Pituitary hemangioblastoma in a patient with yon Hippel-Lindau disease Case report NorL G. DAN,F.R.A.C.S., AND DERMER E. SMITH,F.R.C.P.A.
Departments of Neurosurgery and Histopathology, St. Vincent's Hospital, Sydney, Australia v' A case of von Hippel-Lindau disease is described in which a pituitary hemangioblastoma was present as well as a cerebrovascular anomaly. KEY WORDS yon Hippei-Lindau disease hemangioblastoma "
O our knowledge, no occurrence of a pituitary hemangioblastoma has been previously reported. We are presenting such a case.
T
Case Report
A 26-year-old man first came to St. Vincent's Hospital in June, 1958, with a 9-week history of vertigo when moving his head. Apart from nystagmus with extension of the neck, examination was normal. Lumbar puncture and cerebrospinal fluid examination were normal, as were caloric testing, hemoglobin, and air encephalography. He was readmitted in October, 1964, complaining of occipital headache and blurred vision. Examination. He was plethoric and had bilateral papilledema and ataxia. Hemoglobin was 20 gm% and the hematocrit was 56%. Vertebral angiography demonstrated a midline posterior fossa vascular mass 3 cm in diameter and fed by both superior cerebellar arteries; it also showed 232
9 pituitary
9
a 1.5 cm mass of abnormal vessels just below the foramen magnum to the left of the midline whose main supply was from the left posterior inferior cerebellar artery. The diagnosis was multiple posterior fossa angiomata considered unsuitable for excision. The patient was given a Holter ventriculoatrial shunt followed by cobalt-60 irradiation. The papilledema subsided and symptoms disappeared rapidly; he remained well until late 1970, requiring a shunt revision in 1965. The patient was readmitted in January, 1971, with a 2-month history of occipital headache. The Holter valve was revised because of a blocked ventricular catheter. His postoperative recovery was complicated by fever associated with a low-grade Staphylococcus albus septicemia. During this admission a hemangioblastoma of the left retina was first observed. Subsequently, he had three further admissions because of the septicemia. He could not tolerate removal of the ventriculoatrial shunt, developing severe vertigo,
J. Neurosurg. / Volume 42 / February, 1975
Pituitary hemangioblastoma
FIG. 1. Vertebral angiogram. Left: Arterial phase, anteroposterior view, showing a tumor blush in the vermis. Right: Early venous phase, lateral view, showing the blush above and below the basiocciput of the two posterior fossa tumors. drowsiness, diplopia, and headache when it was removed. At no time during these admissions was there any evidence of abnormal endocrine function. The sella measured 14 X 10 X 7 mm, Vertebral angiography in July, 1971, demonstrated a large vascular lesion low in the vermis of the cerebellum. This was supplied by a large posterior inferior cerebellar artery and drained by large veins which filled early. He was comatose when readmitted in August, 1971, and died of overwhelming infection. Family History. The patient's father died of multiple myeloma, his mother of carcinoma of the colon. Neither of the patient's parents nor his three siblings demonstrated any evidence of von Hippel-Lindau disease. His eldest child, a 15-year-old girl, has a tapetoretinal dystrophy but also has a hemangioblastoma of the right eye which has been treated by photocoagulation; her two siblings, aged 12 and 11 years, are free of angiomatous stigmata to date. Postmortem Findings. Basal meningitis was present. The cerebellum contained a solid tumor 4 cm in its maximum diameter that included a small cyst. This occupied a large part of the vermis, was visible on the surface of the tonsil and expanded anteriorly to occlude the fourth ventricle (Figs. 1 and 2). A discrete and similar tumor 1.5 cm in diameter was present in the area postrema; anterior to this tumor
J. Neurosurg. / Volume 42 / February, 1975
