Orbitofrontal Cholesterol Granuloma ALAN A. McNAB, FRACO, JOHN E. WRIGHT, MD, FRCS
Abstract: Cholesterol granuloma of the orbital bones is a rare but readily recognizable clinical and radiologic entity usually affecting men. Twenty-seven patients are reported, and in all except one, the frontal bone in the region of the lacrimal fossa was involved. These lesions produced an area of osteolysis in the frontal bone with expansion into the extraperiosteal space of the lacrimal fossa, causing fullness of the upper lid and proptosis. The granuloma always remained extraperiosteal and was composed of a granulomatous reaction surrounding cholesterol crystals and altered blood. It is postulated that cholesterol granuloma occurs because of hemorrhage into the diploe of the bone. Extraperiosteal surgical removal cured all patients. Some previous reports have failed to identify the true nature of this lesion and confused its nomenclature.
Ophthalmology 1990; 97:28-32
Cholesterol granuloma of the orbital bones is a rare condition which usually occurs in the frontal bone above the lacrimal fossa. A review of the literature found 42 previously reported cases, 1-24 the first being that ofDenigl in 1902 who reported a "subperiosteal blood cyst" with erosion of bone into the anterior cranial fossa. This report details the findings in 27 new cases.
PATIENTS AND METHODS The records of 27 patients with cholesterol granuloma of the orbit were reviewed. The patients presented to the Orbital Clinic at Moorfields Eye Hospital between 1967 and 1988. All except one were confirmed histopathologically. A detailed history was obtained and a complete ophthalmic examination was performed. Plain radiographs of the skull were obtained in each case and since 1974 the majority has had computed tomographic scans (CT) done. One patient was examined with magnetic resonance imaging (MRI).
Originally received: July 17, 1989. Revision accepted: August 15, 1989. From the Orbital Clinic, Moorfields Eye Hospital, London. Supported by the Royal Australian College of Ophthalmologists-OPSM Travelling Fellowship (Dr. McNab). Reprint requests to John E. Wright, MD, Moorfields Eye Hospital, City Rd, London, EC1V 2PD, England.
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The surgical approach in 21 patients was through a lateral brow incision occasionally extended to the zygomatic arch. Two patients had a lateral orbitotomy, two had an anterior craniotomy, and one was approached through the temporal fossa after raising a scalp flap.
RESULTS Of the 27 patients, 3 were women. At presentation, they ranged in age from 25 to 68 years (median, 43 years; mean, 43.7 years). Almost two thirds 16 of the cases occurred between 35 and 55 years of age. The right and left orbits were similarly affected in 13 and 14 cases, respectively. Symptoms had been present between 1 week and 9 years (median, 8 months; mean 1.1 years). The most common symptom was proptosis which was noted in 15 patients (although 26 patients had measurable proptosis). Ten patients complained of blurred vision and nine experienced a mild dull ache in the brow. Ten patients noticed swelling or drooping of the upper eyelid, and nine complained of double vision, particularly looking upward. Six patients gave a definite history of blunt trauma to the area from 2 years to 1 month before the onset of symptoms. Four patients had been punched, one was headbutted, and the trunk of a Christmas tree jabbed one patient in the eye. The eldest patient, 68 years of age, was known to have hypercholesterolemia and peripheral vascular disease. He gave no history of trauma. Best-corrected visual acuity was 6/6 or better in 15 patients, 6/9 in 3, 6/12 in 7, and 6/18 in 2. Those patients with reduced vision had an acquired astigmatism, cho-
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Fig 1. Plain radiograph of a right orbitofrontal cholesterol granuloma. The osteolysis extends almost to the fronto-zygomatic suture (large arrow). There is a well-defined edge without sclerosis (small arrows). Fig 3. Coronal magnetic resonance image (Tt-weighted). A mass with high-signal intensity in the superotemporal quadrant of the orbit has eroded through both the inner and outer tables of the frontal bone. Notice the large extradural component displacing the frontal lobe of the brain (arrows).
Fig 2. Coronal computed tomographic scan with contrast shows a cholesterol granuloma (isodense with brain) which has eroded the roof of the orbit and is compressing the globe. The intact periosteum is arrowed.
roidal folds, or both. Proptosis was present in 26 patients and ranged from 2 to 8 mm (median, 4 mm; mean, 4.1 mm). The globe was displaced downward in 22 cases with medial displacement in 8 of these. The patient with a lesion in the zygoma had upward and medial displacement of the globe. Eighteen patients had a smooth nontender mass in the upper temporal quadrant. It was usually firm or hard but occasionally felt soft and fluctuant. In some patients, there was appreciable bossing of the frontal bone over the lesion. In two patients, there was a palpable defect in the orbital rim. Ocular motility was abnormal in 23 patients, all of whom had restricted elevation and eight mildly limited abduction as well. The maximal restriction was always in the direction of the mass (i.e., usually elevation in ab-
duction). A ptosis of 2 to 3 mm was present in seven patients. Choroidal folds were seen in 13 patients and this was occasionally associated with significant indentation of the globe. Plain radiographs normally showed a characteristic osteolytic lesion with rounded edges in the region of the lacrimal fossa (Fig 1). There was never any sclerosis of the frontal bone. In the 22 patients in whom the plain xrays were still available for review, the osteolytic process extended into the zygomatic process of the frontal bone in 16 and as far as the fronto-zygomatic suture in 10. Computed tomographic scans were performed in 19 cases and showed a mass in the superotemporal quadrant of the orbit. The attenuation values were not sufficiently characteristic to differentiate the lesion from many other lacrimal fossa lesions, being isodense with the brain. The mass appeared homogeneous with erosion and expansion of the surrounding bone. The edge of the eroded bone was occasionally irregular (Fig 2). In all cases, there was partial or complete loss of the outer table of the bone allowing the lesi~n to expand extraperiosteally into the orbit. In nine cases, there was erosion of the inner table of the skull with exposure of the dura mater and extension of the mass into the extradural space (Fig 3). This was confirmed at surgery in each patient and also in two others who had not had CT or MRI scans performed. Three cases showed erosion into the most lateral part of the frontal sinus and two had eroded into the temporal fossa behind the orbital rim. In several cases, isolated fragments of bone lay within the lesion (Fig 2). Magnetic resonance imaging was performed in one case and clearly demonstrated both orbital and intracranial extension (Fig 3). The contents of the lesion had a high-signal intensity on
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Fig 4. Ph~tomicrograph of the wall of a cholesterol granuloma. There are numerous cholesterol crystals within a chronic inflammatory infiltrate with scattered giant cells (hematoxylineosin; original magnification, XJSO).
