Congenital Nasal Neuroglial Heterotopia and Encephaloceles: An Update on Current Evaluation and Management
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1 The Laryngoscope VC 2016 The American Laryngological, Rhinological and Otological Society, Inc. Congenital Nasal Neuroglial Heterotopia and Encephaloceles: An Update on Current Evaluation and Management Eelam Adil, MD, MBA; Caroline Robson, MB, ChB; Antonio Perez-Atayde, MD; Colleen Heffernan, MB, BAO, Bch; Ethan Moritz, BS; Liliana Goumnerova, MD; Reza Rahbar, DMD, MD Objectives/Hypothesis: To describe our experience and current management approach for congenital nasal neuroglial heterotopia (NGH) and encephaloceles. Study Design: Retrospective chart review at a tertiary pediatric hospital from 1970 to Methods: Thirty patients met inclusion criteria: 21 NGH and nine encephaloceles. Data including demographics, pathology, imaging modality, surgical approach, resection extent, outcomes, and complications were analyzed. Results: Fourteen NGH patients (67%) presented with an internal nasal mass and nasal obstruction. Three patients (14%) presented with an external nasal mass and four (19%) had a mixed lesion. Median age at surgery was 0.51 years (interquartile range 1.32 years). Thirteen (62%) had an intranasal endoscopic approach. Median operative time was 1.6 hours (interquartile range 1.2 hours), and there were no major complications. Nine patients with encephalocele were identified: six (67%) presented with transethmoidal encephaloceles, two (22%) presented with nasoethmoidal encephaloceles, and one (11%) presented with a nasofrontal lesion. The median age at surgery was 1.25 years (interquartile range 1.4 years). All patients required a craniotomy for intracranial extension. Median operative time was 5 hours (interquartile range 1.9 hours), and eight patients (88%) had a total resection. Length of stay ranged from 3 to 14 days. Conclusion: Nasal neuroglial heterotopia and encephaloceles are very rare lesions that require multidisciplinary evaluation and management. At our institution, there has been a shift to magnetic resonance imaging alone for the evaluation of NGH to avoid radiation exposure. Endoscopic extracranial resection is feasible for most intranasal and mixed NGH without an increase in operative time, residual disease, or complications. Key Words: Nasal glioma, neuroglial heterotopia, encephalocele, congenital nasal lesion. Level of Evidence: 4. Laryngoscope, 126: , 2016 INTRODUCTION Congenital frontonasal masses are a group of very rare benign lesions that occur in one out of every 20,000 to 40,000 live births. 1 Neuroglial heterotopia (NGH; previously known as nasal glioma) and encephaloceles are included in this group and often discussed together given their similar neural origins. There are several theories regarding their pathogenesis. Neuroglial heterotopia or sequestration during cribriform plate fusion are two theories that may explain nasal NGH development but not frontonasal encephaloceles. A defect of anterior From the Department of Otolaryngology and Communication Enhancement (E.A., E.M., R.R.); the Department of Radiology (C.R.); the Department of Pathology (A.P-A.); the Department of Neurosurgery (L.G.), Boston Children s Hospital; the Harvard Medical School (E.A., C.R., A.P-A., R.R.), Boston, Massachusetts, U.S.A.; and the Department of Ear, Nose, Throat, Head and Neck Surgery, Galway University Hospital (C.H.), Galway, Ireland. Editor s Note: This Manuscript was accepted for publication December 15, Presented at the Triological Society Combined Sections Meeting, Coronado, California, U.S.A., January 23, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Reza Rahbar, MD, Department of Otolaryngology and Communication Enhancement, Boston Children s Hospital, 300 Longwood Avenue, LO-367, Boston, MA reza.rahbar@ childrens.harvard.edu DOI: /lary neuropore closure during embryogenesis, resulting in herniation or sequestration of tissue through the fonticulus frontalis or foramen cecum, is a more widely accepted theory. 2 Due to their central nervous system origin, both pathologies can have intracranial extension. Given the rarity of these lesions and the changes in evaluation and management of these tumors over the past decade, we sought to update our previously reported experience with NGH and encephaloceles. 