Original Article
Haemangiopericytoma of the orbit Timothy J Sullivan, FRACO, FRACS, FCOphth* John E Wright, MD, FRCS, FRCOphth" Allan E Wulc, MD* Alec Garner, MD, PhD, FRCPatht Ivan Moseley, MD, FRCP, FRCRS Nik Sathananthan, MRCS, MRCP, FRCRS
5. Significant blush in all three phases of carotid
Abstract Orbital haemangiopericytomas are ideally managed by complete surgical excision in the first instance. This is frequently not achieved, because difficulty in making the diagnosis preoperatively results in incisional biopsy and the highly vascular nature of the tumour makes complete excision difficult. A series of 12 patients with orbital haemangiopericytoma seen over a 23-year period is presented. The following combination of clinical and radiological features is suggestive of haemangiopericytoma. 1. Painless non-axial proptosis with downward displacement of the globe. 2. Intermittent upper lid swelling. 3. A soft, superiorly located mass with poorly defined borders, especially with a blue hue. 4. A superiorly located, rounded or elongated extraconal mass on CT, isodense with brain, with smooth, well-defined borders and moderate to marked enhancement with the injection of intravenous contrast medium.
From the Orbital Clinic* and the Radiology Department,$ Moorfields Eye Hospital, London and the Dtpartment of PathoIogy,t The Institute of OphthalmoIogy, London. Dr Sullivan is now Visiting Consultant Ophthalmologist at The . Royal Children's Hospital, Brisbane, Australia. Dr Wulc is now Assistant Professor of Ophthalmology, OcuIopiastic/OrbitaIService, Scheie Eye Institute, Phiiadelphia, Pennsylvania, USA.
angiography, without prominent arteriovenous shunting. Once haemangiopericytoma is suspected, complete surgical excision is recommended. Key words: Angiography, computed tomography, fibrous histiocytoma, haemangiopericytoma, orbit.
Haemangiopericytoma is an uncommon vascular tumour which rarely involves the orbit. Complete surgical excision of orbital haemangiopericytomas is the ideal management,'-3 but is frequently not achieved because difficulty in making the diagnosis preoperatively results in incisional biopsy and the highly vascular nature of the tumour makes complete excision difficult. Certain clinical and radiological features, when seen in combination, suggest the diagnosis of haemangiopericytoma preoperatively. It is advisable to delineate the arterial supply of the tumour angiographically, so as to plan surgery to facilitate complete excision. Patients and methods The authors retrospectively reviewed the records of all patients with a diagnosis of haemangiopericytoma seen at the Orbital Clinic, Moorfields Eye Hospital, from 1968 to 1991. Twelve patients (five female, seven male) aged from 10 to 69 years
Reprint requests: Dr T J Sullivan, Visiting Consultant Ophthalmologist, The Royal Children's Hospital, Herston Road, Herston, Queensland 4029, Australia. Haernangiopericytorna of the orbit
325
surgery. Adjuvant radiotherapy was used in four patients and chemotherapy in one. The diagnosis was based on standard pathological riter ria.^-"
Figure 1 A patient with a left orbital haemangiopericytoma showing typical upper lid swelling, proptosis and downwards displacement of the globe.
(mean 39 years) presented in this 23-year period. After a detailed clinical history was taken and examination was performed on all patients, investigations included plain radiography of the skull, orbital venography (up to 1974), B-scan ultrasonography, computed tomography (CT) (10 patients), and selective carotid angiography (four patients). Six patients underwent biopsy before definitive
Results A summary of patient data can be found in Table 1. All tumours were unilateral (nine right, three left). Five patients presented with upper lid swelling, variable in degree and nature, resembling episodes of angioneurotic oedema (Figure 1). Four presented with proptosis. None had significant pain, although one presented with a one-year history of dull ache. The duration of symptoms before seeking medical attention ranged from one to 96 months (mean 36 months). Vision was decreased in five patients, four of whom had a relative afferent pupillary defect. Proptosis was present in all patients, ranging from 2 to 16 mm (mean 6 mm) (Figure 2). The eye was displaced downwards in 10 patients, ranging from 1 to 7 mm (mean 3 mm) (Figure 3). A soft, compressible mass, with ill-defined margins, was palpable in nine. The mass was non-tender, non-pulsatile, and did not alter with the Valsalva manoeuvre. Six
Figure 2 A patient with an intraconal right orbital haemangiopericytoma (u)showing proptosis and mild chemosis; (b) six weeks later with increased proptosis and gross chemosis.
Figure 3 A patient with a left orbital haemangiopericytoma (a) showing typical upper lid swelling, inferolateral globe displacement and restriction of ocular ductions; (b) after granulation of lid-sacrificing exenteration. 326
Australian and New Zealand Journal of Ophthalmology 1992; 20(4)
Figure 4 Orbital phlebogram. There is mild, generalised enlargement of the rigk orbit, most evident superolaterally (large arrowheads) and the second segment of the superior ophthalmic vein (small arrowheads) is displaced inferomedially; both abnormalities indicate a superolateral extraconal mass.
