Patients typically notice painless, progressive vision loss. Ophthalmoscopically, a diffuse or, rarely, nodular amelanotic thickening of the choroid is noted. Exudative retinal detachment and secondary glaucoma may be present in up to 85% of eyes. Frequently, delay between the onset of symptoms and diagnostic intervention is significant.

This rare disorder is characterized pathologically by localized or diffuse infiltration of the uveal tract by lymphoid cells. The etiology is unknown. Clinically, this condition can simulate posterior uveal melanoma, metastatic carcinoma to the uvea, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, and posterior scleritis. Proptosis of the affected eye occurs in up to 15% of patients who develop simultaneous orbital infiltration with benign lymphoid cells. Ultrasonographic testing reveals a diffuse, homogeneous choroidal infiltrate with associated secondary retinal detachment. Extraocular extension or orbital involvement may be best demonstrated with ultrasonography.

Pathologic studies

Biopsy confirmation should be targeted to the most accessible tissue. If extraocular involvement is present, biopsy of the involved conjunctiva or orbit may be considered. Fine-needle aspiration biopsy or pars plana vitrectomy with biopsy may be indicated for isolated uveal involvement. Coordination with the ophthalmic pathologist is crucial to achieve the greatest likelihood of appropriate confirmation and cell marker studies.

Treatment

Historically, eyes with this type of lymphoid infiltration were generally managed by enucleation because of presumed malignancy. Current management emphasizes globe-conserving therapy aimed at preservation of vision. High-dose oral steroids may induce tumor regression and decrease exudative retinal detachment. Early intervention with low-dose ocular and orbital fractionated external-beam radiotherapy may definitively manage the disease.

Prognosis

The prognosis for survival is excellent for patients with uveal lymphoid infiltration, with the rare exception of patients with systemic lymphoma. Preservation of visual function appears related to primary tumor location and secondary sequelae, including exudative retinal detachment or glaucoma. Early intervention appears to enhance the likelihood of vision preservation.

Ocular Manifestations of Leukemia

Ocular involvement with leukemia is common, occurring in as many as 80% of the eyes of patients examined at autopsy. Clinical studies have documented ophthalmic findings in as many as 40% of patients at diagnosis. Patients may be asymptomatic, or they may complain of blurred or decreased vision. Clinically, the retina is the most commonly affected intraocular structure. Leukemic retinopathy is characterized by intraretinal and subhyaloidal hemorrhages, hard exudates, cottonwool spots, and white-centered retinal hemorrhages (pseudo–Roth spots)—all of which are usually the result of associated anemia, hyperviscosity, and/or thrombocytopenia (Fig 20-11). Leukemic infiltrates appear as yellow deposits in the retina and the subretinal space. Perivascular leukemic infiltrates produce gray-white streaks in the retina. Vitreous involvement by leukemia is rare and most often results from direct extension via retinal hemorrhage. If necessary, a diagnostic vitrectomy can be performed to establish a diagnosis.

Although, clinically, the retina is the most commonly affected ocular structure, histologic studies have shown that the uvea is more commonly affected than the retina. The uveal tract may serve as a

“sanctuary site,” predisposing the eye to be the structure in which recurrent disease first manifests clinically. Choroidal infiltrates may be difficult to detect with indirect ophthalmoscopy; they may be better detected on ultrasonography as diffuse thickening of the choroid. Serous retinal detachments may overlie these infiltrates. Leukemic involvement of the iris manifests as a diffuse thickening with loss of the iris crypts, and, in some cases, small nodules may be seen at the margin of the pupil (see Chapter 17, Fig 17-4D). Leukemic cells may invade the anterior chamber, forming a pseudohypopyon. Infiltration of the angle by these cells can give rise to secondary glaucoma.

Figure 20-11 Retinal involvement in leukemia. A, Leukemic retinopathy. Clinical photograph shows scattered intraretinal hemorrhages, some of which have white centers (arrows). B, White-centered hemorrhages. (Part A courtesy of Robert H. Rosa, Jr,

MD; part B courtesy of Jacob Pe’er, MD.)

A patient with leukemic infiltration of the optic nerve (Fig 20-12) may present with severe vision loss and optic nerve edema. One or both eyes may be affected. This is an ophthalmic emergency and requires immediate treatment to preserve as much vision as possible. Systemic and intrathecal combination chemotherapy is needed with or without radiation.

Figure 20-12 Leukemic infiltration of optic nerve. (Courtesy of Robert H. Rosa, Jr, MD.)

Leukemic infiltrates may also involve the orbital soft tissue, with resultant proptosis. These tumors, which are more common with myelogenous leukemias, are referred to as granulocytic sarcomas or chloromas. They have a predilection for the lateral and medial walls of the orbit.

