Open Access

Multimodal imaging of bilateral diffuse uveal melanocytic proliferation associated with an iris mass lesion

International Journal of Retina and Vitreous20162:13

https://doi.org/10.1186/s40942-016-0038-7

Received: 1 April 2016

Accepted: 27 April 2016

Published: 16 May 2016

Abstract

Background

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.

Case presentation

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.

Conclusions

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.

Keywords

Bilateral diffuse uveal melanocytic proliferation Melanocytes Malignancy Ultra-widefield Swept-source optical coherence tomography Iris tumor

Background

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 [1]. In 1966, Machemer et al. [2] first described this clinical syndrome, although it was not until 1982 that Barr et al. [3] coined the term BDUMP. In 1990, Gass et al. [4] 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 [532] 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).

Case presentation

A 59-year-old white female presented with complaints of decreasing vision and photophobia over the prior month. Her medical history was notable for hypertension and chemotherapy for ovarian carcinoma 5 years prior to presentation. On examination, her best-corrected visual acuity was 20/40 OD and 20/80 OS. The anterior segment examination was remarkable for a pigmented, vascularized iris mass lesion at the superior pupillary border in her right eye (Fig. 1). Her intraocular pressures were normal. Funduscopic examination and color fundus photography (Topcon TRC-50XF; Topcon Medical Systems, Oakland, NJ) showed bilateral exudative macular detachments with multiple scattered darkly pigmented choroidal lesions (Fig. 2a). The extent of the pathology was better seen with ultra-widefield color images (Optos 200Tx; Optos, Scotland, United Kingdom) (Fig. 2b). RPE changes forming a ‘giraffe-pattern’ were noted in the posterior pole of both eyes. Ultra-widefield autofluorescence (AF) imaging (Optos 200Tx; Optos, Scotland, United Kingdom) highlighted and documented the full extent of this pattern with patches of hypo-AF alternating with intervening areas of hyper-AF (Fig. 2c). Fundus camera based ICGA (Topcon TRC-50XF; Topcon Medical Systems, Oakland, NJ) showed the scattered darkly pigmented choroidal lesions as well-circumscribed hypofluorescent areas (Fig. 2d).
Fig. 1

Color photograph of patient’s right eye showing a superior iris melanocytic lesion (a). Higher magnification view of the iris lesion displaying the pigmented mass with some associated vascularity (b)

Fig. 2

Standard flood-illuminated and Ultra-wide field (UWF) color photographs show multiple scattered melanocytic lesions throughout the fundus associated with pigmentary changes extending from the posterior pole (a, b). UWF AF shows round-like patches of hypo-AF alternating with intervening areas of hyper-AF in the posterior pole (c). ICG angiography shows these scattered melanocytic lesions to be hypofluorescent (d)

SD-OCT (Heidelberg Spectralis: Heidelberg Engineering, Heidelberg, Germany) showed areas of subretinal fluid and discrete hyper-reflective choroidal lesions that appear to be compressing the adjacent choriocapillaris. The choroidal lesions were highly reflective on near-infrared reflectance (nIR) (Fig. 3a–c). Enhanced depth imaging OCT (EDI-OCT) performed with the Heidelberg Spectralis showed diffuse choroidal thickening beneath the exudative macular detachments (Fig. 3d, e). Swept-source OCT (DRI OCT-1; Topcon Medical Systems, Oakland, NJ) of the right eye showed alternating RPE thickening and RPE loss that corresponded to the appearance of the “giraffe-pattern” seen on the AF (Fig. 4).
Fig. 3

Spectral-domain optical coherence tomography (SD-OCT) with matching near-infrared reflectance (nIR) localizes these discrete lesions to the choroid with compression of the choriocapillaris (red arrow) and associated subretinal fluid (blue arrow). The choroidal lesions are intensely hyper-reflective on nIR images (ac). EDI-OCT shows markedly increased choroidal thickness with overlying subretinal fluid of the right (d) and left eyes (e)

Fig. 4

Swept-source optical coherence tomography (SS-OCT) through the fovea (a) and through a superior large melanocytic lesion (b) of the right eye highlighting the increased choroidal thickness, subretinal fluid and the alternating RPE thickening (red arrow) and RPE loss (yellow arrow) that corresponds to the appearance of the alternating pattern seen on the UWF AF

The patient was referred back to her oncologist for further evaluation of a presumed recurrence of her ovarian carcinoma.

Conclusions

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 [1].

Of the approximately 50 cases of BDUMP reported in literature [133], only 6 cases have reported the association with iris tumors. [3, 20, 3437] Originally described by Gass et al. [4] 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 [30] 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, [38] 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 [39]. 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.

Abbreviations

BDUMP: 

bilateral diffuse uveal melanocytic proliferation

OCT: 

optical coherence tomography

SS: 

swept source

SD: 

spectral domain

AF: 

autofluorescence

ICGA: 

indocyanine green angiography

RPE: 

retinal pigment epithelium

EDI: 

enhanced depth imaging

UWF: 

ultra-wide field

Declarations

Authors’ contributions

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.

Acknowledgements

None.

Competing interests

K. Bailey Freund Genentech: Consultant, Optovue: Consultant, Optos: Consultant, Heidelberg Engineering: Consultant; ThromboGenics. The authors declare that they have no competing interests.

Consent

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.

Financial support

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.

Authors’ Affiliations

(1)
The Vitreous Retina Macula Consultants of New York
(2)
LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital
(3)
Department of Ophthalmology, New York University School of Medicine
(4)
Department of Ophthalmology, North Shore - Long Island Jewish Health System

References

  1. 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
  2. Machemer R. On the pathogenesis of the flat malignant melanoma. Klin Monbl Augenheilkd. 1966;148:641–52.PubMedGoogle Scholar
  3. 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
  4. 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
  5. Rahimy E, Sarraf D. Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: evaluation and management. Surv Ophthalmol. 2013;58:430–58.View ArticlePubMedGoogle Scholar
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. Reddy S, Finger PT. Unilateral diffuse uveal melanocytic proliferation (DUMP). Br J Ophthalmol. 2007;91:1726–7.View ArticlePubMedPubMed CentralGoogle Scholar
  21. Semenova EA, Chin KJ, Natesh S, et al. Fundus autofluorescence imaging of diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging. 2010;1–3. doi:https://doi.org/10.3928/15428877-20100215-96
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. Leys AM, Dierick HG, Sciot RM. Early lesions of bilateral diffuse melanocytic proliferation. Arch Ophthalmol. 1991;109:1590–4.View ArticlePubMedGoogle Scholar
  34. 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
  35. Rohrbach JM, Roggendorf W, Thanos S, et al. Simultaneous bilateral diffuse melanocytic uveal hyperplasia. Am J Ophthalmol. 1990;110:49–56.View ArticlePubMedGoogle Scholar
  36. 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
  37. 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
  38. 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
  39. Alrashidi S, Aziz AA, Krema H. Bilateral diffuse uveal melanocytic proliferation: a management dilemma. BMJ Case Rep. 2014;22:2014.Google Scholar

Copyright

© Naysan et al. 2016

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