Diagnostic Radiology
The Radiographic Manifestations of von Hippel-Lindau Disease 1 William L. Fill, M.D., James M. Lamiell, M.D., and Norman O. Polk, M.D.
The radiographic findings and method of investigation are presented in the retrospective and prospective study of 221 descendents of an individual affected with von Hippel-Lindau disease. Among 42 affected individuals, most of the reported manifestations were found, such as cerebellar hemangioblastoma, retinal angioma, and renal cell carcinoma. A new manifestation, pancreatic carcinoma, was also seen. Although pheochromocytoma is common in some reported families, no cases were found in this group. An organized multidisciplinary approach is necessary to effectively identify and treat individuals affected with this disease. INDEX TERMS: Cerebellum, neoplasms. Familial conditions. Kidney neoplasms • Pancreas, neoplasms • Retina, neoplasms • (Skull and contents, Hippel-Lindau Syndrome, 1[0] .1834)
Radiology 133:289-295, November 1979
ON HIPPEL-LINDAU disease is an autosomal dominant disorder characterized by retinal angiomas; cerebellar, medullary, and spinal hemangioblastomas; renal carcinoma; and cysts and angiomatous tumors of several visceral organs (1). Pheochromocytoma is also found in some affected families (2). In a study of 221 related individuals, we identified 42 who were affected with the disease and who manifested various of the reported findings. In this article we describe the radiographic manifestations and outline a method of presymptomatic screening when a family with von Hippel-Lindau disease is identified. Detailed reports of the genetic, ophthalmoscopic, and pathological considerations, as well as case reports of affected individuals, are presented elsewhere (3,4).
computed tomography (CT), and myelography were performed. When manifestations of the disease were found, renal angiography was performed in patients over 18 years of age. Vertebral and spinal angiography were performed only when physical signs or symptoms were present, since asymptomatic lesions are not usually treated prophylactically, therefore not justifying the procedural risk (5). For screening of the cerebellum, CT scanning of the posterior fossa was performed in some cases, For retrospective investigation, family members were questioned, medical records examined, and radiographs reviewed. In all, radiographs were available in 11 of 15 retrospectively diagnosed individuals. Twenty-seven cases were prospectively diagnosed.
PATIENTS AND METHOD
RESULTS
A patient presenting with multiple bilateral renal cysts gave a family history of ocular, cerebellar, and renal tumors; this prompted an extensive investigation of the patient's family. The R-family consisted of 221 individuals in six generations, all descended from a man who immigrated to Hawaii about 1901. The geographic confines of the islands facilitated the study of family members; to date 155 (79 %) of the known living descendents have been personally examined by the authors. All family members gave a history and each had physical examination, indirect ophthalmoscopy, various laboratory examinations, abdominal ultrasound (with specific attention to the kidneys and pancreas) if over 12 years of age, and excretory urography (with tomography) if over 18 years of age. The age limits were established by a review of previous reports which show visceral manifestations to be rare before the age of 18. If deemed appropriate, other laboratory studies and radiographic examinations including skull series, brain scanning, head and body
Neurological Findings
V
The most common neurological feature of von HippelLindau disease was cerebellar hemangioblastoma, identified in 11 individuals. Plain skull radiographs were normal except in one case which showed signs of increased intracranial pressure. Angiographically, a hemangioblastoma presented either as a dense nodule or a tangle of vessels (Fig. 1a and b), although cysts without such nodules have also been reported (5). We found good correlation between the angiographic, CT, and surgical appearance of lesions of the posterior fossa (Figs. 1c and d, and 2). Although brain scanning was not generally useful for screening, it did correlate with other modalities in several cases. A hemangioblastoma of the medulla, a much less frequent finding than cerebellar lesions, was seen in one patient at autopsy; associated syringomyelia was noted. Spinal hemangioblastomas were found in five patients. As with the cerebellar tumors, symptoms tended to occur
1 From the Departments ofRadiology (W.L.F., N.O.P.) and Medicine (J.M.L.), Tripier Army Medical Center, HI. Received April 10, 1979, and accepted August 10. jr
289
290
WILLIAM
L.
