PERITONEAL DISSEM INATION FROM
CENTRAL NEUROCYTOM A
Case rep o rt
M aurício Coelho Net o
1, Ricardo Ramina
1, M urilo Sousa de M eneses
1,
Walt er Oleschko Arruda
2, Jerônimo Buzet t i M ilano
1ABSTRACT - Objective: central neurocytom a is a low grade tum or of neuroglial origin and a relatively new histological entity. Only a few cases have been reported and its biological behavior is still uncertain. Som e cases have shown an aggressive behavior (local recurrence, m alignant dedifferentiation or CSF dissem ination) and challenged the initial view of its relative benignity. A case of central neurocytom a with peritoneal dissem ination is presented. Case: a six years-old boy with recurrent neurocytom a of III ventricle and left thalam us showed fast growth of tum or rest and ascites three and a half years after subtotal rem oval of the lesion. Tum or cells were identified in the ascitic fluid and im planted in the peritoneum . Chem otherapy was initiated im m ediately after diagnosis of peritoneal dissem ination (etoposide, carboplatin, doxorubicin and cyclophospham ide). The patient developed m etabolic im balance and respiratory failure due to rapid form ation of ascitic fluid and died 3 days after the diagnosis of peritoneal dissem ination was established. Conclusion: central neurocytom a is a low grade tum or with low values of the proliferative index in the m ajority of cases. In spite of that, som e tum ors m ay present a very aggressive behavior and extraneural dissem ination. Evaluation of proliferative index m ay be a guideline param eter for planning adjuvant therapies after surgical treatm ent in selected cases. Extraneural dissem ination m ay occur in som e cases specially in patients with ventriculoperitoneal shunt.
KEY WORDS: central neurocytom a, intraventricular tum ors, neurog lial tum or, p eritoneal d issem ination.
DIsseminação peritonial de neurocitoma central: relato de caso
RESUMO - Objetivo: Neurocitoma central é tumor de baixo grau, de origem neuroglial e uma entidade neurológica relativam ente nova. Poucos casos foram relatados na literatura e seu com portam ento biológico é ainda incerto. Alguns casos apresentam com portam ento agressivo (recorrência local, diferenciação m aligna ou dissem inação liquórica) e desafiam a visão inicial de sua relativa benignidade. Apresentam os um caso de neurocitom a central com dissem inação peritonial. Caso: Um m enino de seis anos de idade com neurocitom a de III ventrículo e tálam o esquerdo recorrente apresentou rápido crescim ento do resto tum oral e ascite três anos e m eio após ressecção parcial da lesão. Células tum orais foram identificadas no fluido ascítico e im plantadas no peritônio. Quim ioterapia foi iniciada im ediatam ente após o diagnóstico de dissem inação peritonial (etoposide, carboplatina, doxorubicina e ciclofosfam ida). O paciente desenvolveu instabilidade m etabólica e insuficiência respitatória devido à rápida form ação de fluido ascítico e foi a óbito 3 dias após o estabelecim ento do diagnóstico de disseminação peritonial. Conclusão: Neurocitoma central é tumor de baixo grau com baixos índices de proliferação na m aioria dos casos. Apesar disto, alguns tum ores podem apresentar com portam ento m uito agressivo e dissem inação extraneural. A avaliação do índice proliferativo pode ser parâm etro indicativo para o planejam ento de terapias adjuvantes pós tratam ento cirúrgico em casos selecionados. Disssem inação extraneural pode ocorrer em alguns casos, especialm ente em pacientes com derivação ventriculoperitonial.
PALAVRAS-CHAVE: neurocitom a central, tum ores intraventriculares, tum or neuroglial, d issem inação p eritonial.
In st it u t o d e Neu ro lo g ia d e Cu rit ib a, Cu rit ib a PR, Brazil: 1Neu ro su rg ical Dep art m en t ; 2Neu ro lo g ist .
Received 12 March 2003, received in fin al fo rm 2 Ju ly 2003. Accep t ed 16 Ju ly 2003.
Dr. Maurício Coelho Neto - Rua Jeremias Maciel Perreto 300 - 81210-310 Curitiba PR - Brazil. FAX: 55 41 264-1238 - E-mail: [email protected] Sin ce it s first d escrip t io n b y Hasso u n in 19821,
cen t ral n eu ro cyt o m as h ave b een rep o rt ed as a lo w g rad e n eu ro g lial t u m o r, an d in t h e g reat m ajo rit y o f cases t h eir b io lo g ical b eh avio r m at ch es t h e h ist o lo
a n d cereb ro sp in a l flu id (CSF) d issem in a t io n h a ve b een d escrib ed in t h e lit erat u re. Th ese o b servat io n s h ave ch an g ed t h e in it ial co n cep t o f “b en ig n lesio n ” with indication for adjuvant treatm ent (radiotherapy) in ag g ressive t u m o rs2-11.
