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- 2. 2 Introduction highly malignant embryonal small cell tumors, of childhood with predominant location in the cerebellum and a noted capacity for divergent differentiation of variable degree along neuronal, glial, mesenchymal and melanotic lines similarities in histologic appearance belie important differences in oncogene expression, clinical behavior, treatment sensitivity & response Rorke 1997
- 3. 3 History 1837 sarcomas 1925 Bailey & Cushing, Globus & Strauss immature glial cell origin - spongioblastoma medulloblasts - medulloblastoma cerebelli other sites ? medulloblastoma cerebri Kershmann medulloblasts form external granular layer survival 1 / 63 patients at 3 yrs 1930 Cushing - adjuvant, involved field RT 60 – 80 % recurrences outside the field
- 4. 4 history . . . . 1953 Patterson & Farrprophylactic CSRT SR 50 % at 3 yrs 1968 Chang staging of medulloblastomas 1972 Rubenstien MB cerebellar tumor from bipotential EGL 1973 Hart & Earle PNET excluded cerebellar & pineal PNET ! 1980 Becker, Rorke unified PNET concept
- 5. Monotonous, small, round, deeply basopholic nuclii, minimal cytoplasm PNET on light microscopy
- 6. 6 embryogenesis neural plate 3 week neurulation, neural tube single layer of pseudostratified columnar epithelium cellular proliferation, mitosis post mitotic stage, migration undividing neuroblasts, dividing glioblasts non migrating remnant ependymoblasts extraventricular mitosis EGL of cerebellum ? only neuronal precursors intermediate subventricular zone of forebrain
- 7. 7 embryogenesis . . . stem cells in ventricular zone - single, multipotential cell 1889 His committed cells in ventricular zone germinal cell & spongioblast 1963 Schaper, Sauer multipotential uncommitted cell Fujita homogenous cell population( radiolabelling techniques) 1981 Levitt different groups of committed cells GFAP labelling
- 8. 8 Classification of CNS PNET general terminology cerebral / supratentorial PNET cerebral neuroblastoma medulloblastoma medulloepithelioma ependymoblastoma pinealoblastoma AT / RT
- 9. 9 classification . . . Rorke 1983 1. PNET (NOS) 2. PNET with differentiation a. astrocytes b. oligodendrocytes c. ependymal cells d. neurons e. other cell types, e.g., melanocytic, mesenchymal f. Mixed cellular elements common subventricular origin of all PNETs not seen in cerebellum not homogenous
- 10. 10 classification . . . Becker 1983 1. PNET, NOS 2. PNET, with astrocytes polar spongioblastoma 3. PNET, with neuronal cells neuroblastoma 4. PNET, with oligodendroglia 5. PNET, with ependymal cells ependymoblastoma 6. PNET, with melanin pigment melonotic medulloblastoma 7. PNET, with muscle elements myomedulloblastoma 8. PNET, with Flexner- Wintersteiner rosettes retinoblastoma 9. PNET, with neural tube-like structures medulloepithelioma 10.PNET, with olfactory epithelium olfactory neuroblastoma
- 11. 11 classification . . . 1985 Rorke ( modified) PNET – NOS PNET with differentiation Medulloepithelioma PNET ( pinealoblastoma) under pineal region tumors accepted the difficulties in identifying cell of origin 1986 Dehner included peripheral PNETs
- 12. 12 classification . . .WHO 1993 Tumors with neuroblastic or glioblastic elements (embryonal tumors) Medulloepithelioma PNETs medulloblastoma (MB) medullomyoblastoma, melanocytic, desmoplastic Neuroblastoma ganglioneuroblastoma Ependymoblastoma Kleihues 1993 ? Pineoblastoma retained separately
- 13. 13 classification . . . WHO 2000 Embryonal tumors Medulloepithelioma medulloblastoma (MB) medullomyoblastoma, melanocytic, desmoplastic, large cell variant supratentorial PNET Neuroblastoma, ganglioneuroblastoma AT / RT Ependymoblastoma Klieheus 2000 Pineal region tumors Pineoblastoma retained separately