both T[- and Tz-weighted images. In addition, the inversion recovery sequence gave a high-signal intensity. In 17 cases, the diagnosis was confidently made before surgery on the basis of clinical and particularly plain xray features. In nine cases, the diagnosis was considered to be more likely a dermoid or lacrimal tumor. Most of these errors were made early in the series, with four of the first five cases being incorrectly diagnosed preoperatively. The mass was usually approached by a lateral brow incision down to periosteum at the orbital margin. The periosteum was reflected from the anterior surface of the frontal bone to the orbital margin. The underlying bone was usually thin and discolored by the contents of the lesion, giving the bone a yellowish-blue appearance. The orbital rim was often sharp and irregular where it was eroded. As soon as the dissection of the orbital periosteum from the roof was commenced, the lower surface of the granuloma was encountered in the extraperiosteal space. This part of the dissection was usually accompanied by the release of yellowish-brown fluid containing aggregates of more solid yellow material. The contents could be aspirated quite easily but granulomatous material was invariably adherent to the bone and orbital periosteum and required careful dissection for its removal. If dura mater was exposed, then great care was required to avoid creating a breach in this structure with subsequent cerebral spinal fluid leakage. Active bleeding from small vessels in the bone was often seen, but was easily stopped with bone wax. The wound was closed in layers and a drain inserted into the cavity or the subcutaneous tissues and left for 24 hours. The one patient who was not operated on was a 27year-old man who had had multiple blows to the head sustained' both on and off the rugby field. He presented with a periorbital hematoma, and a plain skull x-ray 30
showed a small but typical osteolytic lesion in the frontal bone. There were no ocular symptoms or signs, and he is being observed. Histopathologic examination findings of the contents and lining of the lesion showed a consistent and characteristic appearance (Fig 4). The fluid consisted of altered blood with scattered giant cells, histiocytes laden with hemosiderin or cholesterol, and other inflammatory cells. Solid elements showed cholesterol clefts surrounded by a granulomatous reaction with foreign-body giant cells. Lipid laden macrophages and hemosiderin both extracellularly and within histiocytes were seen with a variable amount of fibrosis in the wall of the lesion and occasionally fragments of bone. In no case was there any suggestion of epithelial elements or keratin. All patients improved as a result of their surgery with loss of proptosis, ptosis, swelling, and diplopia. The followup period varied from 3 months to 10 years. There were no recurrences. One patient complained of bifrontal headache 2 years after surgery. Plain x-ray showed remodeling of the bone to an almost normal appearance and no evidence of recurrence.
DISCUSSION Cholesterol granuloma is a rare but readily recognizable lesion with characteristic radiologic, histopathologic, and clinical features. The latter are caused by the extraperiosteal orbital component ofthe mass. The lesion commences within the diploe of the frontal bone, enlarging so that eventually the outer table of the bone is breached and the contents are spread into the extraperiosteal space above the lacrimal fossa. Occasionally, there is an associated erosion of the inner table of the bone with extradural spread of the granuloma into the anterior cranial fossa ;
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this rarely causes symptoms. It is the extraperiosteal mass in the upper part of the orbit which causes the symptoms of fullness of the upper lid, downward displacement of the globe and proptosis. These patients therefore consult ophthalmologists who should be aware of this entity and its straightforward surgical management. A variety of names has been used to describe these lesions, including cholesteatoma,2,8-1O,14,19 lipid granuloma of the frontal bone,15,18 xanthomatosis of the orbit,4 hematoma, II and chronic hematic cystY- Z4 However, cholesterol granuloma is a better term because the osteolytic lesion contains a granulomatous reaction surrounding cholesterol crystals. The term hematic cyst should be avoided for this is currently used to describe intra-orbital accumulations of blood. Identical lesions have been reported as a dermoid or epidermoid6 but cholesterol granuloma is never associated with any epithelial elements. They also should be distinguished from acute subperiosteal hematomas which often result from trauma in children 25 - 27 or occur spontaneously in adults. 28 ,29 The pathogenesis of cholesterol granuloma and its predilection for the frontal bone in the region of the lacrimal fossa have yet to be explained. Cholesterol granulomas occur in several sites in the head and probably represent a common pathologic response to a number of differing events. They have been seen in the maxilla,3o,31 and they appeared in one of our patients in the zygoma. Cases involving the petro us temporal bone and presenting as posterior fossa masses have been described. 32 The masses are observed in the pneumatized parts of the temporal bone, in the middle ear, and mastoid antrum after hemorrhage. 33 ,34 In this site, they should be distinguished from cholesteatoma, a postinflammatory lesion containing squamous epithelium and keratin debris. The pathologically identical lesions occurring in these other sites are uniformly called cholesterol granulomas. It therefore seems sensible to use the same term in describing the lesions described in this article. Experimentally, cholesterol granulomas have been induced in the pneumatized bones of chickens by the exclusion of air. 35 The majority of orbital cholesterol granulomas are quite separate from the frontal sinus so this mechanism cannot apply. Graham and Michaels 30 thought that the deposition of cholesterol was related to hemorrhage. We have encountered old and occasionally new hemorrhage in all these lesions, and bleeding from the surface of the bone defect at surgery is very common. If hemorrhage does play a part in the development of these lesions, what causes the hemorrhage and how does the lesion expand? The prominence of the frontal bone and the high preponderance of males favor trauma as the cause of bleeding at this site. However, only six of our patients gave a clear history of trauma and only one third of the cases previously reported have been associated with trauma. 1,7,9,11-14,21-24 Some support for the theory is provided by our finding that 15 of the 18 men, in whom an occupational history was obtained, were manual workers. Facial trauma is relatively common in this group and may have been forgotten particularly if the interval between the trauma and onset of symptoms was prolonged, An alternative cause was suggested by Parke et al 19 who