was a single 5 mm cyst extending throughout the lower part of the medulla oblongata to form a syringobulbia. In the cerebral white matter of the right hemisphere in the region of the body of the caudate nucleus and the adjacent internal capsule was a 3 cm lesion consisting of thick-walled blood vessels. There were minute lesions on the right retina and a slightly larger lesion on the left retina. Each kidney weighed 200 gm and contained cysts up to 1.5 cm in diameter and pinkishyellow solid tumors up to 1 cm in diameter. The pancreas contained small thin-walled cysts up to 5 mm in diameter. Adrenals,
F~. 2. Postmortem cross sections showing the lesions of the vermis and medulla. 233
N. G. Dan and D. E. Smith cells indistinguishable from "clear cell" renal carcinoma. A cortical papillary adenoma lacking clear cells was also demonstrated. Discussion
FIG. 3. Section of pituitary lesion showing pituitary tissue below (arrow) and tumor above. H & E , • 140. testes, and epididymi were normal. There was a small irregular tumor 3 • 2 • 2 mm, on the left side of the anterior lobe of the pituitary gland (Figs. 3 and 4). The cerebellar and brain-stem lesions showed the histology characteristic of hemangioblastoma? ~ Numerous thin-walled vascular channels were separated by large polyhedral cells with pale cytoplasm. The tumor in the anterior lobe of the pituitary had an identical histological pattern. Hemangioblastomas were present in both retinae. The lesion in the cerebral white matter consisted of numerous thick-walled blood vessels, several of which had undergone sclerosis and obliteration. The pancreatic cysts were lined by columnar epithelium, an appearance consistent with ductal origin. The multiple renal tumors were composed of "clear" epithelial 234
Panas and Remy 8 first illustrated a retinal hemangioblastoma in 1879, but it was von Hippel 1~ who, in 1904, recognized the significance of the lesion and described its progression. Similarly, Pye-Smith's 9 report of a cystic cerebellar hemangioblastoma was followed by others but was not synthesized into a coherent entity until Lindau's 6 monograph in 1926 brought together the retinal, intracranial, and visceral elements. Lindau first included cerebellar and medulla oblongata hemangioblastomas, syringomyelia cavities, TM pancreatic cysts, renal cysts, and clear cell tumors; he later added epididymal cysts? Bielschowskyla published the first acceptable case of cerebral hemangioblastoma, but it was not until Hoff and Ray's report 3 that this was linked with von Hippel-Lindau disease. Wright 13described a hemangioblastoma of a lumbar spinal nerve root. Other clinical features described include erythrocytosis and phaeochromocytoma. 7 The case reported here demonstrates many of the features that constitute von HippelLindau disease. The patient had a mixed solid and cystic hemangioblastoma of the vermis as well as a solid lesion in the area postrema of the medulla oblongata. Both of these sites are common locations of hemangioblastoma? ~ A syringobulbia was present, and both eyes demonstrated the von Hippel lesion. It is interesting that the only one of these signs that was clinically apparent appeared 13 years after he was first seen. This progression of the retinal lesions 4 as well as that of the cerebellar lesions 7 is well documented. We consider that this is a true hemangioblastoma of the pituitary gland. We do not think that the cerebral lesion can be accepted as a hemangioblastoma on histological grounds despite the other multiple lesions; rather, we classify this as a vascular hamartoma. The pancreatic and renal lesions are those of Lindau's disease? The patient demonstrated erythrocytosis consistently from 1964 to the time of death. This must be considered a feature of the syndrome, especially since Skultety, et al., ~ demonstrated high concentrations of erythropoietin J. ]Veurosurg. / Volume 42 / February, 1975
Pituitary hemangioblastoma
FIG. 4. Left: Photomicrograph of the pituitary hemangioma. H & E, • 300. Right: Cerebellar hemangioma. H & E, • 300. in the solid component of their cerebellar hemangioblastoma. Surgical removal of the lesion was not attempted in 1964 since the radiological appearances could not be differentiated from an arteriovenous malformation and other stigmata were not apparent at that time.
7.
Acknowledgments
9.
The authors are indebted to Dr. Kevin Bleasel, Dr. Vincent Munro and Dr. Michael Harrison for their assistance in the preparation of this report.
10.
8.