- 14. 14 Classification . . . unsolved controversies cell of origin ? primitive neuroepithelial cell ? Single multipotential ? Commited bi / tripotential histological similarities & differences differences in natural history & progression differences in prognosis & approach status of medulloblastomas, pinealoblastomas
- 15. 15 Classification . . . present consensus PNET’s medulloblastomas pinealoblastomas
- 16. 16 Molecular biology isochromosome 17q (i17q) 50% PNET – MB, 1% s PNET 17 p 12 – 13.3 17 p 13.1 normal p53 mutation not seen in s PNET, rarely in MB loss of segments 10q & 9q, amplification of c-myc gene del 22 AT/ RT tumors
- 17. 17 Molecular biology . . . inherited genetic diseases Gorlin syndrome( nevoid BCC syndrome) AD, mutation of PTCH gene – 9 q 22 nevoid BCC, jaw keratocysts, skeletal abnormalities, ovarian fibromas, ectopic calcifications 5% MB - early age, desmoplastic Turcot syndrome AD, mutation of APC gene – 5 q 21 multiple colorectal neoplasms, MB Li-Fraumeni syndrome AD, soft-tissue sarcomas, osteosarcomas, breast cancer, leukemias, brain tumors. Ataxia telangiectasia, neurofibromatosis, tuberous sclerosis
- 18. 18 Molecular alteration Detected rate Clinical association Trk C 48% Low expression unfavorable outcome erbB-2 (HER2) 84% High expression unfavorable outcome PTCH 8%–10% Mutation development of sporadic and nonsporadic desmoplastic MB 17p 35%–50% Deletion unknown significance; putative tumor suppressor gene locus ? Shorter survival Molecular biology . . . Prognostic value
- 19. 19 Molecular biology . . . prognostic value FACTOR CORRELATION DNA ploidy Aneuploid recur Hyperdiploid survive longer Chromosome 22 Loss - poor prognosis intense p53 immunostaining poor outcome Woodburn 2001
- 20. 20 incidence overall 10 – 11 / million till 3 yrs s PNET 2.5 – 7% of childhood brain tumors MB 5 / 10 6 children 15%–20% childhood brain tumors 1% adult brain tumors 40% posterior fossa tumors
- 21. 21 age & sex s PNET 0 – 24yrs ( M - 7 yrs) cerebral neuroblastomas primarily < 2 yrs medulloepitheliomas 6mths – 5 yrs MB 3 – 4 & 8 – 9 yrs second, small peak 21- 40 yrs male predilection 1.5 - 2 : 1
- 22. 22 Pathology gross - large, well demarcated, necrotic, cystic centre, hemorrage L/M - highly cellular, pleomorphic, endothelial hyperplasia cells - small, undifferentiated( 90 – 95%), scant cytoplasm basophilic nuclei - dark, oval, numerous mitotic figures
- 23. 23 pathology . . . differentation ( 5%) L / M neuronal increase in cytoplasm, prominent nucleoli, HW rosettes, ganglion cells glial increase in cell size, glial processes ependyma perivascular pseudorosettes, ependymal rosettes Hart & Earle 1973 E / M neuronal Nissl substance, dense core granules, neurofibrils, microtubules, synaptic vesicles glial 80 – 90 A0 filaments ependymal microvilli, junctional complexes, cilia, basal bodies
- 24. 24 pathology . . . Homer-Wright rosettes tumor cell nuclei disposed in circular fashion about tangled cytoplasmic processes typical, but not always seen not essential for diagnosis when present, frequently associated with marked nuclear pleomorphism & high mitotic activity
- 25. 25 pathology . . . IHC neuroepithelial stem cell nestin neuronal neurofilament protien expression, NSE, tubulin glial GFAP mesenchymal vimentin epithelial cytokeratin retinal, muscle desmin, rhodopsin, retinal – S protien, vimentin neuroendocrine neuropeptide, synoptophysin expresion expressed in parts, combinations multidirectional differentiation frequent event in s PNETs no influence on outcome Visee 2005
