●The tumor is raised and dome shaped with rolled lateral borders and a central keratin core.

●There is occasional pain, irritation or discomfort.

Nodules on the conjunctiva may result in foreign body sensation and tearing; keratoacanthomas on the face may grow larger and regress more slowly than those on other parts of the body and some do not spontaneously regress at all.

Laboratory findings

●Biopsy of keratoacanthomas is essential.

●These lesions can closely resemble squamous cell carcinomas.

REFERENCES

Grossniklaus HE, Martin DF, Solomon AR: Invasive conjunctival tumor with keratoacanthoma features. Am J Ophthalmol 109:736–738, 1990.

Grossniklaus HE, Wojno TH, Yanoff M, Font RL: Invasive keratoacanthoma of the eyelid and ocular adnexa. Ophthalmology 103:937–941, 1996.

Hintschich CR, Stefani FH: Keratoacanthoma of the eyelid area: problems and risks in diagnosis and therapy. Klin Monatsbl Augenheilkd 210:219–224, 1997.

LoSchiavo A, Pinto F, Degener AM, et al: Keratoacanthoma centrifugum marginatum: possible etiological role of papillomavirus and therapeutic response to etretinate. Ann Dermatol Venereol 123:660–663, 1996.

TREATMENT

Surgical

Lesions of periocular or ocular tissue are best treated with wide excisional biopsy.

Other

●Curettage.

●Cryotherapy.

●Radiation.

●Intralesional injections: fluorouracil (5-FU), methotrexate, interferon.

●Topical: 5-FU.

●Oral: etretinate, isotretinoin.

PRECAUTIONS

Whenever there are multiple accepted forms of therapy, the entity can be difficult to treat. Early intervention around the eye is important for both diagnosis and management, so excisional biopsy is the treatment of choice.

Occasional progression and malignant change of keratoacanthomas, especially in immunosuppressed patients, have been reported; however, most of these benign tumors that underwent a change probably were carcinomas that were not recognized initially because of an inadequate biopsy.

Recurrence rates of these lesions require a repeat biopsy because basal cell or squamous cell carcinoma may have developed or may have been missed.

COMMENTS

Aggressive surgical treatment for periocular or ocular keratoacanthoma is necessary because lesions in this area are more aggressive, may be disfiguring and cosmetically unacceptable and are easier to treat when they are small. A diagnosis must be made because the lesions may be malignant or associated with a malignancy. It cannot be predicted when or if spontaneous involution will occur.

133LEIOMYOMA

(Iris Leiomyoma, Ciliary Body Leiomyoma, Orbital Leiomyoma, Ocular Leiomyoma)

Manolette R. Roque, MD

Manila, Philippines

Barbara L. Roque, MD

Manila, Philippines

ETIOLOGY/INCIDENCE

Leiomyoma is a rare, benign smooth muscle tumor representing 2.3% to 14.5% of all primary iris tumors. It may involve the sphincter and dilator muscles of the iris, ciliary muscle of the ciliary body, Müller’s or capsulopalpebral muscle in the orbit.

Ocular leiomyoma is reported most frequently in Caucasian females and younger patients, with cases ranging from 10 to 77 years old.

COURSE/PROGNOSIS

Leiomyoma is usually well-circumscribed and has a tendency for slow growth. Although degeneration may occur within its substance, resulting in hemorrhage and local necrosis, spread by continuity, contiguity, or metastasis has not been recorded. The prognosis for vision depends on the location and size of the tumor and is usually excellent. Prognosis for life is excellent.

DIAGNOSIS

Clinical signs and symptoms

Iris

●Localized, flat to slightly elevated, nonpigmented, transparent, vascular tumor, often at the region of the sphincter muscle.

coma or cataract.

Ciliary body

●Pigmented mass that slowly increases in size and may distort the iris, compress the lens, or locally occlude the filtration angle.

●Asymptomatic until it grows large enough to affect neighboring ocular structures.

body circumference.

Orbital leiomyoma is well encapsulated and usually shells out without difficulty.

COMPLICATIONS

Hyphema, proptosis, glaucoma or localized cataract may result from leiomyoma.

Orbit

●Extremely rare, well-encapsulated, vascular tumor that is usually located in an extraconal position.

●Presents as painless proptosis, sometimes with intermittent episodes of pain.

Laboratory findings

Regardless of the primary site of the tumor, the diagnosis of leiomyoma is only made on histologic examination.

Light microscopy

●A leiomyoma is composed of interlacing, densely packed, elongated, spindle-shaped cells, with long oval nuclei that tend to be arranged in a palisading manner, and granular eosinophilic cytoplasm of the cells and longitudinal myofibrils within the cells and are best seen with phosphotungstic acid hematoxylin stain.

COMMENTS

An iris or a ciliary body leiomyoma cannot be differentiated clinically from a malignant melanoma and is diagnosed on the basis of histologic examination.

Fluorescein iridography was used as a preoperative mapping procedure to determine the actual tumor size, which may extend beyond that noted on clinical observation. In addition, the blood supply of the tumor may be determined before surgery. Radioactive phosphorus uptake may be done before surgery to help assess the vascularity of the tumor. More significantly, the extension of the tumor in the anterior chamber angle can be determined so it can be determined whether an iridectomy or iridocyclectomy is required.

cells are positive for smooth muscle actin, desmin and vimentin. The tumor cells are negative for S-100 and melanin.

Differential diagnosis

Iris amelanotic melanoma; intraocular or iris foreign body; juvenile xanthogranuloma; peripheral anterior synechiae; lymphoid hyperplasia; iridoschisis; iridic neovascularization; atypical vessels of the iris; hemangioma; siderosis; hemosiderosis; iridic abscess; ciliary body melanoma; fully encapsulated orbital tumors.

TREATMENT

Ocular

microscopic verification. Am J Ophthalmol 66:1061–1068, 1968.

