Advanced Uveal Melanoma; Choroidal Melanoma Metastasis; Ciliary Body Melanoma Metastasis; Hepatic Metastases of Uveal Melanoma; Intraocular Melanoma; Iris Melanoma Metastasis; Metastatic Ocular Melanoma; Metastatic UM; Metastatic Uveal Melanoma; mUM; Ocular Melanoma Metastases; Secondary Eye Cancer; Stage 4 Ocular Melanoma; Stage 4 Uveal Melanoma; Stage IV Ocular Melanoma; Stage IV Uveal Melanoma

Uveal melanoma (UM) is a rare cancer of the pigment producing cells (melanocytes) located in the middle layer of the eye known as the uveal tract or uvea. Uveal melanoma with metastases occurs when there is metastases (spread) to adjacent skin or distant sites such as the liver, lungs, or brain.

The uveal tract has three parts: the iris (colored part of the eye), the ciliary body (the ring of muscle tissue that changes the size of the pupil and the shape of the lens), and the choroid (the vascular layer located behind the retina). The UM tumors that occur in the eye are:

Choroidal melanoma is the most common form of UM. This form is more likely to metastasize if it is diagnosed at a later stage. It can spread to other parts of the body, but it typically spreads to the liver.

Ciliary body melanoma is the second most common type of UM. It occurs when the tumor originates in the ciliary body and often grows for a long time before diagnosis, so tumors are usually larger when found. This type of UM is more likely to spread to other parts of the body, often to the liver.

Iris melanoma originates in the iris. It is the least common type of UM. These tumors are often visible, slow-growing, and usually have a better prognosis than the other types of UM. Iris melanoma rarely spread outside of the eye. There is no staging system for iris melanoma.

Although UM is classified as a melanoma, the disease is distinctly different than other skin (cutaneous) melanomas. The mutations found in UM cells are different from those found in other melanoma subtypes. It is characterized by different genetic mutations, the location of mutated cell origin, no connection to sun exposure, and the high likelihood of metastases to the liver through the bloodstream instead of the lymphatic system.

The exact cause of UM is unknown. It is believed to be caused by mutations in the BAP1, EIF1AX, GNA11, GNAQ, and SRSF2/SF3B1 genes.

Diagnostic testing: The diagnosis of metastatic UM is made by:

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  Abdominal/chest computed tomography (CT);

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  Blood tests;

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  Eye examination;

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  Fine needle aspiration biopsy

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  Fluorescein angiography

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  Fundus photography;

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  Laparoscopy;

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  Liver function tests;

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  Magnetic resonance imaging (MRI) with contrast;

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  Ocular ultrasound;

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  Ophthalmoscopy;

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  Optical coherence tomography (OCT); and

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  Ultrasound of affected organ(s).

Physical findings: The symptoms of metastatic UM depend on the location of the tumor and how long it has been there. Individuals with metastatic UM may experience:

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  Bone pain or tenderness;

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  Chest pain;

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  Cough;

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  Enlarged liver;

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  Fatigue;

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  Fractures;

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  Jaundice;

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  Loss of appetite;

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  Lumps or spots under the skin;

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  Nausea;

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  Persistent cough;

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  Shortness of breath;

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  Sweats and fever;

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  Unintended weight loss;

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  Upper right abdominal pain; and

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  Weight loss.

ICD-9: 190.0 ; 190.6; 190.9

ICD-10: C69.3; C69.4; C69.40; C69.90

Over half of individuals with a diagnosis of UM will develop metastatic UM. It is aggressive and spreads quickly, typically to the liver, however it can also spread to the bones, lungs, lymph nodes, kidneys, skin, and soft tissue. This spread can happen years after the initial diagnosis, sometimes decades later. The metastatic tumor is the same type of cancer as the primary tumor from the first diagnosis. For example, if UM spreads to the liver, the cancer cells in the liver are actually UM cells. The disease is metastatic UM, not liver cancer.

Metastatic UM can occur at any age, but it is most often diagnosed in adults between 50 and 70 years old. Risk factors include light-colored eyes, fair skin, dysplastic nevus syndrome (numerous, abnormal looking moles), atypical or common cutaneous nevi (moles), and family history.

The prognosis is extremely poor, with overall survival ranging from three to 12 months after diagnosis of metastases.

The treatment of UM depends on the size and location of metastatic tumors. Treatment focuses on managing symptoms and improving quality of life. In most cases treatment will be used to prolong life but will not likely result in cure.

Treatment depends on the size and location of the metastases and may consist of both systematic and local therapy. These may include:

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  Biological response modifier (BRM) therapy;

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  Chemotherapy;

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  Clinical trials;

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  Embolization;

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  Enucleation;

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  Hepzato Kit;

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  Hormonal therapy;

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  Immunotherapy;

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  Liver-directed therapy;

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  Radiation therapy;

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  Radiofrequency ablation (RFA);

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  Surgical resection of the tumor(s);

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  Targeted therapy; and

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  Tebentafusp-tebn.

Suggested MER for Evaluation:

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  Clinical history and examination that describes the diagnostic features of the impairment;

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  Biopsy results; and

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  Results of imaging studies (i.e., MRI, CT scan, ultrasound) showing evidence of metastases.

Suggested Listings for Evaluation:

13.29B3

Malignant melanoma with metastases