REVIEW URRENT C OPINION

Choroidal melanoma: clinical features, classification, and top 10 pseudomelanomas Carol L. Shields, Janet Manalac, Chandana Das, Kyle Ferguson, and Jerry A. Shields

Purpose of review To review the current features and classification of choroidal melanoma, and to identify the lesions that clinically simulate choroidal melanoma (pseudomelanoma). Recent findings Uveal melanoma is a serious life-threatening intraocular malignancy, most often found in Caucasians (98%) and primarily involving the choroid (90%), ciliary body (7%), or iris (2%). This review will concentrate on choroidal melanoma. At diagnosis, choroidal melanoma usually appears as a pigmented (85%) tumor underlying the retina with a median basal dimension of 11 mm and a mean thickness of 4.5 mm. The American Joint Committee on Cancer classification allows for categorization and staging of melanoma. Following ocular therapy, adjuvant systemic therapy is provided for patients with high-risk melanoma who demonstrate alterations in chromosomes 3, 6, and 8 or those with class 2 on gene-expression profiling, detected by needle biopsy or solid tumor biopsy. The prognosis of choroidal melanoma depends most importantly on the genetic alterations and tumor size. Every millimeter increase in thickness leads to a 5% increased risk for metastasis. The leading conditions that simulate choroidal melanoma include choroidal nevus, peripheral exudative hemorrhagic chorioretinopathy, congenital hypertrophy of the retinal pigment epithelium (RPE), hemorrhagic RPE detachment, choroidal hemangioma, age-related macular degeneration, RPE hyperplasia, and others. These pseudomelanomas can be differentiated from choroidal melanoma by their unique clinical features. Summary Choroidal melanoma is a serious malignancy with characteristic features. Early detection and therapy is important. Pseudomelanomas can lead to diagnostic confusion; however, clinical features aid in differentiation. Keywords choroids, eye, melanoma, pseudomelanoma, tumor, uvea

INTRODUCTION Melanoma is a dangerous malignancy that can involve the skin, the uvea, and other sites [1]. In North America, it is estimated that approximately 2500 persons develop uveal melanoma annually [2]. Worldwide, it is estimated that there are 7095 new cases of uveal melanoma annually, with 4747 in White non-Hispanic, 738 in Hispanic, 1286 in Asian, and 316 in African patients [2]. The incidence of uveal melanoma has been relatively stable over the last decades. The mean age-adjusted incidence of uveal melanoma is 4.3 per million [3]. This figure has remained relatively stable over the last 5 decades. In an analysis of 2493 cases of uveal melanoma from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database,

uveal melanoma at all ages was more common in men at 4.9 per million compared with women at 3.7 per million [3]. The mean age at presentation was 60 years and there was a range of 6–100 years. The agespecific incidence per million population (male/ female) differs depending on the age and includes 0–4 years (0/0), 10–14 years (0.2/0), 20–24 years (0.4/0.6), 30–34 years (1.7/1.7), 40–44 years (3.9/ 2.4), 50–54 years (10.5/6.5), 60–64 years (14.9/ Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA Correspondence to Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107, USA. Email: [email protected]. Curr Opin Ophthalmol 2014, 25:177–185 DOI:10.1097/ICU.0000000000000041

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Retinal, vitreous and macular disorders

KEY POINTS  Melanoma should be detected at the earliest point using the mnemonic ‘To Find Small Ocular Melanoma – Using Helpful Hints Daily’.  The AJCC classification of melanoma can predict the patients’ prognosis.  Patients with ocular melanocytosis and melanoma have double the risk for metastases.  Patients with diffuse choroidal melanoma have particularly a poor prognosis.  Melanoma should be differentiated from the pseudomelanomas.

11.7), 70–74 years (24.5/17.8), and 80–84 years (23.2/16.1). In an analysis of 8033 patients with uveal melanoma from a single tertiary referral center over a 4-decade period, Shields et al. [4 ] reported melanoma primarily involving the choroid (90%), ciliary body (6%), or iris (4%). The tumor affected men (51%) or women (49%), and primarily occurred in Caucasians (98%) compared with African American (10.0

808

23%

35%

58%

7354

8%

13%

25%

Total

Adapted with permission [12]. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.

