Patients presenting with metastases: stage IV uveal melanoma, an international study

Abstract

ObjectiveTo analyse ocular and systemic findings of patients presenting with systemic metastasis.Methods and analysisIt is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases.ResultsOf 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1–T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category.ConclusionsThough higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

“…The most common presenting complications encountered in patients with UM are exudative retinal detachment, glaucoma, cataracts, intraocular hemorrhage, vision loss, changes in the cornea including edema and band keratopathy [ 21 , 22 , 23 ]. Less than 2% of UM patients have long-distance metastases already at presentation ( Figure 1 ) [ 24 ].…”

“…The liver (≈85%) is the preferred site for metastases development in UM, sometimes constituting the initial presentation of the disease [ 41 , 52 ] ( Table 1 ). Other locations of UM metastasis include the lung (≈29%) and bone (≈16%), among others [ 24 , 41 ] ( Table 1 ). In nearly one-third of the metastatic cases, there is involvement of multiple sites by UM metastases [ 24 , 41 ].…”

“…Other locations of UM metastasis include the lung (≈29%) and bone (≈16%), among others [ 24 , 41 ] ( Table 1 ). In nearly one-third of the metastatic cases, there is involvement of multiple sites by UM metastases [ 24 , 41 ]. Despite the advances in the understanding of UM biology and the advent of new therapeutic modalities, the 5-year survival rate for UM (≈80%) has remained stable over the past five decades [ 46 , 47 , 48 ].…”

“…The leading cause of death in patients with UM is metastization, which preferentially occurs to the liver ( Table 1 ) [ 24 ]. Our knowledge on the mechanisms underlying the exquisitely preference of UM cells for the liver microenvironment is still scarce [ 9 ].…”

Expression of Vascular Endothelial Growth Factor in Uveal Melanoma

“…Морфологическую верификацию УМ проводили согласно международным стандартам диагностики опухолей человека, использовали классификацию ВОЗ, 4-е издание, 2018 г., в сложных случаях подтверждали иммуногистохимическими (ИГХ) маркерами меланоцитарного ряда [16,17].…”