—  SHORT COURSE  —

OPHTHALMIC PATHOLOGY FOR THE NON-SPECIALIST


CASE 5 – SCLEROSING INFLAMMATORY PSEUDOTUMOR OF ORBIT

J. Godfrey Heathcote, M.B.,Ph.D.  —  Janice R. Safneck, M.D.




History
A 5-year-old boy was admitted with a diagnosis of orbital cellulitis. A CT scan revealed an orbital mass that was biopsied.

Diagnosis
Sclerosing inflammatory pseudotumor

Histopathology
Sections show fibrofatty tissue with areas of dense collagen. In other areas there is a proliferation of spindled and stellate cells with scanty cytoplasm that do not express muscle-specific actin. Scattered among these fibroblasts are small numbers of inflammatory cells, particularly lymphocytes but with occasional eosinophils.


Case 5, Slide 12 - Sclerosing Inflammatory Pseudotumor of Orbit: Fibro-fatty tissue with areas of dense collagen, fibroblasts and scattered inflammatory cells
Case 5, Slide 13 - Sclerosing Inflammatory Pseudotumor of Orbit: Plump fibroblasts; eosinophils in inflammatory infiltrate

Discussion
A pronounced inflammatory infiltrate is a recognised feature of some soft tissue neoplasms. Inflammatory cells may also form a major component of a variety of non-neoplastic space-occupying lesions in soft tissue, some of which have a histological appearance sufficiently characteristic for the lesion to have been given a specific name, e.g. nodular fasciitis. Fibroinflammatory lesions with a similar histological appearance have been described in several specific locations and coexist often enough for them to be recognised as related diseases. These lesions include retroperitoneal fibrosis, perianeurysmal fibrosis, mediastinal fibrosis, sclerosing cholangitis and Riedel's thyroiditis. Similar lesions have also been recognised in the soft tissues of the head and neck, the paranasal sinuses and particularly the orbit, where it is known as orbital inflammatory pseudotumor.1-3  Some authors prefer the term non-specific orbital inflammatory syndrome.4  In early studies apparently benign, highly cellular lymphocytic proliferations were included among the pseudotumors5  but the introduction of immunophenotyping in the late 1970's led to the separation of these from the relatively hypocellular, fibrosing lesions.

The mass lesions are caused by proliferation of fibroblastic cells, the deposition of variable amounts of mature collagen and a mixed inflammatory infiltrate of variable intensity. The infiltrate often surrounds small veins but there is no vasculitis. Although the majority of the inflammatory cells are lymphoplasmacytic in nature, macrophages and occasional multinucleated giant cells may be observed. Both eosinophils and neutrophils may be present. Intact eosinophils are particularly to be found in inflammatory areas and extracellular eosinophil granule proteins, e.g., the major basic protein, are more a feature of the fibrotic areas.6  The liberation of cytotoxic proteins from the eosinophil granules may promote fibrosis and may also contribute to the degeneration of the extraocular muscles in inflammatory pseudotumor. With chronicity, there is often hyalinization of the collagen and the inflammatory infiltrate may be quite scanty. Rootman7  has suggested that the sclerosing form of orbital inflammation is a separate entity but this is not widely accepted.8 

The clinical presentation of an orbital inflammatory pseudotumor is quite characteristic. It may occur at any age and is usually unilateral. Within the orbit, the lesion may be diffuse and infiltrative but frequently is concentrated on the lacrimal gland or the extra-ocular muscles. In the series from the Mayo Clinic8  the principal signs and symptoms were: unilateral eyelid swelling or drooping (82%); displacement of the eye (67%); disturbance of ocular motility or diplopia (49%); discovery of a mass (33%); pain (33%). The clinical picture of an orbital mass with pain, inflammation and ptosis is generally sufficient to warrant a diagnostic and therapeutic trial of prednisone (80 mg per day); a typical pseudotumor will show some response in 24-48 hours. Failure to respond is an indication for biopsy. It is important that the biopsy should sample the centre of the mass since it is not uncommon to see an inflammatory mantle around orbital lesions such as carcinomas and meningiomas. Because of the association with retroperitoneal fibrosis9,10  measurement of blood pressure is advisable.

Unilateral, eyelid swelling in adults may be caused by a diffuse chalazion or by an inflammatory pseudotumor. In a young child unilateral eyelid swelling is a particularly worrisome sign since it is the principal manifestation of bacterial orbital cellulitis. In children 87% of infections are located anterior to the orbit (pre-septal) and are usually secondary to a local cause such as a skin laceration. In the remaining cases, the infection resides in the deeper orbital tissues and may be secondary to sinusitis. Pre-septal cellulitis may have an explosive onset but the eye itself remains quiet and intravenous antibiotics should cause resolution in 2-3 days. If resolution does not occur a CT scan is indicated to exclude a more serious condition, such as a rhabdomyosarcoma. Rarely a retinoblastoma will present with a picture of orbital cellulitis.11  In the current case, a CT scan performed the day after admission revealed a mass lesion in the lateral orbit. With a possible diagnosis of rhabdomyosarcoma, a biopsy was promptly performed through the upper lid.