FILL AND OTHERS
November 1979
1a,b
1c,d
Fig. 1a and b. Anteroposterior (a) and lateral (b) views from a vertebral angiogram demonstrate two cerebellar hemangioblastomas. c. A nonenhanced CT scan shows cystic areas of the tumors. d. A contrast-enhanced CT scan shows vascular areas of the tumors.
secondary to a cystic component. Myelography demonstrated widening of the cord and showed serpiginous vessels supplying the tumor (Fig. 3a). In these cases spinal angiography showed supply from the vertebral artery or other vessels to the spinal cord (Figs. 3 and 4).
Retinal Findings
Fig. 2. An enhanced CT scan demonstrates two cerebellar hemangioblastomas, each of which although largely cystic, contains a small vascular mural nodule.
Retinal angiomas represented the largest single manifestation of von Hippel-Lindau disease, present in 19 patients (45 %). Although demonstration of such tumors has been reported using internal carotid angiography and double-order subtraction technique (6), we were unable to demonstrate a known 3-mm tumor using this method and thus used indirect ophthalmoscopy and fluorescein angiography (Fig. 5) which are usually sufficient for diagnosing
VON HIPPEL-lINDAU DISEASE
Vol. 133
3a-c
Fig.3a. band c.
A cervical myelogram demonstrates widening of the spinal canal from an intramedullary hemangioblastoma. A subtracted vertebral angiogram shows vascularity of the tumor (arrows) in the area of C-6.
4a,b
Fig. 4. Anteroposterior (a) and lateral (b) views from a right vertebral artery angiogram visualize a small vascular nodule (arrow) at C-1. The tumor was not seen with injection of the left vertebral artery.
and managing such cases. Careful ophthalmoscopic examination and follow-up are mandatory to prevent retinal detachment and subsequent loss of vision. Photocoagulation is usually successful in obliterating tumors if they are discovered at an early stage. Renal Findings
Renal cell carcinoma represents a serious, life-threatening manifestation of von Hippel-Lindau disease, and has a reported incidence of 12-83 % in affected patients. In this series, we identified 16 cases (38 %). Of these, the
--
Fig. 5. A retinal angiogram after the intravenous injection of fluorescein demonstrates the typical appearance of retinal hemangioma.
291
Diagnostic Radiology
292
WILLIAM
L.
FILL AND OTHERS
November 1979
6a,b
6c,d
..
• =
=
=
Fig. 6a. Longitudinal posterior ultrasonogram (LK left kidney, SP spleen, M mass). b. A nephrotomogram shows a collection of contrast medium in the left upper calyx . c. A left renal angiogram demonstrates the large central tumor seen in a but also shows several other vascular tumors (arrows) which proved to be multicentric renal cell carcinoma. d. Pathological specimen.
tumors were multicentric in 87 % and bilateral in 75 %. Six of these cases were identified prospectively. Large tumors, generally greater than 2 cm in diameter, could be identified
by renal ultrasound (Fig. 6a), while peripheral tumors or those which displace the collecting system were seen on bolus tomography urograms (Fig. 6b). However, since
VON HIPPEL-lINDAU DISEASE
Vol. 133
neither of these modalities detects very small tumors, renal angiography was performed in individuals older than 18 years. Angiographically, typical findings included well circumscribed, multicentric lesions with neovascularity (Fig. 6c and d). In several cases in which ultrasound and nephrotomography were negative, renal angiography subsequently demonstrated multiple small tumors. CT of the abdomen was performed in several patients with known renal cell carcinoma, and it correlated well with angiographic and pathological findings. Renal cysts, encountered in 16 cases, ranged from solitary to those simulating polycystic disease (Fig. 7). Cysts were also seen in kidneys affected by renal cell carcinoma, and indeed small tumor foci were seen arising from the wall of the cysts (Fig. 8). Renal adenomas were reported in three individuals; however these were difficult to distinguish from renal cell carcinoma both angiographically and pathologically. Often the arbitrary size of 2 cm is used to differentiate the two, but a continuous spectrum probably exists (8). Other Findings Four patients were found to have carcinoma of the pancreas; in a fifth patient the diagnosis was indicated by an abnormal CT scan but is as yet unproved. The pathology and complications seen were similar to those occurring with pancreatic carcinoma not associated with von Hippel-Lindau disease. A benign hemangioblastoma of the pancreas was found in one patient (Fig. 9). In another, adenocarcinoma of the ampulla of Vater was seen on upper gastrointestinal series (Fig. 10). Pancreatic cysts, a common manifestation of von Hippel-Lindau disease, were identified in eight patients. These cysts may be so
293
Diagnostic Radiology
Fig. 7. Abdominal ultrasonogram shows a very large right kidney (arrows) with multiple cysts.
