Neurosurgery notes/Tumours/Embryonal tumours/Medulloblastoma/Medulloblastoma histologically defined

Medulloblastoma histologically defined

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Medulloblastoma

General

  • When insufficient data for genetic definition or genetic test not done

Medulloblastoma, classic

Definition

  • An embryonal neuroepithelial tumour
  • Arising in the cerebellum or dorsal brain stem,
  • Consisting of densely packed small round undifferentiated cells with mild to moderate nuclear pleomorphism and
  • A high mitotic count

Numbers

  • Account for 72% of all medulloblastomas.
  • Infancy to adulthood

Genetic

  • Found in all 4 molecular medulloblastoma groups

Histology

  • Different vs other histological types:
    • Classic medulloblastoma lack significant intratumoural desmoplasia, the marked nuclear pleomorphism of the anaplastic variant, and the cytological features of the large cell variant
  • Syncytial arrangement of densely packed undifferentiated embryonal cells
  • Intratumoural desmoplasia is lacking, but pericellular desmoplasia is induced where tumour cells invade the leptomeninges.
  • Homer Wright rosettes are found in some classic (and large cell / anaplastic) medulloblastomas.
Fig. 8.11 Histopathological features of the classic medulloblastoma_ A Typical syncytial arrangement of undifferentiated tumour cells. B Area with Homer Wright (neuroblastic) rosettes. C Arranaement of tumour cells in parallel rows (soonaioblastic Dattern)_ Fig. 8.12 Medulloblastoma_ A Focal expression of synaptophysin_ B Focal GFAP staining oftumour cells. C Clusters of medulloblastoma cells expressing retinal S-antigen_ Fig. 8.13 A Classic medulloblastoma with nodules but (B) no desmoplasia_ Retculin staim These medulloblastomas belong to the non-WNT/non-SHH molecular group and should not be confused for desmoplastic/nodularmedulloblastomas.
Histopathological features of the classic medulloblastoma. (A) Typical syncytial arrangement of undifferentiated tumour cells. (B) Area with Homer Wright (neuroblastic) rosettes. (C) Arrangement of tumour cells in parallel rows (spongioblastic pattern).
Fig. 8.11 Histopathological features of the classic medulloblastoma_ A Typical syncytial arrangement of undifferentiated tumour cells. B Area with Homer Wright (neuroblastic) rosettes. C Arranaement of tumour cells in parallel rows (soonaioblastic Dattern)_ Fig. 8.12 Medulloblastoma_ A Focal expression of synaptophysin_ B Focal GFAP staining oftumour cells. C Clusters of medulloblastoma cells expressing retinal S-antigen_ Fig. 8.13 A Classic medulloblastoma with nodules but (B) no desmoplasia_ Retculin staim These medulloblastomas belong to the non-WNT/non-SHH molecular group and should not be confused for desmoplastic/nodularmedulloblastomas.
Medulloblastoma. (A) Focal expression of synaptophysin. (B) Focal GFAP staining of tumour cells. (C) Clusters of medulloblastoma cells expressing retinal S-antigen.
Fig. 8.11 Histopathological features of the classic medulloblastoma_ A Typical syncytial arrangement of undifferentiated tumour cells. B Area with Homer Wright (neuroblastic) rosettes. C Arranaement of tumour cells in parallel rows (soonaioblastic Dattern)_ Fig. 8.12 Medulloblastoma_ A Focal expression of synaptophysin_ B Focal GFAP staining oftumour cells. C Clusters of medulloblastoma cells expressing retinal S-antigen_ Fig. 8.13 A Classic medulloblastoma with nodules but (B) no desmoplasia_ Retculin staim These medulloblastomas belong to the non-WNT/non-SHH molecular group and should not be confused for desmoplastic/nodularmedulloblastomas.
(A) Classic medulloblastoma with nodules but (B) no desmoplasia. Reticulin stain. These medulloblastomas belong to the non-WNT/non-SHH molecular group and should not be confused for desmoplastic/nodular medulloblastomas.

