- Email: [email protected]
Anaplastic Medulloblastoma with Myogenic Differentiation
Journal Pre-proof SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation case report Dr. Shilpa Rao, DM, Assistant Professor, Dr. Alok Mohan Uppar, MCh, Assistant Professor, Dr. Vani Santosh, MD, Professor PII:
S1878-8750(19)33011-6
DOI:
https://doi.org/10.1016/j.wneu.2019.11.161
Reference:
WNEU 13830
To appear in:
World Neurosurgery
Received Date: 31 October 2019 Revised Date:
26 November 2019
Accepted Date: 27 November 2019
Please cite this article as: Rao S, Mohan Uppar A, Santosh V, SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report, World Neurosurgery (2020), doi: https:// doi.org/10.1016/j.wneu.2019.11.161. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Shilpa Rao, Alok Mohan Uppar1, Vani Santosh Departments of Neuropathology and Neurosurgery1, National Institute of Mental Health and Neurosciences
1. Dr. Shilpa Rao, DM Assistant Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] 2. Dr. Alok Mohan Uppar, MCh Assistant Professor Department of Neurosurgery NIMHANS Bangalore-560029 Email:[email protected] 3. Dr. Vani Santosh, MD Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Corresponding author Dr. Vani Santosh Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Phone:080-26995130
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Shilpa Rao, Alok Mohan Uppar1, Vani Santosh Departments of Neuropathology and Neurosurgery1, National Institute of Mental Health and Neurosciences
1. Dr. Shilpa Rao, DM Assistant Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] 2. Dr. Alok Mohan Uppar, MCh Assistant Professor Department of Neurosurgery NIMHANS Bangalore-560029 Email:[email protected] 3. Dr. Vani Santosh, MD Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Corresponding author Dr. Vani Santosh Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Phone:080-26995130
1
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Abstract Medulloblastoma (MB) with myogenic differentiation is a rare histological variant. Case report: We report a case of a seven-year-old female child who presented with a left cerebellar mass. Histopathological examination showed a cellular neoplasm comprising undifferentiated cells along with foci of bizarre giant cells. Immunohistochemistry revealed that the tumour corresponded to MB, SHH-activated subgroup. Conclusion: The case is being reported to document this rare variant of MB which had myogenic differentiation. Molecular characterisation of this variant has been analysed in very few cases so far.
Keywords: Medulloblastoma, LCA, Myogenic, SHH.
2
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Introduction Medulloblastoma (MB) has four histological subtypes and four genetically defined subgroups as per the 2016 World Health Organization (WHO) classification of central nervous system (CNS) neoplasms. MB with myogenic/ melanotic differentiation are the rare histological patterns. Myogenic differentiation has been reported in about fifty cases with most of them seen in association with classic histological subtype. Because of its rarity, molecular alterations in this pattern of MB has been less described. We report a case of large cell/ anaplastic (LCA) MB with myogenic differentiation, SHH- activated. Case Report A seven year old girl presented with headache, vomiting, imbalance and left sided cerebellar signs. Imaging revealed a large solid cystic lesion in the left cerebellar hemisphere with heterogeneous enhancement in the solid component and along the walls of lesion (Fig.1A). The patient underwent left paramedian sub-occipital craniotomy and decompression of the lesion.
