Ocular lymphoma with extrascleral extension as primary manifestation of Richter syndrome

Sir,

Richter syndrome occurs in 3–10% of patients with chronic lymphocytic leukaemia (CLL) and represents a transformation of CLL into diffuse large B-cell lymphoma.¹

We report what we believe to be the first case of Richter-syndrome transformation, presenting as a choroidal lesion with extrascleral extension in a patient with CLL.

Case report

A 62-year-old Caucasian male with CLL presented with sudden painless visual deterioration in the right eye; initial examination only revealed the posterior segment to be affected, with extensive vitreous cells and leopard-like spots on the choroid (Figure 1). The visual acuity in the right eye declined rapidly over the next 4 months to hand movements (left-eye spared), and because MRI of the orbits was clear, biopsies of the choroid and vitreous were performed and were suggestive of lymphoma involvement by B cells (Figures 2a–c). Radiation therapy to the right orbit was discussed, but declined by the patient because of the risk of radiation-induced optic neuropathy to his left eye. Over the next 6 months, the right eye became painful with no perception of light. A CT scan of the orbits revealed a chorioretinal mass with extrascleral extension but could not differentiate between a leukaemic deposit and a melanoma (Figure 3). The general health of the patient began to deteriorate with the spleen enlarging and his red cell count, as well as platelets, declining. The haematologists commenced chemotherapy of fludarabine–cyclophosphamide–rituximab, but this caused prolonged thrombocytopenia after two courses and no improvement in ocular symptoms, and therefore was discontinued. As there was no visual potential in the right eye (left eye remained unaffected) and because it had become painful, enucleation was performed. Histopathology revealed diffuse large B-cell lymphoma (Richter transformation) with optic nerve involvement, extraocular muscle, and orbital infiltration (Figures 2d–f). Because of the aggressive nature of the lymphoma (Figure 4) and despite further chemotherapy, the patient died 6 months after enucleation.

Figure 1

Black and white fundus photograph of the right eye, revealing intraretinal infiltrates in early phase of disease manifestation.

Figure 2

Immunostaining of initial choroidal biopsy from the right eye (a, b, and c) followed by immunostaining of choroid from the enucleated right eye after 6 months (d, e, and f). (a) Choroid immunostained for CD20 (brown, peroxidase technique), demonstrating extensive infiltration by medium-sized B lymphocytes. BV, blood vessel; R, retina. (b) Choroid immunostained for CD5, demonstrating very variable expression of CD5 by the B lymphocytes, although a bone-marrow trephine in 2004 confirmed a diagnosis of the B-cell lymphoma/leukaemia, CLL with cells that were uniformly CD20+ CD79a+ CD5+ and cyclin D1-negative. (c) Choroid immunostained for the proliferation marker, Mib-1, giving a very variable proliferation index that appeared to be up to 50% in places. However, overall it did not definitely exceed 30%, the World Health Organization-defined minimum for diffuse large B-cell lymphoma.⁴ Because of the small size of the biopsy, it was difficult to give a definitive diagnosis of CLL or to determine whether transformation to diffuse large B-cell lymphoma might have occurred. (d) Area of extensive lymphoid infiltration in choroid from enucleated right eye immunostained for CD20, demonstrating extensive infiltration by large pleomorphic B lymphocytes. (e) Enucleation specimen immunostained for CD5, showing very little CD5 expression, as sometimes occurs during high-grade (Richter) transformation of CLL to diffuse large B-cell lymphoma.⁴ (f) Enucleation specimen immunostained for the proliferation marker Mib-1, demonstrating a proliferation index of 90%, confirming the diagnosis of diffuse large B-cell lymphoma.

Figure 3

CT showing a chorioretinal mass (arrow) in the right orbit, predominantly affecting the lateral and posterior parts of the globe, as well as transscleral extension laterally at the time of the choroidal biopsy. No retro-global abnormality is identified.

Figure 4

MRI of orbits with gadolinium, 1 month post right enucleation, showing a medpor orbital implant and enhancing soft-tissue mass surrounding the right optic nerve (arrow) in keeping with recurrent lymphoma.

Comment

We know of only three reported cases of Richter syndrome that involved the eye but none with extrascleral extension.^{2, 3} This must be included in the differential of patients with CLL who present with ocular inflammation.