Von Hippel-Lindau disease

Question 1

What are the cranial manifestations of VHL Disease?

Answer 1

1. CNS Hemangioblastoma (60% in cerebellum, 30% in spinal cord esp CT spine, brainstem)

(look for signs of cranioplasty on CT/MR brain)

2. Endolymphatic Sac Tumors (occurs in 16% of VHL patients, bilateral in 30%). Considered pathognomonic for VHL.
3. Retinal hemangioblastomas (most common presenting feature, 45-60% of patients; they will have vision loss)
4. Choroid plexus papillomas

Question 2

What are the renal / adrenal manifestations of VHL Disease?

Answer 2

1. Renal Cell Carcinoma (usually Clear Cell Type), and frequently bilateral. 70% lifetime risk, and presents at younger age.
2. Renal cysts, bilateral, multiple (can be simple or complex type)
3. Renal angiomyolipomas
4. Pheochromocytomas
5. Extra-adrenal pheochromocytomas/paragangliomas

Question 3

Imaging features of endolymphatic sac tumors?(associated with VHL Disease)

Answer 3

1. Always arise within the vestibular aqueduct, involving the endolymphatic sac or duct. Therefore, the lesion is centred in the posterior (retrolabyrinthine) petrous bone.
2. CT: erosion of petrous bone in an infiltrative or “moth-eaten” pattern;
   central calcific spiculation and posterior rim calcification; often intense enhancement.
3. MRI:
   T1: most show foci of hyperintensity;
   T1 C+ (Gd): heterogeneous enhancement, involving the non-cystic component of the tumour;
   T2: heterogeneous signal.
4. Ddx: Glomus jugulare tumor (center of the lesion at the jugular bulb rather than vestibular aquaduct); Meningioma; Bone mets

Question 4

What is the mutation in Von Hippel-Lindau disease?

Answer 4

VHL disease is characterised by the development of numerous benign and malignant tumours in different organs (at least 40 types) due to mutations in the VHL tumour suppressor gene on chromosome 3.

Patients usually are diagnosed with their first tumor in early adulthood 26 yo.

Autosomal dominant inheritance with high expression and penetrance.

Question 5

What are the other extra-renal manifestations of VHL disease?

Answer 5

1. Liver cysts
2. Pancreatic cysts
3. Pancreatic neuroendocrine tumors (pNET), usually non-func and frequently multiple.
4. Pancreatic serous cystadenoma

Question 6

Imaging features of CNS hemangioma (associated with VHL Disease)

Question 6

Imaging features of CNS hemangioma (associated with VHL Disease)

Answer 6

1. Cystic lesion with avidly enhancing mural nodule. IUf solid, look for flow voids within.

SHOULD NOT have an irregularly thickened cyst wall (which could be mets or glioblastoma)

2. Can be cx by obstructive hydrocephalus.
3. Can have multiple other intra-axial lesions.
4. Ask to screen the spine for intramedullary lesions (cord expansion, enhancing mass, dorsal draining vein/flow void, possibly accompanying a syrinx) in young patients with multiple brain lesions (if VHL not alr known, should screen for other manifestations and genetic counselling)
5. Ddx for cystic posterior fossa mass:
   1) Pilocytic astrocytoma:
   * The imaging appearance is similar, with a
   cystic mass and enhancing mural nodule, but
   unlike with haemangioblastomas, the nodule
   does not abut the pial surface, nor are there
   large vessels related to the enhancing nodule.
   2) Metastases:
   * These are the most common intra-axial posterior
   fossa mass in adults.
   * Usually solid rather than cystic and multiple.
   3) Arteriovenous malformation or cavernoma.
   * These can occasionally appear similar, but
   haemorrhage is rare in haemangioblastomas.
   * Multiple arteriovenous malformations can
   occur as part of a syndrome such as haemorrhagic
   hereditary telangiectasia.