Cranial subdural metastases: A clinicopathological study

CRANIAL SUBDURAL METASTASES: A CLINICOPATHOLOGICAL STUDY G. Sieben*, J. de Reuck, W. de Caster and H. pander Eecken

SUMMARY Duringa period of 10 years, 2782brains were examined at post-mortem and in 17 cases metastases were attached to the dura mater, 8 presenting as mutiple nodules 6 as a single nodule and 3 as diffuse dural thickening. The primary growths were, in equal proportions sarcomas, epitheliomas and lymphoid tumours. Incontrast to the frequent location of metastases in the axial skeleton (9 cases), brain involvement was rarely observed (2 cases). The clinical findings were non-specific. The difference in biological behaviour between subdural and intracerebral metastases is stressed.

INTRODUCTION

The clinical, neurological and neurosurgical aspects of tumours of the cranial vault have been the object of many studies and reviews (MEYER and REAH, 1953; ALLIEZ et al., 1972; GERLACH, 1974; RUSSELL and RUBINSTEIN,. 1977; DEBOIS and VAN DEN BERGH, 1979). In these studies the dural location of metastases at the level of the skull’is scarcely mentioned, in contrast to those of the spine. WILLIS (1952) discussed the way of spreading of cranial subdural metastases. This author stated that direct invasion through the dura mater of a skull-metastasis is rare and found blood-born metastases in 13 cases out of 500 necropsies. In the reviewed cases, the primary growths were in most instances a mammal carcinoma, a pulmona~ carcinoma and a melanoma. In the last instance, Willis mentioned invasion of the dural venous sinuses. RUSSELL and RUBINSTEIN (1977) gave considerable attention to local tumours invading the meninges. They found in many instances penetration of the dura mater by bone metastases. The occurrence of haematogenous dural metastases without bone involvement was considered to be rare. MEYER and REAH (1953) described 20 cases of diffuse dural involvement and 9 cases of pachymeningitis haemorrhagica interna. However, they excluded nodular dural tumours in their series. Out of 167 patients, who underwent craniotomy for a metastatic intracranial tumour, only 2% showed a dural location (HAAR and PATTERSON, 1972). * NeuropathologyUnit, Departmentsof Neurologyand Pathology, University Hospital, De Pintelaan 135 9000 Ghent, Belgium. Clin. Neurol. Neurosurg. 1981. Vol. 83-2 (Accepted 28.4.81).

Fig. I. A solitary subdural metastasis of a plasmocytoma at the convexity of the left hemisphere in the case of an 44 year-old woman (case 9). Inset: histological appearance (Haematoxylin-eosin: 250 x).

In a series of 10477 autopsies AMBIAVAGAR and SHER (1978) observed malignant tumours arising outside the central nervous system in 2508 cases, of which 437 had metastases in the central nervous system. Of the latter 38% involved only the meninges. It is not stated however whether or not spinal dural metastases were included. The present study reports the findings in a series of 2782 autopsies, concerning frequency, way of spreading and pathological appearance of cranial subdural metastases. Whenever on record, the site of other metastases and the clinical implications of the dural location were included.

MATERIAL AND METHODS

During a period of 10 years, 2782 human brains were examined in the Neuropathology Unit. In every instance the cranial dura mater was removed together with the brain and examined after fixation in a 4% formaldehyde solution. 77 intracranial metastases were found. In 17 cases the metastases were attached to the dura mater

Fig. 2. Diffuse thinckening of the dura mater in the case of reticulum cell sarcoma in a 6 year-old child Inset: histological appearance (Giemsa: 640 x).

(case 17).

and extended into the virtual space, known as subdural space (HOUSE and PANSKY, 1960) between the dura and the arachnoidea. Only macroscopical visible tumours were included in this study. Subdural hematomas with secondary invasion of malignant cells (5 cases) and microscopical agglomerations of tumour cells in the dural sinuses in cases of lymphomas were excluded (DE REUCK et al., 1976 and 1979). The subdural metastases were examined histologically on paraffmembedded material with haematoxylin-eosin, trichrome, Periodic acid Shiff, Giemsa and reticulin stains.