CHOLESTEROL GRANULOMA
thought that an anomaly within the diploe could initiate a hemorrhage. Whatever the cause of the hemorrhage, the breakdown of blood would produce cholesterol from the cell membranes of the erythrocytes. If this crystallizes, the crystals would stimulate a granulomatous reaction; this in turn could stimulate capillary growth and further transudation of erythrocytes and inflammatory cells so that the mass would continue to expand. Bone resorption by some malignant tumors, by benign dental cysts, and by mucoceles of the paranasal sinuses has been attributed to prostaglandins (PGs), especially PGE 2.36 ,37 Aggregated platelets within a hematoma are a known source of PGs and could initiate bone resorption and exposure of new diploeic blood vessels. These vessels could act as a continuing source of blood products by transudation or hemorrhage. Support for this theory is the observation that these lesions have a definite blood supply which has been demonstrated by angiographyl7 and observed by us at surgery. Whatever the cause of the expansion of the lesion, it causes an area of osteolysis in the frontal bone which extends to but does not transgress the fronto-zygomatic suture. These features were reported by one of us in 1970 and were encountered in 16 of 22 patients in this series whose plain radiographs were available for review. Computed tomographic and MRI scans will delineate the extent of the granuloma, and CT scans will delineate the areas of bone loss. The extension of the granuloma into the extra-periosteal space can be clearly seen with coronal scans of the orbit. The substance of the granuloma is isodense with brain on CT and gives a high signal with T I, T 2, and inversion recovery sequences with MRI. Such a high signal on inversion recovery also is seen in cysts containing fat or oil such as dermoids, but in these cases CT will show a low-density lesion, clearly differentiating between dermoids and cholesterol granulomas. Carotid angiographyl7 has demonstrated an abnormal circulation in adjacent bone and an intense focus of activity when the frontal bone was scanned with 99mdisphosphanate. However, this change is nonspecific and is seen with both inflammatory and malignant disease. The main differential diagnosis is from invasive lacrimal gland carcinoma and a dermoid or epidermoid cyst; other lesions such as aneurysmal bone cysts, cystic ossifying fibroma, eosinophilic granuloma, or metastases are much less common. A lacrimal gland carcinoma which invades the frontal bone invariably causes pain, which is often severe, and irregular bone destruction on radiographs or CT. Dermoids and epidermoids do not cause pain within the frontal bone. There may be leakage of the contents into the upper orbital tissues with episodes of inflammation in the soft tissues and associated localized pain (not the deep-seated pain seen with carcinomas) and redness. Radiographs. and CT scans demonstrate a regular, often scalloped edge to the bone defect with adjacent sclerosis and no destructive changes. Aneurysmal bone cyst 38 has clinical and pathologic similarities with cholesterol granuloma: evidence of bone destruction, old and recent hemorrhage, and granulomatous inflammation, but cholesterol crystals are notably absent. It usually occurs in the young and has no sex 31
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predilection. Cystic ossifying fibroma also occurs in young patients and has a predilection for the orbital roof. The radiographic appearance is quite different because there is a well-demarcated sclerotic margin with scattered foci of calcification within a less radiodense center. 39 Metastases to the lacrimal gland or frontal bone are usually painful and cause irregular destruction of bone without expansion. Eosinophilic granuloma4o typically occurs in younger patients and radiologically produces an osteolytic lesion with irregular serrated and sclerotic margins. Epidermoid cholesteatoma may occasionally arise in the frontal sinus and mimic a cholesterol granuloma. 19 It is more commonly encountered in the middle ear and mastoid antrum where it is called cholesteatoma. It contains squamous epithelium and keratin debris and produces bone erosion. Pathologically this lesion is quite different, with no male predilection and it will recur if all epithelial elements are not removed. The surgical management of cholesterol granuloma has been straightforward. An extraperiosteal approach allows the surgeon to aspirate the contents, strip or curette the lining, and remain safely extradural should a defect exist in the inner table of the bone. On several occasions we have not attempted to completely remove the lining of the cavity and in all these cases (as in other cases) no recurrences have occurred. Complete extirpation of the involved bone as advocated by Raflo and Hurwitz 18 is unnecessary. Only one possible recurrence is reported in the literature6 : a cystic mass recurred 20 years after an undocumented operation at the same site. Despite its rarity, cholesterol granuloma of the frontal bone can usually be recognized preoperatively by its typical clinical and radiologic features. Surgery is very effective with little chance of recurrence.
