1. Case Study 53 Edward D. Plowey

2. Case History The patient is a 20 year old male with no significant past medical history, who presented with a new-onset severe headache, nausea, photophobia and recent onset blurry vision. The severity of the symptoms precipitated a CT scan and MRI.

3. T1 T1 POST-CONTRAST CT w/o Contrast T2

4. Question 1 Describe the radiologic abnormalities in the following CT and MRI images.

5. Answer A non-contrast CT image shows a densely calcified heterogeneous mass lesion within the body of the left lateral ventricle. A T1 weighted image shows an irregular 6 centimeter mass in the body of the left lateral ventricle associated with the septum pellucidum. Following intravenous contrast administration there is subtle enhancement of the intraventricular mass; no abnormal parenchymal enhancement is identified. There is hydrocephalus of the lateral and 3 rd ventricles and midline shift from left to right. A T2 image shows no significant transependymal CSF accumulation, suggesting chronic, accommodated hydrocephalus. The mass extends inferiorly into the foramen of Monro and superior aspect of the 3rd ventricle (not shown). No potential metastatic lesions were seen.

6. Question 2 What is the differential diagnosis for this lesion?

7. Answer The differential diagnosis of this lesion includes: CENTRAL NEUROCYTOMA EPENDYMOMA CHOROID PLEXUS PAPILLOMA MENINGIOMA CALCIFIED REMOTE HEMATOMA

8. Question 3: Intraoperative Consultation The patient was taken to the operating room for left frontal craniotomy and resection via endoscopic port. The surgeons’ impression was that the tumor was indeed associated with the septum pellucidum. An intraoperative consultation was requested to confirm the clinical impression of central neurocytoma. Identify the findings and render a diagnosis for the intraoperative smear preparation.intraoperative smear preparation

9. Answer The intraoperative smear shows fragments of mineralized tissue and areas of a densely cellular neoplasm comprised of monotonous cells with round nuclei showing granular chromatin. The internuclear areas have a neuropil-like quality with exceedingly delicate processes appearing to emanate from some of the cells. Mitotic activity is not seen. Occasional delicate vessels are seen but there is no endothelial hyperplasia.fragments of mineralized tissuedensely cellular neoplasm comprised of monotonous cells with round nucleineuropil-likeOccasional delicate vessels What is your Intraoperative Diagnosis?

10. Answer Intraoperative diagnosis: A. Neoplastic. B. Central neurocytoma.

11. Question 4: Permanent Sections Examine the following virtual permanent section slides and describe your findings: Permanent of Frozen Section Tissue Additional Permanent Section

12. Answer Consistent with the intraoperative cytology, permanent sections demonstrate a neurocytic neoplasm with areas of confluent sclerosis and calcifications. Neuropil-like processes are seen between cells in densely cellular regions, but neuropil rosettes are not seen in this sample. There are no high grade features consistent with the intraoperative impression. Foci of the tumor show perinuclear clearing reminiscent of “fried egg” artifact seen in oligodendroglioma. No parenchymal infiltration is seen. Rare foci of tumor necrosis are seen.perinuclear clearingtumor necrosis Question 5: What immunostains will you order to confirm your diagnostic impression?

13. Answer Useful immunostains include the following: Synaptophysin (click to view virtual slide) Synaptophysin Ki67 (click to view virtual slide) Ki67 NeuN GFAP EMA

14. Question 6 What information do the special stains convey? What is the final diagnosis?

15. Answer The synaptophysin immunostain is diffusely and strongly positive in the neoplasm. Immunoreactivity is more intense in the intracellular neuropil processes than in the perinuclear cytoplasm, confirming predominantly neuronal differentiation.synaptophysin immunostain is diffusely and strongly positive The Ki67 immunostain shows a very low proliferative index of 1%.Ki67 immunostain A NeuN immunostain often shows nuclear reactivity neurocytomas. GFAP and EMA immunostains would be negative in this tumor. Final Diagnosis: CENTRAL NEUROCYTOMA, WHO GRADE 1.

16. Discussion This case highlights the classic presentation, location, histologic features and immunoreactivity profile of central neurocytoma. Transmission electron microscopy remains an option for tumors that do not react with neuronal markers (synaptophysin, NeuN, neuron specific enolase). Ultrastructural features suggestive of neurocytoma include processes with microtubules, dense core synaptic vesicles and rudimentary synaptic densities. The presence of a small focus of necrosis has no significance in this tumor which shows no high grade features. The prognosis of central neurocytoma is excellent. This patient’s underwent subtotal resection of his tumor. Residual third ventricular tumor was well controlled with gamma-knife radiosurgery at 1 year follow-up.

17. Discussion Oligodendroglioma is an important entity in the differential diagnosis of neurocytoma, especially extraventricular neurocytoma. Differentiation of these two entities has critical clinical implications. The following observations make this differential diagnosis challenging: 1. Oligodendrogliomas can show neurocytic differentiation (Perry et al, 2002). 2. Neurocytomas can mimic oligodendroglial histopathologic features, as in this case (perinuclear clearing artifact and a delicate capillary vasculature). 1p/19q co-deletion has been “reported” in approximately 25% of extraventricular neurocytoma (Rodriquez FJ et al., 2009). Co-deleted tumors show elevated proliferative indices and propensity for recurrence, and thus are similar to oligodendroglioma in terms of molecular abnormalities and clinical behavior. Thus such tumors might better be diagnosed as the Oligodendrogliomas they are ;-)

18. Discussion 1p/19q co-deletion by FISH is not found in central neurocytoma (Perry et al., 2003). However, to test the remote possibility that our tumor represented an exophytic or intraventricular oligodendroglioma, we performed 1p/19q co-deletion FISH analysis. The central neurocytoma in this case did not show 1p/19q co- deletion.

19. References Perry A, Scheithauer BW, Macaulay RJ, Raffel C, Roth KA, Kros JM. (2002). Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol. 61:947-55. Perry A, Fuller CE, Banerjee R, Brat DJ, Scheithauer BW. (2003). Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics. Front Biosci. 8:a1-9. Rodriguez FJ, Mota RA, Scheithauer BW, Giannini C, Blair H, New KC, Wu KJ, Dickson DW, Jenkins RB. Interphase cytogenetics for 1p19q and t(1;19)(q10;p10) may distinguish prognostically relevant subgroups in extraventricular neurocytoma. (2009). Brain Pathol. 19:623-9.