Arq Neuropsiquiatr 2006;64(2-A):300-302

D e p a rtment of Neuro s u rg e ry, Hospital Nossa Senhora das Graças, Curitiba PR, Brazil: 1Resident in Neuro s u rg e ry; 2N e u ro s u rg e o n ;3Neurosurgeon, Federal University of Sergipe (Aracaju SE, Brasil); 4Neurosurgeon Director of the Residency Program.

Received 7 June 2005, received in final form 16 January 2006. Accepted 23 January 2006.

D r. Joacir Graciolli Cord e i ro - Rua Alcides Munhoz 433 - Neuro c i ru rgia - 80810-040 Curitiba PR - Brasil. E-mail: joacirg c @ h o t m a i l . c o m

CEREBRAL META S TASIS OF CERVICAL UTERINE CANCER

Report of three cases

Joacir Graciolli Cordeiro1, Daniel Monte-Serrat Prevedello2, Léo Fernando da Silva Ditzel2, Carlos Umberto Pereira3, João Cândido Araújo4

ABSTRACT - Cervical uterine cancer (CUC) spreads locally (pelvis and paraortic lymphnodes) or distantly(lungs, liver and bones). Metastasis to central nervous system (CNS) are rare. There are about 80 casesre p o rted in the literature. Outcome is poor and survival varies from 3 to 6 months. Three cases of CNSmetastasis from CUC are reported, one infratentorial and two supratentorials in location. In one patient,the initial manifestation was due to the cerebral lesion, a feature re p o rted for the first time. All cases weret reated by surg e ry, radiotherapy and/or chemotherapy. Clinical findings and treatment options of theserare lesions are reviewed.

KEY WORDS: cerebral metastasis, cervical uterine cancer.

Metástases cerebrais de câncer de colo de útero: relato de três casos

RESUMO - Tumores do cólo uterino se disseminam por contigüidade ou via hematogênica (pulmão, fíga-do e ossos). Metástases para sistema nervoso central são incomuns. Apenas cerca de 80 casos são citadosna literatura. Manifestações clínicas são devidas à hipertensão intracraniana e a déficits focais. A sobrevi-da varia de 3 a 6 meses. Três casos são relatados sendo um infratentorial e dois supratentoriais. No primeiro ,o diagnóstico da metástase antecedeu o da lesão uterina. No segundo, houve 5 anos sem recidiva após ac i ru rgia, fato este inédito. O tratamento foi ciru rgia, radioterapia e/ou quimioterapia. A discussão enfati-za manejo multidisciplinar destas raras lesões.

PALAVRAS-CHAVE: metástase cerebral, câncer de colo uterino.

C e rvical uterine cancer (CUC) is responsible for15% of deaths due to cancer in women older than15 years of age in Brazil1. It most often invades locals t ru c t u res, reaching pelvis and paraortic lymphnodes.Distant organs are reached by haematogenous dis-s e m i n a t i o n1 - 4. The frequency of distant organs metas-tasis varies from 38 to 85%5 - 7. Haematogenous spre a dis responsible for a more aggressive behaviour. Mostcommonly affected distant organs are lungs, liverand bones6. Brain involvement is extremely rare1 - 2 4.T h e re are re p o rts of cervical cancer metastasis to pitu-i t a ry gland, pancreas, ure t h e r, kidney, adrenal gland,ovaries, uterine tube, gallbladder, spine cord and toa convexity brain meningioma5,10,18,21,24.

The objective of this article is to re p o rt three cas-es of cerebral metastasis from cervical uterine can-cer and to discuss their clinical features and tre a t-ment options.

This study was perf o rmed with the approval ofthe Ethics Committee of the hospitals where theset h ree patients were treated. Informed consent wasobtained from either the patient or a relative in allcases.

CASESCase 1 – A 60-year-old woman was admitted with a scalp

lesion, history of local trauma and antibiotic therapy with-out improvement 30 days before admission. She had noother complaints. Physical examination revealed only anulcerated left parietal-occipital scalp lesion. Skull X-ray de-monstrated an osteolytic pattern. CT scan revealed a hypo-dense right parietal-occipital cerebral lesion with ringenhancement and perilesional edema. The lesion was sur-gically removed and pathological diagnosis was that of ametastatic adenocarcinoma. Systemic screening re v e a l e dCUC II B clinical stage. She did not return for follow-up.

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Case 2 – A 31-year-old woman was admitted withheadache and visual deficit since 2 weeks before admis-sion. She had been submitted to lung metastasis re s e c t i o nfrom CUC 10 months before admission in another service.She received adjuvant chemotherapy and local radiother-a p y. On physical examination she presented right homony-mous hemianopsia. Cranial MRI revealed a 3 cm diameterleft occipital lesion with ring enhancement, perilesionaledema and central hypointensity in T1 and hyperintensityin T2-weighted images (Fig 1). The lesion was completelyremoved by craniotomy and pathological diagnosis wasthat of low diff e rentiated carcinom a similar to her cerv i-cal uterine cancer. She received adjuvant whole brain radio-t h e r a p y. Postoperative period was unremarkable and shepresented no other deficits. She had no recurrence of the

lesion and no other neurological manifestation in 5 yearsof follow-up (Fig 2).

