Characterisation of ocular melanoma with cutaneous melanoma antibodies.

It can be difficult to distinguish between various forms of pale intraocular tumour, and in particular between an amelanotic malignant melanoma, a choroidal haemangioma, and a solitary metastasis. If a monoclonal antibody specific for melanoma could be identified, it might be radiolabelled to provide a scanning technique which could distinguish between an ocular melanoma and a similar lesion. This pilot, in vitro study was undertaken to determine if monoclonal antibody against cutaneous melanoma recognises any antigenic similarity in ocular melanomas. Three cutaneous melanoma MoAbs 225.28S, 376.96S, and 763-24T and a non-specific MoAb HMFG2 were studied. Cell impressions were obtained from fresh ocular malignant melanomas. Standard staining techniques with immunofluorescence were used. MoAb 225.28S, 376.96S, and 763.24T were positive in melanomas with a dominant epithelioid cell type and in those with a dominant spindle cell type. It is concluded that MoAb 225.28S, 376.96S, and 763.24T may be suitable for imaging ocular melanomas after labelling with 123I, 111In, or 99mTc.     

Human uveal melanoma expresses NG2 immunoreactivity

BACKGROUND/AIMS: NG2 is the rat homologue of the human melanoma proteoglycan (HMP), also known as the high molecular weight melanoma associated antigen. Most cutaneous melanomas, as well as glioblastomas, chondrosarcomas, and some leukaemias express NG2 immunoreactivity, recognised using monoclonal antibody (mAb) 9.2.27. This antibody has also been used for molecular targeting in targeted alpha therapy for melanoma. The purpose of this study was to evaluate the expression of NG2 immunoreactivity in human uveal melanoma and normal ocular tissue using mAb 9.2.27. METHODS: Enucleated eyes from 26 patients with choroidal or ciliary body melanoma (n=26) were available as paraffin sections, and stained with haematoxylin and eosin to assess for tumour cell type and histopathology. Additional slides were investigated for NG2 immunoreactivity using mAb 9.2.27 and alkaline phosphatase anti-alkaline phosphatase (APAAP) immunostaining. Two independent observers graded immunostaining using a semiquantitative scale from 0 (negative) to 3 (strong). RESULTS: Immunostaining for mAb 9.2.27 could not be graded in 7/26 cases with dense pigmentation of the tumour. For the remaining cases, grade 2 (moderate) or more immunostaining was seen in 18/19 tumours (95%). The retina, retinal pigment epithelium (RPE), and choroid displayed weak immunostaining (grade 0.5-1.5) in the majority of melanoma affected eyes. Normal retina and choroid (n=5) appeared negative for mAb 9.2.27. Optic nerve axon bundles in both control and melanoma affected eyes displayed moderate immunostaining. CONCLUSION: In the present study, the majority of human uveal melanomas expressed NG2 immunoreactivity, as detected using mAb 9.2.27. This antibody may be a suitable candidate for radioimmunotherapy to target ocular melanoma.     

HLA-I-Antigenexpression korreliert mit dem histologischen Zelltyp uvealer Melanome

PURPOSE: The prognosis of uveal melanoma is correlated with its histologic cell type. The epithelioid cell type is associated with a higher metastatic rate than the spindle cell type. The Human Leucocyte Antigen Class I (HLA-I) expression of the melanoma also correlates with the prognosis. In this study, we analyzed HLA-I antigen expression of uveal melanomas to determine whether a relationship exist between antigenic expression and melanoma cell type. METHODS: Formalin-fixed, paraffin-embedded spindle cell type (n = 11) and epithelioid cell type (n = 11) uveal melanomas were immunostained with the HC10 antibody (1:80) for HLA-I antigen expression with appropriate positive and negative controls. Sections were assessed semiquantitatively according to the percentage of stained cells. RESULTS: Among the spindle cell type melanomas, 2 out of 11 (18%) stained with HC10 antibodies. The staining intensity was less than 25% of the cells in these two melanomas. Among the epithelioid cell type melanomas, 9 out of 11 (82%) stained with HC10. The staining intensity was more than 25% of the cells in 5 of these 9 melanomas. CONCLUSIONS: It is unknown why spindle and epithelioid cell type uveal melanomas have different prognoses. Human uveal melanoma cell lines with low HLA-I expression are susceptible to NK cell-mediated lysis in vitro and in murine studies. The prognostically more favorable spindle cell type melanoma expresses less HLA-I than the epithelioid cell type melanoma. These results stress the role of NK cells in the rejection of uveal melanoma.     

