Case Study 31

1. Case Study 31 Julia Kofler, M.D.

2. Question 1 A 6-year-old boy was followed for several years for a slowly growing brain lesion. Describe the findings in his MRI scan.

3. T1

4. T2 flair

5. T1 post-contrast

6. Answer • Homogeneously contrast-enhancing mass in the frontal horn of the left lateral ventricle • Minimal mass effect with slight shift of the septum pellucidum • A smaller contrast-enhancing mass is also seen in the frontal horn of the right lateral ventricle (best seen on the axial image) • No evidence of surrounding brain edema • No evidence of hydrocephalus

7. Question 2 What is your differential diagnosis based on the imaging findings?

8. Answer • Ependymoma • Subependymal giant cell astrocytoma • Choroid plexus tumors • Pilocytic astrocytoma • Central neurocytoma • Meningioma • Subependymoma is usually non-enhancing

9. Question 3 A resection of the mass was performed. Describe the findings in the following representative permanent H&E slide. Click hereto view slide.

10. Answer • Clusters of polygonal cells with abundant glassy cytoplasm and eccentric nuclei with prominent nucleoli • Tumor cells vary in size; giant cells and multinucleated cells are present • Tumor cells are embedded in fibrillary background • Focal perivascular pseudopalisading • Rare mitotic figures are present • Scattered infiltrating mast cells are noted • No necrosis or vascular endothelial proliferation is present

11. Question 4 Representative images of immunohistochemical stains can be seen in the following figure. The Ki-67 proliferation index was 1-3%. What is your diagnosis?

12. GFAP S100 NeuN

13. Answer Subependymal giant cell astrocytoma

14. Question 5 Throughout the tumor, there are scattered cells with a different morphology and pale blue cytoplasm as highlighted in the following figure. • What are these cells? • Which stain was used to highlight them? • Which immunohistochemical stains could be used to highlight these cells

16. Answer • Mast cells • Giemsa stain • Tryptase or CD117 (c-kit)

17. Question 6 Further review of the patient’s MRI scan reveals additional findings. The patient also has a history of seizures. Describe the radiologic findings and give the most likely diagnosis.

18. T2 flair

19. T2 flair

20. T2 flair

21. Answer • Multifocal subcortical T2/flair hyperintensities and minimal thickening of the overlying cortex • Cortical tubers

22. Question 7 Other clinical features in this patient include an asymptomatic cardiac tumor, mild learning disability and multiple white patches on his skin. • Based on the clinical, radiological and pathological findings, what is your diagnosis? • What is the most likely diagnosis for the patient’s cardiac tumor?

23. Answer • Tuberous sclerosis • Cardiac rhabdomyoma

24. Question 8 Which genetic test would you order to confirm you diagnosis?

25. Answer Mutational analysis of TSC1 and TSC2 genes, encoding for hamartin and tuberin.

26. Question 9 Name the major clinical features of tuberous sclerosis.

27. Answer • Facial angiofibromas • Nontraumatic ungual or periungual fibroma • Hypomelanotic macules (>3) • Shagreen patch • Retinal nodular hamartomas • Cortical tubers • Subependymal nodules • Subependymal giant cell astrocytoma • Cardiac rhabdomyoma • Lymphangiomatosis • Renal angiomyolipoma

28. Question 10 What are the histopathologic findings in a cortical tuber?

29. Answer • Giant cells (similar to subependymal giant cell astrocytoma) • Dysmorphic neurons • Dysmorphic neurons and giant cells may be seen in all cortical layers and underlying white matter • Disrupted cortical lamination • Gliosis • Calcification of blood vessel walls and/or parenchyma • Myelin loss