Ординатура / Офтальмология / Английские материалы / Tumors of the Eye and Ocular Adnexa_Char_2001

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Diagnostic radiology. San Francisco, CA: Radiological Research and Education Foundation; 1984.

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51.Toller KK, Gigantelli JW, Spalding MJ. Bilateral orbital metastases from breast carcinoma. A case of false pseudotumor. Ophthalmology 1998;105:1897–901.

52.Logrono R, Inhorn SL, Dortzbach RK, Kurtycz DF. Leiomyosarcoma metastatic to the orbit: diagnosis of fine-needle aspiration. Diagn Cytopathol 1997;17:369–73.

53.Balchunas WR, Quencer RM, Byrne SF. Lacrimal gland and fossa masses: evaluation by computed tomography and A-mode echography. Radiology 1983;149:751–8.

54.Char DH, Sobel D, Kelly WM, et al. Magnetic resonance scanning in orbital tumor diagnosis. Ophthalmology 1985;92:1305–10.

55.DiBernardo C, Pacheco EM, Hughes FR, et al. Echographic evaluation and findings in metastatic melanoma to extraocular muscles. Ophthalmology 1996;103:1794–7.

56.Kennerdell JS. Discussion. Ophthalmology 1985;92: 669–70.

57.Cangiarella JF, Cajigas A, Savala E, et al. Fine-needle aspiration cytology of orbital masses. Acta Cytol 1996;40:1205–11.

58.Mottow-Lippa L, Jakobiec FA, Iwamoto T. Pseudoinflammatory metastatic breast carcinoma of the orbit and lids. Ophthalmology 1981;88:575–80.

59.Ratanatharathorn V, Powers WE, Grimm J, et al. Eye metastasis from carcinoma of the breast: diagnosis, radiation treatment and results. Cancer Treat Rev 1991;18:261–76.

60.Orcutt JC, Char DH. Melanoma metastatic to the orbit. Ophthalmology 1988;95:1033–7.

61.Hutchinson BM, Damato BE, Kyle PM, Harnett AN. Choroidal melanoma metastatic to the contralateral orbit. Orbit 1994;13:85–9.

62.Apple DJ. Metastatic orbital neuroblastoma originating in the cervical sympathetic ganglionic chain. Am J Ophthalmol 1969;68:1093–5.

63.Heckemann R, Schmitt G. Ergebnisse der Strahlentherapie metastatischer Orbitatumoren. Strahlentherapie 1978;154:179–81.

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67.Goldberg RA, Rootman J, Cline RA. Tumors metastatic to the orbit: a changing picture. Surv Ophthalmol 1990;35:1–24.

Orbital pseudotumor was first described by BirchHirschfield in 1905. As in idiopathic inflammations of other body sites, a number of pathogenic theories have been proposed, but the etiology of orbital pseudotumor is still unknown and lacks an animal model.1–4 Orbital pseudotumor remains a diagnosis of exclusion.

Histologically, these lesions usually consist of either a monoclonal or heterogenous lymphoid proliferation or an inflammatory-fibrotic process; occasionally, vasculitis or a combination of these types is present. Several classifications have been proposed; some authors separate lymphoid lesions from other inflammatory and fibrotic processes.5 Others have grouped all these idiopathic lesions together under the same rubric of orbital pseudotumor. This chapter includes all these entities. They have not been separated for three reasons: (1) the etiologies are uncertain. While it is likely that several of the entities are distinct and have a different pathogenesis and natural history, until we have better understanding of the nature of these processes, there is no point in having an artificial classification system; (2) often, these lesions can have an overlapping set of symptoms and presentations; and (3) many of these orbital pseudotumors are treated in a similar manner.

The choice between one all-inclusive system or separate systems of classification is, at present, semantic. As we develop a better understanding of the pathogenesis and pathophysiology of these processes, a classification system based on those parameters will be developed. A major point, which will be discussed in detail below, is that in the patient with idiopathic, apparently benign, lymphoid lesions (even those which are heterogenous on flow

cytometry or DNA Southern blots) there is a significant risk for the development of systemic lymphoma. In patients with pure inflammatory and fibrotic processes, this risk is not present.

