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Clinicopathologic Reports, Case Reports, and Small Case Series
February 2002

Bilateral Iridociliary T-Cell Lymphoma

Arch Ophthalmol. 2002;120(2):204-207. doi:

Intraocular lymphoma is generally of the B-cell type, commonly affecting the posterior segment of the eye, and in most cases is associated with central nervous system (CNS) lymphoma.1 Primary involvement of the anterior uvea is very rare.24 T-cell lymphoma is not commonly seen in the eye. We describe a patient with non-Hodgkin lymphoma (NHL) of the T-cell type affecting primarily the iris and ciliary body of both eyes as the first manifestation of the systemic disease.

Report of a Case

A 31-year-old man came to our clinic with left anterior uveitis of 4 weeks' duration that was unresponsive to topical steroids. During the previous weeks, he had noticed a progressive worsening of his vision with mild ocular discomfort in his left eye. No pain or redness was present. His history was remarkable for oral drug abuse (3,4-methylene dioxymethamphetamine [Ecstasy]) and lysergic acid diethylamide. He denied intravenous drug administration. On examination, his visual acuity was 20/20 OD and 20/60 OS. Intraocular pressure readings were 10 mm Hg and 17 mm Hg, respectively. A biomicroscopic examination of the right eye demonstrated tiny white keratic precipitates and cells (+1) and flare (+1) in the anterior chamber (Figure 1). No synechiae were present, and the lens was clear. An examination of the left eye showed a hyperemic bulbar and perilimbal conjunctiva, white keratic precipitates, and cells (+4) and flare (+2) in the anterior chamber with a 2-mm hypopyon. The iris was bulging and was infiltrated by a whitish mass at the 6-o-clock position (Figure 2). Marked engorgement of the iris vessels was present. The pupil was severely distorted (pulled upward) and mid-dilated. The lens was clear. No cells were present in the vitreous, and the posterior segment was normal in both eyes.

Figure 1.
Right eye at time of initial appearance:
tiny keratic precipitates are seen, and the pupil is slightly oval.

Right eye at time of initial appearance: tiny keratic precipitates are seen, and the pupil is slightly oval.

Figure 2.
Left eye at time of initial appearance:
iris white mass and bulging at the 6-o'clock position. Engorgement of the
iris vessels, hypopyon, and a distorted pupil are seen.

Left eye at time of initial appearance: iris white mass and bulging at the 6-o'clock position. Engorgement of the iris vessels, hypopyon, and a distorted pupil are seen.

The combination of iris distortion and infiltration with painless severe intraocular inflammation raised the possibility of a tumor masquerading as anterior uveitis. Investigations included an ultrasound examination (high resolution, 20 MHz) of the eyes that revealed a ciliary body mass pushing the iris forward. This occurred in both eyes but was more pronounced in the left eye (Figure 3 and Figure 4). Bilaterally, the anterior choroid was thickened, whereas the posterior pole was unremarkable (B-scan, 10 MHz). An anterior chamber tap from the left eye was performed twice, but microbiologic and cytologic evaluations were noncontributory. Findings from the uveitis workup, including a complete blood cell count, erythrocyte sedimentation rate, antinuclear antibody test, VDRL test, purified protein derivative (tuberculin) test, human immunodeficiency virus test, and chest x-ray films, were within normal limits. Because of complaints of paresthesia in both legs, the patient underwent a neurologic examination, computed tomography of the brain, and lumbar puncture, which all yielded normal results.

Figure 3
 High-frequency (20-MHz) ultrasound
of the right eye, revealing a ciliary body mass. Rule indicates millimeters.

High-frequency (20-MHz) ultrasound of the right eye, revealing a ciliary body mass. Rule indicates millimeters.

Figure 4.
 High-frequency (20-MHz) ultrasound
of the left eye, showing a bigger ciliary body mass pushing the iris forward.
The anterior chamber angle was closed in inferior quadrants. Rule indicates
millimeters.

High-frequency (20-MHz) ultrasound of the left eye, showing a bigger ciliary body mass pushing the iris forward. The anterior chamber angle was closed in inferior quadrants. Rule indicates millimeters.

Within a few days, the ocular disease progressed rapidly in both eyes. Iris and anterior chamber angle infiltration increased, leading to an increased intraocular pressure reading of 28 mm Hg OS. In view of the lack of response to topical steroids, a diagnostic biopsy of the left eye was performed. During the procedure, the iris was noted to be massively infiltrated and extremely fragile. Behind the iris, a white plaque of cells was seen on the lens surface with localized lens opacity behind it.

