|LETTER TO THE EDITOR
|Year : 2015 | Volume
| Issue : 4 | Page : 660-662
Aggressive spinal glioblastoma in a child with adrenocortical adenoma - Case report and review of literature
J Anam1, K Uday2, P Shetty1, A Moiyadi1, S Epari3, R Jalali2
1 Department of Neurosurgery, Neuro Oncology Group, Tata Memorial Center, Mumbai, Maharashtra, India
2 Department of Radiation Oncology, Neuro Oncology Group, Tata Memorial Center, Mumbai, Maharashtra, India
3 Department of Neuro Pathology, Neuro Oncology Group, Tata Memorial Center, Mumbai, Maharashtra, India
|Date of Web Publication||10-Mar-2016|
Department of Neurosurgery, Neuro Oncology Group, Tata Memorial Center, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Anam J, Uday K, Shetty P, Moiyadi A, Epari S, Jalali R. Aggressive spinal glioblastoma in a child with adrenocortical adenoma - Case report and review of literature. Indian J Cancer 2015;52:660-2
|How to cite this URL:|
Anam J, Uday K, Shetty P, Moiyadi A, Epari S, Jalali R. Aggressive spinal glioblastoma in a child with adrenocortical adenoma - Case report and review of literature. Indian J Cancer [serial online] 2015 [cited 2019 Dec 6];52:660-2. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/660/178392
Adrenocortical tumors in children present very early in the course as functioning tumors. Following a radical resection, most of these tumors achieve long term local control with very good prognosis. Metastasis to neuraxis from an adrenocortical tumor is extremely rare. Spinal tumors in children are mostly ependymomas (myxopapillary variant) followed by astrocytomas. High-grade gliomas do occur in the younger age group but are usually of ependymal origin. Spinal glioblastoma is a relatively rare entity in children less than 10 years of age. We report a rare occurrence of aggressive spinal glioblastoma with ependymal differentiation in a child associated with an adrenocortical adenoma.
| » Case Report|| |
A 9-year-old girl was brought to our outpatient services with a short history of paraplegia and bladder and bowel incontinence.
Four years ago at her age of 5 years, the child had been evaluated for virilizing symptoms and clitoromegaly at another institution, and imaging of the abdomen had revealed a right adrenal mass measuring 2.7 cm × 2 cm in size, for which she had undergone laparoscopic adrenalectomy. The histopathological review confirmed it to be an adrenocortical adenoma. There were no high-risk features identified in the histopathology, and post-operative hormonal levels were found to be within normal limits. The child was asymptomatic for four years.
At presentation to our center, the child had complete paraplegia and a sensory level at D8 with loss of peri-anal sensation. There was discrete left cervical lymphadenopathy. An MRI of the spine showed a diffuse intramedullary mass lesion extending from D6 to D10 with cord expansion. There was heterogenous enhancement and few extramedullary-intradural small focal lesions noted at L1-L4 and at S4 levels with similar contrast-enhancing patterns representing skip lesions [Figure 1] and [Figure 2]. There was diffuse dural thickening from C1 to sacrum, which showed heterogenous enhancement. Radiologically, it seemed more to be a high-grade embryonal tumor or a high-grade glial neoplasm with leptomeningeal deposits. However, in keeping with the history of a previous adrenal tumor, metastatic deposits could not be completely excluded.
|Figure 2: The sagittal section of the thoraco lumbar spine with enhancing nodules|
Click here to view
CSF cytology was negative for malignancy, and hence, open biopsy was planned. At surgery, the cord was diffusely expanded with a small exophytic component of the tumor, which was biopsied. Subsequently, an imaging of brain was performed, which did not show any abnormality. Final histopathology showed atypical round cells with areas of necrosis and microvascular proliferation and frequent mitosis. Typical ependymal-like rosette were not seen [Figure 3]. On immunohistochemistry, the tumor showed positivity for glial fibrillary acidic protein (GFAP) and weak positivity for Mic-2. The tumor was negative for synaptophysin, desmin, and AE1/AE3. INI-1 was retained, and the MIB labeling index was 15-20%. There was positive immunostaining of P53 [Figure 4]. Based on histo-morphological features, the diagnosis of glioblastoma with focal anaplastic ependymal differentiation was made.
|Figure 3: Photomicrographs showing a cellular tumor of the tumor composed of oval to elongated cells (a x200) with cellular crowding (b x200), microvascular proliferation (b x200; as shown by star symbol), mitotic activity (c x400; encircled), and confluent necrosis (d x100)|
Click here to view
|Figure 4: Representative photomicrographs of the tumor with immunopositivity for glial fibrillary acidic protein (a x200; inset x400), negativity for epithelial membrane antigen (EMA: b x200), positivity for p53 protein (c x200), high MIB-1 labeling index (d x200), and retained INI protein (e x200)|
Click here to view
In view of extensive and aggressive disease, the patient was planned for palliative radiotherapy. However, the parents opted for best supportive care only.
