A Word of Caution regarding Risk Factors for Malignant Transformation of Choroidal Nevi.

Abstract

Dear Editor, It is with great interest I read the recently published editorial by Singh and Grossniklaus [1] and the research study by Raval et al. [2] regarding the distinction between choroidal nevi and small choroidal melanomas. The authors should be commended for highlighting a central yet often overlooked issue and for investigating the correlation of growth with histopathological findings. The latter is a much-needed effort in a field where patients rarely undergo diagnostic biopsy prior to treatment. Following pioneering work by Dr. Gass some 50 years ago, as well as later additions by others, Dr. Shields and colleagues coined a widely recognized mnemonic to help us remember risk factors for growth of choroidal nevi into melanoma: “To find small ocular melanoma using helpful hints daily,” (TFSOMUHHD) [3–8]. In 2019, an updated version of the mnemonic was offered: “To find small ocular melanoma doing imaging” (TFSOMDI), representing thickness >2 mm (by ultrasound), subretinal fluid (by OCT), symptoms of vision loss, orange pigment (by autofluorescence), melanoma hollow (by ultrasound), and diameter >5 mm (by photography) [9]. Mnemonics are useful tools for remembering risk factors. By reminding us to evaluate each parameter, they may increase diagnostic accuracy and reproducibility and help us avoid delays in the treatment of choroidal melanomas. My respected colleagues should be praised for these contributions. Nevertheless, caution is warranted. In addition to what is highlighted by Singh and Grossniklaus [1], 3 more issues may be mentioned. The first problem is one of the criteria for classification: if risk factors for malignant transformation are similar or identical to the parameters used for diagnosing choroidal melanoma, the two will correlate regardless of the true biology of the lesion. In the 2009 and 2019 publications by Shields et al. [8, 9], malignant transformation was defined as “enlargement in the basal dimension or thickness of at least 0.5 mm” and “enlargement in basal dimension or thickness by at least 0.5 mm (arbitrary) over a short time period,” respectively. In other words, TFSOMUHHD and TFSOMDI have not actually been shown to identify malignancy, but growth by 0.5 mm. Growth is not the only hallmark of cancer, and very small tumors can harbor BAP1 mutations and seed metastases [10–13]. Further, in a 2019 publication, Dr. Harbour and colleagues [14]found that documented growth of choroidal nevi was not associated with malignant transformation. The latter was defined as having the highly metastatic