1. UPMC Pathology Resident Didactic Series March 31 & April 7, 2009 CNS NEOPLASMS Scott M. Kulich, MD, PhD VA Pittsburgh Healthcare System Assistant Professor Division of Neuropathology Department of Pathology University of Pittsburgh Acknowledgements: Marta Couce, MD, PhD Ronald Hamilton, MD Geoff Murdoch, MD, PhD

2. Outline Neuroradiology for pathologists Familial tumor syndromes CNS neoplasms –Astrocytic neoplasms Diffuse astrocytomas -> GBM –Variants Pilocytic astrocytomas Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma –Oligodendrogliomas Oligoastrocytomas –Other neuroepithelial Angiocentric glioma, chordoid glioma, astroblastoma –Ependymomas

3. Outline (CNS neoplasms cont.) Choroid plexus Neuronal - Neuroglial Tumors –Ganglioglioma –Central neurocytoma –Paraganglioma Embryonal tumors Meningeal tumors

4. Outline Neuroradiology for pathologists Familial tumor syndromes CNS neoplasms –Astrocytic neoplasms Diffuse astrocytomas -> GBM –Variants Pilocytic astrocytomas Pleomorphic xanthoastrocytoma Subependymal giant cell astrocytoma –Oligodendrogliomas Oligoastrocytomas –Other neuroepithelial Angiocentric glioma, chordoid glioma, astroblastoma –Ependymomas

5. NEURORADIOLOGY FOR PATHOLOGISTS Question: Who cares?

6. NEURORADIOLOGY FOR PATHOLOGISTS Question: Who cares? Answer: You will when your favorite neurosurgeon hands you a piece of tissue the size of a grain of salt and tells you he needs you to tell him if he can go ahead and stick Gliadel chemotherapeutic wafers in the patient’s brain

7. NEURORADIOLOGY FOR PATHOLOGISTS Question: Who cares? Neuroradiology = Gross pathology Answer: You will when your favorite neurosurgeon hands you a piece of tissue the size of a grain of salt and tells you he needs you to tell him if he can go ahead and stick Gliadel chemotherapeutic wafers in the patient’s brain

8. NEURORADIOLOGY FOR PATHOLOGISTS Two main imaging techniques –Computerized tomography (CT) 3D X-rays White areas = areas that absorb or “attenuate” the passage of x-ray beam (acute hematoma, bone, calcium = hyperdense/ attenuating) Black areas = areas that do not absorb or “attenuate” the passage of x-ray beam (fat, air, CSF, edema = hypodense/ attenuating) Neuroradiology for

9. Neuroradiology for

10. NEURORADIOLOGY FOR PATHOLOGISTS Magnetic resonance imaging (MRI) Not ionizing radiation but magnetic field to excite protons which emit “signal” upon relaxation Image appearance dependent upon time interval between each excitation and time interval between each collection Two basic “weights” of images based upon TE and TR –T1: Short TE and TR »T1 is the one…that looks like a brain –T2 :Long TE and TR

11. NEURORADIOLOGY FOR PATHOLOGISTS Magnetic resonance imaging (MRI) Not ionizing radiation but magnetic field to excite protons which emit “signal” upon relaxation Image appearance dependent upon time interval between each excitation and time interval between each collection Two basic “weights” of images based upon TE and TR –T1: Short TE and TR »T1 is the one…that looks like a brain –T2 :Long TE and TR

12. NEURORADIOLOGY FOR PATHOLOGISTS Magnetic resonance imaging (MRI) Not ionizing radiation but magnetic field to excite protons which emit “signal” upon relaxation Image appearance dependent upon time interval between each excitation and time interval between each collection Two basic “weights” of images based upon TE and TR –T1: Short TE and TR »T1 is the one…that looks like a brain –T2 :Long TE and TR

13. NEURORADIOLOGY FOR PATHOLOGISTS T1

14. NEURORADIOLOGY FOR PATHOLOGISTS T2

15. NEURORADIOLOGY FOR PATHOLOGISTS Important info to glean from neuroimaging –Age –Location, location, location –Multicentricity –Bilateral hemisphere involvement –Architecture –Contrast enhancement –Interaction with surrounding tissue

16. Location, location, location…

17. CHILDREN

18. Location, location, location… ADULTS

20. NEURORADIOLOGY FOR PATHOLOGISTS Multicentricity –Neoplasms Metastatic disease Others (lymphoma, high-grade glioma,…) –Non-neoplastic Demyelinating disease Infectious Bilateral hemisphere involvement –“butterfly” lesion Glioblastoma multiforme (GBM), lymphoma

21. NEURORADIOLOGY FOR PATHOLOGISTS Multicentricity –Neoplasms Metastatic disease Others (lymphoma, high-grade glioma,…) –Non-neoplastic Demyelinating disease Infectious Bilateral hemisphere involvement –“butterfly” lesion Glioblastoma multiforme (GBM), lymphoma