Case 3 – A 31-year-old woman was admitted with hea-dache, drowsiness, vomiting, visual impairment and diplop-ia since 2 months before admission. Two years earlier shehad been submitted to pan-hysterectomy for mucinous cer-vical uterine adenocarcinoma. She received adjuvant brachy-therapy and teletherapy. On physical examination she pre-sented with disorientation, right dismetria ant gait ataxia.CT scan revealed a right hemispheric cerebellar heteroge-neous lesion and supratentorial hydrocephalus. MRI showeda 5 cm diameter lesion isointense in T1-weighted imagesand irregular contrast enhancement. She was submitted toventricular drainage and lesion removal through a suboc-cipital craniectomy. Specimen was compatible with low dif-f e rentiated adenocarcinoma similar to her cervical uterinec a n c e r. She received adjuvant whole brain radiotherapy.Post-operatively she developed pneumonia and urinarytract infection. Abdominal ultrasound revealed local invasi-ve re c u rrence. She died one month latter due to complica-tions of urinary tract infection.

DISCUSSION

C e rebral metastasis from cervical uterine cancerw e re re p o rted initially by Henriksen in 1949. Theyappear late in the clinical course of this disease1 0.Their occurrence is very uncommon. There are about80 cases re p o rted in literature, with brain involve-ment usually occurring late in the course of the dis-ease, usually preceeded by local pelvic invasion1-24.

Haematogenous spread depends on histologicaltype of the tumor. Cerebral metastasis are more fre-quent in poorly diff e rentiated tumors. Histologicalsubtypes in decreasing frequency are squamous cellsc a rcinoma, adenocarcinoma, carcinoid tumor andadenosquamous carc i n o m a3 , 4 , 1 6. Cases in present re-p o rt comprise one squamous cell carcinoma and twoadenocarcinomas.

A c c o rdding to Kishi, most common clinical p re s-entation include headache (34%), hemiparesis (25.8%),confusion (22.7%), monoparesis (14.4%) and nausea( 9 . 2 % )1 7. In Robinson’s re v i e w, most common initialsymptoms were hemiparesis, headache, facial palsyand seizures. Ikeda related a medium interval bet-ween initial diagnosis and brain metastasis of 28m o n t h s1 6. Case 1 had no previous neurological or sys-temic manifestations and re p resents the only re p o rt-ed case in which diagnosis was initially made out ofa metastatic brain and scalp lesion1 - 2 4. Case 2 is fre ef rom the disease 5 years after diagnosis and surg e ry.To our knowledge this is the first re p o rted case withsuch a long survival in literature1-24.

Fig 1. Case 2. Pre-operative MRI coronal image weighted in T1showing a left occipital 3 cm diameter lesion. The lesion is ro u n d -ed, well limited, with hypointense central core, ring enhance -ment and perilesional edema.

Fig 2. Case 2. Post-operative MRI coronal image weighted in T1showing gliosis and no evidence of re c u rrence 5 years later.

302 Arq Neuropsiquiatr 2006;64(2-A)

CUC brain metastasis are solitary in one third ofthe patients and frontal lobe is the most commona ffected site3 , 9 , 1 1 , 1 3 , 1 4 , 1 8 , 2 2. In Ikeda s re v i e w, 50% weres o l i t a ry lesions and all of them were supratentori-a l .1 6. Cormio re p o rted 6 single lesions, 8 multiple, 10supratentorial, 2 cerebellar and 2 with infra and su-pratentorial involvement2 , 1 2. As opposed to the liter-a t u re, our 3 cases were solitary lesions and none infrontal lobe.

CUC brain metastasis are usually treated by sur-g e ry, chemotherapy and radiotherapy. Surgical re m o-val is a consensus in the literature for solitary le-s i o n s4 , 1 9 , 2 0. Surg e ry may also be considered in case oftwo or more lesions surgically removable in the samec r a n i o t o m y2 3. Other surgical indications are lack ofdiagnosis, life threatening situations (hemorrh a g e ,h y d rocephalus or infection), symptomatic relief afterineffective clinical treatment and insertion of intra-thecal chemotherapy devices23.

Radiotherapy may play an adjuvant role to surg i-cal resection or remains as the only local treatment,associated or not to chemotherapy. Patchell re v e a l e dthat patients treated with surg e ry plus radiotherapyhad longer survival, better neurological conditionand lower re c u rrence of the disease in the nerv o u ssystem, when compared to those who received radio-therapy alone1 9. Most of the authors consider surg e-ry followed by adjuvant radiotherapy the best optionfor solitary CUC brain metastasis5,6,10,12,16,18,21.

S t e reotaxic radiosurg e ry is as effective as conven-tional surgery for local brain metastasis control andmay also be used in inaccessible lesions8. There areno data in literature about radiosurg e ry effects inCUC brain metastasis. The decision between conven-tional craniotomy plus adjuvant radiotherapy andr a d i o s u rg e ry must be made on an individual basis,considering size, number and location of the lesion,clinical condition and available technology4 , 5 , 6 , 8 , 1 6 , 2 0 , 2 3.

Chemotherapy plays an important role in clinicalt reatment of CUC and cisplatin is the most fre q u e n t-ly used drug. Chemotherapy may determine regres-sion of CUC brain metastasis and also has systemice ffect. Its final influence in the outcome of CUC cere-bral metastasis is still unknown2 , 3 , 6 , 1 2. In cases withmultiple lesions, chemotherapy may be the firstchoice of tre a t m e n t5 , 6 , 1 0 , 1 2 , 1 6 , 1 8 , 2 1. Cases 2 and 3 devel-oped brain metastasis despite adjuvant chemother-apy for uterine disease.

Other therapeutic suggested strategies in studyfor clinical treatment of unresecable metastasis in-clude selective intra-arterial chemotherapy, use of

reversible haemato-encephalic barrier modifiers andh o rmonal therapy (melatonin) without, however,w o rthwhile eff e c t2. Outcome of patients with CUCbrain metastasis depends on age, neurological sta-tus, length of clinical history, histological subtypes,number of lesions and clinical comorbidities. Thep rognosis is poor despite any treatment option, withs u rvival of 3 to 6 months after diagnosis of brainmetastasis10.

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