L'hermitte-Duclos Disease: Case Study Summary

1. Case Study 48 Edward D. Plowey

2. Case History • The patient is a 64 y/o woman with a 2.5 year history of a left cerebellar hemisphere lesion initially discovered and followed at an outside hospital on workup for chronic headaches. • The outside impression was initially a benign lesion, possible encephalomalacia. However, interval enlargement of the lesion prompted neurosurgical intervention.

3. Question 1 Describe the major radiologic abnormality on the following MRI.

5. Answer Well-delineated T2 bright lesion in the left cerebellar hemisphere with a thickened foliar architecture pattern. There is minimal surrounding edema, no significant mass effect or midline shift. No hemorrhage is seen on T1 and there is no abnormal contrast enhancement. (There is also a small enhancing left retromastoid lesion with underlying meningeal enhancement felt to be a hemangioma.) L’hermitte-duclos disease was strongly suspected based on these radiologic features. The patient was taken to the OR for resection of the left cerebellar hemisphere lesion.

6. Question Describe the findings in the following images from the intraoperative consultation.

7. Intraoperative Consultation Frozen Frozen Smear

8. Answer • An intraoperative smear preparation shows a heterogeneous cell population with an large increase in the ratio of ganglion cells to small granule neurons than is expected in the cerebellar cortex. Occasional reactive astrocytes are also seen. • A frozen section shows increased numbers of disordered ganglion cells surrounding both sides of the foliar white matter. No normal granule cell layer is seen in this folium. • An intraoperative diagnosis of L’hermitte-Duclos disease was rendered based on these pathologic findings and the MRI findings.

9. Question • Describe the findings on the H&E stained permanent sections of the lesion resection material. • Click here to view virtual slide.

10. Answer Histologic sections demonstrate areas with normal cerebellar cortical architecture that abruptly yield to abnormal cerebellar cortex in which the granule cell layer is replaced by abnormal, disorganized ganglion cells. These areas of cortex also lack Purkinje cells and show expansion of the molecular layer with myelinated axons. These findings are diagnostic of L’hermitte-Duclos disease.

11. Question • A NeuN immunostain was performed on the lesion. Describe the significance of the findings. • Click here to view virtual slide.

12. Answer A NeuN immunostain is positive in both the normal granule neuron layers and in the layer of dysplastic ganglion cells. These findings demonstrate that the ganglion cells are not Purkinje neurons (which are normally NeuN negative); they are phenotypically related to the granule neurons.

13. Question • A neurofilament immunostain was performed on the lesion. Describe the significance of the findings. • Click here to view virtual slide.

14. Answer A neurofilament immunostain highlights axons in the normal white matter of the cerebellar cortex as well as the abnormal molecular layer above the dysplastic ganglion cells. These findings highlight the “inverted cerebellar cortical architecture” characteristic of L’hermitte-Duclos disease. Synaptophysin immunostaining was also found in the abnormal molecular layer (right). Synaptophysin

15. Question L’hermitte-Duclos disease is pathognomonic for which of the following genetic disorders? • Gorlin syndrome • Turcot syndrome • Cowden syndrome • Von Hippel Lindau syndrome

16. Answer L’hermitte-Duclos disease is pathognomonic for which of the following genetic disorders? • Gorlin syndrome • Turcot syndrome • Cowden syndrome • Von Hippel Lindau syndrome Correct Answer: Cowden syndrome

17. Question Which of the following cutaneous lesions are most likely to be found in patients with L’hermitte-duclos disease? • Shagreen Patch • Ash-leaf spot • Café-au lait macule • Trichilemmoma

18. Answer Which of the following cutaneous lesions are most likely to be found in patients with L’hermitte-duclos disease? • Shagreen Patch • Ash-leaf spot • Café-au lait spot • Trichilemmoma Correct Answer: Trichilemmoma

19. Question L’hermitte-Duclos disease patients are likely to harbor germ-line inactivating mutations in which of the following tumor suppressor genes? • INI-1 • PTEN • p16 • TP53 • retinoblastoma

20. Answer L’hermitte-Duclos disease patients harbor germ-line inactivating mutations in which of the following tumor suppressor genes? • INI-1 • PTEN • p16 • TP53 • retinoblastoma Correct Answer: Cowden syndrome is a PTEN hamartoma syndrome

21. Question The diagnosis of L’hermitte-Duclos disease indicates that our patient is at increased risk for which of the following neoplasms? • Breast carcinoma • Endometrial carcinoma • Thyroid carcinoma • All of the above

22. Answer The diagnosis of L’hermitte-Duclos disease indicates that this patient may be at increased risk for which of the following neoplasms? • Breast carcinoma • Endometrial carcinoma • Thyroid carcinoma • All of the above Correct Answer: All of the above.

23. Question Dysplastic cerebellar gangliocytoma is best characterized as a neoplasm or hamartoma?

24. Answer L’hermitte-duclos disease (dysplastic cerebellar gangliocytoma) is a pathognomonic tumor for Cowden syndrome, otherwise known as multiple hamartoma syndrome. L’hermitte-duclos itself is best characterized as a hamartoma (see Ki67 proliferative index of 0% in this case below) and is classified as a WHO Grade 1 tumor, although tumor recurrence has been reported. The clinical importance of recognizing this lesion is its association with Cowden syndrome, a PTEN hamartoma syndrome with increased risk for epithelial malignancies of the breast, endometrium and thyroid. Our patient has a history of multiple thyroid FNAs diagnosed as colloid nodules, but no history of malignancy. Ki67