Key-words:
Collision tumors - glioma - meningioma
Introduction
Glioma and meningioma are the two most common primary intracranial tumors.[[1]] However, the simultaneous development of these tumors at adjacent sites in the same patient without a history of radiotherapy or phakomatosis is extremely rare.[[2]],[[3]],[[4]],[[5]],[[6]] The exact pathogenesis of this condition is still in controversies. Here, we present a case of collision tumors composed of a low-grade glioma and a meningioma. We discuss the challenges in obtaining an accurate preoperative diagnosis for these tumors, as well as review prior reported cases.
Case Report
A 61-year-old female presented with 3 months of progressive headache. Neurological examination at hospitalization revealed mild left hemiparesis.
Magnetic resonance imaging of the brain showed two lesions in the right frontal lobe. One lesion was isointense on T1-weighted images and T2-weighted images and enhanced intensely after gadolinium injection. The second lesion was composed of nonenhancing cysts with a significant amount of surrounding edema [[Figure 1]].
Figure 1: Axial T2-weighted image (left) and axial Tl-weighted image after gadolinium injection (right) revealed a well-defined enhanced tumor and a cystic tumor located at the right frontal lobe
Intraoperatively, the enhancing lesion was found to be an extra-axial tumor attaching to the dura mater and the other lesion was observed to be an intra-axial tumor. Both the lesions were completely removed macroscopically. The patient improved clinically after the surgery and was discharged without any appreciable neurologic deficit. Histological examination of the extra-axial tumor revealed a fibroblastic meningioma [[Figure 2]] and the intra-axial lesion was diagnosed as a Grade II astrocytoma [[Figure 3]]. There was no histological invasion between the two tumors.
Figure 2: H and E staining revealed a fibrous meningioma characterized by parallel fascicles of fibroblastic cells
Figure 3: H and E staining showed a Grade II astrocytoma tumor composed of fibrillary and gemistocytic neoplastic astrocytes on the background of the loosely structured with microcytic stroma
Discussion
Since the first report in 1938, about 67 cases of simultaneous occurrence of meningioma and glioma have been reported in the literature, but the collision of two different histologic tumors in patients without prior radiation therapy or phakomatosis is extremely rare.[[2]],[[3]],[[4]],[[5]],[[7]] The first case of meningioma and glioma collision without a history of radiotherapy or phakomatosis was reported in 1976 by Strong et al.[[8]] We reviewed the literature and found 18 cases reported since then, including 10 males and 8 females with age ranging 12–87 years. Most of the managements for these cases were one-stage tumor removal. Histologically, most of them had high-grade gliomas. The present case is the third case of meningioma and low-grade glioma collision reported. Details of these cases are described in [[Table 1]]. Our understanding of intracranial meningioma and astrocytoma collision remains limited, but several hypotheses have been proposed.
Table 1: Reported cases of collision of meningioma and glioma
Some authors suggest that the initial tumor can act as an oncogenesis agent for the development of the other tumors.[[4]],[[7]],[[21]],[[22]] The tumor growth in these cases follows the autocrinous mechanism, due to the production of growth factor and receptors for these factors. Platelet-derived growth factor (PDGF) is a likely substance.[[21]] It is found that three subunits of PDGF, the PDGF-AA, PDGF-BB, and PDGF-AB, are secreted by astrocytomas.[[23]],[[24]] PDGF-β-R receptor is present in meningioma, and PDGF-BB acting on these receptors is shown to stimulate meningioma cell division.[[21]] As a result, astrocytoma may stimulate adjacent meningioma formation in arachnoid cells by production of a common growth factor. However, this hypothesis fails to elucidate why adjacent meningioma formation does not happen in most cases of the astrocytomas.
Other authors hypothesize that meningiomas may irritate astroglial cells surrounding it, causing local cellular proliferation and eventually tumor formation.[[5]],[[19]] In fact, this hypothesis is supported by a case of collision convexity meningioma and glioma reported by Vaquero et al. in 1990. In this case, histologically, a transient area between the meningioma and the astrocytoma was observed and two kinds of tumor cells were mixed in some areas.[[19]] In 2004, Drlicek et al. reported one case with a meningothelial meningioma WHO-Grade I located within the peripheral glioblastoma WHO-Grade IV, also supporting the above hypothesis.[[16]] Similarly, Prayson reported a meningioma in the sagittal sinus in the frontal lobe and a peripheral glioma invading each other pathologically.[[18]] However, collision tumors without histological invasion have also been reported. For example, in 2007, Nestler et al. reported a case of collision of a meningioma and a glioma, but the histological examination showed no invasion of the tissue between them.[[14]] Tugcu also reported a case of collision of a meningioma and a glioblastoma multiforme at the left parietal cortex without parenchymal invasion.[[5]] We also did not find any histological invasion between the two tumors in our case. This transformation hypothesis fails to explain why adjacent glial formation does not happen in most of the intracranial meningiomas. It also fails to explain the simultaneous occurrence of two distinct tumors in different brain areas.
Genetic factors are also suggested to play a role in the development of collision meningioma and glioma. In fact, a meningioma-associated tumor suppressor gene which is commonly inactivated in clinically aggressive meningiomas was found on the long arm of chromosome 14, identified as the N-myc downstream-regulated gene 2 (NDRG2).[[25]] A study in 2005 found that this gene was suppressed in glioblastoma tissue but expressed in normal brain tissue.[[26]] Thus, the suppression of NDRG2 gene may lead to the formation of meningioma and glioblastoma simultaneously. In 2015, Nestler et al. reported three cases of simultaneous of meningioma and glioblastoma, but specimens from two cases were examined for chromosomal aberration by conventional karyotyping as well as comparative genomic hybridization, and no common genetic aberration in tumor cells with a different histology was found.[[14]]
Therefore, we are in favor of the hypothesis that the association of collision tumors in reported cases may be a coincidental event.[[5]],[[6]],[[14]],[[27]]
To have an accurate preoperative diagnosis for these tumors is really difficult. The area with hyperintensity T2-weighted images surrounding a meningioma usually represents peritumoral edema and should be distinguished from low-grade glioma in collision tumors involving meningioma and glioma.
It is important to have an appropriate surgical strategy for these patients. Most authors agree that removal of both tumors in one stage usually yields good results.[[4]],[[28]] Some authors suggest that the removal of meningioma should be done first to avoid postoperative brain swelling after glioma resection.[[4]],[[5]] However, brain swelling after meningioma resection is not uncommon and can worsen the neurological status. Another approach is to remove the symptomatic tumor first.[[2]],[[3]] In our case, we removed both the lesions in one section because both tumors were located in the noneloquent area, and the approach was not difficult.
Conclusion
The occurrence of collision tumors in patients without a history of radiotherapy or phakomatosis is rare. We report the third case of meningioma and low-grade astrocytoma collision in the frontal lobe. No clear explanation was found, and it is most likely a coincidence. Careful preoperative imaging evaluation is very important in these cases so that we may have a correct diagnosis and surgical strategy. In planning for surgery for collision tumors, one-stage resection is likely the best management.
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.