A few iris pieces were excised, fixed in formalin, and embedded in paraffin. All fluid washed from the anterior chamber during the procedure was collected and underwent a cytologic evaluation. The biopsy specimen from the nodule in the iris was composed of diffuse sheets of large atypical lymphoid cells (Figure 5). Apoptotic bodies and mitotic figures were seen. The specimen underwent immunohistochemical staining; the atypical cells stained with leukocyte common antigen and CD3 (pan-T-cell marker) (Figure 6) but did not stain with CD20, CD79-α, CD30, terminal deoxynucleotidyl transferase, myeloperoxidase, neuron-specific antigen, or HMB-45. The morphologic appearance together with the immunophenotype of the tumor were diagnostic for peripheral large T-cell lymphoma. An additional systemic workup, including a bone marrow examination, total body computed tomography, and brain magnetic resonance imaging, disclosed no systemic involvement.

Figure 5.
Sheets of atypical large lymphoid
cells are seen (hematoxylin-eosin stain, original magnification × 40).

Sheets of atypical large lymphoid cells are seen (hematoxylin-eosin stain, original magnification × 40).

Figure 6.
The atypical lymphoid cells stain
positively with the immunohistochemical stain CD3 (pan-T-cell marker, original
magnification × 40).

The atypical lymphoid cells stain positively with the immunohistochemical stain CD3 (pan-T-cell marker, original magnification × 40).

The patient was treated with systemic chemotherapy consisting of cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone. Signs of uveitis regressed rapidly in both eyes with melting of the iris mass lesion. However, a recurrence was noted in the left eye 2 weeks later. A new well-defined iris mass was seen in addition to a recurrence of the pseudohypopyon and increased intraocular pressure (Figure 7). A newly appearing dense vitreous infiltration was noted. Central nervous system involvement was ruled out with brain magnetic resonance imaging.

Figure 7.
Left eye appearance after the
first course of treatment with cyclophosphamide, doxorubicin hydrochloride,
vincristine sulfate, and prednisone. After an initial good response, regrowth
of the iris lesion was noticed.

Left eye appearance after the first course of treatment with cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone. After an initial good response, regrowth of the iris lesion was noticed.

A more aggressive second course of chemotherapy was started following the Magrath5 protocol. A high dose of intravenous methotrexate and leucovorin calcium was added. Methotrexate was administered intrathecally as well as intravitreally (400 µg/0.1 mL injected twice weekly, 7 times).6 The second course of chemotherapy induced a rapid response. The white lesion resorbed completely, and the patient remained stable during 9 months of follow-up (Figure 8). The vitreous became free of cells after 7 injections of intravitreal methotrexate. The ciliary body mass and choroidal infiltration had totally disappeared at a repeated echographic examination 4 months after the onset of disease. Visual acuity improved to 20/20 OD and 20/40 OS and remained stable. Eight months after the diagnosis of ocular lymphoma, skin lesions were noticed and lymphomatous cells were found in the biopsy specimen.

Figure 8.
Left eye 6 months after chemotherapy.
Complete regression of the iris lesion with residual scarring and posterior
synechiae are seen.

Left eye 6 months after chemotherapy. Complete regression of the iris lesion with residual scarring and posterior synechiae are seen.

Comment

We present an unusual manifestation of bilateral iridociliary T-cell lymphoma masquerading as steroid-resistant uveitis in an otherwise healthy young patient. Similar iris lymphoma cases have been described in 6 patients, all of whom showed systemic involvement of the disease.13,79 In 3 of these patients, primary iris infiltration was noticed clinically3,7,8; these patients were affected by systemic NHL (bone marrow and lymph node–visceral lymphoma). The other 3 reported cases exhibited a late iris involvement, with a delay of more than a year between the initial appearance of nonspecific uveitis and the subsequent clinical iris infiltration. In these cases, the lymphoma involved the CNS as well as the eye.1,2,9

Table 1 summarizes the clinical findings of the 6 cases of intraocular NHL with clinical iris involvement previously reported in the literature, in comparison with our case. Velez et al2 reported 2 cases of large B-cell lymphoma, but only one of them had clinical iris infiltration and appears in our table. One of the reported cases was described as B-cell lymphoma, 2 of them were referred to as reticulum cell sarcoma with no specification of cell type, and 3 were considered T-cell lymphoma. All of the patients with T-cell lymphoma, including ours, had systemic lymphomatous involvement (with only 1 case of additional infiltration of the CNS), and all but one showed an early anterior segment involvement.1

