Ординатура / Офтальмология / Английские материалы / Orbital Tumors Diagnosis and Treatment_Karcioglu_2005

30.Tsokos M, Fauci AS, Costa J. Idiopathic midline destructive disease—a subgroup of patients with the “midline granuloma” syndrome. Am J Clin Pathol 1982;77:162–168.

31.Mann WJ, Riede UN, Bocking A. Midline malignant reticulosis. Acta Otolaryngol 1984;97:365–372.

32.Eichel BS, Harrison EG, Devine KD, et al. Primary lymphoma of the nose including a relationship to lethal midline granuloma. Am J Surg 1966;112:597–605.

33.McDonald TJ, DeRemee RA, Weiland LH. Wegener’s granulomatosis and polymorphic reticulosis—two diseases or one? Arch Otol 1981;107:141–144.

34.DeRemee RA, Weiland LH, McDonald TJ. Polymorphic reticulosis, lymphomatoid granulomatosis—two diseases or one? Mayo Clin Proc 1978;53:634–640.

35.Kwon-Chung KJ, Bennet JE. Mucormycosis. In: Kwon-Chung KJ, Bennet JE, eds. Medical Mycology. Vol 1. Philadelphia: Lea & Febiger; 1992:524–529.

36.Rootman J. Inflammatory diseases. In: Rootman J, ed. Diseases of the Orbit. Vol 1. 2nd ed. Philadelphia: JB Lippincott; 2003: 455–506.

37.Dooley DP, Hollsten DA, Grimes SR, Moss JJ. Indolent orbital

apex syndrome caused by occult mucormycosis. J Clin NeuroOphthalmol 1992;12:245–249.

38.Kameh DS, Gonzalez OR, Pearl GS, et al. Fatal rhino-orbital- cerebral zygomycosis. South Med J 1997;90:1133–1135.

39.Chang WJ, Shields CL, Shields JA, et al. Bilateral orbital involvement with massive allergic fungal sinusitis. Arch Ophthalmol 1996;114:767–768.

40.Dunlop IS, Billson FA. Visual failure in allergic aspergillus sinusitis: case report. Br J Ophthalmol 1988;72:127–130.

41.Torres C, El Naggar AK, Sim SJ, et al. Allergic fungal sinusitis: a clinical pathological study of 16 cases. Hum Pathol 1996; 27:793–799.

42.Michaels L, Lloyd G, Phelps T. Origin and spread of allergic fungal disease of the nose and paranasal sinuses. Clin Otolaryngol Allied Sci 2000;25:518–525.

43.Cruz AAV, Akeishi PMS, Chahud F, Eliac Jr. J. Sclerosing inflammation in the orbit and in the pterygopalatine and infratemporal tissue. Ophthal Plastic Reconstr Surg 2003;19:201–206.

44.Siqueira GB, Jain A, Chahud F, Cruz AAV. Bilateral infraorbital nerve involvement in idiopathic orbital myositis. Ophthal Plastic Reconstr Surg 2002;18:474–478.

Although Graves disease (GD) is a type of orbital inflammation, certain clinical features may be confused with orbital tumors. Therefore, a brief review of GD is included in this book. Graves

disease presents with a great variability of clinical signs; for this there are numerous nomenclatures and classifications in the literature. Among others, thyroidassociated orbitopathy and thyroid-related ophthalmopathy are descriptive names, even though in about 10% of the cases orbital signs are observed without chemically detectable thyroid manifestations. The name Graves disease is the time-honored terminology, used by many ophthalmologists. An orbital inflammation associated with GD can present diverse changes in the orbit, ranging from a cosmetic lid retraction to a loss of vision produced by the compressive optic neuropathy. Management must be directed to the systemic thyroid disease as well as to local ocular and orbital changes.1–4

