Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Javeed S, Qureshi MB, Ud Din N. Glial heterotopia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/nasalglialheterotopia.html. Accessed March 28th, 2024.
Definition / general
- Glial heterotopia is a benign, congenital, nonneoplastic displacement of mature neuroglial tissue at extracranial sites without intracranial connection (Acta Otorhinolaryngol Ital 2022;42:317, Int J Pediatr Otorhinolaryngol 2020;129:109728, J Cutan Aesthet Surg 2020;13:233)
- Very rare malformation that causes tumor-like conditions in newborns and older infants
Essential features
- Most frequent in the nasal area
- Mature brain tissue in the nasal cavity without connection to the dura / meninges and absence of a skull defect
- Radiography is essential to rule out communication of mass with intracranial space and assess bony defects (J Cutan Aesthet Surg 2020;13:233, Medicine (Baltimore) 2018;97:e12000)
Terminology
- Acceptable: ectopic glial - meningeal tissue, neuroglial heterotopia, nasal glial heterotopia, nasal glioma
- Not recommended: heterotopic brain choristoma, ectopic brain tissue
ICD coding
Epidemiology
- Incidence of congenital nasal masses is 1 in 20,000 - 40,000 live births; nasal glial heterotopia accounts for ~5% of them (Head Neck Surg 1980;2:222, Clin Otolaryngol Allied Sci 1982;7:87)
- Rare association with brain or systemic anomalies
- Most patients are diagnosed at birth or before the age of 3 (Int J Pediatr Otorhinolaryngol 2020;129:109728)
- 8% of cases are diagnosed in adults (Acta Otorhinolaryngol Ital 2022;42:317)
- M:F = 3:2
Sites
- Based on location related to nose, glial heterotopia can be
- Intranasal: located in the nasal cavity or sinuses
- Extranasal: protruding from the nasal root within the subcutaneous tissue of the nose
- Mixed type: present in both locations (Int J Pediatr Otorhinolaryngol 2020;129:109728)
- Bridge of nose is the most commonly involved site (Int J Pediatr Otorhinolaryngol 2020;129:109728)
- Rare occurrence at other sites, including orbit, lung, uterine cervix, endometrium, lip, tongue, pharynx, tonsil, palate and maxilla (Ophthalmic Plast Reconstr Surg 2020;36:2, J Cutan Aesthet Surg 2020;13:233, Ophthalmic Plast Reconstr Surg 2015;31:e26, Arch Ophthalmol 2003;121:119)
Pathophysiology
- Congenital, nonhereditary malformation
- Development of nasal cerebral heterotopia is embryologically similar to that of nasal encephalocele or dermoid
- During retraction of the embryonic dural diverticulum, remnants of neural glial tissue become sequestered when their connections to the subarachnoid space are pinched off and obliterated
- Lack of subarachnoid communication distinguishes heterotopia from anterior encephalocele
- Distinction between glioma and encephalocele is not possible based on histopathologic findings because glial tissue may be the predominant or exclusive component in both types of lesions (Acta Otorhinolaryngol Ital 2022;42:317)
Etiology
- See Pathophysiology
Clinical features
- Intranasal: nasal congestion, mass, obstruction or deformity, may be asymptomatic (Ann Diagn Pathol 2003;7:354)
- Extranasal: firm, smooth masses that do not pulsate or expand during crying, coughing or straining (Acta Otorhinolaryngol Ital 2009;29:218)
Diagnosis
- Diagnosis requires strong clinical and radiologic correlation in addition to histology of lesion
- Magnetic resonance imaging (MRI) to exclude communication with the central nervous system and plan a surgical approach
- Additional computed tomography (CT) performed if bony involvement is suspected or necessary for endoscopic surgery (Acta Otorhinolaryngol Ital 2022;42:317)
Radiology description
- Radiology is necessary to determine the location of the mass and its relationship to the skull base
- MRI characteristics of glial heterotopia resemble normal brain tissue in all pulse sequences
- Cystic elements might be present and represent cerebrospinal fluid (CSF)-like fluid filled spaces
