This report describes a case of cancer-associated nummular retinal pigment epithelium loss associated with uterine cancer. The patient had progressive visual loss despite treatment with plasmapheresis, intravenous immunoglobulin, and local injection of corticosteroids. Clinical deterioration was corroborated by extension of the areas of retinal pigment epithelium loss, progression of cataracts, and growth of pigmented choroidal and iris lesions. Previously published cases of cancer-associated nummular retinal pigment epithelium loss did not describe the presence of cataracts or uveal melanocytic lesions. This case expands the clinical spectrum of bilateral diffuse uveal melanocytic proliferation.
Cancer-Associated Nummular Loss of RPE: Expanding the Clinical Spectrum of Bilateral Diffuse Uveal Melanocytic Proliferation
From the Department of Ophthalmology and Vision Sciences (EVN, ERS, HK, DSH, DW, FA), Princess Margaret Hospital; and the Department of Obstetrics and Gynecology (MB), Mount Sinai Hospital, University of Toronto, Toronto, Canada.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Eduardo V. Navajas, MD, PhD, Princess Margaret Hospital, 610 University Avenue, 18th Floor, M5G 2M9 Toronto, Ontario, Canada. E-mail: email@example.com
Received: February 23, 2011
Accepted: September 29, 2011
Posted Online: October 27, 2011
Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome occurring in patients with systemic carcinoma that was described to have five cardinal signs: (1) multiple, round or oval, subtle orange-red patches at the level of retinal pigment epithelium (RPE) in the posterior fundus; (2) a striking pattern of multifocal areas of early hyperfluorescence corresponding with these patches; (3) development of multiple, slightly elevated, pigmented and nonpigmented uveal melanocytic tumors, as well as evidence of diffuse thickening of the uveal tract; (4) exudative retinal detachment; and (5) rapid progression of cataracts.1 Gass et al.1 suggested that the first two signs are highly suggestive of BDUMP and usually antedate the other three. Recently, two cases have been published describing a variant of BDUMP where the most prominent feature was RPE loss. They were named cancer-associated nummular loss of the RPE and had all of the features of BDUMP except for the presence of multiple uveal melanocytic lesions and cataracts.2,3 We describe a case that expands the clinical spectrum of BDUMP.
A 63-year-old woman presented with a 6-week history of bilateral gradual decrease in vision. Her medical history revealed clear cell uterine adenocarcinoma treated with hysterectomy 7 months prior. She had no history of metastasis but was treated with four cycles of taxol and carboplatin because of the aggressive histological type of her tumor. Best-corrected visual acuity was 20/150 in both eyes. Anterior segments were unremarkable. Funduscopy revealed multiple confluent oval hypopigmented patches at the level of the RPE and few pigmented choroidal lesions in both eyes (Figs. 1A and 1B). Fluorescein angiography (FA) revealed areas of transmission hyperfluorescence (Fig. 2). On optical coherence tomography, there was a shallow serous retinal detachment in the macula bilaterally. There were also areas of RPE loss, corresponding with the areas of transmitted hyperfluorescence on FA, interspersed with zones of thickened RPE (Fig. 3). B-scan revealed the presence of subretinal fluid in the inferior peripheral retina. Full-field electroretinography revealed bilateral decrease of a- and b-wave amplitudes under photopic and scotopic conditions.
Figure 1. (A and B) Color fundus photographs at presentation: multiple confluent oval patches of retinal pigment epithelium (RPE) loss. (B) Small choroidal pigmented lesion inferonasal to the optic nerve. This lesion showed progressive enlargement (see Fig. 4, right). (C and D) Color fundus photographs at 8 months showing progressive enlargement of areas of RPE loss.
Figure 2. (A and B) Fluorescein angiography early and late frames of the left eye at presentation showing transmitted hyperfluorescence corresponding to areas of retinal pigment epithelium loss.
Figure 3. (A) Macular spectral domain optical coherence tomography (SD-OCT) of the left eye at presentation showing subretinal fluid (SRF) and minimal retinal pigment epithelium (RPE) damage. (B) Left eye macular SD-OCT 4 months later showing RPE loss interspersed with areas of RPE thickening, SRF, and massive photoreceptor degeneration. The line of hyperreflectivity in areas of “loose” or absent RPE corresponds to Bruch’s membrane (arrow). (C) Macular SD-OCT of the left eye 8 months after presentation showing further RPE loss. Note the line of hyperreflectivity corresponding to Bruch’s membrane (arrow).