PATHOGENESIS

The pathogenesis of GD is not completely understood; it is labeled an autoimmune process.5,6 It occurs in a genetically preselected population, usually affecting middle-aged females four to five times more frequently than males. The propensity for development and severity of the orbital disease may be related to immunogenetic predisposition as well. The hypothesis is that circulating T cells directed against an antigen in thyroid follicular cells recognize a similar antigen in orbital tissues. The activated T cells infiltrate the orbital soft tissues and the fibers of extraocular muscles.6 Thyroid-stimulating hormone receptor mRNA has been detected in orbital fat specimens.7 Clinical and experimental studies suggest that the thyrotropin receptor (TSH-R) is one of the possible antigens stimulating the autoantibodies implicated in the inflammatory changes of orbital soft tissues. The antigen may be recognized by a receptor on CD4 T lymphocytes. After antigen recognition, lymphocytes secrete cytokines that amplify the immune reaction by activating CD8 T lymphocytes or autoantibodyproducing B cells. In GD there is a predominance of T cells with a TH1 profile [interleukin (IL)2, interferon

, tumor necrosis factor ], although a TH2 profile of cytokine production (IL-4, -5, -10) has also been reported.6 The cytokines stimulate fibroblasts to synthesize and secrete glycosaminoglycans. The higher glycosaminoglycan content in GD is largely due to an excess of chondroitin sulfate and hyaluronic acid. Orbital fibroblasts may contribute to perpetuating the immune reaction by protecting T cells from apoptosis. The immune-mediated process leads to inflammation and deposition of hydrophilic mucopolysaccharides and collagen, resulting in muscle injury and scarring. The extraocular muscles are also infiltrated by lymphocytes, plasma cells, and mast cells that cause degenerative changes. Another interesting finding is the observation of degenerative muscle changes in temporal muscle biopsy samples obtained from active GD patients during decompression surgery (personal communication with Dr. Karcioglu, 2003), indicating that other musculature in the vicinity is also affected with the pathologic process. Cell-mediated immune reactions predominate in early GD, whereas humoral immunity plays a greater role in later stages.5–7

SYSTEMIC CLINICAL FEATURES

GD presents with different manifestations of thyroid dysfunction, including hyperthyroidism, hypothyroidism, and Hashimoto’s thyroiditis; it may also be seen in euthyroid patients. Hyperthyroidism is the most frequent thyroid dysfunction related to orbital disease (90%), and its systemic signs and symptoms may include weight loss, smooth skin, tachycardia, pretibial myxedema and clubbing of the fingers and toes, and subperiosteal new bone formation (thyroid dermopathy and thyroid acropathy). When the systemic features of hyperthyroidism are present, the diagnosis is rather straightforward, especially with lid retraction or exophthalmos. GD, however, may occur in apparently euthyroid (6%) or hypothyroid (1%) patients as well as in those with thyroiditis (3%).8 In these settings the diagnosis may be more challenging. All patients with possible thyroid-related orbital disease should be followed jointly with an endocrinologist. However, the ophthalmologist should also be fa-

BOX 28.1. Laboratory Tests to Evaluate Thyroid Function in Patients with Orbital Graves Disease

Serum triiodothyronine (T3) and thyroxine (T4) Triiodothyronine (T3) uptake and free thyroxine

(T4) index

Serum thyrotropin (thyroid-stimulating hormone, TSH)

Thyrotropin receptor antibodies (TRA) Thyroid hormone antibodies

miliar with the thyroid function tests (Box 28.1) and the possible effects of commonly used medications on thyroid functions (Table 28.1).3 GD is most frequent in younger women (Figure 28.1) but presents with more severe symptoms in men and patients older than 50 years of age.9 GD may be seen in children, but they are unlikely to develop severe forms of the disease. In some cases goiter is present, especially in endemic areas. Between 30 and 35% of the patients have family history of thyroid disease. The average age at the time of diagnosis of GD is 46 with an age range of 8 to 88 years.10,11