22. NEURORADIOLOGY FOR PATHOLOGISTS: Butterfly lesion (GBM)

23. NEURORADIOLOGY FOR PATHOLOGISTS Architecture –CYSTIC = LOW-GRADE JPA (juvenile pilocytic astrocytoma), PXA (pleomorphic xanthoastrocytoma), ganglion cell tumors, Others (hemangioblastoma, craniopharygioma, supratentorial ependymomas, extraventricular neurocytoma) Frequently associated with a mural nodule (JPA, PXA, hemangioblastoma, ganglion cell tumors,PGNT, extraventricular neurocytoma) –Dural tail Meningioma

24. NEURORADIOLOGY FOR PATHOLOGISTS: JPA

25. NEURORADIOLOGY FOR PATHOLOGISTS Architecture –CYSTIC = LOW-GRADE JPA (juvenile pilocytic astrocytoma), PXA (pleomorphic xanthoastrocytoma), ganglion cell tumors, Others (hemangioblastoma, craniopharygioma, supratentorial ependymomas, extraventricular neurocytoma) Frequently associated with a mural nodule (JPA, PXA, hemangioblastoma, ganglion cell tumors,PGNT, extraventricular neurocytoma) –Dural tail Meningioma

26. NEURORADIOLOGY FOR PATHOLOGISTS: Meningioma

27. NEURORADIOLOGY FOR PATHOLOGISTS Contrast enhancement –Breached blood-brain barrier –Seen with neoplasms but can be seen with other conditions (e.g. infectious, demyelinating, …) –Pattern of enhancement often helpful Homogeneous versus non-homogeneous –Lymphoma, hemangiopericytoma, meningioma –GBM, mets, abscesses Patchy versus circumferential ( i.e. ring enhancement)

28. NEURORADIOLOGY FOR PATHOLOGISTS Contrast enhancement –Breached blood-brain barrier –Seen with neoplasms but can be seen with other conditions (e.g. infectious, demyelinating, …) –Pattern of enhancement often helpful Homogeneous versus non-homogeneous –Lymphoma, hemangiopericytoma, meningioma –GBM, mets, abscesses Patchy versus circumferential ( i.e. ring enhancement)

29. NEURORADIOLOGY FOR PATHOLOGISTS Heterogeneous enhancement (GBM)

30. NEURORADIOLOGY FOR PATHOLOGISTS Homogeneous enhancement (Meningioma)

31. NEURORADIOLOGY FOR PATHOLOGISTS Interaction with surrounding tissue –Edema “Activity” of lesion –Malignant neoplasms –Inflammatory lesions –Skull Erosion: Long-standing low-grade lesions –Dysembryoplastic neuroepithelial tumor (DNET), PXA, ganglion cell tumors,oligodendrogliomas,epidermoid cysts Hyperostosis –Meningiomas

32. NEURORADIOLOGY FOR PATHOLOGISTS Interaction with surrounding tissue –Edema “Activity” of lesion –Malignant neoplasms –Inflammatory lesions –Skull Erosion: Long-standing low-grade lesions –Dysembryoplastic neuroepithelial tumor (DNET), PXA, ganglion cell tumors,oligodendrogliomas,epidermoid cysts Hyperostosis –Meningiomas

33. NEURORADIOLOGY FOR PATHOLOGISTS Interaction with surrounding tissue –Edema “Activity” of lesion –Malignant neoplasms –Inflammatory lesions –Skull Erosion: Long-standing low-grade lesions –Dysembryoplastic neuroepithelial tumor (DNET), PXA, ganglion cell tumors,oligodendrogliomas,epidermoid cysts Hyperostosis –Meningiomas

34. Approach to intraoperative consults

35. Review of imaging and history Questions for surgeon –What do you NEED to know? –Can you get more tissue if necessary? Specimen preparation –Intraoperative cytology vs frozen sections touch and smear preparations

36. Approach to intraoperative consults Review of imaging and history Questions for surgeon –What do you NEED to know? –Can you get more tissue if necessary? Specimen preparation –Intraoperative cytology vs frozen sections touch and smear preparations

37. Approach to intraoperative consults Review of imaging and history Questions for surgeon –What do you NEED to know? –Can you get more tissue if necessary? Specimen preparation –Intraoperative cytology vs frozen sections touch and smear preparations

38. Approach to intraoperative consults Specimen preparation –Intraoperative cytology Smear preparations

39. Approach to intraoperative consults Specimen preparation –Intraoperative cytology Smear preparations

40. A “Wiley” approach to intraoperative consults

42. A “wiley” approach to intraoperative consults Abnormal versus normal Reactive versus neoplastic Primary versus metastatic Grade of lesion Does diagnosis correlate with clinical and imaging data?

43. A “wiley” approach to intraoperative consults Abnormal versus normal Reactive versus neoplastic Primary versus metastatic Grade of lesion Does diagnosis correlate with clinical and imaging data?

44. A “wiley” approach to intraoperative consults Abnormal versus normal Reactive versus neoplastic Primary versus metastatic Grade of lesion Does diagnosis correlate with clinical and imaging data?

45. A “wiley” approach to intraoperative consults Abnormal versus normal Reactive versus neoplastic Primary versus metastatic Grade of lesion Does diagnosis correlate with clinical and imaging data?

46. A “wiley” approach to intraoperative consults Abnormal versus normal Reactive versus neoplastic Primary versus metastatic Grade of lesion Does diagnosis correlate with clinical and imaging data?

47. Kulich Any questions?