Multimodal imaging of bilateral diffuse uveal melanocytic proliferation associated with an iris mass lesion
© Naysan et al. 2016
Received: 1 April 2016
Accepted: 27 April 2016
Published: 16 May 2016
Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare, paraneoplastic syndrome characterized by bilateral painless visual loss and proliferation of choroidal melanocytes in association with an underlying systemic malignancy. We report a case of bilateral diffuse uveal melanocytic proliferation associated with an underlying gynecological malignancy that also features the infrequent finding of an iris mass lesion, using multimodal imaging including ultra-widefield imaging, spectral domain and swept-source optical coherence tomography.
A 59-year-old white female with a prior history of gynecological malignancy in remission presented with progressive bilateral visual loss over several weeks. The patient was noted to have a focal iris mass lesion in her right eye. Ultra-widefield color fundus photography showed a characteristic bilateral ‘giraffe pattern’ of pigmentary changes extending into the periphery as well as multiple discrete deeply pigmented lesions. Ultra-widefield autofluorescence was useful for visualizing the full extent of involvement. Indocyanine green angiography helped to demarcate the discrete pigmented choroidal lesions. Swept-source OCT clearly delineated the alternating zones of retinal pigment epithelium (RPE) thickening and RPE loss, as well as the prominent choroidal infiltration and thickening.
BDUMP is an important diagnosis to consider in the presence of multiple discrete melanocytic choroidal lesions, diffuse choroidal thickening, characteristic RPE changes, iris mass lesions and exudative retinal detachment. Ultra-widefield imaging may demonstrate more extensive lesions than that detected on clinical examination or standard field imaging. Imaging with SS-OCT shows choroidal and RPE characteristics that correlate well with known histopathology of this entity.
KeywordsBilateral diffuse uveal melanocytic proliferation Melanocytes Malignancy Ultra-widefield Swept-source optical coherence tomography Iris tumor
Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare, paraneoplastic syndrome characterized by bilateral painless, profound visual loss in association with an underlying systemic malignancy . In 1966, Machemer et al.  first described this clinical syndrome, although it was not until 1982 that Barr et al.  coined the term BDUMP. In 1990, Gass et al.  described the five cardinal signs of BDUMP as: (1) multiple orange-red subretinal patches; (2) early hyperfluorescence on fluorescein angiography; (3) multiple elevated pigmented and non-pigmented uveal melanocytic tumors with diffuse choroidal thickening; (4) exudative retinal detachments; and (5) rapidly progressive cataracts.
Since then, about 50 cases have been described in the literature [5–32] and the primary malignancy typically involves the reproductive tract in women, and gastrointestinal or respiratory system in men. We report an unusual case of BDUMP in a patient with a history of ovarian carcinoma. This case also displayed the uncommon finding of an iris mass lesion, which has been rarely described in this entity. This case of BDUMP was evaluated with multimodal imaging techniques that included ultra-widefield color and autofluorescence (AF); indocyanine green angiography (ICGA); and spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT).
The patient was referred back to her oncologist for further evaluation of a presumed recurrence of her ovarian carcinoma.
We present a case of BDUMP using multimodal imaging including the use of ultra-widefield imaging, ICG angiography and SS-OCT that helped to show the full extent of the posterior segment disease. Ultra-widefield color fundus photography allowed greater visualization of pigmentary changes and multiple pigmented lesions in the periphery, while ultra-widefield AF accentuated the characteristic ‘giraffe-pattern’ fundus changes which were more difficult to appreciate on clinical examination. EDI-OCT and SS-OCT readily showed choroidal thickening and alternating zones of RPE thickening and RPE loss. These findings correlate well with the known histopathology of BDUMP. The choroid is diffusely thickened with uveal melanocytic cells including nevoid, spindle cells, and epithelioid cells. There are also aggregates of focal infiltration of pigmented melanocytes in the choroid with overlying areas of RPE destruction alternating with areas of RPE hypertrophy .
Of the approximately 50 cases of BDUMP reported in literature [1–33], only 6 cases have reported the association with iris tumors. [3, 20, 34–37] Originally described by Gass et al.  iris involvement is infrequently seen or documented. We highlight this uncommon occurrence to create awareness that BDUMP can lead to infiltration of the uveal tract including the iris and ciliary body, which may further lead to angle-closure glaucoma and cataracts.
Various treatments for BDUMP, including ocular radiation [1, 3, 19, 32], subretinal fluid drainage  and corticosteroids [15, 16, 24, 35] have been tried without success. Recently, plasmapheresis has been shown to improve visual acuity in few case reports. [1, 11] The rationale is to decrease the circulating autoantibodies, [1, 11, 24] shown to be in the IgG fragment termed cultured melanocyte elongation and proliferation (CMEP) factor,  which stimulates cutaneous and uveal melanocyte cell proliferation. However, success with this treatment has been limited. The overall prognosis for BDUMP is poor with the majority of patients passing within 3 years . Treatment of the underlying systemic malignancy is crucial.
