Combined systemic and ocular chemotherapy for anterior segment metastasis of systemic mantle cell lymphoma

Abstract

Background: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature.

Findings: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and fibrin. The AC cells stained positively for CD20. The iris was thickened and coated with lymphoma cells. Iris neovascularization was present. Given extensive systemic and ocular involvement, the patient was given combination chemotherapy with systemic ibrutinib and intravitreal injections of methotrexate and rituximab. The disease response was monitored using multimodal imaging, including anterior segment optical coherence tomography and ultrasound biomicroscopy. Following combination of systemic and intraocular chemotherapy, there was a marked decrease in the ocular tumor load and the systemic disease.

Conclusions: Combination therapy with intravitreal injections of chemotherapeutic agents targeting monoclonal B-cell population and novel systemic agents may help to achieve remission in anterior segment metastasis of aggressive subtypes of NHL such as blastic variant of MCL. Multimodal imaging may assist in the management of these cases.

Keywords: Ibrutinib; Iris; Mantle cell lymphoma; Metastasis; Methotrexate; Rituximab; Ultrasound biomicroscopy; Uveitis.

Fig. 1

a Slit-lamp photograph showing lymphoma involving the iris and anterior chamber (AC). There was diffuse conjunctival injection, a large hypopyon, fibrin over the pupil, and iris neovascularization (especially nasally). b Slit-lamp photograph taken 2 weeks after initiation of treatment shows a marked decrease in the conjunctival injection, AC inflammation, and hypopyon. The fibrin is no longer seen. Superior iridectomy and suture from prior trabeculectomy are seen

Fig. 2

a The anterior segment optical coherence tomography (AS-OCT) performed using the cornea protocol shows the presence of a large, irregular hyper-reflective cellular material floating in the anterior chamber (AC). b shows the magnified view of the lymphoma cells. c The follow-up AS-OCT scan shows a decrease in AC inflammation. d A single large granulomatous keratic precipitate is captured and its magnified view is shown

Fig. 3

a Photomicrograph of cell block showing cytological details of the anterior chamber fluid cells. a Hematoxylin and eosin (H&E) stain (100×) demonstrates malignant lymphocytes. b Diff-Quik staining (100×) of the sample shows lymphoma cells with atypical, enlarged, irregular nuclei and increased N/C ratio. c Immunostaining with CD3 (100×) shows negative staining of the lymphoma cells. d Immunostaining with pan-B cell marker CD20 (100×) shows strong membranous staining. The findings on histopathology and the immunoprofile are consistent with the diagnosis of mantle cell lymphoma

Fig. 4

a Ultrasound biomicroscopy (UBM) of the right eye shows secondary angle closure due to thickened iris. b UBM of the left eye shows normal appearance of the iris of the fellow eye with open angles. CB indicates the ciliary body. c AS-OCT of the right eye shows the pre-treatment state of the temporal iris. The white arrow indicates the floating lymphoma cells. The angle of the AC appears closed. d The appearance of the iris after institution of therapy reveals a decrease in the thickness and opening up of the angle (double-sided arrow). e The nasal iris shows partially visible posterior surface of the iris and internal hypo-reflectivity (asterisk) due to the increased tissue density anteriorly and poor penetration of the infrared rays through the thick iris. f The follow-up scan of the nasal iris after treatment shows reduction in the thickness and clearly visible posterior iris surface. The angle of AC appears open (double-sided arrow)