The differential diagnosis of inflammatory pseudotumor includes numerous conditions, a list of which is found in Table 26–1.3

Fungal and parasitic infections can involve the orbit and simulate pseudotumors; such entities include aspergillosis, mucormycosis, actinomycosis,

Table 26–1. DIFFERENTIAL DIAGNOSIS OF PSEUDOTUMOR

Benign systemic diseases with associated orbital inflammation Systemic lupus erythematosus

Polyarteritis nodosa Sarcoidosis Lipidosis

Pseudotumor with sclerosing cholangitis

Langerhans’ cell proliferations (histiocytosis syndromes) Pseudorheumatoid nodule

Necrobiotic xanthogranuloma Erdheim-Chester disease Wegener’s granulomatosis

Sinusitis with contiguous orbital inflammation

Malignant lymphoid lesions

Lymphoma

Leukemia

Plasmacytoma

Midline lethal granuloma

Mycosis fungoides

Infectious processes

Fungus (aspergillosis, mucormycosis, actinomycosis, histoplasmosis, coccidiodomycosis, parasitic echinococcosis, cysticercosis, dirofilariasis, bilharziasis, ascariasis, onchocerciasis)

Bacteria

Miscellaneous processes

Ruptured dermoid

Retained orbital foreign body

Amyloidosis

Nodular fasciitis

Metastasis

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histoplasmosis, coccidiomycosis, echinococcosis, cysticercosis, dirofilarisasis, bilharzia, ascariasis, and onchocerciasis.3 In acquired immune deficiency syndrome (AIDS) and with more sophisticated means of salvaging patients with advanced systemic malignancies using agents which may cause further immunosuppression, other rare infectious agents have been shown to produce orbital involvement.

Orbital lymphoid lesions and idiopathic orbital pseudotumors are common; they account for 11 to 20 percent of orbital biopsies.6,7 Orbital malignant lymphoid lesions usually present as an isolated neoplasm; in < 15 percent of these cases, there is either a history of systemic lymphoma or the simultaneous onset of orbital and widespread disease. Generally, pain is a less common presenting symptom in malignant than in benign lymphoid lesions.

DIAGNOSIS

The clinical presentation of orbital pseudotumors is varied and depends on the pattern of orbital and ocular involvement. Inflammation can be isolated to single or multiple extraocular muscles (idiopathic orbital myositis) (Figures 26–1 to 26–4), or it can diffusely involve the orbit and globe (Figure 26–5). Inflammation may present as a lacrimal gland mass (Figure 26–6) and have diffuse infiltration of orbital fat, mus-

Figure 26–1. Axial CT scan shows idiopathic myositis. This case responded completely to high-dose oral steroids. Note: unlike thyroid myopathy, both the muscle and its tendon are involved.

A

B

Figure 26–2. A, Axial CT scan of a patient with lateral rectus myositis. B, Parasagittal reconstruction of a CT scan of a different patient with idiopathic myositis involving the superior rectus complex.

cle, sclera, and nerve (Figure 26–7 and 26–8), or it may focally affect the orbital apex and cavernous sinus area (Tolosa-Hunt syndrome) (Figures 26–8A and B).8–10 Rarely, it can even present with intraocular signs, such as cystoid macular edema.11 If inflammation is limited to the orbital apex, pain, ptosis, and ophthalmoplegia are present; often the pupil is spared.12–14 Any age group may develop orbital lymphoid lesions, but idiopathic myositis appears to be more common in young adults, while other forms of orbital pseudotumors or lymphomas are more common in older patients.15–17

Orbital pseudotumor patients usually present with the history of sudden onset of deep orbital pain and periocular redness. If there is anterior inflammation, an associated diffuse scleritis is usually seen (Figure 26–9), along with lid swelling (Figure 26–10). In cases of posterior orbital inflammation or isolated mass lesions, scleritis may not be visible. Pain is less common in patients who present with an isolated lymphoid mass lesion (Figure 26–11).

Idiopathic orbital myositis is a relatively uncommon form of orbital pseudotumor, and it is more common in young patients (see Figures 26–1 to 26–4).16,17

A

B

Figure 26–3. A, T1-weighted axial MRI scan of a patient with lateral rectus myositis. B, Usually, with gadolinium, there is enhancement of the inflammatory mass. This process completely resolved on a 1-week course of high-dose oral corticosteroids.