Roque MR, Roque BL, Foster CS: Leiomyoma, iris. Emedicine 2005. Online. Available at: http://www.emedicine.com/oph/topic589.htm. Mar 16, 2005.

Sevel D, Tobias B: The value of fluorescein iridography with leiomyoma of the iris. Am J Ophthalmol 74:475–478, 1972.

Shields J, Shields C, Eagle R, DePotter P: Observations on seven cases of intraocular leiomyoma. Arch Ophthalmol 112:521–528, 1994.

134 LIPOSARCOMA 190.1

Alan A. McNab, MBBS, FRANZCO

Melbourne, Victoria

Brown HH, Kersten RC, Kulwin DR: Lipomatous hamartoma of the orbit. Arch Ophthalmol 109:240–243, 1991.

Cai YC, McMenamin ME, Rose GE, et al: Primary liposarcoma of the orbit: a clinicopathological study of seven cases. Ann Diagn Pathol 5:255–266, 2001.

Enziger FM, Weiss SW: Soft tissue tumors. St Louis, CV Mosby, 1983:242–280.

Fezza J, Sinard J: Metastatic liposarcoma to the orbit. Am J Ophthalmol 123:271–272, 1997.

Kindblom LG, Baker LH, Svendsen P: Liposarcoma: a clinicopathological, radiographic and prognostic study. Acta Pathol Microbiol Immunol Scand 253(suppl.):1–71, 1975.

Lane CM, Wright JE: Primary myxoid liposarcoma of the orbit. Br J Ophthalmol 72:912–917, 1988.

McNab AA, Moseley I: Primary orbital liposarcoma: clinical and computed tomographic features. Br J Ophthalmol 74:437–439, 1990.

Authors disagree as to whether lymphangiomas actually represent a distinct clinical or histopathologic entity; some do not differentiate these lesions from a larger spectrum of orbital venous anomalies. Others stress that hemodynamic distinctions do exist and should be used to categorize these lesions as well as guide their management.

Clinical signs and symptoms

●Proptosis: slowly progressive or sudden and painful.

●Ptosis.

●Conjunctival chemosis or hemorrhage: if superficially located.

●Optic neuropathy: if orbital hemorrhage is severe.

●Strabismus: if the lesion is large and infiltrative.

●Cutaneous blood-filled cysts: if superficially located.

●Oral mucosal vascular lesions: in deeply located lesions, with frequent intracranial component.

135 LYMPHANGIOMA 228.1

Michael Kazim, MD

New York, New York

Jennifer Scruggs, MD

New York, New York

Joseph D. Walrath, MD

New York, New York

ETIOLOGY/INCIDENCE

Lymphangioma is a benign vascular hamartoma commonly identified in the head and neck. Lymphangioma is likely derived from vascular mesenchyme that has inappropriately differentiated into isolated lymphatic-like spaces without connection to the systemic circulation. The incidence rate is low.

COURSE/PROGNOSIS

The majority of patients present in the first decade of life. There are two growth patterns. Slow enlargement occurs over decades, producing progressive proptosis. In contrast, explosive growth results from intralesional hemorrhage, likely from intrinsic nutrient vessels, or in association with an upper respiratory tract infection with proliferation of the lymphoid aggregates.

Sequelae include spontaneous resolution of the proptosis, usually over a period of weeks to months; persistent proptosis; cutaneous disfigurement; compressive optic neuropathy; and restrictive strabismus.

DIAGNOSIS

Histologically, there are nonencapsulated, thin-walled, endothe- lium-lined channels and cystic vascular spaces which may contain lymph-like fluid. Scattered lymphoid aggregates or hemorrhage may be present. Clinically, the lesions may be located superficially in the orbit and are cystic. More commonly, they are infiltrative and diffuse in the orbit. Those located apically or with intracranial extension are more likely to be associated with submucosal oral lesions and noncontiguous intracranial vascular anomalies.

Laboratory findings

Ultrasonography

A 10-MHz probe is used to image the anterior two thirds of orbit. The soft-tissue and cystic components of the lesion are identified. Ultrasonography lacks specificity and soft-tissue detail.

Computed tomography

Computed tomography is best for imaging the bone deformity produced by long-standing lesions. There is good soft-tissue detail with this method, but it lacks specificity.

Magnetic resonance imaging

Magnetic resonance imaging provides superior soft-tissue details. The identification of cystic structures and blood-serum interfaces is diagnostic of the lesion. This technique is most helpful in surgical planning.

Differential diagnosis

●Hemangioma.

●Varix.

●Orbital hemorrhage.

●Orbital cellulites.

●Rhabdomyosarcoma.

●Neuroblastoma.

TREATMENT

Supportive

Management of lymphangiomas is difficult and observation is preferred. Except in cases of optic neuropathy, await the spontaneous resolution of hemorrhagic cyst or lymphoid hyperplasia associated with upper respiratory infection. Oral corticosteroids may help in the acute phase to resolve the lymphoid infiltrate.

Surgical

Surgery is generally avoided because manipulation of the tumor may promote further spontaneous hemorrhages. In addition, complete surgical excision is difficult due to the infiltrative nature of the tumor and risk of damage to surrounding structures. Recurrence rate is high.

Indications for surgery include compressive optic neuropathy, disabling diplopia and disfigurement.

Procedures include cyst drainage, which may be accomplished by computed tomography or ultrasound-guided percutaneous

needle or open orbitotomy. Debulking of the lesion, often with multiple partial resections, may achieve satisfactory results. The surgical approach is guided by the location of the tumor. Carbon dioxide laser may be a useful adjuvant in the more solid vascularized variant.

