Case Study: Papillary Glioneuronal Tumor in a 14-Year-Old Boy with Seizures

1. Case Study 49 Edward D. Plowey

2. Case History • This is an outside consultation of a tumor resected from a 14 year-old boy who presented 1 month prior to surgery with a new onset seizure. • Initial MRIs at the outside institution reportedly showed a well-demarcated left temporal lobe tumor with mild hemorrhage. • Images from a preoperative MRI are shown in the next slide.

3. Question 1: Describe the MRI findings. T1 Pre-C T2 FLAIR T1 + Post C

4. Answer • The MRI shows a heterogeneous, well circumscribed, 4 cm left temporal lobe mass with minimal peri-tumoral edema. A large component of the posterior aspect of the mass exhibits contrast-enhancement. • Note: The T1 hyperintensity from prior studies reflecting hemorrhage had reportedly dissipated.

5. Question 2 • What are the most common entities that comprise the differential diagnosis of this mass?

6. Answer • The differential diagnosis would include: ganglioglioma, dysembryoplastic neuroepithelial tumor, pilocytic astrocytoma, low grade glioneuronal tumor, ependymoma, oligodendroglioma.

7. Question 3 An intraoperative consultation was requested and performed by remote telepathology. Describe the smear findings in the following images and formulate an intraoperative diagnosis:

9. Answer • Low power images of the intraoperative smear demonstrate a vascular lesion with degenerating blood. • A high power image shows a neoplasm composed of small round cells with open chromatin and a neurophil background. Some of the cells with more condensed chromatin (darker nuclei) show perivascular structuring. No mitotic figures are seen. Tumor vessels show non-reactive endothelial cells • Intraoperative Diagnosis: • A. Neoplastic • B. Low grade neurocytic tumor or Low grade glioneurocytic tumor

10. Question 4 Describe the findings in the following permanent section: Virtual Slide: http://image.upmc.edu:8080/NeuroPathology/GlialTumors/GlialTumor2/GT.82A.svs/view.apml? Diagnostic Images in the following Powerpoint slides

11. Answer • The histologic section demonstrates a predominantly neurocytic neoplasm with a minority of cells showing larger nuclei with more prominent nucleoli and moderate cytoplasm (ganglioid cells). Frank ganglion cells are not seen. Mitotic figures, endothelial hyperplasia and necrosis are not seen.

12. Answer • Some areas of the neoplasm show a pseudopapillary architecture. Hyalinazed blood vessels are bordered by cells with small round cells with scant cytoplasm.

13. Question 5 • What immunostains do you want to order to further characterize this neoplasm?

14. Answer • Synaptophysin (click the following virtual slide hyperlink) http://image.upmc.edu:8080/NeuroPathology/GlialTumors/GlialTumor2/GT.82B.svs/view.apml? • NeuN (click the following virtual slide hyperlink) http://image.upmc.edu:8080/NeuroPathology/GlialTumors/GlialTumor2/GT.82D.svs/view.apml? • GFAP (click the following virtual slide hyperlink) http://image.upmc.edu:8080/NeuroPathology/GlialTumors/GlialTumor2/GT.82C.svs/view.apml? • Ki67/MIB-1 • Diagnostic images on following Powerpoint slides

15. Synaptophysin

16. NeuN

17. GFAP

18. Ki67/MIB-1

19. Question 6 What information do the immunostains convey?

20. Answer A synaptophysin immunostain is negative in the cytoplasm of the neurocytic cell component, but is positive in the neurophil processes of the neurocytic component of the tumor. A NeuN immunostain is positive in some of the tumor cells with ganglioid differentiation. A GFAP immunostain is strongly positive in the glial cells lining the hyalinized blood vessels. A Ki67/MIB-1 immunostain is positive in less that 1% of the tumor cells.

21. Question 7 • What ancillary molecular diagnostic tests might be helpful in the diagnosis?

22. Answer • The histologic findings are diagnostic and obviate ancillary molecular testing. • 1p/19q co-deletion analysis may be ordered by the pathologist that is unfamiliar with this entity. If the patient is an adult, a negative result could be reassuring that you are not dealing with a Grade 2 oligodendroglioma. However, a negative 1p/19q result in a child or young adult does not rule out oligodendroglioma, and the pathologist must rely on recognition of the characteristic histologic features to arrive at the correct diagnosis.

23. Question 8 Which of the following choices is the correct diagnosis? A. Oligodendroglioma with neurocytic differentiation B. Atypical Extraventricular Neurocytoma C. Ganglioglioma D. Papillary Glioneuronal Tumor E. Angiocentric Glioma

24. Answer: Choice D Final Diagnosis: Papillary Glioneuronal Tumor, WHO Grade 1.

25. Discussion • The typical picture of the rare papillary glioneuronal tumor (PGNT) is a well-demarcated, contrast-enhancing mass in the temporal lobe of a young adult with new onset seizures. By most accounts, these tumors are generally thought to be adequately treated with gross total resection (Komori T et al. Am J Surg Pathol. 22:1171-83, 1998. • As was seen in this case, presentation via cerebral hemorrhage has been previously reported (Buccoliero A. et al., Neuropathol. 26:206-11, 2006).

26. Discussion • Although this rare tumor is considered a WHO Grade 1 neoplasm, recent reports of PGNT with elevated proliferation and tumor recurrence suggest that PGNT should be thoroughly examined for histologic signs of potential aggressive behavior. • Javahery et al., J Neurosurg Pediatrics. 3:46-52, 2009. • Newton et al. Clin Neuropathol. 27:317-24, 2008. • Vaquero and Coca. J Neurooncol. 83:319-23, 2007. • Ishizawa T, et al. Hum Pathol. 37:627-30, 2006. • As is suggested in the GFAP-immunostained slide, the tumor-brain interface is gliotic. Furthermore, Rosenthal fibers and/or eosinophilic granular bodies can be seen. As with any tumor showing a reactive brain border, these features could conceivably cause diagnostic errors in biopsies taken from the tumor periphery.