reporting articles by J.E. Wanebo, R.R. Lonser, JR. J. Weil, H.L. DeVroom, G.M. Glenn, and E.H. Oldfield from the Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, U.S. National Institutes of Health, Bethesda, Maryland

For the past several years physicians and researchers at the U.S. National Institutes of Health (NIH), led by Dr. Edward H. Oldfield, have been reviewing their very large set of case histories of hemangioblastomas of VHL. The goal of their study is to better understand the natural history and growth pattern of the hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel-Lindau (VHL) disease. They would like to be able to learn what characteristics of hemangioblastomas may indicate that they will soon develop symptoms and require treatment.

As better imaging techniques become available, we are finding tumors at much earlier stages. But the existence of a tumor does not necessarily mean that it needs treatment. We know that some tumors may stay at the same small size for 20 or 30 years, while others grow quickly. Is there a way to predict the future growth pattern of a particular tumor? Stereotactic radiosurgery, for example, gives us a tool that might be used to stunt the growth of a tumor. But once we have treated that small tumor, we really do not know whether it failed to grow because of the treatment, or whether it is one of the tumors that was not ready to grow anyway. How do we know which of the several tumors we should treat? We do not want to treat every tumor, because radiation adds up in the body. We need to use each tool wisely and sparingly and to the best advantage for the patient.

The authors review clinical histories and a series of MRI images for 160 patient over as many as 15 years. For each image they measured the volume of each tumor and any associated cysts. A total of 650 hemangioblastomas were identified in these 160 patients: in the cerebellum (250 tumors), in the brainstem (64 tumors, all of which were located in the posterior medulla oblongata), in the spinal cord (331 tumors, 96% of which were located in the posterior half of the spinal cord), and in the supratentorial brain (10 tumors). (See Figure 1.) They mapped the growth of each tumor over the course of the series of MRI’s.

Figure 1:
Of 650 total hB there were
250 in the cerebellum
64 in the brainstem
331 in the spinal cord
10 supratentorial

As the patients progressed from no symptoms to increasingly severe symptoms and required surgery, the hemangioblastomas were seen to increase in size. In all cases, the symptoms were related to a mass effect, the effect of the pressure created by the volume of the tumor and/or the cyst. Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions. (See Figure 2.)

Ninety-five percent of symptom-producing spinal hemangioblastomas had cysts, which are elongated and take the shape of a hotdog in the confined space of the spinal column and are called syrinx or syringomyelia. Symptoms were unpredictable. Among the 88 patients who had a series of MRIs over a period of 6 months or longer (an average of about 3 years), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. None of the tumors or cysts got smaller.

Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them.

Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) had tumors with at least two such cycles. Of 160 patients with hemangioblastomas, 34 patients followed for an average of 4.25 years were found to have 115 new hemangioblastomas, and 15 patients had new cysts.

In conclusion, cysts were commonly associated with hemangioblastomas of the CNS. The pace of enlargement was faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of symptoms were caused by mass-effect from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients, and for evaluating the timing and results of treatment.

Implications for managing hemangioblastomas

There are no clear guidelines for optimal management of brainstem tumors. In an attempt to clarify some of the uncertainty about the operative treatment of these lesions and its outcome, the authors reviewed all cases of VHL in which resection of brainstem hemangioblastomas was performed at the NIH during a 10-year period.

Twelve patients with VHL, six male and six female, ranging in age from 15 to 46 years old, underwent a total of 13 operations to remove 17 brainstem hemangioblastomas. A series of examinations, hospital charts, MRI’s, and operative records were reviewed. Clinical grades were assigned to each patient before and after surgery.

The best predictor of long-term outcome was the level of neurological function before the surgery. Patients who underwent CNS surgeries for hemangioblastomas were more likely to improve or to remain neurologically stable. Tumor or cyst size, the presence of a cyst, or the location of the tumor did not affect the outcome. No patient was neurologically worse after brainstem surgery. At long-term follow-up review only one patient had declined neurologically and this was due to the cumulative neurological effects caused by eight additional hemangioblastomas of the spinal cord and their surgical treatment.

