Management of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP)-A Case Report.

Background and Objectives: This study reports a case of a 62-year-old patient experiencing a significant decline in vision over the past three months. The initial best-corrected visual acuity (BCVA) of 20/20 in both eyes diminished to 20/200 in the right eye (RE) and counting fingers (CF) in the left eye (LE) within this timeframe. The patient was diagnosed with stage 4 ovarian cancer just one month before the significant vision deterioration. Materials and Methods: A thorough ophthalmologic examination revealed a notable progression of cataracts and the presence of subretinal fluid on the posterior pole, accompanied by choroidal thickening. The right eye exhibited multifocal, orange-pigmented, and elevated choroidal lesions, while the left eye's fundus examination was impeded by dense cataracts. Optical coherence tomography (OCT) revealed bilateral choroidal thickening with overlying folds and subretinal fluid, and ultrasound imaging of the choroidal lesions indicated moderate homogenous internal reflectivity. Results: The patient received a diagnosis of BDUMP (bilateral diffuse uveal melanocytic proliferation), a paraneoplastic syndrome marked by simultaneous, bilateral, painless vision loss and the rapid onset of bilateral cataracts with serous retinal detachments. Despite cataract extraction, the expected visual recovery was not achieved (RE: CF; LE: 2/200, respectively). Plasmapheresis showed some success in stabilizing vision loss attributed to serous retinal detachments. Conclusions: BDUMP necessitates addressing the underlying malignancy for effective treatment. Left untreated, it can lead to near blindness within a year. The prognosis remains grim, with an average survival time ranging from 12 to 15.7 months from the time of diagnosis. Considering this case report, it is crucial to establish effective management plans and further investigate potential treatment methods and predictive markers centered around BDUMP. Collaboration between healthcare professionals and researchers is crucial in addressing the complexities of BDUMP, as the timely diagnosis and treatment of the disease remains a top priority.

[Bilateral diffuse uveal melanocytic proliferation : a rare paraneoplasic syndrome to be diagnosed early]. / Cas clinique. Prolifération mélanocytique uvéale bilatérale diffuse : un syndrome paranéoplasique rare à reconnaître précocement.

Diffuse bilateral uveal melanocytic proliferation is a rare paraneoplastic ophthalmologic syndrome. The increase in life expectancy in oncology partly explains the gradual increase in its incidence. In almost half of the cases, the syndrome manifests itself before the diagnosis of primary neoplasia. It should be suspected in cases of bilateral uveal pigmented lesions that do not meet the clinical criteria for other known eye pathologies. Legal blindness occurs for the majority of patients during the first year after the initial clinical presentation. Death, due to the severity of the underlying pathology, occurs statistically within three years. Here we display the case of such a diffuse bilateral uveal melanocytic proliferation in a patient with relapsed colonic adenocarcinoma, initially treated for age-related macular degeneration.

La prolifération mélanocytique uvéale bilatérale diffuse est un syndrome paranéoplasique ophtalmologique rare. L'augmentation de l'espérance de vie en oncologie explique, en partie, la majoration progressive de son incidence. Dans près de la moitié des cas, le syndrome se manifeste antérieurement au diagnostic de la néoplasie primaire. Il doit être suspecté en cas de lésions pigmentées uvéales bilatérales ne répondant pas aux critères cliniques d'autres pathologies oculaires connues. La cécité légale s'établit chez la majorité des patients durant la première année suivant la présentation clinique initiale. Un décès, dû à la sévérité de la pathologie sous-jacente, survient presque toujours dans les trois ans. Nous rapportons ici le cas d'une telle prolifération mélanocytique uvéale bilatérale diffuse, chez une patiente atteinte d'un adénocarcinome colique en rechute, traitée initialement pour une dégénérescence maculaire liée à l'âge.

Diagnosis of bilateral diffuse uveal melanocytic proliferation unveils primary gastric adenocarcinoma: a case report.

BACKGROUND: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is an extremely rare paraneoplastic syndrome, with most cases reported as secondary to female urogenital and male lung malignancies. We reported this case of BDUMP patient whose primary malignancy was gastric adenocarcinoma verified with gastroscopy and subsequent pathological test. CASE PRESENTATION: A patient complaining blurred vision was suspected of bilateral diffuse uveal melanocytic proliferation (BDUMP), due to bilateral round oval patches at the posterior pole and cardinal signs in retinal angiography. Malignancy screening was suggested, and pathological report from gastroscopy confirmed the primary lesion as gastric adenocarcinoma. The patient chose palliative care due to late stage and unresectable nature of the malignancy. CONCLUSIONS: Identifying BDUMP warrants further investigation of a primary malignancy. Our case provided evidence for the link between gastric adenocarcinoma and BDUMP.

