Ectopic orbital brain tissue: a case report with radiographic and clinical review

ABSTRACT Orbital heterotopic brain tissue is a rare entity with heterogenous clinical features requiring a multi-faceted diagnostic approach. The authors present a case of ectopic orbital brain tissue in an infant with a comprehensive literature review to highlight the radiographic findings of these lesions. Imaging findings are variable but describe well-circumscribed homogenous lesions with variable enhancement, without communication intracranially. The combination of computed tomography and magnetic resonance imaging can identify associated bony abnormalities, lesion-specific features, and effects on surrounding structures, which in combination with the clinical exam can be a valuable diagnostic and surveillance tool. Although ectopic orbital brain tumors are benign with excellent outcomes following complete resection, conservative management with observation and serial imaging may be an alternative method of management in patients with mild, non-vision threatening, non-distorting tumors.

Orbital heterotopic brain tissue arises when there is sequestration of neuroglial tissue isolated within the orbit during development. It is an extremely rare clinical entity and has been reported to consist of differentiated glial tissue, cerebellar tissue, and neuronal tissue. [1][2][3][4][5][6][7][8] These lesions may present as a diagnostic challenge as they can clinically mimic other orbital tumors. 8,9 An orbital biopsy is often required to confirm the diagnosis. Imaging studies are important to establish the diagnosis and guide management, but previous data regarding radiographic features, which can present with wide variability, are sparse. Herein, we present a case of orbital ectopic brain in an infant and perform a comprehensive review of the literature to characterize its most salient radiographic features that may aid in disease diagnosis and surveillance.

Case report
A male infant was born to a healthy mother via a noncomplicated vaginal delivery. On day 3 of life, the right pupil was noted to be mydriatic and non-reactive to light. A review of outside records did not identify any abnormality in ocular motility, ptosis, or proptosis. Magnetic resonance imaging (MRI) of the brain and orbit with contrast identified a mass within the inferior right orbit (Figure 1). Given an initial concern for neuroblastoma, the patient underwent an orbitotomy and incisional biopsy at an outside institution, which was reported to contain neuroglial tissue consistent with ectopic brain tissue. Immunochemistry was positive for synaptophysin and PGP9.5, with GFAP highlighting mild gliosis. PHOX2B immune-studies were negative, and there was no evidence of malignancy identified. Post-operatively, the patient was noted to have intermittent exotropia, a right hypotropia, and anisocoria, although the right pupil was mildly reactive to light. At 7 months of age, the patient underwent strabismus surgery to improve the right hypotropia. At 13 months of age, the patient presented to our clinic and an ocular exam revealed a persistent 14-prism diopter right hypotropia with the right pupil 2 mm larger than the left with preserved light reflex. A repeat MRI showed residual tissue along the inferolateral right orbit extending from near the orbital apex to the retrobulbar region, which was T1 isointense and T2 hypointense to brain parenchyma. These findings were consistent with ectopic brain tissue, which had also been confirmed by a re-review of histopathology, therefore a CT scan was not obtained. No intervention was taken at this time and on follow-up imaging at 20 months, there was no progression of the lesion. At present, the patient is planned to undergo additional revision strabismus surgery and will continue to be treated for amblyopia.

