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Journal of Clinical Neuroscience 15 (2008) 122–126

Clinical Study

Adult medulloblastoma: Clinical profile and treatmentresults of 18 patients

Girish Menon *, K. Krishnakumar, S. Nair

Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Medical College P.O. Trivandrum Kerala, 695011, India

Received 18 April 2007; accepted 4 June 2007

Abstract

The objective of this article is to examine the clinicoradiological features and surgical outcomes of adult patients (>16 years) withmedulloblastoma. An attempt was made to identify the predictors of poor outcome and assess patterns of relapse and to compare thesewith pediatric medulloblastoma. Retrospective case record analyses were performed on 18 adults (>16 years) and 79 children (<16 years)operated upon after January 1990, who had at least 5 years of follow-up. The following variables were assessed by bivariate analyses: age,location of the lesion, brainstem invasion, extent of excision and histological subtype. Statistical analysis was performed using chi-squaretest, Fischer’s exact test and Student’s t-test. Results revealed there was no gender preference. The tumor was located in the vermis in 12patients (66.6%) and in the cerebellar hemisphere in six (16.6%). Calcification was observed in two cases (11.1%) and hydrocephalus wasseen in six (33.3%). MRI evidence of brainstem infiltration was seen in three patients (16.6%). Total excision was achieved in 13 cases(72.2%), near total excision in four (22.2%) and subtotal excision in one. Major complications included fresh cranial nerve deficits in fourpatients (22.2%), hemiparesis and gait unsteadiness in three (16.6%), mutism in one and meningitis in two. All patients underwent adju-vant radiotherapy in the form of craniospinal irradiation with a posterior fossa boost. On follow-up, 11 patients (61.1%) were observedto have recurrence and all were located in the posterior fossa. All 11 subsequently underwent chemotherapy. Two patients had re-operation for residual/recurrent lesions causing raised intracranial symptoms. Five-year follow-up data showed that 10 patients(55.5%) were alive, five (27.7%) had died while three (16.6%) were lost to follow-up. In spite of recent advances in management, patientswith medulloblastoma still have a poor prognosis. However, adults fared better than children. Vermian location had a better outcome inadults, but not in children. Desmoplastic variant histology was not observed to be a significant prognostic factor in the adult group whilebrain stem invasion carried a poor prognosis.� 2007 Elsevier Ltd. All rights reserved.

Keywords: Medulloblastoma; Radiotherapy; Chemotherapy

1. Introduction

Medulloblastoma is a common malignancy in the pedi-atric population, accounting for 25% of all childhood braintumors.1,2 It is a highly invasive tumor arising from the cer-ebellum with a tendency to disseminate throughout thecentral nervous system (CNS) early in its course. The med-ian age at diagnosis is 5 years, with 80% of cases beingdiagnosed in the first 15 years. However, medulloblastomas

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doi:10.1016/j.jocn.2007.06.007

* Corresponding author. Tel.: +91 471 2443152.E-mail address: gmr@sctimst.ker.nic.in (G. Menon).

account for only approximately 1% of all adult braintumors and data for adults are sparse.3–13 A retrospectiveanalysis of our surgical series of medulloblastoma was car-ried out to study the clinicoradiological features and surgi-cal outcomes of adult medulloblastoma, and to comparethem with pediatric patients. An attempt was made to iden-tify the predictors of poor outcome and to assess patternsof relapse.

2. Materials and methods

During the period from January 1990 to December1999, a total of 97 patients underwent surgery for medullo-

Table 3Histopathological variants of medulloblastoma

Variant Adults Children

Classical 3 50Desmoplastic 6 9Glial differentiation 9 20

G. Menon et al. / Journal of Clinical Neuroscience 15 (2008) 122–126 123

blastoma. There were 18 adults in this study (age >16years). The present study was conducted retrospectivelyby analyzing the clinicoradiological data of these patients.The radiological outcome was analyzed in the post-opera-tive period as well as during follow-up. All patients wereevaluated by an oncologist and underwent adjuvant ther-apy. The various modalities of adjuvant therapy were ana-lyzed. All patients were called to the outpatient departmentand detailed neurological examination was done on review.Information regarding the status of patients was obtainedfrom relatives for those who could not report for review.Statistical analysis was performed using chi-square test,Fischer’s exact test and Student’s t-test

