Medulloblastoma, the most common embryonal tumor of the central nervous system, affects both children and adults. It poses a significant therapeutic challenge in that age-dependent differences exist, not only in their pathobiology, but in the efficacy of chemotherapy and radiotherapy. This is particularly the case in very young children, whose still developing nervous system exhibits a low tolerance to radiotherapy. We review the epidemiology, clinical presentation, radiologic features, and current therapeutic concepts relative to this unique neoplasm. Efforts are made to highlight clinical controversies. (J Child Neurol 1992;7:142-155).
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References
1.
Boring CC, Squires TS, Tong T.: Cancer statistics, 1991. CA1991;41:19-36.
2.
Young JL, Miller RW: Incidence of malignant tumors in US children. J Pediatr1975;86:254-258.
3.
Farwell JR, Dohrmann GJ, Flanney JT: Central nervous system tumors in children. Cancer1977;40:3123-3132.
4.
Schoenberg BS , Schoenberg DG, Christine BW, Gomez MR: The epidemiology of primary intracranial neoplasms of childhood. Mayo Clin Proc1976 ;51:51-56.
5.
McFarland DR , Horwitz H., Saenger EL, Bahr GK: Medulloblastoma—a review of prognosis and survival. Br J Radiol1969;42:198-214.
6.
Allen JC, Bloom J., Ertel I., et al: Brain tumors in children: Current cooperative and institutional chemotherapy trials in newly diagnosed and recurrent disease. Semin Oncol1986;13:110-122.
7.
Evans AE, Jenkin Rdt, Sposto R., et al: The treatment of medulloblastoma: Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone . J Neurosurg1990;72:572-582.
8.
Hughes EN, Shillito J., Sallan SE, et al: Medulloblastoma at the joint center for radiation therapy between 1968 and 1984. Cancer1988;61:1992-1998.
9.
Levin VA, Rodriguez LA, Edwards Msb, et al: Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine. J Neurosurg1988;68:383-387.
10.
Packer RJ, Sutton LN, Goldwein JW, et al: Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg1991;74:433-440.
11.
Tait DM, Thornton-Jones H., Bloom Hjg, et al: Adjuvant chemotherapy for medulloblastoma: The first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I) . Eur J Cancer1990;26:464-469.
12.
Roberts RO, Lynch CF, Jones MP, Hart MN: Medulloblastoma: A population-based study of 532 cases. J Neuropathol Exp Neurol1991;50:134-144.
13.
Zulch KJ: Poorly differentiated and embryonal tumors, in Zulch KJ (ed): Brain Tumors: Their Biology and Pathology. Berlin, Springer-Verlag, 1986, pp 307-343.
14.
Janisch W., Haas JF, Schreiber D., Gerlach H.: Primary central nervous system tumors in stillborns and infants. Epidemiological considerations. J Neurooncol1984;2:113-116.
15.
Kepes JJ, Morantz RA, Dorzab WE: Cerebellar medulloblastoma in a 73-year-old woman. Neurosurgery1987;21: 81-83.
16.
Finlay JL: Natural history and epidemiology of medulloblastoma, in Zelter PM, Pochedly C (eds): Medulloblastoma in Children: New Concepts in Tumor Biology, Diagnosis and Treatment. New York, Praeger Press, 1986, pp 22-36.
17.
Cushing H (ed): Intracranial Tumors. Springfield, CC Thomas, 1932.
18.
Yates PO: Tumours of the central nervous system in children. J Clin Pathol1964;17:418-423.
19.
Cohen A., Modan B.: Some epidemiologic aspects of neoplastic diseases in Israeli immigrant population. III. Brain tumors. Cancer1968 ;22:1323-1328.
Tijssen CC: Genetic factors and family studies in medulloblastoma, in Zelter PM, Pochedly C (eds): Medulloblastoma in Children: New Concepts in Tumor Biology, Diagnosis and Treatment. New York, Praeger Press, 1986, pp 61-75.
22.
Hung K-L., Wu C-M., Huang J-S., How S-W.: Familial medulloblastoma in siblings: Report in one family and review of the literature. Surg Neurol1990;33:341-346.
23.
Rice JS, Fischer DS: Blue rubber-bleb nevus syndrome. Arch Dermatol1962;86:503-511.
24.
Balsa RE, Ingratta SM, Galeano FA, et al: Sindrome nevo basocelular: Presentacion de dos casos uno, asociado a meduloblastoma. Med Cutan Ibero Lat Am1985 ;13:5-11.
25.