Immunophenotype

  • Positive
    • NCAM1
    • MAP2
    • Neuron-specific enolase
    • Synaptophysin
    • NeuN
    • GFAP
      • In 10% only
      • When present aren't as widespread as astrocytic tumours and are scattered throughout the tumour
    • SMARCB1 and SMARCA4
  • Negative
    • NFPs

Desmoplastic/nodular medulloblastoma (D/NMB)

Definition

  • An embryonal neural tumour
  • Arising in the cerebellum and
  • Characterized by
    • Nodular, reticulin-free zones and intervening densely packed, poorly differentiated cells that produce an intercellular network of reticulin-positive collagen fibres

Numbers

  • 20% of all medulloblastomas
  • Aged < 3 years, desmoplastic/nodular medulloblastoma accounts for 47-57% of all medulloblastoma

Localisation

  • Both midline and cerebellar hemisphere

Radiology

  • More solid than cystic lesion
Machine generated alternative text: Fig. 8.16 Desmoplastic/nodular medulloblastoma_ A T I-weighted. (B) T2-weighted contrast-enhanced MRI of tumours in the cerebellar hemisphere. C Tl-weighted, contrast- enhanced MRI of a tumour in the vermis_
Desmoplastic/nodular medulloblastoma. (A) T1-weighted. (B) T2-weighted contrast-enhanced MRI of tumours in the cerebellar hemisphere. (C) T1-weighted, contrast-enhanced MRI of a tumour in the vermis

Histology

  • Must have both not just one of them to be called
    • Nodular pattern
    • Increased reticulin fibres (desmoplasia: increased fibrosis)
  • The nodules contain tumour cells with features of variable neurocytic maturation embedded in a neuropil-like fibrillary matrix.
  • Neuroblastic rosettes are not found in desmoplastic/nodular medulloblastoma.
Fig. 8.17 Desmoplastic/nodular medulloblastoma_ A Pale nodular areas surrounded by densely packed hyperchromatic cells. B Reticulin silver impregnation showing the reticulin free pale islands. C MIBI monoclonal antibody staining shows that the proliferative activity predominates in the highly cellular, intermodal areas. D Neuronal differentiation, shown by immunoreactivity for neuron-specific enolase, occurs mainly in the pale islands.
Desmoplastic/nodular medulloblastoma. (A) Pale nodular areas surrounded by densely packed hyperchromatic cells. (B) Reticulin silver impregnation showing the reticulin-free pale islands. (C) MIB1 monoclonal antibody staining shows that the proliferative activity predominates in the highly cellular, intermodal areas. (D) Neuronal differentiation, shown by immunoreactivity for neuron-specific enolase, occurs mainly in the pale islands.

Immunophenotype

  • Positive
    • Activation of SHH pathways
      • GAB1
      • TNFRSF16
  • Variable:
    • Synaptophysin
    • NeuN
    • GFAP
    • TP53
  • Negative
  • Ki67 is higher internodular areas than in nodules

Genetic

  • Early childhood, it is associated with naevoid basal cell carcinoma syndrome (gorlin syndrome)
    • Pathological activation of SHH pathway
    • 22.7% of patients with D/NMB
  • No isochromosome 17q
    • IsoChr 17q is a marker of midline classic (non-WNT) and large cell / anaplastic medulloblastomas

Outcome

  • Early childhood has an excellent outcome with surgery and chemotherapy alone
  • In infant medulloblastoma, progression-free or overall survival at 8 years was significantly better for desmoplastic variants than for other medulloblastomas

Medulloblastoma with extensive nodularity

Definition

  • An embryonal tumour
  • of the cerebellum
  • Characterized by
    • Many large reticulin-free nodules of neurocytic cells against a neuropil- like matrix and
    • By narrow internodular strands of poorly differentiated tumour cells in a desmoplastic matrix.

Numbers

  • 4% of all medulloblastoma variants overall
  • <3 yrs old account for 20% of all cases
    • Just behind desmoplastic/nodular medulloblastoma

