“NASAL GLIOMAS” AND RELATED BRAIN HETEROTOPIAS: A Pathologist‘s Perspective

INTRODUCTION

Nasal gliomas arc rare congenital malformatiuns c.on1posc.d o f matiit-c neural tissue that present as intranasal (36%), cxtranasal (33%), 01-

combined ( 1 1%) masses, with over 130 cascs ~rcported thtrs f ~ r . ~ - ~ ! Ictcrotopic ncitral tissuc. a t other locations in thc hcad and neck region is even lcss common hu t has been reported in the n a s o p h a ~ - y n x , ~ - ’ ~ pal- ate ,’* ’ 3 3 l4 paranasal sinuses,’ ’- l su\>mantiit)uIar rcgion , ’‘ tonsillar fossa, ’’* ’’ orbit l S and scalp.’l Wc present here the clinical ;ind pithologic fcaturcs o f 3 casc‘s o f hctcrotopic h r a i n tissuc seen in o u r labolator), ovcr thc past 1 ?I ycars.

This paper was prcsr,ntcd i r i part at t hc intcrirn Iricc.ting uf tht. Pvdiatric I’atholoq Club, Vancouvrr, British Columbia, Canada, Ortobvr 6 , 1982.

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354 K. PATTERSON ET A L

CLINICAL MATERIAL

'I'hc clinical findings in the 5 patients are srimmari/.cd in 'Iablc 1. l h c a!;c's 'it the time o f surgct-). \,arictl f r o m ne\vborn t o 23 motiths. Thcrc \ w t x ~ 4 nialc ;itid 1 fcnialc. patients. Onlj, 1 patient (ciisc 4) hat1 respirator!. t l i s t r c . s h associated ivith the mass. Thrcc o f the masses ivcrc intranasal, onc W A S cxtt.itnasal, and one, which has been prc\.iouslJ. reported,20 was in the n:isoI)hiir!~ns aiid tonsilliir region. Preoperative radiologic cvidcticc. o f ;in

associated I,oii!. defect \viis seen in onlJ. 1 casc (caw 2), and tlural attac.hment o f that miiss \\'as docxinicntcd a t surgery. A second casc (casc .3) tviis found to have ;I CSF leak al ter removal o f a n intratiasal mass, and cr;iniotom). i.e\ritled ;in absent cristii galli and extension o f the tumcir t o t t i c s dur;i. Thc tiinlot- \v;is completely excised a t initial surger) in 2 exes. 1 1 1 1 ('asc (casc IS). the mass was incomplctcl)~ cxciscd, b u t tlicrc lids I)ccii t i o cliriic;il o r histologic cvidcncc o f recurrence in 24 months of f o l l o \ v - t i p . O n c c,isc (ciisc 4) undc~i.\vcnt an additional surgical pi-oc'cdittx* t o i-cmo\e tc,sidiial mass 2 months . i t tcr the primary cxcision.

'I'hc pithologic t indings i n ;ill 3 cases \vcrc siniilat-. Grossl>. the nasal 1niisu.s consisted ot' viirious-sixd picccs o f firm, lol>ulatcd, gray-tan tissue; tlic. i ) ha i~ .ngca l mass c:onsistcd o f I'lcshy rcd-1li-oit.n tissue ivith focal arcas ( 1 I' 1icmorrh:igc. hlicroscopic findings at-c siimmarizctl in 'Table. 2. Nodules o f titattitx. neural tissue. \ z ~ t - c cmbccidctl in a f ib rouscu la r stroma (Fig. 1). 'I'lit. pi-cdoniinantly glial nature oI' thc nodules wits confirmed 1)). l''I'i\II staining i t t ciise 1 and 1)) glial fibrillary acidic protcin staining etnplo) in!; 1 Ii c i i n in i i ti ( ) pc I'( ) xi tlasc, t c cl t n i q iic on lo r ma1 i t i - f i xc d , pai.;i f t i ti -c ni t)c.ddc d t issue (kit supplicd 1)). Imtnuiiolok o f Carpintcria, California) in thc I c.m;iitiinS c ~ * s . ;Ill (.;is( 'h I-cvcalcd reactive glial chatiqch including incrc.iiscd ( c l l ~ t l i i r i t ~ and gemisroc.! t i c - a s t r c q t c s . Xcurons \vcrc. idcntit ' ical~lc in 3 01' the ri c'iscs (Fig. 2) . 1lic.roscopic c;ilcit'ication was seen in 2 ciiscs (Fig. 2). .I'hc I)liara),ngcal miiss ( c x e 3 ) ivas distincti\.c f o r the prcs("ncc o f (icc;isiotial clefts lincd 1)) cpcndJ.mal cells (Fig. 3 ) .