Anterior Uveal Lymphoma: Review of the Literature*
Anterior Uveal Lymphoma: Review of the Literature*
13,79

Intraocular lymphoma may involve the uveal tract, retina, vitreous, or optic nerve head. Typically affecting older people, intraocular lymphoma has also been described in young patients.8 Bilateral involvement is seen in about 80% of cases. Although several types of intraocular lymphoma have been recognized, large cell lymphoma is the most common one. Intraocular lymphoma is generally of the B-cell type, similar to NHL elsewhere in the body, whereas T-cell lymphoma is quite rare.1

Malignant lymphoma is usually a systemic disease affecting multiple organs. Occasionally, intraocular involvement may be the initial manifestation of the systemic disease. Two different forms of NHL can affect the eye: the CNS type and the systemic (lymph node–visceral) form.

Intraocular lymphoma affecting only the eye is rare. The intraocular involvement can be divided into 2 general types of disease. The first is vitreoretinal lymphoma and is the most common form; it is found in association with CNS lymphoma, which is usually of the B-cell type.1 The second is uveal lymphoma, which is associated with visceral or nodal involvement. In the early stages the disease may assume one of these 2 variations, but in more advanced stages they may overlap considerably.10

Ocular signs and symptoms of lymphoma may occur before the onset of systemic or CNS manifestations. In NHL of the CNS, the presence of vitreous cells masquerading as vitritis is the most common ocular finding, followed by an anterior uveitis–like picture and subretinal yellow infiltrates. At the time of intraocular appearance, CNS involvement is seen in 60% of patients.

Diagnosis of ocular lymphoma with CNS involvement requires a sampling of the vitreous or subretinal space and identification of malignant lymphocytic cells. With the use of immunohistochemical stains, the type of lymphoma can easily be defined. Although primary intraocular lymphoma cells have been identified by histopathologic diagnosis in the iris, ciliary body, and optic nerve in a few patients, lymphoma in these sites has rarely been observed clinically.2

The mechanism allowing uveal invasion by lymphoma cells remains unknown. Hematogenous spread should be considered. Previous histopathologic reports demonstrate a perivascular distribution of malignant cells in the iris,11 supporting this possibility. Velez et al2 have proposed that long-standing aggressive tumors of the posterior segment break through the Bruch membrane and invade the choroid, thus gaining access to the anterior uveal structures.

In our patient, the iris, ciliary body, and anterior choroid were initially the only sites of lymphomatous involvement. The vitreous of the left eye was infiltrated during a second exacerbation of the disease. Our case is a rare, T-cell NHL with an affinity for the anterior uvea and a later infiltration of the skin during chemotherapy, showing the aggressive nature of the patient's disease.

Corresponding author and reprints: Jacob Pe'er, MD, Department of Ophthalmology, Hadassah University Hospital, PO Box 12000, Jerusalem 91120, Israel (e-mail: peer@md2.huji.ac.il).

References
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2.
Velez  Gde Smet  MDWhitcup  SMRobinson  MNussenblatt  RBChan  CC Iris involvement in primary intraocular lymphoma: report of two cases and review of the literature. Surv Ophthalmol. 2000;44518- 526Article
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Jensen  OAJohansen  SKiss  K Intraocular T-cell lymphoma mimicking a ring melanoma: first manifestation of systemic disease: report of a case and survey of the literature. Graefes Arch Clin Exp Ophthalmol. 1994;232148- 152Article
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Goldey  SHStern  GAOblon  DJMendenhall  NPSmith  LJDuque  RE Immunophenotypic characterization of an unusual T-cell lymphoma presenting as anterior uveitis. Arch Ophthalmol. 1989;1071349- 1353Article
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Cooper  ELRiker  JL Malignant lymphoma of the uveal tract. Am J Ophthalmol. 1951;341153- 1158
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Raju  VKGreen  W Reticulum cell sarcoma of the uvea. Ann Ophthalmol. 1982;14555- 560
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Shields  JAShields  CL Intraocular Tumors: A Text and Atlas.  Philadelphia, Pa WB Saunders Co1992;
11.
Vogel  MHFont  RLZimmerman  LELevine  RA Reticulum cell sarcoma of the retina and uvea: report of six cases and review of the literature. Am J Ophthalmol. 1968;66205- 215
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