There have been recent reports of the successful use of OK432 (Picibanil; a sclerosing agent) in the treatment of macrocystic lymphangiomas located elsewhere in the head and neck region. There are few reports of the use of OK-432 in orbital lymphangiomas. Anticipated side effects of OK-432, including a profound local inflammatory response with edema, may produce elevated orbital pressure resulting in acute glaucoma or compressive optic neuropathy. More data is needed to determine the efficacy and safety of this treatment for orbital lesions.

COMPLICATIONS

●Optic neuropathy: pressure from tumor growth or hemorrhagic cyst.

●Strabismus: due to infiltration of the tumor.

●Ptosis.

●Amblyopia: secondary to occlusion or astigmatism.

●Orbital bone asymmetry: due to pressure effect of the tumor mass.

●Disfigurement.

COMMENTS

Lymphangioma is a histologically benign but clinically aggressive lesion. It generally is first identified in childhood, when it can adversely affect vision development. In most cases, it cannot be safely extirpated and therefore may result in a lifelong series of hemorrhages that threaten visual acuity, produce severe pain, and ultimately result in disfigurement that is socially challenging. The role of the treating physician is supportive, knowing that the acute episodes are generally self-limited. Surgery should be reserved for the more severe cases of disfigurement, diplopia or optic neuropathy.

Kazim M, Kennerdell JS, Rothfus W, et al: Orbital lymphangioma: correlation of magnetic resonance imaging and intraoperative findings. Ophthalmology 99:1588–1594, 1992.

Kennerdell JS, Maroon JC, Garrity JA, et al: Surgical management of orbital lymphangioma with carbon dioxide laser. Am J Ophthalmol 102:308– 314, 1986.

Pitz S, Dittrich M: Orbital lymphangioma. Br J Ophthalmol 84:124–125, 2000.

Rootman J, Kao SCS, Graeb DA: Multidisciplinary approaches to complicated vascular lesions of the orbit. Ophthalmology 99:1588, 1992.

Skalka HW, Callahan MA: Ultrasonically-aided percutaneous orbital aspiration. Ophthalmic Surg 10:41–43, 1979.

Suzuki Y, Obana A, Gohto Y, et al: Management of orbital lymphangioma using intralesional injection of OK-432. Br J Ophthalmol 84:614–617, 2000.

Tunc M, Sadri E, Char DH: Orbital lymphangioma: an analysis of 26 patients. Br J Ophthalmol 83:76–80, 1999.

Wilson ME, Parker PL, Chavis RM: Conservative management of childhood orbital lymphangioma. Ophthalmology 96:484, 1989.

Wright JE, Sullivan TJ, Garner A, et al: Orbital venous anomalies. Ophthalmology 104:905–913, 1997.

136 LYMPHOID TUMORS 202.8

(Inflammatory Pseudotumor, Ocular

Adnexal Lymphoma, Intraocular

Lymphoma, Neoplastic

Angioendotheliomatosis, Reactive

Lymphoid Hyperplasia)

Michael D. Eichler, MD

St. Cloud, Minnesota

Ocular lymphoid tumors represent an intriguing and diverse area of ophthalmology. Our knowledge of the pathology, natural histories and treatment responses of these tumors continues to evolve. Areas of overlap in histology create diagnostic challenges, although immunohistochemistry and molecular genetic analysis have greatly aided this effort. Three main categories of ocular lymphoid tumors exist based on natural history: orbital inflammatory pseudotumor, ocular adnexal lymphoid tumors and intraocular lymphoid tumors.

REFERENCES

Coll GE, Goldberg RA, Krauss H, et al: Concomitant lymphangioma and arteriovenous malformation of the orbit. Am J Ophthalmol 112:200, 1991.

Giguere CM, Bauman NM, Sato Y, et al: Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial. Arch Otolaryngol Head Neck Surg 128:1137–1144, 2002.

Harris GJ: Orbital vascular malformations: a consensus statement on terminology and its clinical implications. Am J Ophthalmol 127:453–455, 1999.

Harris GJ, Sakol PJ, Bonavolenta G, et al: An analysis of thirty cases of orbital lymphangioma. Ophthalmology 97:1583–1592, 1990.

Jackson IT, Carreno R: Hemangiomas, vascular malformations and lymphovenous malformations: classification and methods of treatment. Plast Reconstr Surg 91:1216, 1993.

Jones IS: Lymphangiomas of the ocular adnexa: an analysis of sixty-two cases. Am J Ophthalmol 51:481–509, 1961.

Katz SE, Rootman J, Vangveeravong S, et al: Combined venous lymphatic malformations of the orbit (so-called lymphangiomas): association with noncontiguous intracranial vascular anomalies. Ophthalmology 105:176–184, 1998.

ORBITAL INFLAMMATORY PSEUDOTUMOR

ETIOLOGY/INCIDENCE

Orbital inflammatory pseudotumor is a localized disease that mimics an orbital tumor in causing proptosis due to diffuse multifocal infiltration of inflammatory cells; only rarely does it form a discrete mass.

Orbital inflammatory pseudotumor accounts for approximately 10% of orbital lesions. The age of onset is earlier than that of lymphoma, most commonly occurring in the third to fifth decades of life. About 10% of patients present in the first two decades of life.

COURSE/PROGNOSIS

●Orbital inflammatory pseudotumor typically responds rapidly to treatment, with complete resolution of symptoms in 1 to 2 months.

●Pseudotumor usually occurs as a single episode, but recurrences have been reported after 7 years.

●Intracranial extension of chronic pseudotumor has been reported.

●Pseudotumor is a diagnosis of exclusion based on the clinical, radiologic, and occasional histopathologic data. Systemic disease is associated in 5–10% of cases; these associated diseases are endocrinopathy, neoplasm or vasculitis. Infection must be ruled out prior to treatment.

●Orbital inflammatory pseudotumor does not have the potential for malignant transformation, however, neoplasm may present with inflammation.