Correlation of heterogeneity for chromosome 3 copy number with cell type in choroidal melanoma of mixed-cell type

PURPOSE: To study heterogeneity for chromosome 3 copy number in mixed choroidal melanoma with discrete populations of spindle and epithelioid cells using chromosome in situ hybridization (CISH) and to correlate chromosomal loss with cell type. METHODS: Twenty-two archival cases of choroidal melanoma with discrete populations of spindle and epithelioid cells were identified. CISH was used to identify chromosome 3 copy number in spindle and epithelioid areas. RESULTS: Monosomy 3 was detected in 12 (55%) of 22 choroidal melanomas. Of these, 10 (45%) had two copies of chromosome 3 in both epithelioid and spindle cells, 7 (32%) showed monosomy 3 in the epithelioid areas only, and 5 (23%) showed monosomy 3 in both epithelioid and spindle areas. CONCLUSIONS: CISH is a useful technique for analyzing chromosome copy number in different cell populations within a tumor. In mixed choroidal melanomas with discrete spindle and epithelioid cell populations, there may be heterogeneity for chromosome 3 copy number that correlates with areas of different cell type.     

Possibilities and limitations of radioimmunoscintigraphy and conventional diagnostic modalities in choroidal melanoma.

A prospective clinical study to assess the value of immunoscintigraphy with a monoclonal antibody (MoAb) against high molecular weight melanoma associated antigen (225.28S) was performed in 43 patients with choroidal melanoma; in six patients with a lesion suspected of being choroidal melanoma, and in seven patients with a benign lesion simulating a choroidal melanoma. The results of immunoscintigraphy in choroidal melanoma were compared with results of conventional diagnostic modalities like ultrasonography and fluorescein angiography. Planar scintigraphy showed a detection rate of 49% which is comparable with other studies. The detection with scintigraphy was correlated to the size of the choroidal melanoma. The use of single photon computed tomography did not increase the sensitivity of immunoscintigraphy. Ultrasonography yielded a correct diagnosis in 37 of 42 melanomas (88%). With fluorescein angiography a correct diagnosis was obtained in 11 of 30 melanomas (36.6%). The value of immunoscintigraphy with MoAb 225.28S in small choroidal melanomas is limited; its reliability increases in large tumours. Immunohistochemistry with MoAb 225.28S showed antigen expression in 95% of the stained tissue specimens of choroidal melanoma.     

Monoclonal antibodies in detection of choroidal melanoma

Three monoclonal antibodies (MoAbs) prepared against cutaneous melanomas were tested against one group of 12 choroidal melanomas with indirect immunofluorescence in frozen sections. A fourth MoAb was tested in paraffin sections of a second group of 47 choroidal melanomas. One MoAb (NKI-M7) did not react with choroidal melanoma, even though it had a high sensitivity for cutaneous melanoma. A second MoAb (NKI-M6) showed a positive reaction with only 2/12 choroidal melanomas. The third MoAb (NKI/beteb) reacted with all choroidal melanomas, regardless of the cell type. MoAb NKI/C-3 was positive with 38/47 (81%) choroidal melanomas. We conclude that NKI/C-3 and NKI/beteb have a high sensitivity for both cutaneous and choroidal melanomas in frozen sections. Of these two antibodies NKI/beteb was the most specific for cutaneous naevi and melanomas.     

Radioimmunoscintigraphy of ocular melanoma with 99mTc labelled cutaneous melanoma antibody fragments.