3. Results and analysis

There were 18 adults in the study which included ninemales and nine females (Table 1). Age distribution rangedfrom 16 to 47 years with a mean age of 31.5 years. Dura-tion of symptoms varied from 2 months to over a year.Headache was the predominant symptom in most of thepatients while cerebellar symptoms in the form of gaitunsteadiness were present in 14 (77.7%). The tumor was lo-cated in the vermis in 12 patients (66.6%) and in the cere-bellar hemisphere in six (16.6%). Lesions werepredominantly isodense/hyperdense to grey matter (13 le-sions, 72.2%) on CT scan. Calcification was observed intwo (11.1%) and hydrocephalus in six (33.3%). MRI evi-dence of brainstem infiltration was present in three patients(16.6%). Total excision could be achieved in 13 cases(72.2%), near total excision in four (22.2%) and subtotalexcision in one (Table 2). Our institute’s protocol is toplace an extraventricular drain post-operatively for 2-3days and to avoid placement of a ventriculoperitoneal(VP) shunt as far as possible. In patients who presentedwith symptoms of raised intracranial pressure, endoscopicthird ventriculostomy was kept as a treatment option incase of deterioration. However, three patients (16.6%) withraised intracranial pressure in the post-operative periodunderwent VP shunt placement. Histopathological exami-

Table 1Gender distribution of medulloblastoma

Gender Adults (n = 18) Children (n = 79)

Male 9 44Female 9 35

Table 2Extent of resection of medulloblastoma

Extent ofresection

Percentage adults(n = 18)

Percentage children(n = 79)

Total 72.2 35.4Near total 22.2 39.2Subtotal 0.18 22.7Partial 0 2.7

nation showed classical medulloblastoma in three cases(16.6%) while desmoplastic variant was observed in six(33.3%). Eight patients (44.4%) had medulloblastoma withglial differentiation and one patient had medulloblastomawith neuronal differentiation (Table 3). Major complica-tions included new cranial nerve deficits in four patients(22.2%), hemiparesis and gait unsteadiness in three(16.6%), mutism in one and meningitis in two. All patientsunderwent adjuvant radiotherapy in the form of craniospi-nal irradiation with a posterior fossa boost. On follow-up,11 patients (61.1%) were observed to have recurrence onCT scans and all were in the posterior fossa (Table 4).Three patients in this group underwent chemotherapyimmediately following radiotherapy, while 11 of them weresubjected to chemotherapy on detection of secondaries.Two patients had to undergo re-operation due to resid-ual/recurrent lesion causing raised intracranial pressure.Incidences of post-operative complications such as mutismand gait unsteadiness were lower in the adult population.Five-year follow-up data showed 10 patients (55.5%) tobe alive, five (27.7%) had died and three (16.6%) were lostto follow-up. This was in comparison with the pediatric pa-tients in whom less than 24% were alive on long-term fol-low-up (Table 5).

Among the children, near total to total excision could beachieved in 59 (74.6%) cases. Twenty three patients(29.11%) required CSF diversion procedures. Histopathol-ogy revealed features of classical medulloblastoma in 50(63.2%), desmoplastic variant in nine (11%) and glial differ-entiation in 20 (25.3%) cases. Postoperative mutism wasseen in 14 patients. On follow-up 34 patients were foundto have posterior fossa recurrence and four underwent

Table 4Recurrence of medulloblastoma alter surgery and radiotherapy

Site of recurrence Adults Children

Posterior fossa 11 34Spinal 17Supratentorial 15

Table 5Five-year follow-up of patient with medulloblastoma

Follow-up Adults (%) Children (%)

PFS 10 (55.5) 19 (24.05)Dead 05 (27.7) 23 (29.11)Lost to follow up 03 (16.7) 37 (46.84)

PFS = progression-free survival.

Table 7Prognostic significance of histopathology of lesion in childhoodmedulloblastoma

FUMORTAL Total

0 1

Crosstab

HISTOPAT 0 Count 12 11 23% within HISTOPAT 52.2% 47.8% 100.0%

1 Count 3 1 4% within HISTOPAT 75.0% 25.0% 100.0%

2 Count 1 8 9% within HISTOPAT 11.1% 88.9% 100.0%

Total Count 16 20 36% within HISTOPAT 44.4% 55.6% 100.0%

Value df Asymp. Sig. (2-sided)

Chi-Square Tests

Pearson Chi-Square 6.119a 2 .047Likelihood Ratio 6.842 2 .033Linear-by-Linear Association 3.385 1 .066N of Valid Cases 36

0 = classical; 1 = desmoplastic; 2 = others Follow-up 0 = Alive;1 = Expired. HISTOPAT = histopathology; FUMORTAL = mortality atfollow up.

a 3 cells (50.0%) have expected count less than 5. The minimum expectedcount is 1.78.