3 Over the past 20 years, there has been a trend toward endoscopic management of nasal masses. There are several unique challenges with approaching the skull base in pediatric patients when compared to their adult counterparts. The relatively smaller size of the nose is an obvious obstacle to endoscopic approaches. A smaller orifice inhibits both the size and maneuverability of endoscopic instruments. There are also potential effects of both open and endoscopic approaches on the developing craniofacial skeleton. Finally, variation in the location of anatomic landmarks in the developing basicranium is an issue in pediatric skull base surgery. However, advances in image guidance have helped dramatically with this concern. In addition to shifting to endoscopic management, the imaging evaluation of nasal masses has evolved because of concerns regarding cancer risk in pediatric patients exposed to ionizing radiation. It is generally 2161
2 accepted that pediatric computerized tomography (CT) has the potential for a significantly increased lifetime radiation risk over adult CT due to increased patient dose per milliampere-second (mas) and increased lifetime risk per unit dose. 4 Because of these concerns, the Society for Pediatric Radiology has developed the Image Gently campaign advocating for radiation dose reduction strategies. Lower mas can be used while preserving the diagnostic quality of CT exams in order to decrease patient radiation dose. Alternatively replacing CT exams with magnetic resonance imaging (MRI) avoids radiation exposure altogether. The purpose of this study is to review the presentation, lesion characteristics, and management strategy of our patients with nasal NGH and encephaloceles with a focus on what has changed since the publication of our initial manuscript 12 years ago. MATERIALS AND METHODS The Boston Children s Hospital Institutional Review Board approved this study, and its guidelines were followed. A retrospective chart review was performed on all patients under age 18 diagnosed with nasal NGH or encephalocele based on final pathology results at Boston Children s Hospital from 1970 to Patients with traumatic or iatrogenic nasal encephaloceles were excluded. Encephaloceles without a nasal component were excluded (ie., occipital, nasoorbital, sphenoethmoidal, transsphenoidal, and sphenomaxillary) because of the heterogeneity of these lesions. A total of 21 patients with NGH and nine patients with congenital nasal encephaloceles met inclusion criteria. Patient records and imaging were reviewed to identify patient demographics, lesion location, imaging strategy, surgical approach, reconstruction technique, and postoperative course. RESULTS Neuroglial Heterotopia Data regarding the 21 pediatric patients with NGH is summarized in Table I (note that the 10 NGH patients reported in our previous case series are indicated in bold). There was a male:female ratio of 2:1. Fourteen patients (67%) presented with an internal nasal mass and symptoms of nasal obstruction. In the youngest patient (0.02 years), nasal obstruction led to respiratory distress that required urgent surgical intervention. Three patients (14%) presented with an external nasal mass, and four (19%) had a mixed lesion. Four patients had their initial resection at outside institutions and presented to our facility with recurrences. All patients underwent imaging prior to surgery (Figs. 1 and 2). Five (24%) patients had a CT scan, 10 (48%) underwent MRI, and six (29%) had both. In our original report, three patients (30%) with NGH had a MRI alone, whereas seven (64%) were evaluated solely with MRI in our most recent experience. 3 The median age at the time of surgery was 0.51 years (interquartile range 1.32 years). Thirteen (62%) patients had an intranasal endoscopic approach, five (24%) had an external approach, and two (10%) had an intranasal. One (5%) patient had a cleft palate and the lesion was excised transorally. Median operative time was 1.6 hours (interquartile 2162 range 1.2 hours) and there were no major hemorrhages. Length of stay ranged from 0 to 3 days. All patients had a total resection. There were no early or late major complications. One patient developed erythema of the nasal vestibule, likely secondary to pressure from the endoscope, and this resolved within 8 days. There were no reported recurrences during the follow-up period. Encephaloceles A total of nine patients with congenital nasal encephaloceles were identified during the study period (Table II; note that the 6 encephalocele patients from our original article are highlighted in bold). There was a female