diffuse as to virtually replace the entire pancreas (Fig. 11); when discovered during routine screening they may be the first indication of disease in an individual patient. Pheochromocytoma reportedly may be present in up to 17 % of affected patients (2) although its incidence varies; no cases were found in our patients. Diagnosis of pheochromocytoma is made through screening of the urine for catecholamines and by visualization during abdominal angiography. Cysts may occur in virtually any of the visceral organs, including the liver, omentum, mesentery, spleen, and adrenal. Epididymal cysts are rather common and were found by physical examination in 6 of 22 affected males in this series. The cysts, not usually significant in themselves, are important in identifying individuals with von Hippel-Lindau disease, thereby prompting more invasive
8a,b
Fig. 8a. A longitudinal posterior Ultrasonogram shows two cystic masses in the lower left kidney, although some internal echoes are seen. b. Selective injection into the lower left renal artery. Two cysts are demonstrated, one with a small focus of renal cell carcinoma (arrow).
WILLIAM L. FILL AND OTHERS
294
November 1979
Fig. 9. Selective injection of the splenic artery in a patient who had undergone splenectomy and partial pancreatectomy 16 years previously. Biopsy revealed recurrent hemangioblastoma of the pancreas.
Fig. 10. Mass effect is seen on the second portion of the duodenum (arrowheads) from adenocarcinoma of the ampulla of Vater.
Fig. 11. Abdominal CT scan demonstrates multiple pancreatic cysts and bilateral renal tumors.
diagnostic procedures. Other manifestations of the disease include hemangiomas of the liver (three patients) paragangliomas (none in this series), and polycythemia (none in this series). DISCUSSION
Although von Hippel-Lindau disease appears to have variable penetrance, manifestations often occur with increasing age, and thus the penetrance may approach 100 %. Affected individuals in this series presented at ages between 11 and 62 years. Most family members are now under 20 years of age, and therefore more affected individuals are expected as time passes. Two were identified as being affected because of eye tumors in their children, even though they themselves presented no manifestations at ages 34 and 37, respectively. Follow-up examination, which is similar to the screening procedure, in family members not diagnosed as affected
should 'probably be performed yearly, especialy for those at 50 % risk, i.e., children with one affected parent. Abdominal CT is a recommended method of yearly follow-up which is necessary if renal tumors are to be detected when still amenable to local resection. In cases in this series where nephrectomy was performed, microscopic foci of renal cell carcinoma were found within cysts and within the renal parenchyma, demonstrating the necessity of close follow-up when initial examination is normal or after a partial resection. To further determine whether CT can replace renal angiography in the initial evaluation, as a recent study of four patients indicates (9), we are presently attempting to obtain CT scans on all affected individuals in this kindred. ACKNOWLEDGMENT: The various examinations were performed at different institutions. We wish to thank the following radiologists for their assistance and for case material: Dr. Sankaran Babu, Letterman Army Medical Center, San Francisco, CA; Dr. Raymond Brust, St. Francis Hospital, Honolulu, HI (Fig. 11); Dr. Virgil Jobe, Straub Clinic and Hospital, Honolulu, HI (Figs. 1a and b, and 3); Dr. Michael Meagher, Queens Hospital, Honolulu, HI (Figs. 1c and d, and 10); Dr. Thomas H. Newton, University of California, San Francisco, CA.
