Case Study 27

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Case Study 27

• Julia Kofler, M.D.

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Question 1

• A 5-year-old girl presents with a 6 week
  history of early morning headaches. Describe the
  findings in her MRI scan.

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T1
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T1 plus contrast
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T1 plus contrast
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Answer

• Large mixed cystic and solid midline mass in the
  posterior fossa
• Inhomogeneous contrast-enhancement of the solid
  component
• Mass effect with displacement of the brainstem
• Obstructive hydrocephalus

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Question 2

• What is your major differential diagnosis for
  posterior fossa tumors in children?

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Answer

• Ependymoma
• Pilocytic astrocytoma
• Medulloblastoma

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Question 3

• An intraoperative consultation was requested and
  performed via telepathology. Describe the
  findings in the intraoperative smear preparation
  on the following representative snapshots
  obtained via the telepathology system.

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Answer

• Hypercellular smear
• Small round blue cells with scant cytoplasm,
  finely speckled chromatin and inconspicuous
  nucleoli
• No glial processes apparent
• Numerous mitotic figures and apoptotic bodies

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Question 4

• What is your intraoperative diagnosis?

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Answer

• Medulloblastoma

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Question 5

• A resection of the mass was performed. Describe
  the findings in the following representative
  permanent HE slide.
• Click here to view slide.

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Answer

• Densely packed round to oval cells with high N/C
  ratio, scant cytoplasm and inconspicuous nucleoli
• Occasional nuclear molding
• Frequent apoptotic cells and scattered mitoses
• Multiple foci of necrosis
• Scattered Homer Wright rosettes
• Large areas with a nodular appearance nodules
  display decreased cellular density, reduced N/C
  ratio and a fibrillary matrix
•  No anaplastic features are present

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Question 6

• Identify the rosette types in the following
  images and give example(s) of tumors where these
  rosettes can be found.

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A
Image sources Ellison and Love, Neuropathology,
2nd ed, 2007Wippold and Perry, Am J Neuroradiol
2006 27488-492
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B
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C
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D
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Answer

• Pseudovascular pseudorosette Ependymoma,
  glioblastoma, medulloblastoma, PNET, pilomyxoid
  astrocytoma
• Flexner Wintersteiner rosette Retinoblastoma,
  pineoblastoma
• Ependymal rosette Ependymoma
• Homer Wright rosette Neuroblastoma,
  medulloblastoma, PNET, pineoblastoma

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Question 7

• Medulloblastomas can present with distinct
  histopathologic subtypes.
• Name major histopathologic subtypes
• Which is the predominant subtype in our case?
• Which stains can be used to highlight this growth
  pattern in our case?

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Answer

• - Desmoplastic/nodular medulloblastoma-
  Medulloblastoma with extensive nodularity-
  Anaplastic medulloblastoma- Large cell
  medulloblastoma- Medulloblastoma with myogenic
  differentiation- Medulloblastoma with melanotic
  differentiation
• Desmoplastic/nodular medulloblastoma
• Synaptophysin, reticulin, Ki-67

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Question 8

• Describe the findings in the following
  immunohistochemical slides for synaptophysin and
  Ki-67.
• Click here to view slide (GT.59B synaptophysin,
  GT.59C Ki-67).

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Answer

• Synaptophysin is positive within the nodular
  areas indicating regions of neuronal maturation
• Ki-67 shows high proliferative activity in the
  internodular areas and lower proliferation rates
  within the nodules
• These stains support a diagnosis of
  desmoplastic/nodular medulloblastoma

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Question 9

• Name clinical, pathological and molecular factors
  that have been associated with adverse or
  favorable outcome of medulloblastomas.

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Answer

• Adverse outcome
• Age lt3 years
• Incomplete surgical resection
• Metastatic disease
• Large cell/anaplastic variant
• Isochromosome 17q, loss of 17p, amplification of
  MYCC or MYCN genes
• Favorable outcome
• Desmoplastic/nodular variant
• Nuclear accumulation of beta-catenin

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Question 10

• Which familial cancer predisposition syndrome is
  associated with the desmoplastic/nodular variant
  of medulloblastoma?

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Answer

• Naevoid basal cell carcinoma syndrome (Gorlin
  syndrome)