RESULTS

a Pathologic findings (Table 1) In 6 cases of subdural metastases a solitary nodule was present, attached to the dura mater, with extensions into the subdural space (Fig. 1). The maximum diameter was 5 cm. There was an impression on the underlying brain but no ingrowth. In 8 cases multiple small nodules with a diameter of less than 1 cm were

Neuroblastoma

Synoviosarcoma

Plasmocytoma

Melanosarcoma

Immunocytoma

Anaplastic epithelioma Lymphosarcoma Epithelioma

7

a

9

10

11

12

17

15 16

13 14

Lymphoma Anaplastic epithelioma Reticulum cell sarcoma

Rhabdomyosarcoma Liposarcoma

5

6

Adenocarcinoma

Lymphonodi

Reticulum cell sarcoma Rhinopharynxcarcinoma Leiomyosarcoma

Lymphonodi Probably breast Probably lymphonodi

Lymphonodi Nasopharynx

Breast

Probably meninges Lymphonodi

Bone Marrow

Rhinopharynx Surrenal gland Left knee

rynx

Thinopharynx Funiculus spermaticus Probably lung Rhinopha-

Primary location

Histological Type

4

3

2

C A S E 1

1 nodule Multiple nodules Diffuse invasion

Multiple nodules Brownish diffuse thickening Multiple nodules Multiple nodules Diffuse thicckening Multiple nodules 1 nodule 1 nodule

1 nodule

Multiple nodules Multiple nodules 1 nodule

Multiple nodules 1 nodule

Subdural metastasis

Table 1. Pathological and clinical findings in 17 cases of cranial subdural metastases.

+

+

+

+

?

!

n

?

Vertebrae Skull

Skull

Vertebrae

Sternum

Multiple nodules

Multiple nodules

Not listed

Diabetes insipidus None Intracranial hypertension None Not listed

Meningeal irritation None

Unilateral exophthalmy Pseudohermaphroditism Meningeal irritation None

None

Ptosis right eyelid Intracranial hypertension Headaches

Neurological symptoms

+

Cerebral involvement

Not listed

Non related bone metastasis

+

Related bone metastasis

85

seen. These nodules were scattered throughout the dura or confined to one area. In 3 cases a diffuse dural involvement was found (Fig. 2). In 2 of these only a diffuse thickening and slight discoloration of the dura was noted, while in the 3rd case the dura had a brownish colour. The brain was normal in 15 cases. Only in 2 cases additional cerebral metastases were present. Axial bone invasion was found in 9 cases. In 6 of the 9 cases the bone invasion of the skull was directly related to the subdural metastasis while in 3 the bone and subdural metastases were at a distance from each other. The type of primary tumour and its location are labeled in Table 1. In 5 cases an epithelioma was found, in 5 cases a sarcoma, in 6 cases a lymphoid tumour and in 1 case a neuroblastoma. b Clinical findings The clinical findings are labeled in Table 1. In 3 cases the clinical tiles were not available. In 5 other patients symptoms were absent. In 5 cases the clinical symptoms could be attributed to intracranial hypertension. In 2 cases, involvement of the cranial nerves, due to destruction by the tumour, was the main feature. In 1 case pseudohermaphroditism was present, and in another patient there was diabetes insipidus.

DISCUSSION

This series of subdural metastases, although rather limited, leads to some interesting conclusions. Subdural metastases can present varying macroscopical appearances, either as a large solitary mass, or as diffuse dural thickening and discoloration. These differences can not be attributed to the histological type of the tumour, nor to the formation of the metastasis (by local invasion or haematogenous spread). Furthermore, it is impossible to recognize clinically these varying appearances. Subdural metastases per se mostly seem to have no specific clinical significance. The presence of neurological symptoms solely depends on the extent of the tumours, their location, and the involvement of other nearby structures such as the cranial nerves. It should be noted that in this series there are no signs of cortical irritation, which are frequently observed in cases of meningeomas (GILROY and MEYER, 1975). There seems to be a close relation between the occurrence of dural and axial bone metastases. On one hand their frequent association is due to the number of bone metastases invading the dura mater directly, and in addition to the existance of a communicating venous plexus between bone and dura mater, which makes venous spreading of tumour cells at a distance more frequent (BATSON, 1940). In the present series, subdural metastases originating from bone invasions or local growths are as frequent as the ones in which haematogenous spread is presumed because of the absence of nearby tumour growth in bone. There are, however, only 5 cases in which there is no skeletal involvement at all, which makes in these cases a blood-born process highly probable. There is a clear-cut difference in the type of tumours giving metastases to the

86 brain and to the dura mater. Cerebral metastases most frequently originate from epitheloid malignant growths (SIMIONBSCU, 1960; RUBINSTEIN, 1972), whereas in our se&s, there is a high proportion of sarcomas and lymphoid tumours. Even so, it appears that cerebral and dural metastases do not frequently occur together in the same patient. These findings could suggest a preferential site of metastasis of epitheliomas into the brain parenchyma, whereas sarcomas and lymphoid tumours tend to have a predilection for subdural metastases with sparing of the cerebral tissue. These findings correlate with those reported for spinal dural metastases (HILDEBRAND, 1978). This study stresses the difference in biological behaviour and clinical significance between cranial subdural and intracerebral metastases.

