Title: Low grade astrocytoma presenting as brain "stone”
Hsiao-Yue Wee1, Jinn-Rung Kuo1,2, Yao- Lin, Lee1, Tzu-Ju, Chen3, Yi-Ying, Lee3
1
Departments of 1Neurosurgery Chi-Mei Medical Center, Tainan, Taiwan
2
Department of Biotechnology, Southern Taiwan University of Science and
Technology, Tainan, Taiwan
3
Departments of pathology Chi- Mei Medical center, Tainan, Taiwan
Corresponding Author: Jinn-Rung Kuo, MD, Department of Neurosurgery, Chi-Mei
MedicalCenter, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan 710
Title: Low grade astrocytoma presenting as brain “stone”
Abstract
We present a 21-year-old male patient with a history of generalized-tonic-clonic
seizure induced by a near completely and densely calcified intra-axial tumor located
at the left frontal lobe. The tumor displayed a heretofore unpublished combination of
extensive ossification and calcification with minimal cytologic atypia and positive
findings for glial fibrillary acidic protein. The final diagnosis was intracerebral low
grade astrocytoma. This is an extremely rare tumor in the literature.Here, we also
review similar cases, as well as mechanisms of tumor calcification, and the current
treatment of low grade astrocytoma.
Key Words: Low grade astrocytoma, seizure, ossification, metaplastic
Introduction
The image appearance of low grade astrocytoma (LGA) in computed tomography
usually presents with a low density intra-axial lesion with or without minor
calcification. The MRI image usually presents with low T1 signal and high T2 signal
without obvious enhancement. Low grade astrocytomas are the most common
glialneoplasms to demonstrate calcifications (oligodendroglioma account for 90%,
pilocystic astrocytoma account for 25% and other LGAs are rare), but only calcified
in minor parts of these tumors 1. However, it is rare for low grade astrocytomas to
present as a near completely and densely calcified lesion whether in macro or
microscopic proportion.
The etiology of intracranial calcification includes physiologic, posttraumatic and
dystrophic, such as congenital disorders, vascular disorders, infections, inflammatory
disorders, metabolic disorders and tumors.1 In fact, intracranial calcification seen on
computed tomography is a common finding in the everyday practice of a
1
neurosurgeon. However, some intracranial calcifications may be critical to the
diagnosis of the underlying pathology.
As with our case, the near completely calcified intra-axial lesion could be due to
neoplastic processes rather than benign physiological processes. Although some
idiopathic brain stones without any pathological change have been reported,2 we have
confirmed a pathological diagnosis for the calcified intra-axial lesion. According to
current literature reviews, surgical treatment rather than observation is favored in the
current treatment of LGA.3,4
Case Report
A previously healthy 21-year-old man presented to the emergency department with
acute onset generalized tonic-clonic seizure. Neurological examination showed no
abnormalities. Brain computer tomography (CT)(Fig. 1a) showed a right frontal
subcortical calcified lesion. Contrast-enhanced T1 weighted magnetic resonance
imaging (Figure 1b) demonstrated a heterogeneously enhanced mass, and T2weighted magnetic resonance imaging (Figure 1c) showed the lesion was surrounded
with equivocal dark signal (suspect old hemosiderin deposition related to previous
hemorrhage) and minimal adjacent superior frontal gyrus edematous change.
He underwent a total surgical resection by utilizing a frontal approach under the
impression of oligodendroglioma or cavernous hemangioma. The tumor was adherent
to the surrounding frontal lobe with a hard consistency but no prior hemorrhage could
be found.
The pathology disclosed tumor fragments with extensively ossification and
calcification (Fig. 2), leaving several reserved foci of vague fascicles of spindle cells
with minimal cytologic atypia. Neither mitotic activity nor necrosis was found. In the
immunohistochemical study, the positivity of glial fibrillary acidic protein (GFAP)
(Fig. 3) demonstrated the glial cell nature of the tumor cells. Also, the tumor cells in
this case did not express the honeycomb appearance (monomorphic cells with
uniform round nuclei and perinuclear halo) characteristic for oligodendroglioma.
According to the bland-looking nuclear appearance and the young age of the patient,
the final diagnosis was intracerebral metaplastic LGA with extensive ossification and
calcification. The course of the patient’s operation was smooth, and the patient was
discharged 7 days after its completion.
2
Discussion
Low grade astrocytoma, a primary brain tumor, accounts for 15% of all adult brain
gliomas. Peak incidence occurs in young adults, with a male predominance, and
epilepsy is the most common presenting symptom in all cases. Our case is consistent
with previous epidemiological studies and clinical manifestation.
The special feature of this case is a LGA presenting as near completely and densely
calcified intra-axial lesion. According to literature review, calcification may be in the
form of calcospherites or as deposits within the microvasculture of the neoplasm.
