Tumor Heterogeneity in Uveal Melanomas

    Research output: Types of ThesisDoctoral Thesis


    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults with an incidence of 7-10/ million and has a predilection for hematogenous dissemination to the liver. Despite improvements in diagnosis and treatment of this intraocular tumor, there has not been a change in survival in the past decades. There is no effective treatment for liver metastases resulting in tumor-related death in about 45% of UM patients within 15 years after the initial diagnosis. Uveal melanoma usually arises ‘de novo’ from melanocytes derived from neural crest cells that have migrated to the epidermis and uveal tract during embryogenesis. Intraocular melanoma may arise in the choroid (70-80%), ciliary body (10-20%) and iris (5-10%). Iris melanomas are the least common and tend to present at a smaller size, probably because pigmented lesions of the iris are usually visible to the patient. Iris melanomas can cause drainage angle blockage and secondary elevation of the intraocular pressure.4 Melanomas located in the ciliary body are associated with a high metastatic potential. Choroidal melanomas compromise the majority and grow subretinal in a discoid, dome-shaped or mushroom-shaped pattern. The diagnosis is based on the clinical appearance of the tumor on ophthalmic examination. Ancillary tests include (Doppler-) ultrasonography, transillumination, fluorescein angiography and optical coherence tomography. For the diagnosis of melanoma, biopsy is reserved for tumors of uncertain origin. Conversely, tumor biopsy gains territory in vision-sparing therapies for cytogenetic analysis providing risk assessment of metastatic disease. Upon diagnosis of the primary tumor, patients are screened for metastases by liver enzyme tests and liver ultrasound. At time of diagnosis less than 2% of the patients have detectable metastases.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • Paridaens, Dion, Supervisor
    Place of PublicationRotterdam
    Publication statusPublished - 2010


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