Uptodate: Intracranial Subependymoma

Intracranial Subependymoma

Intracranial subependymomas are rare, mostly incidentalomas and therefore did not receive much attention in previous literature.

Many supratentorial subependymomas appear to be centered in the cortex or subcortical white matter. Therefore, a lack of ventricular involvement does not exclude subependymoma from the differential diagnosis.

By being classified as benign grade I in the World Health Organization Classification of Tumors of the Central Nervous System, they are given a special status compared to the other ependymal tumors. Tumor recurrences are a rarity, spinal “drop metastases” do not occur. While etiological, pathological and therapeutic characteristics have been subject of several publications over the last few decades and have meanwhile been well studied, the imaging characteristics are much less well received 1).

Epidemiology

They occur in middle to late adulthood.

Representing approximately 10% of ependymal tumors, subependymomas most often “present” as incidental autopsy findings in the brains of the elderly.

Most frequently they arise in the fourth ventricle (50-60%), followed by the lateral ventricle (30-40%), and less frequently in the septum pellucidum and spinal cord 2) 3).

Intraparenchymal subependymomas are extremely rare; only 6 cases have been reported in English literature. All of them were located in the supratentorial region 4) 5) 6) , and there has been only one report of infratentorial subependymoma 7)

see Subependymoma of the fourth ventricle

Histology

Subependymomas are small, discrete tumors of adults lying most often at the foramen of Monro or the fourth ventricle. It is composed of clusters of ependymal and astrocyte-like cells in a dense fibrillary stroma. It is typically attached to a ventricular wall and the most common site is the fourth ventricle.

Histologically, the tumor may be either compact or microcystic, but extensive microcystic change is rarely reported.

The histogenesis of subependymomas is still a matter of debate, with candidates including subependymal glia, astrocytes, ependymal cells, or some mixture of these cells. A recent theory hypothesizes that they originate from tanycytes, which are cells normally located in the subependymal zone 8).

Clinical features

They are likely to remain asymptomatic throughout life and some were found by autopsy. If symptomatic, tumor location and size are critical factors for presentation.

Diagnosis

Subependymomas have typical image morphologic characteristics that differentiate them from tumors of other entities, however, the rare subgroup of histopathological mixtures of subependymomas with ependymal cell fractions has no distinctly different imaging properties.

Knowing the imaging characteristics of subpendymoma and their differential diagnoses is of particular importance in order to be able to decide between the necessity of follow-up controls, an early invasive diagnosis or, depending on the entity, tumor resection.

KEY POINTS:

· Subependymomas have typical imaging characteristics that are clearly distinguishable from other entities.. · Increased incidence in middle/ older aged men, most frequent localization: 4th ventricle..

· Symptomatic subependymomas, often located in lateral ventricles, are usually characterized by hydrocephalus..

· Radiological identification of mixed subependymoma with ependymal cell fractions is not possible..

· Image based differentiation from other entities is important for the procedure.. 9).

Treatment

The surgical aims are the maximal safe tumoral resection, the decompression of neural elements, and establishment of a pathological diagnosis and the restoration of normal CSF pathways. As subependymomas are low-grade lesions with low rates of cell proliferation and a benign clinical course, complete surgical removal is usually curative.

Case series

33 patients with subependymoma, including 4 patients with a mixture of subependymomas with ependymal cell fractions in terms of imaging and clinical aspects and with reference to a current literature review.

Subependymomas have typical image morphologic characteristics that differentiate them from tumors of other entities, however, the rare subgroup of histopathological mixtures of subependymomas with ependymal cell fractions has no distinctly different imaging properties.

Knowing the imaging characteristics of subpendymoma and their differential diagnoses is of particular importance in order to be able to decide between the necessity of follow-up controls, an early invasive diagnosis or, depending on the entity, tumor resection.

KEY POINTS:

· Subependymomas have typical imaging characteristics that are clearly distinguishable from other entities.. · Increased incidence in middle/ older aged men, most frequent localization: 4th ventricle..