- 26. 26 Clinical Symptoms : Irritability, lethargy, decreased social interaction 60% Intermittent vomiting 40% Headache 40% Visual blurring/change 30% Nausea 5% Imbalance 40%
- 27. 27 clinical . . . physical Papilledema 60% Ataxia 50% Nystagmus + / - gaze palsy 40% Lower cranial nerve palsy 20% Dysdiadochokinesia, hypotonia, dysmetria 20% Increased head circumference 30%
- 28. 28 clinical . . . physical Hydrocephalus younger, nonverbal patient - behavioral change, listlessness, irritability, vomiting, decreased social interactions. older children / adults - headache, vomiting without nausea, double vision, visual disturbances Cerebellar symptoms Children - gait ataxia, Adults - ipsilateral dysmetria head tilt neck stiffness (meningeal irritation, tonsillar herniation, trochlear nerve palsy ) Leptomeningeal dissemination back / neck pain, weakness, radiculopathy
- 29. 29 Imaging CT plain iso – hyperdense ( hypercellular) large, well defined margins, mass effect minimal peritumoral edema calcification 50 – 70% contrast heterogenous enhancement 90-95%
- 30. 30 imaging . . . MRI T1 iso – hyperintense T2 iso – hyperintense contrast enhance 91% DWI hyperintense, restricted diffusion reflects high cellularity, dense packing MRS nonspecific elevation of choline peak, decreased aspartate peak, variable lipid and lactate pre – op brain & spine imaging post – op brain imaging, < 72 hrs after surgery
- 31. 31 cerebral PNET location frontal 40% parietal 29% temporal 16% occipital 8% wide range of differentiation, astrocytic differentiation common
- 32. highly cellular, composed of small round to ovoid cells with hyperchromatic nuclei and little cytoplasm cerebral PNET . . .
- 33. c PNET, with normal adjacent brain
- 35. Occipital PNET hemispheric PNET T1 Contrast T1
- 36. ependymoblastoma large, deep periventricular tumor dense cellularity, ependymoblastic rosettes, no perivascular pseudorosettes, ependymal rosettes Rosettes – pseudostratified, luminal blepharoplasts apical microvilli & cilia
- 37. Hemispheric ependymoblastoma with cystic component
- 38. 38 Medulloepithelioma most primitive periventricular location, massive mimics embryonic neural tube - papillary, tubular, trabecular arrangement pseudo - stratification with external & internal limiting membrane multiple differentiation - glial, neuronal, oligoendroglial, ependymoblastic, muscle , bone IHC - nestin, EMA, cytokeratins etc iso – hypodense, NE
- 39. Glandular arrangement External limiting Basement membrane – PAS +
- 41. Atypical Teratoid / Rhabdoid Tumor rare < 5 yrs site PF 54%, ST 30% Rt CP angle AT/RT Cystic supratentorial AT/RT
- 42. AT / RT . . . highly cellular mixture of rhabdoid, glial, neuronal, epithelial cells rhabdoid cells – large eosinophilic cytoplasm with filament inclusions IHC - + EMA, vimentin , others - Desmin / Actin / AFP cell of origin ? Cs 22 q 11.2 – hSNF5 / INI 1 gene mutation poorer prognosis
- 43. 43 Cerebral neuroblastoma resembles c PNET no glial differentiation classical, transitional, desmoplastic increasing fibrous stroma, Indian file cellular streaming Neuronal line HW rosettes, ganglion cells Plain CT peri / intra ventricular locations commoner iso – hypo dense cystic with mural nodule hemorrage & necrosis less common Horten & Rubenstien 1976 Bennet 1984
- 44. 44 Mature ganglion cells with poorly differentiated surround Cerebral ganglioneuroblastoma . . . neuronal differentiation & streaming of cells Cerebral neuroblastoma
- 45. T1 TI C T2 Cerebral neuroblastoma