Th is case is t h e first o n e rep o rt in g ext ran eu ral t u m o r d issem in at io n o f a cen t ral n eu ro cyt o m a an d em p h asizes t h e clin ical an d h ist o lo g ical m alig n an t b eh avio r t h at cen t ral n eu ro cyt o m as m ay p resen t .
CASE
A 3-year-o ld b o y p resen t ed rig h t h an d d yst o n ia an d sig n s o f in t ra cra n ia l h yp e rt e n sio n . MRI a n d CT sca n e xa m in a t io n s d isclo se d a ve ry la rg e le sio n , w it h ca l-cificat io n s, in sid e t h e III ven t ricle, w it h ext en sio n t o t h e le ft t h a la m u s (Fig s 1 A, 1 B). As t h e p a t ie n t p re se n t e d hyd rocep halus, a ventriculop eritoneal shunt w as inserted . Th e p a t ien t w a s referred t o o u r clin ic fo r t rea t m en t o f t h e tum or. A stereotactic b iop sy w as p erform ed and the initial n e u ro p a t h o lo g ica l e va lu a t io n in d ica t e d a lo w g ra d e g lio m a . He u n d erw en t st ereo t a ct ic-g u id ed su rg ery, a n d t h e t u m o r w as su b t o t ally resect ed , w it h a sm all lesio n left in sid e t h e lat eral ven t ricle (Fig 2). Th e d efin it ive p at h o -lo g ical d iag n o sis w as cen t ral n eu ro cyt o m a (Fig 3).
Th e p o st o p erat ive p erio d w as u n even t fu l an d t h e p a-t ien a-t sh o w ed n o fu ra-t h er d eficia-t . Ra d ia a-t io n a-t h era p y o r ch e m o t h e ra p y w e re n o t in d ica t e d d u e t o t h e b e n ig n p at h o lo g ic ch aract erist ics (n eit h er at yp ias n o r n ecro sis) o f t h e lesio n . In sp it e o f revisio n o f t h e sh u n t 18 m o n t h s aft er su rg e ry, h e h a d a ve ry g o o d e vo lu t io n fo r t w o ye a rs (Karn o fsky p erfo rm an ce scale 100). Tw o years aft er t u -m o r re-m o val t h e p at ien t re-m ain ed asy-m p t o -m at ic b u t a fo llo w u p MRI exam in at io n sh o w ed t u m o r g ro w t h o f resi-d u al t u m o r. A n ew su b t o t al resect io n w as carrieresi-d o u t .
Th ree an d a h alf years aft er d iag n o sis t h e p at ien t p re-sented norm al social and school life. But on the 43rd m onth o f fo llo w u p , h yd ro cep h a lu s a n d t u m o r g ro w t h led t o in creased in t racran ial p ressu re syn d ro m e. An ad d it io n al sh u n t w a s in sert ed fro m t h e left la t era l ven t ricle t o t h e p erito n eu m . A w eek later, th e p atien t p resen ted in creased ab d o m in al vo lu m e an d vo m it in g . Ab d o m in al u lt raso u n d sh o w e d a scit e s. Pe rit o n e a l sh u n t d ysfu n ct io n w a s su sp ect ed an d t h e p erit o n eal cat h et er w as rem o ved an d a ve n t ricu lo a t ria l sh u n t w a s p la ce d . To re lie ve t h e resp irat o ry d ist ress cau sed b y ascit es, 1.3 lit ers o f ascit ic flu id w as d rain ed . Flu id an alysis d id n o t sh o w acu t e o r ch ro n ic in fect io n . In sp it e o f p erit o n eal cat h et ers rem o val, ascit es kep t in creasin g an d a vid eo lap aro sco p y revealed th e p resen ce o f sm all n o d u lar lesio n s in sid e th e p erito n eal cavit y. A b io p sy o f t h ese t u m o rs w as t aken .
Th e p a t ien t ’s co n d it io n d et erio ra t ed ra p id ly d u e t o m etab olic im b alance and resp iratory d istress. Patholog ical e xa m in a t io n o f t h e p e rit o n e a l le sio n s sh o w e d h ig h ly m alignant cells, with characteristics of central neurocytom a (Fig u re 4a, 4b ). Ch em o t h erap y (et o p o sid e, carb o p lat in , d o xo rru b icin e a n d cyclo p h o sp h a m id e ) w a s in it ia t e d im m ediately after peritoneal dissem ination was diagnosed. Th e p at ien t d ied t h ree d ays lat er.
DISCUSSION
Cen t ral n eu ro cyt o m a, d escrib ed in 1982 b y Has-soun et al.1, is a tum or with controversial histogenesis.