REFERENCES 1. Denig R. Subperiosteal bloodcyst of the orbit; report of a case. Ophthal Rec 1902; 11:187. 2. Pincus F. Uber "Cholesteatom" der Orbita. Klin Monatsbl Augenheilkd 1933; 90:145-53. 3. Awerbach MI. Les tumeurs sanguines de la cavite orbitaire. Ann Ocul 1933; 170:863-82. 4. Knapp A. Xanthomatosis of the orbit: report of two cases. Arch Ophthalmol1934; 11:141-7. 5. Kreibig W. Zur Kenntnis seltener Orbitaltumoren. Ztschr f Augenh 1938; 95:113-28. 6. Pfeiffer RL, Nicholl RJ. Dermoids and epidermoids of the orbit. Trans Am Ophthalmol Soc 1948; 46:218-43. 7. Ramsey GS, Laws HW, Pritchard JE, Elliot H. Post-traumatic granuloma of the bony orbit simulating tumour. Can Med Assoc J 1948; 59:20611. 8. Ingalls RG. Tumors of the Orbit and Allied Pseudo Tumors. An Analysis of 216 Case Histories. Springfield: Charles C. Thomas, 1953; 188206. 9. Alport B, Dame LR. Orbital cholesteatoma: report of a case. Trans Am Acad Ophthal Otolaryng 1954; 58:575-9. 10. Djacos C, Papazotos B. Cholesteatome de I'orbite. Ann Ocul 1954; 187:748. 11. Roberts W. Hematoma of the orbit: report of two cases. Am J Ophthalmol1955; 40:215-9. 12. Hanbery JW, Rayport M. Unilateral exophthalmos due to orbitofrontal cholesterol granuloma. Am J Surg 1955; 89: 1144-62.
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13. Nicholls JVV. Cholesterol-containing granuloma of the orbital wall. Am J Ophthalmol1956; 41:234-47. 14. Fran90is J, Ectors L, Verriest G. Le cholesteatome de I'orbite. Ophthalmologica 1957; 133:175-87. 15. Wright JE. Lipid containing granuloma of the frontal bone. Trans Ophthalomol Soc UK 1970; 90:295-8. 16. Chwirot R. Podokostnowy ziaminiak cholesterolowy stropu oczodolu. Klin Oczna 1977; 47:155-7. 17. Eugenidis N, Gessaga E, Chrzanowski R. Bone scan and angiography for orbitofrontal cholesterol granuloma. Neuroradiology 1980; 19:934. 18. Raflo GT, Hurwitz JJ. Lipid granuloma of the frontal bone presenting as a space-occupying lesion of the orbit. Can J Ophthalmol 1981; 16:153-5. 19. Parke OW II, Font RL, Boniuk M, McCrary JA III. "Cholesteatoma" of the orbit. Arch Ophthalomol1982; 100:612-6. 20. Hellquist H, Lundgren J, Olofsson J. Cholesterol granuloma of the maxillary and frontal sinuses. ORL J Otorhinolaryngol Relat Spec 1984; 46:153-8. 21. Shapiro A, Tso MOM, Putterman AM, Goldberg MF. A clinicopathologic study of hematic cysts of the orbit. Am J Ophthalmol1986; 102:23741. 22. Milne HL III, Leone CR, Kincaid MC, Brennan MW. Chronic hematic cyst of the orbit. Ophthalmology 1987; 94:271-7. 23. Kersten RC, Kersten JL, Bloom HR, Kulwin DR. Chronic hematic cyst of the orbit. Role of magnetic resonance imaging in diagnosis. Ophthalmology 1988; 95:1549-53. 24. Bergin OJ, McCord CD, Dutton JJ, Garrett SN. Chronic hematic cyst of the orbit. Ophthalmic Plast Reconstr Surg 1988; 4:31-6. 25. Mund ML. Subperiosteal hematic cyst of the orbit. Ophthalmology 1981; 88:992-6. 26. Wolter JR. Subperiosteal hematomas of the orbit in young males: a serious complication of trauma or surgery in the eye region. Trans Am Ophthalmol Soc 1979; 77:104-20. 27. Wolter JR, Leenhouts JA, Coulthard SW. Clinical picture and management of subperiosteal hematoma of the orbit. J Pediatr Ophthalmol 1976; 13: 136-8. 28. Carrion LT, Edwards WC, Perry LD. Spontaneous subperiosteal orbital hematoma. Ann Ophthalmol 1979; 11: 1754-7. 29. Whitwell J. Spontaneous haematoma of the orbit. Br J Ophthalmol 1956; 40:250-1. 30. Graham J, Michaels L. Cholesterol granuloma of the maxillary antrum. Clin Otolaryngol1978; 3:155-60. 31. Lloyd GAS. Cholesterol granuloma of the facial skeleton. Br J Radiol 1986; 59:481-5. 32. Sabin HI, Bordi LT, Symon L. Epidermoid cysts and cholesterol granulomas centered on the posterior fossa: twenty years of diagnosis and management. Neurosurgery 1987; 21 :798-805. 33. Friedmann I, Graham MD. The ultrastructure of cholesterol granuloma of the middle ear: an electron microscopic study. J Laryngol Otol 1979; 93:433-42. 34. Nager GT, Vanderveen TS. Cholesterol granuloma involving the temporal bone. Ann Otol Rhinol Laryngol 1976; 85:204-9. 35. Beaumont GO. The effects of exclusion of air from pneumatized bones. J Laryngol Oto11966; 80:236-49. 36. Harris M, Jenkins MV, Bennett A, Wills MR. Prostaglandin production and bone resorption by dental cysts. Nature 1973; 245:213-5. 37. Lund VJ. Anatomical considerations in the aetiology of fronto-ethmoidal mucoceles. Rhinology 1987; 25:83-8. 38. Johnson TE, Bergin OJ, McCord CD. Aneurysmal bone cyst of the orbit. Ophthalmology 1988; 95:86-9. 39. Jakobiec FA, Font RL. Orbit. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook, 3rd ed. Vol 3, Philadelphia: WB Saunders, 1986; 2591-3. 40. Jakobiec FA, Trokel SL, Aron-Rosa 0, et al. Localized eosinophilic granuloma (Langerhans' cell histiocytosis) of the orbital frontal bone. Arch Ophthalmol1980; 98:1814-20.