Gorlin RJ, Vickers RA, Kelln E., Williamson JJ: The multiple basal-cell nevi syndrome: An analysis of a syndrome consisting of multiple nevoid basal-cell carcinoma, jaw cysts, skeletal anomalies, medulloblastoma, and hyporesponsiveness to parathormone. Cancer1965;18:89-104.
26.
Lynch HT: SBLA syndrome, in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology , vol 42. Amsterdam, North Holland, 1981, pp 769-771.
27.
Pearson Adj , Craft AW, Ratcliffe JM, et al: Two families with the Li-Fraumeni cancer family syndrome. J Med Genet1982;19:362-365.
28.
Shuster J., Hart Z., Stimson CW, et al: Ataxia telangiectasia with cerebellar tumor. Pediatrics1966;37:776-786.
29.
Giannelli F. , Avery J., Polani PE, et al: Xeroderma pigmentosum and medulloblastoma: Chromosomal damage to lymphocytes during radiotherapy . Radiat Res1981;88:194-208.
30.
Fraumeni JF Jr: Glioma-polyposis syndrome (Turcot syndrome) , in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology, vol 42. Amsterdam, North Holland, 1981, pp 735-736.
31.
Russell DS, Rubinstein LJ: Tumors of central neuroepithelial origin, in Pathology of Tumours of the Nervous System. Baltimore, Williams & Wilkins, 1989, pp 83-350.
32.
Liwnicz BH, Rubinstein LJ: The pathways of extraneural spread in metastasizing gliomas: A report of three cases and a critical review of the literature. Hum Pathol1979;10: 453-467.
33.
McComb JG, Davis RL, Isaacs H. Jr, Landing BH: Medulloblastoma presenting as neck tumors in 2 infants. Ann Neurol1980;7:113-117.
34.
Pollak ER, Miller HJ, Vye MV: Medulloblastoma presenting as leukemia. Am J Clin Pathol1980;76:98-103.
35.
Hubbard JL, Scheithauer BW, Kispert DB, et al: Adult cerebellar medulloblastoma: The pathological, radiographic, and clinical disease spectrum. J Neurosurg1989;70:536-544.
36.
Bailey P., Cushing H.: Medulloblastoma cerebelli: A common type of midcerebellar glioma of childhood . Arch Neurol Psychiatry1925;14:192-224.
37.
Adams RA, Victor M (eds): Intracranial neoplasms, in Principles of Neurology, 4th ed. New York, McGraw-Hill, 1989, pp 516-553.
38.
Packer RJ, Schut L., Sutton LN, Bruce DA: Brain tumors of the posterior cranial fossa in infants and children , in Youmans JR (ed): Neurological Surgery, 3rd ed. Philadelphia , WB Saunders, 1990 , pp 3017-3039.
39.
Park TS, Hoffman HJ, Hendrick EB, et al: Medulloblastoma: Clinical presentation and management. J Neurosurg1983;58:543-552.
40.
Cohen ME, Duffner PK: Medulloblastoma, in Brain Tumors in Children: Principles of Diagnosis and Treatment. New York, Raven Press, 1984, pp 103-121.
41.
Schut L., Bruce DA, Sutton LN: Medulloblastoma, in Wilkins RW, Rengachary SS (eds): Neurosurgery. New York, McGraw-Hill, 1985, pp 758-761.
42.
Tomita T., McLone DG: Brain tumors during the first 24 months of life. Neurosurgery1985;6:913-919.
43.
Duffner PK, Cohen ME, Myers MH, Heise HW: Survival of children with brain tumors: SEER program, 1973-1980. Neurology1986;36:597-601.
44.
Arnstein LH , Boldrey E., Naffziger HC: A case report and survey of brain tumors during the neonatal period. J Neurosurg1950 ;8:315-319.
45.
Raskind R., Biegel F.: Brain tumors in early infancy—probably congenital in origin . J Pediatr1964;65:727-732.
46.
Solitare GB , Krigman MR: Congenital intracranial neoplasm: A case report and review of the literature. J Neuropathol Exp Neurol1964;23:280-292.
47.
Berry MP, Jenkin Rdt, Keen CW, et al: Radiation treatment for medulloblastoma: A 21-year review. J Neurosurg1981;55:43-51.
48.
Bloom Hlg, Walsh LS: Tumors of the central nervous system, in Bloom HLG, Lemerle J, Neidhart MK, et al (eds): Cancer in Children: Clinical Management . Berlin, Springer-Verlag, 1975, pp 93-119.
49.