ORBITAL HISTOPATHOLOGY

The histopathologic changes can be divided into two stages. The first is the active inflammatory stage, in which one can find perivascular groups of inflammatory cells in loose edematous tissue; these include plasma cells and lymphocytes. Lymphoid follicles are

FIGURE 28.1. Bilateral proptosis due to Graves disease with a massively enlarged multinodular goiter (G).

less frequent in GD than in pseudotumors. In the second stage, the volume of the orbital content is increased by infiltration of fibroblasts, collagen, mucopolysaccharides, and glycoproteins. The mucopolysaccharides are hygroscopic. This property leads to the edema of all orbital soft tissues, particularly muscles. Increased numbers of interstitial fibroblasts and chronic inflammatory cells infiltrate the muscle fibers. In this chronic stage, the muscles become fibrotic and the anti-inflammatory treatment is no longer effective. Fibrotic phase of the disease can be demonstrated with the absence of high signal intensity in T2-weighted magnetic resonance (MR) images.12,13

TABLE 28.1. Effects of Some Commonly Used Drugs on Thyroid Function Tests.

ORBITAL CLINICAL FEATURES

The orbital clinical manifestations may present in an acute, subacute, or chronic pattern and may also start with any of the different clinical signs. All the orbital clinical signs can be unilateral or bilateral, but they may present unilaterally at the outset and later become bilateral as the disease progresses. Upper lid retraction is the most frequent orbital clinical sign in early GD (75% at initial diagnosis and 90% at some point in the clinical course) and may lead to the false impression of proptosis.14 Generally, upper lid retraction is produced by sympathetic tonicity of the Müller muscle at the beginning of the clinical course and then by the inflammation and fibrosis of the levator muscle. Less frequently, the inferior lid may also be retracted.

C H A P T E R 2 8 :

GD can also be divided into noninfiltrative or infiltrative disease.2 The noninfiltrative subgroup shows as part of the thyroid disease lid retraction, which may regress with the control of the thyroid endocrinopathy. In other cases lid retraction and proptosis are not related to the underlying endocrine disorder. The infiltrative disease manifests itself with soft tissue alterations and muscle disease.

RADIOLOGIC FEATURES

The best tests to evaluate the orbital changes of GD are the computed tomography (CT) scan and MR imaging (Figure 28.2B) (Boxes 28.2 and 28.3).21–23 The CT scan is a valuable means of depicting the enlargement of the EOMs; it also helps to document infiltrative versus noninfiltrative disease. The axial films show the medial and the lateral recti and their relationship to the optic nerve. The coronal sections are more useful to evaluate the enlargement of the muscles and the orbital apex. “Crowded” apex is an apt name to describe the hypertrophy of the muscles in the posterior orbit that may lead to compressive optic neuropathy (Figure 28.4). MR imaging is more useful than CT to evaluate the nature of the pathology within the muscle, especially in cases of EOM enlargement due to pseudotumor or metastasis.

Orbital ultrasonography can also be helpful in establishing the diagnosis of GD by showing intramuscular changes (Figure 28.5). Although muscle enlargement typically presents as a bilateral condition, affecting multiple extraocular muscles, it may begin as an asymmetrical presentation with significant changes in one orbit and none in the other. Echography is particularly useful here because this technique

BOX 28.2. The CT Features of

Graves Disease

Enlargement of muscle body (70–75% have muscle hypertrophy, mainly medial and inferior recti)

Compression of optic nerve in the orbital apex by the enlarged extraocular muscles

Increased orbital fat volume

Convex shape of ethmoidal wall in chronic disease

Image of the enlargement of the inferior rectus in back third of orbit in axial views may mimic orbital tumor

Elongation of the globe and stretch of the optic nerve secondary to proptosis

BOX 28.3. MRI Features of

Graves Disease

Increased volume of intraand extraconal space Heterogeneous fat in T1-weighted image due to vascularization and congestion (hypointense

signal)

Hypointense signal in the middle of the muscle (fat and inflammatory cell infiltration) with T1-weighted image

