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We describe a patient with a 6-year history of chronic lymphocytic leukemia
who developed iris, ciliary body, and choroidal tumors associated with ocular
pain and uveitis that were unresponsive to topical anti-inflammatory steroids.
Because the eye was not salvageable with conservative treatment, enucleation
was performed. Findings from histopathologic examination of the enucleated
eye showed a high-grade B-cell lymphoma. This case represents an example of
Richter syndrome (high-grade lymphoma arising in patients with chronic lymphocytic
leukemia) clinically mimicking uveal melanoma.
Report of a Case
An 81-year-old woman complained of 4 weeks of blurred vision and 10
days of pain in the right eye. The eye had been treated with topical corticosteroids
and cycloplegics, prescribed by another ophthalmologist, for the 2 weeks preceding
our evaluation. Her vision was 6/200 OD and 20/25 OS. Intraocular pressure
was 18 mm Hg OU. There was no injection or chemosis of the conjunctiva. The
right eye had keratic precipitates and a hypopyon. The iris touched the cornea
temporally and was infiltrated by tumor from the 7- to 11-o'clock positions.
The vitreous had 2+ cells and flare. Funduscopy showed choroidal tumors through
hazy media. A total serous retinal detachment was present. Ultrasound performed
a few days later showed a diffuse, irregular mass of the choroid and ciliary
body with a maximum height of 9.5 mm (Figure
A, Ultrasound of the right eye 5 weeks after the onset of symptoms.
The arrows point to a mass seen in the ciliary body and choroid on both sides.
A retinal detachment is also evident. Scale bar is in millimeters. B, Gross
examination of the enucleated globe shows the uveal tumor (denoted by arrows)
in the locations approximately equivalent to those seen at ultrasound. C,
Section of the globe showing tumor in the ciliary body (CB). The haptic of
a lens prosthesis (H) is seen within in a lens remnant (hematoxylin-eosin,
original magnification ×6.25). D, High-power view of the tumor showing
cells with scant cytoplasm and nuclei with clumped chromatin. The arrow points
to a mitosis (hematoxylin-eosin, original magnification ×100). E, Low-power
view of the uveal tumor showing numerous small, round cells and scattered
larger cells (starry-sky appearance) (hematoxylin-eosin, original magnification
×25). F, Peripheral blood smear with 2 large lymphoid cells with prominent
nucleoli and deep-blue cytoplasm (Wright-Giemsa, original magnification ×250).
The patient had a 6-year history of chronic lymphocytic leukemia, RAI
stage 0 (lymphocytosis only). At an examination by her oncologist 6 months
prior to onset of ocular symptoms, she was without symptoms of the disease
and taking no systemic medications. Her white blood cell count at that time
was 17 000/mm3 (normal, 4800-10 800/mm3) and
her hematocrit was 36.9% (normal, 37%-40%). Three months before the onset
of ocular symptoms, her white blood cell count had decreased to 9900/mm3, and her hematocrit had decreased to 33.7%.
Because of the hypopyon and keratic precipitates, which are rarely found
in patients with uveal melanoma, the presumptive diagnosis was leukemic infiltrate
of the uveal tract. However, uveal melanoma could not be ruled out. In view
of the pain and no potential for vision, and because the uveal tumors were
too large for radiotherapy, the right eye was enucleated 7 weeks after the
onset of symptoms (Figure 1, B).
Findings from histologic evaluation showed that the uveal tumor (Figure 1, C and D) was composed of medium
to large cells with scant cytoplasm and vesicular nuclei with areas of clumped
chromatin and prominent nucleoli. There were more than 2 mitoses per high-power
field (Figure 1, D). Scattered among
these tumor cells were tingible body macrophages that produced the starry-sky
pattern seen in some high-grade lymphomas, especially those of Burkitt lymphoma
(Figure 1, E).
Immunoperoxidase studies showed that the tumor cells expressed bcl2
(an oncoprotein that inhibits apoptosis) and the B-lymphocyte antigen CD20.
They lacked the lymphocyte subset–associated markers CD10, CD5, and
TdT, as well as the melanoma markers HMB45 and MART1. Depending on the region
of the tumor evaluated, 60% to 90% of the tumor cells were positive for Ki67,
indicating a high fraction of proliferating cells. A few admixed nonneoplastic,
small T cells (expressing the pan-T-cell antigens CD3 and CD5) were present.
The diagnosis was high-grade B-cell lymphoma. The immunophenotype excluded
Burkitt lymphoma (which typically expresses CD20, CD10, and, in 100% of cells,
Ki67, and which lacks bcl2) and precursor B lymphoblastic lymphoma (which
typically expresses CD10 and TdT but not CD20).
Six weeks after the enucleation the patient felt weak and had palpable
axillary and inguinal lymph nodes and splenomegaly. The hematocrit fell to
20% and the white blood cell count rose to 146 000/mm3. Review
of a peripheral blood smear revealed 27% neutrophils, 1% bands, 27% lymphocytes,
5% monocytes, 38% blasts, and 2% nucleated red blood cells. The cells counted
as blasts were medium to large cells with deep-blue agranular cytoplasm and
ovoid nuclei with chromatin that was usually irregularly clumped. Most lacked
discrete nucleoli, but occasional cells had prominent nucleoli (Figure 1, F). The appearance was that of abnormal lymphoid cells
similar to those seen in the eye, but not typical of prolymphocytes. Only
palliative treatment was administered, and the patient died 4 months after
About 3% of patients with chronic lymphocytic leukemia develop non-Hodgkin
lymphoma (usually large B-cell lymphoma); this sequence of malignancies is
called Richter syndrome.1-3 The
onset of the lymphoma is usually abrupt. Clinical features include fever,
weight loss, increasing lymphadenopathy, lymphocytopenia, and dysglobulinemia.3 Based on studies of immunoglobulin isotypes and
gene rearrangements, the lymphoma in most cases of Richter syndrome appears
to be the progression of chronic lymphocytic leukemia into a more aggressive
tumor; however, in a minority of cases, the lymphoma likely represents a second
independently arising tumor.4
We know of only 2 previously reported cases of Richter syndrome that
involved the eye. In one case the malignant lymphocytes were confined to the
vitreous5; in the other, the tumor was in
the vitreous and the subretinal space.6 This
pattern of involvement is characteristic of retinal/central nervous system
lymphoma, a form of lymphoma that is not usually associated with disease outside
the central nervous system. Neither case had clinically apparent uveal involvement,
and neither case had the rapid downhill course typical after the development
of Richter syndrome. In contrast, the lymphoma in our case predominantly involved
the uveal tract, a feature that correlates with systemic lymphomas.7 The clinical findings mimicked uveal melanoma rather
than retinal/central nervous system lymphoma. The patient had a rapid downhill
course and died soon after the diagnosis was made. Our case represents what
we consider to be a novel presentation of Richter syndrome and demonstrates
that Richter syndrome should be included in the differential diagnosis of
None of the authors has proprietary or commercial interests related
to the report.
Corresponding author: Thaddeus P. Dryja, MD, Massachusetts Eye and
Ear Infirmary, 243 Charles St, Boston, MA 02114 (e-mail: firstname.lastname@example.org).
Fernandez-Suntay JP, Gragoudas ES, Ferry JA, Anderson ME, Dacey MP, Dryja TP. High-grade Uveal B-Cell Lymphoma as the Initial Feature in Richter Syndrome. Arch Ophthalmol. 2002;120(10):1383–1385. doi:
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