In summary, we show the benefit of multimodal imaging in BDUMP to demonstrate the full extent of the disease. We highlight the occurrence of iris lesions in this condition and the difficulties with treatment options.
bilateral diffuse uveal melanocytic proliferation
optical coherence tomography
indocyanine green angiography
retinal pigment epithelium
enhanced depth imaging
JN: Acquisition of data, Conceptualization of manuscript, review of literature, drafting/editing of the report. CP: Acquisition of data, Conceptualization of manuscript, editing the report, preparation of image panels. RK: Conceptualization of manuscript, editing the report. KBF: Design of project, Conceptualization of manuscript, editing the report, analysis and interpretation final approval of manuscript. All authors read and approved the final manuscript.
K. Bailey Freund Genentech: Consultant, Optovue: Consultant, Optos: Consultant, Heidelberg Engineering: Consultant; ThromboGenics. The authors declare that they have no competing interests.
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The Macula Foundation, Inc., New York, NY, USA. The funding organization had no role in the design or conduct of this research.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Rb Mets, Golchet P, Adamus G, et al. Bilateral diffuse uveal melanocytic proliferation with a positive ophthalmoscopic and visual response to plasmapheresis. Arch Ophthalmol. 2011;129(9):1235–8.View ArticleGoogle Scholar
- Machemer R. On the pathogenesis of the flat malignant melanoma. Klin Monbl Augenheilkd. 1966;148:641–52.PubMedGoogle Scholar
- Barr CC, Zimmerman LE, Curtin VT, et al. Bilateral diffuse melanocytic uveal tumors associated with systemic malignant neoplasms. A recently recognized syndrome. Arch Ophthalmol. 1982;100:249–55.View ArticlePubMedGoogle Scholar
- Gass JD, Gieser RG, Wilkinson CP, et al. Bilateral diffuse uveal melanocytic proliferation in patients with occult carcinoma. Arch Opthalmol. 1990;108:527–33.View ArticleGoogle Scholar
- Rahimy E, Sarraf D. Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: evaluation and management. Surv Ophthalmol. 2013;58:430–58.View ArticlePubMedGoogle Scholar
- Yonekawa Y, Shildkrot Y, Elliot D. Inferior Peripheral nonperfusion in bilateral diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging Retina. 2013;44:190–2.View ArticlePubMedGoogle Scholar
- Mudhar HS, Scott I, Ul-Hassan A, et al. Bilateral diffuse uveal melanocytic hyperplasia: molecular characterization and novel association with bilateral renal papillary carcinoma. Histopathology. 2012;61:751–4.View ArticlePubMedGoogle Scholar
- Navajas EV, Simpson ER, Krema H, et al. Cancer-associated nummular loss of RPE: expanding the clinical spectrum of bilateral diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging. 2011;42:e103–6.PubMedGoogle Scholar
- Bruggemann A, von Bulow M, Finas D, et al. Bilateral diffuse uveal melanocytic proliferation associated with the recurrence of a Bartholin gland carcinoma. Br J Ophthalmol. 2011;95:888–9.View ArticlePubMedGoogle Scholar
- De Salvo G, Prakash P, Rennie CA, et al. Long-term survival in a case of bilateral diffuse uveal melanocytic proliferation. Eye (Lond). 2011;25:1385–6.View ArticleGoogle Scholar
- Jaben EA, Pulido JS, Pittock S, et al. The potential role of plasma exchange as a treatment for bilateral diffuse uveal melanocytic proliferation: a report of two cases. J Clin Apher. 2011;26:356–61.View ArticlePubMedGoogle Scholar
- Shinmura M, Hamasaki D, Matsuyama T, et al. A case of squamous cell carcinoma of the lung with bilateral diffuse uveal melanocytic proliferation (BDUMP) diagnosed by visual disturbance. Nihon Kokyuki Gakkai Zasshi. 2011;49:187–91.PubMedGoogle Scholar
- Ulrich JN, Garg S, Escaravage GK Jr, et al. Bilateral diffuse uveal melanocytic proliferation presenting as small choroidal melanoma. Case Rep Ophthalmol Med. 2011;2011:1–3.View ArticleGoogle Scholar
- Kiratli H, Erkan K. Loss of retinal pigment epithelium associated with bilateral diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging. 2010;5:1–4.Google Scholar
- Mora P, Gonzales S, Crafa P, et al. Peculiar findings in a case of bilateral uveal pigmented lesions. Ocul Immunol Inflamm. 2010;18:379–82.View ArticlePubMedGoogle Scholar
- Besirli CG, Comer GM. High-resolution OCT imaging of RPE degeneration in bilateral diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging. 2010;41(Suppl):S96–100.View ArticlePubMedGoogle Scholar