REFERENCES 1. Melmon KL, Rosen SW: Lindau's disease. Review of the literature and study of a large kindred. Am J Med 36:595-617, Apr 1964 2. Horton WA, Wong V, Eldridge R: Von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med 136:769-777, Jul 1976
Vol. 133
VON HIPPEL-LINDAU DISEASE
3. Lamiell JM: Von Hippel-Lindau disease in a large kindred. In preparation. 4. Salazar F: Retinal angiomas in von Hippel-Lindau disease. Accepted for publication by the American Journal of Ophthalmology. 5. Wolpert SM: The neuroradiologyof hemangioblastomas of the cerebellum. Am J RoentgenoI110:56-66, Sep 1970 6. HanafeeW, DaytonGOJr, Weidner W: Orbital angiography and venography aided by subtractiontechnique. Trans Am Acad Ophthalmol Otolaryngol 70: 1027-1033, Nov-Dec 1966 7. Lee KR, Wulfsberg E, Kepes JJ: Some important radiological aspects of the kidney in Hippel-Lindau syndrome: the value of pro-
295
Diagnostic Radiology
spective study in an affected family. Radiology 122:649-653, Mar 1977 8. Bennington JL: Proceedings: Cancer of the kidney-etiology, epidemiology, and pathology. Cancer 32:1017-1029, Nov 1973 9. Levine E, Lee KR, Weigel JW, et al: Computed tomography in the diagnosisof renal carcinoma complicating Hippel-Lindau syndrome. Radiology 130:703-706, Mar 1979
Department of Radiology Brooke Army Medical Center Fort Sam Houston, TX 78234
The Radiographic Manifestations of von Hippel-Lindau Disease 1 William L. Fill, M.D., James M. Lamiell, M.D., and Norman O. Polk, M.D.
The radiographic findings and method of investigation are presented in the retrospective and prospective study of 221 descendents of an individual affected with von Hippel-Lindau disease. Among 42 affected individuals, most of the reported manifestations were found, such as cerebellar hemangioblastoma, retinal angioma, and renal cell carcinoma. A new manifestation, pancreatic carcinoma, was also seen. Although pheochromocytoma is common in some reported families, no cases were found in this group. An organized multidisciplinary approach is necessary to effectively identify and treat individuals affected with this disease. INDEX TERMS: Cerebellum, neoplasms. Familial conditions. Kidney neoplasms • Pancreas, neoplasms • Retina, neoplasms • (Skull and contents, Hippel-Lindau Syndrome, 1[0] .1834)
Radiology 133:289-295, November 1979
ON HIPPEL-LINDAU disease is an autosomal dominant disorder characterized by retinal angiomas; cerebellar, medullary, and spinal hemangioblastomas; renal carcinoma; and cysts and angiomatous tumors of several visceral organs (1). Pheochromocytoma is also found in some affected families (2). In a study of 221 related individuals, we identified 42 who were affected with the disease and who manifested various of the reported findings. In this article we describe the radiographic manifestations and outline a method of presymptomatic screening when a family with von Hippel-Lindau disease is identified. Detailed reports of the genetic, ophthalmoscopic, and pathological considerations, as well as case reports of affected individuals, are presented elsewhere (3,4).
computed tomography (CT), and myelography were performed. When manifestations of the disease were found, renal angiography was performed in patients over 18 years of age. Vertebral and spinal angiography were performed only when physical signs or symptoms were present, since asymptomatic lesions are not usually treated prophylactically, therefore not justifying the procedural risk (5). For screening of the cerebellum, CT scanning of the posterior fossa was performed in some cases, For retrospective investigation, family members were questioned, medical records examined, and radiographs reviewed. In all, radiographs were available in 11 of 15 retrospectively diagnosed individuals. Twenty-seven cases were prospectively diagnosed.