●When orbital pseudotumors are bilateral, the chance that a systemic disorder will be discovered is increased, especially in adults.

DIAGNOSIS

Clinical signs and symptoms

Orbital inflammatory pseudotumor is characterized by a wide spectrum of presentations including acute pain, hyperemia, chemosis, periocular edema and erythema, extraocular motility disturbances, ptosis and the rapid development of proptosis. Inflammatory involvement adjacent to the optic nerve may produce visual disturbances and papillitis. Orbital inflammatory pseudotumor frequently affects the lacrimal gland, creating diagnostic confusion. A chronic form of pseudotumor exists that can lead to unrelenting severe pain and ophthalmoplegia due to sclerosis of orbital tissues.

Laboratory findings

●Computed tomography (CT) aids in the diagnosis of orbital inflammatory pseudotumor with diffuse infiltration and enlargement of orbital fat, extraocular muscles, optic nerve, and/or lacrimal gland with blurring of the margins. Rarely a mass and/or infiltration of the orbital apex or cavernous sinus may be seen. Bone erosion does not occur.

●Sjögren’s syndrome.

●Vasculitis: Wegener’s granulomatosis, polyarteritis nodosa, giant cell arteritis.

●Neoplasia.

●Vascular disorders: dural-cavernous sinus arteriovenous fistula, orbital varix.

TREATMENT

●Systemic steroids are most helpful in patients with acute or subacute lesions and least effective in those exhibiting the histologic features of a chronic sclerotic phase. Chronic pseudotumor typically requires adjuvant therapy with radiation or chemotherapy.

●High doses of prednisone (80–100 mg/day) should be continued for a total of 3 weeks and tapered over a 3- to 6-week period to prevent a rebound.

●Radiation may be necessary for steroid-resistant or steroiddependent lesions, with 20 cGy over 10 days.

●Recalcitrant cases may respond to immunosuppression therapy with methotrexate, cyclosporine, azathioprine, or cyclophosphamide.

●Surgical debulking is rarely necessary.

OCULAR ADNEXAL LYMPHOID TUMOR

ETIOLOGY/INCIDENCE

Ocular adnexal lymphoid tumors encompass both reactive lymphoid hyperplasia (RLH) and lymphoma (OAL). These disorders have similar natural histories, histologic features, and responses to therapy. While the incidence of lymphoma is increasing, this is in part due to an aging population and an increase in AIDSrelated lymphomatous diseases. Chronic antigenic stimulation of mucosa associated lymphoid tissue leading to hyperplasia and potential genetic aberrations and malignant transforma-

entation typically does not require a biopsy. A full response to treatment without recurrence is diagnostic.

●Histologic features of pseudotumor are a light dispersal of lymphocytes, plasma cells, macrophages, neutrophils and occasional eosinophils (particularly in children) around blood vessels and interstitially within the orbital fat, extraocular muscles, Tenon’s space, and lacrimal gland. The involved tissue is variably fibrotic and the lymphoid component is not hyperplastic or sheet-like.

●Histologic features of chronic pseudotumor are increasing amounts of fibrosis with bridging septa replacing orbital fat and encasing extraocular structures.

●Graves’ disease mimics or produces the clinical picture of an orbital pseudotumor, and the histopathologic appearance is remarkably similar to that of inflammatory pseudotumor.

●Orbital cellulitis of bacterial origin can usually be differentiated by historical features, sinus involvement and resolution with intravenous antibiotics.

Differential diagnosis

●Grave’s orbitopathy.

●Infection: bacterial, fungal, parasitic.

●Granulomatous disease: sarcoidosis, idiopathic noninfectious granulomatous inflammation, Erdheim–Chester disease, necrobiotic xanthogranulomatosis.

associated with lymphoid tumor pathogenesis.

Ocular adnexal lymphoid tumors occur in 1.5% to 4.0% of systemic lymphomas and fewer than 1% of patients have ocular involvement as the initial presentation. Nearly all ocular adnexal lymphomas are non-Hodgkin’s lymphomas (NHLs) of B-cell origin. The age of onset for lymphomas typically is the sixth or seventh decade of life.

COURSE/PROGNOSIS

●A continuum of disease from RLH to NHL has been supported by DNA analysis showing monoclonal cells within RLH lesions and progression to systemic lymphoma. Because of the potential dissemination of both lesions, they are evaluated and treated similarly.

●Ocular adnexal lymphoma is categorized according to the World Health Organization (WHO) Classification of Lymphoid Neoplasms.

●The most common histological subtype identified in OAL is extranodal marginal zone B-cell lymphoma of MALT type (EMZL). This type accounts for 60–75% of OAL. EMZL and follicular lymphoma (FL) comprise nearly all low grade lesions; FL occurs in approximately 10% of cases.

entation is painless visual loss, with the examination showing vitritis, yellow-white subretinal infiltrates, or disk edema or a combination. Relapsing idiopathic vitritis may be a presenting sign. Focal neurologic deficits may present related to cerebral lesions. Patients with lymphoid tumors of the uvea may present with painless decreased vision, visual field defects, or both; yellow-white choroidal elevations may be seen on examination. The most common signs and symptoms of neoplastic angioendotheliomatosis relate to skin and CNS involvement, although ophthalmic manifestations may be present.

Laboratory findings

●Ocular ultrasound is a valuable diagnostic tool in the setting of dense vitritis, and it is useful for following the size of lesions and treatment response.

most common and responds well to treatment. Lymphoma and lymphoid hyperplasia should be evaluated and treated similarly. The lesion histology, site of involvement and the patient age are the most influential factors related to the development of systemic disease and lymphoma related death. Similar to other mucosa-associated lymphoid tumors of the lung and gut, local therapy offers an excellent prognosis. Intraocular lymphoma is uncommon and has an ominous prognosis.