Abstract: Cholesterol granuloma of the orbital bones is a rare but readily recognizable clinical and radiologic entity usually affecting men. Twenty-seven patients are reported, and in all except one, the frontal bone in the region of the lacrimal fossa was involved. These lesions produced an area of osteolysis in the frontal bone with expansion into the extraperiosteal space of the lacrimal fossa, causing fullness of the upper lid and proptosis. The granuloma always remained extraperiosteal and was composed of a granulomatous reaction surrounding cholesterol crystals and altered blood. It is postulated that cholesterol granuloma occurs because of hemorrhage into the diploe of the bone. Extraperiosteal surgical removal cured all patients. Some previous reports have failed to identify the true nature of this lesion and confused its nomenclature.
Ophthalmology 1990; 97:28-32
Cholesterol granuloma of the orbital bones is a rare condition which usually occurs in the frontal bone above the lacrimal fossa. A review of the literature found 42 previously reported cases, 1-24 the first being that ofDenigl in 1902 who reported a "subperiosteal blood cyst" with erosion of bone into the anterior cranial fossa. This report details the findings in 27 new cases.
PATIENTS AND METHODS The records of 27 patients with cholesterol granuloma of the orbit were reviewed. The patients presented to the Orbital Clinic at Moorfields Eye Hospital between 1967 and 1988. All except one were confirmed histopathologically. A detailed history was obtained and a complete ophthalmic examination was performed. Plain radiographs of the skull were obtained in each case and since 1974 the majority has had computed tomographic scans (CT) done. One patient was examined with magnetic resonance imaging (MRI).
Originally received: July 17, 1989. Revision accepted: August 15, 1989. From the Orbital Clinic, Moorfields Eye Hospital, London. Supported by the Royal Australian College of Ophthalmologists-OPSM Travelling Fellowship (Dr. McNab). Reprint requests to John E. Wright, MD, Moorfields Eye Hospital, City Rd, London, EC1V 2PD, England.
28
The surgical approach in 21 patients was through a lateral brow incision occasionally extended to the zygomatic arch. Two patients had a lateral orbitotomy, two had an anterior craniotomy, and one was approached through the temporal fossa after raising a scalp flap.
RESULTS Of the 27 patients, 3 were women. At presentation, they ranged in age from 25 to 68 years (median, 43 years; mean, 43.7 years). Almost two thirds 16 of the cases occurred between 35 and 55 years of age. The right and left orbits were similarly affected in 13 and 14 cases, respectively. Symptoms had been present between 1 week and 9 years (median, 8 months; mean 1.1 years). The most common symptom was proptosis which was noted in 15 patients (although 26 patients had measurable proptosis). Ten patients complained of blurred vision and nine experienced a mild dull ache in the brow. Ten patients noticed swelling or drooping of the upper eyelid, and nine complained of double vision, particularly looking upward. Six patients gave a definite history of blunt trauma to the area from 2 years to 1 month before the onset of symptoms. Four patients had been punched, one was headbutted, and the trunk of a Christmas tree jabbed one patient in the eye. The eldest patient, 68 years of age, was known to have hypercholesterolemia and peripheral vascular disease. He gave no history of trauma. Best-corrected visual acuity was 6/6 or better in 15 patients, 6/9 in 3, 6/12 in 7, and 6/18 in 2. Those patients with reduced vision had an acquired astigmatism, cho-
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Fig 1. Plain radiograph of a right orbitofrontal cholesterol granuloma. The osteolysis extends almost to the fronto-zygomatic suture (large arrow). There is a well-defined edge without sclerosis (small arrows). Fig 3. Coronal magnetic resonance image (Tt-weighted). A mass with high-signal intensity in the superotemporal quadrant of the orbit has eroded through both the inner and outer tables of the frontal bone. Notice the large extradural component displacing the frontal lobe of the brain (arrows).
Fig 2. Coronal computed tomographic scan with contrast shows a cholesterol granuloma (isodense with brain) which has eroded the roof of the orbit and is compressing the globe. The intact periosteum is arrowed.
roidal folds, or both. Proptosis was present in 26 patients and ranged from 2 to 8 mm (median, 4 mm; mean, 4.1 mm). The globe was displaced downward in 22 cases with medial displacement in 8 of these. The patient with a lesion in the zygoma had upward and medial displacement of the globe. Eighteen patients had a smooth nontender mass in the upper temporal quadrant. It was usually firm or hard but occasionally felt soft and fluctuant. In some patients, there was appreciable bossing of the frontal bone over the lesion. In two patients, there was a palpable defect in the orbital rim. Ocular motility was abnormal in 23 patients, all of whom had restricted elevation and eight mildly limited abduction as well. The maximal restriction was always in the direction of the mass (i.e., usually elevation in ab-
duction). A ptosis of 2 to 3 mm was present in seven patients. Choroidal folds were seen in 13 patients and this was occasionally associated with significant indentation of the globe. Plain radiographs normally showed a characteristic osteolytic lesion with rounded edges in the region of the lacrimal fossa (Fig 1). There was never any sclerosis of the frontal bone. In the 22 patients in whom the plain xrays were still available for review, the osteolytic process extended into the zygomatic process of the frontal bone in 16 and as far as the fronto-zygomatic suture in 10. Computed tomographic scans were performed in 19 cases and showed a mass in the superotemporal quadrant of the orbit. The attenuation values were not sufficiently characteristic to differentiate the lesion from many other lacrimal fossa lesions, being isodense with the brain. The mass appeared homogeneous with erosion and expansion of the surrounding bone. The edge of the eroded bone was occasionally irregular (Fig 2). In all cases, there was partial or complete loss of the outer table of the bone allowing the lesi~n to expand extraperiosteally into the orbit. In nine cases, there was erosion of the inner table of the skull with exposure of the dura mater and extension of the mass into the extradural space (Fig 3). This was confirmed at surgery in each patient and also in two others who had not had CT or MRI scans performed. Three cases showed erosion into the most lateral part of the frontal sinus and two had eroded into the temporal fossa behind the orbital rim. In several cases, isolated fragments of bone lay within the lesion (Fig 2). Magnetic resonance imaging was performed in one case and clearly demonstrated both orbital and intracranial extension (Fig 3). The contents of the lesion had a high-signal intensity on
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Fig 4. Ph~tomicrograph of the wall of a cholesterol granuloma. There are numerous cholesterol crystals within a chronic inflammatory infiltrate with scattered giant cells (hematoxylineosin; original magnification, XJSO).