PATIENTS AND METHOD
RESULTS
A patient presenting with multiple bilateral renal cysts gave a family history of ocular, cerebellar, and renal tumors; this prompted an extensive investigation of the patient's family. The R-family consisted of 221 individuals in six generations, all descended from a man who immigrated to Hawaii about 1901. The geographic confines of the islands facilitated the study of family members; to date 155 (79 %) of the known living descendents have been personally examined by the authors. All family members gave a history and each had physical examination, indirect ophthalmoscopy, various laboratory examinations, abdominal ultrasound (with specific attention to the kidneys and pancreas) if over 12 years of age, and excretory urography (with tomography) if over 18 years of age. The age limits were established by a review of previous reports which show visceral manifestations to be rare before the age of 18. If deemed appropriate, other laboratory studies and radiographic examinations including skull series, brain scanning, head and body
Neurological Findings
V
The most common neurological feature of von HippelLindau disease was cerebellar hemangioblastoma, identified in 11 individuals. Plain skull radiographs were normal except in one case which showed signs of increased intracranial pressure. Angiographically, a hemangioblastoma presented either as a dense nodule or a tangle of vessels (Fig. 1a and b), although cysts without such nodules have also been reported (5). We found good correlation between the angiographic, CT, and surgical appearance of lesions of the posterior fossa (Figs. 1c and d, and 2). Although brain scanning was not generally useful for screening, it did correlate with other modalities in several cases. A hemangioblastoma of the medulla, a much less frequent finding than cerebellar lesions, was seen in one patient at autopsy; associated syringomyelia was noted. Spinal hemangioblastomas were found in five patients. As with the cerebellar tumors, symptoms tended to occur
1 From the Departments ofRadiology (W.L.F., N.O.P.) and Medicine (J.M.L.), Tripier Army Medical Center, HI. Received April 10, 1979, and accepted August 10. jr
289
290
WILLIAM
L.
FILL AND OTHERS
November 1979
1a,b
1c,d
Fig. 1a and b. Anteroposterior (a) and lateral (b) views from a vertebral angiogram demonstrate two cerebellar hemangioblastomas. c. A nonenhanced CT scan shows cystic areas of the tumors. d. A contrast-enhanced CT scan shows vascular areas of the tumors.
secondary to a cystic component. Myelography demonstrated widening of the cord and showed serpiginous vessels supplying the tumor (Fig. 3a). In these cases spinal angiography showed supply from the vertebral artery or other vessels to the spinal cord (Figs. 3 and 4).
Retinal Findings
Fig. 2. An enhanced CT scan demonstrates two cerebellar hemangioblastomas, each of which although largely cystic, contains a small vascular mural nodule.
Retinal angiomas represented the largest single manifestation of von Hippel-Lindau disease, present in 19 patients (45 %). Although demonstration of such tumors has been reported using internal carotid angiography and double-order subtraction technique (6), we were unable to demonstrate a known 3-mm tumor using this method and thus used indirect ophthalmoscopy and fluorescein angiography (Fig. 5) which are usually sufficient for diagnosing
VON HIPPEL-lINDAU DISEASE
Vol. 133
3a-c
Fig.3a. band c.
A cervical myelogram demonstrates widening of the spinal canal from an intramedullary hemangioblastoma. A subtracted vertebral angiogram shows vascularity of the tumor (arrows) in the area of C-6.
