Recurrence of medulloblastoma 19 years after the initial diagnosis

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  • Received: 17 January 1998Revised: 24 April 1998

    Abstract A 25-year-old woman pre-sented with recurrent medulloblasto-ma. She had been diagnosed withcerebellar medulloblastoma andtreated for it at the age of 5 years.The new tumor was partially resect-ed and chemotherapy was begun.However, a disseminated tumor ofthe spine was discovered and, de-spite radiotherapy, the patient be-came comatose and died. Histologi-cal examination of the tumor speci-men showed characteristics similarto those of the first tumor. Late re-

    currence of medulloblastoma is rare,and a latency period of 19 years isthe longest reported. This case vio-lates Collins rule and exceeds otherproposed periods of risk. Extensionof the period of follow-up in patientswith medulloblastoma is advocated.

    Key words Medulloblastoma Late recurrence Period of risk

    Childs Nerv Syst (1999) 15:482485 Springer-Verlag 1999 C A S E R E P O RT

    Kenichi AmagasakiHiromichi YamazakiHidehito KoizumiKazuhiro HashizumeNobuo Sasaguchi

    Recurrence of medulloblastoma19 years after the initial diagnosis

    Introduction

    Medulloblastoma is a common posterior fossa tumor ofchildhood. Recent imaging and therapeutic techniqueshave improved the recurrence-free period for patientswith medulloblastoma. Collins rule states that a dis-ease-free period of greater than the age at diagnosis plus9 months is equivalent to cure [3, 4]. This rule was firstapplied to Wilms tumor, and its application in the caseof medulloblastoma has been proposed. However,whether this rule can be applied to medulloblastomaseems doubtful, since some cases have not conformedwith it [1, 5, 6, 10, 11, 14]. Recently its application tomedulloblastoma in the case of children below the ageof 8 years was proposed [2]. Other reviews of the periodof risk have concluded that freedom from recurrence formore than 8 years after the diagnosis could be consid-ered as a cure [1] and that 810 years after the initialtreatment is the period of risk for recurrence [14]. Fewcases have recurred more than 10 years after the initialdiagnosis [10, 11]. Since late recurrence is not common,the natural history of late recurrence in medulloblasto-ma is not well known. We describe a case of medullo-

    blastoma that recurred 19 years after the initial diagno-sis.

    Case report

    A 25-year-old woman was admitted to our institution in August1996, with persistent headache and nausea for 2 weeks. She hadpreviously presented in 1977, aged 5 years, with vomiting thathad persisted for a week and a 2-year history of gait disturbance.Neurological examination detected left dysmetria, dysdiadocho-kinesis, and truncal ataxia. Computed tomography (CT) revealedmarked hydrocephalus with a high-density mass in the vermisand left cerebellar hemisphere, which was enhanced after the ad-ministration of contrast medium. A ventriculoperitoneal shuntwas implanted for the hydrocephalus. She then underwent a sub-total resection via a suboccipital craniectomy and a C-1 laminec-tomy. Histological examination of the surgical specimen revealeda medulloblastoma (Fig. 1). Subsequently she received radiationtherapy: 50 Gy to the posterior fossa and 20 Gy to the spine.Chemotherapy was not given. Her cerebellar symptoms improvedand she was discharged from the hospital; she was able to walkand had only slight truncal ataxia. In 1980, when aged 9 years,she complained of headache and vomiting. Neurological and ra-diological examinations revealed no remarkable changes, so shereceived an additional 20 Gy of prophylactic irradiation to theposterior fossa. Follow-up with CT was continued for 10 years

    K. Amagasaki H. Yamazaki H. KoizumiK. Hashizume N. SasaguchiDepartment of Neurosurgery,Yamanashi Prefectural Central Hospital,Kofu, Yamanashi, JapanK. Amagasaki (

    )

    )Department of Neurosurgery,Yamanashi Medical College,1110 Shimokato Tamaho-cho,Nakakoma-gun,Yamanashi, 4093898 JapanTel.: +81552736786Fax: +81552742468

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    after the initial diagnosis, until 1987. The last follow-up CT ex-amination demonstrated no regrowth of the residual tumor (Fig.2). Her neurological condition remained unchanged in the fol-low-up period and thereafter. She had done a normal desk jobwith no problems before her admission in 1996. There was nofamily history of neurofibromatosis.

    Examination

    Neurological examination at the present admission showed leftdysmetria, dysdiadochokinesis, and truncal ataxia. No remarkabledeterioration in her neurological condition had occurred during thelast 19 years.

    CT revealed an irregularly shaped low-density mass with het-erogeneous enhancement in the vermis and extending into thepreviously irradiated area in the left cerebellar hemisphere. Mag-netic resonance (MR) imaging demonstrated similar enhance-ment (Fig. 3). Digital subtraction angiography showed fine tumorvessels in the arterial phase, which persisted into the capillaryphase.

    Operation

    Partial removal of the tumor was performed under the operatingmicroscope to achieve decompression and provide histologicalconfirmation. The posterior fossa was exposed by the same medi-an skin incision as had been used in the previous operation. Thetumor was poorly demarcated from the surrounding left tonsil,partially necrotic and hemorrhagic.