- Mandelcorn E, McGuire K, Dixon W, et al. Ocular paraneoplastic syndrome: a case of bilateral diffuse uveal melanocytic proliferation. Retina. 2009;29:1375–6.View ArticlePubMedGoogle Scholar
- Bahar I, Weinherger D, Kremer MR, et al. Ocular manifestation of bronchogenic carcinoma: simultaneous occurrence of diffuse uveal melanocytic proliferation and uveal metastases. Harefuah. 2007;146:2–3.PubMedGoogle Scholar
- Duong HV, McLean IW, Beahm DE. Bilateral diffuse melanocytic proliferation associated with ovarian carcinoma and metastatic malignant amelanotic melanoma. Am J Ophthalmol. 2006;142:693–5.View ArticlePubMedGoogle Scholar
- Reddy S, Finger PT. Unilateral diffuse uveal melanocytic proliferation (DUMP). Br J Ophthalmol. 2007;91:1726–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Semenova EA, Chin KJ, Natesh S, et al. Fundus autofluorescence imaging of diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging. 2010;1–3. doi:10.3928/15428877-20100215-96
- Sen J, Clewes AR, Quah SA, et al. Presymptomatic diagnosis of bronchogenic carcinoma associated with bilateral diffuse uveal melanocytic proliferation. Clin Experiment Ophthalmol. 2006;34:156–8.View ArticlePubMedGoogle Scholar
- Wu S, Slakter JS, Shields JA, et al. Cancer-associated nummular loss of the pigment epithelium. Am J Ophthalmol. 2005;139:933–5.View ArticlePubMedGoogle Scholar
- Saito W, Kase S, Yoshida K, et al. Bilateral diffuse uveal melanocytic proliferation in a patient with cancer associated retinopathy. Am J Ophthalmol. 2005;140:942–5.View ArticlePubMedGoogle Scholar
- O’Neal KD, Butnor KJ, Perkinson KR, et al. Bilateral diffuse uveal melanocytic proliferation associated with pancreatic carcinoma: a case report and literature review of this paraneoplastic syndrome. Surv Ophthalmol. 2003;48:613–25.View ArticlePubMedGoogle Scholar
- Yu S, Ikeda T, Ikeda N, et al. Coloration of fundus lesions in bilateral diffuse uveal melanocytic proliferation. Jpn J Ophthalmol. 2003;47:612–5.View ArticlePubMedGoogle Scholar
- Frau E, Lautier-Frau M, Labetoulle M, et al. Bilateral diffuse uveal melanocytic proliferation associated with systemic carcinoma: two case reports. J Fr Ophtalmol. 2002;25(10):1032–5.PubMedGoogle Scholar
- Chen YC, Li CY, Kuo YH, et al. Bilateral diffuse uveal melanocytic proliferation in a woman with uterine leiomyoma: case report. Chang Gung Med J. 2001;24(4):274–9.PubMedGoogle Scholar
- Chahud F, Young RH, Remulla JF, Khadem JJ, Dryja TP. Bilateral diffuse melanocytic proliferation associated with extraocular cancers. Review of a process particularly associated with gynecologic cancers. Am J Surg Pathol. 2001;25:212–8.View ArticlePubMedGoogle Scholar
- Ritland JS, Eide N, Tausjo J. Bilateral diffuse uveal melanocytic proliferation and uterine cancer. A case report. Acta Ophthalmol Scand. 2000;78:366–8.View ArticlePubMedGoogle Scholar
- Makino S, Fukazawa M, Nakayama T. A case of bilateral diffuse uveal melanocytic proliferation. Rinsho Ganka (Jpn J Clin Ophthalmol). 1993;47:1794–5.Google Scholar
- Borruat FX, Othenin-Girard P, Uffer S, Othenin-Girard B, Regli F, Hurlimann J. Natural history of diffuse uveal melanocytic proliferation. Ophthalmology. 1992;99:1698–704.View ArticlePubMedGoogle Scholar
- Leys AM, Dierick HG, Sciot RM. Early lesions of bilateral diffuse melanocytic proliferation. Arch Ophthalmol. 1991;109:1590–4.View ArticlePubMedGoogle Scholar
- Prause JU, Jensen OA, Eisgart F, et al. Bilateral diffuse malignant melanoma of the uvea associated with large cell carcinoma, giant cell type, of the lung. Case report of a newly described syndrome. Ophthalmologica. 1984;189:221–8.View ArticlePubMedGoogle Scholar
- Rohrbach JM, Roggendorf W, Thanos S, et al. Simultaneous bilateral diffuse melanocytic uveal hyperplasia. Am J Ophthalmol. 1990;110:49–56.View ArticlePubMedGoogle Scholar
- Tsukahara S, Wakui K, Ohzeki S. Simultaneous bilateral primary diffuse malignant uveal melanoma: case report with pathological examination. Br J Ophthalmol. 1986;70:33–8.View ArticlePubMedPubMed CentralGoogle Scholar
- Joseph A, Rahimy E, Sarraf D. Bilateral diffuse uveal melanocytic proliferation with multiple iris cysts. JAMA Ophthalmol. 2014;132(6):756–60.View ArticlePubMedGoogle Scholar
- Miles SL, Niles RM, Pittock S, et al. A factor found in the IgG fraction of serum of patients with paraneoplastic bilateral diffuse uveal melanocytic proliferation causes proliferation of cultured human melanocytes. Retina. 2012;32:1959–66.View ArticlePubMedGoogle Scholar
- Alrashidi S, Aziz AA, Krema H. Bilateral diffuse uveal melanocytic proliferation: a management dilemma. BMJ Case Rep. 2014;22:2014.Google Scholar