So m e au t h o rs su g g est it s o rig in fro m t h e g erm in al periventricular m atrix, which has the capability to d if-feren t iat e in t o n eu ro n al o r g lial t issu e12. Ot h er au
-thors attribute a neuronal origin of neurocytom as d ue t o t h e u n iq u e im u n o h ist o ch em ical o r u lt rast ru ct u -ra l fin d in g s su g g est in g n eu ro n a l d ifferen t ia t io n13-14.
On t h e o t h e r h a n d , g lia l co m p o n e n t , w h e n p re
-Fig 1A. CT scan show ing a large calcif icat ion i n si d e t h e l esi o n , o n e o f t h e cen t r al neurocyt oma pat t erns.
Fig 1B. M RI (T2-w eigt h) demonst rat ing a large lesion coming f rom III vent ricle and invading t he lef t t halamus.
Fig 3. Higher magnification demonstrates the diffusely dispersed and delicate chromatin pattern in the uniform round nuclei, and perinuclear halos. Anuclear zones with dense fibrillary processes are present. Magnification, X400 H.E.
Fig 4A. Invasion of perit oneum by cent ral neurocyt oma. M agnif icat ion, X400, H.E.
se n t , is m o re freq u en t in ext raven t ricu lar t u m o rs15.
Th is t u m o r is t yp ically lo cat ed in sid e t h e lat eral ven tricles, usually next to the Monro’s foram en and sep -t u m p ellu cid u m , an d m ay reach -t h e -t h ird ven -t ricle an d p eriven t ricu lar t issu e. It s freq u en cy is ext rem ely
low. It represents 0.5% of all intracranial tum ors15-16.
It is m ore freq uent from 20 to 40 years of ag e (ab out 7 0 % o f d e scrib e d ca se s). It is e xt re m e ly ra re in ch ild ren15. Du e t o b en ig n ch aract erist ics an d g o o d
Fig 4B. Synapt ophysin immunoreact ivit y consist ent w it h t he neurocyt ic nat ure of t he t umor cells in perit oneum. Avidin-biot in-peroxidase met hod, magnif icat ion, X400.
classified as b en ig n (g rad e I) b y t h e WHO Classifica-t io n u n Classifica-t il 19932.
The description of cases with poor evolution due to aggressive behavior, recurrence or CSF dissemination, leaded to change of classification of neurocytomas to grade II by the WHO in 1999 (low or uncertain ma-lignant potential or borderline m alignancy)2-11,15,17-19.
Thirty-two p atients were d escrib ed as having aggressive tum or b ased on clinical sig ns, rad iolog ical chan -ges (progression or recurrence) or by histological fin-dings (e.g. atypias, vascular proliferation or necrosis) 2-5,9-11,17,19-21. On ly 6 cases p resen t ed in t ran eu ral CSF
d issem ination of the tum or3-4,9,22.This is the first case
rep orting CSF d issem ination outsid e the CNS. Th is case p resen t ed an in it ial g o o d clin ical evo lu -t io n , b u -t sh o w ed a fo rm o f p ro g ressio n u n kn o w n for this type of tum or. The actual pattern of biological b e h a vio r o f t h e ce n t ra l n e u ro cyt o m a s is p o o rly understood. Schild et al.16 described a series of central
neurocytomas with benign histology and postoperative survival rate of 80% in 5 years of follow up. Different treatm en t sch em es, fo llo w u p criteria an d clin ical evolution have been observed in other series2-3,16,18,23-24.
Th is kin d o f t u m o r is ext rem ely rare in ch ild ren15.
Com pared to other low grade tum ors in children with b en ig n b eh avio r an d a lo n g su rvival (m o re t h an 5 ye a rs), ce n t ra l n e u ro cyt o m a s in ch ild h o o d m a y even t u ally b eh ave as a h ig h g rad e t u m o r. Calcifica-t io n , a co m m o n fin d in g in Calcifica-t h is kin d o f Calcifica-t u m o rs, m ay
reflect slo w t u m o r g ro w t h25. Th e p resen ce o f h ig h
p ro liferat io n in d ex areas, m easu red t h ro u g h MIB-1, m ig h t b e h elp fu l t o p red ict recu rren ce an d d issem i-nation22.
