The Freiburg University Clinics are one of the centers in Europe with experience and focus on clinical care for people with VHL. I have seen approximately 100 patients, descendents of more than thirty families.

Following publication of my first article in an international journal,¹ I had a telephone call from a woman in Italy, Luisa G., who had read that article, and was looking for help for her brother, Roberto. They came to Freiburg to meet with me.

Roberto is now 39 years old. He was 22 when he had his first symptoms of VHL. Roberto had a history of several weeks with headaches and ataxia [difficulty in walking straight] before his first operation for cerebellar hemangioblastoma in 1976. In 1983 he experienced the same symptoms, and a similar tumor on the other side. Again the same symptoms in 1989, caused this time by a huge cyst. During surgery to remove the cyst, however, no tumor was found. Roberto and Luisa brought an MRI done after the surgery. Their question was whether the cyst shown on this MRI was left over from his first surgery, or was caused by another tumor not yet removed.

Although they came with one clear question, I knew that there were other questions to be answered as well. As documented in the series of articles I published in 1992, in the Journals of Neurosurgery, Neurology, and Psychiatry, I knew that we should look beyond the brain for possible VHL issues.

I began by asking about the family: parents and three siblings alive and healthy. I recommended a full medical evaluation for Roberto, beginning with ophthalmoscopy, which disclosed a small retinal angioma on the left eye, which was treated with laser photocoagulation. This confirmed the diagnosis of von Hippel-Lindau disease.

Roberto had had a motorbike accident in 1969 which traumatized his testicles. He was told that the left testicle had atrophied [degenerated] as a result of this accident, and that he had a cyst on the right. In 1981 he was found to have a zero sperm count. He and his wife adopted a baby girl in 1984.

On his second day in Freiburg an abdominal CT disclosed a 6 cm right renal mass and several cystic masses in the left kidney up to 2 cm. In the pancreas there were a few small cysts. Physical examination and later ultrasound of the scrotum revealed cysts in both epididymes, but no atrophic testicles. His infertility was caused by his epididymal cysts.²

Consultation with the neurosurgeon revealed three solid lesions in the brain and two cysts. Luisa asked what to do. She was especially interested in gamma knife treatment, done by Dr. Linquist in Stockholm or Dr. Steiner who had introduced that method and had moved to Charlottesville, North Carolina, USA. This was the first time we had heard about this method, and we were surprised to learn of it from a non-physician! The family had previously consulted with a colleague of theirs in Vicenza, Italy, for electron accelerator radiation, who at that time had no experience working with brain tumors. We recommended waiting, since there were no neurological complaints.

Confronted with this new situation, Roberto and Luisa decided to go home for six weeks, before returning for additional angiography and kidney surgery. The angiography confirmed one right kidney tumor. In the left kidney there were irregular vascular structures, but no tumors.

Surgery was planned to remove the kidney tumors and spare the kidneys. However during surgery additional lesions were found on the upper right kidney, resulting in total nephrectomy [removal of the right kidney]. A total of four small and one large tumors was found. We were disappointed that we had not seen these tumors on the CT before.

In June 1990 the family invited me to accompany them to Stockholm to consult with Dr. Linquist and his gamma knife team. I was very impressed with the accuracy of the planning of the procedure, and how exactly every one of the 201 cobalt60 radiators was focused in the radiation helmet. We discussed the risk of bleeding and swelling of nearby tissues, which seemed to be low. At that time only very few hemangioblastomas had been treated.³ He could not at that time give any assurance of quick positive results. The cyst was already quite large. They set a date of mid-July for treatment, but during the next month the headaches and ataxia increased, forcing another solution to the problem,⁴

Roberto and Luisa contacted Dr. Claude Lapras, a neurosurgeon in Lyon, who removed three hemangioblastomas and created a drainage path for the cyst.

Roberto recovered completely, is working, and undergoes regular abdominal CT and MRI of the head, which have shown no new lesions and no growth of the known existing lesions.