124 G. Menon et al. / Journal of Clinical Neuroscience 15 (2008) 122–126

re-operation. An additional 17% of patients were found tohave either spinal or supratentorial metastasis on follow-up. The overall 5-year recurrence-free survival rate was19 (24.05%). Mortality was recorded in 23 patients, andnearly 37 who were severely disabled on follow-up were re-ferred to terminal care centers.

The following variables were assessed by bivariate anal-ysis for the adult and pediatric groups: age, location oflesion, brainstem invasion, total excision of tumor and his-tological subtype. CSF seeding and MRI evidence ofmetastasis could not be analyzed due to insufficient data.As all the patients were subjected to the same pattern ofadjuvant radiotherapy, the role of radiotherapy in prog-nostication was not attempted.

Poor outcome was observed in the pediatric popula-tion with age <7 years and better outcome for those>9 years. Bivariate analysis showed the influence of CTscan location of tumor with the outcome in adult medul-loblastoma–vermian location carrying better prognosisthan other locations (Table 6). Significant associationwas observed between radiological evidence of brainsteminvolvement and outcome in adult medulloblastoma.Desmoplastic variant of medulloblastoma was observedto be a significant prognostic factor in the pediatricgroup (Table 7). The known predictors of outcome suchas gender and extent of resection, did not have any sta-tistically significant effect on outcome in our series. Theeffects of radiotherapy on outcome were difficult to assessas all the patients received the same dose. However,patients who received chemotherapy immediately follow-

Table 6Prognostic significance of CT scan location of lesion in adultmedulloblastoma

FUMORTAL Total

0 1

Crosstab

CTLOCAT 0 Count 9 1 10% within CTLOCAT 90.0% 10.0% 100.0%

1 Count 1 1 2% within CTLOCAT 50.0% 50.0% 100.0%

2 Count 2 2% within CTLOCAT 100.0% 100.0%

3 Count 1 1% within CTLOCAT 100.0% 100.0%

Total Count 10 5 15% within CTLOCAT 66.7% 33.3% 100.0%

Value df Asymp. Sig. (2-sided)

Chi-Square Tests

Pearson Chi-Square 8.700a 3 .034Likelihood Ratio 9.821 3 .020Linear-by-Linear Association 7.721 1 .005N of Valid Cases 15

Location 0 = vermis; 1 = right hemisphere; 2 = left hemisphere; 3 = othersites. Follow-up 0 = Alive; 1 = Expired. CTLOCAT = CT location;FUMORTAL = mortality at follow up.

a 7 cells (87.5%) have expected count less than 5. The minimum expectedcount is 0.33.

ing radiotherapy had a better outcome than those whoreceived chemotherapy following the detection ofrecurrence.

4. Discussion

Medulloblastoma is the most common malignant braintumor in childhood, accounting for 20-25% of pediatricCNS neoplasms. Medulloblastomas are undifferentiatedembryonal neuroepithelial tumors of the cerebellum1,2,14

arising predominantly from the cerebellar vermis and pri-marily affecting children in the first decade of life. The cellof origin and the exact histological classification of thishighly malignant tumour is still controversial.3,14 Althoughthe majority occur as sporadic cases, hereditary conditionshave been associated with medulloblastoma, including: (i)Gorlin syndrome (nevoid basal cell carcinoma syndrome);(ii) blue rubber-bleb nevus syndrome; (iii) Turcot syndrome(glioma polyposis syndrome); and (iv) Rubenstein-Taybisyndrome. The most frequent cytogenetic abnormality insporadic medulloblastoma is an isochromosome 17q [i(17q)].1 Of tumors analyzed, 40-50% had a deletion ofthe short arm of chromosome 17, implicating the presenceof a tumor suppressor gene that maps to 17p. Recently,Raffle et al. have shown that medulloblastomas have p53mutations as identified by cDNA sequencing, suggestinginactivation or faulty transcription of the active protein en-coded by p53. These p53 mutations may be important inthe pathogenesis of human medulloblastoma.4,15 Recentlythe role of biologic markers in risk stratification and prog-nostication is assuming greater relevance.15,16 The predic-

G. Menon et al. / Journal of Clinical Neuroscience 15 (2008) 122–126 125

tive value of these markers is still controversial and a focusof research.