- 46. 46 Pineoblastomas 11 - 45% of all pineal tumors soft, friable, necrosis – common calcification rare HW rosettes photoceptor differentiation – Flexner – Winterstiener rosettes metastases common 60 – 70% Siffert 1997 uniformly poor prognosis
- 47. 47 Pineoblastomas . . . Clinical features hydrocephalus Parinaud's syndrome tectal plate compression Up gaze paresis, convergence / retraction nystagmus, disturbed light reflex paresis of down gaze or horizontal gaze Collier's sign dorsal midbrain compression lid retraction / ptosis 4th N palsies with diplopia / head tilt Ataxia / dysmetria (superior cerebellar peduncles) hearing disturbances (inferior colliculi) endocrine disturbance (hypothalamus)
- 48. 48 Flexner – Winterstiener rosettes Patternless sheets of small cells, hyperchromatic nuclei Homer Wright rosettes
- 50. T1 T1 C T2
- 51. 51 Trilateral retinablastoma bilateral retinoblastomas & pineoblastoma hereditary cancer, 13 q 14 mutation positive family history in 75% patients common photoreceptor cell origin uniformly poor prognosis mean survival 6.6 mths
- 52. 52 Medulloblastomas histogenesis ? Medulloblast fetal external granular layer persisting cell nests in medullary velum. inner granular layer ( older children / adults ) subependymal multipotential cell similar to other PNETS Rorke 1983
- 53. 53 MB. . . gross 75% - vermis 25% - lateral cerebellum solid, occasional cystic change, pseudocapsule, soft to firm, friable, necrosis, calcification ( 10%) hemorrhage rare ( 15%) diffuse arachnoid thickening(sugar coating)
- 54. 54 MB. . . varieties classic desmoblastic (20%) nodular “pale islands,” - cells with small, round, bland nuclei, abundant cytoplasm internodular regions - tightly packed, more proliferative, nuclei larger, atypical reticulin stain + connective tissue ? Misnomer - critical feature is nodular differentiation, not presence of connective tissue ? MB with limited nodularity Medulloblastoma with extensive nodularity nodular, well differentiated, little internodular component previously called “cerebellar neuroblastoma” Eberhart 2003
- 55. 55 desmoplastic MB with extensive nodularity
- 56. 56 MB . . . varieties Large cell / Anaplastic large nuclii, prominent nucleolus, abundant mitotic figures focally / difuuse poor prognosis anaplasia in nodular MB
- 58. 58 MB . . . Grading mitotic index poor prognosis glial differentiation poor necrosis poor desmoplasia good apoptosis index good Kopelson grading 0 -3 > 5 poor prognosis Eberhart 2003
- 59. 59 MB . . . CT NCCT - high-density midline mass varying degree of hydrocephalus (90%) variable asymmetric edema (90%) calcifications (13%). necrotic, cystic areas(10-16%) hemorrhage (3%) contrast CT marked homogeneous enhancement metastatic nodular seeding 10 – 15% nonenhancing
- 60. medulloblastoma
- 61. medulloblastoma T1 T2 T1 C
- 62. proton MR spectroscopy high CHO, low CR & NACC peaks 3.30 and 3.40 ppm - taurine high Cho:NAA ratio ? neuroepithelial origin , mature neurons required for NAA Krieger 2004
- 63. 63 Metastases cranial 20 – 30% spinal 20% CSF 15 – 20% c MRI > c CT myelo > myelography extra cranial 2 - 7% Bone 80%, LN 30%, lung/pleura 15%, liver 14%
- 64. Metastases along inner surface of dural membrane Cauda equina metastases
- 65. 65 subpial & subarachnoid space infiltration Metastasis . . .
- 66. 66 CSF for malignant cells - small blue cell neuroepithelial malignant tumor Metastasis . . .
- 67. Pineoblastoma with extensive leptomeningeal metastasis
- 68. Surviellance imaging detected diffuse leptomeningeal metastasis nonenhancing deposits - T2 - areas of distortion of subarachnoid spaces - abnormal signal on FLAIR or diffusion images.
