Abstract
Purpose :
Choroidal nevi are relatively common lesions seen in mostly asymptomatic eyes, with low potential for progression to melanoma. However, choroidal melanoma often develop from a nevus, and most nevi already carry mutations in GNAQ or GNA11 (Vader 2017). To investigate whether the immunological profile of choroidal nevi resembles that of melanoma we analysed the histopathological and immunological characteristics of 16 nevi observed incidentally in post mortem eyes.
Methods :
Post-mortem adult human eyes (Lions NSW Eye Bank, n=13, 54 to 90 years), with no history of choroidal melanoma, were observed to have pigmented lesions (n=16 lesions) when examined using transillumination. Paraffin sections were subsequently cut, stained with hematoxylin & eosin (H&E) or Periodic acid Schiff (PAS) reagent and their histopathology examined. We used immunohistochemistry to assess the localisation and distribution of macrophages (CD68 or CD163 antibodies) and lymphocytes (CD3, CD4 and CD8 antibodies), and to confirm melanocytic origin (MelanA antibody).
Results :
Most lesions (15/16) were within the posterior pole. H&E and PAS stained sections showed pigmented nevi (diameter up to 7mm, thickness <1.5mm), predominantly oval or dome-shaped, comprised of either spindle cells (n=8) or mixed cells (n=8). Nevi located just beneath Bruch’s membrane were more often associated with choriocapillaris (CC) thinning and RPE disruption. Overlying drusen were observed for 8/16 nevi. Large choroidal vessels bordered 11/16 nevi, with normal vessels seen in all nevi. Immunohistochemistry showed a variable number of inflammatory cells within nevi, with macrophages outnumbering lymphocytes. Compared to the surrounding choroid, CD163+ and CD68+ macrophages (CD163+>CD68+) were seen localised within and around nevi, often associated with vessels. For nevi, a significant correlation was found between density of CD3+ cells and presence of CC thinning (P=0.009), and between the densities of CD3+ and CD8+ cells (P=0.023).
Conclusions :
We confirmed earlier histopathology studies of choroidal nevi, including the presence of drusen, and spindle and mixed cell phenotypes. Choroidal nevi affected the normal choroidal vasculature including CC integrity, consistent with more recent OCT studies. Strikingly, the patterns of infiltrating macrophages and lymphocytes seen in these nevi appeared similar to that observed in choroidal melanoma; the significance of this remains to be discovered.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.