Choux M., Lena G., Hassoun J.: Prognosis and long term follow-up in patients with medulloblastoma . Clin Neurosurg1983;30:246-277.
50.
Hughes PG: Cerebellar medulloblastoma in adults. J Neurosurg1984;60:994-997.
51.
Rosenbloom SB , Rosenbaum AE: Radiology of posterior fossa tumors , in Wilkins RH, Rengachary SS (eds): Neurosurgery. New York, McGraw-Hill, 1985, pp 730-754.
52.
Zimmerman RA , Bilaniuk LT, Pahlajani H.: Spectrum of medulloblastomas demonstrated by computed tomography. Radiology1978;126:137-141.
53.
Segall HD, Zee C-S., Naidich TP, et al: Computed tomography in neoplasms of the posterior fossa in children . Radiol Clin North Am1982;20:237-253.
54.
Naidich TP, Lin JP, Leeds NE, et al: Primary tumors and other masses of the cerebellum and fourth ventricle: Differential diagnosis of computed tomography. Neuroradiology1977;14:153-174.
55.
Deutsch M., Laurent JP, Cohen ME: Myelography for staging medulloblastoma. Cancer1985;56:1763-1766.
56.
Deutsch M., Riegel DH: The value of myelography in the management of childhood medulloblastoma . Cancer1980; 45:2194-2197.
57.
Dorwart RH, Wara WM, Norman D., Levin VA: Complete myelographic evaluation of spinal metastases from medulloblastoma . Radiology1981;139:403-408.
58.
Flannery AM , Tomita T., Radkowski M., McLone DG: Medulloblastomas in childhood: Postsurgical evaluation with myelography and cerebrospinal fluid cytology. J Neurooncol1990;8:149-151.
59.
George RE, Laurent JP, McCluggage CW, Cheek WR: Spinal metastasis in primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa: Evaluation with CT myelography and correlation with patient age and tumor differentation. Pediatr Neurosci1985-1986;12:157-160.
60.
Stanley P., Suminski N.: The incidence and distribution of spinal metastases in children with posterior fossa medulloblastomas. Am J Pediatr Hematol Oncol1988;10:283-287.
61.
Waluch V., Dyck P.: Magnetic resonance imaging of posterior fossa masses, in Wilkins RH, Rengachary SS (eds): Neurosurgery Update. New York , McGraw-Hill, 1990, 30-46.
62.
Rollins N., Mendelsohn D., Mulne A., et al: Recurrent medulloblastoma: Frequency of tumor enhancement on Gd-DTPA MR imaging. Am J Roentgenol1990;115:153-157.
63.
Klein DM: Principles of neurosurgery, in Cohen ME , Duffner PK (eds): Brain Tumors in Children: Principles of Diagnosis and Treatment. New York, Raven Press, 1984, pp 92-102.
64.
Kornblith PL : Treatment of tumors of the posterior fossa: Astrocytoma, medulloblastoma, ependymoma and hemangioblastoma, in Kornblith PL, Walker MD, Cassady JR (eds): Neurologic Oncology. Philadelphia, JB Lippincott, 1987 , pp 163-180.
65.
Duckworth J. , Schmidek HH: Surgical management of posterior fossa tumors , in Schmidek HH, Sweet WH (eds): Operative Neurosurgical Techniques: Indications, Methods and Results. Orlando , Grune & Stratton, 1988, pp 653-664.
66.
Edwards Msb, Hudgins RJ: Medulloblastomas and primitive neuroectodermal tumors of the posterior fossa , in McLaurin RL, Venes JL, Schut L , Epstein F (eds): Pediatric Neurosurgery. Philadelphia, WB Saunders , 1989, pp 347-356.
67.
Hoffman HH, Hendrick EB, Humphreys RP: Management of medulloblastoma in childhood. Clin Neurosurg1983;30: 226-245.
68.
Kempes LG: Suboccipital craniectomy—median incision, in Kempes LG (ed): Operative Neurosurgery . Berlin , Springer-Verlag, 1962, pp 14-17.
69.
Shillito J. , Matson DD: Excision of cerebellar medulloblastoma, in Shillito J, Matson DD (eds): An Atlas of Pediatric Neurosurgical Operations . Philadelphia , WB Saunders, 1982 , pp 406-411.
70.
Cushing H.: Experience with medulloblastoma: A critical review. Acta Pathol Microbiol Scand1930;7:1-86.
71.
Inoya H., Takakura K., Shitara N., Manaka S.: Treatment of medulloblastoma. Prog Exp Tumor Res1987;30:91-99.
72.