- 69. 69 recurrence in MB median time to recurrence 13 – 18 mths median survival after recurrence 5 mths local recurrence 71% Muraszko 2004
- 70. 70 treatment Surgery role of surgery histological diagnosis maximal cytoreduction neural decompression, reduce mass effect relieve hydrocephalus complete excision difficult large tumors, deep location, multilobar involvement, highly vascular
- 71. 71 Surgery . . . approaches standard procedures supratentorial infratentorial midline retromastoid pineal tumors supratentorial parietal interhemispheric occipital transtentorial infratentorial supracerebellar
- 72. 72
- 73. 73 Surgery . . . for hydrocephalus ( in i PNET) permanent shunts 25 – 30% patients routine shunts not recommended shunt complications reverse herniation ( 3%) intra tumoral hemorrage peritoneal seeding (7 -19 %) Hoffman 1976 recommended strategy steroids 2 – 3 days, EVD s.o.s + semi urgent surgery shunt after 7 – 10 days , if required persistent raised ICP clinically, high CSF drain, radiological younger patients, large ventricles, long standing venticulomegaly, large tumors - usually require shunts
- 74. 74 Surgery . . . complications supratentorial infratentorial procedures cerebellar ataxia, nystagmus, dysmetria resolve VI, VII, lower cranial nerve dysfunction cerebellar mutism 10 %, 24 – 48 hrs post – op, resolve by 3 mths ? disruption of Dentatothalamocortical pathways assosciated emotional lability, abulia, later dysarthria, high pitched cry,oral motor apraxia, drooling bilateral edema in brachium pontis
- 75. 75 Radiotherapy post op total neuraxis radiation 3 - 10 wks post op standard dose tumor bed 56 Gy craniospinal (CSRT) 36 Gy
- 76. 76 Monitor blood counts Avoid in < 3 yrs age group Prone position Lateral opposed portals to brain, neck Direct posterior to spine RT . . . technique
- 77. 77 RT . . . sequelae transient hair loss decrease in WBC, platelets, red cell counts progressive vascular stroke (10 to 20 yrs post RT) short stature, scoliosis (spine irradiation)
- 78. 78 RT . . . Long term sequelae cognitive impairment 20 – 30 point reduction by 2 – 3 yrs whole brain irradiation young age greater deficits < 7 yrs age hydrocephalus neuroendocrinal GH defieciency, hypothyroidism oncogenesis 6 – 9 X meningiomas, malignant gliomas, thyrorid tumors, hemopoietic
- 79. 79 RT . . . Neurocognitive deficits Performance IQ consistently impaired deficits motor output, verbal memory, visuospatial processing & memory only few severely impaired - suggesting overall mild to moderate morbidity Neuroimaging white matter changes, changes in gray matter located around the tumor, myelination changes Carpentieri 2003
- 80. 80 RT . . . modifications low dose CSRT 24Gy poor outcome hyperfractionated RT 70 – 72 Gy 100 – 120 cGy, twice daily Stereotaxic RT, Fractionated stereotactic RT well defined residual brachytherapy / interstitial RT (small radioactive seeds) intensity modulated 3 – D conformal RT using microleaf collimators spares temporal lobes, hypothalamus, auditory apparatus radiosensitizers topotecan, paclitaxel, gadolinium texaphyrin increase free radical production & longetivity
- 81. 81 Chemotherapy adjuvant therapy study protocols 8 in 1 VinC, CCNU, ProC, HydUr, CisP, Cyt A, MethP, CycP PNET poorly chemosensitive, ? survival advantage MB chemosensitive
- 82. 82 Novel treatment strategy Desired effect HDCT and ASC support Penetrate BBB, high CNS drug level IT chemotherapy Prevent / treat LM disease BBB disruption increase CNS drug level Biologic therapy Target essential tumor bioactivity CT . . . innovations