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Retinal, vitreous and macular disorders

overview of metastasis of uveal melanoma by millimeter size in 8033 patients and found that each millimeter increase in thickness caused 5% increased rate of metastasis (Table 4). Thus, the rate of metastasis for choroidal melanomas measuring 4 or 8 mm in thickness would be estimated at 20 or 40%, respectively. Clinical factors predictive of metastasis by multivariate analysis included increasing patient age, ciliary body location, increasing tumor diameter, increasing tumor thickness, pigmented melanoma, and the presence of subretinal fluid, intraocular hemorrhage, or EOE [12]. Diffuse melanoma has a clinically distinct, relatively flat melanoma growth pattern, with tumor thickness of 3 mm or less and thickness to base ratio less than 20% [13 ]. This tumor is often mistaken for benign choroidal nevus. In an analysis of 8033 patients with uveal melanoma, diffuse melanoma represented 3% of all cases and imparted a 3.84 relative risk for metastasis compared with nondiffuse melanoma [13 ]. Recent analysis of 1751 cases of diffuse choroidal melanoma disclosed melanoma-related metastasis (diffuse vs. nondiffuse) was 17 vs. 10% at 10 years [13 ]. Even in the &&

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thinnest tumors of 2 mm or less, diffuse configuration has worse prognosis with melanoma-related death (diffuse vs. nondiffuse) of 10 vs. 2% at 10 years. Ocular melanocytosis imparts an increased risk for melanoma and leads to higher risk for metastatic disease. In an assessment of 7872 patients with uveal melanoma, metastasis was 2.6 times higher with choroidal melanocytosis (P ¼ 0.021) and 1.9 times higher with scleral melanocytosis (P < 0.001) [26 ]. By Kaplan–Meier estimates, metastasis in patients with ocular melanocytosis vs. no melanocytosis was 48 vs. 24% at 10 years [26 ]. It is unclear at what size choroidal melanoma poses a risk for metastasis. On the basis of the clinical studies, small melanoma, at approximately 1 mm in thickness, has occasionally shown metastasis [27]. On the basis of the mathematical studies of tumor doubling time of choroidal melanoma and related metastasis, some authors have estimated that 30 doubling times of a metastatic tumor will occur before a metastasis is clinically detectable, at 1000 mm3 in size [27,28]. These authors theorized that the average volume of a uveal melanoma at the &

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(b)

(c)

(d)

FIGURE 2. Choroid pseudomelanoma. (a) Choroid nevus with overlying drusen. (b) Peripheral exudative hemorrhagic chorioretinopathy with extensive subretinal hemorrhage. (c) Congenital hypertrophy of the retinal pigment epithelium with crisp margin. (d) Retinal pigment epithelial hemorrhagic detachment with partial resolution of blood. 182

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Choroidal melanoma and pseudomelanoma Shields et al. Table 5. Choroidal pseudomelanomas in 1739 cases. Top diagnoses Rank

Diagnosis

Number

%

1

Choroidal nevus

851

49%

2

Peripheral exudative hemorrhagic chorioretinopathy

139

8%

3

Congenital hypertrophy of retinal pigment epithelium (RPE)

108

6%

4

Idiopathic hemorrhagic detachment retina or pigment epithelium

86

5%

5

Circumscribed choroidal hemangioma

79

5%

6

Age-related macular degeneration

76

4%

7

Hyperplasia or RPE

42

2%

8

Optic disc melanocytoma

37

2%

9

Choroidal metastasis

34

2%

10

Hemorrhagic choroidal detachment

29

2%

11

Vasoproliferative tumor

20

1%

12

Rhegmatogenous retinal detachment

18

1%

13

Choroidal detachment

17

1%

14

Uveal effusion syndrome

17

1%

15

Choroidal or disc granuloma

14

1%

16

Adenoma RPE or CPE

13

Choroidal melanoma: clinical features, classification, and top 10 pseudomelanomas.

To review the current features and classification of choroidal melanoma, and to identify the lesions that clinically simulate choroidal melanoma (pseu...
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