Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) associated with B-cell lymphoma: report of a rare case

This unique case illustrates that BDUMP should be considered in the differential diagnosis of patients with atypical diffuse pigmented fundus lesions. The five cardinal signs of BDUMP described by Gass et al. [1] are: (1) multifocal, faintly visible, round or oval, red, subretinal patches, with (2) associated striking pattern of associated hyperfluorescence during the early phases of angiography; (3) development of multiple, slightly elevated, pigmented and non-pigmented uveal melanocytic tumors, as evidence of diffuse thickening of uveal tract; (4) exudative retinal detachment; and (5) rapid progression of cataract [1].

Our case demonstrated some of these features, indicating an earlier stage of BDUMP, before the onset of exudative retinal detachment and progression of cataract. However, multifocal, faintly visible, roundish oval subretinal lesions, which were hyperfluorescent on FA suggested the diagnosis of BDUMP. The precise correspondence of the focal areas of early hyperfluorescence and the subretinal patches suggest that they are fenestrations of the pigment epithelium caused by its depigmentation and focal destruction in the absence of RPE and excrescences in inner segment-outer segment (IS-OS) junction demonstrated the level of lesions in the RPE. The same was also demonstrated in our case on spectral-domain OCT scan. To our knowledge, this case is distinct in the literature in demonstrating those changes in RPE on real time non-invasive scans. The other possible differential diagnoses of choriocapillaritis or stromal choroiditis were less likely as there were no classical clinical signs of any of those entities. Birdshot retinochoroidopathy was the closest differential diagnosis but due to lack of classical clinical and angiographic signs, the diagnosis of masquerade syndrome was kept and hence the patient was investigated for possible systemic association. Lymphoma-associated retinopathy as described by To et al. [6], was a pigmentary retinopathy occurring on the onset of chemotherapy for Hodgkin lymphoma. Our case had pale gray brown nummular lesions, rather than retinitis pigmentosa-like pigmentary migration of lymphoma-associated retinopathy. Our case fits in with BDUMP features as described by Gass: multifocal, faintly visible, round or oval, red, subretinal patches, with associated striking pattern of associated hyperfluorescence during the early phases of angiography [1].

Two types of melanocytes are found in the normal uveal tract: the normal melanocytes and, in many patients, nevus cells. Normal melanocytes are nonreactive cells that rarely, if ever, proliferate. Nevus cells that are present, either focally or diffusely (melanocytosis), do have the capability of proliferation that, in part, is subject to hormonal control and that normally is limited to the prepubertal and early adult years [7].

Suggestions for the pathogenesis of BDUMP have been postulated as either the de novo development of uveal melanocytic proliferation and the systemic carcinoma in response to a common oncogenic stimulus, [8] or the de novo development of uveal melanocytic proliferation in response to a hormone-secreting visceral carcinoma, or possibly coincidental development of bilateral low-grade diffuse uveal melanomas and a systemic carcinoma in patients genetically predisposed to neoplasia [1]. In addition, Miles et al. have recently shown that there is cultured melanocytic elongation and proliferation factor (CMEP) factor, in the serum that causes uveal melanocytes to proliferate [7].

Systemic carcinomas reported with BDUMP are ovarian, lung, gall bladder, cervical, uterine, kidney, pancreatic, breast, esophageal, and colorectal cancers. They may also be associated with melanocytic proliferation in other tissues [8,9]. Although rare, BDUMP has consistently resulted in devastating visual consequences. Usually during the year preceding death, patients with this paraneoplastic syndrome have severe bilateral vision loss. Vision decline has been attributed to destruction of photoreceptors and underlying RPE, serous retinal detachments, and, later, cataracts [1].

In the current case, the prompt diagnosis and immediate referral was key, with detailed systemic evaluation by internists and oncologists. As per the original description by Gass et al. [1] ocular signs precede manifestation of systemic carcinoma by 3–12 months, highlighting the need for the appropriate index of suspicion and prompt evaluation [10]. It is uncertain whether earlier intervention for the systemic malignancy will impact survival, as this paraneoplastic phenomenon is thought to occur in advanced malignancy.

Treatment of BDUMP is usually directed towards the primary cancer. Although transient visual improvement has been reported in patients with BDUMP in response to systemic corticosteroids and chemotherapy, [9] most cases have shown no effect of corticosteroid therapy alone [3] and no significant effect of radiotherapy [1]. Our case responded to systemic chemotherapy along with topical non-steroidal anti-inflammatory drops.