4a,b
Fig. 4. Anteroposterior (a) and lateral (b) views from a right vertebral artery angiogram visualize a small vascular nodule (arrow) at C-1. The tumor was not seen with injection of the left vertebral artery.
and managing such cases. Careful ophthalmoscopic examination and follow-up are mandatory to prevent retinal detachment and subsequent loss of vision. Photocoagulation is usually successful in obliterating tumors if they are discovered at an early stage. Renal Findings
Renal cell carcinoma represents a serious, life-threatening manifestation of von Hippel-Lindau disease, and has a reported incidence of 12-83 % in affected patients. In this series, we identified 16 cases (38 %). Of these, the
--
Fig. 5. A retinal angiogram after the intravenous injection of fluorescein demonstrates the typical appearance of retinal hemangioma.
291
Diagnostic Radiology
292
WILLIAM
L.
FILL AND OTHERS
November 1979
6a,b
6c,d
..
• =
=
=
Fig. 6a. Longitudinal posterior ultrasonogram (LK left kidney, SP spleen, M mass). b. A nephrotomogram shows a collection of contrast medium in the left upper calyx . c. A left renal angiogram demonstrates the large central tumor seen in a but also shows several other vascular tumors (arrows) which proved to be multicentric renal cell carcinoma. d. Pathological specimen.
tumors were multicentric in 87 % and bilateral in 75 %. Six of these cases were identified prospectively. Large tumors, generally greater than 2 cm in diameter, could be identified
by renal ultrasound (Fig. 6a), while peripheral tumors or those which displace the collecting system were seen on bolus tomography urograms (Fig. 6b). However, since
VON HIPPEL-lINDAU DISEASE
Vol. 133
neither of these modalities detects very small tumors, renal angiography was performed in individuals older than 18 years. Angiographically, typical findings included well circumscribed, multicentric lesions with neovascularity (Fig. 6c and d). In several cases in which ultrasound and nephrotomography were negative, renal angiography subsequently demonstrated multiple small tumors. CT of the abdomen was performed in several patients with known renal cell carcinoma, and it correlated well with angiographic and pathological findings. Renal cysts, encountered in 16 cases, ranged from solitary to those simulating polycystic disease (Fig. 7). Cysts were also seen in kidneys affected by renal cell carcinoma, and indeed small tumor foci were seen arising from the wall of the cysts (Fig. 8). Renal adenomas were reported in three individuals; however these were difficult to distinguish from renal cell carcinoma both angiographically and pathologically. Often the arbitrary size of 2 cm is used to differentiate the two, but a continuous spectrum probably exists (8). Other Findings Four patients were found to have carcinoma of the pancreas; in a fifth patient the diagnosis was indicated by an abnormal CT scan but is as yet unproved. The pathology and complications seen were similar to those occurring with pancreatic carcinoma not associated with von Hippel-Lindau disease. A benign hemangioblastoma of the pancreas was found in one patient (Fig. 9). In another, adenocarcinoma of the ampulla of Vater was seen on upper gastrointestinal series (Fig. 10). Pancreatic cysts, a common manifestation of von Hippel-Lindau disease, were identified in eight patients. These cysts may be so
293
Diagnostic Radiology
Fig. 7. Abdominal ultrasonogram shows a very large right kidney (arrows) with multiple cysts.
diffuse as to virtually replace the entire pancreas (Fig. 11); when discovered during routine screening they may be the first indication of disease in an individual patient. Pheochromocytoma reportedly may be present in up to 17 % of affected patients (2) although its incidence varies; no cases were found in our patients. Diagnosis of pheochromocytoma is made through screening of the urine for catecholamines and by visualization during abdominal angiography. Cysts may occur in virtually any of the visceral organs, including the liver, omentum, mesentery, spleen, and adrenal. Epididymal cysts are rather common and were found by physical examination in 6 of 22 affected males in this series. The cysts, not usually significant in themselves, are important in identifying individuals with von Hippel-Lindau disease, thereby prompting more invasive
8a,b
Fig. 8a. A longitudinal posterior Ultrasonogram shows two cystic masses in the lower left kidney, although some internal echoes are seen. b. Selective injection into the lower left renal artery. Two cysts are demonstrated, one with a small focus of renal cell carcinoma (arrow).
