Terminology for melanocytic skin lesions and the <scp>MPATH‐Dx</scp> classification schema: A survey of dermatopathologists

Radick, Andrea C.; Reisch, Lisa M.; Shucard, Hannah; Piepkorn, Michael; Kerr, Kathleen F.; Elder, David E.; Barnhill, Raymond L.; Knezevich, Stevan R.; Oster, Natalia V.; Elmore, Joann G.

doi:10.1111/cup.13873

Cited by 14 publications

(12 citation statements)

References 28 publications

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“…Despite a general subjective susceptibility for misinterpretation, the dysplastic nevi presented mild dysplasia and were included into class 1 according to the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) diagnostic schema [ 18 ], which presents a 92% interobserver accuracy of diagnosis correctitude in skin biopsies [ 19 ]. Our cases were represented by cutaneous sections with a low Ki67 proliferation index, thus enhancing the accuracy level, as well as offering sufficient clinical information about melanocytic lesions, as previously reported [ 20 ]. Even if, for Spitz nevi, the reported interobserver accuracy level is 40% in skin biopsies [ 19 ], in our case, full slide evaluation associated with the Ki67 index enhanced the diagnostic precision.…”

Section: Methodsmentioning

confidence: 92%

Relevance of BRAF Subcellular Localization and Its Interaction with KRAS and KIT Mutations in Skin Melanoma

Beleaua

Jung²,

Braicu

et al. 2021

IJMS

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Although skin melanoma (SKM) represents only one-quarter of newly diagnosed skin malignant tumors, it presents a high mortality rate. Hence, new prognostic and therapeutic tools need to be developed. This study focused on investigating the prognostic value of the subcellular expression of BRAF, KRAS, and KIT in SKM in correlation with their gene-encoding interactions. In silico analysis of the abovementioned gene interactions, along with their mRNA expression, was conducted, and the results were validated at the protein level using immunohistochemical (IHC) stains. For IHC expression, the encoded protein expressions were checked on 96 consecutive SKMs and 30 nevi. The UALCAN database showed no prognostic value for the mRNA expression level of KRAS and BRAF and demonstrated a longer survival for patients with low mRNA expression of KIT in SKMs. IHC examinations of SKMs confirmed the UALCAN data and showed that KIT expression was inversely correlated with ulceration, Breslow index, mitotic rate, and pT stage. KRAS expression was also found to be inversely correlated with ulceration and perineural invasion. When the subcellular expression of BRAF protein was recorded (nuclear vs. cytoplasmatic vs. mixed nucleus + cytoplasm), a direct correlation was emphasized between nuclear positivity and lymphovascular or perineural invasion. The independent prognostic value was demonstrated for mixed expression of the BRAF protein in SKM. BRAF cytoplasmic predominance, in association with KIT’s IHC positivity, was more frequently observed in early-stage nonulcerated SKMs, which displayed a low mitotic rate and a late death event. The present study firstly verified the possible prognostic value of BRAF subcellular localization in SKMs. A low mRNA expression or IHC cytoplasmic positivity for KIT and BRAF might be used as a positive prognostic parameter of SKM. SKM’s BRAF nuclear positivity needs to be evaluated in further studies as a possible indicator of perineural and lymphovascular invasion.

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Section: Methodsmentioning

confidence: 92%

Relevance of BRAF Subcellular Localization and Its Interaction with KRAS and KIT Mutations in Skin Melanoma

Beleaua

Jung²,

Braicu

et al. 2021

IJMS

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“…The MPATH-Dx structure for describing melanocytic lesions is increasingly adopted by pathologists as a method to improve diagnostic consistency and communication between healthcare providers [9,10].…”

Section: Introductionmentioning

confidence: 99%

Translation of a circulating melanoma microRNA profile into a solid tissue assay to improve diagnostic accuracy

