Case #08 Discussion:

PATIENT IDENTIFICATION: A 38 year old female with known Von Hippel- Lindau Syndrome who comes for follow up CT after having been sent by her primary care physician for evaluation.

Von Hippel-Lindau Syndrome (VHL) is an autosomal dominant genetic defect in the VHL tumor suppressor gene on chromosome 3p25-26. The disease has equal incidence in both males and females and the age of onset is usually from the late teens to 40. It is diagnosed by the presence of hemangiomas of the CNS, visceral lesions, and family history.

The CNS component of the hemangioma (the other being retinal) is the Lindau tumor and occurs in 40% of cases. It most often presents in the cerebellum and brainstem with 15- 20% of tumors presenting in the spinal cord as in the case of the patient MW. Incidentally, cerebellar hemangioblastomas often cause an elevation in erythropoetin levels resulting in polycythemia. The primary manifestations are related to the site of the tumor. Cerebellar symptoms will present with positive Romberg sign and vertigo. Hemangiomas of the spinal cord are much less common and the symptoms they produce also are rare. A retinal hemangioma (Von Hippel tumor) may result in glaucoma, cataracts, worsening vision, and pain.

The disease can also have renal manifestations as well. The most common finding is cortical renal cysts which present in 75% of cases. Less common but still strongly associated (20-40%) is renal cell carcinoma. Renal adenoma and renal hemangiomas are less common renal findings in VHL. Polycythemia may also result secondary to renal manifestations.

Pancreatic findings include cysts (most common), hemangioblastomas, and cystadenomas. In more rare cases, one may find islet cell tumors. Other findings include pheochromocytomas (15%), liver hemangiomas, and cystic disease throughout the body. The diagnosis can be made radiologically in different ways depending upon the affected organ system of the body. Retinal hemangiomas are much more difficult to detect radiologically and are often picked up by the opthamologist with a thorough opthalmoscope exam. Flourescein angiography may aid in the diagnosis. Lindau tumors can be detected by MR and CT. CT findings are most often consistent with a large cyst without calcifications. Astrocytomas are in the differential for calcified cystic lesions. Occasionally, the lesion may be solid enhancing (10%). MR shows a cystic area as well often with areas of flow void within the nodule which is contrast enhanced. Angiography may also be used to show a "tumor blush."

Renal findings of renal cell carcinoma is best discovered by CT (sensitivity of 45%), then ultrasound, and finally angiography. The differential diagnosis includes an atypical cyst and a cancer within the cyst as well as renal cell carcinoma. CT is also the modality of choice for diagnosing pheochromocytomas, liver hemangiomas, and pancreatic abnormalities.

In this patient, a CT was performed and many of the findings described above are noted. CT gives the advantage of diagnosing multiple cysts that may present with this disease by giving a full body imaging.

The prognosis of patient's with VHL is not good given the plethora of carcinomas which they can develop. CNS manifestations are the leading cause of mortality and morbidity. Surgical resection of the tumor is often followed by immediate recurrence. The patient is at risk for developing cancer of the pancreas, liver angioma, or cancer of the kidney as well as pheochromocytoma. The hemangioblastoma may also manifest itself retinally causing significant visual discomfort and problems to the point of globe distortion.