WILLIAM L. FILL AND OTHERS
294
November 1979
Fig. 9. Selective injection of the splenic artery in a patient who had undergone splenectomy and partial pancreatectomy 16 years previously. Biopsy revealed recurrent hemangioblastoma of the pancreas.
Fig. 10. Mass effect is seen on the second portion of the duodenum (arrowheads) from adenocarcinoma of the ampulla of Vater.
Fig. 11. Abdominal CT scan demonstrates multiple pancreatic cysts and bilateral renal tumors.
diagnostic procedures. Other manifestations of the disease include hemangiomas of the liver (three patients) paragangliomas (none in this series), and polycythemia (none in this series). DISCUSSION
Although von Hippel-Lindau disease appears to have variable penetrance, manifestations often occur with increasing age, and thus the penetrance may approach 100 %. Affected individuals in this series presented at ages between 11 and 62 years. Most family members are now under 20 years of age, and therefore more affected individuals are expected as time passes. Two were identified as being affected because of eye tumors in their children, even though they themselves presented no manifestations at ages 34 and 37, respectively. Follow-up examination, which is similar to the screening procedure, in family members not diagnosed as affected
should 'probably be performed yearly, especialy for those at 50 % risk, i.e., children with one affected parent. Abdominal CT is a recommended method of yearly follow-up which is necessary if renal tumors are to be detected when still amenable to local resection. In cases in this series where nephrectomy was performed, microscopic foci of renal cell carcinoma were found within cysts and within the renal parenchyma, demonstrating the necessity of close follow-up when initial examination is normal or after a partial resection. To further determine whether CT can replace renal angiography in the initial evaluation, as a recent study of four patients indicates (9), we are presently attempting to obtain CT scans on all affected individuals in this kindred. ACKNOWLEDGMENT: The various examinations were performed at different institutions. We wish to thank the following radiologists for their assistance and for case material: Dr. Sankaran Babu, Letterman Army Medical Center, San Francisco, CA; Dr. Raymond Brust, St. Francis Hospital, Honolulu, HI (Fig. 11); Dr. Virgil Jobe, Straub Clinic and Hospital, Honolulu, HI (Figs. 1a and b, and 3); Dr. Michael Meagher, Queens Hospital, Honolulu, HI (Figs. 1c and d, and 10); Dr. Thomas H. Newton, University of California, San Francisco, CA.
REFERENCES 1. Melmon KL, Rosen SW: Lindau's disease. Review of the literature and study of a large kindred. Am J Med 36:595-617, Apr 1964 2. Horton WA, Wong V, Eldridge R: Von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med 136:769-777, Jul 1976
Vol. 133
VON HIPPEL-LINDAU DISEASE
3. Lamiell JM: Von Hippel-Lindau disease in a large kindred. In preparation. 4. Salazar F: Retinal angiomas in von Hippel-Lindau disease. Accepted for publication by the American Journal of Ophthalmology. 5. Wolpert SM: The neuroradiologyof hemangioblastomas of the cerebellum. Am J RoentgenoI110:56-66, Sep 1970 6. HanafeeW, DaytonGOJr, Weidner W: Orbital angiography and venography aided by subtractiontechnique. Trans Am Acad Ophthalmol Otolaryngol 70: 1027-1033, Nov-Dec 1966 7. Lee KR, Wulfsberg E, Kepes JJ: Some important radiological aspects of the kidney in Hippel-Lindau syndrome: the value of pro-
295
Diagnostic Radiology
spective study in an affected family. Radiology 122:649-653, Mar 1977 8. Bennington JL: Proceedings: Cancer of the kidney-etiology, epidemiology, and pathology. Cancer 32:1017-1029, Nov 1973 9. Levine E, Lee KR, Weigel JW, et al: Computed tomography in the diagnosisof renal carcinoma complicating Hippel-Lindau syndrome. Radiology 130:703-706, Mar 1979
Department of Radiology Brooke Army Medical Center Fort Sam Houston, TX 78234
