Clinical Radiology(1992) 45, 37-39
Case Report: Multiple Hepatic and Pulmonary Haemangioblastomas- A New Manifestation of yon Hippel-Lindau Disease F. P. M C G R A T H ,
R. G . G I B N E Y ,
D. C. M O R R I S ,
D. A. O W E N *
a n d S. R. E R B ' ~
Departments of Radiology, *Pathology and ~Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, Canada Capillary haemangioblastomas rarely occur outside the central nervous system and have not been described previously in the lung or liver. We describe such lesions developing in a patient with von HippeI-Lindau complex who previously had cerebellar and spinal haemangioblastomas resected. M c G r a t h , F.P., G i b n e y , R . G . , M o r r i s , D . C . , O w e n , D . A . & E r b , S.R. (1992).
Clinical Radiology 45, 37 39. C a s e R e p o r t : M u l t i p l e H e p a t i c a n d P u l m o n a r y H a e m a n g i o blastomas
A New Manifestation ofvor
V o n H i p p e l - L i n d a u d i s e a s e ( V H L ) is a h e r e d i t a r y m u l t i system d i s o r d e r c h a r a c t e r i z e d by h a e m a n g i o b l a s t o m a s o f the c e r e b e l l u m , spinal c o r d and r e t i n a ( M e l m o n a n d R o s e n , 1964). D i s e a s e o u t s i d e the c e n t r a l n e r v o u s s y s t e m ( C N S ) usually i n c l u d e s s i m p l e h e p a t i c , renal a n d p a n creatic cysts or t u m o u r s o f the k i d n e y or p a n c r e a s . H a e m a n g i o b l a s t o m a s h a v e b e e n r e p o r t e d in the k i d n e y , p a n c r e a s a n d u r i n a r y b l a d d e r (Bird a n d M e n d e l o w , 1959). T h e r a d i o g r a p h i c f i n d i n g s in a p a t i e n t with m u l t i p l e h e p a t i c a n d p u l m o n a r y h a e m a n g i o b l a s t o m a s a r e described. T h e h i s t o p a t h o l o g y o f this case has been r e p o r t e d elsewhere ( R o j i a n i et al., 1991).
CASE REPORT
Hippel-Lindau Disease
no new tumour; thoracic CT demonstrated multiple enhancing nodules throughout both lungs (Fig. 5). Histological examination of the liver following OLTX, and of the pulmonary lesions after open lung biopsy, revealed these to be vasoformative capillary haemangioblastomas morphologically identical with the previously resected CNS tumours.
DISCUSSION V H L is c h a r a c t e r i z e d by the d e v e l o p m e n t o f n e u r o ectodermal tumours. Retinal angiomas and cerebellar h a e m a n g i o b l a s t o m a s are the m o s t c o m m o n a n d well r e c o g n i z e d early m a n i f e s t a t i o n s . A f f e c t e d i n d i v i d u a l s are at risk o f d e v e l o p i n g m a n y o t h e r lesions, the m o s t serious o f w h i c h are renal cell c a r c i n o m a s , p h a e o c h r o m o c y t o mas, and CNS haemangioblastomas (Hardwig and R o b e r t s o n , 1984).
A 39-year-old female with previously resected cerebellar and spinal haemangioblastomas presented with recurrent bouts of right upper quadrant pain. Ultrasound (US) demonstrated a single (9 × l I cm) solid hyperechoic mass with a hypoechoic central component in the right lobe of the liver (Fig. 1). An unenhanced computed tomography (CT) scan revealed a hypodense lesion, that following contrast infusion showed intense peripheral enhancement with incomplete centripetal fill-in (Fig. 2). Fine needle aspiration biopsy of the mass yielded blood with no malignant or endothelial cells. A diagnosis of a giant cavernous haemangioma was made. Over the next 3 years the attacks of right upper quadrant pain increased in frequency, severity and duration. Repeat US revealed an increase in size and multiplicity of the turnout mass (Fig. 3a). Contrast CT examination demonstrated the same peripheral enhancement pattern within two of the satellite lesions as was present in the dominant tumour (Fig. 3b). A common hepatic angiogram showed a markedly vascular early phase with extensive tumour blush involving almost the entire liver (Fig. 4). The patient underwent orthotopic liver transplantation (OLTX) 3½years after initial presentation because of'increasing symptoms and a virtual bedridden state. Cerebellar haemangioblastomas had been removed 26, 16 and 13 years before OLTX. A high cervical spinal haemangioblastoma, with the same angiographic features as those of the hepatic lesions, had been resected 4 years earlier. Despite adequate Surgical resection with no evidence of residual tumour a polycythaemia had persisted, requiring repeated phlebotomy. After OLTX the polycythaemia abated and the patient was discharged pain-free 5 weeks later with normal haemoglobin level. Six months after OLTX the polycythaemia recurred although the patient remained asymptomatic. CT of the head and abdomen revealed Correspondence to: Dr Frank P. McGrath, Department of Radiology, McMaster University Medical Centre, 1200 Main St. West, ttamilton, Ontario, Canada L8N 3Z5.