Radiology

  • MRI
    • Very large multinodular lesion with enhancing grape-like structures involving the vermis and sometimes the cerebellar hemispheres
    • Rare cases
      • A peculiar gyriform presentation, in which the cerebellar folia are well-delineated and enlarged, with contrast enhancement.
      • Downward herniation of the cerebellar tonsils and effacement of the cisternal spaces of the posterior fossa can be observed.
        • Medulloblastoma with extensive nodularity. (A) Multinodular and gyriform pattern. (B) in a 1-month-old girl, the gadolinium-enhanced sagittal T1-weighted MRI shows a huge lesion involving both cerebellar hemispheres and the vermis. The lesion has a multinodular and gyriform pattern of enhancement. (C) Note the downward herniation of the tumour through the foramen magnum (arrow) and the marked effacement of the cisternal spaces of the posterior fossa. There is also supratentorial hydrocephalus and macrocrania.
        Medulloblastoma with extensive nodularity. (A) Multinodular and gyriform pattern. (B) in a 1-month-old girl, the gadolinium-enhanced sagittal T1-weighted MRI shows a huge lesion involving both cerebellar hemispheres and the vermis. The lesion has a multinodular and gyriform pattern of enhancement. (C) Note the downward herniation of the tumour through the foramen magnum (arrow) and the marked effacement of the cisternal spaces of the posterior fossa. There is also supratentorial hydrocephalus and macrocrania.

Histology

  • Differs from the related desmoplastic/ nodular variant in that is has an expanded lobular architecture due to the fact that the reticulin-free zones become unusually enlarged and rich in neuropil-like tissue.
    • So MBEN has neuropil like tissue within the reticulin free zones these are lighter pink than the N/DMN
      •  
Medulloblastoma with extensive nodularity. (A) Lobular architecture with large, elongated, reticulin-free zones. (B) Elongated, reticulin-free zones containing streams of small round neurocytic cells on a fibrillary background. (C) Strong immunoreactivity for NeuN in neurocytic cells of pale islands. (D) High MIB1 immunolabelling in internodular regions, contrasting with minimal proliferation in pale islands.
Medulloblastoma with extensive nodularity. (A) Lobular architecture with large, elongated, reticulin-free zones. (B) Elongated, reticulin-free zones containing streams of small round neurocytic cells on a fibrillary background. (C) Strong immunoreactivity for NeuN in neurocytic cells of pale islands. (D) High MIB1 immunolabelling in internodular regions, contrasting with minimal proliferation in pale islands.

Immunophenotype

  • Positive
    • SHH pathway
      • GAB1
      • TNFRSF16
  • Negative
  • NeuN and the Ki-67 proliferation index is much higher in internodular areas (like N/DMB)

Genetic susceptibility

  • SHH muatation gortin syndrome
    • 41% of pt with MBEN → need genetic counselling for family if kids have this disease

Outcome

  • Excellent outcome in the majority of cases
    • 8 years progression free survival 86% and overall survival 95%, respectively

Large cell/anaplastic medulloblastoma (LC/AMB)

Definition

  • An embryonal neural tumour
  • of the cerebellum or dorsal brain stem
  • Characterised by
    • Undifferentiated cells with marked nuclear pleomorphism,
    • Prominent nucleoli,
    • Cell wrapping, and
    • High mitotic and apoptotic counts

Numbers

  • 10% of all medulloblastomas and occurs
  • Across the patient age range of the medulloblastoma.

Histology

  • Intratumoural desmoplasia is not a feature of this variant, but desmoplasia can be evident when tumour cells overrun the leptomeninges
  • ‘Severe anaplasia’ combines marked nuclear pleomorphism with abundant mitotic activity and apoptosis
    • Other histological variant can have some nuclear pleomorphism and mitotic activity but these features are not as extensive as LC/AMB
Large cell / anaplastic medulloblastoma. A, B Increased nuclear size, pleomorphism, and prominent nucleoli. Tumour “cell wrapping” is also evident (B).
Large cell / anaplastic medulloblastoma. A, B Increased nuclear size, pleomorphism, and prominent nucleoli. Tumour “cell wrapping” is also evident (B).

Genetic

  • Found in all 4 genetic groups
    • Most fq in
      • group 3
      • SHH activated medulloblastomas
  • Overexpression of MYC (MYCN)
  • SHH-activated
    • GLI2
  • TP53 mutation

Outcome

  • Poor
    • 5-year progression-free survival rate for LC/A medulloblastomas is 30-40%
    • SHH-activated LC/AMB tumours with a TP53 mutation and group 3 tumours with MYC amplification can behave even more aggressively

Medulloblastoma, NOS

Definition

  • Embryonal neural tumour is located in the fourth ventricle or cerebellum and the nature of biopsied tissue prevents classification of the tumour into one of the genetically or histologically defined categories of medulloblastoma.