were in the upper lid, and three had a blue hue suggesting a vascular tumour. Ocular ductions were reduced in seven patients, with generalised restriction in four, and restricted elevation in three (Figure 3). Mild to moderate optic atrophy was present in two patients, sectorial optic disc swelling in two others, and choroidal folds were seen in another two. Plain films of the orbits were normal in two patients but showed generalised or smooth focal enlargement respectively in two others, without evidence of invasion of the surrounding bone (Figure 4). C T demonstrated the tumour in every patient; two-thirds lay in the upper orbit and only two were within the muscle cone (Figure 5). The haemangiopericytomas were rounded or lobulated, although four, one of which had a more nodular surface, were elongated in the long axis of the orbit; only one tumour was poorly defined. The masses were generally 1 to 2.5 cm in greatest diameter at the time of the C T study, and in five patients enlarged the orbit. C T examinations 14 months apart documented enlargement of one tumour (Figure 6), while another, in a boy aged 10, increased in length from 24 to 33 mm in six weeks (Figure 2). Before intravenous contrast medium the tumours were uniformly isodense with brain. Two showed only minor contrast enhancement, but in all others increase in density was marked. Dynamic CT immediately after injection in one of these showed a rapid rise and fall of CT numbers within the tumour with the first pass of contrast medium (Figure 7), indicating that the contrast enhancement was due largely to intrinsic vascularity. Haemangiopericytorna of the orbit
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Figure 5 CT of one of the intraconal haemangiopericytomas in this series. (a)Axial section, after intravenous contrast medium, showing the homogeneous tumour, slightly denser than brain, between the medially displaced optic nerve (arrows) and the lateral rectus muscle; (b) parasagittal reformatted image shows the superior and inferior rectus muscles (arrowheads) enclosing the mass.
Carotid angiography was abnormal and showed dilatation of the ophthalmic artery in all patients examined, its branches supplying dense tumour vascularity, slightly inhomogeneous in the arterial phase, but becoming more uniform in the venous phase. The superficial temporal and maxillary arteries also contributed in one patient (Figure 8).
Venous drainage was via prominent ophthalmic veins, but an orbital phlebogram in one patient showed merely venous displacement (Figure 4). Six of the 12 tumours were biopsied before definitive surgery; three of the biopsied tumours were later treated by exenteration. One (Case 12) was thought to be a rhabdomyosarcoma (Figure 2) and biopsy suggested a malignant nerve sheath tumour. It progressed, despite adjuvant radiotherapy and chemotherapy, and after exenteration the larger, more representative pathological sections revealed haemangiopericytoma. The other three biopsied tumours were excised, together with the biopsy tract. Cases 2 and 3, seen before the availability of CT, had exploratory lateral and anterior orbitotomies, respectively, as definitive procedures. Macroscopically complete excision was obtained in nine patients; but pathological examination revealed possible microscopic breaches of the tumour capsule in Cases 6 and 7. Complete excision was not possible in the two patients with recurrent disease. In Case 12, extension of tumour through the superior orbital fissure was noted at exenteration. Follow-up ranged from seven months to 16 years (mean five years four months). Two patients had recurrences during follow-up; both had been referred with recurrent tumours. One patient refused exenteration (Case 10) and has been followed for over 16 years, with several episodes of local recurrence, without evidence of systemic spread. The other patient with aggressive local recurrence and intracranial spread (Case 11) has been lost to follow-up.
Figure 6 Rapidly enlarging haemangiopericytoma, same patient as in Figure 3. CT in (a) April 1988 and (b)June 1989, the latter showing displacement and distortion of the globe, and flattening of the medial wall of the orbit. 328
Australian and New Zealand Journal of Ophthalmology 1992; 20(4)
Pathology The tumours were all fairly circumscribed and were found to have a definite, if sometimes tenuous, capsule. They varied in size with maximum diameters between 28 and 39 mm (mean 30.4 mm) in the nine cases in which measurements were recorded. Histological examination revealed a more or less uniform cell type within individual tumours, the cells having round or ovoid nuclei with inconspicuous nucleoli (Figure 9) and cytoplasmic borders which, while usually indistinct, in four instances presented a definite spindle shape. The cells were generally compacted with little intervening stroma, although five tumours included some foci of fibrosis and in three there were scattered myxoid areas. In eight cases sinusoidal, thin-walled vessels were seen coursing throughout the tumour, sometimes exhibiting branching in a characteristic ‘staghorn’ pattern (Figure 10). Smaller capillary channels were present in all 12 tumours. Staining for pericellular reticulin fibres was prominent in 10 cases (Figure l l ) , but in the remaining two cases, such fibres were sparse. Mast cells were observed in five cases. Scattered or small groups of atypical cells with slightly enlarged and hyperchromatic nuclei were a feature of five tumours, albeit in small numbers, and mitotic figure counts ranged from none to seven per 10 highpower fields (10 HPF).