Hyperintense signal of the muscle with T2weighted image

Increased muscle vascularization with GDPA

can reveal very early changes in the orbit. The most commonly enlarged muscles as detected by echography are the superior rectus–levator complex and the medial rectus, followed by inferior and lateral recti. On the other hand, the most common clinical motility problem in GD is the limitation of the superior gaze, indicating the involvement of the inferior rectus muscle.24 The internal reflectivity of the involved muscle in GD is typically medium during the active inflammatory phase; it becomes high when the muscle develops fibrosis in later stages of the disease (Figure 28.5B).25 Echography can be done in the clinic quickly and inexpensively. However, ultrasonography is not effective for evaluating the posterior orbit, particularly the apex area.

Echography may also be helpful to differentiate myositis from GD. Although myositis may involve multiple muscles, unlike GD, it typically presents acutely and with severe pain.26 The involved muscle in myositis shows diffuse thickening, in the muscle itself and in its tendon. In contrast, in thyroid disease the tendon is classically spared. The internal reflec-

FIGURE 28.4. Coronal CT scan show bilateral “crowding” of the orbital apex with compression of the muscles onto the optic nerves (arrows).

FIGURE 28.5. Echograms of an enlarged right medial rectus muscle (RMR) in a patient with Graves disease.

tivity in myositis is usually low during the acute stages of the disease; however, it may change to medium or high when fibrosis has developed within the muscle after several episodes of myositis.

Echography can also be useful to differentiate neoplastic diseases of extraocular muscles from inflammatory pathology. Metastatic tumors to the intraocular muscles usually present with rapidly developing unilateral proptosis involving a single muscle.27 Color Doppler imaging can be used to monitor patients with GD for alterations in orbital blood flow parameters and their correlations with EOM enlargement, proptosis, and intraocular pressure.28,29

FIGURE 28.6. Unilateral proptosis of a patient who presented with asymmetrical Graves disease. However, 11 months after initial diagnosis, she developed bilateral involvement of all horizontal recti.

ical presentation of GD consists of bilateral proptosis with lid retraction, chemosis, and vascular tortuosity at the insertion sites of extraocular muscles, along with the typical complaint of burning sensation and tearing and pressure behind the globe, diagnosis is not difficult. In other instances, patients may develop asymmetrical proptosis, and there will be absence of congested conjunctiva and upper eyelid ptosis instead of lid retraction. These cases may be confused with the tumors of the orbit. The retraction of the upper eyelid must be distinguished from the pseudoretraction, which may occur in an effort to overcome ptosis. The most confusing picture may be an isolated enlargement of an extraocular muscle. Myositis usually presents with pain, and the imaging workup reveals the enlargement of the muscle insertion (tendon). Another feature of the pseudotumor is its rapid response to steroid treatment.33 Lymphoma is another tumor that needs to be considered in unilateral GD.34 Careful examination of imaging studies usually reveals that the lymphoproliferative process is not limited to the muscle but homogeneously extends into other soft tissues of the orbit.

Orbital metastatic disease may be confusing if it limits itself to the EOM, in which case, the imaging workup depicts nodular enlargement on CT and MRI (Figure 28.7). Irregular intramuscular neoplastic for-

DIFFERENTIAL DIAGNOSIS

It should be kept in mind that GD is the most frequent cause not only of bilateral proptosis but also of unilateral proptosis as well (Figure 28.6). The early presentation of the disease may be with asymmetrical proptosis, secondary to more active disease in one orbit. Slowly progressive unilateral presentation of GD may be confused with orbital pseudotumors (orbital myositis, fibrosclerosis) and neoplasia (lymphoma, leukemia, metastatic tumors).30,31 In certain instances, solitary vascular lesions, such as an orbital varix, may also be confused with GD.32 When the clin-

FIGURE 28.7. An enlarged right lateral rectus muscle, secondary to metastatic colon cancer, showing slight proptosis of the right eye. Note the heterogeneity of the belly of the muscle, due to infiltrating carcinoma. All other muscles are within normal limits.

mations are best depicted with T2-weighted hypersignal of MRI. Systemic workup to identify a possible primary tumor should be started immediately in these cases.

