Case Study 27 Julia 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

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

Answer Ependymoma Pilocytic astrocytoma Medulloblastoma

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.

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

Question 4 What is your intraoperative diagnosis?

Answer Medulloblastoma

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

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

Question 6 Identify 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, 2 nd ed, 2007 Wippold and Perry, Am J Neuroradiol 2006; 27: A

B

C

D

Answer A. 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 7 Medulloblastomas 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?

Answer 1) - 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 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).here

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

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

Answer Adverse outcome: Age <3 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

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

Answer Naevoid basal cell carcinoma syndrome (Gorlin syndrome)