Calcification can occur anywhere within neoplasm, but is especially common where
the tumor has infiltrated into the cortical gray matter, where it may form an irregular
gyriform ribbon. Classically, four morphological types of glial pathological
calcification may be distinguished on plain skull x-ray i.e. localized, diffuse, multiple
scattered and multiple symmetric.5
There are some theories about the tumor calcification.6 Mukade et al. suggested
that intratumoral bleeding and secondary degeneration of tumor cells may initiate
dystrophic ossification. Ke et al. stated that tumor calcification may be due to a
secondary ischemic effect induced by tumor compression, which may result in the
proliferation of mesenchymal cells and initiation of the differentiation process of
progenitor cells into osteoblasts. Endocrine effects such as elevation of prolactin level
is also associated with enhanced osteogenesis. In addition, maldevelopmental or
embryonal neoplasms with bone arising from misplaced or trapped mesenchymal
cells could also be the cause of tumor calcification. However, it must be noted that
none of these theories can explain the formation of a near completely and densely
calcified LGA compared with previously presented LGAs.
Besides, the calcified LGA might be different from other LGA in nature. Three
cases of massively calcified astrocytomas were classified to another pathology group
in the international society of Pediatric Oncology (SIOP) LGG1 tumor series.7 In the
gene molecular analysis of Gupta at el, no tumor demonstrated an IDH1:p.R132H
mutation, KIAA1549-BRAF duplication, upregulation of MYB expression, or copy
number alterations at the MYB or CDKN2A loci, which are variably associated with
pediatric or adult-type LGGs.7
There have been similar cases reporting completely and densely calcification with
LGA.7,8,9,10 Compared to our case, they presented in a different location (brainstem,
cerebellum, ventricle, medial temporal lobe and spinal cord), and some of these
reports are mixed with other tumors such as ependymoma, cartilage and cystic
3
formations in histologic feature, and some cases are of a younger group.
Current treatment of low grade astrocytoma favors early radical surgical resection,
especially in young individuals and in non-eloquent regions because it has been
increasingly shown to correlate with improved outcome.3,4 Jakola et al. published a
study in JAMA that showed the biopsy and watchful waiting group tend to have more
malignant transformations than the resection group (56% vs 37%, P=0.02%) in ten
years.3 Although a calcified LGA may differ from other LGA, its outcome still lacks
long term observation. As LGA has the potential risk of malignant change, early
surgery with radical resection is still favored.
Conclusion
In the present case, we want to emphasize that among patients with near
completely calcified intra-axial lesions whether macro or microscopic, that the
possibility of low grade astrocytoma must be considered. Early radical resection is
favored in young patients and in non-eloquent brain areas, as the procedure could be
safely done without morbidity and with decreased potential risk of malignant change
in our case.
Figure Legends
Figure 1a
Brain CT shows a calcified mass in the left frontal lobe
Figure 1b Contrast-enhanced T1 weighted magnetic resonance imaging demonstrates
a heterogeneously enhanced mass
Figure 1c T2- weighted magnetic resonance imaging shows the lesion surrounded
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with equivocal dark signal (suspect old hemosiderin deposition related to previous
hemorrhage) and minimal adjacent superior frontal gyrus edematous change.
Figure 2.Tumor seen at low power showing cellular areas (arrow head) with areas of
extensive ossification (thick arrow) and calcification (thin arrow), x 200
Figure 3.Section of the tumor was stained with anti- Glial fibrillary acidic protein
(GFAP)primary antibodies. The tumor expresses the GFAP positive (arrow) antigen,
x 200
Reference:
1.
Erini Makariou, MD, and Athos D. Patsalides, MD Intracranial Calcification.
Applied Radiology 2009;11:48-60
2.
Hashimoto M, Tanaka T, Ohgami S, Yonemasu Y, Fujita M. A case of idiopathic
brain stone presenting as psychomotor epilepsy. No shinkei geka Neurological
surgery 1986;14:1457-1461.
3.
Jakola AS, Myrmel KS, Kloster R, et al. Comparison of a strategy favoring early
surgical resection vs a strategy favoring watchful waiting in low-grade gliomas.
JAMA : the journal of the American Medical Association 2012;308:1881-1888.
4.
Pedersen CL, Romner B. Current treatment of low grade astrocytoma: a review.
Clinical neurology and neurosurgery 2013;115:1-8.
5.
Gupta V, Singh D, Sinha S, Tatke M, Singh AK, Kumar S. An oligo astrocytoma
with widespread calcification along axonal fibres. Neurology India 2001;49:174-177.
5
6.
Ke C, Deng Z, Lei T, et al. Pituitary prolactin producing adenoma with
ossification: a rare histological variant and review of literature. Neuropathology :
official journal of the Japanese Society of Neuropathology 2010;30:165-169.
7.
Gupta K, Harreld JH, Sabin ND, Qaddoumi I, Kurian K, Ellison DW. Massively
calcified low-grade glioma - a rare and distinctive entity. Neuropathology and applied
neurobiology 2014;40:221-224.
8.
Siomin V, Willinsky R, Shannon P, Guha A. Metaplastic bone formation in a low
grade conus glioma: case report and review of the literature. Journal of
neuro-oncology 2003;62:275-280.
9.
Tamura M, Kohga H, Ono N, et al. Calcified astrocytoma of the
amygdalo-hippocampal region in children. Child's nervous system : ChNS : official
journal of the International Society for Pediatric Neurosurgery 1995;11:141-144.
10. Shuto T, Ohtsubo Y, Sekido K, Iwamoto H, Yamamoto I. Rapidly growing
calcified cerebellar astrocytoma in infants. Child's nervous system : ChNS : official
journal of the International Society for Pediatric Neurosurgery 1996;12:107-109.
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