Case Study 27Julia Kofler, M.D.

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

Question 1

T1

T1 plus contrast

T1 plus contrast

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

Answer

Question 2What is your major differential diagnosis for posterior fossa tumors in children?

AnswerEpendymoma

Pilocytic astrocytoma

Medulloblastoma

Question 3An 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.

AnswerHypercellular smear

“Small round blue cells” with scant cytoplasm, finely speckled chromatin and inconspicuous nucleoli

No glial processes apparent

Numerous mitotic figures and apoptotic bodies

Question 4What is your intraoperative diagnosis?

AnswerMedulloblastoma

Question 5A resection of the mass was performed. Describe the findings in the following representative permanent H&E slide.

Click here to view slide.

AnswerDensely 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

Question 6Identify the rosette types in the following images and give example(s) of tumors where these rosettes can be found.

Image sources: Ellison and Love, Neuropathology, 2nd ed, 2007Wippold and Perry, Am J Neuroradiol 2006; 27:488-492

A

B

C

D

AnswerA. Pseudovascular pseudorosette: Ependymoma,

glioblastoma, medulloblastoma, PNET, pilomyxoid astrocytoma

B. Flexner Wintersteiner rosette: Retinoblastoma, pineoblastoma

C. Ependymal rosette: Ependymoma

D. Homer Wright rosette: Neuroblastoma, medulloblastoma, PNET, pineoblastoma

Question 7Medulloblastomas can present with distinct histopathologic subtypes.

1)Name major histopathologic subtypes

2)Which is the predominant subtype in our case?

3)Which stains can be used to highlight this growth pattern in our case?

Answer1) - Desmoplastic/nodular medulloblastoma

- Medulloblastoma with extensive nodularity- Anaplastic medulloblastoma- Large cell medulloblastoma- Medulloblastoma with myogenic differentiation- Medulloblastoma with melanotic differentiation

2) Desmoplastic/nodular medulloblastoma

3) Synaptophysin, reticulin, Ki-67

Question 8Describe the findings in the following immunohistochemical slides for synaptophysin and Ki-67.

Click here to view slide (GT.59B synaptophysin, GT.59C Ki-67).

AnswerSynaptophysin 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

Question 9Name clinical, pathological and molecular factors that have been associated with adverse or favorable outcome of medulloblastomas.

AnswerAdverse outcome:

Age <3 yearsIncomplete surgical resectionMetastatic diseaseLarge cell/anaplastic variantIsochromosome 17q, loss of 17p, amplification

of MYCC or MYCN genes

Favorable outcome:Desmoplastic/nodular variantNuclear accumulation of beta-catenin

Question 10Which familial cancer predisposition syndrome is associated with the desmoplastic/nodular variant of medulloblastoma?

AnswerNaevoid basal cell carcinoma syndrome (Gorlin syndrome)