Fig. 1 t986. Sagittal sonogram through the right lobe of liver demonstrating a 9 × 11 cm hyperechoic mass with a central hypoechoic component.
38
CLINICAL RADIOLOGY
(a)
(b) Fig. 2 1986. (a) Hepatic unenhanced CT showing a large low density lesion with additional cleft-like low density areas (arrow) and (b) postcontrast scan demonstrating irregular peripheral enhancement pattern.
The diagnostic criteria for the V H L complex include the presence o f a CNS haemangioblastoma in association with at least one other visceral manifestation of the disease, or a documented CNS haemangioblastoma occurring in a family member (Melmon and Rosen, 1964). Features supporting the diagnosis of VHL in this case include the presentation of cerebellar and spinal haemangioblastomas, and secondary polycythaemia. The hepatic manifestation presented 23 years following the initial resection of a cerebellar haemangioblastoma. The US and CT appearances of hepatic haemangioblastoma have not been reported previously. Scatarige et al. (1987) described the CT appearances of giant cavernous haemangiomas in eight patients. The hepatic haemangioblastoma, as in seven of eight patients in the above report, appeared less dense than the surrounding normal liver on the unenhanced scan. A stellate or cleft-like low density central zone was also present; this exhibited early peripheral enhancement and partial centripetal isodense fill-in. The differential diagnosis of this vascular tumour would also include a hepatoma or angiosarcoma. At presentation there was much discussion about the appropriate investigation and management of the liver lesion. A magnetic resonance (MR) examination was recommended in an effort to distinguish between a hepatoma and an angiosarcoma or haemangioma, the latter two entities usually having a relatively higher intensity on longer TR sequences. The patient declined this investigation because of claustrophobia. The negative fine needle
(b) Fig. 3 1988. (a) Transverse liver sonogram showing multiple hyperechoic loci involving both lobes in addition to the dominant right
lobe lesion (shown in Fig. 1) and (b) a contrast CT showing irregular peripheral enhancement within the satellite lesions identical with that within the main tumour (shown in Fig. 2b). aspiration biopsy made a diagnosis of malignancy unlikely. In addition, the initial US and CT appearances of this rare lesion were understandably taken to represent a giant hepatic haemangioma and a decision was made to follow the patient clinically. In retrospect it would have been interesting and possibly valuable to have performed angiography at that time. A comparison with the anglographic images of the previous spinal haemangioblastoma may have suggested a possible connection. Hepatic lesions previously reported in V H L include cysts and, rarely, adenomata and angiomata. Zeitlin (1942) reported a case of V H L with multiple cavernous haemangiomata in the liver. These lesions were morphologically distinct from the cerebellar haemangioblastoma occurring in the same patient. Capillary haemangioblastomas are uncommon vasoformative lesions most frequently seen in the posterior cranial fossa and though rarely occurring in extraneural axial sites, have not been described previously in the liver or lungs in patients with V H L (Rojiani et al., 1991). The turnout is not known to metastasize to extraneural sites although subarachnoid spread has been reported previously (Mohan et al., 1976). The manifestation of the
MULTIPLE HEPATIC AND PULMONARY HAEMANGIOBLASTOMAS
39
Fig. 5 1990. CT of thorax demonstrating multiple enhancing pulmonary nodules. REFERENCES
Fig. 4 1988. A delayed image from a common hepatic angiogram showing extensive blush involving almost the entire liver and angiographically very similar to the CNS haemangioblastomas previously resected.