both T[- and Tz-weighted images. In addition, the inversion recovery sequence gave a high-signal intensity. In 17 cases, the diagnosis was confidently made before surgery on the basis of clinical and particularly plain xray features. In nine cases, the diagnosis was considered to be more likely a dermoid or lacrimal tumor. Most of these errors were made early in the series, with four of the first five cases being incorrectly diagnosed preoperatively. The mass was usually approached by a lateral brow incision down to periosteum at the orbital margin. The periosteum was reflected from the anterior surface of the frontal bone to the orbital margin. The underlying bone was usually thin and discolored by the contents of the lesion, giving the bone a yellowish-blue appearance. The orbital rim was often sharp and irregular where it was eroded. As soon as the dissection of the orbital periosteum from the roof was commenced, the lower surface of the granuloma was encountered in the extraperiosteal space. This part of the dissection was usually accompanied by the release of yellowish-brown fluid containing aggregates of more solid yellow material. The contents could be aspirated quite easily but granulomatous material was invariably adherent to the bone and orbital periosteum and required careful dissection for its removal. If dura mater was exposed, then great care was required to avoid creating a breach in this structure with subsequent cerebral spinal fluid leakage. Active bleeding from small vessels in the bone was often seen, but was easily stopped with bone wax. The wound was closed in layers and a drain inserted into the cavity or the subcutaneous tissues and left for 24 hours. The one patient who was not operated on was a 27year-old man who had had multiple blows to the head sustained' both on and off the rugby field. He presented with a periorbital hematoma, and a plain skull x-ray 30
showed a small but typical osteolytic lesion in the frontal bone. There were no ocular symptoms or signs, and he is being observed. Histopathologic examination findings of the contents and lining of the lesion showed a consistent and characteristic appearance (Fig 4). The fluid consisted of altered blood with scattered giant cells, histiocytes laden with hemosiderin or cholesterol, and other inflammatory cells. Solid elements showed cholesterol clefts surrounded by a granulomatous reaction with foreign-body giant cells. Lipid laden macrophages and hemosiderin both extracellularly and within histiocytes were seen with a variable amount of fibrosis in the wall of the lesion and occasionally fragments of bone. In no case was there any suggestion of epithelial elements or keratin. All patients improved as a result of their surgery with loss of proptosis, ptosis, swelling, and diplopia. The followup period varied from 3 months to 10 years. There were no recurrences. One patient complained of bifrontal headache 2 years after surgery. Plain x-ray showed remodeling of the bone to an almost normal appearance and no evidence of recurrence.
DISCUSSION Cholesterol granuloma is a rare but readily recognizable lesion with characteristic radiologic, histopathologic, and clinical features. The latter are caused by the extraperiosteal orbital component ofthe mass. The lesion commences within the diploe of the frontal bone, enlarging so that eventually the outer table of the bone is breached and the contents are spread into the extraperiosteal space above the lacrimal fossa. Occasionally, there is an associated erosion of the inner table of the bone with extradural spread of the granuloma into the anterior cranial fossa ;
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this rarely causes symptoms. It is the extraperiosteal mass in the upper part of the orbit which causes the symptoms of fullness of the upper lid, downward displacement of the globe and proptosis. These patients therefore consult ophthalmologists who should be aware of this entity and its straightforward surgical management. A variety of names has been used to describe these lesions, including cholesteatoma,2,8-1O,14,19 lipid granuloma of the frontal bone,15,18 xanthomatosis of the orbit,4 hematoma, II and chronic hematic cystY- Z4 However, cholesterol granuloma is a better term because the osteolytic lesion contains a granulomatous reaction surrounding cholesterol crystals. The term hematic cyst should be avoided for this is currently used to describe intra-orbital accumulations of blood. Identical lesions have been reported as a dermoid or epidermoid6 but cholesterol granuloma is never associated with any epithelial elements. They also should be distinguished from acute subperiosteal hematomas which often result from trauma in children 25 - 27 or occur spontaneously in adults. 28 ,29 The pathogenesis of cholesterol granuloma and its predilection for the frontal bone in the region of the lacrimal fossa have yet to be explained. Cholesterol granulomas occur in several sites in the head and probably represent a common pathologic response to a number of differing events. They have been seen in the maxilla,3o,31 and they appeared in one of our patients in the zygoma. Cases involving the petro us temporal bone and presenting as posterior fossa masses have been described. 32 The masses are observed in the pneumatized parts of the temporal bone, in the middle ear, and mastoid antrum after hemorrhage. 33 ,34 In this site, they should be distinguished from cholesteatoma, a postinflammatory lesion containing squamous epithelium and keratin debris. The pathologically identical lesions occurring in these other sites are uniformly called cholesterol granulomas. It therefore seems sensible to use the same term in describing the lesions described in this article. Experimentally, cholesterol granulomas have been induced in the pneumatized bones of chickens by the exclusion of air. 35 The majority of orbital cholesterol granulomas are quite separate from the frontal sinus so this mechanism cannot apply. Graham and Michaels 30 thought that the deposition of cholesterol was related to hemorrhage. We have encountered old and occasionally new hemorrhage in all these lesions, and bleeding from the surface of the bone defect at surgery is very common. If hemorrhage does play a part in the development of these lesions, what causes the hemorrhage and how does the lesion expand? The prominence of the frontal bone and the high preponderance of males favor trauma as the cause of bleeding at this site. However, only six of our patients gave a clear history of trauma and only one third of the cases previously reported have been associated with trauma. 1,7,9,11-14,21-24 Some support for the theory is provided by our finding that 15 of the 18 men, in whom an occupational history was obtained, were manual workers. Facial trauma is relatively common in this group and may have been forgotten particularly if the interval between the trauma and onset of symptoms was prolonged, An alternative cause was suggested by Parke et al 19 who
