1. Case Study 13 Gabrielle Yeaney, M.D.

2. 40-year-old female with headache and word-finding problems, no other past medical history. Describe the MRI findings (location, enhancement, mass effect). Question 1

3. Sagittal T1

4. Axial T2 FLAIR

5. Coronal T1 post contrast

6. There is a heterogenous cystic mass within the right lateral ventricle (4.4 x 2.5 x 2.5 cm). The mass demonstrates minimal to no enhancement. There is mild enlargement of the right lateral ventricle, including the temporal horn. The mass is associated with the septum pellucidum. There is mild leftward deviation of the septum. Answer

7. Question 2 What is your differential diagnosis based on MRI?

8. Answer Ependymoma Subependymoma Central neurocytoma Choroid plexus tumors (lateral and third--children; fourth--adults) Pilocytic astrocytoma Subependymal giant cell astrocytoma (h/o tuberous sclerosis) Meningioma (rare)

9. Question 3 A craniotomy is performed and you do a smear prep for intraoperative diagnosis. Describe the cytologic features of the smear. Click here to view slide.here

10. Answer This hypercellular smear prep consists of a monomorphic population of cells with small-to- medium-sized round nuclei, finely granular chromatin and scant cytoplasm. Cells are process-poor and are present individually, not in clusters. A faint light pink matrix is noticeable in the background. There is no myxoid material, unlike oligodendroglioma. Nucleoli and mitotic figures are not readily found. Vessels are thin (one-cell-layer) for the most part.

11. Question 4 What is your intraoperative diagnosis (A. Neoplastic/Defer/Non-neoplastic, B. ______)

12. Answer A. Neoplastic B. Low grade neoplasm with round nuclei; favor central neurocytoma

13. Question 5 Review the permanent section. Describe the histologic features. Click here to view slide.here

14. Answer Histologic sections show tumor cells in sheets with occasional paucicellular islands of neuropil. There are scattered fine capillaries within the tumor. Cytology is similar to that seen on the smear (round cells, "salt-and-pepper" chromatin), except that well defined cell borders and perinuclear halos are seen on paraffin sections. Rare cells show a slight increase in cytoplasm and a small nucleolus suggestive of neuronal differentiation. Mitotic figures are not appreciated. There is no necrosis.

15. Question 6 What is your differential diagnosis (at least 2) after reviewing the H&E sections?

16. Answer Central neurocytoma vs oligodendroglioma. (Most supratentorial ependymomas are not intraventricular but maybe you could include clear cell ependymoma. However, there are no perivascular pseudorosettes on the H&E section.)

17. Question 7 What confirmatory immunohistochemical or other ancillary studies would you get?

18. Answer The most important stain to order would be synaptophysin. Other helpful studies include IHC for GFAP, Ki-67 and FISH for 1p/19q deletion. The histologic features of neurocytoma and oligodendroglioma can be quite similar. Neurocytoma is typically well defined on imaging and lacks diffuse tissue infiltration, a feature that leads to trapped neurons in oligodendroglioma. IHC for synaptophysin is usually negative in oligodendroglioma and positive in neurocytoma. But even the rare oligodendroglioma may have synaptophysin-positive rosettes. In that case, FISH studies showing lack of 1p/19q co-deletion should confirm the diagnosis of neurocytoma. GFAP would be positive in other glial neoplasms such as ependymoma.

19. Question 8 How would you describe the results of the following immunohistochemical studies? Given these results, what is your final diagnosis? Click here to view slides.here

20. Answer Tumor cells diffusely express synaptophysin. Glial fibrillary acidic protein (GFAP) highlights some reactive astrocytes but the tumor cells do not express GFAP. A few tumor cells show weak to strong expression for neuronal marker NeuN. Ki-67 shows a tumor cell proliferation index of 2-3% overall. Final diagnosis: Central neurocytoma.

21. Question 9 What is the WHO grade?

22. Answer Central neurocytoma is a WHO grade II lesion.

23. Question 10 Though mitotic figures are typically rare to absent in this lesion, a range of mitotic activity, microvascular proliferation and even necrosis is possible. Generally, increased proliferation index (Ki-67/MIB-1 labeling) is used to predict more aggressive behavior. What is the threshold for "grading" this tumor based on Ki-67/MIB-1 labeling?

24. Answer A threshold of 2% has been found to predict greater likelihood of recurrence. From Mackenzie IR (1999) Central neurocytoma: histologic atypia, proliferation potential, and clinical outcome. Cancer. 85:1606- 10: Although central neurocytomas are considered benigh, recent reports suggest that some patients with histologic atypia and/or elevated proliferation potential may have a poor outcome. A retrospective review identified 15 cases of central neurocytoma. Histologic atypia was identified in 3 tumors (20%). The MIB-1 LI ranged from 0.1% to 6.0%, and 5 cases (33%) had a MIB-1 LI > 2%. The proliferation potential of central neurocytoma is a useful predictor of clinical outcome, whereas histologic atypia alone is not prognostically significant. It would be appropriate to recognize a subgroup of central neurocytomas with elevated proliferation potential as WHO Grade 2 lesions. The terms "atypical" and "anaplastic" are not appropriate to describe these lesions, as they imply a certain histologic appearance. The most accurate designation would be "proliferating neurocytoma."

25. Question 11 Neurocytomas can occur outside of the ventricular system. True or False?

26. Answer True. Darn those pesky neurocytomas can occur in many locations. So called extraventricular, or intraparenchymal, neurocytomas have been reported in the cerebral hemispheres, thalamus, amygdala, pineal gland, retina, skull base, cerebellum, pons, spinal cord and cauda equina.