to male ratio of 2:1. Six patients (67%) presented with transethmoidal encephaloceles. Most of these patients presented with symptoms of nasal obstruction, and one presented with meningitis. Two patients (22%) presented with nasoethmoidal encephaloceles, and one (11%) presented with a nasofrontal lesion. The median age at surgery was 1.25 years (interquartile range 1.4 years). All lesions were found to have intracranial extension, and all underwent a craniotomy. The nasal portion of the lesion was approached endoscopically in three patients (33%), through the craniotomy incision in three patients (33%), transnasally in two patients (22%), and through a lateral rhinotomy in one patient (11%). The median operative time was 5 hours (interquartile range 1.9 hours), and blood loss was 50 cc (interquartile range 70cc). Eight patients (88%) had a total resection of their lesion. There were three (33%) postoperative complications: epiphora, cerebrospinal fluid (CSF) leak, and hydrocephalus. Length of stay ranged from 3 to 14 days. DISCUSSION Patient and Tumor Demographics Similar to prior studies, we found that NGH and congenital nasal encephaloceles are extremely rare. In the 43-year span of this study, only 21 NGH and nine nasal encephaloceles that met our inclusion criteria were identified. This makes conclusions about demographics very difficult. Previous reports indicate that NGH occur in a male to female ratio of 3:2 and encephaloceles are evenly distributed. 5 Similarly, NGH was more common in males (2:1) in our series. Nasal encephaloceles were more common in females (2:1) in our series, but we excluded traumatic, iatrogenic, and any encephaloceles without a nasal component that may explain the discrepancy. It has also been reported that most NGH are extranasal (60%), 30% are intranasal, and 10% are mixed. 6,7 During our total study period, most patients (67%) had intranasal lesions. Nine of 11 patients over the past 10 years had intranasal lesions. It is difficult to know whether this is a true trend or based on our referral pattern. Only one patient in our series (5%) had intracranial extension, which is lower than the 10% to 25% reported in the literature. 2
3 TABLE I. Characteristics of 21 Pediatric Nasal Neuroglial Heterotopia Patients. Age at Surgery (years) Gender Presenting Symptoms Tumor Site Recurrence on Presentation Initial Surgical Approach Time to Recurrence (years) Imaging Intracranial Extension Surgical Approach Operative Time (hours) Length of Stay (days) Length of Follow-up (years) 0.51 Male Nasal mass, nasal Anterior nasal cavity No CT No Intranasal Male Nasal mass, nasal Anterior nasal cavity No CT/MRI No Intranasal endoscopic Male Nasal mass Nasal dorsum No MRI No Lateral rhinotomy Male Recurrent nasal mass, Glabella Yes Craniotomy 2.5 CT/MRI No Lateral rhinotomy nasal swelling 0.07 Female Nasal mass, nasal Anterior nasal cavity No CT/MRI Intranasal endoscopic Male Nasal mass, recurrent disease Septum, upper lateral cartilage Yes Intranasal 0.83 MRI No External rhinoplasty Male Nasal mass Glabella/nasal dorsum No CT/MRI No Median rhinotomy Female Nasal mass, nasal, growth of mass Nasal dorsum, lateral nasal wall No MRI No External rhinoplasty Female Nasal mass Posterior nasal cavity No CT No Transoral (cleft palate) Male Nasal mass, Anterior nasal cavity No CT No Intranasal Male Nasal mass Anterio nasal cavity No CT No Intranasal endoscopic Female Growth of residual disease noted Posterior nasal cavity Yes Craniotomy, intranasal 2 CT/MRI Yes Frontotemporal craniotomy, intranasal endoscopic Male Nasal mass Nasoethmoid No CT No Intranasal endoscopic Male Nasal obstruction, Anterior nasal cavity No MRI No Intranasal endoscopic nasal 0.42 Female Nasal mass, snoring Anterior nasal cavity No MRI No Intranasal endoscopic Male Nasal Anterior nasal cavity No MRI No Intranasal endoscopic Female Periorbital edema, Anterior nasal cavity No CT/MRI No Intranasal endoscopic rhinorrhea 0.1 Male Nasal obstruction, Anterior nasal cavity No MRI No Intranasal endoscopic rhinorrhea 7.48 Male Nasal mass, residual disease 0.02 Female Nasal mass, respiratory distress, difficulty feeding Anterior nasal cavity Yes Intranasal Skull base, lateral nasal wall 0.51 Male Nasal mass Skull base, lateral nasal wall 5 MRI No Intranasal endoscopic No MRI No Intranasal endoscopic No MRI No Intranasal endoscopic Patients in bold are those that were reported in our previous article. 3 CT 5 computed tomography; MRI 5 magnetic resonance imaging.