liver l e s i o n s o v e r 20 y e a r s f o l l o w i n g t h e first p r e s e n t a t i o n o f c e r e b e l l a r h a e m a n g i o b l a s t o m a m o r e likely r e p r e s e n t s c o i n c i d e n t a l de novo h e p a t i c t u m o u r t h a n m e t a s t a t i c s p r e a d f r o m t h e n e u r a l axis. T h e s u b s e q u e n t d e v e l o p m e n t of multiple pulmonary haemangioblastomas 6 months f o l l o w i n g t h e O L T X is b e l i e v e d t o h a v e b e e n c a u s e d b y inadvertent haematogenous tumour seeding at the time of surgery.
Bird, AV & Mendelow, H (1959). Lindau's disease in a South African family: a report on 3 further cases. British Journal of Surgery, 47, 173 176. Hardwig, P & Robertson, DM (1984). Von Hippel-Lindau disease: a familial, often lethal, multi-system phakomatosis. Ophthahnology, 91,263-270. Melmon, KL & Rosen, SW (1964). Lindau's disease. Review of the literature and study of a large kindred. American Journal of Medicine, 36, 595-617. Mohan, J, Brownell, B & Oppenheimer, DR (1976). Malignant spread of hemangioblastoma: report on two cases. Journal of Neurology, Neurosurgery and Psyehiatry, 39, 515 525. Rojiani, AM, Owen, DA, Berry, K, Woodhurst, B, Anderson, FH, Scudamore, C H e t al. (1991). Hepatic hemangioblastoma: an unusual presentation in a patient with von Hippel-Lindau disease. American Journal of Surgical Pathology, 15, 81 86. Scatarige, JC, Kenny, JM, Fishman, EK, Herlong, FH & Siegelman, SS (1987). CT of giant cavernous hemangioma. American Journal of Roentgenology, 149, 83-85. Zeitlin, H (1942). Hemangioblastomas of the meninges and their relationship to Lindau's disease. Journal c~f Neuropathology and Experimental Neurology, 1, I4-23.
Case Report: Multiple Hepatic and Pulmonary Haemangioblastomas- A New Manifestation of yon Hippel-Lindau Disease F. P. M C G R A T H ,
R. G . G I B N E Y ,
D. C. M O R R I S ,
D. A. O W E N *
a n d S. R. E R B ' ~
Departments of Radiology, *Pathology and ~Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, Canada Capillary haemangioblastomas rarely occur outside the central nervous system and have not been described previously in the lung or liver. We describe such lesions developing in a patient with von HippeI-Lindau complex who previously had cerebellar and spinal haemangioblastomas resected. M c G r a t h , F.P., G i b n e y , R . G . , M o r r i s , D . C . , O w e n , D . A . & E r b , S.R. (1992).
Clinical Radiology 45, 37 39. C a s e R e p o r t : M u l t i p l e H e p a t i c a n d P u l m o n a r y H a e m a n g i o blastomas
A New Manifestation ofvor
V o n H i p p e l - L i n d a u d i s e a s e ( V H L ) is a h e r e d i t a r y m u l t i system d i s o r d e r c h a r a c t e r i z e d by h a e m a n g i o b l a s t o m a s o f the c e r e b e l l u m , spinal c o r d and r e t i n a ( M e l m o n a n d R o s e n , 1964). D i s e a s e o u t s i d e the c e n t r a l n e r v o u s s y s t e m ( C N S ) usually i n c l u d e s s i m p l e h e p a t i c , renal a n d p a n creatic cysts or t u m o u r s o f the k i d n e y or p a n c r e a s . H a e m a n g i o b l a s t o m a s h a v e b e e n r e p o r t e d in the k i d n e y , p a n c r e a s a n d u r i n a r y b l a d d e r (Bird a n d M e n d e l o w , 1959). T h e r a d i o g r a p h i c f i n d i n g s in a p a t i e n t with m u l t i p l e h e p a t i c a n d p u l m o n a r y h a e m a n g i o b l a s t o m a s a r e described. T h e h i s t o p a t h o l o g y o f this case has been r e p o r t e d elsewhere ( R o j i a n i et al., 1991).