MANAGEMENT AND PROGNOSIS

A detailed discussion of GD management is not within the scope of this book. It is briefly mentioned, however, that there are different therapies for GD. The orbital disease may have a self-limited course from 6 months to 3 years, but the evolution of the disease cannot be predicted. Medical therapies include artificial tears and ointments, elevation of the head during sleep, and ice compress. Oral and intravenous corticosteroid treatments are recommended by some for acute or subacute advancing disease that affects the cornea and the optic nerve.35–38 In case of severe neuropathy, it may be necessary to use intravenous corticosteroid pulse (Tg/day) 1 g methyprednisolone for 3 days. Peribulbar triamcinolone (20 mg of triamcinolone into each orbit every week for 4 weeks) may be effective to improve proptosis and diplopia, especially in acute cases.39 The peribulbar administration does not cause local or systemic adverse effects. A poor response to local or systemic steroids does not exclude a good response to radiation. Radiotherapy has been used for many years with mixed benefits, especially for optic neuropathy, but recent reports question its effectiveness.40,41

Decompression is the time-honored surgical treatment for reducing exophthalmos and for optic neu- ropathy.42–44 EOM imbalance, which may develop as a manifestation of the disease or as a complication of orbital decompression, requires surgery after 6 months of stability.45 Eyelid surgery may be used as the last surgical intervention for retraction and cosmesis.46

In 1996 Bartley reported that about 75% of 120 patients required either no therapy or only supportive measures, 6% were treated with systemic corticosteroids, and 20% underwent one or more surgical procedures.11

References

1.Char DH. Thyroid Eye Disease. Baltimore: Williams & Wilkins; 1995.

2.Rootman J, ed. Diseases of the Orbit. Philadelphia: JB Lippincott; 1988.

3.Felig P, Baxter JD, Frohman LA. Endocrinology and Metabolism. 3rd ed. New York: McGraw-Hill; 1995.

4.Pérez Moreiras José V, Prada Sánchez MC. Oftalmopatia Distiroidea. Barcelona: Edika Med; 1997.

5.Warwar R. New insights into pathogenesis and potential therapeutic options for Graves orbitopathy. Curr Opin Ophthalmol 1999;10:358–361.

6.Diez J. Therapy of Graves’ ophthalmopathy: a novel application of somatostatin analogues. Expert Opin Pharmacother 2001–2;9:1361–1365.

7.Bradley E. Graves’ ophthalmopathy. Curr Opin Ophthalmol 2001;12:347–351.

8.Bartley G, et al. Clinical features of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol 1996;121:284–290.

9.Kendler DL, Lippa J, Rootman J. The initial clinical characteristics of Graves’ orbitopathy vary with age and sex. Arch Ophthalmol 1993;111:197–201.

10.Bartley G, et al. The chronology of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol 1996;121:426–434.

11.Bartley G, et al. Long-term follow-up of Graves’ ophthalmopathy in an incidence cohort. Ophthalmology 1996;103: 958–962.

12.Ohnishi T, Noguchi S, Murakami N, et al. Extraocular muscles in Graves’ ophthalmopathy: usefulness of T2 relaxation time measurements. Radiology 1994;190:857–862.

13.Utech CI, Khatibnia U, Winter PF, Wulle KG. MR T2 relaxation time for the assessment of retrobulbar inflammation in Graves’ ophthalmopathy. Thyroid 1995;5:185–193.

14.Bartley G. The differential diagnosis and classification of eyelid retraction. Ophthalmology 1996;103,1:168–176.

15.Danesh-Meyer H, Savino P, Deramo V, et al. Intraocular pressure changes after treatment for Graves’ orbitopathy. Ophthalmology 2001;108:145–150.