REFERENCES ALLIEZ, FL, J. E. PAILLAS, M. VIGOUROLJX, J. F. PELISSIER and

A. DEBAENE (1972) Tumeurs cerebrales la dure-mere. Etude anatomoqie, clinique et radiologique. Neurochirurgie 18: 453. P. c. and J.SHER (1978) Subdural hematoma secondary to metastatic neoplasm. Cancer 42:

envahissant AMBIAVAGAR,

2015. BATSON, o. v. (1940) Function

of the vertebral veins and their role in the spread of metastases. Ann. Surg. 112: 138. DEBOIS, v. and R. VAN DEN BERGH (1979) Benign tumours of the cranial vault. Clin. Neurol. Neurosurg. 81: 1. GERLACH, J.(1974) Tumours of the cranial vault. In: ‘Handbook of Clinical Neurology’, P. .I. Vinken and G. W. Bruyn, vol. 17, North Holland Publishing Company, Amsterdam: 104. GILROY, J.and J.s.MEYER (1975) ‘Medical Neurology’. Mac Millan Publishing Co. Inc., New York. HAAR, F. and R. H. PATTERSON (1972) Surgery for metastatic intracranial neoplasm. Cancer 30: 1241. HILDEBRAND, J.(1978) Lesions of the nervous system in cancer patients. Monograph series of the european organization for research on treatment of cancer. Vol. 5. Raven Press, New York. HOUSE, E. and B. PANSKY (1960) A functional approach to neuro-anatomy. McGraw-Hill Book Company,’ Inc., New York. MEYER, P. c. and T. G. REAH (1953) Secondary neoplasms of the central nervous system and meninges. Brit. J. Cancer 7: 438. REUCK DE, J.,H. ROELS and H. VANDER EECKEN (1976) Complications of the chronic subdural hematoma. Clin. Neurol. Neurosurg. 79: 203. REUCK DE, J.,w. DE COSTER and H. VANDER EECKEN (1979) Communicating hydrocephalus in treated leukemic patients. Eur. Neurol. 18: 8. RUBINSTEIN, L. J.(1972) In : ‘Tumours of the central nervous system’. Atlas of tumour pathology. Armed Forces Institute of Pathology. Washington D.C. RUSSELL, D. s.and L. J.RUBINSTEIN (1977) Secondary neoplasms of the nervous system. In: ‘Pathology of tumours of the nervous system’. Fourth edition. Edward Arnold Publishers Ltd. SIMIONESCU, M. D. (1960) Metastatic tumours of the brain. A following-up study of 195 patients with neurosurgical consideration. J. Neurosurg. 17: 361. WILLIS, R. A. (1952) The spread of tumours in the human body. Butterworth and Co (publishers ltd). London, England.

DO~~lD~td~ft~nlsal, MSD) is ee” lang werkend analgetrcum dat bll de behandekng van chronlsche en acute p~fn meestal goed wordt verdragen. ‘D&c& kan tweemaai daags worden toegediend. ‘Doioc~d’ wordt na orale toadlenlng ~rv.‘~el geheel geresorbeerd en “a ongeveer twee uur wordan de maxtmale plasmaspiegels bereikt Pifn~erl~chtl~g treedt me&al op bvnnen 6Bn uur na lnnemlng van eenenkelvoud~ge therapeuttsche dosls Aangazlen ‘Dolocld’ een dlfluorofenyldenvaat “a” saticylzuur IS, kan een lnvloed op de Piaatfesaggregatle wet warden uitgesloten lndiwtiar ‘Dolocici IS gendiceerd vow verlrchtng van acute en chronwhe pqn en IS onderzocht bq de volgande aandoanlngen. arthrosls deformans tosteoartrose).\lumbago. POsttraumatlscba piin bif VerrekkinQan en verstuikmgen, plf” “a eplslotomle, PI,” na orthopedlsche operatles a” klesplln “a tandheelkundige ~“greper

Contra-indlceti.4 Overgevoeligheld war d!flunisal. Patlenten met acute astma-aanvallen I” de anamnese als gevolg van het gebrulk van salicyfaten ot nlet-hormonale antI-lnfiam~atolre mlddelen. 1 Het mlddel mag nlet worden toegedlend aan patlenten met een actwe maag-darmbloeuing. Het gebrulk van ‘Dolocid’ dlent vermeden te worden bl patlenten met een actlef ulcus peptlcum en bil patlenten met ernstw mar-

funcllestoornlssen

Gebruik bil zran@emchap .n ti]dms Iactatle. Over het gebrulk van deze stof in de zwangerschap by de mans bestaan onvoldoende gegevens om de mogelqke schadellfkhe!d te beoordelen Over de effecten in de dlerproef bestaan Onvoldoende gagevens omde mogelllke schaoeilfkhald te beoordelen. Zoals met atie orostaglandlneremmers IS op grand van farmacologlsche werkzaamheld schadellfkheld blj gebrwk trfdens zwangerschap mogelijk Aangezten de velligheid voor deze toepasslng nag met IS vastgesteld. dtent ‘Dolocld’ net te worden toegedlend aa” zwangeren Zogende moeders mogen gee” ‘Doloc~d‘ gebruiken of dlenen de borstvoedlng te staken ‘Dolood dtent&?! voornchtig
metJntlcoll~ti&

wlsnlwuklyi (zle Waarschuwlngen

en voorzorgsmaatregelen)