The possibility of using radiolabelled monoclonal antibody fragments to image uveal melanomas has been assessed in a pilot study. 99mTc labelled F(ab')2 fragments of MoAb 225.28S raised against cutaneous melanomas were used. Initially 10 patients were imaged. In five patients the clinical findings were typical of uveal melanoma. Immunoscintigraphy was positive in all five cases. In a further five patients there was doubt about the diagnosis. One was though to have a choroidal haemangioma but failed to respond to treatment and immunoscintigraphy was positive, suggesting a diagnosis of melanoma. Two patients were assigned a diagnosis of choroidal haemangioma, one of melanocytoma or possible retinal pigment epithelium carcinoma, and one of metastasis. Immunoscintigraphy was negative in all these four cases. In combination with established diagnostic tests immunoscintigraphy may have a part to play in differentiating uveal melanoma from other similar tumours.     

HLA expression in choroidal melanomas: correlation with clinicopathological features

PURPOSE: In this retrospective study, we analyzed the relevance of human leukocyte antigen (HLA) expression to clinical behavior of uveal melanoma and correlated it with conventional light microscopic parameters. METHODS: HLA class I antigen and Beta 2 microglobulin expression were analyzed in 45 primary choroidal melanoma lesions by immunoperoxidase staining with monoclonal antibodies to HLA class I antigen and beta 2 microglobulin and correlated with the known clinicopathological parameters. Immunoanalysis was done by a semi quantitative method. The tumors were divided into 3 groups. Group A: Tumors with no extrascleral extension/no liver metastases, group B: tumors with only extrascleral extension and group C: tumors with liver metastases. For statistical analysis we analyzed the negative, weak (heterogeneous) and the positive expression of HLA and beta 2 microglobulin with known clinicopathological parameters. RESULTS: In-group A (n = 35) tumors with no extrascleral extension and no liver metastases HLA class I antigen and beta 2 microglobulin are negative (absent staining) in 30 choroidal melanomas. In-group B (n = 4) they are weak (heterogeneous) in 3 tumors. In-group C (n = 6) all the 6 tumors have a positive (bright staining) immunoexpression. No statistical significance was obtained when HLA and beta 2 microglobulin immunoreactivity was compared against largest tumor diameter (LTD), tumor infiltrating lymphocytes (TIL), mitosis and nuclear grade. The difference of HLA class I and beta 2-microglobulin imunoreactivity among the various cell types spindle, mixed and epithelioid was statistically significant (p = 0.003), (p = 0.004). The difference in immunoreactivity between tumors with no liver metastases and tumors with liver metastases was statistically significant (p < 0.001). CONCLUSIONS: HLA class I antigen and beta 2 microglobulin are negative in melanomas with no extrascleral extension and liver metastases and weak in melanomas with extrascleral extension and are positive in melanomas with liver metastases. HLA expression is independent of the conventional markers in uveal melanoma.     

Distribution of melanoma-associated antigens (HMB 45 and S 100) in benign and malignant melanocytic tumors of the conjunctiva]

The reactivity of the monoclonal antibody HMB 45 was evaluated in melanocytic tumors of the conjunctiva. Among these are 10 acquired melanoses, 19 nevi and 34 melanomas. Results were compared with the presence of the S 100 antigen. Especially the intraepithelial and junctional components of primarily benign lesions were stained with HMB 45. Within malignant melanoma this antibody reacts with melanocytes in the epithelial, junctional and subepithelial areas. The polyclonal antibody S 100 stains all melanocytes in pigmented lesions of the conjunctiva. Intraepithelial or subepithelial malignant infiltrating tumor cells show very intense staining with HMB 45. HMB 45 has therefore high specificity for stimulated melanocytes, but it does not distinguish benign and malignant proliferating melanocytic cells.     

Immunoimaging of choroidal melanoma: assessment of its diagnostic accuracy and limitations in 101 cases.