Discussion Stout and Murray first described a subgroup of vascular tumours derived from pericytes and coined the term haemangiopericytoma to distinguish them from glomus tumours, capillary haemangiomas, and other soft-tissue tumours with a highly vascular c ~ m p o n e n t Stout .~ presented three turnours with secondary orbital involvement in his original work^.^-^ Subsequently single and larger seriesl-3.1 7 - 1 9 of primary orbital haemangiopericytomas have been reported. More recently, there have been reports of intraocular and adnexal invol~ement.~~-~~
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Figure 7 Dynamic CT. (a)Region-of-interest marker (2) shows pixels sampled during first passage of contrast medium bolus note dense enhancement of intracranial arteries; (b) curve of Hounsfield units ( C T numbers) against time, showing rapid rise and fall characteristic of a vascular lesion. Haemangiopericytoma of the orbit
329
Most of our patients’ signs and symptoms could be attributed to a mass displacing or compressing tissues. The exception was the occurrence of intermittent lid swelling resembling angioneurotic oedema. Other authors have reported swelling or oedema of the eyelids with haemangiopericyt~ma.’-~,’’ Henderson also described a bluish or reddish discolouration of the ocular adnexae, and we had three patients with a blue hue to the skin overlying their tumours.2 C T characteristics in our series were fairly uniform but non-specific. Tumour blush was seen angiographically, demonstrating the highly vascular nature of the lesion, but high-volume arteriovenous shunts were not seen in any of the lesions; other workers have suggested that the absence of prominent arteriovenous shunts in a known vascular tumour is highly suggestive of haemangiopericytoma.26Importantly, angiography allowed the accurate identification of the arterial supply to the tumour. Currently, clinical and investigative diagnostic criteria do not allow a reliable preoperative diagnosis of orbital haemangiopericytoma and diagnosis depends upon histological confirmation. Henderson stated that ‘clinically, nothing that would suggest a definitive preoperative diagnosis differentiates these lesions from other slow growing vascular neoplasms of the orbit’.2 Indeed, Batsakis, in 1979, pointed out that a pre-histologicaldiagnosis of hemangiopericytoma has never been made.27The diagnosis was correctly made preoperatively in one of our cases. However, we believe that the following combination of clinical and radiological features is suggestive of haemangiopericytoma.
1. Gradual onset of painless non-axial proptosis with downward displacement of the globe. 2. Intermittent upper lid swelling, clinically resembling angioneurotic oedema. 3. A soft superiorly located mass with poorly defined borders, especially with a blue hue. 4. A superiorly located, rounded or elongated extraconal mass on CT, isodense with brain, with smooth, well-defined borders and moderate to marked enhancement with the injection of intravenous contrast medium. 5. Significant blush in all three phases of carotid angiography, without prominent arteriovenous shunting. In patients who present with these clinical and CT features (numbers 1 to 4) an angiogram should be performed. The histological diagnosis of haemangiopericytoma is based on the presence of thin-walled, sinusoidal and branching blood vessels surrounded by cells with round or ovoid nuclei and a frequently plump, spindle morphology. The presence of reticulin fibres between the individual tumour cells is another well-established criterion. The degree of vascularity can vary, however, some lesions presenting a predominately solid appearance, and because there are no specific immunohistochemical markers for pericytes, the diagnosis of haemangiopericytoma is, to some extent, presumptive. Transmission electron microscopy shows that pericytes may have numerous pinocytotic vesicles but even that cannot be regarded as ~pecific.~ The histopathological differential diagnosis includes the
Figure 8 Superselective carotid angiogram, lateral arterial phase digital subtraction images (same patient as Figure 3). (a) Internal carotid artery - a dilated ophthalmic artery (large arrows) feeds a richly vascularised tumour, through which the anteriorly displaced choroidal crescent (small arrows) can be discerned; (b)external carotid artery - supraorbital branches (open arrowheads) of the superficial temporal artery (arrows) feed the upper part of the tumour, less densely opacified than in (a). 330
Australian and N e w Zealand Journal of Ophthalmology 1992; 20(4)
Figure 9 The tumour comprises a compact mass of cell with ill-defined borders and small, ovoid or round nuclei in the presence of a network of branching, thin-walled blood vessels. (Haematoxylin and eosin, original magnification x 185).
Figure 10 Haemangiopericytorna showing characteristic 'staghorn' pattern of vascular branching. (Haematoxylin and eosin, original magnification x 185).
Figure I 1 Solid type of haemangiopericytoma showing a prominent reticulin content with the fibres surrounding individual tumour cells. (Gomori's reticulin stain, original magnificarion x 185). Haernangiopericytorna of the orbit
various types of spindle-cell lesion with, in the context of the orbit, fibrous histiocytoma constituting the most frequent alternative. T h e cells in the latter tumour usually have a rather more obvious spindle shape and tend to be matted or whorled in a storiform pattern. Some tumours show areas suggestive of both haemangiopericytoma and fibrous histiocytoma and Enzinger and Weiss comment that such hybrid forms occur most frequently in the A diagnosis of fibrous histiocytoma was initially considered in two of the present cases. Other tumours which may have similar histologic features include haemangioendothelioma, angiosarcoma, mesenchymal chondrosarcoma, angiomyoma, and angioblastic meningioma. Most haemangiopericytomas are benign, but malignant forms occur and can be difficult to recognise since marked pleomorphism is not a feature. T h e number of mitoses is commonly used to make the distinction on histological grounds, fewer than two to three mitotic figures per 10 HPF being usual in benign tumours and four or more being associated with a predisposition to recurrence and metastasis.28In our series, seven tumours had counts of three or less and five of five or more. Unfortunately the follow-up information does not allow us to evaluate the prognostic value of these counts, except that the two tumours known to have recurred had counts of six and seven respectively. Croxatto and Font in their analysis of 30 cases of orbital haemangiopericytoma with a mean followup of 5.5 years found that, while there was broad agreement between the mitotic figure index and prognosis, a fifth of tumours with one or fewer mitoses per HPF recurred and 7% metasta~ised.'