When the diagnosis of lymphoma or lymphoid hyperplasia is made, a thorough evaluation is required for systemic or CNS disease depending on the primary site of involvement. Staging evaluation should include consultation with an internist/oncologist with laboratory findings (complete blood count, serum protein electrophoresis, chemistry panels), CT scan of chest versus chest radiographs, CT scan of abdomen, bone marrow

sitive for the early detection of CNS lymphomas.

●Intraocular lesions require closed vitrectomy with vitreous fluid sampling. Pars plana fine needle aspiration of subretinal lesions may be necessary. Occasionally a full thickness chorioretinal biopsy is utilized.

●Nearly all PIOL are diffuse large B-cell lymphoma (DLBCL). Rarely T-cell lymphoma is diagnosed. The histopathology of uveal tumors is the same as that of ocular adnexal lymphoid tumors.

Differential diagnosis

●Toxoplasmosis.

●Herpes zoster ophthalmicus.

●Frosted branch angiitis.

●Cytomegalovirus retinitis.

●Syphilis.

●Tuberculosis.

●Sarcoidosis.

●Acute posterior multifocal placoid pigment epitheliopathy.

●Acute retinal necrosis.

●Retinal vasculitis.

●Branch retinal artery obstruction with coexistent multifocal.

●Chorioretinal scars.

●Birdshot choroidopathy.

followed every 6 months by an ophthalmologist and internist/ oncologist to evaluate for local recurrence or systemic/CNS lymphoma.

REFERENCES

Chan CC, Wallace DJ: Intraocular lymphoma: update on diagnosis and management. Cancer Control 11:285–295, 2004.

Coupland SE, Heimann H, Bechrakis NE: Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features. Graefe’s Arch Clin Exp Ophthalmol 240:901–913, 2004.

Coupland SE, Hellmich M, et al: Prognostic value of cell-cycle markers in ocular adnexal lymphoma: an assessment of 230 cases. Graefe’s Arch Clinic Exp Ophthalmol 1–31, 2003.

Fung CY, Tarbell NJ, et al: Ocular adnexal lymphoma: clinical behavior of distinct World Health Organization classification subtypes. Int J Radiation Oncology Biol Phys 57:1382–1391, 2003.

Jakobiec FA, Font RL: Non-infectious orbital inflammation. In: Spencer WH, ed: Ophthalmic pathology: an atlas and textbook. Philadelphia, WB Saunders, 1986:3.

Jenkins C, Rose GE, et al: Clinical features associated with survival of patients with lymphoma of the ocular adnexa. Eye 17:809–820, 2003.

Knowles DM, Jakobiec FA, McNally L, et al: Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa (orbit, conjunctiva, and eyelids). Hum Pathol 21:959–973, 1990.

Shields CL, Shields JA, et al: Conjunctival lymphoid tumors: Clinical analysis of 117 cases and relationship to systemic lymphoma. Ophthalmology 108:979–984, 2001.

TREATMENT

●Radiation therapy traditionally has been the main form of therapy for intraocular lymphoid tumors with ocular and whole brain treatment. Unfortunately, toxicity and recurrent disease were high.

●Chemotherapy protocols have increased survival rates. High dose methotrexate and/or cytosine arabinoside (Ara-c) are typically given. Intrathecal and/or intravitreal methotrexate may be used. Bone marrow transplant is an option.

●Lesions may respond to systemic steroids but recur during or after treatment.

●Uveal lesions are typically treated with systemic chemotherapy, although adjuvant radiation therapy may be needed for visually threatening lesions.

Yuen SJ, Rubin PA: Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome. Arch Ophthalmol 121:491–499, 2003.

137 MEDULLOEPITHELIOMA 225.0

(Diktyoma)

Michael O’Keefe, MB, FRCS, FRCOphth

Dublin, Ireland

Caitriona Kirwan, MB, MRCOphth

Dublin, Ireland

less commonly affects the optic nerve, iris and retina. There are two main types of tumors:

1.Nonteratoid, or diktyoma, which contains multilayered sheets or cords of poorly differentiated neuroepithelial cells, with some having a netlike appearance that accounts for the term diktyoma; and

2.Teratoid, which contains neuroepithelial cells and demonstrates varying degrees of heteroplasia. The tumor usually occurs in children between the ages of 2 and 4 and rarely occurs in infants and older patients. It is usually unilateral and has no hereditary or sexual predilection.

COURSE/PROGNOSIS

The roles of radiation, chemotherapy and exenteration are not clearly defined. Local recurrence or metastasis to distant organs requires one or a combination of these treatment modalities.

REFERENCES

Broughton WI, Zimmerman LE: A clinicopathologic study of 56 cases of intraocular medulloepitheliomas. Am J Ophthalmol 85:407–418, 1978.

Canning CR, McCartney ACE, Hungerford J: Medulloepithelioma (diktyoma). Br J Ophthalmol 72:764–767, 1988.

Foster RE, Murray TG, Frazier Byrne S, et al: Echographic features of medulloepithelioma. Am J Ophthalmol 130:364–366, 2000.

Grinker RR: Gliomas of the retina including results of studies with silver impregnations. Arch Ophthalmol 5:920–935, 1931.

Medulloepithelioma may present with loss of vision, pain, leukocoria, mass in the iris or ciliary body, rubeosis iridis, ectopia lentis, heterochromia, exophthalmos and hyphema. These tumors may be locally aggressive but rarely metastasize in the absence of extraocular extension. Broughton and Zimmerman established histologic criteria for the subclassification of tumors as benign or malignant. On the basis of cell differentiation and degree of spread, two thirds are classed as malignant. Medulloepitheliomas are slow growing and early diagnosis of an intraocular tumor with early enucleation results in a high survival rate. Death may occur secondary to intracranial extension.

