Emma Kujala

Staging of Ciliary Body and Choroidal Melanomas Based on Anatomic Extent

PURPOSE To refine the anatomic classification and staging of ciliary body and choroidal melanomas in the TNM classification. PATIENTS AND METHODS Tumor largest basal diameter and thickness of 7,369 patients were analyzed based on registry data from five ocular oncology centers. T categories were derived empirically by dividing data into blocks representing 3- × 3-mm fractions. Blocks with similar survival were grouped together so that no T category comprised a large majority of tumors, and each was uniform in survival, using randomly drawn 60% building and 40% validation data sets. Presence of ciliary body involvement (CBI) and extraocular extension (EXE) was analyzed among 5,403 patients to define T subcategories. Stages were generated by iteratively combining subcategories with similar survival. RESULTS Of the 7,369 tumors analyzed, 24% were classified as T1, 33% as T2, 31% as T3, and 12% as T4. Ten-year Kaplan-Meier survival estimates for the T categories were 89%, 77%, 58%, and 39%, respectively (P < .001). Survival of patients in four subcategories based on presence or absence of CBI and EXE differed significantly within each T category (P = .018 for T1; P < .001 for T2 to T4). EXE exceeding 5 mm in largest diameter carried a worse prognosis than smaller extensions (P < .001) and was assigned a separate subcategory. Ten-year Kaplan-Meier survival estimates for stages I, IIA to IIB, and IIIA to IIIC were 88%, 80%, 67%, 45%, 27%, 10%, respectively (P < .001). CONCLUSION This evidence-based anatomic classification provides a basis for staging ciliary body and choroidal melanomas in the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer.

Metastatic uveal melanoma.

Metastatic melanoma (stage IV in Tumor, Node, Metastasis Classification) is believed to be the unresolved problem in managing patients with malignant melanoma of the choroid and ciliary body. More than half of these patients will eventually develop hematogenous metastases, which only exceptionally are curable. Metastasis is the single leading cause of death of patients with uveal melanoma, both short term and long term. Kaplan-Meier estimates of 5and 15-year melanoma-related mortality range from 26% to 32% and from 45% to 50%, respectively (see ). However, this method does not take into account competing causes of death. By 15 years, these competing causes gradually outnumber annual melanoma-related deaths, but metastases still amount to one third of annual deaths long term. Overall, 7 and 2 times as many patients die of uveal melanoma as die of second cancer and nonneoplastic disease, respectively. The first site of metastasis is the liver in approximately 90% of patients, but later spread to the lungs, bone, and skin is frequent. Of patients with newly diagnosed metastases who participate in annual reviews that include liver imaging, 80% have only hepatic metastases, 12% have hepatic and extrahepatic, and 8% have only extrahepatic dissemination. This pattern of dissemination differs from that of cutaneous melanoma, which typically metastasizes to the lymph nodes, lungs, and brain, and it is important to understand that these 2 are distinct diseases. Uveal melanoma rarely metastasizes to the regional lymph nodes, but it can do so if it invades the conjunctiva. This focused review summarizes the latest findings with regard to epidemiology, kinetics, diagnostic screening, staging, and management of metastases from uveal melanoma.

Mortality after uveal and conjunctival melanoma: which tumour is more deadly?

Purpose:  We aimed to model and compare mortality rates for uveal melanoma (UM) and conjunctival melanoma (CM) by adjusting for differences in tumour size and local recurrence.

Macrophages and microcirculation in regressed and partially regressed irradiated choroidal and ciliary body melanomas.

Purpose. To investigate how tumour-infiltrating macrophages and microcirculation attributes of uveal melanomas regressed after brachytherapy and whether primarily enucleated melanomas differ. Methods. A case-control analysis of 34 matched pairs of irradiated and nonirradiated choroidal and ciliary body melanomas with main outcome variables being area of necrosis, extravascular matrix loops and networks, tumour-infiltrating macrophages in nonnecrotic areas identified with mAb PG-M1 to the CD68 epitope, and microvascular density (MVD) determined by mAb QBEND/10 to the CD34 epitope. Results. Comparison of primarily enucleated eyes to eyes with irradiated, secondarily enucleated melanomas revealed significantly more necrosis (median difference, +9%, P = 0.0012) and lower MVD (median difference, -10 counts/0.313mm 2, P = 0.011) in the latter. In eyes managed with brachytherapy, loops and networks tended to be less frequent (P = 0.077). Number and type of macrophages weresimilarly distributed, being moderate to high in about 95% (P = 0.67) of the matched pairs, and intermediate to dendritic in 79% (P = 0.90). In the irradiated eyes, presence of epithelioid cells and the number and type of macrophages showed no association with microcirculation attributes, whereas in the primarily enucleated tumours, high number of macrophages was associated with high MVD (P < 0.001). Conclusions. This study suggests that regression after brachytherapy reduces MVD. The difference cannot be attributed to different numbers of tumour-infiltrating macrophages and different cell type in nonnecrotic areas of the tumour.