~ Recurrence is not necessarily indicative of malignancy; recurrence of an ostensibly benign orbital haemangiopericytoma has been reported 22 years after initial excision.L6 Definitive surgery should be directed at complete surgical removal with a wide resection clear of tumour. T h e tumour should be approached so as to allow early identification and ligation of the main arterial supply (as determined by angiography) before its dissection from surrounding structures. Where an incisional biopsy has been performed, wide local excision with excision of the biopsy tract or exenteration should be carried out. Exenteration should be considered for more posteriorly located lesions and when biopsy may have caused seeding of tumour cells into the orbit. Our experience confirms that of Sear1 and Ni, who found that recurrences tend to be infiltrative 331
rather than well-circumscribed.3 T o achieve tumour clearance we believe recurrences should be treated by exenteration, or craniofacial resection. While there are reports of successful treatment with radiotherapy or chemotherapy in haemangiopericytoma elsewhere, these modalities have not been established in the ~ r b i t . ~ . ~ It, ' would ~ , ~ ~seem ,~~ reasonable to reserve adjuvant radiotherapy and chemotherapy for cases in which there is doubt about the completeness of excision, where the tumour has recurred, or for palliation. Acknowledgements D r Sullivan's work is supported in part by the RACO/OPSM fellowship. T h e authors would like to thank M r G E Rose for reviewing the manuscript. References 1. Jakobiec FA, Howard GM, Jones IS, Wolff M. Hemangiopericytoma of the orbit. Am J Ophthalmol 1974;78:8 16-34. 2. Henderson JW, Farrow GM. Primary orbital hemangiopericytoma. Arch Ophthalmol 1978;96:666-73. 3. Sear1 SS, Ni C. Hemangiopericytoma. Int Ophthalmol Clin 1982;22: 141-62. 4. Stout AP, Murray MR. Hemangiopericytoma. A vascular tumor featuring Zimmerman's pericytes. Ann Surg 1942;116:26-33. 5. Stout AP. Hemangiopericytoma. A study of twenty-five new cases. Cancer 1949;2:1027-35. 6. Ramsey HJ. Fine structure of hemangiopericytoma and hemangio-endothelioma. Cancer 1966;19:2005-18. 7. Murad TM, vonHaam E. Ultrastructure of a hemangiopericytoma and a glomus tumour. Cancer 1968;22: 1239-49. 8. Kuhn C 111, Rosai J. Tumors arising from pericytes. Ultrastructure and organ culture of a case. Arch Path 1969;88:653-63. 9. Battifora H . Hemangiopericytoma; ultrastructural study of five cases. Cancer 1973;31: 1418-32. 10. Enzinger FM, Smith BH. Hemangiopericytoma. An analysis of 106 'cases. Hum Path 1976;7:61-82. 11. Dardick I, Hammar SP, Scheithauer BW. Ultrastructural spectrum of hemangiopericytoma: a comparative study of
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fetal, adult, and neoplastic pericytes. Ultrastruct Pathol 1988;13:111-54. 12. Goodman SA. Hemangiopericytoma of the orbit. Am J Ophthalmol 1955;40:237-43. 13. Fox SA. Hemangiopericytoma ofthe orbit. Am J Ophthalmol 1955;40:786-9. 4. Haney RF. Hemangiopericytoma of the orbit. Arch Ophthalmol 1964;71:206-8. 5. Macoul KL. Hemangiopericytoma ofthe lid and orbit. Am J Ophthalmol 1968;66:731-3. 6. Panda A, Dayel Y, Singhal V, Pattnaik NV. Haemangiopericytoma. Br J Ophthalmol 1984;68: 124-7. 17. Brown DN, MacCarty CS, Soule E. Orbital hemangiopericytoma. Review of the literature and report of four cases. J. Neurosurg 1965;22:354-61. 18. Henderson JW. Orbital tumors. Philadelphia: WB Saunders, 1973:151-7. 19. Croxatto JO, Font RL. Hemangiopericytoma of the orbit: a clinicopathologic study of 30 cases. Hum Pathol 1982; 13:210-18. 20. Gurney N, Chalkley T, O'Grady R. Lacrimal sac hemangiopericytoma. Am J Ophthalmol 1971;71:757-9. 21. Ni C, D'Amico DJ, Fan CQ, Kuo PK. Tumours of the lacrimal sac: a clinicopathological analysis of 82 cases. Int Ophthalmol Clin 1982;22: 121-40. 22. Carnevali L, Trimarchi F, Ross0 R, Stringa M. Haemangiopericytoma of the lacrimal sac: a case report. Br J Ophthalmol 1988;72:782-5. 23. Grossniklaus HE, Green WR, Wolff SM, Iliff NT. Hemangiopericytoma of the conjunctiva. Ophthalmology 1986;93:265-7. 24. Brown HH, Brodsky MC, Hembree K. Mrak RE. Supraciliary hemangiopericytoma. Ophthalmology 1991;98:378-82. 25. Roth SI, August CZ, Lissner GS, OGrady RB. Hemangiopericytoma of the lacrimal sac. Ophthalmology 1991:98:925-7. 26. Angervall L, Kindblom LG, Neilsen JM, Stener B. Hemangiopericytoma. Cancer 1980;42:2412. 27. Batsakis JG. Vasoformative tumors. In: Tumours of the head and neck. Baltimore: Williams & Wilkins, 1979;227-9. 28. Enzinger FM, Weiss SW. Soft tissue tumours. 2nd ed. St Louis: CV Mosby, 1988:596-613. 29. Mira HG, Chu FCH, Fortner JG. The role of radiotherapy in the management of malignant haemangiopericytoma. Cancer 1977;39:1254-9. 30. Wong PP, Yagoda A. Chemotherapy of malignant hemangiopericytoma. Cancer 1978;41:1256-60,
Australian and New Zealand Journal of Ophthalmology 1992; 20(4)
Haemangiopericytoma of the orbit Timothy J Sullivan, FRACO, FRACS, FCOphth* John E Wright, MD, FRCS, FRCOphth" Allan E Wulc, MD* Alec Garner, MD, PhD, FRCPatht Ivan Moseley, MD, FRCP, FRCRS Nik Sathananthan, MRCS, MRCP, FRCRS
5. Significant blush in all three phases of carotid
Abstract Orbital haemangiopericytomas are ideally managed by complete surgical excision in the first instance. This is frequently not achieved, because difficulty in making the diagnosis preoperatively results in incisional biopsy and the highly vascular nature of the tumour makes complete excision difficult. A series of 12 patients with orbital haemangiopericytoma seen over a 23-year period is presented. The following combination of clinical and radiological features is suggestive of haemangiopericytoma. 1. Painless non-axial proptosis with downward displacement of the globe. 2. Intermittent upper lid swelling. 3. A soft, superiorly located mass with poorly defined borders, especially with a blue hue. 4. A superiorly located, rounded or elongated extraconal mass on CT, isodense with brain, with smooth, well-defined borders and moderate to marked enhancement with the injection of intravenous contrast medium.