CASE REPORT
Hippel-Lindau Disease
no new tumour; thoracic CT demonstrated multiple enhancing nodules throughout both lungs (Fig. 5). Histological examination of the liver following OLTX, and of the pulmonary lesions after open lung biopsy, revealed these to be vasoformative capillary haemangioblastomas morphologically identical with the previously resected CNS tumours.
DISCUSSION V H L is c h a r a c t e r i z e d by the d e v e l o p m e n t o f n e u r o ectodermal tumours. Retinal angiomas and cerebellar h a e m a n g i o b l a s t o m a s are the m o s t c o m m o n a n d well r e c o g n i z e d early m a n i f e s t a t i o n s . A f f e c t e d i n d i v i d u a l s are at risk o f d e v e l o p i n g m a n y o t h e r lesions, the m o s t serious o f w h i c h are renal cell c a r c i n o m a s , p h a e o c h r o m o c y t o mas, and CNS haemangioblastomas (Hardwig and R o b e r t s o n , 1984).
A 39-year-old female with previously resected cerebellar and spinal haemangioblastomas presented with recurrent bouts of right upper quadrant pain. Ultrasound (US) demonstrated a single (9 × l I cm) solid hyperechoic mass with a hypoechoic central component in the right lobe of the liver (Fig. 1). An unenhanced computed tomography (CT) scan revealed a hypodense lesion, that following contrast infusion showed intense peripheral enhancement with incomplete centripetal fill-in (Fig. 2). Fine needle aspiration biopsy of the mass yielded blood with no malignant or endothelial cells. A diagnosis of a giant cavernous haemangioma was made. Over the next 3 years the attacks of right upper quadrant pain increased in frequency, severity and duration. Repeat US revealed an increase in size and multiplicity of the turnout mass (Fig. 3a). Contrast CT examination demonstrated the same peripheral enhancement pattern within two of the satellite lesions as was present in the dominant tumour (Fig. 3b). A common hepatic angiogram showed a markedly vascular early phase with extensive tumour blush involving almost the entire liver (Fig. 4). The patient underwent orthotopic liver transplantation (OLTX) 3½years after initial presentation because of'increasing symptoms and a virtual bedridden state. Cerebellar haemangioblastomas had been removed 26, 16 and 13 years before OLTX. A high cervical spinal haemangioblastoma, with the same angiographic features as those of the hepatic lesions, had been resected 4 years earlier. Despite adequate Surgical resection with no evidence of residual tumour a polycythaemia had persisted, requiring repeated phlebotomy. After OLTX the polycythaemia abated and the patient was discharged pain-free 5 weeks later with normal haemoglobin level. Six months after OLTX the polycythaemia recurred although the patient remained asymptomatic. CT of the head and abdomen revealed Correspondence to: Dr Frank P. McGrath, Department of Radiology, McMaster University Medical Centre, 1200 Main St. West, ttamilton, Ontario, Canada L8N 3Z5.
Fig. 1 t986. Sagittal sonogram through the right lobe of liver demonstrating a 9 × 11 cm hyperechoic mass with a central hypoechoic component.
38
CLINICAL RADIOLOGY
(a)
(b) Fig. 2 1986. (a) Hepatic unenhanced CT showing a large low density lesion with additional cleft-like low density areas (arrow) and (b) postcontrast scan demonstrating irregular peripheral enhancement pattern.