Discussion
Ectopic sequestration of brain tissue in the orbit is an extremely rare clinical entity. With the addition of the current case, only 34 cases have been reported in the literature (Table S1).  The mean age of presentation was 8.9 years (range: 0-59 years). A diagnostic delay was reported in 56% (19/34) of patients who experienced symptoms for a mean of 3.6 years (range: 0-20 years) prior to diagnosis. The left orbit was more commonly affected than the right, 59% (20/34) vs. 35% (12/34). Two (6%) patients had bilateral involvement. 20,21 Eyelid and periorbital swelling were the most common presenting signs in 62% (21/34) of patients, followed by globe displacement (32%), proptosis (26%), restrictions in ocular motility (21%), strabismus (18%), and ptosis (15%). Children under the age of six more commonly presented with eyelid and periorbital edema (62%), while adults presented with headaches and visual changes, such as decreased visual acuity, blurry vision, and diplopia (15%). 9,20,26,30 Visual acuity was reported on presentation in eight cases and ranged from 20/20 to no light perception with the latter lesion occupying the entire orbit. 27 Best correct visual acuity was noted to be decreased on presentation in 75% (6/8) of patients. Four reported visual acuity post-operatively which ranged from 20/80 to 20/1200, all unchanged from initial presentation. 9,11,28,30 All diagnoses of ectopic orbital brain tissue were confirmed with histopathology with neuroglial cells reported in 71% (24/34) of cases. Surgical resection was the primary method of treatment in 82% (28/34) of cases with an overall recurrence rate of 9%.
Orbital heterotopic brain tissue is usually best evaluated with various imaging modalities, which can help confirm the diagnosis and monitor progression. Based on all published cases to date, 62% (21/34) were evaluated with computed tomography (CT), while 50% (17/ 34) were evaluated with MRI, 20% (7/34) with ultrasound, and 9% (3/34) with X-ray or cerebral angiography. CT imaging noted bony abnormalities in 41% (14/ 34) of patients and 18% (6/34) presented with orbital wall defects associated with lesions located in the medial orbit and orbital apex. Orbital wall thinning, orbital wall expansions, scalloping of the orbital wall, and concave deformities were also frequently described. On CT Figure 1. MRI demonstrating ectopic orbital brain tissue. Axial T2 (A), axial pre-contrast T1 (B), axial postcontrast fat saturated T1 (cC, coronal T2 (D), coronal post contrast fat saturated T1 (E), and axial diffusion weighted imaging shows a relatively well-circumscribed mass in the inferior mid orbit, extending to the apex, just underneath the optic nerve, with mild associated mass effect. It is relatively T2 hypointense to visualized brain tissue, T1 isointense to brain tissue, without restricted diffusion, and demonstrates mild diffuse and prominent rim enhancement.
Magnetic resonance imaging (MRI) included descriptions of various tissue features of ectopic orbital brain tissue and their relationship to surrounding structures. Ectopic orbital brain tissue was described as isointense relative to brain parenchyma on T1 weighted imaging in 18% (3/17) of patients and hyperintense on T2 weighted imaging in 29% (5/17) of patients. One case was observed to have T2 hyperintensity relative to skeletal muscle. 12 The current case presented a relative hypointensity to brain parenchyma on T2 imaging, which has been less commonly reported. 14 Similar to the current case, lesions have been described as well-circumscribed (12%) with various tissue enhancement patterns (47%). Peripheral rim enhancement was reported in 18% (3/17) of patients, while 12% (2/17) presented with heterogenous tissue enhancement. Irregular borders were described in two patients, one with tumor regrowth at four years. 1,15 Cystic features were described in 32% (11/34) of patients with six described on MRI. Three cases reported cystic fluid consistent with cerebrospinal fluid. 2,21,32 Cystic features were associated with systemic or ocular abnormalities, such as microphthalmia, clinical anophthalmia, agenesis of the corpus callosum, and optic nerve colobomas in 55% (6/11) of patients.
Regarding growth patterns, ectopic orbital brain lesions may extend into the orbital apex, a feature described in 18% (3/17) of MRI descriptions. 13,26 Displacement of extraocular muscles, orbital fat, or the optic nerve was reported in 18% (3/17) of patients by lesions located inferiorly or superomedially. These lesions were managed with total resection with no recurrences reported at 1 year for two patients. 7,25,29 In the current case, MRI showed the ectopic mass inferior to the optic nerve with mild associated mass effect for which serial imaging was elected over surgical resection with no tumor growth observed at 20 months. Recognizing interval growth patterns such as tissue extension with serial imaging may be helpful in identifying specific growth behavior which may be important when monitoring lesions in close proximity to the optic nerve whose growth may threaten vision. Bony changes were less commonly reported in MRI with only one case describing orbital wall displacement with a medially located lesion. 7 No cases demonstrated connection with intracranial contents on CT or MRI, which is a feature that can help differentiate orbital heterotopia from encephaloceles and meningoceles. 5,16 While ultrasonography was less commonly used for evaluation, lesions were described as solid, hypoechoic, un-encapsulated, with or without vascular features. Two of the six cases that utilized ultrasound were initially described antenatally during the third trimester when fetal eyelid swelling was identified. 6,14 One antenatal case was described as a combination of peripheral and central vascularization with postnatal MRI describing hematic areas centrally. 