From the Orbital Clinic* and the Radiology Department,$ Moorfields Eye Hospital, London and the Dtpartment of PathoIogy,t The Institute of OphthalmoIogy, London. Dr Sullivan is now Visiting Consultant Ophthalmologist at The . Royal Children's Hospital, Brisbane, Australia. Dr Wulc is now Assistant Professor of Ophthalmology, OcuIopiastic/OrbitaIService, Scheie Eye Institute, Phiiadelphia, Pennsylvania, USA.
angiography, without prominent arteriovenous shunting. Once haemangiopericytoma is suspected, complete surgical excision is recommended. Key words: Angiography, computed tomography, fibrous histiocytoma, haemangiopericytoma, orbit.
Haemangiopericytoma is an uncommon vascular tumour which rarely involves the orbit. Complete surgical excision of orbital haemangiopericytomas is the ideal management,'-3 but is frequently not achieved because difficulty in making the diagnosis preoperatively results in incisional biopsy and the highly vascular nature of the tumour makes complete excision difficult. Certain clinical and radiological features, when seen in combination, suggest the diagnosis of haemangiopericytoma preoperatively. It is advisable to delineate the arterial supply of the tumour angiographically, so as to plan surgery to facilitate complete excision. Patients and methods The authors retrospectively reviewed the records of all patients with a diagnosis of haemangiopericytoma seen at the Orbital Clinic, Moorfields Eye Hospital, from 1968 to 1991. Twelve patients (five female, seven male) aged from 10 to 69 years
Reprint requests: Dr T J Sullivan, Visiting Consultant Ophthalmologist, The Royal Children's Hospital, Herston Road, Herston, Queensland 4029, Australia. Haernangiopericytorna of the orbit
325
surgery. Adjuvant radiotherapy was used in four patients and chemotherapy in one. The diagnosis was based on standard pathological riter ria.^-"
Figure 1 A patient with a left orbital haemangiopericytoma showing typical upper lid swelling, proptosis and downwards displacement of the globe.
(mean 39 years) presented in this 23-year period. After a detailed clinical history was taken and examination was performed on all patients, investigations included plain radiography of the skull, orbital venography (up to 1974), B-scan ultrasonography, computed tomography (CT) (10 patients), and selective carotid angiography (four patients). Six patients underwent biopsy before definitive
Results A summary of patient data can be found in Table 1. All tumours were unilateral (nine right, three left). Five patients presented with upper lid swelling, variable in degree and nature, resembling episodes of angioneurotic oedema (Figure 1). Four presented with proptosis. None had significant pain, although one presented with a one-year history of dull ache. The duration of symptoms before seeking medical attention ranged from one to 96 months (mean 36 months). Vision was decreased in five patients, four of whom had a relative afferent pupillary defect. Proptosis was present in all patients, ranging from 2 to 16 mm (mean 6 mm) (Figure 2). The eye was displaced downwards in 10 patients, ranging from 1 to 7 mm (mean 3 mm) (Figure 3). A soft, compressible mass, with ill-defined margins, was palpable in nine. The mass was non-tender, non-pulsatile, and did not alter with the Valsalva manoeuvre. Six
Figure 2 A patient with an intraconal right orbital haemangiopericytoma (u)showing proptosis and mild chemosis; (b) six weeks later with increased proptosis and gross chemosis.
Figure 3 A patient with a left orbital haemangiopericytoma (a) showing typical upper lid swelling, inferolateral globe displacement and restriction of ocular ductions; (b) after granulation of lid-sacrificing exenteration. 326
Australian and New Zealand Journal of Ophthalmology 1992; 20(4)
Figure 4 Orbital phlebogram. There is mild, generalised enlargement of the rigk orbit, most evident superolaterally (large arrowheads) and the second segment of the superior ophthalmic vein (small arrowheads) is displaced inferomedially; both abnormalities indicate a superolateral extraconal mass.