16.Nunery WR, Martin TR. The association of cigarette smoking with clinical subtypes of ophthalmic Graves’ disease. Ophthalmic Plast Reconstr Surg 1993;9:77–82.

17.Bartley G. Evolution of classification systems for Graves’ ophthalmopathy. Ophthalmic Plast Reconstr Surg 1995;11,4:229– 237.

18.Werner SC. Modification of the classification of the eye changes of Graves’ disease. Am J Ophthalmol 1977;83:5,725–726.

19.Van Dyck H. Orbital Graves’ disease. A modification of the “NO SPECS” classification. Ophthalmology 1981,88:479–483.

20.Werner SC. Classification of the eye changes of Graves’ disease. J Clin Endocrinol 1969;29:782.

21.Peyster GR. Hoover E. Computerized Tomography in Orbital Disease and Neuro-Ophthalmology. Chicago: Year Book Medical Publishers; 1984:97–114.

22.De Potter PV, Shields JA, Shields CL. MRI of the Eye and Orbit. Philadelphia: JB Lippincott; 1995.

23.Oguz V, Yolar M, Pazarli H. L’Intérêt de l’IRM dans le traitement de la myopathie de l’orbitopathie dysthyroidienne. J Fr Ophtalmol 2001;24:842–846.

24.Rootman, J. Graves’ orbitopathy. In: Rootman J, ed. Diseases of the Orbit. Philadelphia: JB Lippincott; 1988:248.

25.Ossoinig, KC. The role of standardized ophthalmic echography in the management of Graves’ ophthalmopathy. Dev Ophthalmol 1989;20:28.

26.Kennerdell, JS, Dresner, SC. The non-specific orbital inflammatory syndromes. Surv Ophthalmol 1984;29:97.

27.Slamovits, TL, Burde, RM. Bumpy muscles. Surv Ophthalmol 1988;33:189.

28.Numan AM, Günalp I. Color Doppler imaging of the orbital vasculature in Graves’ disease with computed tomographic correlation. Br J Ophthalmol 2000;84:1027–1030.

29.Williamson TH, Harris A. Color Doppler ultrasound imaging of the eye and orbit. Surv Ophthalmol 1996;40:255–267.

30.Van der Pol R, Nieuewenhuis MG, Mourtis MP. Multifocal fibrosclerosis presenting as Grave’s orbitopathy. Bilateral exophthalmos. Graefe Arch Clin Exp Ophthalmol 1999;237: 256–258.

31.Lam A, Faye M, Seck CM, et al. Non-sarcomatous bilateral exophthalmos disclosing acute myeloblastic leukemia in children. J Fr Ophtalmol 1996;19:283–286.

32.Yazici B, Yazici Z, Gelisken O. An unusual case: bilateral orbital varices. Acta Ophthalmol Scand 1999;77:453–455.

33.Srivastava S, Newman J. Pseudo-pseudotumor. Surv Ophthalmol 2000;45:135–138.

34.Jones IS, Jakobiec FA. Diseases of the Orbit. New York: Harper & Row; 1979.

35.Fatourechi V. Medical treatment of Graves’ ophthalmopathy.

Ophthalmol Clin North Am 2000;13,4:683–691.

36.Marcocci C, Bartalena L, Tanda ML, et al. Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves’ ophthalmopathy: results of a prospective, sin- gle-blind randomized study. J Clin Endocrinol Metab 2001; 86:3562–3567.

37.Werner SC. Prednisone in emergency treatment of malignant exophthalmos. Lancet 1966;7:1004.

38.Bartalena L, Marocci C, Pinchera A. Treating severe Graves’ ophthalmopathy. Baillieres Clin Endocrinol Metab 1997;11: 521–536.

39.Ebner R, et al. Tratamiento de la oftalmopatia asociada con distiroidismo con triancinolona periocular. Arch Oftalmol Buenos Aires 2001;76:55–66.