Heterogeneity of cultured melanocyte elongation and proliferation factor in bilateral diffuse uveal melanocytic proliferation.

A patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with endometrial cancer was treated with plasmapheresis, but failed therapy with progressive serous retinal detachment. We collected plasma before and after plasmapheresis therapy. Our goal was to determine if the cultured melanocyte elongation and proliferation (CMEP) factor and hepatocyte growth factor (HGF) was present in the IgG enriched fraction and understand why our patient failed plasmapheresis therapy. Melanocytes were cultured for 3-5 days in the presence of control medium, unfractionated pre-plasmapheresis BDUMP medium, IgG enriched or IgG depleted BDUMP medium, or unfractionated post-plasmapheresis BDUMP medium. Subretinal fluid was collected from patients with BDUMP and control retinal detachments and analyzed by electropheresis with immunoblotting. Medium with unfractionated BDUMP plasma stimulated melanocyte growth 1.4-1.5 fold compared to control medium on days 3-5 (p < 0.001 for all). Both IgG enriched and IgG depleted BDUMP medium mildly increased melanocyte growth 1.3 fold (p < 0.05 for enriched, p < 0.01 for depleted) compared to control. In comparison, unfractionated BDUMP medium caused a 1.7-fold increase in melanocyte growth, which was significantly more than the enriched (p < 0.01) and depleted (p < 0.05) fractions. Pre-plasmapheresis and post-plasmapheresis unfractionated BDUMP medium equally stimulated melanocyte growth 1.7-fold (p < 0.05) compared to control. HGF was present in IgG depleted, pre-plasmapheresis, and post-plasmapheresis samples, but absent in the IgG enriched fraction. There was no enrichment of IgG in the subretinal fluid from eyes with BDUMP. In conclusion, CMEP factor is not concentrated in the IgG enriched plasma fraction in our patient who failed plasmapheresis therapy. HGF levels have no correlation with melanocyte growth. Because plasmapheresis preferentially removes immunoglobulins from the plasma, our patient responded poorly to plasmapheresis treatment with worsening retinal detachment.

Giraffe or leopard spot chorioretinopathy as an outstanding finding: case report and literature review.

PURPOSE: Presentation of two typical cases with characteristic leopard retinopathy secondary to bilateral diffuse uveal melanocytic proliferation (BDUMP) and idiopathic uveal effusion syndrome (IUES) and brief review of the literature about leopard spot retinopathy. CASE REPORT: A 43-year-old women, who was a known case of ovarian carcinoma, referred with gradual bilateral visual loss. In ophthalmic examination, subretinal fluid, multiple patchy subretinal hyperpigmented lesions and leopard spot chorioretinopathy were evident in her both eyes. Fluorescein angiography showed multiple nummular hyperfluorescent lesions surrounded by zones of hypofluorescence. Spectral domain optical coherence tomography revealed increased retinal thickness, subretinal fluid and RPE irregularities in both eyes. Enhanced depth imaging OCT (EDI-OCT) showed bilateral subfoveal choroidal thickening. During next 2-year follow-up, she underwent cataract surgery and later on developed neovascular glaucoma in her both eyes. The second case was a 45-year-old man who had developed decreased visual acuity in his left eye for 3 years. Anterior segment examination was unremarkable, and both eyes had normal intraocular pressure. No vitreous inflammation was observed. Fundoscopy revealed diffuse exudative retinal detachment in his left eye. Fluorescein angiography showed leopard spot retinopathy of posterior pole, and EDI-OCT disclosed subfoveal choroidal thickening. After exclusion of other causes of exudative retinal detachment and with diagnosis of IUES, he underwent intravitreal triamcinolone injection (2 mg) which improved his final vision to 20/40. CONCLUSION: Leopard spot retinopathy is an uncommon but clinically distinct manifestation of various disorders. BDUMP may present with leopard spot retinopathy, anterior uveal tract involvement and neovascular glaucoma. As EDI-OCT showed involvement and increased thickening of choroid in both cases of BDUMP and IUES, it may be better to consider such cases as leopard chorioretinopathy and categorize these entities as a member of pachychoroid pigment retinopathy disorders.