References
1. Bielchowsky M: Zur Histologie und Pathologie der Gehirngeschwfilste. Dtseh Z Nervenheilk 22:54-99, 1902 2. Cushing H, Bailey P: Tumours Arising from the Blood Vessels of the Brain. Angiomatous Malformations and Hemangioblastoma. Springfield, Ill, Charles C Thomas, 1928 3. HoffJT, Ray BS: Cerebral hemangioblastoma occurring in a patient with von Hippel-Lindau disease. J Neurosurg 28:365-368, 1968 4. Jesburg DO, Spencer WH, Hoyt WF: Incipient lesions of von Hippel-Lindau disease. Arch Ophthalmol 80:632-640, 1968 5. Lindau A: Zur Frage der Angiomatosis Retinae und ihrer Hirnkomplikationen. Acta Ophthaimol 4:193-226, 1927 6. Lindau A: Studien tiber Kleinhirncysten. Bau,
J. Neurosurg. / Volume 42 / February, 1975
11.
12. 13. 14.
Pathogenese und Beziehungen zur Angiomatosis Retinae. Acta Pathoi Microbioi Seand Suppl 1:1-128, 1926 Melmon KL, Rosen SW: Lindau's disease. Review of the literature and study of a large kindred. Am J Med 36:595-617, 1964 Panas F, Remy DA: Anatomie Pathologique de i'Oeii. Paris, Delahaye & Cie, 1879, p 88 Pye-Smith PH: Cyst of the cerebellum with numerous small cysts in the pancreas and kidneys. Trans Pathoi Soe Load 36:17-21, 1885 Russell DS, Rubinstein LJ: Pathology of Turnouts of the Nervous System. London, Edward Arnold, 1971, ed 3 Skultety FM, Sorrell MF, Burklund CW: Hemangioblastoma of the cerebellum associated with erythrocytosis and an unusual blood supply. Case report. J Neurosurg 32:700-705, 1970 von Hippel E: Uber eine sehr seltene Erkrankung der Netzhaut. Arch Ophthalmol 59:83-106, 1904 Wright AL: Familial yon Hippel-Lindau's disease. J Neurosurg 30:281-285, 1969 Wyburn-Mason R: The Vascular Abnormalities and Turnouts of the Spinal Cord and its Membranes. London, H Kimpton, 1943
Address reprint requests to: Noel G. Dan, F.R.A.C.S., Department of Neurosurgery, St. Vincent's Hospital, Sydney, Australia. 235
Departments of Neurosurgery and Histopathology, St. Vincent's Hospital, Sydney, Australia v' A case of von Hippel-Lindau disease is described in which a pituitary hemangioblastoma was present as well as a cerebrovascular anomaly. KEY WORDS yon Hippei-Lindau disease hemangioblastoma "
O our knowledge, no occurrence of a pituitary hemangioblastoma has been previously reported. We are presenting such a case.
T
Case Report
A 26-year-old man first came to St. Vincent's Hospital in June, 1958, with a 9-week history of vertigo when moving his head. Apart from nystagmus with extension of the neck, examination was normal. Lumbar puncture and cerebrospinal fluid examination were normal, as were caloric testing, hemoglobin, and air encephalography. He was readmitted in October, 1964, complaining of occipital headache and blurred vision. Examination. He was plethoric and had bilateral papilledema and ataxia. Hemoglobin was 20 gm% and the hematocrit was 56%. Vertebral angiography demonstrated a midline posterior fossa vascular mass 3 cm in diameter and fed by both superior cerebellar arteries; it also showed 232
9 pituitary
9
a 1.5 cm mass of abnormal vessels just below the foramen magnum to the left of the midline whose main supply was from the left posterior inferior cerebellar artery. The diagnosis was multiple posterior fossa angiomata considered unsuitable for excision. The patient was given a Holter ventriculoatrial shunt followed by cobalt-60 irradiation. The papilledema subsided and symptoms disappeared rapidly; he remained well until late 1970, requiring a shunt revision in 1965. The patient was readmitted in January, 1971, with a 2-month history of occipital headache. The Holter valve was revised because of a blocked ventricular catheter. His postoperative recovery was complicated by fever associated with a low-grade Staphylococcus albus septicemia. During this admission a hemangioblastoma of the left retina was first observed. Subsequently, he had three further admissions because of the septicemia. He could not tolerate removal of the ventriculoatrial shunt, developing severe vertigo,
J. Neurosurg. / Volume 42 / February, 1975