Medulloblastoma is rare in older people and represents1% of CNS tumors in adults. Over the last decade, severalretrospective institutional or multicenter studies have de-scribed the characteristics, response to treatment, progno-sis, and pattern of relapse in adult medulloblastoma.3–14

Large cooperative and epidemiological studies have con-tributed to better-defined risk groups and improved treat-ment modalities and outcomes.2 Many aspects of adultmedulloblastoma differ markedly from that in youngerchildren. As in other reported series, we also found thatsymptoms due to raised intracranial pressure as well as cer-ebellar symptoms were distributed equally in both the pop-ulations.1,2,5 However, the incidences of episodes of loss ofconsciousness, seizures and cranial nerve palsies were defi-nitely higher in the adult population. Bloom et al. notedthat the difference in presentation of medulloblastoma inadults was due to a greater incidence of lateral tumors.11

Approximately 50% of adult medulloblastomas are later-ally located, compared with <10% of childhood medullo-blastomas.4,6 Non-vermian locations enabled totalresection of tumors, resulting in improved long-term sur-vival in adults. Incidence of tumor calcification was lowerin the pediatric population and so was contrast enhance-ment. Incidence of hydrocephalus was lower in the adultpopulation as opposed to the pediatric patients in almostall reported series. This could be attributable to the morelateral location of the tumour.4 Our experience is similarto that reported above except for the location, with nearly66% of adult medulloblastomas having a vermian location.Gender is a debatable prognostic factor in pediatric series.Weil et al.18 and Prados et al.7 found female gender to be asignificant favorable prognostic factor in medulloblastoma.Gender is an inconsistent and frequently overlooked prog-nostic factor in adult series, although some studies have re-vealed better outcomes for the female sex.5 Gender did nothave any bearing on the outcome in our series.

Complete resection should be performed if possible asseveral studies have correlated outcome with the extent ofresection and amount of residual tumour.14,17 In spiteof a predominant midline location of the tumor in mostof our adult patients, total excision of the lesion could beperformed in a significant number of adults (72.2%). Inthe pediatric population only 35.4% underwent total exci-sion. Establishment of a CSF pathway was more easilyachieved in the adult population when compared to thepediatric population. However, our results are similar toTabori et al.4 who found similar rates of local relapse be-tween patients with gross total resection and patients withless extensive surgery.

We noted a higher incidence of brain stem infiltration inour adult population series, unlike others who found 36%of patients with radiological evidence of brainstem infiltra-tion. Brain stem infiltration was one of the major reasonsfor a relatively high incidence of subtotal excision in ourseries. Infiltration of the floor of the 4th ventricle was con-

firmed as a strong independent negative predictor in ourseries, as in most others.3,5,14,17

Histopathological examination of tumors in the presentstudy showed clear predominance of the desmoplastic var-iant of medulloblastoma in the adult population, whereasclassical medulloblastoma was predominant in children.The available literature suggests the desmoplastic histolog-ical variant to be of favourable prognostic signifi-cance.4,6,14–17 Chan et al.6 and Bloom et al.11 in theiranalyses of adult medulloblastomas have found that thedesmoplastic variant, though common in the adult popula-tion, bears no importance to the outcome. Our series couldnot establish a statistically significant correlation amongadults, though the desmoplastic variant was associatedwith better outcome in children.

Standard therapy consists of total surgical removal ofthe tumor followed by radiation to the entire craniospinalaxis with a boost to both the primary tumor site and focalCNS metastatic sites.3,4,15 In contrast to a previous report3

we did not find an influence on survival of the interval be-tween surgery and the start of radiotherapy. Certain studieshave shown a correlation between improved posterior fossacontrol and shorter periods for the completion of radio-therapy.6,19 In Chan et al’s series the 5-year posterior fossacontrol rate was 81% for patients who completed radio-therapy in less than 48 days, compared with 51% for pa-tients who completed radiotherapy in 48 days or more.6

As we followed a uniform protocol of radiotherapy, wefailed to observe any difference in outcome related to eitherthe surgery-radiotherapy interval or the total duration ofradiotherapy.

Recently, adjuvant chemotherapy has also been shownto be beneficial in children with medulloblastoma.20 Theaddition of chemotherapy for high-risk patients seems toimprove their survival and has contributed to better out-comes even in average-risk patients. However, the role ofchemotherapy in adults is controversial.20 In our seriesthose patients who received chemotherapy immediately fol-lowing radiotherapy were found to have a better outcomethan those who received chemotherapy following the detec-tion of recurrence. Among children, even after a good re-sponse to surgery and radiation, recurrence is common;most recurrences occur within 2 years of treatment. A pat-tern observed in adult studies is a high incidence of late re-lapse and a relatively prolonged time from relapse todeath.3,6–11 Our findings are, in this regard, similar to thosein the pediatric population, with a very short and relentlesscourse from relapse to death. Prolonged close monitoringfor late relapses is probably warranted for this group.