If it is present, there is usually painful limitation of the muscle, especially toward its field of action. This pattern is usually distinct from that observed in thyroid orbitopathy. In thyroid eye disease, if the inferior rectus is involved, the patient can look down but is restricted in upgaze. In contrast, with idiopathic myositis, if the inferior rectus is involved, usually, the patient can look up but has problems looking down. This pattern is not always the case and during the natural history of this disease alterations can occur. In one series, 13 of the 15 reported cases involved patients between the ages of 18 and 30 years.18,19 These patients have acute onset of pain, double

A

B

Figure 26–4. A, Direct parasagittal MRI scan of a lymphoid lesion of the superior muscle complex. B, Gadolinium of the lesion shown in Figure 26–4A.

vision, and eyelid swelling. They are extremely responsive to short-term systemic steroids.20,21 In retrospective analysis, one group noted that a solitary muscle was involved in 68 percent of cases.18 The two most common muscles involved are the medial and lateral recti. In about one-third of cases, there was

Figure 26–5. Axial MRI scan demonstrating diffuse orbital inflammation of biopsy-proven pseudotumor.

Figure 26–6. Axial MRI scan shows a pseudotumor arising bilaterally in the region of the lacrimal glands.

coexistent scleritis.18 In that study, 68 percent responded to oral steroids, but 20 percent had one or more recurrences. In a series of 26 patients in a report from London, 6 had recurrent disease, and factors associated with recurrence were male gender, lack of proptosis, eyelid retraction, and bilateral involvement. Eighty-five percent of patients responded to a 3-week course of nonsteroidal medications. Nine of the 26 who did not respond to this had a good response to midrange oral prednisone, although 23 percent of these patients had recurrences.

A small minority of these patients with idiopathic myositis have later been diagnosed with thyroid orbitopathy. Rarely, the strabismus due to orbital myositis does not resolve, and a few patients have been treated with botulinum injection. In one series, 3 of 5 had a reasonable response.22

In addition to the marked difference in symptoms between idiopathic orbital myositis and thyroid orbitopathy, either magnetic resonance imaging

Figure 26–7. Axial CT scan shows the pseudotumor that involves the sclera, optic nerve, and the orbit diffusely.

B

C

D

Figure 26–8. A and B, Tolosa-Hunt syndrome: clinical photographs of a patient who presented with ophthalmoplegia. C, Axial CT scan with coronal reconstruction showing apical and cavernous sinus inflammation. D, Fine-needle aspiration biopsy confirming diagnosis.

A

B

Figure 26–9. Clinical photographs of scleritis in a patient with orbital pseudotumor. (From Char et al.,25 with permission).

(MRI) or computed tomography (CT) usually shows sparing of the tendinous portion of the muscle in thyroid myopathy versus the involvement of the entire muscle in orbital myositis (see Figures 26–1 to 26–4).17 In older patients, lymphoid lesions can involve the extraocular muscles (see Figures 19–2 and 19–3), but often, there are less dramatic muscular symptoms associated with those processes.

A paucity of associated systemic signs or symptoms accompanies orbital pseudotumor; the presence of other nonocular signs or symptoms or bilateral orbital inflammation suggests a systemic disease process.23 Blodi and Gass noted that the incidence of

systemic disease was significantly higher in patients with bilateral orbital inflammation.23 Orbital inflammation is more prevalent in the middle or superior orbit than in the inferior orbital area. Some authors feel that there is a higher predilection for lymphoid lesions in the anterior orbit while pseudotumor is more likely to have posterior involvement. My experience and the experience of most others have not mirrored this.24–26

A number of less common findings have been reported with orbital pseudotumor, including optic neuritis, which can simulate a meningioma, posterior scleritis, which can simulate a melanoma, and uveitis (see Figure 26–7).27,28 The uveitis associated with orbital pseudotumor is variable. If there is predominantly anterior inflammation, it is more common to see an iridocyclitis; in diffuse orbital disease, diffuse (anterior and posterior) uveal inflammation is more prevalent. Extraorbital extension of orbital pseudotumor is rare. We believe that unless proven otherwise with a representative biopsy, extraorbital extension suggests malignant disease. Nevertheless, central nervous system (CNS) (Figure 26–12) and contiguous sinus involvement (Figure 26–13) have both been reported with orbital pseudotumors.29–34 Rarely, idiopathic inflammation can involve a single nerve, as shown in Figure 26–14. Orbital pseudotumors can rarely be a presenting sign of temporal arteritis.35 Other findings that are helpful to establish the diagnosis of temporal arteritis are jaw claudication, neck pain, elevated erythrocyte sedimentation rate (ESR), and elevated cross-reactive protein.36

Sclerosing orbital pseudotumors have been described since the 1960s and account for around 20

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Figure 26–12. Axial CT scan demonstrates biopsy-proven orbital pseudotumor with involvement of the contiguous central nervous system.