Immunoscintigraphy (IS) was performed on 101 patients with space occupying intraocular lesions including choroidal melanomas (85), choroidal naevi (11), non-melanoma metastases (three), and other melanoma simulating lesions (two). Scintigraphic images with conventional and emission computer tomography techniques were obtained after the intravenous injection of 99mTc-labelled F(ab')2 fragments of monoclonal antibody (MoAb) 225.28S directed against the high molecular weight-melanoma associated antigen (HMW-MAA). Immunohistochemistry was performed on sections of four out of 10 melanoma-containing eyes to confirm MoAb binding. IS demonstrated positive scans in 66 out of 85 choroidal melanomas, offering a sensitivity of 78%. Sensitivity was dependent on the lesion size. True negative results were obtained in 15 out of 16 non-melanoma lesions (specificity 94%). False positive antibody accumulation was found in one patient with a post-traumatic subretinal haemorrhage. Immunohistochemistry demonstrated positive MoAb 225.28S binding in all melanoma sections. In summary IS offered substantial sensitivity and specificity in the differentiation of intraocular lesions, particularly choroidal melanomas, naevi, and metastases. In combination with other diagnostic procedures such as ultrasound echography and fluorescein angiography IS proved to be a valuable method in the diagnosis of choroidal melanoma.     

Radioimmunoscintigraphy and immunohistochemistry with melanoma-associated monoclonal antibodies in choroidal melanoma: a comparison of the clinical and immunohistochemical results.

Radioimmunoscintigraphy with monoclonal antibodies (MoAbs) to melanoma associated antigens is a new technique that can be used as an additional test to detect ocular melanomas in clinically difficult cases. Immunoscintigraphy with 99mtechnetium-labelled monoclonal antibody fragments of MoAb 225.28S in 14 patients with melanoma yielded a positive image in only six cases (43%). The expression of high molecular weight melanoma-associated antigen (HMW-MAA) was immunohistochemically assessed in melanoma tissue obtained from these 14 patients to find a possible correlation between the results of immunoscintigraphy and expression of the HMW-MAA. The melanoma tissues were immunohistochemically stained by a sensitive immunoperoxidase procedure with three different monoclonal antibodies to the HMW-MAA: 225.28S, Mel-14, and AMF-6. Expression of the antigen detected by MoAb 225.28S was found in 13 of 14 melanomas; the MoAbMel-14 reacted positively with all 14 melanomas; staining with MoAb AMF-6 was achieved in 10 melanomas. No correlation was found between the immunohistochemical staining results, the conventional histopathological findings, and the immunoscintigraphic results. The immunohistochemical staining results suggest that anti-HMW-MAA MoAbs bind to the melanoma tissue and are therefore potentially suitable for immunoscintigraphy.     

Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study

AIM: To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy. METHODS: Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 microm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods. RESULTS: The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups. CONCLUSIONS: The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need for treating regrowing posterior uveal melanoma either by enucleation or re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal melanomas there are viable cells with potential for proliferation, although fewer in number, with unknown capacity for metastatic spread. Therefore, the irradiated tumours should be followed for many years, probably for life.     

Iris mammillations as the only sign of ocular melanocytosis in a child with choroidal melanoma

An 8-year-old girl had visual loss in her left eye over 2 months. Ocular examination showed that visual acuity was counting fingers in the left eye. The left iris was moderately pigmented and thickened with numerous confluent, dome-shaped elevations on its surface, consistent with iris mammillations arising from ocular melanocytosis. There was total retinal detachment and an inferiorly located large amelanotic choroidal mass compressing the optic nerve. A specimen from a fine-needle aspiration biopsy showed spindle and epithelioid melanoma cells. The eye was enucleated. Pathologic examination showed that the bland melanocytes comprising the anterior border layer of iris formed focal aggregates, corresponding to the iris mammillations observed clinically. The uvea was diffusely thickened. Arising from the posterior choroid and obscuring the optic nerve head was a moderately pigmented spindle and epithelioid cell choroidal melanoma with diffuse lymphocytic infiltration and high mitotic activity. This case demonstrates that iris mammillations can be the initial manifestation of ocular melanocytosis in the absence of scleral pigmentation.     

