Table 1. WHO pathways of melanoma development.

Adapted from ⁸.

	Low CSD melanoma (I)	High CSD melanoma (II)	Desmoplastic melanoma (III)	Spitz melanoma (IV)	Acral melanoma (V)	Mucosal melanoma (VI)	Melanoma arising from congenital nevus (VII)	Melanoma arising in blue nevus (VIII) and uveal melanoma (iX)
Nevus (common mutations)	Conventional nevus (BRAF V600E, NRAS)	No known benign precursor	No known benign precursor	Spitz nevus (HRAS, kinase fusion)	Minority arises from conventional nevus (BRAF V600E) Other benign precursors unknown	No known benign precursor	Congenital nevus (NRAS mutation, BRAF V600E)	Blue and uveal nevi (GNAQ, GNA11, CYSTLTR1, or PLCB4 mutation)
Melanocytoma (common secondary mutations)	Deep penetrating melanocytoma (CTNNB1, APC) BAP1-inactivated melanocytoma PRKAR1A-inactivated melanocytoma Dysplastic nevus (TERT promoter)	Melanoma in situ (NRAS mutation, BRAF non-V600 mutation, KIT mutation)	Occasionally arises from melanoma in situ	Spitz melanocytoma (previously known as atypical Spitz tumor, CDKN2A inactivation)	Melanoma in situ (focal amplifications of CCND1 and other genes, KIT mutation)	Melanoma in situ (focal amplifications of CCND1 and other genes, KIT mutation)	Proliferative nodule (copy number alterations of whole chromosomes) Melanoma in situ	intermediate lesion unknown atypical blue nevus?
Mutations in Melanoma	Mutation of TERT promoter, TP53, inactivation of CDKN2A, PTEN	Inactivation of NF1, CDKN2A, PTEN, mutation of TERT promoter TP53, RAC1	NRAS mutation, NF1 inactivation, amplification of ERBB2, MAP2K1, MAP3K1, BRAF, EGFR, MET, NFKBIE mutation, PIK3CA mutation, PTPN11 mutation	TERT promoter mutation, CDKN2A inactivation	Amplification of TERT, YAP1, EP300, CDK4, MDM2, inactivation of NF1, CDKN2A, ATRX, mutation of NRAS	Amplification of CDK4, MDM2, inactivation of SPRED1, NF1, ATRX, mutation of NRAS, SF3B1	Mutation of TERT promoter	Inactivation of BAP1, mutation of SF3B1, EIF1AX