On histopathological examination, the tumor was highly cellular, composed of sheets of medium-sized cells with scant to moderate cytoplasm, hyperchromatic nuclei, frequent cell to cell wrapping, nuclear moulding and brisk mitotic activity (Fig.1B). Interestingly, there were foci of cells that were unusually large, pleomorphic with few tumor giant cells (Fig.1C). Dense aggregates of tumour infiltrating lymphocytes were seen. Histological diagnosis considered was a large cell/anaplastic MB, with differential diagnoses of atypical teratoid/rhabdoid tumour (AT/RT) or a high grade glioma. On immunohistochemistry (IHC), there was diffuse vimentin immunopositivity, variable patchy expression for both synaptophysin (Fig.1E) and Glial fibrillary acidic protein (GFAP, Fig.1D) , while the large cells were negative for both GFAP and synaptophysin. Strong, diffuse p53 immunopositivity was noted. Patchy desmin staining was seen, including in an occasional large cell (Fig.1F). S100 protein, epithelial membrane antigen (EMA), pan-cytokeratin and BRAF V600E were negative. Integrase interactor 1 (INI1) nuclear positivity was retained, thus excluding AT/RT. HMB-45 was negative. Histological diagnosis provided was large cell/ anaplastic MB. Molecular subtyping was performed utilising a panel of IHC markers (Fig.2). Tumour cells 3
revealed immunopositivity for GAB-1 and YAP-1. β-catenin was negative. Interesting finding was that the large cells did not express GAB-1 or YAP-1. Fluorescence in situ hybridisation did not reveal amplification of c-myc. A final diagnosis of large cell/ anaplastic medulloblastoma with myogenic differentiation, SHH-activated and p53 mutant was offered.
DISCUSSION The four histological subtypes of MB include classic, desmoplastic/ nodular, MB with extensive nodularity and LCA MB.1 In addition, there are rare histological variants such as MB with myogenic/ melanotic differentiation. The 2016 WHO classification has also incorporated genetically defined subgroups; WNT- activated, SHH- activated [p53 mutant/p53 wild type] and the non WNT/ non SHH subgroup. We report a case of LCA MB, SHH- activated, p53 mutant with myogenic differentiation in a seven year old girl. LCA MB accounts for 20-25% of all MB cases and has a high rate of cmyc amplification.1,2 Myogenic differentiation in MB is rare and about fifty cases of this variant have been reported in the literature so far, the majority of patients being younger than 10 years of age, 3 similar to our patient. These patients have a poor prognosis, with a median overall survival of two years post-therapy. Myogenic differentiation is usually observed in the classic MB subtype and rarely in LCA, as seen in our case.3 Several theories regarding the origin of medullomyoblastomas indicate that myogenic differentiation occurs from undifferentiated neural crest cells, ectomesenchyme, pluripotent stem cells or as variations of malignant teratoma.4,5 In our case, in addition to the myogenic differentiation a subset of tumour cells were large and bizarre with immunonegativity for all the markers expressed by rest of the tumour which probably indicate a distinct form of differentiation of the stem cells. Few studies reported medullomyoblastomas to harbour alterations in chromosome 17 or cmyc amplification.3 However, our case belonging to the SHH- activated and p53 mutant subgroup, did not exhibit c-myc amplification as was also reported by Bergmann et al.6 Gupta et al analysed seven cases of MB with myogenic and/or melanotic differentiation and found that these cases did not align with the known molecular subgroups.7
Another interesting finding in our case was the immunopositivity for GFAP in the tumour cells. Medulloblastoma, being an embryonal tumour expresses synaptophysin. GFAP immunopositivity is unusual and probably indicates a glial differentiation. Mannoji et al 4
analysed GFAP immunopositivity in 24 MB.8 In 16 cases of classic MB, they found variable numbers of GFAP-positive cells. They classified the cells as three different types according to size and shape. Type 1 cell was morphologically identical to the tumor cell. Type 2 cell had abundant cytoplasm and type 3 cell was considered a reactive astrocyte. In one case of desmoplastic MB, the majority of GFAP-positive cells were arranged in "islands", and had delicate fibrillated processes. However, there was no LCA MB in their series. We have seen GFAP positivity in the tumour cells, corresponding to type 1 cell. Although some authors believe that MB with myogenic differentiation is associated with a poor prognosis,9 others have reported their behaviour to be similar to classic subtype.2 Our case belongs to the SHH- activated, p53 mutant subgroup and these tumours have been shown to belong to the ‘very high risk’ category with <50% five year survival.10 Recent classification of MB based on integrative analysis found children with SHH-activated, p53 mutant MB belonged to the alpha subgroup of SHH MB and these patients had a poor prognosis.11 Taking together the results of our study case and that reported in literature, it still remains unclear if MB with myogenic differentiation belongs to one of the known molecular subgroups, or is a distinct histological entity with different molecular alterations. Awareness of the unusual histological patterns of MB is essential for accurate diagnosis.
Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Financial support: None
Acknowledgement: The authors wish to acknowledge the technical assistance of Mr. M R Chandrashekar and Mr. Manjunath.
References: 1. Ellison DW, Eberhart CG, Pietsch T, Pfiser S (2016). Medulloblastoma. In: Louis D, Ohgaki H, Weistler O, Cavenee W,ed., WHO Classification of Tumours of the Central Nervous System, Revised 4th ed. France: IARC, p.184-200. 5
2. Fathaddin AA, Bakhash EA, Sabbagh AJ, Al-Dandan SW (2014). Large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation: A case report of a rare tumor. Indian Journal of Pathology and Microbiology. 57(2):294. 3. Helton KJ, Fouladi M, Boop FA, Perry A, Dalton J, Kun L, et al (2004). Medullomyoblastoma: a radiographic and clinicopathologic analysis of six cases and review of the literature. Cancer 101(6):1445–54. 4.
Kalimo H, Paljärvi L, Ekfors T, Pelliniemi LJ (1987). Pigmented primitive neuroectodermal tumor with multipotential differentiation in cerebellum (pigmented medullomyoblastoma).
A
case
with
light-
and
electron-microscopic,
and
immunohistochemical analysis. Pediatr Neurosci 13(4):188–95 5. Nozza P, Milanaccio C, Piatelli G, Rossi A, Raso A, Cama A, et al (2008). Cerebellar medullomyoblastoma with melanotic tubular structures. Pediatric Blood & Cancer. 50(1):183–5 6. Bergmann M, Pietsch T, Herms J, Janus J, Spaar H-J, Terwey B (1998). Medullomyoblastoma:
a
histological,
immunohistochemical,
ultrastructural
and
molecular genetic study. Acta Neuropathol. 95(2):205–12 7. Gupta K, Jogunoori S, Satapathy A, Salunke P, Kumar N, Radotra BD, et al (2018). Medulloblastoma with myogenic and/or melanotic differentiation does not align immunohistochemically with the genetically defined molecular subgroups. Hum Pathol. 75:26–33. 8.
Mannoji H, Takeshita I, Fukui M, Ohta M, Kitamura K (1981). Glial fibrillary acidic protein in medulloblastoma. Acta Neuropathol. 55(1):63–9.
9. Sarkar P, Halder A, Arun I, Chatterjee U, Chatterjee S (2017).Medullomyoblastoma: A report of two cases. Neurol India. 65:647-50. 10. Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, et al (2016). Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol. 131(6):821–31.
6
11. Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, et al (2017). Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. 31(6):73754
7
Medulloblastoma legend Figure 1 Magnetic resonance imaging T1W contrast image showed a left cerebellar solid cystic lesion with enhancement of the solid component (A). On histopathological examination, a cellular high grade embryonal tumour with features of a large cell/ anaplastic medulloblastoma (B,H&E,x200) and unusual foci of large bizarre cells with abundant eosinophilic cytoplasm was noted (C,H&E,x400). These cells revealed variable immunopositivity with glial fibrillary acidic protein (GFAP,D,x100) and synaptophysin (E,x200), which also showed dot like positivity. Desmin was positive in small as well as large cells (F and inset,x200).
