Metastatic Ocular Melanoma to the Liver Exhibits Infiltrative and Nodular Growth Patterns

Abstract

Purpose : The purpose of this study was to examine the growth patterns and stages of these patterns in persons who succumbed from metastatic uveal melanoma to the liver.

Methods : Fourteen liver specimens from patients who died from hepatic metastasis of uveal melanoma were obtained post-mortem. Representative sections were obtained from these livers and stained with hematoxylin/eosin, Masson trichrome, using IHC for HMB45, CD31, BAP1, and using immunofluorescence for endoglin, CD56, MMP2, MMP9, VEGF and with dual labeling for HMB45/CD133 to evaluate for the presence and pattern of metastatic uveal melanoma.

Results : We found two growth patterns of metastasis: infiltrative (n=11) and nodular (n=3). In the infiltrative pattern, individual melanoma cells with a CD133+ cancer stem cell phenotype were present and formed aggregates of Stage I (<50µm diameter) micrometastases in the sinusoidal space which expanded and destroyed adjacent hepatocytes and formed Stage II (50µm to 500µm diameter) and then Stage III (>500µm diameter) metastases which were encapsulated by collagenized fibrous septae. The stem cell phenotype was lost as the tumors grew. In the nodular growth pattern, melanoma cells aggregated adjacent to portal venules then grew and effaced the adjacent hepatocytes to form 50µm to 500µm diameter nodules. These avascular nodules further expanded to form >500µm diameter nodules that exhibited angiogenesis with minimal fibrosis. The infiltrative growth pattern of melanoma cells appeared to be controlled in part by NK cells within the sinusoidal space. The nodular growth pattern of melanoma cells exhibited MMP2, MMP9 and VEGF at its advancing edge. Melanoma cells in both growth patterns exhibited variable BAP1 expression.

Conclusions : Our results correlate with radiographic counterparts to these growth patterns and different treatment strategies may be needed to control these differing growth patterns.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Cartoon of metastatic uveal melanoma to the liver. These cells spread to the liver, first as individual melanoma cells with cancer stem cell properties, either into the sinusoidal spaces or peri-portal area. Melanoma cells in the sinusoidal spaces then progress to the Stage I, II or III infiiltrative growth pattern which eventually replaces the hepatic lobule. Melanoma cells in the immune-privileged peri-portal area progress to the Stage I, II or III nodular growth pattern.