A Case of Bilateral Diffuse Uveal Melanocytic Proliferation Followed by Massive Unilateral Uveal Proliferation.

OBJECTIVE: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) followed by massive unilateral uveal proliferation. METHODS: Retrospective case report. RESULTS: A 47-year-old female with history of metastatic ovarian carcinoma initially presented with bilateral vision loss and multifocal red patches on posterior poles consistent with BDUMP. Five years later, she presented with bilateral neovascular glaucoma and unilateral iris and ciliary body mass concerning for malignancy. Enucleation revealed diffuse uveal growth involving almost the entirety of the uveal tract. CONCLUSIONS: BDUMP can rarely be associated with uveal proliferation. Routine examinations are recommended to monitor for any changes concerning malignancy.

Bilateral Diffuse Uveal Melanocytic Proliferation in a Patient with Recurrent Frontal Lobe Meningioma.

BACKGROUND: Bilateral diffuse uveal melanocytic proliferation (B-DUMP) is a paraneoplastic disorder that may be seen in patients with a known malignancy but more commonly is seen in those without any history of cancer. It leads to multiple uveal tumors with exudative retinal detachment along with thickening of the choroid and generally carries a poor prognosis. Its etio-pathogenesis is poorly understood but is said to involve factors secreted by the systemic malignancy that lead to proliferation of melanocytes in the uvea. METHODS: We report the presentation and management of a female with history of treated frontal lobe meningioma who presented with neovascular glaucoma along with B-DUMP and was found to have recurrence of the meningioma on neuro-imaging. CONCLUSIONS: Central nervous system meningiomas can cause B-DUMP and management of the malignancy may lead to partial resolution of posterior segment manifestations of B-DUMP.

Bilateral diffuse uveal melanocytic proliferation: Report of a novel optical coherence tomography finding and clinical response to plasmapheresis.

PURPOSE: To describe a novel optical coherence tomography (OCT) finding in a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) and to report the clinical response to plasmapheresis. OBSERVATIONS: We report the case of a 54-year-old man who was being treated with adjuvant immune checkpoint inhibitors for metastatic renal cell carcinoma. He had suffered from bilateral progressive vision loss without ocular pain. At presentation in the retina clinic, visual acuity was counting fingers bilaterally. Examination revealed characteristic findings suggestive of a peculiar paraneoplastic intraocular syndrome called BDUMP. Multiple choroidal nevi-like melanocytic tumors were noted bilaterally. The diagnosis was confirmed using multimodal imaging with fluorescein angiography and fundus autofluorescence, which revealed a typical leopard pattern. Ultrasonography revealed choroidal thickening extending to the ciliary body. OCT showed multiple pockets of serous retinal detachment (SRD) and bacillary layer detachment (BALAD), a newly recognized and rarely described manifestation of the disease. The clinical response to plasmapheresis was robust with resolution of the BALAD and SRD and improvement of the vision to 20/30 in both eyes at the seven-month follow-up. CONCLUSIONS AND IMPORTANCE: BALAD is a newly recognized manifestation of BDUMP. Early recognition of this paraneoplastic syndrome and prompt initiation of plasmapheresis has the potential to improve and stabilize vision.

Case Report: Blurred Vision and Eruptive Nevi - Bilateral Diffuse Uveal Melanocytic Proliferation With Mucocutaneous Involvement in a Lung Cancer Patient.