Figure 2 Molecular subtyping revealed immunonegativity for β-catenin (A) with immunopositivity for GAB-1 (B) and YAP-1 (C). Large cells were not labelled by GAB-1 (inset,B).There was diffuse strong immunoreactivity to p53 (D). [A-D: immunoperoxidase, x200]
Abbreviations
MB Medulloblastoma LCA Large cell/anaplastic WHO World health organisation CNS Central nervous system GFAP Glial fibrillary acidic protein
S1878-8750(19)33011-6
DOI:
https://doi.org/10.1016/j.wneu.2019.11.161
Reference:
WNEU 13830
To appear in:
World Neurosurgery
Received Date: 31 October 2019 Revised Date:
26 November 2019
Accepted Date: 27 November 2019
Please cite this article as: Rao S, Mohan Uppar A, Santosh V, SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report, World Neurosurgery (2020), doi: https:// doi.org/10.1016/j.wneu.2019.11.161. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Shilpa Rao, Alok Mohan Uppar1, Vani Santosh Departments of Neuropathology and Neurosurgery1, National Institute of Mental Health and Neurosciences
1. Dr. Shilpa Rao, DM Assistant Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] 2. Dr. Alok Mohan Uppar, MCh Assistant Professor Department of Neurosurgery NIMHANS Bangalore-560029 Email:[email protected] 3. Dr. Vani Santosh, MD Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Corresponding author Dr. Vani Santosh Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Phone:080-26995130
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Shilpa Rao, Alok Mohan Uppar1, Vani Santosh Departments of Neuropathology and Neurosurgery1, National Institute of Mental Health and Neurosciences
1. Dr. Shilpa Rao, DM Assistant Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] 2. Dr. Alok Mohan Uppar, MCh Assistant Professor Department of Neurosurgery NIMHANS Bangalore-560029 Email:[email protected] 3. Dr. Vani Santosh, MD Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Corresponding author Dr. Vani Santosh Professor Department of Neuropathology NIMHANS Bangalore-560029 Email:[email protected] Phone:080-26995130
1
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Abstract Medulloblastoma (MB) with myogenic differentiation is a rare histological variant. Case report: We report a case of a seven-year-old female child who presented with a left cerebellar mass. Histopathological examination showed a cellular neoplasm comprising undifferentiated cells along with foci of bizarre giant cells. Immunohistochemistry revealed that the tumour corresponded to MB, SHH-activated subgroup. Conclusion: The case is being reported to document this rare variant of MB which had myogenic differentiation. Molecular characterisation of this variant has been analysed in very few cases so far.
Keywords: Medulloblastoma, LCA, Myogenic, SHH.
2
SHH-activated Large cell/Anaplastic medulloblastoma with myogenic differentiation - case report Introduction Medulloblastoma (MB) has four histological subtypes and four genetically defined subgroups as per the 2016 World Health Organization (WHO) classification of central nervous system (CNS) neoplasms. MB with myogenic/ melanotic differentiation are the rare histological patterns. Myogenic differentiation has been reported in about fifty cases with most of them seen in association with classic histological subtype. Because of its rarity, molecular alterations in this pattern of MB has been less described. We report a case of large cell/ anaplastic (LCA) MB with myogenic differentiation, SHH- activated. Case Report A seven year old girl presented with headache, vomiting, imbalance and left sided cerebellar signs. Imaging revealed a large solid cystic lesion in the left cerebellar hemisphere with heterogeneous enhancement in the solid component and along the walls of lesion (Fig.1A). The patient underwent left paramedian sub-occipital craniotomy and decompression of the lesion.