- 83. 83 CT . . . recent advances neo – adjuvant CT pre RT, in < 3 yrs age group CT only in < 3 yrs age group MOPP regime HDCT + Au SCR for metastatic, recurrent tumors ThioT, EtoP, CarbP - high myeloablative doses marrow / peripheral stem cells harvested, cryopreserved reinfused 48 h after completion of CT intrathecal topotecan, mafosfamide BBB disruption lobradimil (bradykinin agonists) + systemic CarbP
- 84. 84 Staging Modified Chang’S staging per op impression, pre op MRI, post op MRI, post op LP CSF T T1 : <3cm, involving one PF structure – vermis, roof of IV v, cerebellar hemisphere T2 : <3cm, invading 2 or more PF structures, partially filling IV v T3a : >3cm, invading 2 or more PF structures, hydrocephalus T3b : Tumor invading the floor of IV ventricle, brain stem T4 : Tumor extending out of IV v, into III v, caudally into CM, severe hydrocephalus M Mo : No evidence of tumor dissemination M1 : Positive lumbar CSF cytology M2 : Intracranial tumor dissemination M3 : Intraspinal dissemination M4 : Systemic dissemination low stage T1, T2, M0 high stage > T3, M1 - 4
- 85. 85 Current staging for medulloblastomas Factor standard risk poor risk 1. extent of disease PF, no brainstem involvement disseminated intracranial no mets ( < 3A) extraneural disease 2. extent of resection near total, < 1.5 cm2 residual subtotal 3. age > 3 yrs < 3 yrs 4. histology differentiated undifferentiated Packer 1999
- 86. 86 Results PNETS 5 yr SR overall 34% - 60% standard risk 65% poor risk 25% operative mortality < 1% Timmermann 2002 extent of resection 52 children 4 yr SR residual disease < 1.5 cm2 40% > 1.5 cm2 13% not significant (p = 0.19) Cohen 1995
- 87. 87 results . . . multimodality therapy for PNET 53 pts surgery + CSRT + HDCT / Au SCR 2-year PFS rate - 93.6 % standard risk disease 73.7 % high-risk patients. Strother 2001 14 pts poor prognosis PNETs overall response rate 86% (72% CR, 14% PR) overall 2 - yr survival 50%. Bertuzzi 2002
- 88. 88 results . . . multimodality therapy for PNET (no radiation) Sx + HDCT / Au SCR 7 children < 4 yrs busulfan 16 mg/kg, melphalan 140 mg/m2, thiotepa 250 mg/m2, topotecan 2 mg/m2 median follow-up of 21 months (range 5–64) 5 CR, 1 PR, no treatment-related mortality 2 year PFS 71.43 Perez – Martinez 2004
- 89. 89 results . . . MB 5 yr SR surgery total resection - 64%, subtotal - 56 %, biopsy - 33% 10 yr SR 43 % near total Vs complete resection no outcome difference operative mortality 0% morbidity, complication rate 25% Albright 1996 Cohen 1996
- 90. 90 results . . . multimodality therapy for MB < 3 yrs vincristine, lomustine, prednisone 5 yr PFS standard risk tumor residual < 1.5 cm2 78% - 90% > 1.5 cm2 53% - 60% high risk 54% > 3 yrs RT/ vincristine + CCNU, VinC, CisP ( 8 cycles) 5 yr PFS standard risk (Low dose RT) 90% high risk ( standard RT) 67% Packer 1996
- 91. 91 results . . . CT alone 43 patients 3 cycles of IV CT (cycP, vinC, methX, carbP, etoP) intraventricular methoX 5 yr PFS complete resection (17) 82% residual tumor (14) 50% macroscopic metastases (12) 33%, 19 / 23 children asymptomatic leukoencephalopathy on MRI mean IQ significantly lower than healthy controls higher than those who received RT Rutkowski 2005
- 92. 92 results . . . newer RT regimes low dose RT (24 Gy) Vs standard RT at 3 yr local control 56% 80% recurrence 29% 8% Deustsh 1996 HFRT CSRT 30 Gy + brain 72Gy 3 yr PFS SR( % ) std risk(19) 63 79 high risk(20) 60 70 ( + CT) Prados 1999