14 Surgical resection with either total or sub-total/partial removal was the primary method of treatment in 82% (28/34) of patients. There were no recurrences for those who underwent total resection. Of those that were partially excised, 20% (3/15) experienced tumor growth on follow-up imaging, which clinically presented as recurrent eyelid and periorbital edema between 1 and 4 years post-operatively. 1,2,22 With the addition of the current case, 18% (6/34) were managed conservatively with serial imaging and observation after incisional biopsy with no evidence of continued tumor growth. While surgical resection appeared to be the preferred method of treatment in earlier studies, four of the most recent reports elected observation with serial imaging, suggesting clinicians may be moving toward a more conservative approach. 9,14,20 The mean follow-up was 1.6 years and ranged from 45 days to 6 years. Residual symptoms such as proptosis, ptosis, strabismus, optic nerve swelling, keratitis, decreased vision, and mydriasis were observed in 50% (11/22) of patients. The patient in the current study developed right exotropia and hypotropia postoperatively, which required strabismus surgery. Postoperative complications were reported in two other cases and included double vision and neurotrophic keratitis. 3,9 The true post-operative course of these ectopic lesions is difficult to assess given the limited and variable follow-up. Furthermore, imaging features were not reported in a standardized fashion, and more details of lesion-specific features and their relation to surrounding structures in future reports may be beneficial in identifying specific diagnostics and growth patterns.
The radiographic differential diagnosis of ectopic orbital brain tissue includes vascular lesions such as orbital hemangiomas and lymphangiomas and soft tissue tumors such as orbital rhabdomyosarcoma. [33][34][35][36][37] Radiographic presentations of orbital hemangiomas and lymphangiomas can vary with lesions demonstrating homogenous hypointensity to moderate hyperintensity with homogenous enhancement on T1 weighted MRI and peripheral hyperintensity to homogenous hyperintensity on T2 weighted MRI. 33,36,37 This is in contrast to ectopic orbital brain tissue, which may more frequently present with T1 isointensity and T2 hyperintensity with peripheral rim enhancement or heterogenous tissue enhancement. Though benign, orbital lymphangiomas may present with acute hemorrhagic cysts, which on CT imaging may demonstrate cystic structures with peripheral rim enhancement similar to what is observed in ectopic orbital brain tissue. However, in contrast, orbital lymphangiomas with acute intrinsic hemorrhage tend to be poorly defined and may be differentiated with a clinical history of acute and painful proptosis. 36 Orbital rhabdomyosarcoma, the most common primary orbital malignancy in children, has been described as a moderately well-defined homogenous mass primarily isolated to the extraocular muscles in the superior orbit on CT imaging. 34 In contrast to ectopic orbital brain tissue, orbital rhabdomyosarcomas are more often associated with bony destruction on CT imaging and homogenous hypointensity on T1 weighted MRI. [33][34][35] Orbital rhabdomyosarcoma can be clinically differentiated from ectopic orbital brain tissue by its rapid proptosis and globe displacement. 35,37 In addition to traditional imaging with CT and MRI, diffusion-weighted imaging (DWI), a noninvasive component of MRI that analyzes water diffusion in various diseased tissue, has also been used in differentiating various orbital lesions. 33 Generally, increased diffusion has been reported with benign lesions such as orbital hemangiomas, while restricted diffusion is more often present with malignant tumors, such as orbital rhabdomyosarcomas. 33 In our review, one case reported no diffusion restriction, but similar descriptions were not reported in other studies, although reporting diffusion behavior in future cases may provide an additional differentiating characteristic. The lack of large-scale reviews in the literature on radiologic features of orbital tumors suggests the need for consistent, standardized radiographic reporting to better delineate diagnosis.
This case presents a rare diagnosis of ectopic orbital brain tissue, which may present a diagnostic challenge with variable clinical and radiographic features. A combination of CT and MRI can identify bony and soft tissue abnormalities, lesion-specific features, anatomic location, and interval changes to help establish diagnosis and guide management. Only a few patients published to date have undergone both CT and MRI. We believe that additional imaging with more descriptive and standardized reporting of ectopic orbital brain tissue would reveal a greater proportion of lesions exhibiting well-defined borders with contrast enhancement on MRI with T1 isointensity relative to brain parenchyma, cystic structures, and potential interval growth into the orbital apex, although a greater sample size is needed to more reliably assess these features. However, the benign nature of these ectopic lesions suggests that assessing growth patterns may be challenging, although such data may be valuable in establishing surveillance guidelines. Our review suggests that observation with serial clinical and radiographic surveillance may be appropriate for those with mild, stable, or non-vision threatening symptoms. Additional studies utilizing multimodal imaging with more standardized and consistent data reporting for diagnosis and surveillance are needed to identify consistent key features and patterns suggestive of ectopic orbital brain tissue presentation and growth to aid clinicians in establishing a radiographic diagnosis and thus avoiding surgical complications. For cases with severe symptoms or large, vision threatening tumors causing distortion or erosion of orbital bones, complete surgical resection in combination with surveillance imaging is the preferred method of management.

Disclosure statement
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding
The author(s) reported that there is no funding associated with the work featured in this article.