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BRAIN HETEROTOPIAS 355

TABLE 2. littcrotopic Brain-Microscopic Ftaturrs

Cast. Location Astrocytrs Neuron Kpcndyma Calcification

1 Intranaral PTAH + - 2 Nasal bridge, c ; k h P t t

orbital rim

tonsil 3 Nasopharynx, G F A P + I

4 Intrariasal G F A P t- 5 In t ranasal ( ; IAP I t

Electron microscopy was performed in cases 3 and 5 on tissue fixed in glutaraldehyde, postfixed in osmic acid, and counterstained with iiran),l acetatc and lead citrate. By EhI abundant closcl). packed anisomorphic glial processes contained prominent loosely t o denscly packcd 1 0-nni filaments (Fig,. 4). Scattered cell bodies showed nuclei with varying amounts of associated cytoplasm containing promincnt 1 0-mi1 filaments, occasional mitochondria, and scattered glycogen pal-ticks. A well-defined basal lamina scparatcd cell processes from collagen bundles. Two nonglial

FICC'KE 1. Nodules of ccllular mature ncuroglial tissue embedded in a fibrovascular stroma. II&F., x 125.

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356 K . PATTERSON ET AL.

D I SCU SS I0 N

Clinicall>., it m;tss i l l [lie nose o r pharynx o f an infant or child presents ;I \viclc range o f diffcwntial diagnostic- p o s ~ i b i l i t i c s . ' ~ * ~ ~ I;,x;~min;ition of t h ( . tissue yvssl!; and especially microscopically n;irro\vs this rangc o f possihilitics. iVhcin ii biopsy spccimen reveals mature neural tissue, the tlil'l'crcntial diagnosis is limitcd t o three entities: teratoma, encephalocclc, or hcterotopic brain tissue ("nasal glioma").

:I teratoma is a neoplasm containing tissue from all three gcrm l ; i ) ~ ~ r s . ~ ~ Accurate niic.roscopic diagnosis is possiblc in an cxciscd lesion thrciiigh careful sampling of grossly varying arcas of tissue includiiig ;it least one tissuc block pcr ccntimeter o f specimen. B ~ C ~ L I W o f sampling

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BRAIN HETEROTOPIAS 357

limitations, a finding of mature neural tissue only in 11 biopsy sample does not rule ou t the possibility of a tcratoma.

An cncephalocele is a developmental anomal). that rcsults in herniation o f neural tissue and its accompanying leptomcningcs through a bony defect in the skull.2s ’I’herc arc two major categories of encephalocclcs: occipital, accounting for 75% of all encephalocclcs, and frontal, accounting for the vast majority o f the Frontal enccphalocclcs arc furthcr subdivided into two classcsZ6 : sincipital, accounting for 60% o f frontal enccphalocelcs, and basal, accounting f o r 40% (Table 3) . In most cascs, frontal enccph;docclcs can be distinguished clinicall), from other frontal masses by physical examination and radiological e v a l u a t i o r ~ . ~ ” ~ ~ Pathologic material from an cncephalocele consists 01’ mature neural tissue Liith varying degress of organization.*’ I h r a and leptomeninges ma)’ be recognizable and, i f s o , indicate that the tissue is from an encephaloccle. U’hcn recognizable lcptomeninges are absent, encephiiloceles can be distin- ,y 11 is h c d fro in h e t C I ( ) 1. o p i c b r ai n t i s s 11 e on I J, aft c r c 1 in i c ( ) p at h ol ogi c c or re 1 a- tion.

Hctcrotopic brain tissuc. in the head and neck region is matiirc neural tissue that docs not have a dircct cunncction wi1.h the subarachnoid

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BRAIN HETEROTOPIAS 359

TABLE 3. Frontal Enccphalocclr ___ - . -. -

Sitc or rclatcd T y pc Sitr o l ht,rniation Sitc of mass hctcrotopia

Sincipital ._ . . . . . _. . - . __ - -. . . - . -. . . - -

Nasofrontal Fonticulus nasofrontalis Forchcad: nasal Forc,hc.ad; nasal

Nasorthmoidal korarncn cc'cum Nasal bridge Nasal bridgc Nasoorbital Medial orbital wall Orbit Orbit

bridge hridgc

Basal Transc th moidal Cribriform plate In tranasal I n t ranasal

Sphcnocthmoidal R c t w e ~ n t.thrnoit1 arid Nasophar\ 11s Nasophai-) 11s

s phr noi d Transsphcnoidal Craniophar) ngcal canal Nasopharvrix I'alatc.

Sphcnornaxillary Supra- arid infraorbital Ptcrygopalatinr fossa -

(adenoid arra)

fissure __- __ - - __ . -. -. . __ ... ... . .

These heterotopias occur most commonly i n association with thc nose, where they have been traditionally but itiappropriatel\. called nasal gliomas. The mature neural tissue in these masses is not neoplastic in origin, as implied by the term glioma, but rather represents a dcvelopmcntal anomaly. The pathogenesis of these heterotopias is not positivc.1). cstab- lishcd. The following mechanisms have bccn proposed and extensively rcvic,.ed.2-4,6, 11 ,12 , l4- l6 , l9 ,27 ,29-35 .

