Abstract
Simple SummaryHistopathological, immunohistochemical and molecular investigation of melanocytic lesion is the standard for the diagnosis of melanocytic lesions that are difficult to classify. To ensure correct diagnosis, mass spectrometry has been proposed, specifically in the differential diagnosis of spitz nevi and melanoma. Imaging mass spectrometry is an evolving technology, able to discriminate various tumor entities, which combines morphological features and mass spectrometry. The aim of this study is to apply imaging mass spectrometry to melanocytic lesion to discriminate melanoma from nevi.The discrimination of malignant melanoma from benign nevi may be difficult in some cases. For this reason, immunohistological and molecular techniques are included in the differential diagnostic toolbox for these lesions. These methods are time consuming when applied subsequently and, in some cases, no definitive diagnosis can be made. We studied both lesions by imaging mass spectrometry (IMS) in a large cohort (n = 203) to determine a different proteomic profile between cutaneous melanomas and melanocytic nevi. Sample preparation and instrument setting were tested to obtain optimal results in term of data quality and reproducibility. A proteomic signature was found by linear discriminant analysis to discern malignant melanoma from benign nevus (n = 113) with an overall accuracy of >98%. The prediction model was tested in an independent set (n = 90) reaching an overall accuracy of 93% in classifying melanoma from nevi. Statistical analysis of the IMS data revealed mass-to-charge ratio (m/z) peaks which varied significantly (Area under the receiver operating characteristic curve > 0.7) between the two tissue types. To our knowledge, this is the largest IMS study of cutaneous melanoma and nevi performed up to now. Our findings clearly show that discrimination of melanocytic nevi from melanoma is possible by IMS.
Highlights
Melanoma is the fifth most common cancer among men and women according to statistics from the American Cancer Society’s (ACS) publication, Cancer Facts & Figures 2021 [1]
Benign as well as atypical nevi have been shown to exist in histologic continuity with melanoma, suggesting that these melanocytic proliferations are susceptible to malignant transformation [4]
We have demonstrated a high accuracy (98%) for a supervised linear discriminant analysis (LDA) classifier distinguishing malignant melanoma and melanocytic nevi on independent data
Summary
Melanoma is the fifth most common cancer among men and women according to statistics from the American Cancer Society’s (ACS) publication, Cancer Facts & Figures 2021 [1]. Benign as well as atypical nevi have been shown to exist in histologic continuity with melanoma, suggesting that these melanocytic proliferations are susceptible to malignant transformation [4]. There are melanocytic lesions with an ambiguous histopathologic appearance demonstrating some but not all of the features associated with common melanomas, making their classification difficult, with a certain interobserver variability among pathologists [5]. The exact diagnosis of melanocytic lesions is required for adequate therapy and prognosis. Despite the application of next-generation sequencing, definite discrimination of melanomas from nevi may be challenging
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