CHOLESTEROL GRANULOMA
thought that an anomaly within the diploe could initiate a hemorrhage. Whatever the cause of the hemorrhage, the breakdown of blood would produce cholesterol from the cell membranes of the erythrocytes. If this crystallizes, the crystals would stimulate a granulomatous reaction; this in turn could stimulate capillary growth and further transudation of erythrocytes and inflammatory cells so that the mass would continue to expand. Bone resorption by some malignant tumors, by benign dental cysts, and by mucoceles of the paranasal sinuses has been attributed to prostaglandins (PGs), especially PGE 2.36 ,37 Aggregated platelets within a hematoma are a known source of PGs and could initiate bone resorption and exposure of new diploeic blood vessels. These vessels could act as a continuing source of blood products by transudation or hemorrhage. Support for this theory is the observation that these lesions have a definite blood supply which has been demonstrated by angiographyl7 and observed by us at surgery. Whatever the cause of the expansion of the lesion, it causes an area of osteolysis in the frontal bone which extends to but does not transgress the fronto-zygomatic suture. These features were reported by one of us in 1970 and were encountered in 16 of 22 patients in this series whose plain radiographs were available for review. Computed tomographic and MRI scans will delineate the extent of the granuloma, and CT scans will delineate the areas of bone loss. The extension of the granuloma into the extra-periosteal space can be clearly seen with coronal scans of the orbit. The substance of the granuloma is isodense with brain on CT and gives a high signal with T I, T 2, and inversion recovery sequences with MRI. Such a high signal on inversion recovery also is seen in cysts containing fat or oil such as dermoids, but in these cases CT will show a low-density lesion, clearly differentiating between dermoids and cholesterol granulomas. Carotid angiographyl7 has demonstrated an abnormal circulation in adjacent bone and an intense focus of activity when the frontal bone was scanned with 99mdisphosphanate. However, this change is nonspecific and is seen with both inflammatory and malignant disease. The main differential diagnosis is from invasive lacrimal gland carcinoma and a dermoid or epidermoid cyst; other lesions such as aneurysmal bone cysts, cystic ossifying fibroma, eosinophilic granuloma, or metastases are much less common. A lacrimal gland carcinoma which invades the frontal bone invariably causes pain, which is often severe, and irregular bone destruction on radiographs or CT. Dermoids and epidermoids do not cause pain within the frontal bone. There may be leakage of the contents into the upper orbital tissues with episodes of inflammation in the soft tissues and associated localized pain (not the deep-seated pain seen with carcinomas) and redness. Radiographs. and CT scans demonstrate a regular, often scalloped edge to the bone defect with adjacent sclerosis and no destructive changes. Aneurysmal bone cyst 38 has clinical and pathologic similarities with cholesterol granuloma: evidence of bone destruction, old and recent hemorrhage, and granulomatous inflammation, but cholesterol crystals are notably absent. It usually occurs in the young and has no sex 31
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JANUARY 1990
predilection. Cystic ossifying fibroma also occurs in young patients and has a predilection for the orbital roof. The radiographic appearance is quite different because there is a well-demarcated sclerotic margin with scattered foci of calcification within a less radiodense center. 39 Metastases to the lacrimal gland or frontal bone are usually painful and cause irregular destruction of bone without expansion. Eosinophilic granuloma4o typically occurs in younger patients and radiologically produces an osteolytic lesion with irregular serrated and sclerotic margins. Epidermoid cholesteatoma may occasionally arise in the frontal sinus and mimic a cholesterol granuloma. 19 It is more commonly encountered in the middle ear and mastoid antrum where it is called cholesteatoma. It contains squamous epithelium and keratin debris and produces bone erosion. Pathologically this lesion is quite different, with no male predilection and it will recur if all epithelial elements are not removed. The surgical management of cholesterol granuloma has been straightforward. An extraperiosteal approach allows the surgeon to aspirate the contents, strip or curette the lining, and remain safely extradural should a defect exist in the inner table of the bone. On several occasions we have not attempted to completely remove the lining of the cavity and in all these cases (as in other cases) no recurrences have occurred. Complete extirpation of the involved bone as advocated by Raflo and Hurwitz 18 is unnecessary. Only one possible recurrence is reported in the literature6 : a cystic mass recurred 20 years after an undocumented operation at the same site. Despite its rarity, cholesterol granuloma of the frontal bone can usually be recognized preoperatively by its typical clinical and radiologic features. Surgery is very effective with little chance of recurrence.