Su rg ery o f d eep -seat ed b rain t u m o rs h as g reat ly im p ro ved in t h e last 10 years. St ereo t act ic-g u id ed n eu ro su rg ery an d n eu ro n avig at io n h ave im p ro ved t h e rat e o f t o t al t u m o ral resect io n26. Su rg ical t reat
-m en t o f t h ese t u -m o rs sh o u ld t ake in t o acco u n t t h e invasion of the periventricular tissue. Com plete resec-t io n is easier in p u rely in resec-t raven resec-t ricu lar resec-t u m o rs, w h en co m p ared t o t u m o rs w it h t h alam ic in vo lvem en t . Se-veral au t h o rs rep o rt ext en sio n o f resect io n as a key fact o r in p ro g n o sis. Su b t o t al resect io n w o u ld lead t o h ig h e r ra t e s o f re cu rre n ce a n d lo w e r su rvi-va l11,16,25,27. A lit erat u re review o f 127 cases h as sh o
w ed t h at o n ly ab o u t h alf cases t h e cen t ral n eu ro -cyt o m a s w e re t o t a lly re se ct e d25. Ext ra ve n t ricu la r
ext en sio n h as b een co n sid ered b y so m e au t h o rs as a fact o r o f b ad p ro g n o sis27,28. So m e au t h o rs h ave
tried to correlate find ings of p ositron em ission tom o-g rap h y (PET) w it h p ro o-g n o sis24. Sp ect ro sco p y m ay b e
a helpful diagnostic tool to define differentiation pat-t ern s23. Measu rem en t o f p ro liferat ive in d ex t h ro u g h
MIB-1 h as b een sh o w n t o b e a reliab le p ro g n o st ic fact o r. Tu m o rs w it h a p ro liferat ive in d ex h ig h er t h an 2 h ave a t en d en cy t o p resen t a w o rse p ro g n o sis2,6,8.
Th e u se o f rad iat io n t h erap y h as b een in d icat ed for cases with sub total resection16. Rad iation therap y
w o u ld b e h elp fu l fo r it s in d irect effect , w it h t h ro m -b o sis o f feed in g vessels t o t u m o r rem n an t s5. So m e
au t h o rs h ave d isag reed w it h t h is p ro ced u re d u e t o it s lo w effect in t u m o rs w it h lo w p ro liferat ive in -d ex5,29. Rad io su rg ery h as b een m en t io n ed as a very
e ffe ct ive a d ju va n t t re a t m e n t fo r re cu rre n ce s, ach ievin g co n t ro l o f t h e d isease in t h e t o t alit y o f t h e reported cases in the literature18,30-31. Radiosurgery also
could avoid re-op erations for sm all recurrences30-31.
Rad iat io n t h erap y o f t u m o r b ed w it h d o ses ran g in g fro m 48 t o 60 Gy is reco m m en d ed5,16. A few cases
o f CSF d isse m in a t io n w e re re p o rt e d3 -4 ,9 ,2 2 a n d
rad iation therap y of the neuraxis and the use of che-m o t h erap y fo r in t rat h ecal iche-m p lan t s w ere in d icat ed . To o u r kn o w led g e, t h ere are n o d escrip t io n s o f ca-ses w it h ext ran eu ral m et ast asis o f cen t ral n eu ro cy-tom a caused b y ventriculop eritoneal shunt. Ad juvant t h erap ies sh o u ld p ro b ab ly b e in d icat ed in cases like o u rs. Rad iat io n t h erap y w as n o t u sed at first h an d in o u r case d u e t o p at ien t ’s lo w ag e at t h e t im e o f d iag n o sis an d t h e b en ig n h ist o lo g ical fin d in g s. Rad iat io n t h erap y m ig h t b e p erfo rm eRad in cases o f su b -total resection of high p roliferative ind ex tum ors (≥2) an d /o r vascu lar p ro liferat io n , t u m o rs w it h cellu lar at yp ias an d n ecro sis, an d in cases o f recu rren ce an d t u m o r rest g ro w t h even w it h lo w p ro liferat ive in d ex (< 2). In cases with intrathecal im plants cerebrospinal irrad iat io n w o u ld b e in d icat ed .
Th ere are very few rep o rt s u sin g ch em o t h erap y as ad ju van t t reat m en t3-4,22,32. A g o o d in d icat io n fo r
t h is p ro ce d u re w o u ld b e ca se s w it h CSF t u m o r d issem in at io n an d sm all ch ild ren .
In co n clu sio n , cen t ra l n eu ro cyt o m a sh o u ld b e co n sid ered as a p o t en t ially ag g ressive t u m o r w it h u n ce rt a in b e h a vio r. Dist a n t im p la n t in sid e a n d o u t sid e t h e n eu ro axis is rep o rt ed in t h e lit erat u re an d in o u r case. Early d ist an t im p lan t s sh o u ld b e so u g h t w it h MRI exam in at io n o f t h e n eu ro axis an d cyt o lo g ical st u d ies o f CSF. Rad io su rg ery co u ld b e in -d icate-d for cases with recurrence an-d for cases when a su b t o t al resect io n w as ach ieved an d t h e p ro lifera-t ive in d ex is h ig h .
Acknow ledgments - We t h an k Lu iz Fern an d o Bleg g i To rres, MD, Ph .D. an d Mario Mo n t em o r, MD fo r p ro vid in g t h e p at h o lo g ical st u d ies an d p ict u res.
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