4 Fig. 1. A 41-day-old male with a left intranasal NGH. (A) Coronal T2-weighted MRI demonstrating a partially cystic intranasal mass protruding superomedial to the left inferior turbinate (long arrow). The nasal septum is bowed to the right (short arrow). The anterior cranial fossa appears intact. (B) High-resolution, thin-section axial-t2 and (C) axial T1-weighted MRI show the partially cystic, anterior nasal cavity mass with a solid component that is isointense with cortex. (D) Fat-suppressed axial T1-weighted MR reveals only peripheral enhancement (arrowhead). The location superomedial to the inferior turbinate and solid component distinguishes this lesion from a nasolacrimal duct cyst. The absence of intracranial connection excludes an encephalocele. The absence of enhancement differentiates NGH from an intranasal tumor or venous malformation. MRI 5 magnetic resonance imaging; NGH 5 nasal neuroglial heterotopia Evaluation As noted in our prior publication, these lesions require a thorough multidisciplinary approach, which includes otolaryngology, neuroradiology, neurosurgery, and possibly a reconstructive team. 3 Evaluation begins with a thorough history and physical exam. On examination, it is important to note the location of the lesion and whether or not it is pulsatile. Expansion of the nasal lesion with compression of the internal jugular vein (Furstenberg s sign) can indicate an intracranial connection. If a NGH or encephalocele is suspected, biopsy should be avoided and imaging pursued instead. There has been a shift at our institution toward MRI imaging alone for NGH, given the improved soft tissue characterization when compared to CT imaging and the presumed increased risk of carcinogenesis with ionizing radiation in the pediatric age group. Three patients in our recent experience had CT scans because they were initially evaluated at outside institutions, and one had a CT scan because of intracranial extension. No patients in our series of NGH evaluated with MRI alone had a subtotal resection or unexpected intracranial extension, which indicates that MRI alone is an adequate imaging study for NGH without intracranial extension. Therefore, the authors recommend MRI alone for patients with NGH isolated to the nasal cavity. This may not be feasible at all institutions; some institutions may not have access to MRI and/or pediatric anesthesiology, the latter being necessary for some pediatric patients who require sedation during image acquisition. In these cases, transfer to an outside facility for both image acquisition and operative management can be considered. Pulse sequences should consist of high-resolution, thin-section, fat-suppressed multiplanar T2; multiplanar Fig. 2. A 77-day-old male with solid prenasal nasal neuroglial heterotopia versus encephalocele. (A) Sagittal fast-spin echo inversion recovery magnetic resonance imaging shows a prenasal mass that is isointense with gray matter connected via a small stalk (arrow) to the anterior cranial fossa. Absence of continuity with the frontal lobes distinguishes this from an encephalocele in spite of the presence of the small stalk. (B) Helical axial computed tomography delineates the bony defect (arrow) prior to surgical resection.