were in the upper lid, and three had a blue hue suggesting a vascular tumour. Ocular ductions were reduced in seven patients, with generalised restriction in four, and restricted elevation in three (Figure 3). Mild to moderate optic atrophy was present in two patients, sectorial optic disc swelling in two others, and choroidal folds were seen in another two. Plain films of the orbits were normal in two patients but showed generalised or smooth focal enlargement respectively in two others, without evidence of invasion of the surrounding bone (Figure 4). C T demonstrated the tumour in every patient; two-thirds lay in the upper orbit and only two were within the muscle cone (Figure 5). The haemangiopericytomas were rounded or lobulated, although four, one of which had a more nodular surface, were elongated in the long axis of the orbit; only one tumour was poorly defined. The masses were generally 1 to 2.5 cm in greatest diameter at the time of the C T study, and in five patients enlarged the orbit. C T examinations 14 months apart documented enlargement of one tumour (Figure 6), while another, in a boy aged 10, increased in length from 24 to 33 mm in six weeks (Figure 2). Before intravenous contrast medium the tumours were uniformly isodense with brain. Two showed only minor contrast enhancement, but in all others increase in density was marked. Dynamic CT immediately after injection in one of these showed a rapid rise and fall of CT numbers within the tumour with the first pass of contrast medium (Figure 7), indicating that the contrast enhancement was due largely to intrinsic vascularity. Haemangiopericytorna of the orbit
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Figure 5 CT of one of the intraconal haemangiopericytomas in this series. (a)Axial section, after intravenous contrast medium, showing the homogeneous tumour, slightly denser than brain, between the medially displaced optic nerve (arrows) and the lateral rectus muscle; (b) parasagittal reformatted image shows the superior and inferior rectus muscles (arrowheads) enclosing the mass.
Carotid angiography was abnormal and showed dilatation of the ophthalmic artery in all patients examined, its branches supplying dense tumour vascularity, slightly inhomogeneous in the arterial phase, but becoming more uniform in the venous phase. The superficial temporal and maxillary arteries also contributed in one patient (Figure 8).
Venous drainage was via prominent ophthalmic veins, but an orbital phlebogram in one patient showed merely venous displacement (Figure 4). Six of the 12 tumours were biopsied before definitive surgery; three of the biopsied tumours were later treated by exenteration. One (Case 12) was thought to be a rhabdomyosarcoma (Figure 2) and biopsy suggested a malignant nerve sheath tumour. It progressed, despite adjuvant radiotherapy and chemotherapy, and after exenteration the larger, more representative pathological sections revealed haemangiopericytoma. The other three biopsied tumours were excised, together with the biopsy tract. Cases 2 and 3, seen before the availability of CT, had exploratory lateral and anterior orbitotomies, respectively, as definitive procedures. Macroscopically complete excision was obtained in nine patients; but pathological examination revealed possible microscopic breaches of the tumour capsule in Cases 6 and 7. Complete excision was not possible in the two patients with recurrent disease. In Case 12, extension of tumour through the superior orbital fissure was noted at exenteration. Follow-up ranged from seven months to 16 years (mean five years four months). Two patients had recurrences during follow-up; both had been referred with recurrent tumours. One patient refused exenteration (Case 10) and has been followed for over 16 years, with several episodes of local recurrence, without evidence of systemic spread. The other patient with aggressive local recurrence and intracranial spread (Case 11) has been lost to follow-up.
Figure 6 Rapidly enlarging haemangiopericytoma, same patient as in Figure 3. CT in (a) April 1988 and (b)June 1989, the latter showing displacement and distortion of the globe, and flattening of the medial wall of the orbit. 328
Australian and New Zealand Journal of Ophthalmology 1992; 20(4)
Pathology The tumours were all fairly circumscribed and were found to have a definite, if sometimes tenuous, capsule. They varied in size with maximum diameters between 28 and 39 mm (mean 30.4 mm) in the nine cases in which measurements were recorded. Histological examination revealed a more or less uniform cell type within individual tumours, the cells having round or ovoid nuclei with inconspicuous nucleoli (Figure 9) and cytoplasmic borders which, while usually indistinct, in four instances presented a definite spindle shape. The cells were generally compacted with little intervening stroma, although five tumours included some foci of fibrosis and in three there were scattered myxoid areas. In eight cases sinusoidal, thin-walled vessels were seen coursing throughout the tumour, sometimes exhibiting branching in a characteristic ‘staghorn’ pattern (Figure 10). Smaller capillary channels were present in all 12 tumours. Staining for pericellular reticulin fibres was prominent in 10 cases (Figure l l ) , but in the remaining two cases, such fibres were sparse. Mast cells were observed in five cases. Scattered or small groups of atypical cells with slightly enlarged and hyperchromatic nuclei were a feature of five tumours, albeit in small numbers, and mitotic figure counts ranged from none to seven per 10 highpower fields (10 HPF).