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Histology from a penile biopsy was compatible with a melanoma in situ. Due to the distribution pattern and elevated serum tumor marker S100B, metastatic melanoma was considered. Staging examinations using PET-CT scan however, revealed a lung tumor, later confirmed as a Non-small-cell lung cancer (NSCLC). Primary radio chemotherapy was initiated to treat NSCLC. Shortly after initiation of radio chemotherapy the patient developed massive vision impairment and a NSCLC-associated BDUMP was diagnosed which led to the correct classification of melanocytic skin lesions as mucocutaneous BDUMP manifestation. Plasmapheresis was started resulting in a rapid improvement of vision starting ten days after the first plasmapheresis. In contrast skin manifestations started to disappear with a marked delay 4 months after the last plasmapheresis cycle. This case highlights the importance of memorizing multiple rapidly progressing melanocytic skin and/or mucous membrane spots together with visual impairment as a possible paraneoplastic BDUMP that needs a fundamentally different therapeutic approach compared to multifocal melanoma in situ. What is already known about this topic? Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a paraneoplastic syndrome with melanocytic uveal proliferation leading to vision impairment. Extraocular manifestation is rare, mainly affect the subepidermal compartment and is hard to treat. Plasmapheresis has been shown to be an effective treatment mainly for vision improvement in some but not all cases. What does this study add? Our BDUMP case with widespread skin and mucosal involvement initially mimicked a multifocal melanoma in situ and showed an excellent treatment response to plasmapheresis. Improvement of mucocutaneous lesions has not been documented well in the literature so far. We show a more than one year lasting follow up still underlining the beneficial effect of plasmapheresis in this case. In-vitro data supports the hypothesis that plasma exchange eliminates a "Cultured melanocyte elongation and proliferation (CMEP)" factor out of patient blood leading to decreased melanocyte proliferation shown numerically in-vitro and clinically in-vivo. Our case clearly indicates that before establishing a definite diagnosis and therapy in patients with rapidly evolving melanocytic skin and/or mucosal lesions BDUMP mimicking multifocal melanoma in situ should be considered making a thorough diagnostic workup mandatory.

Prevalence of Hepatocyte Growth Factor and Autoantibodies to α-HGF as a New Etiology for Bilateral Diffuse Uveal Melanocytic Proliferation Masquerading as Neovascular Age-Related Macular Degeneration.

OBJECTIVE: The goal was to test the hypothesis that high serum hepatocyte growth factor (HGF) and retinal autoantibodies against α-HGF contribute to the pathology of bilateral diffuse melanocytic proliferation (BDUMP). METHODS: Case report of an elderly diagnosed with neovascular age-related macular degeneration (n-AMD) treated with bilateral Bevacizumab injections. Examination included comprehensive ophthalmic examination and images obtained by fundus photography, fundus autofluorescence, fluorescein angiography, spectral-domain optical coherence tomography (OCT), and B-scan ultrasonography. The levels of HGF and circulating HGF receptor (c-MET) were measured in the serum by ELISA and anti-retinal autoantibodies by western blotting. RESULTS: Patient received Bevacizumab injections for presumed n-AMD and had a history of papillary renal cell carcinoma stage 4 with a tumor containing gene mutation Y1230C in the mesenchymal-epithelial transition factor (MET). Visual acuity was 20/200 OD and CF OS. Multimodal imaging was consistent with BDUMP. Plasma exchange therapy was recommended but could not be started until 10 months later due to deterioration in his medical condition. Pre- and post-plasma exchange sera demonstrated anti-retinal autoantibodies against 69-kDa protein of the same molecular weight as the α-HGF. Serum autoantibodies reacted with purified recombinant α-HGF on the blot. CONCLUSIONS: BDUMP can mimic n-AMD, which can delay treatment. Plasma exchange resulted in resolved inflammation, resolution of exudative detachments and improved vision after cataract surgery. Consideration of the tumor genetics led to the recognition of elevated HGF levels and autoantibodies to α-HGF (anti-69-kDa), which suggested a new pathogenic mechanism of BDUMP. We believe that therapy with tyrosine kinase inhibitors and a checkpoint inhibitor may contribute to the high HGF levels and subsequent immune response.

Bilateral diffuse uveal melanocytic proliferation as a precursor to multiple systemic malignancies.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare, intraocular paraneoplastic syndrome characterized by multiple, elevated, pigmented uveal lesions, diffuse thickening of the uveal tract, and rapidly progressive cataracts. We report a 70-year-old Caucasian male with an inferotemporal conjunctival-scleral pigmented lesion of the right eye. Funduscopy and ultrasonography revealed multiple elevated pigmented choroidal lesions in both eyes. Genome-wide single nucleotide polymorphism (SNP) analysis of intraoperative transscleral fine-needle aspiration biopsies from both eyes revealed a whole gain on chromosome 5. BDUMP was diagnosed, and the patient underwent a thorough systemic investigation, which was negative for an underlying malignancy; however, by maintaining a high index of suspicion, multiple malignancies were uncovered and appropriately treated over the ensuing years. This report presents the clinical, cytologic, and cytogenetic features of BDUMP, and is the first to demonstrate a novel finding of a whole gain in chromosome 5 by SNP analysis of the choroidal lesions. Additionally, this is the first case to potentially associate BDUMP and both transitional cell carcinoma of the bladder as well as renal clear cell carcinoma.