Pituitary hemangioblastoma
FIG. 1. Vertebral angiogram. Left: Arterial phase, anteroposterior view, showing a tumor blush in the vermis. Right: Early venous phase, lateral view, showing the blush above and below the basiocciput of the two posterior fossa tumors. drowsiness, diplopia, and headache when it was removed. At no time during these admissions was there any evidence of abnormal endocrine function. The sella measured 14 X 10 X 7 mm, Vertebral angiography in July, 1971, demonstrated a large vascular lesion low in the vermis of the cerebellum. This was supplied by a large posterior inferior cerebellar artery and drained by large veins which filled early. He was comatose when readmitted in August, 1971, and died of overwhelming infection. Family History. The patient's father died of multiple myeloma, his mother of carcinoma of the colon. Neither of the patient's parents nor his three siblings demonstrated any evidence of von Hippel-Lindau disease. His eldest child, a 15-year-old girl, has a tapetoretinal dystrophy but also has a hemangioblastoma of the right eye which has been treated by photocoagulation; her two siblings, aged 12 and 11 years, are free of angiomatous stigmata to date. Postmortem Findings. Basal meningitis was present. The cerebellum contained a solid tumor 4 cm in its maximum diameter that included a small cyst. This occupied a large part of the vermis, was visible on the surface of the tonsil and expanded anteriorly to occlude the fourth ventricle (Figs. 1 and 2). A discrete and similar tumor 1.5 cm in diameter was present in the area postrema; anterior to this tumor
J. Neurosurg. / Volume 42 / February, 1975
was a single 5 mm cyst extending throughout the lower part of the medulla oblongata to form a syringobulbia. In the cerebral white matter of the right hemisphere in the region of the body of the caudate nucleus and the adjacent internal capsule was a 3 cm lesion consisting of thick-walled blood vessels. There were minute lesions on the right retina and a slightly larger lesion on the left retina. Each kidney weighed 200 gm and contained cysts up to 1.5 cm in diameter and pinkishyellow solid tumors up to 1 cm in diameter. The pancreas contained small thin-walled cysts up to 5 mm in diameter. Adrenals,
F~. 2. Postmortem cross sections showing the lesions of the vermis and medulla. 233
N. G. Dan and D. E. Smith cells indistinguishable from "clear cell" renal carcinoma. A cortical papillary adenoma lacking clear cells was also demonstrated. Discussion
FIG. 3. Section of pituitary lesion showing pituitary tissue below (arrow) and tumor above. H & E , • 140. testes, and epididymi were normal. There was a small irregular tumor 3 • 2 • 2 mm, on the left side of the anterior lobe of the pituitary gland (Figs. 3 and 4). The cerebellar and brain-stem lesions showed the histology characteristic of hemangioblastoma? ~ Numerous thin-walled vascular channels were separated by large polyhedral cells with pale cytoplasm. The tumor in the anterior lobe of the pituitary had an identical histological pattern. Hemangioblastomas were present in both retinae. The lesion in the cerebral white matter consisted of numerous thick-walled blood vessels, several of which had undergone sclerosis and obliteration. The pancreatic cysts were lined by columnar epithelium, an appearance consistent with ductal origin. The multiple renal tumors were composed of "clear" epithelial 234