5. Conclusions

Although pediatric and adult medulloblastomas shareseveral clinicopathological features, adult medulloblasto-mas are more amenable to complete surgical clearanceand carry a complete overall prognosis compared tochildren. In our series of medulloblastomas, among the

126 G. Menon et al. / Journal of Clinical Neuroscience 15 (2008) 122–126

classical predictors of outcome, only location, histologicalsubtype and brain stem invasion were found to have anysignificant correlation on outcome. Favorable prognosticindicators include a vermian location in adults, and a des-moplastic variant in children. Radiological evidence ofbrain stem invasion on MRI was associated with poor out-come in adults as well as children. Classical outcome deter-minants like age, extent of excision and residual tumor, didnot show any correlation with outcome in our series.

References

1. James TR, Hoffman H. A critical review of medulloblastoma : from adifficult past to a promising future. Neurosurg Q 1991;1:54–78.

2. Jakacki RI. Treatment strategies for high risk medulloblastoma andsupratentorial prmitive neuroectodermal tumours. J Neurosurg (Pedi-

atrics I) 2005;102:44–52.3. Herrlinger U, Steinbrecher A, Rieger J. Adult medulloblastoma.

Prognostic factors and response to therapy at diagnosis and at relapse.J Neurol 2005;252:291–9.

4. Tabori U, Sung L, Hukin J, et al. Distinctive clinical course andpattern of relapse in adolescents with medulloblastoma. Int J Radiat

Oncol Biol Phys 2005;64:402–7.5. Abacioglu U, Uzel O, Sengoz M. Medulloblastoma in adults:

Treatment results and prognostic factors. Int J Radiat Oncol Biol

Phys 2002;54:855–60.6. Chan AW, Black PM. Adult medulloblastoma; prognostic factors and

patterns of relapse. Neurosurgery 2000;47:623–32.7. Prados MD, Warnick RE, Wara WM, et al. Medulloblastoma in

adults. Int J Radiat Oncol Biol Phys 1995;32:1145–52.8. Frost PJ, Laperriere NJ, Wong CS, et al. Medulloblastoma in adults.

Int J Radiat Oncol Biol Phys 1995;32:951–7.

9. Aragones MP, Magallon R, Piqueras C, et al. Medulloblastoma inadulthood: Prognostic factors influencing survival and recurrence.Acta Nurochir (Wien) 1994;127:65–8.

10. Hartsell WF, Montag AG, Lydon J, et al. Treatment of medullo-blastoma in adults. Am J Clin Oncol 1992;15:207–11.

11. Bloom HJG, Bessell EM. Medulloblastoma in adults: A review of 47patients treated between 1952 and 1981. Int J Radiat Oncol Biol Phys

1990;18:763–72.12. Hughes PG. Cerebellar medulloblastoma in adults. J Neurosurg

1984;60:994–7.13. Miles J, Bhandari YS. Cerebellar medulloblastoma in adults -review

of 18 cases. J Neurol Neurosurg Psychiatry 1970;33:208–11.14. Gajjar A, Hernan R, Kocak M, et al. Clinical, histopathologic, and

molecular markers of prognosis: toward a new disease risk stratifi-cation system for medulloblastoma. J Clin Oncol 2004;22:984–93.

15. Taylor MD, Mainpriz TG, Rutka JT. Molecular insight intomedulloblastoma and central nervous system primitive neuroectoder-mal tumor biology from hereditary syndromes: a review. Neurosur-

gery 2000;47:888–901.16. Fisher PG. Biologic risk stratification of medulloblastoma: the real

time is now. J Clin Oncol 2004;22:971–4.17. Carrie C, Lasset C, Alapetite C, et al. Multivariate analysis of

prognostic factors in adult patients with medulloblastoma: Retro-spective study of 156 patients. Cancer 1994;74:2352–60.

18. Weil MD, Lamborn K, Edwards MS, et al. Influence of a child’s sexon medulloblastoma outcome. JAMA 1998;279:1474–6.

19. Skolyszewski J, Glinski B. Results of postoperative irradiation ofmedulloblastoma in adults. J Radiat Oncol Biol Phys 1988;16:479–82.

20. Taylor RE, Bailey CC, Robinson K, et al. Results of a randomizedstudy of preradiation chemotherapy versus radiotherapy alone fornonmetastatic medulloblastoma: The International Society of Paedi-atric Oncology/United Kingdom Children’s Cancer Study GroupPNET-3 Study. J Clin Oncol 2003;21:1581–91.