Laar¹,

King²,

McCoy³

et al. 2021

Preprint

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Background: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-microRNA signature (“Mel38”) was identified in melanoma patient plasma and validated as a novel biomarker. In this study, Mel38 expression in solid tissue biopsies representing the benign naevi to metastatic melanoma spectrum is examined. Methods: Nanostring digital gene expression assessment of the Mel38 signature was performed on 308 formalin fixed paraffin embedded biopsies of naevi, melanoma in-situ and invasive melanoma. Genomic data were interrogated using hierarchical clustering, univariate, and multivariate statistical approaches. Classification scores computed from the Mel38 signature were analysed for their association with demographic data and histopathology results, including MPATH-DX class, AJCC disease stage and tissue subtype. Results: The Mel38 score can stratify higher-risk melanomas (MPATH-Dx Class V or more advanced) from lower-risk skin lesions (Class I-IV) with an area-under-the curve of 0.96 (P<0.001). The genomic score ranges from 0 to 10 and is positively correlated with melanoma progression, with an intraclass correlation coefficient of 0.85 with stage 0 to IV disease. Using an optimised classification threshold of ≥2.3 accurately identifies higher-risk melanomas, associated with poorer outcomes and more intensive suggested clinical actions with 95% sensitivity and 83% specificity. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Application of the Mel38 signature to spitz naevi reveal an intra-subtype profile, with elements of the profile in common to both naevi and melanoma. Conclusion: Melanoma-specific circulating microRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The Mel38 signature is an accurate and reproducible metric of melanoma status, based on changes in microRNA expression that occur as the disease develops and spreads. Inclusion of the Mel38 score into routine practice would provide physicians with previously unavailable, personalised genomic information about their patient’s skin lesions. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, healthcare resource utilisation, and patient outcomes.

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“…The MPATH-Dx structure for describing melanocytic lesions is increasingly adopted by pathologists as method to improve consistency and communication between healthcare providers [12,13]. However, Despite this and other improvements in related areas such as dermoscopy, multiple studies into the accuracy and reproducibility of melanoma diagnosis by histopathology alone is not accurate, nor reproducible [9,10,[14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Translation of a Circulating microRNA Signature of Melanoma to a Novel Solid-Tissue Biomarker to Improve Diagnostic Accuracy and Reproducibility.

Laar¹,

King²,

McCoy³

et al. 2021

Preprint

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Background Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Currently, histopathology examination of excised skin lesions is considered the ‘gold standard’ for diagnosis of melanoma. Multiple studies have shown the low accuracy and reproducibility of this method, underscoring the urgent need for new diagnostic tools, including disease-specific biomarkers. Previously, a 38-microRNA signature of melanoma (‘Mel38’) was previously identified in plasma and validated as novel circulating biomarker. In this study, Mel38 expression in solid biopsy tissue is examined to determine its ability to contribute to accurate and reproducible melanoma diagnoses.Methods Nanostring digital gene expression profiling was used to apply the Mel38 signature in a cohort of 308 formalin fixed paraffin embedded skin biopsies (‘Mel38’). Genomic data were interrogated using hierarchical clustering, univariate and multivariate statistical approaches. Mel38 classification scores (range 0 to 10) were compared to consensus histopathology results, including MPATH-DX class, AJCC disease stage, histological subtype as well as technical assay factors.Results The Mel38 score can identify high-risk melanomas (MPATH-Dx Class IV) from less-malignant forms of the disease with an area-under-the curve of 0.96 (P < 0.001). The genomic score ranges from 0 to 10 and is positively correlated with the melanoma progression, from benign naevi to metastatic disease (intraclass correlation coefficient: 0.85). Using a score threshold of > 2.3 identifies higher-risk melanomas, associated with poorer outcomes and more intensive suggested clinical actions. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Analysis of the Mel38 signature in spitz naevi reveal an intra-subtype profile, in common to both benign and malignant conditions.Conclusion Melanoma-specific circulating microRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The Mel38 signature is an accurate and reproducible metric of melanoma status, based on changes in microRNA expression that occur as the disease develops and spreads. Inclusion of the Mel38 score into routine practice would give physicians a genomic assessment of a patient’s disease status. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, reproducibility, and patient outcomes.

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Terminology for melanocytic skin lesions and the MPATH‐Dx classification schema: A survey of dermatopathologists

Cited by 14 publications

References 28 publications

Relevance of BRAF Subcellular Localization and Its Interaction with KRAS and KIT Mutations in Skin Melanoma

Relevance of BRAF Subcellular Localization and Its Interaction with KRAS and KIT Mutations in Skin Melanoma

Translation of a circulating melanoma microRNA profile into a solid tissue assay to improve diagnostic accuracy

Translation of a Circulating microRNA Signature of Melanoma to a Novel Solid-Tissue Biomarker to Improve Diagnostic Accuracy and Reproducibility.

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