The behaviour of inflammatory pseudotumors can be quite unpredictable. Some will resolve spontaneously and some will respond to corticosteroids. In other cases the response to steroids is transient and, as the dose is tapered, the lesions recur. If there is no response to steroids, subtotal excision with or without radiation therapy may be required. Although there is no correlation between the histology of the lesion and the clinical presentation, Chavis et al5  pointed out that the histological appearance could provide some guide to its behaviour. Those containing eosinophils and lymphoid follicles with germinal centres are more likely to resolve spontaneously or with steroid therapy. Occasional cases of lymphoma arising within inflammatory pseudotumor have been described but some of these lesions may have been lymphoid proliferations ab initio.

Orbital Lymphoid Proliferation
The orbit does not contain lymph nodes and lymphatics are only present within the lacrimal parenchyma and in the superficial substantia propria of the conjunctiva. Orbital lymphoid proliferations are thought to arise from the hematogenous introduction of non-resident lymphocytes or, in the lacrimal gland, from interstitial lymphocytes and plasma cells. Within the orbit 46% of lymphoid proliferations involve the lacrimal gland.12  The presenting signs and symptoms do not differ markedly from those of inflammatory pseudotumor, i.e. a mass, displacement of the eye, ocular motility disturbance, and ptosis, although pain is unusual. A hyperplastic lesion cannot be distinguished from a lymphoma on clinical grounds. The lesions are slightly more common in women and over the age of 50 years.12  Approximately 70% are non-Hodgkin's lymphomas, almost always of B-cell type, and only 19% are associated with systemic lymphoma. Very few incontrovertible cases of Hodgkin's disease have been described in the orbit13  and T-cell lymphoma is also extremely rare.14  Mycosis fungoides not infrequently involves the skin of the eyelid15  and occasionally may produce orbital masses.16 

The majority of orbital lymphomas are densely cellular with diffuse sheets of small lymphoid cells. Unlike the situation with inflammatory pseudotumor there is very little connective tissue stroma. In lymphoid hyperplasias the infiltrate is often less dense, more polymorphous and polyclonal; any germinal centres have well-defined mantle zones. Despite their polyclonal nature, occult foci of clonal B-cells have been identified within the lymphoid hyperplasias, indicating malignant potential.12 

References

  1. Wold LE, Weiland LH. Tumefactive fibro-inflammatory lesions of the head and neck. Am J Surg Pathol 1983;7:477-482.
  2. Olsen KD, DeSanto LW, Wold LE, Weiland LH. Tumefactive fibroinflammatory lesions of the head and neck. Laryngoscope 1986;96:940-944.
  3. Han MH, et al. Fibrosing inflammatory pseudotumors involving the skull base: MR and CT manifestations with histopathologic comparison. Am J Neuroradiol 1996;17:515-521.
  4. Kennerdell JS, Dresner SC. The non-specific orbital inflammatory syndromes. Surv Ophthalmol 1984;29:93-103.
  5. Chavis RM, Garner A, Wright JE. Inflammatory orbital pseudotumor. A clinicopathologic study. Arch Ophthalmol 1978;96:1817-1822.
  6. Noguchi H, et al. Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor. Ophthalmology 1991;98:928-932.
  7. Rootman J, McCarthy M, White V, Harris G, Kennerdell J. Idiopathic sclerosing inflammation of the orbit. A distinct clinicopathologic entity. Ophthalmology 1994;101:570-584.
  8. Henderson JW. Inflammatory orbital tumors. In Orbital Tumors, 3rd Ed., Raven Press, New York, 1994, pp 391-400.
  9. Richards AB, Skalka HW, Roberts FJ, Flint A. Pseudotumor of the orbit and retroperitoneal fibrosis. A form of multifocal fibrosclerosis. Arch Ophthalmol 1980;98:1617-1620.
  10. Schonder AA, Clift RC, Brophy JW, Dane LW. Bilateral recurrent orbital inflammation associated with retroperitoneal fibrosclerosis. Brit J Ophthalmol 1985;69:783-787.
  11. Ben Meir A, Bardenstein DS, Peiffer RL. Retinoblastoma presenting with orbital cellulitis. A mechanistic hypothesis. Invest Ophthalmol Vis Sci 1995;36(4) S492.
  12. Knowles DM, Jakobiec FA. Malignant lymphomas and lymphoid hyperplasias that occur in the ocular adnexa (orbit, conjunctiva, and eyelids). In Neoplastic Hematopathology. DM Knowles, Ed., Williams & Wilkins, Baltimore, 1992, pp 1009-1046.
  13. Case Records of the Massachusetts General Hospital (Case 7-1989). N Engl J Med 1989;320:447-457.
  14. Henderson JW, Banks PM, Yeatts RP. T-cell lymphoma of the orbit. Mayo Clin Proc 1989;64:940-944.
  15. Probst, LE, Burt WL, Heathcote JG. Mycosis fungoides causing lower lid ectropion. Can J Ophthalmol 1993;28:333-338.
  16. Zucker JL, Doyle MF. Mycosis fungoides metastatic to the orbit. Arch Ophthalmol 1991;109:688-691.