- MRI findings (J Cutan Aesthet Surg 2020;13:233, Acta Otorhinolaryngol Ital 2022;42:317)
- Circumscribed, ovoid soft tissue intensity lesion
- Isointense signal in T1 weighted imaging
- Heterogeneously hyperintense signal in T2 weighted imaging
- Moderate enhancement postintravenous gadolinium contrast
- No connection between the mass and the dura or brain
- Noncontrast computed tomography (NCCT): soft tissue density, space occupying lesion with no communication with nasal cavity or brain (J Cutan Aesthet Surg 2020;13:233)
Radiology images
Prognostic factors
- Benign lesion with good prognosis (Int J Pediatr Otorhinolaryngol 2020;129:109728)
- Local recurrence rate: up to 30% with incomplete excision
- Histological evaluation of surgical margins can reduce the risk of recurrence
- Most recurrences occur within the first 12 months
Case reports
- 2 month old boy presented with nasal obstruction and shortness of breath since birth (Medicine (Baltimore) 2020;99:e21200)
- 6 month old infant with a congenital mass located at the root of the nose (J Cutan Aesthet Surg 2020;13:233)
- 16 year old girl presented with sore throat and feeling of lump in her throat (BJR Case Rep 2020;6:20190116)
- 37 year old man presented with right nasal obstruction, epistaxis and headache (Head Neck 2008;30:549)
Treatment
- Complete surgical resection is the curative treatment (Int J Pediatr Otorhinolaryngol 2020;129:109728, J Cutan Aesthet Surg 2020;13:233)
- Surgical approach depends on the location and extent of lesion: external rhinotomy, endoscopic resection or combined approach are the most common techniques
Clinical images
Gross description
- Size range: 1 - 3 cm; can grow up to 7 cm
- Firm, globular to polypoidal smooth mass with homogenous gray to pearly white cut surface (J Cutan Aesthet Surg 2020;13:233)
- Grows slowly in proportion to adjacent tissue
Microscopic (histologic) description
- Nonencapsulated lesion with ill defined edges
- Composed of variable sized mats and nests of benign and mature brain tissue in a background of vascularized connective tissue
- Histologically, brain tissue shows a predominant glial component and minimal neuronal component if present
- Glial component shows evenly dispersed astrocytes in a fine, neurofibrillary matrix
- Interspersed large gemistocytes, ependyma, choroid plexus, retinal epithelium, cerebellar tissue and leptomeninges may be present (J Cutan Aesthet Surg 2020;13:233)
- Rare proliferation of eccrine ducts
- Longstanding lesions show fibrosis and collagen
- Large amount of fibrotic tissue can undermine the glial tissue in H&E sections
- Inflammation, focal calcification may be seen
- Mitoses are absent
Microscopic (histologic) images
Positive stains
- GFAP (cytoplasmic) (Br J Ophthalmol 1993;77:817)
- S100
- Neurofilament: stains axons
- NeuN: stains neurons
- SSTR2A: highlights leptomeninges and arachnoid cells (Childs Nerv Syst 2022;38:63)
- Special stain Masson trichrome shows red staining of the glial tissue, whereas the background fibrosis appears blue (J Cutan Aesthet Surg 2020;13:233)
Negative stains
Molecular / cytogenetics description
- Not required for routine diagnosis
- Copy number profiling from global DNA methylation data showed a balanced genome
- One case showed significant copy number variation involving loss of chromosomes 16, 17 and 19 and gain of chromosomes 4 and 5 (Childs Nerv Syst 2022;38:63)
Sample pathology report
- Nasal swelling, excision:
- Glial heterotopia, intranasal type (see comment)
- Resection margin is free
- Comment: The tissue shows respiratory epithelium covered unencapsulated polypoid lesion with poorly defined borders. The lesion is composed of nests and patches of mature glial tissue showing evenly dispersed astrocytes in a fine, neurofibrillary matrix. Mitosis is absent. Based on combined radiologic features and histologic findings, the lesion is best characterized as nasal glial heterotopia. This lesion is typically benign with recurrence associated with incomplete excision.
