliomas associated with Ollier disease. To the best of our knowledge, our case is the 13th reported case with multicentric gliomas with Ollier's disease with less than 10 cases having a molecular diagnosis and mutation analysis. Our case adds to the knowledge of the pattern of mutation on immunohistochemistry in this very rare association of gliomas in patients with Ollier's disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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