Radioimmunoscintigraphy with melanoma-associated monoclonal antibody fragments in choroidal melanoma

A prospective pilot study on radioimmunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was carried out in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma-associated antigen were labeled with 740 mBq^99mTc and injected IV; images were made with a gamma camera at 6 h after injection. With a double-pinhole collimator, radioactivity was counted thrice in both eyes at 6 h after injection. In 6 of 16 patients (37.5%), the melanoma could be imaged with the gamma camera. With the double-pinhole collimator, a significantly higher activity was measured in the melanomatous eye in 13 of 16 patients (82.4%). In two patients a false negative result was obtained, and in one patient the difference between the left and right eye was not significant. Considering these results, radioimmunoscintigraphy may be valuable in ocular melanoma diagnostics, but the specificity of MoAb 225.28S needs to be assessed.     

脉络膜恶性黑色素瘤中Ki—67的表达和肿瘤主要组织病理特性的关系

目的利用抗Ki-67单克隆抗体对石蜡包埋的葡萄膜黑色素瘤组织作免疫组化染色,研究细胞增殖活性和肿瘤重要的组织病理特性之间的关系.方法对1988～1997年问57例葡萄膜黑色素瘤眼球摘除眼作组织病理检查和Ki-67免疫组化染色.所有患眼在接受眼球摘除术前均没有接受过其他治疗.结果Ki-67指数分布范围为0～4.89,平均(0.75±1.02).含有上皮样细胞肿瘤的Ki-67指数高于梭形细胞肿瘤,差异具显著性(P=0.037).大肿瘤组的Ki-67指数比中等大肿瘤组高,两者比较差异有高度显著性(P=0.007).肿瘤大小和细胞类型问存在内在的相关性(X2=4.528,P＜0.05),大肿瘤多为上皮样细胞肿瘤而中等大肿瘤则多为恶性度较低的梭形细胞肿瘤.未发现Ki-67表达与肿瘤位置;肿瘤巩膜外蔓延及年龄有关.结论Ki-67表达与肿瘤的组织细胞类型及大小有关.眼科学报2001;17114～117.     

Characterization of uveal melanoma cell lines that grow as xenografts in rabbit eyes

Two cell lines, OCM-1 and OCM-2, were established from biopsied specimens of choroidal melanomas of spindle B and mixed cell type morphologies. Both cell lines were phenotypically malignant. Karyotypic analyses revealed human chromosomes with a modal number of 95 and 85, respectively. These cell lines have been passaged for over 2 years and are essentially immortal. The cells grew without contact inhibition as monolayers in liquid culture or as clones in soft agar. Electron microscopy revealed melanoma cells containing premelanosomes and cultures free from contamination by fibroblasts. To categorize the morphologies of these cultured cells better by the Callender classification, they were grown as xenografts in the anterior chambers of rabbits immunosuppressed with daily i.m. doses of Cyclosporin A (10 mg/kg). Tumor plaques were detected after 10 days. The eyes were enucleated and fixed in formalin and stained with hematoxylin and eosin for histopathological evaluation. The xenograft from OCM-1 was found to consist predominantly of spindle B-type melanoma cells. In contrast, the xenograft from OCM-2 contained epithelioid, spindle B and clear cell ("balloon") melanoma cells. The ability of these cell lines to grow as xenografts confirmed their neoplastic origin. In fact, the types of the uveal melanoma cells in the xenografts resembled those in the original biopsied tumors. This suggests that the morphology of human uveal melanoma cells is an inherited trait and may be genetically fairly stable.     