5 TABLE II. Characteristics of Congenital Nasal Encephalocele Patients. Age at Surgery (years) Gender Laterality Presenting symptoms Type Imaging Type of Craniotomy ORL Approach Reconstruction Extent of Resection Operative time (hours) Estimated blood loss (cc) Complications Time to Resolution of complication (days) Length of Stay (days) Length of follow-up (years) 0.58 Female Left Respiratory distress, rhinorrhea, nasal obstruction 2 Female Left Nasal obstruction, rhinorrhea 1.9 Female Right Nasal mass Transethmoidal Skull X-ray Male Left Respiratory distress, rhinorrhea, nasal obstruction Transethmoidal MRI Bifrontal Intranasal endoscopic Transethmoidal CT Bifrontal Lateral rhinotomy Transethmoidal Skull X-ray Bifrontal Intranasal Bifrontal Intranasal Fascia graft from left temporal to dura, Pericranial Pericranial Pericranial 0.58 Female Bilateral Nasal mass Nasoethmoidal CT/MRI Subcranial None Pericranial 6 Female Left Nasal mass Nasoethmoidal CT/MRI Bifrontal None Pericranial 0.6 Female Right Nasal obstruction Transethmoidal CT/MRI Bifrontal Intranasal endoscopic Bone tiseel, 1.25 Male Bilateral Nasal mass Nasofrontal CT/MRI Bifrontal None Bilateral frontoorbital advancement. Calvarial bone graft nasal reconstruction 13 Male Right Meningitis Transethmoidal CT/MRI Bifrontal Intranasal endoscopic Mucoperiosteal graft Total None N/A 3 3 Subtotal 5 80 Epiphora Total CSF leak Total None N/A 4 3 Total None N/A Total None N/A 4 5 Total 5 30 None N/A Total Hydrocephalus Total None N/A Patients in bold are those that were reported in our previous article. 3 CSF 5 cerebral spinal fluid; CT 5 computed tomography; MRI 5 magnetic resonance imaging; N/A 5 not applicable.
6 Fig. 3. Light microscopy of nasal glioma: (A) Bundles of neuroglial tissue with hypertrophic astrocytes are separated by vascular, collagenous septa. (B) Bundles of neuroglial tissue are diffusely and strongly immunoreactive (brown color) for glial fibrillary acidic protein. Light microscopy of encephalocele: (C) Neuroglial tissue with hypertrophic astrocytes (arrowheads) and scattered neurons (arrows). (D) Choroid plexus component. [Color figure can be viewed in the online issue, which is available at high resolution T1; and nonecho planar diffusionweighted images (Figs. 1 and 2). Gadolinium-enhanced fat-suppressed T1-weighted images should also be obtained if a mass other than encephalocele is demonstrated. Every attempt is made to obtain the exam while the patient is naturally asleep in order to avoid sedation or general anesthetic. This may require obtaining intravenous access ahead of the infant falling asleep. For patients in whom an intracranial connection is found on MRI, a limited sinus CT scan is then indicated for assessment of the calvarium and for use with image guidance systems. Because the soft tissue characteristics of the lesion are well characterized by MR, when required, CT is obtained for assessment of bony detail alone and consists of helical axial images utilizing a lowdose technique, with multiplanar reformatted images. The MR exam provides a guide as to whether contrast is required for CT. For assessment of nasofrontal encephaloceles, contrast is not required. However if there is a question regarding the integrity of the anterior cranial fossa (the anterior cranial fossa is incompletely ossified in an infant under the age of 2 years), contrast will be required in order to demonstrate the integrity of the unossified enhancing cartilage in this region. Management In our original series, five out of 10 patients had an external approach to their NGH. Since that time, we have been able to resect all of our NGH through an endonasal endoscopic approach. The median operative time was lower for our transnasal endoscopic cases (0.75 hours; interquartile range hours) when compared to cases that required a facial incision (2.55 hours; interquartile range hours). Only one patient 2166 had transient nasal alar erythema in the transnasal endoscopic group. This occurred in a 3-month-old infant and was secondary to stretch of the nasal ala