Subependymomas are rare benign gliomas with a prevalence of 0.4% in asymptomatic patients versus 0.7% in symptomatic patients [1
] and have been more commonly reported in elderly males with a mean age of 39–59 years [2
]. Although the histogenesis of these tumors is still uncertain, they correspond histologically to WHO grade I of glial tumor classification [6
] which accounts for their likelihood to remain asymptomatic throughout life [7
In 1945 Scheinker first described subependymoma as tumor of the fourth ventricle arising from the subependymal glial layer surrounding the cerebral ventricles that was observed in a series of seven cases. These tumors are characterized by expansile growth that lacks an infiltrative pattern on histological examination [8
These tumors arise more frequently in the fourth ventricle (50–60%), with the majority of the remainder occurring in the lateral ventricle (30–40%) [4
]. In the lateral ventricle, subependymomas have an affinity to the anterior portions [10
]. Small number of cases has been incidentally reported in the brain parenchyma [11
], cerebellopontine angle [12
], septum pellucidum and the third ventricle [13
According to Maiuri and co-workers [7
], the most important factor related to the presenting symptoms in subependymoma is the tumor location. Tumor size at presentation is directly related to tumor location, with tumors blocking CSF pathways (e.g., fourth ventricle, foramen of Monro) presenting with smaller dimensions than tumors not impeding CSF (e.g. atrium of lateral ventricle) [7
]. Our patient however, presented with hydrocephalus and clinical symptoms described above, when his tumor was larger than 5 cm.
Although the exact histogenesis of subependymomas is still uncertain, they most likely arise from subependymal glial cells. Although most tumors are pure subependymomas, about 10% may present with an admixture of ependymoma and subependymoma. Such combined tumors are classified as mixed ependymoma/subependymoma and are graded based on the ependymoma component [4
Histologically, subependymoma is characterized by the presence of clusters of round cells supported by a fibrillary background and exhibiting discrete cytoplasmic borders. Microcystic degeneration may be identified in some areas. Nuclear pleomorphism may be encountered but mitotic activity is uncommon. Vascular proliferation, necrosis, foci of mineralization, hemosiderin, and focally sclerotic vessel changes may also be seen [15
]. Perivascular pseudorosettes or true ependymal rosettes are not usually observed in subependymomas but are rather characteristic of ependymomas, unless admixture of the two tumors is present.
The role of MIB-1 staining index (an important and well-recognized marker of cell proliferation) in the diagnosis of subependymoma is well-documented. Prayson and Suh [15
] reviewed 14 cases of subependymomas and reported a MIB-1 index range of 0–1.4 (mean 0.3). Subependymomas are characterized by an extremely low mean MIB-1 labeling index when compared to myxopapillary ependymomas and low-grade ependymomas [16
]. Histologically, subependymomas are graded as WHO grade I due to absent mitoses and extremely low MIB-1 index [16
]. It is noteworthy to mention that our case demonstrated only 0.8% MIB-1 labeling index; further confirming the diagnosis. Although this is an extremely benign tumor, rarely they may have tumoral melanization [17
], or may undergo rhabdomyosarcomatous differentiation [18
] or sarcomatous transformation of vascular stromal elements [19
The MR imaging features of supratentorial subependymomas seems to differ from infratentorial subependymomas in most cases. The presence of calcification is one of the differentiating features. Lobato et al. [13
] reported that six of 11 infratentorial and one of 11 supratentorial subependymomas had calcification while Silverstein and colleagues [20
] reported no calcification on CT images of a lateral ventricular subependymoma. Chiechi and colleagues [21
] described the presence of calcification in all six cases of fourth ventricular subependymomas and the absence of calcification in all 11 lateral ventricular subependymomas on CT images. We found no evidence of calcification on MR images in our patient with supratentorial subependymoma although CT scans, if obtained, would have been more sensitive.
The enhancement pattern of supratentorial subependymomas is different from infratentorial subependymomas in most cases. Supratentorial subependymomas tend to show minimal or no enhancement, while infratentorial subependymomas tend to enhance heterogeneously. Combined reports of 21 lateral ventricular subependymomas describe 16 (76%) cases as showing minimal or no enhancement [13
], and 5 (24%) cases as showing heterogeneous enhancement [13
]. Conversely, among 34 fourth ventricular subependymomas, only 5 (15%) cases showed minimal or no enhancement [2
], whereas 29 (85%) cases showed heterogeneous enhancement [2
]. Our case was among the exceptions that showed heterogeneous enhancement despite its supratentorial location.