On histopathological examination, the tumor was highly cellular, composed of sheets of medium-sized cells with scant to moderate cytoplasm, hyperchromatic nuclei, frequent cell to cell wrapping, nuclear moulding and brisk mitotic activity (Fig.1B). Interestingly, there were foci of cells that were unusually large, pleomorphic with few tumor giant cells (Fig.1C). Dense aggregates of tumour infiltrating lymphocytes were seen. Histological diagnosis considered was a large cell/anaplastic MB, with differential diagnoses of atypical teratoid/rhabdoid tumour (AT/RT) or a high grade glioma. On immunohistochemistry (IHC), there was diffuse vimentin immunopositivity, variable patchy expression for both synaptophysin (Fig.1E) and Glial fibrillary acidic protein (GFAP, Fig.1D) , while the large cells were negative for both GFAP and synaptophysin. Strong, diffuse p53 immunopositivity was noted. Patchy desmin staining was seen, including in an occasional large cell (Fig.1F). S100 protein, epithelial membrane antigen (EMA), pan-cytokeratin and BRAF V600E were negative. Integrase interactor 1 (INI1) nuclear positivity was retained, thus excluding AT/RT. HMB-45 was negative. Histological diagnosis provided was large cell/ anaplastic MB. Molecular subtyping was performed utilising a panel of IHC markers (Fig.2). Tumour cells 3
revealed immunopositivity for GAB-1 and YAP-1. β-catenin was negative. Interesting finding was that the large cells did not express GAB-1 or YAP-1. Fluorescence in situ hybridisation did not reveal amplification of c-myc. A final diagnosis of large cell/ anaplastic medulloblastoma with myogenic differentiation, SHH-activated and p53 mutant was offered.
DISCUSSION The four histological subtypes of MB include classic, desmoplastic/ nodular, MB with extensive nodularity and LCA MB.1 In addition, there are rare histological variants such as MB with myogenic/ melanotic differentiation. The 2016 WHO classification has also incorporated genetically defined subgroups; WNT- activated, SHH- activated [p53 mutant/p53 wild type] and the non WNT/ non SHH subgroup. We report a case of LCA MB, SHH- activated, p53 mutant with myogenic differentiation in a seven year old girl. LCA MB accounts for 20-25% of all MB cases and has a high rate of cmyc amplification.1,2 Myogenic differentiation in MB is rare and about fifty cases of this variant have been reported in the literature so far, the majority of patients being younger than 10 years of age, 3 similar to our patient. These patients have a poor prognosis, with a median overall survival of two years post-therapy. Myogenic differentiation is usually observed in the classic MB subtype and rarely in LCA, as seen in our case.3 Several theories regarding the origin of medullomyoblastomas indicate that myogenic differentiation occurs from undifferentiated neural crest cells, ectomesenchyme, pluripotent stem cells or as variations of malignant teratoma.4,5 In our case, in addition to the myogenic differentiation a subset of tumour cells were large and bizarre with immunonegativity for all the markers expressed by rest of the tumour which probably indicate a distinct form of differentiation of the stem cells. Few studies reported medullomyoblastomas to harbour alterations in chromosome 17 or cmyc amplification.3 However, our case belonging to the SHH- activated and p53 mutant subgroup, did not exhibit c-myc amplification as was also reported by Bergmann et al.6 Gupta et al analysed seven cases of MB with myogenic and/or melanotic differentiation and found that these cases did not align with the known molecular subgroups.7
Another interesting finding in our case was the immunopositivity for GFAP in the tumour cells. Medulloblastoma, being an embryonal tumour expresses synaptophysin. GFAP immunopositivity is unusual and probably indicates a glial differentiation. Mannoji et al 4
analysed GFAP immunopositivity in 24 MB.8 In 16 cases of classic MB, they found variable numbers of GFAP-positive cells. They classified the cells as three different types according to size and shape. Type 1 cell was morphologically identical to the tumor cell. Type 2 cell had abundant cytoplasm and type 3 cell was considered a reactive astrocyte. In one case of desmoplastic MB, the majority of GFAP-positive cells were arranged in "islands", and had delicate fibrillated processes. However, there was no LCA MB in their series. We have seen GFAP positivity in the tumour cells, corresponding to type 1 cell. Although some authors believe that MB with myogenic differentiation is associated with a poor prognosis,9 others have reported their behaviour to be similar to classic subtype.2 Our case belongs to the SHH- activated, p53 mutant subgroup and these tumours have been shown to belong to the ‘very high risk’ category with <50% five year survival.10 Recent classification of MB based on integrative analysis found children with SHH-activated, p53 mutant MB belonged to the alpha subgroup of SHH MB and these patients had a poor prognosis.11 Taking together the results of our study case and that reported in literature, it still remains unclear if MB with myogenic differentiation belongs to one of the known molecular subgroups, or is a distinct histological entity with different molecular alterations. Awareness of the unusual histological patterns of MB is essential for accurate diagnosis.
Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Financial support: None
Acknowledgement: The authors wish to acknowledge the technical assistance of Mr. M R Chandrashekar and Mr. Manjunath.
References: 1. Ellison DW, Eberhart CG, Pietsch T, Pfiser S (2016). Medulloblastoma. In: Louis D, Ohgaki H, Weistler O, Cavenee W,ed., WHO Classification of Tumours of the Central Nervous System, Revised 4th ed. France: IARC, p.184-200. 5
2. Fathaddin AA, Bakhash EA, Sabbagh AJ, Al-Dandan SW (2014). Large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation: A case report of a rare tumor. Indian Journal of Pathology and Microbiology. 57(2):294. 3. Helton KJ, Fouladi M, Boop FA, Perry A, Dalton J, Kun L, et al (2004). Medullomyoblastoma: a radiographic and clinicopathologic analysis of six cases and review of the literature. Cancer 101(6):1445–54. 4.
Kalimo H, Paljärvi L, Ekfors T, Pelliniemi LJ (1987). Pigmented primitive neuroectodermal tumor with multipotential differentiation in cerebellum (pigmented medullomyoblastoma).
A
case
with
light-
and
electron-microscopic,
and
immunohistochemical analysis. Pediatr Neurosci 13(4):188–95 5. Nozza P, Milanaccio C, Piatelli G, Rossi A, Raso A, Cama A, et al (2008). Cerebellar medullomyoblastoma with melanotic tubular structures. Pediatric Blood & Cancer. 50(1):183–5 6. Bergmann M, Pietsch T, Herms J, Janus J, Spaar H-J, Terwey B (1998). Medullomyoblastoma:
a
histological,
immunohistochemical,
ultrastructural
and
molecular genetic study. Acta Neuropathol. 95(2):205–12 7. Gupta K, Jogunoori S, Satapathy A, Salunke P, Kumar N, Radotra BD, et al (2018). Medulloblastoma with myogenic and/or melanotic differentiation does not align immunohistochemically with the genetically defined molecular subgroups. Hum Pathol. 75:26–33. 8.
Mannoji H, Takeshita I, Fukui M, Ohta M, Kitamura K (1981). Glial fibrillary acidic protein in medulloblastoma. Acta Neuropathol. 55(1):63–9.
9. Sarkar P, Halder A, Arun I, Chatterjee U, Chatterjee S (2017).Medullomyoblastoma: A report of two cases. Neurol India. 65:647-50. 10. Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, et al (2016). Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol. 131(6):821–31.
6
11. Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, et al (2017). Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. 31(6):73754
7
Medulloblastoma legend Figure 1 Magnetic resonance imaging T1W contrast image showed a left cerebellar solid cystic lesion with enhancement of the solid component (A). On histopathological examination, a cellular high grade embryonal tumour with features of a large cell/ anaplastic medulloblastoma (B,H&E,x200) and unusual foci of large bizarre cells with abundant eosinophilic cytoplasm was noted (C,H&E,x400). These cells revealed variable immunopositivity with glial fibrillary acidic protein (GFAP,D,x100) and synaptophysin (E,x200), which also showed dot like positivity. Desmin was positive in small as well as large cells (F and inset,x200).
Figure 2 Molecular subtyping revealed immunonegativity for β-catenin (A) with immunopositivity for GAB-1 (B) and YAP-1 (C). Large cells were not labelled by GAB-1 (inset,B).There was diffuse strong immunoreactivity to p53 (D). [A-D: immunoperoxidase, x200]
Abbreviations
MB Medulloblastoma LCA Large cell/anaplastic WHO World health organisation CNS Central nervous system GFAP Glial fibrillary acidic protein