Treatment of leukemic involvement of the eye generally consists of low-dose radiation therapy to the eye and systemic chemotherapy. The prognosis for vision depends on the type of leukemia and the extent of ocular involvement.

APPENDIX

American Joint Committee on Cancer (AJCC) Staging Forms, 2010

[The material in this appendix is used with permission from Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, eds. Ophthalmic Sites. In: AJCC Staging Manual. 7th ed. New York, NY: Springer; 2010:part X, pp 521–589.]

Histologic Grade (G)

Grade is reported in registry systems by the grade value. A two-grade, three-grade, or four-grade system may be used. If a grading system is not specified, generally the following system is used:

GX Grade cannot be assessed

G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

G4 Undifferentiated

Histopathologic Type

The primary eyelid carcinoma tumors include the following group and list of histologies:

Basal cell carcinoma

Squamous cell carcinoma

Mucoepidermoid carcinoma

Sebaceous carcinoma

Primary eccrine adenocarcinoma

Primary apocrine adenocarcinoma Adenoid cystic carcinoma

Merkel cell carcinoma

Histopathologic Type

The classification applies only to carcinoma of the conjunctiva.

Conjunctival intraepithelial neoplasia (CIN) including in situ squamous cell carcinoma Squamous cell carcinoma

Mucoepidermoid carcinoma Spindle cell carcinoma

Sebaceous gland carcinoma including pagetoid (conjunctival) spread Basal cell carcinoma

Histologic Grade (G)

Grade is reported in registry systems by the grade value. A two-grade, three-grade, or four-grade system may be used. If a grading system is not specified, generally the following system is used:

GX Grade cannot be assessed G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

G4 Undifferentiated

Histopathologic Type

This categorization applies only to melanoma of the conjunctiva.

Histologic Grade (G)

Histologic grade represents the origin of the primary tumor.

Histopathologic Type

The histopathologic types are as follows:

Spindle cell melanoma (greater than 90% spindle cells)

Mixed cell melanoma (>10% epithelioid cells and <90% spindle cells)

Epithelioid cell melanoma (greater than 90% epithelioid cells)

Histologic Grade (G)*

GX Grade cannot be assessed

G1 Spindle cell melanoma

G2 Mixed cell melanoma

G3 Epithelioid cell melanoma

*Note: Because of general lack of agreement regarding which proportion of epithelioid cells classifies a tumor as mixed and epithelioid in type, some ophthalmic pathologists currently combine grades 2 and 3 (nonspindle, epithelioid cells detected) and contrast them with grade 1 (spindle, no epithelioid cells detected).

Histologic Grade (G)

Grade is reported in registry systems by the grade value. A two-grade, three-grade, or four-grade system may be used. If a grading system is not specified, generally the following system is used:

GX Grade cannot be assessed G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

G4 Undifferentiated

Histopathologic Type

This classification applies only to retinoblastoma.

Histologic Grade (G)

In most cases, the histology defines the grade of malignancy in lacrimal gland carcinomas as in salivary gland carcinomas.

GX Grade cannot be assessed G1 Well differentiated

G2

Moderately differentiated: includes adenoid cystic carcinoma without basaloid (solid) pattern

G3 Poorly differentiated: includes adenoid cystic carcinoma with basaloid (solid) pattern G4 Undifferentiated

Histopathologic Type

The major malignant primary epithelial tumors include the following:

Low Grade

Carcinoma ex pleomorphic adenoma [where the carcinoma is noninvasive or minimally invasive

as defined by the WHO classification (extension <1.5 mm beyond the capsule—into surrounding tissue)]

Polymorphous low-grade carcinoma Mucoepidermoid carcinoma, grades 1 and 2 Epithelial-myoepithelial carcinoma

Cystadenocarcinoma and papillary cystadenocarcinoma Acinic cell carcinoma

Basal cell adenocarcinoma Mucinous adenocarcinoma

High Grade

Carcinoma ex pleomorphic adenoma (malignant mixed tumor) that includes adenocarcinoma and adenoid cystic carcinoma arising in a pleomorphic adenoma [where the carcinoma is invasive as defined by the WHO classification (extension >1.5 mm beyond the capsule—into surrounding tissue)]

Adenoid cystic carcinoma, not otherwise specified Adenocarcinoma, not otherwise specified Mucoepidermoid carcinoma, grade 3

Ductal adenocarcinoma Squamous cell carcinoma Sebaceous adenocarcinoma Myoepithelial carcinoma Lymphoepithelial carcinoma

Other Rare and Unclassifiable Carcinomas

Histologic Grade (G)

Grade is reported in registry systems by the grade value. A two-grade, three-grade, or four-grade system may be used. If a grading system is not specified, generally the following system is used:

GX Grade cannot be assessed G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

G4 Undifferentiated

Histopathologic Type

Malignancies of the orbit primarily include a broad spectrum of malignant soft tissue tumors.