- 93. 93 results . . . Neo – adjuvant CT in infants Neo adjuvant CT + delayed RT ( after 3 yrs) baby POG regime VinC + CycP 2 cycles later, CisP + etoP mthly, till 36 mths delayed RT 1 yr SR 72% 2 yr SR 46% MOPP CR 75% 3 cycles PFS 42% 24 cycles salvage RT or CT SR 66% 10 yrs good cognitive function, no endocrine deficits 1 – 3 yr no benefit ! Ater et al
- 94. 94 results . . . recurrent tumors HDCT + Au SCR 1. cisP, cycP, etoP, vinC 5 cycles thioT, etoP, carboP 1 cycle 2 yr overall SR 61% Finlay 1996 2. 23 pts 3 yr SR 46% Dunkel 1998
- 95. 95 results . . . metastatic disease 5 yr SR PNET overall SR 12 % Albright 1995 MB M0 70% M1 57% M2 40%
- 97. 97 Surviellance Surviellance neuroimaging cost anesthesia low frequency 17% detection rate no change in outcome
- 98. 98 Children's Cancer Group Surveillance recommendations for MB Brain MRI 3,6,9,12,16,20,24,30,36,48,60,84,120 mths Spinal MRI 12, 24, 36 mths or with each brain MRI (evidence of dissemination, residual tumor) CSF Cytology Repeat CSF cytology with each brain MRI if prior dissemination If no dissemination, repeat only as clinically Packer RJ 1994
- 99. 99 Summary 1. cell of origin not clear, not identified as many similarities as there are differences ? Single primitive neuroepithelial cell / commited progenitor cell at different sites better understanding of embryogenesis needed 2. no definite classification, only working consensus varaible interpretation of the term difficulty in reporting, collection, analysis of literature 2. pathological diagnosis is difficult IHC is not fully helpful in differentiating different vareities
- 100. 100 Summary . . . 3. Increasing number of histological subtypes and variants ? Clinical & prognostic significance 4. Role of surgery is mainly cytoreductive, cure requires multimodality therapy 5. Refinements in adjuvant therapy still going on rare tumors, most reports have small numbers, ? Interpretation good initial control, high late failures, high toxicity rates 6. Prognosis MB > PNET > Pineoblastoma
- 101. 101 7. MB distinct group Most common, larger age range, better studied Genetic predisposition, Familial syndromes well identified ? early detection, better prognosis Treatment protocols better defined , more chemosensitive Prognosis better, especially in some subtypes ? Cure PNET or not a PNET !
- 102. 102 9. PNET changing concept initially site based classsification different entities later histologic similarities recognized same group now increasing knowledge separate
- 103. 103 KMIO Regimen A vinC + CycP Regimen B CisP + VP 16 2 cycles alternating pre – RT post – RT (> 4 weeks)
- 104. 104 NIMHANS publications 1. Medulloepithelioma of the optic nerve with intradural extension - report of 2 cases Chidambaram B, Santosh V, Balasubramaniam V. Child’s Nerv Syst 2000;16:329 – 33 2. Medulloblastoma with extensive nodularity ; a variant ocurring in the very young - clinicopathological and immunohistochemical study of four cases Suresh TN, Santosh V, Yasha TC, Anandh B, Mahanty A, Indiradevi B, Sampath S, Shankar SK high degree of neurocytic differentiation, Bcl – 2 protien expression, better prognosis Child’s Nerv Syst 2004;20:55 - 60
- 105. 105 NIMHANS Data (Medulloblastoma) n-125 Year Classical MB Focal desmo. Desmoplastic LC / A Others 1999 17 1 3 0 1 2000 19 0 3 1 1 2001 17 0 4 1 0 2002 14 3 5 1 6 2003 21 1 3 1 2 Total 88(70.4%) 5(4%) 18(14.4%) 4(3.2%) 10(8%)
- 106. 106