| » Discussion|| |
Adrenocortical adenoma is extremely rare in children. Although a bimodal age distribution has been described with the first peak in children less than 5 years of age, this is seen in less than 5% of the cases, and the median age of occurrence is 45 years. At presentation, most of them are functioning tumors, and these pediatric adrenal adenomas have very good prognosis compared to non-functioning tumors and those tumors in adults. Adrenal adenomas occurring in children present more commonly as the virilizing syndrome. Thirty-six percent of adrenal adenomas in children are p53-positive. Occurrence of P53 immunopositive, high-grade glial neoplasm in the spinal cord of a young child with previous history of adrenocortical adenoma raises a possibility of abnormality in the gene function of TP53.
Germline mutations of TP53 (Li Fraumeni Syndrome),, although are known to present with adrenal carcinomas and not adenomas (along with other cancers like sarcomas and gliomas), it raises a strong suspicion that the initial diagnosis of the child was probably an adrenal carcinoma rather than an adenoma. However, in view of a long disease-free interval of about 5 years between occurrence of adrenal adenoma and spinal cord glioblastoma, this is unlikely.
Description or reporting of a high-grade spinal cord neoplasm associated with an adrenal adenoma in a young child is very rare. Spinal cord tumors and the tumors of the cauda equina constitute 4.8% of all the CNS tumors. Among the age group of 0-19 yrs, spinal glioblastoma forms 11.9% and spinal ependymoma form 23% of the cases. In spinal location and in pediatric age group, low grade tumors predominate over high grade that constitute only 10-15% of the cases, and in this, primary glioblastoma of the spine is seen in only 2-3%. Literature on the spinal GBM in children is very sparse, and there are only few old case reports that explain the occurrence, characteristics, and treatment of these rare and very aggressive tumors. Spinal GBM are more commonly seen in the cervicothorasic location when compared to ependymoma, which is usually seen in the conus medullaris.
Holocord involvement of spinal GBM is an extremely rare entity. There is usually, however, presence of extensive intra-cranial disease. In view of the extensive ependymal differentiation, the closest pathological differential was ependymoma. Histological hallmarks of ependymoma are perivascular rosettes, arranged radially around the blood vessels and which are usually not seen in highly cellular or when the tumor cell density is low and the other hallmark is presence of ependymal rosettes. Ependymomas are positively labeled for GFAP and vimentin. Anaplastic ependymomas are histologically characterized by mitoses >4/10 hpf, hypercellularity, endothelial proliferation and necrosis, and presence of any two of these features attributes a very poor prognosis. Giant cell glioblastoma is the closest differential diagnosis to giant cell ependymoma, and there is only one case report of spinal giant cell glioblastoma.
| » Conclusion|| |
Pediatric spinal glioblastoma is a very rare entity, and holocord dissemination and ependymal differentiation leads to a worse prognosis. Whether the association with an adrenal tumor is coincidental is unclear.
| » References|| |
Stratakis CA, Chrousos GP. Adrenal cancer. Endocrinol Metab Clin North Am 2000;29:15-25.
Nichols KE, Malkin D, Garber JE, Fraumeni JF Jr, Li FP. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev 2001;10:83-7.
Pantziarka P. Li Fraumeni syndrome, cancer and senescence: A new hypothesis. Cancer Cell Int 2013;13:35.
Frebourg T, Abel A, Bonaiti-Pellie C, Brugières L, Berthet P, Bressac-de Paillerets B, et al
. [Li-Fraumeni syndrome: Update, new data and guidelines for clinical management]. Bull Cancer 2001;88:581-7.
Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol 2012;14 Suppl 5:v1-49.
Houten JK, Cooper PR. Spinal cord astrocytomas: Presentation, management and outcome. J Neurooncol 2000;47:219-24.
Ciappetta P, Salvati M, Capoccia G, Artico M, Raco A, Fortuna A. Spinal glioblastomas: Report of seven cases and review of the literature. Neurosurgery 1991;28:302-6.
Cohen AR, Wisoff JH, Allen JC, Epstein F. Malignant astrocytomas of the spinal cord. J Neurosurg 1989;70:50-4.
Mori K, Imai S, Shimizu J, Taga T, Ishida M, Matsusue Y. Spinal glioblastoma multiforme of the conus medullaris with holocordal and intracranial spread in a child: A case report and review of the literature. Spine J 2012;12:e1-6.
Ho DM, Hsu CY, Wong TT, Chiang H. A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma. J Neurooncol 2001;54:77-85.
Adamek D, Dec M, Sobol G, Urbanowicz B, Jaworski M. Giant cell ependymoma: A case report. Clin Neurol Neurosurg 2008;110:176-81.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]