DIAGNOSIS

Clinical signs and symptoms

The tumor appears as a white, gray or yellow to pink fleshy mass with a characteristic cystic appearance. It may be associated with a cyclitic membrane. Local invasion may result in the development secondary glaucoma, cataract or rubeosis iridis.

Laboratory findings

Indirect ophthalmoscopy, slit-lamp examination and echography aid in diagnosis. Computed tomography scanning and magnetic resonance imaging may also be helpful. The diagnosis is confirmed on histological examination.

Differential diagnosis

Hasain SE, Husain N, Boniuk M, et al: Malignant nonteratoid medulloepithelioma of the ciliary body in an adult. Ophthalmology 105:596–599, 1998.

O’Keefe M, Fulcher T, Kelly P, et al: Medulloepithelioma of the optic nerve head. Arch Ophthalmol 115:1325–1327, 1997.

Shields JA, Shields CL: Tumours of the nonpigmented ciliary epithelium: intraocular tumors: a text and atlas. Philadelphia, WB Saunders; 1992:465–481.

Zimmerman LE: The remarkable polymorphism of tumours of the ciliary epithelium. Trans Aust Coll Ophthalmol 2:114–125, 1970.

138 MENINGIOMA 225.2

Robert A. Egan, MD

Portland, Oregon

ETIOLOGY/INCIDENCE

Meningiomas are generally benign, slow-growing tumors that arise from the dura and they account for about 15–25% of intracranial tumors. Twice as common in females than in males, meningiomas reach a peak incidence in the seventh decade of life, although those that arise from the sphenoid bone and result in visual complaints usually present in the fifth to sixth decades. An estimated 2–3% of the population harbors an incidental meningioma. Most meningiomas are sporadic, but

conditions.

●Persistent hyperplastic primary vitreous.

●Congenital glaucoma.

●Pars planitis.

●Retinoblastoma.

●Malignant melanoma.

●Adenomas.

●Adenocarcinomas of the pigmented or nonpigmented ciliary epithelium.

●Juvenile xanthogranuloma.

TREATMENT

There is no well-established treatment. Iridocyclectomy is indicated for small tumors of the ciliary body. Enucleation is recommended for large tumors of the ciliary body, retina and optic nerve or in the presence of extraocular extension and in practice is required in the majority of cases.

including neurofibromatosis type 2 (NF2). It is currently unclear if the risk of meningioma increases after cranial radiation.

CLINICAL PRESENTATION

Meningiomas are seldom invasive; they produce symptoms by compressing adjacent structures, and these symptoms depend on the site of origin. Because of the characteristic slow tumor growth, clinical findings may have been present for a long time before the correct diagnosis is made. Also, in this day and age of computed tomography (CT) and magnetic resonance imaging (MRI) many meningiomas are found incidentally. These tumors commonly present with seizures as well as increased intracranial pressure and papilledema. Occasionally, they may mimic transient ischemic attacks or present with intracranial hemorrhage.

Due to the myriad types of presentations that meningiomas can portray, it is beyond the scope of this chapter to describe

REFERENCES

Char DH: Tumors of the eye and ocular adnexa: Toronto, Canada BC Decker, 2001.

Ferry AP, Font RL: Carcinoma metastatic to the eye and orbit. A clinicopathologic study of 227 cases. Arch Ophthalmol 92:276–286, 1974.

Gutzeit A, Antoch G, Kuhl H, et al: Unknown primary tumors: detection with dual-modality PET/CT — Initial experience. Radiology 234:227– 234, 2005.

Shields CL, Shields JA, Gross NE, et al: Series of 520 eyes with uveal metastases. Ophthalmology 104:1265–1267, 1997.

of patients. Sphenoid sinus mucopyoceles may cause sudden visual loss due to compression or inflammation of the adjacent optic nerve. Patients often complain of headache radiating to the apex of the skull.

●Maxillary sinus lesions usually lead to upward displacement of the globe but have been reported to cause enophthalmos.

Mucopyoceles are usually associated with acute inflammatory signs and symptoms including pain, erythema and edema of overlying soft tissues and mucopurulent nasal drainage.

140 MUCOCELE 376.81

(Pyocele, Mucopyocele)

Robert C. Kersten, MD

Cincinnati, Ohio

ETIOLOGY

A mucocele is a cystic lesion arising from the accumulation and retention of mucus secretions, usually from an obstructed, often chronically inflamed paranasal sinus. As the mucous accumulates the mucocele expands and can erode through the sinus wall into the orbit leading to ophthalmic signs and symptoms. If the mucoid material becomes secondarily infected, the lesion is termed a pyocele or mucopyocele. The most common form is the frontoethmoidal lesion, with the ethmoidal or sphenoidal varieties being less common. Maxillary sinus mucocele is rare.

Causes of a mucocele include chronic sinusitis, cystic fibrosis (in children), fractures involving the nasofrontal duct, sinus polyps, previous sinus or orbital decompression surgery, primary sinus tumors (squamous cell carcinoma of ethmoid sinus), metastatic tumors and allergies.

DIAGNOSIS

Clinical signs and symptoms

●Mucoceles usually occur in adults with a history of chronic sinusitis. They usually present with progressive proptosis or globe displacement.

●Chronic headache and visual disturbance are less common complaints.

●Frontoethmoidal lesions typically produce outward and downward displacement of the globe and proptosis. Ptosis and limited supraduction and adduction of the globe may occur. Acquired Browns syndrome has also been reported. A fluctuant mass may be palpable beneath the orbital rim superonasally. Posterior erosion may produce epidural or subdural abscess formation.

●Isolated frontal sinus lesions lead to downward and outward displacement with minimal proptosis; ptosis and limited elevation may occur.

●Sphenoid and posterior ethmoid lesions tend to present with functional abnormalities related to the optic nerve, cavernous sinus, or orbital apex. Patients may have visual symptoms, retrobulbar pain, nerve palsies and nasal symptoms. Disk edema or optic atrophy can be present. Extraocular palsies (often the third nerve) occur in approximately half

Laboratory findings

●An imaging study should be obtained to make the diagnosis and determine the extent and location of the lesion.