Discussion Stout and Murray first described a subgroup of vascular tumours derived from pericytes and coined the term haemangiopericytoma to distinguish them from glomus tumours, capillary haemangiomas, and other soft-tissue tumours with a highly vascular c ~ m p o n e n t Stout .~ presented three turnours with secondary orbital involvement in his original work^.^-^ Subsequently single and larger seriesl-3.1 7 - 1 9 of primary orbital haemangiopericytomas have been reported. More recently, there have been reports of intraocular and adnexal invol~ement.~~-~~
0 b
2
4
6
8
10
M I NUTES
Figure 7 Dynamic CT. (a)Region-of-interest marker (2) shows pixels sampled during first passage of contrast medium bolus note dense enhancement of intracranial arteries; (b) curve of Hounsfield units ( C T numbers) against time, showing rapid rise and fall characteristic of a vascular lesion. Haemangiopericytoma of the orbit
329
Most of our patients’ signs and symptoms could be attributed to a mass displacing or compressing tissues. The exception was the occurrence of intermittent lid swelling resembling angioneurotic oedema. Other authors have reported swelling or oedema of the eyelids with haemangiopericyt~ma.’-~,’’ Henderson also described a bluish or reddish discolouration of the ocular adnexae, and we had three patients with a blue hue to the skin overlying their tumours.2 C T characteristics in our series were fairly uniform but non-specific. Tumour blush was seen angiographically, demonstrating the highly vascular nature of the lesion, but high-volume arteriovenous shunts were not seen in any of the lesions; other workers have suggested that the absence of prominent arteriovenous shunts in a known vascular tumour is highly suggestive of haemangiopericytoma.26Importantly, angiography allowed the accurate identification of the arterial supply to the tumour. Currently, clinical and investigative diagnostic criteria do not allow a reliable preoperative diagnosis of orbital haemangiopericytoma and diagnosis depends upon histological confirmation. Henderson stated that ‘clinically, nothing that would suggest a definitive preoperative diagnosis differentiates these lesions from other slow growing vascular neoplasms of the orbit’.2 Indeed, Batsakis, in 1979, pointed out that a pre-histologicaldiagnosis of hemangiopericytoma has never been made.27The diagnosis was correctly made preoperatively in one of our cases. However, we believe that the following combination of clinical and radiological features is suggestive of haemangiopericytoma.
1. Gradual onset of painless non-axial proptosis with downward displacement of the globe. 2. Intermittent upper lid swelling, clinically resembling angioneurotic oedema. 3. A soft superiorly located mass with poorly defined borders, especially with a blue hue. 4. A superiorly located, rounded or elongated extraconal mass on CT, isodense with brain, with smooth, well-defined borders and moderate to marked enhancement with the injection of intravenous contrast medium. 5. Significant blush in all three phases of carotid angiography, without prominent arteriovenous shunting. In patients who present with these clinical and CT features (numbers 1 to 4) an angiogram should be performed. The histological diagnosis of haemangiopericytoma is based on the presence of thin-walled, sinusoidal and branching blood vessels surrounded by cells with round or ovoid nuclei and a frequently plump, spindle morphology. The presence of reticulin fibres between the individual tumour cells is another well-established criterion. The degree of vascularity can vary, however, some lesions presenting a predominately solid appearance, and because there are no specific immunohistochemical markers for pericytes, the diagnosis of haemangiopericytoma is, to some extent, presumptive. Transmission electron microscopy shows that pericytes may have numerous pinocytotic vesicles but even that cannot be regarded as ~pecific.~ The histopathological differential diagnosis includes the
Figure 8 Superselective carotid angiogram, lateral arterial phase digital subtraction images (same patient as Figure 3). (a) Internal carotid artery - a dilated ophthalmic artery (large arrows) feeds a richly vascularised tumour, through which the anteriorly displaced choroidal crescent (small arrows) can be discerned; (b)external carotid artery - supraorbital branches (open arrowheads) of the superficial temporal artery (arrows) feed the upper part of the tumour, less densely opacified than in (a). 330
Australian and N e w Zealand Journal of Ophthalmology 1992; 20(4)
Figure 9 The tumour comprises a compact mass of cell with ill-defined borders and small, ovoid or round nuclei in the presence of a network of branching, thin-walled blood vessels. (Haematoxylin and eosin, original magnification x 185).
Figure 10 Haemangiopericytorna showing characteristic 'staghorn' pattern of vascular branching. (Haematoxylin and eosin, original magnification x 185).
Figure I 1 Solid type of haemangiopericytoma showing a prominent reticulin content with the fibres surrounding individual tumour cells. (Gomori's reticulin stain, original magnificarion x 185). Haernangiopericytorna of the orbit