40.Schaefer U, Hesselmann S, Micke O, Willich N. A long-term

follow-up study after retro-orbital irradiation for Graves’ ophthalmopathy. Int J Radiat Oncol Biol Phys. 2002;52:192–197.

41.Gorman C, Garrity J, Bartley G. A prospective, randomized, double-blind placebo-controlled study of orbital radiotherapy for Graves’ ophthalmopathy. Ophthalmology 2001;108,9: 1523–1534.

42.Meyer D. Surgical management of Graves’ orbitopathy. Curr Opin Ophthalmol 1999;10:343–351.

43.Tarrus-Montaner S, Lucarelli J, Lemke B, Dortzbach R. The surgical treatment of Graves’ orbitopathy. Ophthalmol Clin North Am 2000;13:693–704.

44.Goldberg RA. The evolving paradigm of orbital decompression surgery. Arch Ophthalmol 1998;116:95–96.

45.Nguyen VT, Park DJ, Levin L, Feldon SE. Correction of restricted extraocular muscle motility in surgical management of strabismus in Graves’ ophthalmopathy. Ophthalmology 2002;109:384–388.

46.Harvey JT, Anderson RL. The aponeurotic approach to eyelid retraction. Ophthalmology 1981;88:513.

Many inflammatory conditions, ranging from simple foreign body granuloma (Figure 29.1) to the most complex vasculitis of a collagen

tissue disease, may cause proptosis owing to volume increase in the orbit.1–3 The great majority of these disorders present with typical ocular/orbital signs and symptoms, as well as systemic manifestations, that would differentiate them from neoplastic conditions. Others, however, particularly the ones that tend to develop localized mass lesions rather than infiltrating inflammation, may simulate orbital neoplasms. This chapter summarizes the salient clinical features of the more common, mass-forming inflammatory lesions, which can be confused with orbital neoplasms; others are listed in Tables 29.1 and 29.2. Some related clinical presentations are detailed in Chapter 27 with illustrations from cases.

INFECTIONS

Tuberculosis

Ocular and adnexal tuberculosis is usually seen with typical manifestations secondary to systemic Mycobacterium infection, and it is rather unlikely that this entity will be confused with neoplastic disor- ders.4–6 However, the clinical picture of the disease is changing, with many cases developing from atypical mycobacteria that are resistant to traditional multidrug treatment.7,8 With the increase in the numbers of immunologically suppressed individuals secondary to viral epidemics and the wider use of immunosuppressant antimetabolites in longer surviving cancer and transplant patients, the incidence of tuberculosis has been rising steadily during the past two decades. It has been reported that individuals with HIV/AIDS have an incidence of tuberculosis 500-fold greater than that of the general population.9

Extrapulmonary tuberculosis, including the orbital disease, is more often seen in children and nonwhite patients.10 Although ocular and adnexal infections due to atypical mycobacteria are rare, occasional cases presenting as dacryocystitis, endophthalmitis, localized

periostitis, or periorbital and orbital mass lesions have been reported.11,12 Orbital tuberculosis due to atypical mycobacteria may present as a well-delineated mass lesion, causing gradual displacement of the eye and extraocular motility disturbances.13,14 The history of an antecedent penetrating injury is a well-known presentation of tuberculosis, due to atypical mycobacteria. If tuberculosis is suspected clinically, tuberculin skin testing will be helpful in differential diagnosis; but a biopsy, with or without positive cultures, is necessary for the confirmation of the disease. Histopathology of tuberculosis consists of zonal granulomatous inflammation with numerous epithelioid histiocytes surrounding a necrotic (caseating) center. Tissue diagnosis is pathognomonic only with the documentation of positive acid-fast organisms. However, it is well known that acid-fast positive mycobacteria often are not demonstrated in tuberculosis, even though cultures of orbital tissue may grow M. tuberculosis or atypical mycobacteria.