●Computed tomography scanning is helpful to outline bony changes, including the status of orbital walls and the cranial cavity.

●Magnetic resonance imaging with gadolinium may be helpful in differentiating mucoceles from neoplasms in the paranasal sinuses.

Differential diagnosis

The differential diagnosis includes retrobulbar tumor; paranasal sinus, nasal, or pharyngeal tumors; thyroid disease; retrobulbar neuritis; meningocele; meningoencephalocele; subperiosteal hematoma; orbital pseudotumor; acute or chronic sinusitis; and temporal arteritis.

TREATMENT

Surgical

●A multidisciplinary approach involving an orbital surgeon and an otorhinolaryngologist is usually necessary, with neurosurgical backup if indicated by intracranial invasion.

●Access to the mucocele can be approached via an anterior orbitotomy (lid-crease incision) or transcaruncular incision (for isolated ethmoid lesion). Exposure of the frontal sinus itself may also include the creation of an osteoplastic bone flap.

●Surgical goals may include re-establishment of normal sinus drainage or removal of all sinus mucosa and obliteration of the sinus with fat.

●An isolated mucocele may be treated with complete removal of the lining, removal of degenerated bone with the use of a high-speed drill and re-establishment of drainage between the exenterated sinus and the nose.

●Silastic tubing, a nasal flap, or silicone rubber sheeting can be used to reconstruct the frontal-nasal duct and provide drainage to the nose.

●Another option is obliteration of the sinus after complete removal of the cyst lining and degenerated bone. Fat from the abdominal wall can then be packed into the sinus space.

●Endoscopic decompression of sphenoidal and ethmoidal mucoceles is a newer method of dealing with these lesions. Recurrence rates may be higher when endoscopy is used as the sole intervention.

COMPLICATIONS

Recurrence can be due to incomplete excision of sinus lining or restenosis of the new osteum. Infection can occur, as can

preservation of the nerve function frequently possible. Tumors are not highly vascular, so bleeding is rarely a problem.

Radiation

When histologic examination of the tissue confirms malignancy or radiographic recurrence has been documented, focal application of up to 6000 rads of 10-MeV photons may be used for local treatment.

COMPLICATIONS

Occasionally, the extent and location of the tumor prevent complete excision. Surgery can cause damage to the nerve, the eye and adjacent tissues. If growth continues, repeated excision, irradiation, chemotherapy, or a combination is indicated.

PRECAUTIONS

Accurate diagnosis of the tumor is only achieved histologically, although the results of radiographic studies can be suggestive. The histologic evaluation must be done by a pathologist who is extremely familiar with this type of tumor. Studies indicate that the morphology and histology of the collagen of such tumors can be useful in their differentiation. Electron microscopy often is useful when standard histologic techniques are not definitive. Human glia-specific proteins, S100 and GFA, have been useful in characterizing the malignant status of these tumors.

The importance of a surgically aggressive approach to patients with malignant neurilemomas cannot be overemphasized. The 5-year survival rate in one study was 48%. Even tumors initially classified as low grade histologically often eventually metastasize and cause death. Prognosis of any lesion is dependent on its location and size, the adequacy of excision and the malignant potential of that particular neurilemoma.

COMMENTS

The occurrence of multiple tumors usually implies hereditary disease, such as neurofibromatosis type 2. The increased incidence of malignant neurilemomas in association with neurofibromatosis type 2 and in sites of prior irradiation should be recognized.

Mafee MF, Putterman A, Valvassori GE, et al: Orbital space-occupying lesions: role of computed tomography and magnetic resonance imaging: an analysis of 145 cases. Radiol Clin North Am 25:529–559, 1987.

Matsuo T, Notohara K: Choroidal schwannoma: immunohistochemical and electron-microscopic study. Ophthalmologica 214:156–160, 2000.

Minor LB, Haslwanter T, Straumann D, Zee DS: Hyperventilation-induced nystagmus in patients with vestibular schwannoma. Neurology 53:2158–2168, 1999.

Rose GE, Wright JE: Isolated peripheral nerve sheath tumours of the orbit. Eye 5:668–673, 1991.

Santoreneos S, Hanieh A, Jorgensen RE: Trochlear nerve schwannomas occuring in patients without neurofibromatosis: case report and review of the literature. Neurosurgery 41:282–287, 1997.

Senoy SN, Raja A: Cystic trochlear nerve neurinoma mimicking intrinsic brainstem tumour. Br J Neurosurg 18:183–186, 2004.

Shields JA, Font RL, Eagle RC, Jr, et al: Melanotic schwannoma of the choroid: immunohistochemistry and electron microscopic observations. Ophthalmology 101:843–849, 1994.

Zbieranowski I, Bedard YC: Fine needle aspiration of schwannomas: value of electron microscopy and immunocytochemistry in the preoperative diagnosis. Acta Cytol 33:381–384, 1989.

142 NEUROBLASTOMA 194.0

Devron H. Char, MD

San Francisco, California

ETIOLOGY/INCIDENCE

Neuroblastoma is a neoplastic proliferation of immature sympathetic ganglion cells. This tumor is the most common pediatric extracranial solid tumor; approximately half of these patients present with metastases at diagnosis. There are approximately 650 new cases per year in this country, with half presenting in children younger than 2 years. In whites, the annual incidence is approximately 10.5 per 1 million. Most patients with neuroblastoma ophthalmic metastases present to the ophthalmologist before the discovery of a primary neoplasm.

In approximately 3% of all neuroblastomas, orbital involvement can be the initial manifestation of the disease. Neuroblastoma can also present with other ophthalmic findings not directly related to ocular or adnexal metastases.