Panas and Remy 8 first illustrated a retinal hemangioblastoma in 1879, but it was von Hippel 1~ who, in 1904, recognized the significance of the lesion and described its progression. Similarly, Pye-Smith's 9 report of a cystic cerebellar hemangioblastoma was followed by others but was not synthesized into a coherent entity until Lindau's 6 monograph in 1926 brought together the retinal, intracranial, and visceral elements. Lindau first included cerebellar and medulla oblongata hemangioblastomas, syringomyelia cavities, TM pancreatic cysts, renal cysts, and clear cell tumors; he later added epididymal cysts? Bielschowskyla published the first acceptable case of cerebral hemangioblastoma, but it was not until Hoff and Ray's report 3 that this was linked with von Hippel-Lindau disease. Wright 13described a hemangioblastoma of a lumbar spinal nerve root. Other clinical features described include erythrocytosis and phaeochromocytoma. 7 The case reported here demonstrates many of the features that constitute von HippelLindau disease. The patient had a mixed solid and cystic hemangioblastoma of the vermis as well as a solid lesion in the area postrema of the medulla oblongata. Both of these sites are common locations of hemangioblastoma? ~ A syringobulbia was present, and both eyes demonstrated the von Hippel lesion. It is interesting that the only one of these signs that was clinically apparent appeared 13 years after he was first seen. This progression of the retinal lesions 4 as well as that of the cerebellar lesions 7 is well documented. We consider that this is a true hemangioblastoma of the pituitary gland. We do not think that the cerebral lesion can be accepted as a hemangioblastoma on histological grounds despite the other multiple lesions; rather, we classify this as a vascular hamartoma. The pancreatic and renal lesions are those of Lindau's disease? The patient demonstrated erythrocytosis consistently from 1964 to the time of death. This must be considered a feature of the syndrome, especially since Skultety, et al., ~ demonstrated high concentrations of erythropoietin J. ]Veurosurg. / Volume 42 / February, 1975
Pituitary hemangioblastoma
FIG. 4. Left: Photomicrograph of the pituitary hemangioma. H & E, • 300. Right: Cerebellar hemangioma. H & E, • 300. in the solid component of their cerebellar hemangioblastoma. Surgical removal of the lesion was not attempted in 1964 since the radiological appearances could not be differentiated from an arteriovenous malformation and other stigmata were not apparent at that time.
7.
Acknowledgments
9.
The authors are indebted to Dr. Kevin Bleasel, Dr. Vincent Munro and Dr. Michael Harrison for their assistance in the preparation of this report.
10.
8.
References
1. Bielchowsky M: Zur Histologie und Pathologie der Gehirngeschwfilste. Dtseh Z Nervenheilk 22:54-99, 1902 2. Cushing H, Bailey P: Tumours Arising from the Blood Vessels of the Brain. Angiomatous Malformations and Hemangioblastoma. Springfield, Ill, Charles C Thomas, 1928 3. HoffJT, Ray BS: Cerebral hemangioblastoma occurring in a patient with von Hippel-Lindau disease. J Neurosurg 28:365-368, 1968 4. Jesburg DO, Spencer WH, Hoyt WF: Incipient lesions of von Hippel-Lindau disease. Arch Ophthalmol 80:632-640, 1968 5. Lindau A: Zur Frage der Angiomatosis Retinae und ihrer Hirnkomplikationen. Acta Ophthaimol 4:193-226, 1927 6. Lindau A: Studien tiber Kleinhirncysten. Bau,
J. Neurosurg. / Volume 42 / February, 1975
11.
12. 13. 14.
Pathogenese und Beziehungen zur Angiomatosis Retinae. Acta Pathoi Microbioi Seand Suppl 1:1-128, 1926 Melmon KL, Rosen SW: Lindau's disease. Review of the literature and study of a large kindred. Am J Med 36:595-617, 1964 Panas F, Remy DA: Anatomie Pathologique de i'Oeii. Paris, Delahaye & Cie, 1879, p 88 Pye-Smith PH: Cyst of the cerebellum with numerous small cysts in the pancreas and kidneys. Trans Pathoi Soe Load 36:17-21, 1885 Russell DS, Rubinstein LJ: Pathology of Turnouts of the Nervous System. London, Edward Arnold, 1971, ed 3 Skultety FM, Sorrell MF, Burklund CW: Hemangioblastoma of the cerebellum associated with erythrocytosis and an unusual blood supply. Case report. J Neurosurg 32:700-705, 1970 von Hippel E: Uber eine sehr seltene Erkrankung der Netzhaut. Arch Ophthalmol 59:83-106, 1904 Wright AL: Familial yon Hippel-Lindau's disease. J Neurosurg 30:281-285, 1969 Wyburn-Mason R: The Vascular Abnormalities and Turnouts of the Spinal Cord and its Membranes. London, H Kimpton, 1943
Address reprint requests to: Noel G. Dan, F.R.A.C.S., Department of Neurosurgery, St. Vincent's Hospital, Sydney, Australia. 235
