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Abstract
PurposeFluid-conducting extracellular matrix patterns known as vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma and other cancers. We investigate the correlations between VM, presenting symptoms, mortality, and the area density of periodic acid-Schiff positive histological patterns (PAS density).MethodsSixty-nine patients that underwent enucleation for uveal melanoma between 2000 and 2007 were included. Clinicopathological parameters presenting symptoms and outcomes were collected. Histological tumor sections were evaluated for VM and PAS density was quantified with digital image analysis.ResultsThirty-four patients (49%) presented with blurred vision. 18 (26%) with a shadow in the visual field, 7 (10%) with photopsia and/or floaters, and 2 (3%) with metamorphopsia. Nine patients (13%) had no symptoms at all. Median follow-up was 16.7 years (SD 2.6). A shadow in the visual field, but no other symptom, was positively correlated with the presence of VM (φ 0.70, p < 0.001) and greater PAS density (p < 0.001). In multivariate regression, retinal detachment (RD), presence of VM, and PAS density ≥ median were independent predictors of a shadow, but not tumor distance to the macula, tumor apical thickness, tumor diameter, or ciliary body engagement. The presence of VM was associated with significantly shorter cumulative disease-specific survival (Wilcoxon p = 0.04), but not PAS density ≥ median, presenting symptoms or RD (p > 0.28).ConclusionTumors from uveal melanoma patients that report a visual field shadow are likely to display VM and greater PAS density, likely explaining the previously reported association between this symptom and poor prognosis.
Highlights
Uveal melanoma is the most common malignant intraocular tumor in adults
Two of the strongest prognostic factors for the risk of developing macrometastases are the presence of periodic acid-Schiff (PAS) positive extracellular matrix patterns forming fluid-conducting channels, and the presence of a dense network of microvessels (Folberg et al 1992, 1996; Foss et al 1996; Mäkitie et al 1999; Folberg and Maniotis 2004; Cao et al 2013; Stålhammar et al 2019)
The presence of vasculogenic mimicry (VM) was associated with significantly shorter disease-specific survival (p = 0.04, Fig. 5a), but not PAS density ≥ median (p = 0.65, Fig. 5b)
Summary
Uveal melanoma is the most common malignant intraocular tumor in adults. At the time of diagnosis, about 2% of patients have detectable metastases (Garg et al 2021). Eugeniavägen 12, 17164 Stockholm, Sweden 3 Department of Pathology, Västmanland Hospital Västerås, Västerås, Sweden attributed to early seeding of micrometastases from the eye to distant organs, primarily the liver (Singh 2001; Callejo et al 2007; Uner et al 2021). Once these seeded clusters of dormant tumor cells grow into larger, radiologically detectable, macrometastases, median patient survival is a year or less (Khoja et al 2019; Rantala et al 2019). Two of the strongest prognostic factors for the risk of developing macrometastases are the presence of periodic acid-Schiff (PAS) positive extracellular matrix patterns forming fluid-conducting channels (vasculogenic mimicry, VM), and the presence of a dense network of microvessels (Folberg et al 1992, 1996; Foss et al 1996; Mäkitie et al 1999; Folberg and Maniotis 2004; Cao et al 2013; Stålhammar et al 2019)
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