Case Study 27

1. Case Study 27 Julia Kofler, M.D.

2. Question 1 A 5-year-old girl presents with a ~6 week history of early morning headaches. Describe the findings in her MRI scan.

3. T1

4. T1 plus contrast

5. T1 plus contrast

6. 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

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

8. Answer • Ependymoma • Pilocytic astrocytoma • Medulloblastoma

9. 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.

13. 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

14. Question 4 What is your intraoperative diagnosis?

15. Answer Medulloblastoma

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

17. 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

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

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

20. B

21. C

22. D

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

24. 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?

25. 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

26. Question 8 Describe the findings in the following immunohistochemical slides for synaptophysin and Ki-67. Click hereto view slide (GT.59B synaptophysin, GT.59C Ki-67).

27. 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

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

29. 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

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

31. Answer Naevoid basal cell carcinoma syndrome (Gorlin syndrome)