various types of spindle-cell lesion with, in the context of the orbit, fibrous histiocytoma constituting the most frequent alternative. T h e cells in the latter tumour usually have a rather more obvious spindle shape and tend to be matted or whorled in a storiform pattern. Some tumours show areas suggestive of both haemangiopericytoma and fibrous histiocytoma and Enzinger and Weiss comment that such hybrid forms occur most frequently in the A diagnosis of fibrous histiocytoma was initially considered in two of the present cases. Other tumours which may have similar histologic features include haemangioendothelioma, angiosarcoma, mesenchymal chondrosarcoma, angiomyoma, and angioblastic meningioma. Most haemangiopericytomas are benign, but malignant forms occur and can be difficult to recognise since marked pleomorphism is not a feature. T h e number of mitoses is commonly used to make the distinction on histological grounds, fewer than two to three mitotic figures per 10 HPF being usual in benign tumours and four or more being associated with a predisposition to recurrence and metastasis.28In our series, seven tumours had counts of three or less and five of five or more. Unfortunately the follow-up information does not allow us to evaluate the prognostic value of these counts, except that the two tumours known to have recurred had counts of six and seven respectively. Croxatto and Font in their analysis of 30 cases of orbital haemangiopericytoma with a mean followup of 5.5 years found that, while there was broad agreement between the mitotic figure index and prognosis, a fifth of tumours with one or fewer mitoses per HPF recurred and 7% metasta~ised.'~ Recurrence is not necessarily indicative of malignancy; recurrence of an ostensibly benign orbital haemangiopericytoma has been reported 22 years after initial excision.L6 Definitive surgery should be directed at complete surgical removal with a wide resection clear of tumour. T h e tumour should be approached so as to allow early identification and ligation of the main arterial supply (as determined by angiography) before its dissection from surrounding structures. Where an incisional biopsy has been performed, wide local excision with excision of the biopsy tract or exenteration should be carried out. Exenteration should be considered for more posteriorly located lesions and when biopsy may have caused seeding of tumour cells into the orbit. Our experience confirms that of Sear1 and Ni, who found that recurrences tend to be infiltrative 331
rather than well-circumscribed.3 T o achieve tumour clearance we believe recurrences should be treated by exenteration, or craniofacial resection. While there are reports of successful treatment with radiotherapy or chemotherapy in haemangiopericytoma elsewhere, these modalities have not been established in the ~ r b i t . ~ . ~ It, ' would ~ , ~ ~seem ,~~ reasonable to reserve adjuvant radiotherapy and chemotherapy for cases in which there is doubt about the completeness of excision, where the tumour has recurred, or for palliation. Acknowledgements D r Sullivan's work is supported in part by the RACO/OPSM fellowship. T h e authors would like to thank M r G E Rose for reviewing the manuscript. References 1. Jakobiec FA, Howard GM, Jones IS, Wolff M. Hemangiopericytoma of the orbit. Am J Ophthalmol 1974;78:8 16-34. 2. Henderson JW, Farrow GM. Primary orbital hemangiopericytoma. Arch Ophthalmol 1978;96:666-73. 3. Sear1 SS, Ni C. Hemangiopericytoma. Int Ophthalmol Clin 1982;22: 141-62. 4. Stout AP, Murray MR. Hemangiopericytoma. A vascular tumor featuring Zimmerman's pericytes. Ann Surg 1942;116:26-33. 5. Stout AP. Hemangiopericytoma. A study of twenty-five new cases. Cancer 1949;2:1027-35. 6. Ramsey HJ. Fine structure of hemangiopericytoma and hemangio-endothelioma. Cancer 1966;19:2005-18. 7. Murad TM, vonHaam E. Ultrastructure of a hemangiopericytoma and a glomus tumour. Cancer 1968;22: 1239-49. 8. Kuhn C 111, Rosai J. Tumors arising from pericytes. Ultrastructure and organ culture of a case. Arch Path 1969;88:653-63. 9. Battifora H . Hemangiopericytoma; ultrastructural study of five cases. Cancer 1973;31: 1418-32. 10. Enzinger FM, Smith BH. Hemangiopericytoma. An analysis of 106 'cases. Hum Path 1976;7:61-82. 11. Dardick I, Hammar SP, Scheithauer BW. Ultrastructural spectrum of hemangiopericytoma: a comparative study of
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fetal, adult, and neoplastic pericytes. Ultrastruct Pathol 1988;13:111-54. 12. Goodman SA. Hemangiopericytoma of the orbit. Am J Ophthalmol 1955;40:237-43. 13. Fox SA. Hemangiopericytoma ofthe orbit. Am J Ophthalmol 1955;40:786-9. 4. Haney RF. Hemangiopericytoma of the orbit. Arch Ophthalmol 1964;71:206-8. 5. Macoul KL. Hemangiopericytoma ofthe lid and orbit. Am J Ophthalmol 1968;66:731-3. 6. Panda A, Dayel Y, Singhal V, Pattnaik NV. Haemangiopericytoma. Br J Ophthalmol 1984;68: 124-7. 17. Brown DN, MacCarty CS, Soule E. Orbital hemangiopericytoma. Review of the literature and report of four cases. J. Neurosurg 1965;22:354-61. 18. Henderson JW. Orbital tumors. Philadelphia: WB Saunders, 1973:151-7. 19. Croxatto JO, Font RL. Hemangiopericytoma of the orbit: a clinicopathologic study of 30 cases. Hum Pathol 1982; 13:210-18. 20. Gurney N, Chalkley T, O'Grady R. Lacrimal sac hemangiopericytoma. Am J Ophthalmol 1971;71:757-9. 21. Ni C, D'Amico DJ, Fan CQ, Kuo PK. Tumours of the lacrimal sac: a clinicopathological analysis of 82 cases. Int Ophthalmol Clin 1982;22: 121-40. 22. Carnevali L, Trimarchi F, Ross0 R, Stringa M. Haemangiopericytoma of the lacrimal sac: a case report. Br J Ophthalmol 1988;72:782-5. 23. Grossniklaus HE, Green WR, Wolff SM, Iliff NT. Hemangiopericytoma of the conjunctiva. Ophthalmology 1986;93:265-7. 24. Brown HH, Brodsky MC, Hembree K. Mrak RE. Supraciliary hemangiopericytoma. Ophthalmology 1991;98:378-82. 25. Roth SI, August CZ, Lissner GS, OGrady RB. Hemangiopericytoma of the lacrimal sac. Ophthalmology 1991:98:925-7. 26. Angervall L, Kindblom LG, Neilsen JM, Stener B. Hemangiopericytoma. Cancer 1980;42:2412. 27. Batsakis JG. Vasoformative tumors. In: Tumours of the head and neck. Baltimore: Williams & Wilkins, 1979;227-9. 28. Enzinger FM, Weiss SW. Soft tissue tumours. 2nd ed. St Louis: CV Mosby, 1988:596-613. 29. Mira HG, Chu FCH, Fortner JG. The role of radiotherapy in the management of malignant haemangiopericytoma. Cancer 1977;39:1254-9. 30. Wong PP, Yagoda A. Chemotherapy of malignant hemangiopericytoma. Cancer 1978;41:1256-60,
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