Cyclooxygenase-2 expression in uveal melanoma: novel classification of mixed-cell-type tumours

BACKGROUND: The expression of cyclooxygenase-2 (COX-2), an inducible prostaglandin (PG) synthase, has been investigated in various human malignant diseases, such as cutaneous melanoma. We investigated the expression of COX-2 in uveal melanoma and related the findings to prognostic factors. METHODS: In 40 cases of uveal melanoma, immunostaining for COX-2 was done. COX-2 expression was related to histopathological prognostic markers, such as cell type, the presence of lymphocytic infiltration and vascular closed loops in the tumour, and cytomorphometry results. RESULTS: COX-2 expression was found in 58% of the cases, and it correlated with markers of poor prognosis, such as epithelioid cell type and the presence of lymphocytic infiltration and vascular closed loops. The uveal melanomas expressing COX-2 had larger nuclei, as determined by cytomorphometry. INTERPRETATION: Whereas epithelioid tumours carry a worse prognosis than spindle cell tumours, until now it has not been possible to give a strong indication of prognosis in mixed-cell tumours. This study showed that mixed-cell tumours, representing the majority of uveal melanomas, may be further subclassified according to COX-2 expression, which serves as a marker of poor prognosis. The role of COX-2 in uveal melanoma should be further elucidated, and the use of COX-2 inhibitors warrants investigation as adjuvant treatment for this life-threatening malignant disease.     

Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases

Purpose: This study aimed to investigate the relationship between hepatic metastasis and the mean diameter of the 10 largest nucleoli (MLN) in uveal melanoma. Methods: A cross‐sectional histopathological analysis of 37 metastases (13 surgical or needle biopsies, 24 autopsies) and corresponding primary choroidal and ciliary body melanomas was conducted, using statistical tests appropriate for paired data. The largest nucleoli were measured from digital photographs of silver‐stained sections along a 5‐mm‐wide linear field. Confounders considered were presence of epithelioid cells and microvascular density (MVD), counted as the number of discrete elements labelled by monoclonal antibody QBEND/10 to the CD34 epitope. Results: Hepatic metastases had more frequent epithelioid cells (p = 0.0047) and a higher MVD (median difference, 7.5 counts/0.313 mm² more; p = 0.044) than their corresponding primary tumours. Hepatic metastases, especially in autopsy specimens rather than surgical biopsies, tended to have a smaller MLN (median 3.6 μm) than the corresponding primary tumour (median difference, 0.55 μm; p = 0.066). The MLN in hepatic metastases was not associated with presence of epithelioid cells and MVD. Overall survival after diagnosis of metastasis was comparable whether hepatic metastases had a large or small MLN (p = 0.95), whereas a high MVD tended to be associated with shorter survival (p = 0.096) among the 13 patients with known survival. Conclusions: The results suggest that MLN is not a useful marker for assessing prognosis after diagnosis of hepatic metastasis from uveal melanoma.     

Ocular melanoma: epidemiology, clinical presentation and relationship with dysplastic nevi

PURPOSE: Ocular melanoma is a rare entity compared to cutaneous malignant melanoma. We examined the frequency of the tumor in a defined geographic region, its clinical presentation and its relationship with dysplastic nevi in 136 patients. METHODS: 136 patients (64 men and 72 women; mean age 61.7 years, range 20-92 years) with ocular melanoma were treated at the University Hospital of Graz between June 1996 and December 2001. 129 had primary uveal melanoma in one eye (117 choroidal melanomas, 11 melanomas of the ciliary body and 1 of the iris), 2 patients had uveal melanoma in both eyes, 4 patients had conjunctival melanoma and 1 patient had a melanoma of the lacrimal sac. Epidemiology, history, potential risk factors, clinical presentation and relationship with dysplastic (= atypical) nevi were documented. RESULTS: 48 patients (35.3%) showed more than five dysplastic nevi, compared to only 1.2% in the general population (chi(2) test: p < 0.001). 5 (3.7%) had additional cutaneous melanoma and 7 (5.1%) had a family history of melanoma. The lifelong risk for the occurrence of an additional primary cutaneous melanoma was 2.9%, which is significantly higher than the usual estimate of 1% for the general population. CONCLUSIONS: Patients with primary ocular melanoma have an increased risk to develop cutaneous melanoma and should therefore be examined regularly by dermatologists.