· Symptomatic subependymomas, often located in lateral ventricles, are usually characterized by hydrocephalus..

· Radiological identification of mixed subependymoma with ependymal cell fractions is not possible..

· Image based differentiation from other entities is important for the procedure.. 10).


With the SEER-18 registry database, information from all patients with intracranial subependymoma diagnosed during 2004-2013 were extracted, including age, sex, race, occurrence of surgery, extent of primary surgery, receipt of radiation, tumor size, and follow-up data. Age-adjusted incidence rates, overall survival, and cause-specific survival were calculated. Cox proportional hazards model was used for both univariate and multivariate analyses.

Four hundred sixty-six cases were identified. The overall incidence of intracranial subependymoma is 0.055 per 100,000 person-years (95% confidence interval, 0.05-0.06). Through multivariate analysis, age <40 years (hazard ratio [HR], 0.21; P = 0.03), female sex (HR, 0.34; P = 0.03), location within ventricles or near brainstem (HR, 0.49; P = 0.04), and occurrence of surgery (HR, 0.50; P = 0.02) were significant independent positive prognostic factors. Receipt of radiation did not show a significant relationship.

Clinical factors such as younger age, female sex, and location within ventricles or near brain stem demonstrated positive relationship with overall survival. For treatment options, surgery remains a mainstay option. No support for radiation therapy was identified 11).


Forty-three cases of pathologically confirmed, surgically treated intracranial subependymoma were identified. Thus in this patient population, subependymomas accounted for approximately 0.07% of intracranial tumors (43 of an estimated 60,000). Radiologically, 79.1% (34/43) of intracranial subependymomas were misdiagnosed as other diseases. Pathologically, 34 were confirmed as pure subependymomas, 8 were mixed with ependymoma, and 1 was mixed with astrocytoma. Thirty-five patients were followed up for 3.0 to 120 months after surgery. Three of these patients experienced tumor recurrence, and one died of tumor recurrence. Univariate analysis revealed that shorter progression-free survival (PFS) was significantly associated with poorly defined borders. The association between shorter PFS and age < 14 years was almost significant (p = 0.51), and this variable was also included in the multivariate analysis. However, multivariate analysis showed showed only poorly defined borders to be an independent prognostic factor for shorter PFS (RR 18.655, 95% CI 1.141-304.884, p = 0.040). In patients 14 years of age or older, the lesions tended to be pure subependymomas located in the unilateral supratentorial area, total removal tended to be easier, and PFS tended to be longer. In comparison, in younger patients subependymomas tended to be mixed tumors involving the bilateral infratentorial area, with a lower total removal rate and shorter PFS.

Intracranial subependymoma is a rare benign intracranial tumor with definite radiological features. Long-term survival can be expected, although poorly defined borders are an independent predictor of shorter PFS. All the features that differ between tumors in younger and older patients suggest that they might have different origins, biological behaviors, and prognoses 12).


24 pathologically proved cases of intracranial subependymomas in 17 male and seven female patients with a mean age of 48.1 years. All patients were symptomatic. CT and MR images were used to characterize the size, shape, and location of the subependymomas; the degree of hydrocephalus; tumor calcification; and the density, signal, and enhancement characteristics of the tumors.

Eighteen of 24 tumors were 3 cm or more in greatest dimension. Nineteen were lobulated, and hydrocephalus was seen in 21. Fourteen were in the lateral ventricle, and 10 were in the posterior fossa. Calcifications were present in five (all fourth ventricular) and absent in 10 (all lateral ventricular) subependymomas imaged with unenhanced CT. On 18 contrast-enhanced CT scans, five of six subependymomas with heterogeneous enhancement were in the fourth ventricle, and nine of 12 tumors with minimal or no enhancement were in the lateral ventricle. Small internal foci with a signal intensity similar to that of CSF were seen on images of all 10 lateral ventricular subependymomas obtained with both T1-weighted and T2-weighted sequences. On 13 contrast-enhanced T1-weighted images, seven of eight tumors with heterogeneous enhancement were in the fourth ventricle, and all five with minimal or no enhancement were in the lateral ventricle.