It should be remembered that atypical mycobacterial infections generally are resistant to routine antituberculous chemotherapy; clarithromycin, an oral macrolide antibiotic, has been reported to be an effective medication for atypical mycobacterial infections.12

Fungal Infections

Commonly encountered fungal infections of the orbit are mucormycosis and aspergillosis. Mucormycosis rarely produces clinical manifestations to mimic orbital tumors. The fulminant course of orbital disease with pain, massive proptosis, extensive extraocular motility disturbance, and hemorrhagic chemosis, coupled with necrotic eschars of the nasal, oropharyngeal mucosa or periorbital skin, is typical of this infection and does not leave too much room for differential diagnosis.15 Imaging may be helpful by demonstrating a relationship between the orbital and sinus disease. T2-weighted magnetic resonance imaging (MRI) usually reveals hypointensity of fungal disease, and computed tomography (CT) shows focal calcification of the orbitosinusoidal mass.16 However, certain cases involving the eyelids and the orbit may present with gradually de-

FIGURE 29.1. Foreign body granuloma of the superior orbit in a 9- year old girl. At surgery, infiltrating foreign body granuloma composed of epithelioid cells and multinucleated giant cells was identified. The nature of the foreign body (arrow) could not be determined.

veloping, localized lesions, which may be confused with rapidly growing tumors, such as rhabdomyosarcoma and Ewing’s sarcoma (see Chapter 27). Diagnosis is established by documentation of typical, large mucor hyphae, which show lack of septation in tissue examination by histopathology or cytopathology.

Orbital mucormycosis is an emergency situation because it causes rapidly progressing necrotizing inflammation secondary to the propensity of the fungus to involve blood vessels. Orbital exploration should be done immediately to establish the diagnosis by identifying the broad, nonseptated hyphae and for extensive surgical debridement as well as irrigation with antifungal agents.

Orbital aspergillosis usually presents with a more insidious onset, particularly when it develops in individuals who are not immunocompromised.17 In these cases, the disease may follow a protracted course with a well-delineated mass developing within the orbit without diagnostic features on CT or MRI.17,18 The latter group produces a densely sclerosed, chronic inflammatory reaction with granulomatous foci. These

are the cases that are difficult to diagnose and may be confused with neoplasms (Figure 29.2). The diagnosis is dependent on the confirmation of septate hyphae that branch at a typical 45° angle. The Gomori methenamine silver (GMS) technique highlights the walls of the hyphae. Although the diagnosis can easily be established by the identification of the organisms in fulminating cases, the sclerosing type may not readily reveal the causative organism in small biopsy samples. The tissue sample may show only dense fibrous tissue, without any granulomas or organisms. Although fine-needle aspiration biopsy (FNAB) has been used to diagnose fungal infections, when aspergillosis is suspected, it is better to perform incisional biopsies on the lesions. The limited sample obtained by FNAB is more likely to be nondiagnostic in sclerosing cases. The management of orbital aspergillosis includes surgical debridement and antifungal therapy. Wide surgical excision of the involved tissues is suggested in the sclerosing type, since the infection has a tendency to recur.19,20

Parasitic Infections

Echinococcus granulosus, otherwise known as hydatic cyst, is probably the most common parasitic disease of the orbit. Hydatid disease is most commonly encountered in the liver (60–70%) and lungs but may spread hematogenously into the systemic circulation and infect multiple extrahepatic sites. Orbital hydatid disease is rare, comprising less than 1% of all cases in the body. Once in the orbit, most lesions lie within the muscle cone in children and young adults.21,22 The diagnosis of orbital hydatid disease is suggested by signs and symptoms of a unilateral, orbital spaceoccupying mass, such as gradual progressive proptosis and diminished extraocular motility. Eosinophilia is present in approximately 25% of cases. CT findings usually include a hypodense, nonenhancing, often unilocular (but occasionally multilocular) cystic lesion, well delineated by a thin capsule that may or may not show enhancement in contrast studies. MRI discloses a low intensity signal on T1-weighted images and a high-intensity signal on T2-weighted images. Microscopic examination of the cyst fluid