percent of orbital pseudotumors.37–39 Several investigators have commented on the possibility that this reflects a systemic process, and that often these will respond to cytotoxic agents.38,39

Wegener’s granulomatosis can simulate orbital pseudotumor.40–42 Ocular involvement is common; in one series, the eye and adnexa were involved in 58 percent of the cases. This entity is characterized by necrotizing granulomas of the respiratory tract and both necrotizing granulomas and angiitis of the

Figure 26–13. Orbital pseudotumor on axial CT scan with coronal reconstruction demonstrating involvement of the maxillary sinus.

sinuses, kidney, and orbit. Ocular involvement usually coincides with sinus disease but may include scleritis, marginal keratitis, and isolated involvement of the extraocular muscles, cranial nerves, or lacrimal gland.43 In a series of 13 cases with orbital involvement, all eventually developed sinus disease.44 Iris neovascularization can also occur. A limited form of Wegener’s granulomatosis has been described with pulmonary, but not renal, involve-

A

B

Figure 26–14. A, Direct T1-weighted coronal MRI scan of idiopathic inflammation of an orbital nerve. B, Gadolinium-enhanced biopsy shows only inflammation.

ment. The ocular findings are similar to the generalized disease.45 The CT or MRI pattern of orbital disease in Wegener’s granulomatosis is nondiagnostic; many cases have shown diffuse orbital inflammation (Figure 26–15).46 An orbital biopsy is not always diagnostic. In one series of 13 cases, giant cells were very rarely seen. In only 7 of the 13 was the classic triad of vascularitis, necrosis and granulomas noted.47,48 As part of the standard laboratory workup, tests for antinuclear antibody (ANA), blood urea nitrogen (BUN), and creatinine should be done; urinalysis should include examination of sediment. A chest radiograph should be obtained to help exclude pulmonary involvement from Wegener’s granulomatosis. The development of an antineutrophil cytoplasmic antibody (ANCA) test has made the diagnosis of Wegener’s granulomatosis easier. A subset of the ANCA, antimyeloperoxidase (AMPO), and antiproteinase 3(PR3) are possibly more specific for Wegener’s granulamatosis, and these antibody studies often correlate with disease status.49–52 Unfortunately, with greater experience, the false negatives associated with ANCA tests can be seen to be at least 30 percent.53 In a prospective study from Duke University, the specificity of the c-ANCA was 96 percent, and the sensitivity was 28 percent.54

The treatment of Wegener’s granulomatosis is outside the purview of this book. Most patients receive intravenous cyclophosphamide, although modifications of that approach have been reported.55 Other options have also been used, including antithymocyte globulin for orbital Wegener’s granulomatosis.56

Several rare processes can also simulate orbital pseudotumor. In contrast to Wegeners granulomatosis, midline lethal granuloma does not involve areas below to the cervical region; malignant histiocytosis or lymphoma can also simulate this entity.57–59 Rarely, a sino-orbital giant cell granuloma can give a medial canthal mass with an osteolytic expansile lesion that also involves the sinuses; it is a less common idiopathic inflammatory disease that involves the orbit.60 Langerhans’ cell histocytosis is discussed in the chapter of pediatric orbital tumors, and there has been a marked alteration in both our understanding of the disease and its management.61,62

Erdheim-Chester disease often will present with bilateral exophthalamos and can simulate orbital

Figure 26–15. MRI scan demonstrates a lesion in a patient with Wegener’s granulomatosis. Imaging findings are not diagnostic in this entity, although often the sinuses are involved.

pseudotumor.63,64 There have been approximately 15 cases reported since 1983, and usually these patients die of either cardiovascular or renal carcinoma. The classic hallmark of Erdheim-Chester disease is infiltration with multinucleated Touton giant cells.64

Similarly, rare patients with sarcoidosis can present in an atypical manner, such as those > 70 years old with a confusing clinical picture.65 Kimura’s disease, which is lymphoid hyperplasia with a plasma cell infiltrate can involve the sinuses and orbit in both younger and older patients; this has been more common among the Japanese.66,67 Castleman’s disease can also produce the pseudotumor pattern.68 Roseai-Dorfman disease can present with orbital disease as well, although this finding is described in only about 10 percent of patients. It is an idiopathic histoproliferative disorder, associated with cervical adenopathy, fever, and weight loss.69

Orbital tuberculosis and orbital luetic diseases are much less common today than previously. An MRI scan in a case of orbital luetic disease is shown in Figure 26–16. A chest radiograph, purified protein derivative of tuberculin (PDT) skin test, serum venereal disease research laboratories (VDRL or RPR) test, and fluorescence Treponema antibodies (FTA-ABS) should be obtained to rule out other