Norris DG, Bruce DA, Byrd RL, et al: Improved relapse-free survival in medulloblastoma utilizing modern techniques. Neurosurgery1981;9:661-664.
73.
Albright AL : The value of precraniotomy shunts in children with posterior fossa tumors. Clin Neurosurg1983;30:278-285.
74.
McLaurin RL : Disadvantages of the preoperative shunt in posterior fossa tumors. Clin Neurosurg1983 ;30:286-292.
75.
Campbell AN , Chan Hsl , Becker LE, et al: Extracranial metastases in childhood primary intracranial tumors. A report of 21 cases and review of the literature . Cancer1984 ;53: 974-981.
76.
Hoffman HJ, Hendrick EB, Humphreys RP: Metastasis via ventriculoperitoneal shunt in patients with medulloblastoma . J Neurosurg1976;44:562-566.
77.
Bellani FF, Gasparini M., Lombardi F., et al: Medulloblastoma, results of a sequential combined treatment . Cancer1984;54:1956-1961.
78.
Berger MS, Baumstein B., Geyer JR, et al: The risks of metastases from shunting in children with primary central nervous system tumors. J Neurosurg1991;74:872-877.
Chatty EM, Earle KM: Medulloblastoma. A report of 201 cases with emphasis on the relationship of histological variants to survival. Cancer1971;28:977-983.
81.
Tomita T., Das L., Radkowski MA: Bone metastases in childhood: Correlation with flow cytometric DNA analysis . J Neurooncol1990;8:113-120.
82.
Chang CH, Housepain EM, Herbert C.: An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology1969 ;93:1351-1359.
83.
Beahrs OH, Hansen DE, Hutter RVP, Myers M (eds): Manual for Staging of Cancer , 3rd ed. Philadelphia, JB Lippincott, 1988.
84.
Chin HW, Maruyama Y.: Prognostic factors in medulloblastoma. Am J Clin Oncol1982;5:359-369.
85.
Van Dyk J.,Jenkin Rdt, Leung Pmk,Cunningham JR:Medulloblastoma: Treatment technique and radiation dosimetry . Int J Radiat Oncol Biol Phys1977;2:993-1005.
86.
Bloom Hjg , Wallace Enk , Henk JM: The treatment and prognosis of medulloblastoma in children. A study of 82 verified cases. Am J Roentgenol Radium Ther Nucl Med1969; 105:43-62.
87.
Chin HW, Maruyama Y.: Results of radiation treatment of cerebellar medulloblastoma. Int J Radiat Oncol Biol Phys1981;7:737-742.
88.
Harisiadis L. , Chang CH: Medulloblastoma in children: A correlation between staging and results of treatment. Int J Radiat Oncol Biol Phys1977;2:833-841.
89.
Silverman CL , Simpson JR: Cerebellar medulloblastoma: The importance of posterior fossa dose to survival and patterns of failure. Int J Radiat Oncol Biol Phys1982;8:1869-1876.
90.
Brand WN, Schneider PA, Tokars RP: Long term results of a pilot study of low dose cranial-spinal irradiation for cerebellar medulloblastoma. Int J Radiat Oncol Biol Phys1987;13: 1641-1645.
91.
Deutsch M., Thomas P., Boyett J., et al: Low stage medulloblastoma: A Children's Cancer Study Group (CCSG) and Pediatric Oncology Group (POG) Study of standard vs reduced neuraxis irradiation , Proc Am Soc Clin Oncol1991;10:124.
92.
Hershatter BW, Halperin EC, Cox EB: Medulloblastoma: The Duke University Medical Center experience. Int J Radiat Oncol Biol Phys1986;12:1771-1777.
93.
Garton GR, Schomberg PJ, Scheithauer BW, et al: Medulloblastoma—Prognostic factors and outcome of treatment: Review of the Mayo Clinic experience. Mayo Clin Proc1990;65:1077-1086.
94.
Dritschillo A., Bruckman JE, Cassady JR, et al: Tolerance of brain to multiple courses of radiation therapy—clinical experiences . Br J Radiol1981;54:782-786.
95.
Deutsch M., Reigel DH: Myelography and cytology in the treatment of medulloblastoma. Int J Radiat Oncol Biol Phys1981;7:721-725.
96.
Jereb B., Krishnaswami S., Reid A., Allen JC: Radiation for medulloblastoma adjusted to prevent recurrence to the cribriform plate region. Cancer1984;54:602-604.
97.
