Anorectal melanoma with a KIT-activating mutation, which is a target for tyrosine kinase inhibitor

Abstract

Recent advances in our understanding of the genetic mutations associated with melanoma have led to the classification of distinct melanoma subtypes. A number of reports have consistently demonstrated that mucosal and acral melanomas more commonly harbor KIT-activating mutations than do other subtypes. Success in treating gastrointestinal stromal tumors with imatinib has led to speculation that KIT-mutated melanoma might also be effectively managed using this approach. A 78-year-old woman presented with a 4-month history of rectal bleeding. A colonoscopy revealed a black polypoid mass, 30 mm in diameter, originating near the dentate line, and a biopsy revealed malignant melanoma. Computed tomography showed multiple liver and lung metastases. A KIT mutation analysis showed the L576P mutation in exon 11. The patient did not want to undergo chemotherapy including a tyrosine-kinase inhibitor, so palliative radiotherapy for rectal symptoms was performed, but the patient died 4 months later due to disease progression. We describe the first case of anorectal melanoma with a KIT-activating mutation in Japan and summarize findings from the literature regarding the efficacy of KIT kinase inhibitors on this melanoma subtype.

KIT mutations in Russian patients with mucosal melanoma

“…1. Three out of these mutations (L576P, K642E, D816N) are recurrent in MM, with the L576P substitution accounting for approximately a third of all KIT sequence alterations [5,6]. Three out of these mutations (L576P, K642E, D816N) are recurrent in MM, with the L576P substitution accounting for approximately a third of all KIT sequence alterations [5,6].…”

“…MMs have worse outcomes as compared with the skin melanomas, that is at least in part attributed to their hidden location and, consequently, late diagnosis. imatinib, sunitinib, sorafenib, dasatinib) to this category of patients resulted in unprecedented tumor responses [5,6]. Systematic studies on somatic mutations in MM have revealed that these tumors differ from other melanoma subtypes by a unique spectrum of molecular alterations [4].…”

“…KIT mutations identified in this study Prediction of sensitivity to TKI is based on the experience with similar mutations in melanoma or non-melanoma patients[5,13,14] …”

A secondary jejunal malignant melanoma from nasal mucosal melanoma: Case report

“…The mean survival of patients with GNAQ/11 was significantly shorter than that of wild-type GNAQ/11. 5 Furthermore, Itoh et al 6 suggest C-KIT (CD117) is overexpressed in over 80% of cases. B-type Raf (BRAF) mutations are uncommon (less than 10% of cases) in mucosal melanoma.…”

Management of Acral Lentiginous Melanoma

“…These cases have marked a tendency to respond to imatinib mesylate which inhibits tyrosine kinase. Although case reports are accumulating [82,83], more data, including long-term control and prognostic data, will be necessary to confirm the effect of this agent.…”