Ond&toekrngen van de belde middefen 10wtro naar de plasmablnding brachten gee” belangrtjkt verdrlnglng van fenprocoumon aan het kcht Een gennge whoglng van de trombosetestWaardeniprotromblnet~Jd werd vermeid bq dne van de zeven patlenten die ‘Dolocld’ in een dosertng van tweemaal daags 375 mg kregen &amen met fenpiocoumon In de warden van Factor II, VII en X deden zlch gee” klinlsch belangqke vetanderlngen ‘voor

Een verlenglng van 2-3 seconden in de protrombinett)Q werd geconstateerd btfdrlevand6 zes patlenten die ‘Dolocid’ kregen in een dosetinS van tweemaal daags 375 mg &amen met acenocwmarol Er werden geen klnsch belangwke wanderingen ,n Factor /I. VII en X gevooden Dosering en tobdienlng De doserlng moet aan de aard en de lntensltell van de olln worden aanoeoast en het mlddel dent b&emaai daags tg &den toegedvand De hoogste bll de mens onderzochte doserlng IS 1 g per daQ Da laagste &nmallge doses die b\t de me”s de pi!” bleek te stillen was 125 mg Dowlng blj acute kortdumnde pijn De aanvangsdosls dlent twee tabletten te zljn Daama naai behoefte tweemaal hen of twee tabletten

600 mgl drags

Dowins blj chronische, mcldiverende ptjn De aanvangsdosls IS twee tabletien I500 mg) Daarna tweemaal daags BBn tablet met een mawnum van 750 mg/dag De meeste patlenten reageren op de aanbevoien dosering van tweemaai daags &n tablet

‘Doioc~d’ wordt me&al goed verdiagen De bqwerklngen die zlch voordoen. betreffen de regel het maag-datmkanaal

in

htasg-dannkanasl Maagplfn. zuurbranden, dlarree. mrsselqkheld en braken zlfn vermeld Enkele gavallen van maag~ darmulceia en -bloedingen zttn voorgekomen

Prurltus. huldultslag. urt!carla. erythema morbill~formum, hyperhtdrosis. lrfltatre van het slilmvlles van mend en/of tong z~]n beschreven. Enkele gevallen van erythema multlforme waaronder het Stevens-Johnsonsyndroom zqn vermeld; een oorzakeiitk verband met ‘Doloc~ti IS nlet vastgesteld Krulsovergevoellgheld met sallcylaten komt mogellfk voor Centraei zenuw*teieal Dutzellgheld en Slaperlgheld

LI]” vermeld.

Overdowring Et IS weimg ervartng met de objectleve en subjectleve symptomen of de behandellng van overdosertng Wanneer een acute ovardos~s IS genomen. de maag door braken of spa&n te wotden geleegd. hoewel er waarschljnllfk weinlg geneesmlddel zal worden teruggevonden ais er meei dan e&n bwr na innemng is v&open Probeer de nrerfunctle tn stand te houden om de ultscheldlng van het mlddel met de wne te bevorderen AlkalwJle van de urine en dlurese kunnen de ~itschelding verhcgen Vanwege de hoge mate van elwttblndlng wordt hemodlalyse ontraden

dent

VsrWkkina ‘Dolccld’ IS verkrltgbaar per 10 doordrukstrlps van 10 tabletten ti 250 mg Codenummer MSD 675 In het register ngeschreven onder RVG 07680 UltVoerlQer lnilchtlngen gaarne verstrekt.

-

WOrden u ol, verzoek

Postbus 581. 2003 PC Haarlem. Teleloon 023.319330

GiJ 0 0

individuele ~~de~gv~ de ziekte vanPar!~n

mogelijk 10 tng carbidopa 100 mg levt>cfopa cock MSD 647

2 5 mg I()() cock

cdrbiciopa

Flkg k\Vcit

)pd

MSD 60

2 5 tng carbictopa 2 S0 mg levcxk~pa code MSD 654

Divisie van Merck Sharp & Dohme B.V. Postbus 581, 2003 PC Haarlem, Telef?)on 023 3 193 30