Chin HW, Maruyama Y., Young B.: Medulloblastoma: Recent advances and directions in diagnosis and management— Part II. Curr ProblCancer1984;7:25-42.
98.
Hornback NB : Radiation therapy in treatment of medulloblastoma in childhood, in Zeltzer PM, Pochedly C (eds): Medulloblastomas in Children: New Concepts in Tumor Biology, Diagnosis and Treatment. New York, Praeger, 1986, pp 164-181.
99.
Clemente CD , Yamazaki JN, Bennett LR, McFall RA: Brain radiation in newborn rats and differential effects of increased age. II. Microscopic observations . Neurology1960;10:669-675.
100.
Deutsch M. : Radiotherapy for primary brain tumors in very young children. Cancer1982;50:2785-2789.
101.
Hoffman HJ: Craniofacial anomalies, in Wilkins RW, Rengachary SS (eds): Neurosurgery. New York, McGraw-Hill , 1985, pp 2192-2202.
102.
Rapoport SI (ed): Blood-Brain Barrier in Physiology and Medicine. New York, Raven Press, 1976.
103.
Ater JL, Woo SY, van Eyes J.: Update on MOPP chemotherapy as primary therapy for infant brain tumors . Pediatr Neurosci1988;14:153-154.
104.
van Eys J. , Cangir A., Coody D., Smith B.: MOPP regimen as primary chemotherapy for brain tumors in infants. J Neurooncol1985 ;3:237-243.
105.
Shitara N. , Kohno T., Takakura K.: New approach to brain tumour chemoradiotherapy with cellular synchronization by Colcemid. Acta Neurochir1976;35:123-133.
106.
Yamamoto H. , Shitara N., Takakura K., Sano K.: Recruitment-chemoradiotherapy with VM 26 (epipodophyllotoxin) for induction treatment of malignant brain tumours. Acta Neurochir Suppl1979;28:616-618.
107.
Zeltzer PM: Chemotherapy for medulloblastoma: A review of treatment in recurrent and de novo tumors, in Zeltzer PM, Pochedly C (eds): Medulloblastomas in Children: New Concepts in Tumor Biology, Diagnosis and Treatment. New York, Praeger, 1986, p 182.
108.
Heideman RC , Packer RJ, Albright LA, et al: Tumors of the central nervous system , in Pizzo PA, Poplach DG (eds): Pediatric Oncology. Philadelphia, JB Lippincott, 1989 .
109.
Miser J., Arndt C., Smithson W., et al: Treatment of high grade osteosarcoma with ifosfamide, MRS, adiamycin, and high dose methotrexate, abstract. Proc Am Soc Clin Oncol , 1991;10:1088.
110.
Pendergrass TW, Milstein JM, Geyer JR, et al: Eight drugs in one day chemotherapy for brain tumors: Experience in 107 children and rationale for preradiation chemotherapy. J Clin Oncol1987;5:1221-1231.
111.
Horowitz ME , Mulhern RK, Kun LE, et al: Brain tumors in the very young child . Cancer1988;61:428-434.
112.
Kuhl J., Rating D., Berthold F., et al: Intensive chemotherapy after surgery and before radiotherapy in children with malignant brain tumors: Preliminary results of the West German pilot study hit '88/'89. Pediatr Neurosci1989;15:140-160.
113.
Grekow AK, Bailey C., Michaelis J., et al: SIOP/GPO Medulloblastoma II Trial: Sandwich chemotherapy and reduced dose radiotherapy for standard risk patients tested in a prospectively randomized international study. Pediatr Neurosci1989;15:144-145.
114.
Finlay J.: High-dose chemotherapy and autologous bone marrow rescue. Presented at the International Symposium on Pediatric Neuro-oncology, Philadelphia, May 24-26, 1990.
115.
Hartmann O. , Kalifa C., Vassal G., et al: Phase II study of high-dose Busulfan and thiotepa in children with recurrent brain tumors . Pediatr Neurosci1989;15:147.
116.
Kovner EH, Kellie SJ, Horowitz ME, et al: Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system: A phase II study. J Clin Oncol1990 ;8:330-336.
117.
Tomlinson FH, Lihou MG, Smith PJ: Comparison of in vitro activity of epipodophyllotoxins with other chemotherapeutic agents in human medulloblastomas. Br J Cancer, in press.
118.
Packer RJ, Sutton LN, Atkins TA, et al: A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg1989;70:707-713.
119.
Horowitz ME , Kun LE, Mulhern RK, et al: Feasibility and efficacy of preirradiation chemotherapy for pediatric brain tumors. Neurosurgery1988;22:687-690.
