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Bilateral Iridociliary T-Cell Lymphoma
Arch Ophthalmol. 2002;120:204-207.
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.2-4
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.
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Figure 1. Right eye at time of initial appearance:
tiny keratic precipitates are seen, and the pupil is slightly oval.
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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.
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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.
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Figure 3. High-frequency (20-MHz) ultrasound
of the right eye, revealing a ciliary body mass. Rule indicates millimeters.
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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.
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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- , 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.
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Figure 5. Sheets of atypical large lymphoid
cells are seen (hematoxylin-eosin stain, original magnification x 40).
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Figure 6. The atypical lymphoid cells stain
positively with the immunohistochemical stain CD3 (pan-T-cell marker, original
magnification x 40).
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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.
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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.
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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.
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Figure 8. Left eye 6 months after chemotherapy.
Complete regression of the iris lesion with residual scarring and posterior
synechiae are seen.
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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.1-3,7-9
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
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Anterior Uveal Lymphoma: Review of the Literature*
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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.
AUTHOR INFORMATION
Claudia Yahalom, MD;
Yossi Cohen, MD;
Edward Averbukh, MD;
Irene Anteby, MD;
Gail Amir, MB, ChB;
Jacob Pe'er, MD
Jerusalem, Israel
Corresponding author and reprints: Jacob Pe'er, MD, Department of
Ophthalmology, Hadassah University Hospital, PO Box 12000, Jerusalem 91120,
Israel (e-mail: peer{at}md2.huji.ac.il).
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and review of the literature. Surv Ophthalmol. 2000;44:518-526.
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SECTION EDITOR: W. RICHARD GREEN, MD
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience
Frenkel et al.
Br. J. Ophthalmol. 2008;92:383-388.
ABSTRACT
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