REFERENCES

Bickler-Bluth ME, Custer PL, Smith ME: Neurilemoma as a presenting feature of neurofibromatosis. Arch Ophthalmol 106:665–667, 1988.

Byrne BM, van Heuven WAJ, Lawton AW: Echographic characteristics of benign orbital schwannomas (neurilemomas). Am J Ophthalmol 106:194–198, 1988.

Capps DH, Brodsky MC, Rice CD, et al: Orbital intramuscular schwannoma. Am J Ophthalmol 110:535–539, 1990.

Costello F, Kardon RH, Wall M, et al: Papilledema as the presenting manifestation of spinal schwannoma. J Neuroophthalmol 22:199–203, 2002.

Fan JT, Campbell RJ, Robertson DM: A survey of intraocular schwannoma with a case report. Can J Ophthalmol 30:37–41, 1995.

Jacque CM, Kujas M, Poreau A, et al: GFA and S100 protein levels as an index for malignancy in human gliomas and neurinomas. J Natl Cancer Inst 62:479–483, 1979.

COURSE/PROGNOSIS

Presentation can mimic that of a battered child syndrome and can be either unilateral or bilateral. Approximately 30% to 40% of treated patients have good long-term survival rates. With treatment, the local ophthalmic prognosis is good, however most of these patients die of systemic diseases.

DIAGNOSIS

Clinical signs and symptoms

The diagnosis of metastatic neuroblastoma to the ocular adnexa may be difficult. In a child younger than 2 years who presents with orbital proptosis, the possibility of metastases must be considered.

Laboratory findings

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) often is diagnostic; metastatic orbital bone involvement has a typical pattern. Diagnosis can be established with fine needle aspiration biopsy; ancillary studies can be performed on biopsy material, including cytogenetic studies, comparative genomic hybridization (CGH) studies, N-myc analysis, and microarray urine analysis shows elevations of vanillylmandelic acid (VMA) and homovanillic acid (HVA).

All patients require a complete metastatic evaluation including body CT/MRI bone scan, multiple bone marrow biopsies (including fluorescence for Gd2 cells), metaiodobenzylguanidine (I-131 MIBG) imaging studies, and cytogenetic analysis of the tumor, including ploidy analysis, N-myc amplification, alterations in the area of chromosome 1p, 3p, 11q, 17q, and studies of ferritin, NSE, CD 44, nerve growth factor expression, and mRNA expression of trk. Serum lactate dehydrogenase levels are helpful, as may be telomerase levels. All of these tests are correlative with survival rates.

TREATMENT

Multimodality evaluation and therapy are optimal with pediatric oncology, radiation oncology and ophthalmic oncology.

Systemic

In most centers, a combination of systemic consolidation chemotherapy and either autologous bone marrow transplantation or stem cell transplantation appears to be better than continuous chemotherapy. Approximately 35% of patients will have longterm regression with this approach. Newer molecular trials with anti-GD2 drugs and newer agents such as rebeccamycin are in phase II trials.

Local

Local therapy often can be deferred until response to systemic treatment is observed. Radiation is useful for orbital palliation. These tumors will respond to 2000 cGy of external-beam photon radiation.

Surgical

Surgery to remove gross residual disease may be helpful in some cases.

REFERENCES

Char DH: Tumors of the eye and ocular adnexa. Hamilton, BC Decker, 2001.

Goldsby RE, Matthay KK: Neuroblastoma. Evolving therapies for a disease with many faces. Pediatric Drugs 6:107–122, 2004.

Ladenstein R, Philip T, Gardner H: Autologous stem cell transplantation for solid tumors in children. Curr Opin Pediatr 9:55–69, 1997.

Maris JM: The biologic basis for neuroblastoma heterogeneity and risk stratification. Curr Opin Pediatr 17:7–13, 2005.

143 OPTIC GLIOMAS 225.1

Cameron F. Parsa, MD

Baltimore, Maryland

ETIOLOGY/INCIDENCE

Juvenile pilocytic astrocytoma type I tumors intrinsic to the optic nerve, chiasm, or tracts are termed optic gliomas. Because of the static or slow growth of the astrocytic (glial) cells surrounding the nerve axons, in many cases followed by spontaneous regression, prolonged survival is the rule. These tumors do not metastasize in the usual sense; during infancy, rarely ‘drop’ metastases, often asymptomatic in nature, may occur to the leptomeninges via the cerebrospinal fluid passageways, particularly after ventricular shunt placement for elevated intracranial pressure.

About half of patients who present with optic gliomas also have neurofibromatosis type 1 (NF1) which is due to a mutation and loss of function of a tumor suppressor gene. While over 25% of NF1 patients may have detectable gliomas in MRI surveillance studies, most remain asymptomatic. Optic gliomas should be considered hamartomas with growth potential during childhood.

COURSE/PROGNOSIS

Gliomas of the optic nerve can be unilateral or bilateral. They often present within the first decade of life with proptosis. Acuity loss may be mild or profound; visual function correlates poorly with tumor size. They can be left alone until proptosis becomes unsightly.

Gliomas affecting the chiasm more often present with visual loss. In patients with hypothalamic involvement, hormonal dysfunction may be present. Involvement and obstruction of the third ventricle can produce elevated intracranial pressure.

Tumor growth is slow and by the time the tumor is discovered, often no further growth is noted. While tumor can extend along optic pathways, cell growth can also be multicentric. Spontaneous regression can occur.

DIAGNOSIS

Clinical signs and symptoms

Glioma affecting the optic nerve

The diagnosis can be suggested by proptosis in a child. There may be an afferent pupil defect or a swollen or pale optic nerve with optociliary shunt vessels. For reasons still unclear, the elongated nerve within the orbit has a predisposition to kink downward, producing upward rotation of the posterior aspect of the globe. Thus, a hypotropia is often noted.