Differential diagnosis
- True encephalocele:
- Extracranial hernias of the meninges or brain caused by congenital defects in the skull
- Intracranial connection present (Medicine (Baltimore) 2018;97:e12000)
- Histologically similar to heterotopia; imaging required for correlation
- Due to shared molecular alterations in a subset of nasal glial heterotopia and encephalocele, there is a strong suggestion that these 2 entities represent the same histopathologic entity (Childs Nerv Syst 2022;38:63)
- Teratoma:
- Congenital or developmental tumor derived from multipotent cells
- Extremely rare (2%) in head and neck region (Int J Pediatr Otorhinolaryngol 2015;79:1991)
- May present as a congenital nasal midline mass
- Differentiate into diverse types of tissue derived from the 3 germ layers (Chest 2005;128:2893)
- Histology shows derivatives of germ layers in variable combination
- Mature type contains neural tissue, teeth, skin, hair, fat, bone, cartilage, respiratory or intestinal epithelium
- Immature type has additional primitive neuroepithelium with rosettes, pseudorosettes or neurofibrillary matrix in some tumors (Iran J Otorhinolaryngol 2018;30:355)
- Neurofibroma:
- Neural tumor occurs in second or third decades of life
- Wide anatomic distribution but diffuse type neurofibromas usually arise in the head and neck region
- Histology shows spindle cells with wavy, tapering nuclei arranged haphazardly or in fascicles
- Stroma shows collagenous (shredded carrot collagen or homogeneous pink) rather than fibrillary appearance
- CD34 positive
- Ectopic meningioma / meningothelial hamartoma:
- Meningothelial neoplasm arises in children and young adults
- Usually occurs in the head and neck
- Histology shows syncytial lobules and whorls of spindle cells with regular nuclei and pale intranuclear cytoplasmic inclusions
- May show psammomatous calcifications
- Meningothelial hamartoma arises in infants; most common site is posterior scalp
- Shows slit-like pseudovascular spaces lined by spindle cells along with small clusters in a fibrocollagenous stroma
- EMA positive
- Congenital hemangioma:
- Benign vascular tumor, fully developed at birth (BMJ Paediatr Open 2020;4:e000816)
- Superficial, occurs commonly in head and neck region
- Have similar clinical presentations as heterotopia
- Usually presents as a reddish purple limited lesion covered with fine or coarse telangiectasia
- Frequently shows a pale peripheral halo (BMJ Paediatr Open 2020;4:e000816)
- Prenatal ultrasound diagnosis between nasal glial heterotopia and congenital hemangioma is difficult
- Fetal MRI is not very specific for distinguishing between the 2 lesions but excludes the presence of an intracerebral connection in case of heterotopia
- Postnatal exams are more specific (J Stomatol Oral Maxillofac Surg 2017;118:298)
- Histology shows poorly canalized vessels and mitotically active endothelium in rapid growth phase
- Lumina become prominent with maturation and a combination of solid and vascular areas in varying proportions may be seen
- Ganglioglioma:
- Glioneuronal tumor that makes up ~2% of all primary intracranial tumors (Childs Nerv Syst 2016;32:1839)
- Predilection for children and young adults (median age: 12 years)
- Mostly occurs in temporal lobe
- Histology shows biphasic tumor with variable mixture of mature appearing ganglion-like cells and atypical glial cells
- Large ganglion-like cells may show bi or multinucleation
- Atypical glial cells show moderate enlargement with hyperchromasia and mimic those of fibrillary astrocytomas, pilocytic astrocytoma or oligodendroglioma
- May show perivascular lymphocytic cuffing, eosinophilic granular bodies and dystrophic calcifications (Childs Nerv Syst 2022;38:63)
Additional references
Board review style question #1
A 6 month old infant presented with swelling in the nose since birth. Radiology showed a well circumscribed lesion with no connection to brain or dura. Histological examination revealed nests of glial tissue embedded in a fibrillary stroma. Which immunostain will be most likely expressed by the lesional cells?
- CD34
- Desmin
- EMA
- GFAP
- SMA
Board review style answer #1
D. GFAP. The glial tissue will be immunopositive for GFAP (J Cutan Aesthet Surg 2020;13:233, Br J Ophthalmol 1993;77:817). Answer A is incorrect because CD34 is a vascular marker and also shows positive expression in some fibrohistiocytic lesions. Answer B is incorrect because desmin is a myogenic marker expressed in skeletal muscle and smooth muscle lesions. Answer C is incorrect because EMA is positive in meningeal and epithelial cells (Oncol Lett 2013;5:768, J Oral Maxillofac Pathol 2023;27:604). Answer E is incorrect because SMA is expressed in smooth muscle cells and myofibroblasts in normal, reactive or neoplastic tissue.
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Reference: Glial heterotopia
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Reference: Glial heterotopia
Board review style question #2
Board review style answer #2
A. Benign. Nasal glial heterotopia is a benign lesion with a very good prognosis. Recurrence rate is low and related to incomplete excision (Int J Pediatr Otorhinolaryngol 2020;129:109728). Answers B - E are incorrect because the lesion does not show intermediate or malignant features.
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Reference: Glial heterotopia
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Reference: Glial heterotopia