Molecular pathology of malignant melanoma: changing the clinical practice paradigm toward a personalized approach

The clinical features, treatment, and prognosis of primary mediastinal malignant melanoma

“…About half of all primary and metastatic MMs have BRAF mutations, with the V600E substitution (which is associated with ultraviolet radiation and intermittent sun exposure) accounting for 80% of BRAF -mutated melanomas; a V600K mutation is found in 10% to 20% of remaining cases. [28,29] Dabrafenib and vemurafenib, oral targeted BRAF-V600E inhibitors, have been approved for the treatment of advanced MM patients or those where surgery is not indicated, who carry the V600E BRAF mutation, and these drugs have demonstrated some therapeutic effect in clinical application. [27,30] …”

Cancer of Unknown Primary: The Pathologist’s Approach

“…With lymphomas [ 39 ] the situation is even more diffi cult. Lymphocytes are per se able to invade tissue and "metastasize," and consequently, an identifi able primary source of tumor "seeding" is usually not present.…”

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Melanoma

“…Of these mutations, 95% occur at amino acid 600, most commonly as Val600Glu (V600E) or sometimes Val600Lys (V600K), and lead to constitutive MAPK pathway activation. 4 A randomized phase III trial of a targeted inhibitor of V600E mutated BRAF, vemurafenib, was first published in 2011. This trial was limited to BRAF V600-mutated melanomas and demonstrated a significant improvement in overall survival at 6 months in patients treated with vemurafenib as compared to dacarbazine, the only chemotherapeutic agent approved for treatment of metastatic melanoma at the time.…”

“…There are now a large number of publications demonstrating excellent correlation between BRAF V600E (VE1) mutation-specific immunohistochemistry and molecular-based analysis. 4 However, in the absence of established proficiency testing or clear regulatory guidelines, laboratories using this immunohistochemistry assay should perform rigorous validation and have available confirmatory molecular testing.…”

“…The most common alterations occur in exons 11 and 13, with L576P and K642E accounting for close to 50% of melanoma-specific mutations in this gene. 4 Small insertions and deletions in exon 11 are rare in melanoma. Targeted inhibitors of KIT and related tyrosine kinase receptors have demonstrated some efficacy in KITmutated but not in KIT wild-type melanomas in case reports and clinical trials, with best response documented most consistently in patients with tumors harboring mutations in the L576 and K642 hotspots.…”