by Christine J Ko, MD

Dermatopathology is very important to patient care because sometimes a diagnosis is only possible after evaluation of histopathologic findings. Biopsies can give critical information and change treatment and management. As an example, thickness of a malignant melanoma, measured by Breslow depth in tissue sections, remains one of the most important prognostic parameters for patients with malignant melanoma.

Because even thin melanomas sometimes have a poor prognosis, researchers continue to search for biomarkers of malignancy and ultimate prognosis. Dr. Seykora reviewed several recent studies of importance. First, microsatellites, defined as collections of melanoma cells that are discontiguous from the main bulk of the primary tumor, are a predictor of an overall adverse prognosis, with greater distance of the microsatellite from the primary tumor correlating with a negative outcome. Microsatellites are also an important predictor of sentinel lymph node positivity. It is important to correctly categorize microsatellites, by doing serial sections to ensure that a potential microsatellite does not actually connect to the main tumor.

Another biomarker of malignant melanoma, as compared to benign melanocytic nevi, is the ciliation index. Malignant melanoma on acral sites can be difficult to distinguish, using histopathologic criteria alone, from acral melanocytic nevi, particularly in partial samples. The ciliation index is markedly different in these 2 entities, with a very low ciliation index in malignant melanoma. The ciliation index is calculated as the number of cells with SOX-10 positivity and presence of a primary cilium divided by the total number of SOX-10-positive cells, counting at least 100 cells.

Third, microRNAs, a type of noncoding RNA, are stable within formalin-fixed tissue and have been correlated with prognosis in malignant melanoma. miR-146 and miR-21 are 2 microRNAs that are upregulated in thicker superficial spreading melanomas, correlating with lower survival. miR-146a has been shown to increase melanoma cell migration and invasion. miR-21 knockdown in melanoma cell lines results in reduced proliferation and increased apoptosis.

While all three of the biomarkers addressed by Dr. Seykora may be clinically meaningful for patients, microsatellites may be the most useful at this time, as microsatellites can be evaluated directly in routinely-stained tissue sections, without the need for fluorescent staining or extraction of RNA.

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References

• Karakousis GC, et al. Microsatellitosis in patients with melanoma. Ann Surg Oncol 2019;26:33-41.
• Niebling MG, et al. The prognostic significance of microsatellites in cutaneous melanoma. Mod Pathol 2020:33:1369.