An update on genomic aberrations in Spitz naevi and tumours

Clinical, Morphologic, and Molecular Features of Benign and Intermediate-grade Melanocytic Tumors With Activating Mutations in MAP2K1

“…Among the goals of incorporation of genomics into the classification system of melanocytic tumors is to allow for better prediction of tumor behavior and better interobserver diagnostic agreement 3 . The presence of a Spitz-associated genomic fusion or HRAS mutation in a morphologically Spitzoid neoplasm allows for precise classification into the Spitz family 2 . A common feature of Spitz neoplasms is that the overwhelming majority are either entirely benign or intermediate grade.…”

“…MAP2K1 is a proto-oncogene found on chromosome 15p, which, in turn, encodes a dual-specific serine-threonine and tyrosine protein kinase, involved in the RAF-MEK-ERK pathway. 2,6,7,[23][24][25][26][27][28] Neoplastic conditions in which MAP2K1 activating mutations have been identified include melanoma, DPNs, lung adenocarcinoma, serous ovarian cancer, thyroid cancer, colorectal cancer, histiocytic sarcoma, Langerhans cell histiocytosis, Erdheim-Chester disease, and hairy cell leukemia. 5,7,8,10,11,[29][30][31][32][33][34][35][36][37][38] Activating mutations in MAP2K1 were identified in 6% of melanomas from the COSMIC database 12 and 20% of melanomas from The Cancer Genome Atlas (TCGA) atlas database.…”

“…Morphologic features were assessed by a board-certified dermatopathologist with experience in the assessment of melanocytic neoplasms. The following morphologic features were assessed: silhouette (plaque, wedge, or nodular), cytology (epithelioid, spindled, or both), nuclear atypia (mild, moderate, or severe), pigmentation (absent, focal, or extensive), cell size (small, intermediate, or large), and the presence or absence of Spitzoid cytomorphology, Kamino bodies, ulceration, epidermal hyperplasia, plexiform growth, pagetosis, convergence of nests around the skin adnexa and neurovascular bundles, and mitotic figures per mm 2 . In addition, clinical follow-up was obtained by phone using a standard questionnaire evaluating the following: (1) if follow-up care was performed with a dermatologist or primary care physician, (2) evidence of recurrence, (3) if a sentinel lymph node biopsy or complete lymph node dissection was performed and the results, and (4) the general state of health of the patient.…”

“…T he discovery of chromosomal rearrangements resulting in chimeric fusion proteins as the primary genomic drivers of Spitz neoplasms has greatly advanced our ability to integrate genomics into the classification system for melanocytic neoplasms. 1,2 This has allowed for a more consistent, precise, and reproducible classification of Spitz neoplasms and better interobserver agreement as to what is a Spitz neoplasm. 3 One recent study showed over 70% of spitz neoplasms harbor a characteristic Spitz-associated genomic fusion or have an HRAS mutation.…”

“…Metanalysis of Previously Reported MAP2K1 Mutations Across Different Melanocytic NeoplasmsMAP2K1 alteration type Spitzoid neoplasms DPN Melanoma fusion or HRAS mutation in a morphologically Spitzoid neoplasm allows for precise classification into the Spitz family 2. A common feature of Spitz neoplasms is that the overwhelming majority are either entirely benign or intermediate grade.…”