Hoeffel et al [28
] evaluated 8 patients with intracerebral and spinal subependymomas. One supratentorial tumor was heterogeneous and pathological correlation revealed regions of necrosis, calcification, tumor vascularity, microcystic and macrocystic changes accounting for this heterogeneity. Lindboe et al [12
] reported a case of highly vascularized subependymoma of the septum pellucidum with acute hemorrhage in the tumor and surrounding brain parenchyma. In our case, the tumor was hypervascular as evidenced by presence of signal void on MR and hyalinized vessel on histology.
A thorough clinicopathological and radiographic evaluation is required to distinguish subependymoma from other supratentorial ventricular tumors including ependymomas, choroids plexus tumors, subependymal giant cell astrocytoma, neurocytoma, meningioma, astrocytoma and metastatic disease [29
]. These tumors generally tend to be heterogeneous on T1, T2 and FLAIR sequences due to areas of hemorrhage, necrosis and calcification and most of them tend to enhance heterogeneously, making their MR features indistinguishable from our case.
Diffusion weighted imaging is a unique MRI sequence that detects water motion in the tissue microenvironment. In normal tissue, water motion is maximum in the extracellular compartment due to less hindrance. In highly cellular tumor, there is constriction of extracellular space due to too many cells in a given voxel. This restricts free water motion, which is detected by diffusion weighted imaging [31
]. Diffusion characteristics of subependymoma are poorly reported in literature. In our case, there was subtle diffusion restriction on diffusion imaging with minimum ADC value of 753 × 10–6 mm2/s secondary to moderately increased cellularity. Low ADC value secondary to increased cellularity is a feature of high grade tumors rather than low grade tumors (like subependymoma). In low grade tumors ADC value is usually higher than normal appearing white matter (varies from 790–890 × 10–6 mm2/s).
Perfusion characteristic of subependymoma is also not well documented in literature. On perfusion imaging, there were multiple areas of high rCBV, higher than the contralateral NAWM. Although intratumoral neoangiogenesis is the most common cause of high rCBV in high grade tumors, in this particular tumor multiple intratumoral thick hyalinized vessels rather than neoangiogenesis was probably the explanation of higher rCBV.
The prognosis of a patient with an intraventricular subependymoma is good, with gross surgical resection being curative [6
]. In symptomatic patients, total surgical resection is the goal of therapy [13
], since these tumors are benign, grow by slow expansion, and are not infiltrative [3
]. Knowing that a tumor is a subependymoma before resection may sway the neurosurgeon to operate in a difficult location because gross total resection can often be achieved without removing normal brain structures [13
The differential diagnosis of supratentorial intraventricular subependymoma include; ependymoma, central neurocytoma, subependymal giant cell astrocytoma, choroid plexus papilloma and carcinoma, intraventricular meningioma and metastasis. Consideration of the tissue within and composing the ventricular lining and the clinical findings provide the means to limit the differential diagnosis when analyzing an intraventricular mass on an imaging study [10
]. Ependymomas are typically calcified, are more common in children, are more common in the fourth ventricle, and show intense enhancement on contrast enhanced images. Subependymomas and central neurocytomas have an affinity for the anterior portion of the lateral ventricle, and the later commonly demonstrate a heterogeneous cystic appearance on cross sectional images. Subependymomas are more common in older adults, whereas central neurocytomas are more common before 40 years of age. Subependymal giant cell astrocytomas always lie near the foramen of Monro and are characterized by frequent calcification, intense enhancement on contrast enhanced studies, and the presence of other stigmata seen in tuberous sclerosis. When a mass is centered on the choroid plexus, a highly vascular tumor such as choroid plexus papilloma, choroid plexus carcinoma, meningioma, or metastasis should be suspected. The characteristic heavily lobulated appearance of a choroid plexus tumor favors this diagnosis over other possibilities, although it is not always possible to distinguish between the more common benign form, the choroid plexus papilloma, and the less common malignant counterpart, the choroid plexus carcinoma. By using clinical, demographic, and imaging findings, one can significantly limit the differential diagnosis for many of the most common supratentorial intraventricular neoplasms [10