The study concludes that hemangioblastomas can be removed safely. They generally should be resected when they become symptomatic, or when the tumor has reached a size such that further growth will increase the risks associated with surgery, or the presence of an enlarging cyst. MRI imaging is usually sufficient for preoperative evaluation, and presurgical embolization is not necessary. The goal of surgery is complete resection of the lesion before the patient experiences a disabling neurological deficit.

Implications for managing spinal cord hemangioblastomas

The authors set out to determine factors that predict which patients with spinal cord hemangioblastomas need surgery or what outcomes of this procedure should be expected. They reviewed a series of patients with VHL who underwent resection of spinal hemangioblastomas at one institution (NIH). Their goal is to identify features that might guide surgical management of these patients.

Forty-four patients with VHL (26 men and 18 women ranging in age from 20 to 58 years old) underwent 55 operations with resection of 86 spinal cord hemanbioblastomas. They were followed an average of four years following these surgeries. Patient examination, review of hospital charts, operative findings, and MRI imaging studies were used to analyze surgical management and its outcome. To evaluate the clinical course, clinical grades were assigned to patients before and after surgery. The best predictors of postoperative outcome were preoperative neurological status, tumor size, and tumor location. Patients with no or minimal preoperative neurological dysfunction, with lesions smaller than 500 mm3 (the size of a kernel of corn), and with dorsal lesions (on the back side of the spine) were more likely to have no or minimal neurological impairment. The syrinx (cyst) deflated when the tumor was removed, and was not influenced by whether the syrinx cavity was entered.

The study concludes that spinal cord hemangioblastomas can be safely removed in the majority of patients with VHL. Generally in these patients hemangioblastomas of the spinal cord should be removed when they produce symptoms or signs.

Anterior and Posterior Surgical Approaches

Spinal hemangioblastomas arise mostly in the posterior aspect (the back side) of the spinal cord and are often associated with an intraspinal cyst or syrinx. Rarely, the tumor develops in the anterior or ventral (belly) side of the spinal cord. Ventral spinal hemangioblastomas are a surgical challenge because of difficult access and because vessels feeding the tumor originate from the anterior spinal artery. The goal of the study was to clarify whether an anterior or posterior surgical approach is better for management of hemangioblastomas of the ventral spinal cord.

The authors reviewed cases of eight patients (two women and six men, ranging in age from 19 to 49) who underwent resection of ventral spinal hemangioblastomas (nine tumors: five cervical and four thoracic). Two surgical approaches were used to resect these tumors. A posterior approach was used for five patients; an anterior approach was selected to treat the remaining three patients. Immediately after surgery the ability to walk remained unchanged in patients in whom an anterior approach had been performed, but deteriorated significantly in patients in whom a posterior approach had been used, because of motor weakness (four of five patients) and/or loss of sensation in the muscles. While the patients in the posterior group improved significantly, there was still a significant difference between the two groups even six months after surgery. In all cases MR images showed that the tumors had been removed completely and five of the six cysts were gone.

The outcomes of these eight patients indicate that both immediate and long-term results are better when an anterior approach is selected for resection of hemangioblastomas of the anterior side of the spinal cord.

1. JE Wanebo, RR Lonser, GM Glenn, EH Oldfield, "The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease." J. Neurosurg, 2003 Jan; 98(1):82-94.

2. RJ Weil, RR Lonser, HL DeVroom, JE Wanebo, EH Oldfield, "Surgical management of brainstem hemanbioblastomas in patients with von Hippel-Lindau disease." J. Neurosurg 2003 Jan; 98(1):95-105.

3. RR Lonser, RJ Weil, JE Wanebo, HL DeVroom, EH Oldfield, "Surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease." J. Neurosurg 2003 Jan; 98(1): 106-16

4. R.M. Pluta, B. Iuliano, H.L. DeVroom, T. Nguyen, E.H. Oldfield, "Comparison of anterior and posterior surgical approaches in the treatment of ventral spinal hemanbioblastomas in patients with von Hippel-Lindau disease." J. Neurosurg 2003 Jan; 98(1):117-24.

As printed in the VHL Family Forum 11:1, March 2003. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org.