Intracranial subependymomas were seen in symptomatic middle-aged adults and showed different CT and MR imaging features, depending on their anatomic location. Calcification and heterogeneous contrast enhancement were common features of fourth ventricular subependymomas showed a lack of calcification as well as minimal or no contrast enhancement of CT and MR images 13).

1)

Kammerer S, Mueller-Eschner M, Lauer A, Luger AL, Quick-Weller J, Franz K, Harter P, Berkefeld J, Wagner M. Subependymomas – Characteristics of a “Leave me Alone” Lesion. Rofo. 2018 Jun 18. doi: 10.1055/a-0576-1028. [Epub ahead of print] PubMed PMID: 29913520.

2)

Ragel BT, Osborn AG, Whang K, Townsend JJ, Jensen RL, Couldwell WT. Subependymomas: an analysis of clinical and imaging features. Neurosurgery. 2006;58:881–890. discussion 881-890.

3)

Nishio S, Morioka T, Mihara F, Fukui M. Subependymoma of the lateral ventricles. Neurosurg Rev. 2000;23:98–103.

4)

Natrella F, Mariottini A, Rocchi R, Miracco C. Supratentorial neurenteric cyst associated with a intraparenchymal subependymoma. BMJ Case Rep. 2012;2012

5)

Hankey GJ, Davies L, Gubbay SS. Long term survival with early childhood intracerebral tumours. J Neurol Neurosurg Psychiatry. 1989;52:778–781.

6)

Shuangshoti S, Rushing EJ, Mena H, Olsen C, Sandberg GD. Supratentorial extraventricular ependymal neoplasms: a clinicopathologic study of 32 patients. Cancer. 2005;103:2598–2605.

7)

Kim Y, Lee SY, Yi KS, Cha SH, Gang MH, Cho BS, Lee YM. Infratentorial and intraparenchymal subependymoma in the cerebellum: case report. Korean J Radiol. 2014 Jan-Feb;15(1):151-5. doi: 10.3348/kjr.2014.15.1.151. Epub 2014 Jan 8. Review. PubMed PMID: 24497806; PubMed Central PMCID: PMC3909849.

8)

Sarkar C, Mukhopadhyay S, Ralte AM, Sharma MC, Gupta A, Gaikwad S, Mehta VS. Intramedullary subependymoma of the spinal cord: a case report and review of literature. Clin Neurol Neurosurg. 2003;106:63–68.

9) , 10)

Kammerer S, Mueller-Eschner M, Lauer A, Luger AL, Quick-Weller J, Franz K, Harter P, Berkefeld J, Wagner M. Subependymomas – Characteristics of a “Leave me Alone” Lesion. Rofo. 2018 Jun 18. doi: 10.1055/a-0576-1028. [Epub ahead of print] PubMed PMID: 29913520.

11)

Nguyen HS, Doan N, Gelsomino M, Shabani S. Intracranial Subependymoma: A SEER Analysis 2004-2013. World Neurosurg. 2017 May;101:599-605. doi: 10.1016/j.wneu.2017.02.019. Epub 2017 Feb 15. PubMed PMID: 28232153.

12)

Bi Z, Ren X, Zhang J, Jia W. Clinical, radiological, and pathological features in 43 cases of intracranial subependymoma. J Neurosurg. 2015 Jan;122(1):49-60. doi: 10.3171/2014.9.JNS14155. PubMed PMID: 25361493.

13)

Chiechi MV, Smirniotopoulos JG, Jones RV. Intracranial subependymomas: CT and MR imaging features in 24 cases. AJR Am J Roentgenol. 1995 Nov;165(5):1245-50. PubMed PMID: 7572512.

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