A diagnosis of cancer-associated nummular loss of the pigment epithelium was made. The patient was treated systemically with five sessions of plasmapheresis and intravenous immunoglobulin, and locally with bilateral sub-Tenon’s triamcinolone acetonide injection (40 mg) and an intravitreal triamcinolone acetonide injection (4 mg) in the left eye. Despite treatment, 8 months after presentation she had worsening vision to light perception in both eyes, progression of RPE loss (Figs. 1C and 1D), enlargement of one pigmented choroidal lesion (Fig. 4), and persistent retinal detachments. Twelve months after presentation, she developed total cataracts, iris pigmented lesions, and iris neovascularization in both eyes (Fig. 5). Retroperitoneal lymph node metastases were confirmed 6 months after the ocular presentation.
Figure 4. Color fundus photograph showing pigmented choroidal lesion (A). After 8 months follow-up (B), note the increase in size of the lesion located inferonasal to the disc.
Figure 5. (A and B) Anterior segment photographs at presentation with no evident abnormalities. (C and D) Anterior segment photographs 4 months after presentation showing discrete iris pigmented lesions (arrows). (E and F) Anterior segment photographs 12 months after presentation showing total cataracts, multiple iris pigmented lesions, and iris neovascularization.
At presentation, the hypopigmented patches seen in our patient resembled paraneoplastic vitelliform retinopathy described in patients with metastatic melanoma of the skin and choroid. In this condition, the accumulation of a yellow material in the RPE and sub-retinal space causes blocked fluorescence on FA and a high reflectivity thickening of the RPE and outer retina.4–6 In our case, the presence of transmitted hyperfluorescence and loss of RPE on optical coherence tomography in the areas of patch hypopigmentation was consistent with a diagnosis of cancer-associated nummular RPE loss rather than paraneoplastic vitelliform retinopathy.
Cancer-associated nummular RPE loss was first described in 2005 in a patient with uterine cancer.2 The second case was reported in 2007 in a patient with hepatocellular carcinoma.3 It has been considered a variant of BDUMP in which the RPE involvement is the most prominent feature.2,3 In BDUMP, the patches of RPE atrophy have a diffuse redness that is barely discernible biomicroscopically from the normal reddish orange of the surrounding RPE and is probably related to the hypopigmented diffuse melanocytic in-filtration that hides from view details of the underlying large choroidal vessels and sclera.1 In cancer-associated nummular RPE loss, the higher contrast between the patches of RPE atrophy and the surrounding RPE may be explained by less melanocytic infiltration.
Histopathologic studies have demonstrated that BDUMP has a limited outer-choroidal melanocytic infiltration with frequent sparing of the choriocapillaris that cannot explain the extensive RPE damage seen in this condition.1 Therefore, a toxic or immune reaction secondary to a byproduct of the carcinoma-uveal melanocytic interaction or to a hormonal interaction between the carcinoma and RPE has been implicated in the pathogenesis of RPE damage.1 Considering the possibility of an immunologic mechanism, steroids were locally injected in our patient and, similar to reported BDUMP cases, showed a poor therapeutic response.7 To remove any circulating factor released by the uterine carcinoma, our case was treated with plasmapheresis and intravenous immunoglobulin, but also with a poor response. One possible explanation is that an endogenous factor released by the primary tumor caused widespread RPE damage early in the disease course.
Gass et al.1 suggested that the subtle red patches and their marked tendency to fluoresce are characteristic of BDUMP. They also suggested that after the appearance of multifocal pigmented choroidal tumors in addition to the RPE changes, the diagnosis of BDUMP becomes certain.1 Unlike the two previously reported cases of cancer-associated nummular RPE loss, our patient had pigmented choroidal and iris lesions that showed growth over time. In addition, our patient had rapidly progressing cataracts, which is one of the cardinal signs of BDUMP.1 This supports the idea that cancer-associated nummular RPE loss represents a variant of BDUMP, and expands the clinical spectrum of this unique paraneoplastic syndrome.
- Gass JD, Gieser RG, Wilkinson CP, Beahm DE, Pautler SE. Bilateral diffuse uveal melanocytic proliferation in patients with occult carcinoma. Arch Ophthalmol. 1990;108:527–533.
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- O’Neal KD, Butnor KJ, Perkinson KR, Proia AD. Bilateral diffuse uveal melanocytic proliferation associated with pancreatic carcinoma: a case report and literature review of this paraneoplastic syndrome. Surv Ophthalmol. 2003;48:613–625. doi:10.1016/j.survophthal.2003.08.005 [CrossRef]