1. Frontal cncephalocelc losing its cranial connection 2. Isolated totipotential cells giving rise t o .I glial tumor (i.c.,

3. Abnormal entrapment or migration o f glial cells from the olfactory monophasic tcratonia)

bulbs

The encephaloccle theory is now largcly accepted, with support for the theory from two sources. First, numerous reports describe transitional forms between enccphaloceles and heterotopias. L:p t o 25% o f nasal gliomas arc associated with an underlying bony defect Lvith o r withotit at tachment to the underlying dura by a fibrous stalk. ' 9 1 5 7 2 1 , 2 9 * 3 1 In addition, mature glial tissue may be present in the Second, locations of encephalocclcs and most rcportcd brain heterotopiiis arc similar (Table 3) . 'The submandibular massI8 and one lateral nasopharyngcal mass8 cannot be related to the reported cnccphaloc.ele sites, bu t in both cases the mass was traced t o a connection with the base of the skull.

The pathologic features of heterotopic brain tissue are wcll illustrated by the 5 cases presented here. In all 5 cases, irrespective of location, the masses were composed o f nests of mature neural tissue, without mitoses, and often showing reactive changes, embedded in varying amounts o f

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360 K. PATTERSON ET AL.

fibrovascular stronia. Occasional netirons have been reported in tip to 10% of c ; I s c s , ~ * ~ ~ ~ I s with 2 ( x s c s reporting al>undant n ( ! ~ i r o i i s . ~ ~ ~ ~ ~ 'I'hrcc o f the .i ciiscs rcportcd hcrc contained occasional iiciirons. Focal calcifications, UISO Imviously reported, \ v ( w prcscnt in 2 o f the current cases. Reactive changes, paiicity o f neurons, and focal calcifications arc iiorinal reactions o l neural tissue to poor vascular pcrfusion. These findings in hetcrotopic I>riiiIi tissue iire pr0l);ihly b ~ s t cxpliiincd by poor V ; I S C U I ~ ~ supply in the almormal In addition to the above findings. hctcrotopic brain tissue arising in thc ph;iryns frcqucntly shows morc complcx structures. Kpciidymal-lined structures, ;is sccn in casc 3 , arc reported in two-thirds o f the pharynpxd c;1scs4 '* lo* 13* 14- l9 but rarcly if' cver in "nasal slicinias." Choroid plcsuslikc striictiircs arc sccii dmost as frcqiiciitly. Pigmented cells, thought to rclwcsciit rctiniil differentiation, have idso bccn ol:casionally dcscril)ccl in thc pharyngeal hctcrotopias.'* I ' 111 1 rcportccl C;ISC a iiiclanotic iicnlocc.to<lcrnial tumor, thought to I)c o f neural crest oi'igiii, \vus iticorporiltctl in the pharyngcal hctcrotopia." Although the signit'ic*ancc o f tlicsc structures is not known, they arc postulated t o

iiidic;itc origin of the pharyngeal hctcrotopias at an earlier point o f ciiil~ryogcncsis than that o f the nasal h c t c r o t o p i a ~ . ~ * ' ~

I'Icctron microscop). \v;is done in 2 previously rcportcd cascs.1s*30 IN

I c;~sc t'i~)rous astrocytcs were found entrapped ~)ct\vccn coIlagcn fibrils." 111 t tic ~ t h c * r , ' ~ the iixiss was coniposcd o f fibrous and gcmistoc).tic iistrocytcs \vith occ:asion;il myelinatcd nerve fibers. 'I'hc astrocytc's \vcrc s(*rJitratcd from collagen hundlcs by a Ixisal lamina. Electron microscopic studies o i i 2 o f thc cuscs rcportcd here disclosed closcly packed glial procc'sscs containing iiiiint*roiis 10-nm filaments as well as nonglial structures appircntly rcl~rcscntiiig inicrogliiil cells and anosal proccsscs. Myth sheaths surrounding the asonal proccsscs \vcrc not sceii in this casc. perhaps because o f the \cry yoting age of the child at the time o f biopsy.

'I'\vo clinical fcitttircs o f 1)raiii hctcrotopias d c s c r ~ ~ coninicnt. Ilitrilcriiliiid cstcnsion u.ith dural ;ittachnicnt may bc difficult to dcmonstratc prcop- crativcly but u.hcn prcsciit can lead to a postoperative CSF leak with siibscqucnt risk of mciiiiil:itis. So cases o f intracranial attachment involving lesions o f the pharyiis liavc bccn r~portcd, suggesting that the potential fo r a CSF leak is much less in hctcrotopias in this location. Second, lit*tcrotopias exhibit the biologic bchii\Iior o f a slow-growing bcnign lesion. Kcciirrcnccs have hcvn r q o r t e d in only 4 - 1 0% of cascs2*29*30 and h a w tx*(*ii casily controllctl 1)). repeat surgery. Though ciirly cscision t o relieve respiratory cnibarrsssnicnt and t o prcvcnt continued Ilony dcforinity is often ~icccssary, aggressive and mutilating surgery in these lesions is not

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BRAIN HETEROTOPIAS 361

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