    Histological examination

    Examination of the tumor specimen showed high cellularity withsmall carrot-shaped cells, hyperchromatic nuclei and scant cyto-plasm (Fig. 4). Immunohistochemical staining revealed that the tu-mor cells were weakly positive for S-100 protein only, and werenegative for glial fibrillary acidic protein, neuron-specific enolase,and neurofilament. The histological diagnosis, reviewed by a neu-ropathologist, was recurrent medulloblastoma.

    Postoperative course

    The patients headache and nausea improved, and she subsequent-ly received chemotherapy using a 4-week cycle. Carboplatin,320 mg/m2, was administered intravenously on day 1 and etopo-side, 60 mg/m2, was administered intravenously on days 3, 4, and5 of each cycle. The size of the tumor remained unchanged.

    Fig. 1 Photomicrograph of the surgical specimen obtained at thefirst operation, showing typical findings of medulloblastoma as ahighly cellular tumor with ovoid cells, hyperchromatic nuclei, andscant cytoplasm, and a Homer-Wright rosette in the center. (H&E,original magnification 132)

    Fig. 2 The last computed tomography scan after contrast mediumadministration in the follow-up period, showing a small enhancedarea persisting at the vermisFig. 3 A Axial and B sagittal T1-weighted magnetic resonanceimages after gadolinium administration, showing that the tumorhad spread from the vermis to the left cerebellar hemisphere withirregular enhancement

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    Fig. 4 Photomicrographs of the surgical specimen from the recur-rent tumor, showing a highly cellular tumor with small carrot-shaped cells. Some nuclei are large and hypochromatic. (H&E,original magnification 132)

    recurrent tumor represents a dedifferentiation of the pri-mary tumor or a second radiation-induced tumor is con-troversial. Radiation-induced tumors occasionally occurmany years after radiotherapy, and some cases of glio-mas have developed at the site of a primary medullo-blastoma after radiotherapy, suggesting the histologicalchange was possibly due to radiotherapy [7, 15, 19]. Incontrast, recurrent medulloblastoma has been describedas dedifferentiation of the primary tumor or other tu-mors [5, 10]. A capacity of medulloblastoma for astro-cytic differentiation both in vitro and in clinical aspectshas also been demonstrated [11, 15, 17].

    The question as to why the residual tumor stayed sta-ble for such a long time remains. One possible answer isthat tumor regrowth was suppressed by the radiotherapy.Recent studies have demonstrated that radiotherapy iseffective in improving survival [1, 9, 16]. The other pos-sibility is that biological eradication of the tumor hadbeen achieved by the initial treatment, but kinetics ofsurrounding cells had been altered by the treatment andit was these that led to a second occurrence of medullo-blastoma. Currently there are not enough clinical or lab-oratory data to answer these questions.

    Follow-up studies of patients with medulloblastomarely mainly on MR imaging and have demonstrated thesignificance of pial-arachnoidal or focal nodular brainenhancement and the importance of T2-weighted MRimaging in the detection of recurrence [13, 18]. Current-ly, follow-up examinations are scheduled every 3 monthsfor the first few years, then every 6 months for the fol-lowing few years, and yearly thereafter [8, 12, 20].Whether radiological images should be obtained inasymptomatic patients remains controversial [12, 20].Furthermore, the length of follow-up period necessaryremains unclear. In the present case, follow-up examina-tions were continued for 124 months after the initial di-agnosis, but in retrospect this period was not longenough. The present case is very unusual, but still sug-gests that long-term follow up over 10 years should becontinued at yearly intervals for patients with medullo-blastoma. The establishment of a period of risk for closesurveillance would be helpful.

    Acknowledgements The authors thank Prof. Yoichi Nakazato forassistance with the histological diagnosis and Dr. Hirofumi Nag-anuma for the photographic work.

    During the third cycle of chemotherapy, she complained ofpain in her back and both feet, with difficulty in walking. SagittalMR imaging revealed a disseminated tumor at the T-3 level of thespinal cord. Subsequently she received local irradiation to the spi-nal tumor, but her condition deteriorated during the radiotherapyand she became comatose. CT demonstrated a tumor infiltratingthe IV ventricle. She died in March 1997, 8 months after diagnosisof the recurrence. Permission for postmortem examination was re-fused.

    Discussion

    Cases of late recurrence of medulloblastoma are beingreported more frequently, but include tumors of differ-ent types or in locations remote from the primary site[1, 5, 6, 8, 10, 11]. If we define recurrence strictly asthe occurrence of a tumor of the same histologically de-fined type as the original tumor in the original location,recurrent medulloblastoma more than 10 years after di-agnosis is extremely rare, with only four previouscases: two in which the interval was 12 years 5 months,one with an interval of 10 years and 3 months, and onewith 11 years before the recurrence [10, 11]. One caseof adult medulloblastoma recurred within the period ofrisk defined by Collins rule. In our case, the recurrencewas located at the same site and was similar in histolog-ical type to the primary tumor. The present case clearlydid not conform to Collins rule, and the interval of 19years is almost double the period of risk proposed pre-viously.

    The clinical behavior of late recurrence is malignantin general and, as in our case, the prognosis is very poor[6, 11]. However, the specific kinetics of late recurrencein medulloblastoma is unclear. Recurrent medulloblasto-mas that occur many years after the period of risk areoften of a somewhat different histology. Whether late

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