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- Presentation
Adjunct Tools for Diagnosing Dysplastic Nevi and Melanoma
Description
The speaker discusses adjunct tools for diagnosing dysplastic nevi and melanoma, emphasizing that diagnosis should begin with histopathology but can be refined with immunohistochemistry and molecular testing. Key stains include P16, which often shows loss in melanoma and retained expression in nevi, Ki-67 as a proliferation marker, SOX10 to highlight melanocytes, and PRAME as a useful but sometimes overused marker that is usually positive in melanoma and negative in dysplastic nevi, though exceptions exist. The talk illustrates how these markers can help in borderline cases, including dysplastic nevi that mimic melanoma and thin melanomas that resemble nevi. The speaker also reviews genomic approaches such as comparative genomic hybridization, FISH, and next-generation sequencing, explaining that melanoma typically shows progressive accumulation of mutations, whereas nevi often have fewer alterations. Finally, the talk describes emerging molecular patterns in dysplastic nevi across age groups, noting differences between younger BRAF V600E-mutant lesions and older non-BRAF lesions with more alterations, and concludes that integrating morphology, immunostains, and molecular studies yields the best diagnosis.
View moreConclusions
- Adjunct immunostains and molecular tests can improve diagnostic confidence when histopathology alone cannot clearly distinguish dysplastic nevus from melanoma.
- P16 loss, Ki-67 elevation, and PRAME positivity generally support melanoma over nevus, but none of these markers is perfectly specific and each has important gray zones.
- PRAME is the most useful single immunostain in this setting, yet it is still overutilized and can be positive in a minority of bona fide dysplastic nevi, especially in older males.
- SOX10 is best used as a highlighting stain to better visualize melanocytes and architecture rather than as a discriminator of benign versus malignant behavior.
- When lesions are morphologically straightforward, immunostains usually corroborate the diagnosis, but in borderline lesions they are most helpful as part of an integrated interpretation rather than as standalone answers.
- Genomic instability is a major distinguishing feature of melanoma compared with nevi, as shown by copy-number and sequencing studies.
- Melanoma appears to progress through stepwise accumulation of genetic alterations, with benign precursor areas showing fewer events and overt melanoma showing additional mutations such as TERT promoter, CDKN2A, PTEN, MDM2, or ARID1A changes.
- Small biopsy or limited-tissue cases often cannot support broad genomic testing, which limits the practical use of CGH or next-generation sequencing in many dysplastic nevus evaluations.
- Dysplastic nevi are biologically heterogeneous, with younger BRAF V600E-type lesions and older non-BRAF lesions representing different pathways and levels of risk.
- The most clinically important conclusion is that diagnosis and management of dysplastic nevi should rely on an integrated approach combining histology, immunohistochemistry, molecular findings, and clinical context to reach the best patient-specific answer.
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- The Genetic Evolution of Melanoma from Precursor Lesions. New England Journal of Medicine.#10.1056/nejmoa1502583
- Distinct senescence mechanisms restrain progression of dysplastic nevi. PNAS Nexus. 2024;3:1–8.#10.1093/pnasnexus/pgae041