In 1990 all Roberto’s parents and siblings (ages 65, 62, 40, 33, and 30) were screened by ophthalmoscopy, abdominal ultrasound, 24-hour urine assay, and physical neurological examination. The parents and the father’s blind sister (age 66) were also screened using CT of the abdomen and brain. All we found was one renal cyst in the father, which is not necessarily related to VHL. All of them remain healthy in 1994.

Until Roberto’s diagnosis in 1990, none of the Italian doctors he had consulted knew enough about VHL to do a complete screening and make a coordinated treatment plan. All his treatments were planned only to solve a particular problem at a particular time, without taking into account the more general situation and possible future recurrences. The family feels that there is still little knowledge about VHL in Italy, as most doctors still consider it quite rare and not worth an investment in learning. As readers of the VHL Family Forum know, knowledge about VHL is not widespread in any country. I could certainly relate similar examples in Germany.

Doctors learn from every patient, even when they already know a lot about a disease. I certainly learned from my experiences with this family. I was surprised how well informed they were. They taught me about gamma knife and linear accelerator treatments.

I was disappointed that we found more tumors in Roberto’s kidneys than we had seen on the CT, resulting in the loss of one kidney. This convinced me not only that we should use intravenous contrast medium, but that the timing of the injection and the imaging should be calculated to give optimal detail on the pictures of the normal and abnormal kidney structures. Furthermore, we are still wrestling with the question of how long we can leave tiny renal tumors where they are without risk to the patient.

We also learned that infertility can be related to VHL cysts in the epididymus. Roberto had undergone repeated and costly fertility tests without receiving clear information about the cysts, nor the VHL diagnosis.

Roberto may also be a "new mutation," the first in his family to have VHL. In Freiburg we have a patient in a similar family, and a few more cases of apparently isolated VHL. While their children are at 50% risk of having VHL, we will have to wait for DNA tests to confirm whether the parents are in fact free of VHL, or carry the gene quietly, with no clear expression of VHL. VHL does not "skip a generation," but it may appear that way, being very mild in a parent and more serious in a child.

Since his surgery in 1990, Roberto has remained free of recurrence for three years. From experiences with this and other patients I wonder if tumor growth declines in older people with VHL. I don’t have a convincing answer yet, but it is an interesting question. As people with VHL are living longer and longer, we will learn more about its long-term course.

1. Journal of Neurosurgery, 1989.

2. Epididymal cysts do not usually affect fertility, but they can block the vas deferens. Editor's Update, March 2000: for more information about cysts in the epididymis, see Caring for your Reproductive Health.

3. See VHL Family Forum 1:3 (1993), 10-12 [and a more recent article, 1998] for an update on use of stereotactic radiosurgery on hemangioblastomas.

4. Editor's update, March 2000: We have learned a great deal since 1994 about the use of stereotactic radiosurgery, or gamma knife surgery, with hemangioblastomas. It is a useful tool, but not for every tumor. Please be sure to read Caution Urged on Stereotactic Radiosurgery and Questions to Ask Your Doctor.

5. Editor's update, March 2000: There are now several centers of expertise in Italy, especially in Padua. As in all countries, though, most doctors are uninformed about VHL, and second opinions must be sought from centers of expertise.

What We Learned from our Experience

by Luisa G., Italy

As VHL is a disease with various recurrences and at this time can only be treated surgically, every surgery has to be planned very carefully and possibly performed by the most qualitifed surgeon you can find, especially where the brain is concerned.

We learned not to trust the doctors 100%, but to always get a second or third opinion until we are satisfied with the plan. Each of us is our own best advocate.

Families should never be afraid of the truth. It is only through knowledge that we can handle each situation in the best possible way.

As published in the VHL Family Forum 2:1, March 1994. For permission to reprint, please contact the VHL Family Alliance at editor@vhl.org. Further information is available from the VHL Family Alliance at info@vhl.org.

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