The diagnostic criteria for the V H L complex include the presence o f a CNS haemangioblastoma in association with at least one other visceral manifestation of the disease, or a documented CNS haemangioblastoma occurring in a family member (Melmon and Rosen, 1964). Features supporting the diagnosis of VHL in this case include the presentation of cerebellar and spinal haemangioblastomas, and secondary polycythaemia. The hepatic manifestation presented 23 years following the initial resection of a cerebellar haemangioblastoma. The US and CT appearances of hepatic haemangioblastoma have not been reported previously. Scatarige et al. (1987) described the CT appearances of giant cavernous haemangiomas in eight patients. The hepatic haemangioblastoma, as in seven of eight patients in the above report, appeared less dense than the surrounding normal liver on the unenhanced scan. A stellate or cleft-like low density central zone was also present; this exhibited early peripheral enhancement and partial centripetal isodense fill-in. The differential diagnosis of this vascular tumour would also include a hepatoma or angiosarcoma. At presentation there was much discussion about the appropriate investigation and management of the liver lesion. A magnetic resonance (MR) examination was recommended in an effort to distinguish between a hepatoma and an angiosarcoma or haemangioma, the latter two entities usually having a relatively higher intensity on longer TR sequences. The patient declined this investigation because of claustrophobia. The negative fine needle
(b) Fig. 3 1988. (a) Transverse liver sonogram showing multiple hyperechoic loci involving both lobes in addition to the dominant right
lobe lesion (shown in Fig. 1) and (b) a contrast CT showing irregular peripheral enhancement within the satellite lesions identical with that within the main tumour (shown in Fig. 2b). aspiration biopsy made a diagnosis of malignancy unlikely. In addition, the initial US and CT appearances of this rare lesion were understandably taken to represent a giant hepatic haemangioma and a decision was made to follow the patient clinically. In retrospect it would have been interesting and possibly valuable to have performed angiography at that time. A comparison with the anglographic images of the previous spinal haemangioblastoma may have suggested a possible connection. Hepatic lesions previously reported in V H L include cysts and, rarely, adenomata and angiomata. Zeitlin (1942) reported a case of V H L with multiple cavernous haemangiomata in the liver. These lesions were morphologically distinct from the cerebellar haemangioblastoma occurring in the same patient. Capillary haemangioblastomas are uncommon vasoformative lesions most frequently seen in the posterior cranial fossa and though rarely occurring in extraneural axial sites, have not been described previously in the liver or lungs in patients with V H L (Rojiani et al., 1991). The turnout is not known to metastasize to extraneural sites although subarachnoid spread has been reported previously (Mohan et al., 1976). The manifestation of the
MULTIPLE HEPATIC AND PULMONARY HAEMANGIOBLASTOMAS
39
Fig. 5 1990. CT of thorax demonstrating multiple enhancing pulmonary nodules. REFERENCES
Fig. 4 1988. A delayed image from a common hepatic angiogram showing extensive blush involving almost the entire liver and angiographically very similar to the CNS haemangioblastomas previously resected.
liver l e s i o n s o v e r 20 y e a r s f o l l o w i n g t h e first p r e s e n t a t i o n o f c e r e b e l l a r h a e m a n g i o b l a s t o m a m o r e likely r e p r e s e n t s c o i n c i d e n t a l de novo h e p a t i c t u m o u r t h a n m e t a s t a t i c s p r e a d f r o m t h e n e u r a l axis. T h e s u b s e q u e n t d e v e l o p m e n t of multiple pulmonary haemangioblastomas 6 months f o l l o w i n g t h e O L T X is b e l i e v e d t o h a v e b e e n c a u s e d b y inadvertent haematogenous tumour seeding at the time of surgery.
Bird, AV & Mendelow, H (1959). Lindau's disease in a South African family: a report on 3 further cases. British Journal of Surgery, 47, 173 176. Hardwig, P & Robertson, DM (1984). Von Hippel-Lindau disease: a familial, often lethal, multi-system phakomatosis. Ophthahnology, 91,263-270. Melmon, KL & Rosen, SW (1964). Lindau's disease. Review of the literature and study of a large kindred. American Journal of Medicine, 36, 595-617. Mohan, J, Brownell, B & Oppenheimer, DR (1976). Malignant spread of hemangioblastoma: report on two cases. Journal of Neurology, Neurosurgery and Psyehiatry, 39, 515 525. Rojiani, AM, Owen, DA, Berry, K, Woodhurst, B, Anderson, FH, Scudamore, C H e t al. (1991). Hepatic hemangioblastoma: an unusual presentation in a patient with von Hippel-Lindau disease. American Journal of Surgical Pathology, 15, 81 86. Scatarige, JC, Kenny, JM, Fishman, EK, Herlong, FH & Siegelman, SS (1987). CT of giant cavernous hemangioma. American Journal of Roentgenology, 149, 83-85. Zeitlin, H (1942). Hemangioblastomas of the meninges and their relationship to Lindau's disease. Journal c~f Neuropathology and Experimental Neurology, 1, I4-23.
