Bilateral choroidal lesions as first sign of recurrence in multiple myeloma - histopathological findings and treatment response to bevacizumab.

Abstract

Multiple myeloma is a neoplasia of plasma cells producing monoclonal immunoglobulin. Symptoms are fatigue, frequent infections, spontaneous bleedings and pathological fractures due to anaemia, leukopenia, thrombocytopenia and osteolytic lesions (Palumbo & Anderson 2011). Common extraskeletal localizations include spleen, liver, lymph nodes and kidneys. While there is only little knowledge about uveal involvement of multiple myeloma (Coupland et al. 2013), we hereby present the recurrence of multiple myeloma by bilateral choroidal manifestation, confirmed by biopsy, after successful stem cell transplantation and treatment response to bevacizumab. In April 2014, a 35-year-old woman presented with decreased visual acuity since 2 months. Multiple prominent lesions surrounding the macula were seen on the right eye (0.0 logMAR); and a large prominent juxtapapillar mass and several yellow-white spots were present on the left eye (1.0 logMAR; Fig. 1A,B). Multiple myeloma was diagnosed in January 2013, followed by chemotherapy and autologous stem cell transplantation. In May 2014, a choroidal biopsy with laser coagulation and silicone oil implantation was performed on the left eye in her home country. Thereof, we performed advanced immunohistochemistry. Sections were positive for CD38, CD138 and CD79a (Fig. 1E-G), while p53, MelanA and CD117 were negative. Regarding the vascular endothelial growth factor (VEGF), sections were slightly positive for VEGF-A (Fig. 1H). The right eye underwent intravitreal injections of bevacizumab (Avastin®, F. Hoffmann-La Roche AG, Basel, Switzerland) in May and June 2014 in her home country. In July 2014, no prominences were found on the right eye (0.0 logMAR), the left eye presented the remaining juxtapapillar tumour with fibrosis after biopsy and laser scars surrounding previous smaller lesions (Fig. 1C,D), and the visual acuity diminished to 2.0logMAR. So far, data on choroidal metastasis of plasmacytoma are limited. Coupland and colleagues (2013) analysed a collision tumour consisting of choroidal plasmacytoma and melanoma. Diagnosis was made by positive CD138 staining after enucleation, negative systemic staging confirmed a solitary extramedullary plasmacytoma. In our patient, choroidal lesions occurred as first sign of multiple myeloma recurrence 1 year after successful stem cell transplantation. Palamar and coworkers (2008) published a case of unilateral choroidal lesions 2 years after bone marrow transplantation for multiple myeloma. Diagnosis was confirmed by fine-needle aspiration, and lesions were treated by external beam radiotherapy. Based thereon, we have to keep in mind that external and transscleral radiotherapy imply adverse side effects such as cataract, scleral necrosis and skin destruction (Morgan et al. 2003). In contrast to radiotherapy, intravitreal anti-VEGF has limited side effects. In our patient, the response to bevacizumab occurred before the second chemotherapy began and nearly all lesions disappeared completely after two intravitreal injections. In this line, Zhou and colleagues (2013) reported a case with masquerade syndrome and history of multiple myeloma, developing neovascular glaucoma. Here, the secondary glaucoma was controlled by bevacizumab treatment – yet, it is unclear whether this was due to the reduction of choroidal lesions or secondary neovascularization. We know from bone marrow and cell line studies that myeloma cells contribute to tumour growth via VEGF secretion (Kumar et al. 2003). In this regard, we found VEGF-A expression in choroidal tissue, which may explain the treatment response to bevacizumab. Although choroidal biopsies are inevitable to confirm presumed diagnosis, only small tissue samples are required. Surgical damage may be avoided using small biopsy forceps or 23-gauge cutters. Laser coagulation is a destructive treatment and does not alter the underlying pathology of this generalized disease, thus laser coagulation of retinal lesions due to plasmacytoma should be avoided. Taken together, the systemic haematooncological treatment remains the basic therapy in patients with choroidal involvement of multiple myeloma and anti-VEGF might be used as adjunctive treatment.