REFERENCES 1. Denig R. Subperiosteal bloodcyst of the orbit; report of a case. Ophthal Rec 1902; 11:187. 2. Pincus F. Uber "Cholesteatom" der Orbita. Klin Monatsbl Augenheilkd 1933; 90:145-53. 3. Awerbach MI. Les tumeurs sanguines de la cavite orbitaire. Ann Ocul 1933; 170:863-82. 4. Knapp A. Xanthomatosis of the orbit: report of two cases. Arch Ophthalmol1934; 11:141-7. 5. Kreibig W. Zur Kenntnis seltener Orbitaltumoren. Ztschr f Augenh 1938; 95:113-28. 6. Pfeiffer RL, Nicholl RJ. Dermoids and epidermoids of the orbit. Trans Am Ophthalmol Soc 1948; 46:218-43. 7. Ramsey GS, Laws HW, Pritchard JE, Elliot H. Post-traumatic granuloma of the bony orbit simulating tumour. Can Med Assoc J 1948; 59:20611. 8. Ingalls RG. Tumors of the Orbit and Allied Pseudo Tumors. An Analysis of 216 Case Histories. Springfield: Charles C. Thomas, 1953; 188206. 9. Alport B, Dame LR. Orbital cholesteatoma: report of a case. Trans Am Acad Ophthal Otolaryng 1954; 58:575-9. 10. Djacos C, Papazotos B. Cholesteatome de I'orbite. Ann Ocul 1954; 187:748. 11. Roberts W. Hematoma of the orbit: report of two cases. Am J Ophthalmol1955; 40:215-9. 12. Hanbery JW, Rayport M. Unilateral exophthalmos due to orbitofrontal cholesterol granuloma. Am J Surg 1955; 89: 1144-62.
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13. Nicholls JVV. Cholesterol-containing granuloma of the orbital wall. Am J Ophthalmol1956; 41:234-47. 14. Fran90is J, Ectors L, Verriest G. Le cholesteatome de I'orbite. Ophthalmologica 1957; 133:175-87. 15. Wright JE. Lipid containing granuloma of the frontal bone. Trans Ophthalomol Soc UK 1970; 90:295-8. 16. Chwirot R. Podokostnowy ziaminiak cholesterolowy stropu oczodolu. Klin Oczna 1977; 47:155-7. 17. Eugenidis N, Gessaga E, Chrzanowski R. Bone scan and angiography for orbitofrontal cholesterol granuloma. Neuroradiology 1980; 19:934. 18. Raflo GT, Hurwitz JJ. Lipid granuloma of the frontal bone presenting as a space-occupying lesion of the orbit. Can J Ophthalmol 1981; 16:153-5. 19. Parke OW II, Font RL, Boniuk M, McCrary JA III. "Cholesteatoma" of the orbit. Arch Ophthalomol1982; 100:612-6. 20. Hellquist H, Lundgren J, Olofsson J. Cholesterol granuloma of the maxillary and frontal sinuses. ORL J Otorhinolaryngol Relat Spec 1984; 46:153-8. 21. Shapiro A, Tso MOM, Putterman AM, Goldberg MF. A clinicopathologic study of hematic cysts of the orbit. Am J Ophthalmol1986; 102:23741. 22. Milne HL III, Leone CR, Kincaid MC, Brennan MW. Chronic hematic cyst of the orbit. Ophthalmology 1987; 94:271-7. 23. Kersten RC, Kersten JL, Bloom HR, Kulwin DR. Chronic hematic cyst of the orbit. Role of magnetic resonance imaging in diagnosis. Ophthalmology 1988; 95:1549-53. 24. Bergin OJ, McCord CD, Dutton JJ, Garrett SN. Chronic hematic cyst of the orbit. Ophthalmic Plast Reconstr Surg 1988; 4:31-6. 25. Mund ML. Subperiosteal hematic cyst of the orbit. Ophthalmology 1981; 88:992-6. 26. Wolter JR. Subperiosteal hematomas of the orbit in young males: a serious complication of trauma or surgery in the eye region. Trans Am Ophthalmol Soc 1979; 77:104-20. 27. Wolter JR, Leenhouts JA, Coulthard SW. Clinical picture and management of subperiosteal hematoma of the orbit. J Pediatr Ophthalmol 1976; 13: 136-8. 28. Carrion LT, Edwards WC, Perry LD. Spontaneous subperiosteal orbital hematoma. Ann Ophthalmol 1979; 11: 1754-7. 29. Whitwell J. Spontaneous haematoma of the orbit. Br J Ophthalmol 1956; 40:250-1. 30. Graham J, Michaels L. Cholesterol granuloma of the maxillary antrum. Clin Otolaryngol1978; 3:155-60. 31. Lloyd GAS. Cholesterol granuloma of the facial skeleton. Br J Radiol 1986; 59:481-5. 32. Sabin HI, Bordi LT, Symon L. Epidermoid cysts and cholesterol granulomas centered on the posterior fossa: twenty years of diagnosis and management. Neurosurgery 1987; 21 :798-805. 33. Friedmann I, Graham MD. The ultrastructure of cholesterol granuloma of the middle ear: an electron microscopic study. J Laryngol Otol 1979; 93:433-42. 34. Nager GT, Vanderveen TS. Cholesterol granuloma involving the temporal bone. Ann Otol Rhinol Laryngol 1976; 85:204-9. 35. Beaumont GO. The effects of exclusion of air from pneumatized bones. J Laryngol Oto11966; 80:236-49. 36. Harris M, Jenkins MV, Bennett A, Wills MR. Prostaglandin production and bone resorption by dental cysts. Nature 1973; 245:213-5. 37. Lund VJ. Anatomical considerations in the aetiology of fronto-ethmoidal mucoceles. Rhinology 1987; 25:83-8. 38. Johnson TE, Bergin OJ, McCord CD. Aneurysmal bone cyst of the orbit. Ophthalmology 1988; 95:86-9. 39. Jakobiec FA, Font RL. Orbit. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook, 3rd ed. Vol 3, Philadelphia: WB Saunders, 1986; 2591-3. 40. Jakobiec FA, Trokel SL, Aron-Rosa 0, et al. Localized eosinophilic granuloma (Langerhans' cell histiocytosis) of the orbital frontal bone. Arch Ophthalmol1980; 98:1814-20.