from the transnasal instrumentation during resection. This resolved spontaneously in 8 days without any permanent sequelae. Similarly, we have been able to achieve total resection for all of our recent nasal encephaloceles using a transnasal endoscopic approach and/or transcranial endoscopic approach (i.e., accessing the intranasal component of the encephalocele through the craniotomy and skull base defect created by the lesion). Therefore, the authors advocate for avoiding all facial incisions for all sinonasal pathology if technically feasible. For all patients with intracranial extension, the use of image guidance as an adjunct is also recommended. In particular, when accessing intranasal components of tumors through limited craniotomy defects, the use of image guidance has been quite useful for ensuring complete resection. Reconstruction of skull base defects in patients with intracranial extension has been accomplished through the use of an anteriorly based pericranial flap in all patients. Most recently, we have been augmenting the pericranial flap with a free inferior turbinate mucoperiosteal graft. No recent patients have developed a complication such as meningitis or CSF leak. Given the anterior location and relatively small residual skull base defect following of lesions with intracranial extension, a nasoseptal flap has not been utilized for skull base reconstruction. Length of stay (LOS) ranged from 0 to 3 days for most NGH patients. One patient had a prolonged stay (45 days) because of congenital heart disease that required management. The LOS of encephalocele
7 patients ranged from 3 to 14 days. In general, LOS was longer for younger patients, those travelling from outside of the region for resection, and those in need of a craniotomy. Pathology It can be difficult to distinguish NGH and encephaloceles based on histopathology. Nasal neuroglial heterotopia is characterized by fibroconnective tissue with focal infiltration by bundles of glial tissue (Fig. 3). This is typically immunoreactive for glial fibrillary acid protein, S-100, synaptophysin, and epithelial membrane antigen. Encephaloceles can also contain variable amounts of glial tissue. The presence of leptomeninges helps distinguish encephalocele from NGH. If no ependymal tissue is present, then the diagnosis is based on clinicopathological and imaging findings. Since our original publication, no new staining or imaging techniques have improved our ability to detect these lesions. CONCLUSION Nasal neuroglial heterotopia and encephaloceles are very rare lesions that must be considered in the differential of congenital nasal masses. Magnetic resonance imaging alone is adequate for imaging evaluation of lesions limited to the nasal cavity. Low dose sinus CT imaging is necessary for both bony evaluation and image guidance for patients with intracranial extension. Most tumors can be completely resected without the use of any facial incisions through the use of a transnasal endoscopic approach and/or endoscopic transcraniotomy approach. Operative time is shorter with endoscopic approaches without compromising tumor resection or increasing complications. BIBLIOGRAPHY 1. Hughes GB, Sharpino G, Hunt W, Tucker HM. Management of the congenital midline nasal masses: a review. Head Neck Surg 1980;2: Patterson K, Kapur S, Chandra RS. Nasal glial heterotopias and related brain heterotopias: a pathologist s perspective. Pediatr Pathol 1986;5: Rahbar R, Resto VA, Robson CD, et al. Nasal glial heterotopia and encephalocele: diagnosis and management. Laryngoscope 2003;113: Brenner DJ, Elliston CD. Estimated radiation risks potentially associated with full-body CT screening. Radiology 2004;232: Rouev P, Dimov P, Shomov G. A case of nasal glial heterotopia in newborn infant. Int J Pediatr Otorhinolaryngol 2001;58: Jaffe BF. Classification and management of anomalies of the nose. Otolaryngol Clin North Am 1981;14: Pensler JM, Ivescu AS, Ciletti SJ, et al. Craniofacial gliomas. Plas Reconstr Surg 1996;98:
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