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Figure 26–16. Axial MRI scan demonstrating luetic involvement of both lacrimal glands.

causes of orbital inflammation. Orbital tuberculosis can occasionally present as a mass with both lytic and blastic involvement of the orbital bones. In the United States, most of the patients are immigrants with pulmonary disease, and the chest radiographs are positive. Such patients will usually respond to antituberculous therapy.70

In the evaluation of a patient with a suspected orbital pseudotumor, active orbital infection, lymphoma, and systemic disease processes should be ruled out. A review of systems should include questions regarding sinus disease, arthritis, primary malignancies, respiratory problems, and changes in renal function.

Other processes that can simulate orbital pseudotumor should be suspected, if there are either signs or symptoms of systemic disease or bilateral orbital involvement (see Table 26–1).

Chest radiography is useful to detect tuberculosis or possible hilar adenopathy associated with sarcoidosis. Usually, the latter condition presents with bilateral lacrimal gland inflammation, although other patterns of orbital involvement occur (Figure 26–17).71 A limited gallium scan, along with serum angiotensin converting enzymes (ACE), has approx-

imately 95 percent sensitivity in detecting sarcoidosis, if the patient is not on systemic steroids. A typical example of this is illustrated in Figure 20–14.

To determine whether orbital inflammation is associated with systemic vasculitis, such as polyarteritis nodosa or with systemic lupus eyrthematosus (SLE), a complete blood count (CBC), erythrocyte sedimentation rate (ESR), platelet levels, ANCA, serum ANA, complement levels, immune complex titers, and liver function tests should be obtained. SLE with involvement of the lacrimal glands is shown in Figure 26–18. To rule out Sjögren’s syndrome in a patient with xerostomia or dry eye and bilateral lacrimal gland inflammation, a labial biopsy should be obtained, since the various antibody titers are only positive in approximately 60 percent of primary Sjögren’s syndrome patients and are often negative in patients with Sjögren’s disease secondary to other processes.

Rheumatoid scleritis can simulate pseudotumor; occasionally, patients will present with a pseudorheumatoid nodule.72 The CT pattern of orbital inflammation associated with rheumatoid disease is similarly nondiagnostic.

Mixed collagen vascular disease and necrobiotic xanthogranuloma (Figure 26–19) are rarer systemic processes that can also produce orbital inflammation. The spectrum of these processes can vary widely but usually there is some systemic involvement.77,78

Figure 26–17. Axial CT scan showing biopsy-proven sarcoidosis in an atypical pattern.

Figure 26–18. SLE shown on an axial T1-weighted MRI scan, with involvement of both lacrimal glands.

One of the two more recently described syndromes include an orbital myositis as a variant of perineoplastic syndrome. In this case, the patient presented with a pattern that appeared to simulate thyroid eye disease on imaging. The patient had a high-grade lymphoma with other neuropathies, and on biopsy, there was extensive destruction of the muscles.79 Lyme disease can also produce an orbital myositis.

Leib and colleagues reported a case of a patient who had another pattern that on imaging appeared to simulate thyroid disease but who also had a giant cell myocarditis. There have been three reports of this entity, and all patients had poor outcomes due to cardiac disease.80 A number of the histiocytoses can involve the orbit, and there is often involvement in the orbit with fever and systemic manifestations.81

Sinus histiocytosis has an associated cervical lymphadenopathy, low-grade fever, anemia, leukocytosis, and elevated immunoglobulin G (IgG) levels.81,82 Orbital cellulitis, from either hematogenous spread or contiguous sinus disease, should manifest itself with significant systemic symptoms of infection.

Histiocytic disorders of the orbit are rare, and account for < 1 percent of orbital biopsies.83,84 Most of the benign and malignant histiocytosis syndromes are due to abnormal Langerhans’ cell proliferation.83 Unlike orbital pseudotumor, patients with unifocal or multifocal eosinophilic granuloma have marked orbital bone changes apparent on clinical and radiographic examination (see Figures 16–41 and 16–42). These histiocytic processes range from obviously benign to frankly malignant; in cases of multifocal eosinophilic granuloma and diffuse histiocytosis, other body systems are involved. Usually, patients with widespread disease are younger than most patients with idiopathic orbital pseudotumor. Rarely, patients with malignant histiocytosis have orbital involvement, as shown in Figure 26–20.