Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • Although there was no difference in the mean age of

    2018-11-12

    Although there was no difference in the mean age of onset between acral and mucosal melanomas, KIT mutation in mucosal melanomas occurred more than a decade earlier than that in acral melanomas. Regarding the sex factor, we noticed that KIT mutation among our few cases is more commonly seen in male patients with acral melanoma despite a male predominance in prevalence is characteristic for acral melanoma. By contrast, however, KIT mutation is more commonly seen in female patients with mucosal melanoma (a male-to-female ratio of 1:5) even though a female predominance is already noticed in mucosal melanomas (a male-to-female ratio of 1:2.5). To our knowledge, there are 66 KIT-mutated acral melanomas and 102 KIT-mutated mucosal melanomas reported in the literature, including this study (Table 6). Among the analyzed exons in these melanomas, KIT mutation was most commonly seen in KU-60019 manufacturer 11, followed by exon 13, and finally exon 17. Exon 18 mutation was not found in all acral melanomas, but was present in one mucosal melanoma. Of these, a total of 104 different point mutations of KIT have been described (Table 6). The most common one is L576P (30%), followed by K642E (14%), then V559A (6%) and D820Y (5%). These four mutations account for 55% of all KIT mutations in the literature, suggesting that efforts should be focused on these hot spots when budget for mutational analysis is limited. Indeed, 81% of KIT mutations in our series occur in these hot spots. Because mutational analysis may not be available in some areas around the world, it will be important to know whether KIT mutation more commonly occurs in certain subsets of melanoma so that imatinib can be empirically given to this subset of patients. From this point of view, it appears that male patients with acral melanoma and female patients with mucosal melanoma of the anorectal and genitourinary regions belong to this mutation-prone subset. In our series, 10 of 13 KIT mutants belong to this subset. More specifically, five of 13 male patients with acral melanoma and five of 11 female patients with mucosal melanoma of the anorectal and genitourinary regions had KIT mutation. In short, approximately 42% (10/24) of melanomas belong to this mutation-prone subset. However, it should be addressed that mutant D820Y is reported to be resistant to imatinib. Therefore, one-third (8/24) of patients in this subset will be responsive to imatinib treatment. From this point of view, future clinical trials should select the patients of the mutation-prone subset if KIT mutation is not one of the inclusion criteria. Ideally, those with tumors harboring D820Y should be excluded. In summary, we showed that acral and mucosal melanomas have a higher KIT mutation rate than cutaneous melanoma. Furthermore, KIT mutation is most commonly seen in male patients with acral melanoma and female patients with mucosal melanomas of the anorectal and genitourinary regions. When mutational analysis is to be performed, exons 11, 13, and 17 should be examined. Alternatively, four hot spots of KIT should be checked if laboratory analysis is limited. Although no definite conclusions can be drawn from a study with a small sample size, our study shows some characteristics of KIT mutation in melanoma, which may provide practical information in the era of targeted therapy for patients with melanoma.
    Acknowledgments This study was supported in part by Cathay General Hospital (CGH-MR-10126) and Novartis Oncology (Taiwan). The authors thank Ms Hsiang-Hua Yang in the Department of Molecular Medicine of Cathay General Hospital for technical expertise.
    Introduction Azathioprine, a prodrug of 6-mercaptopurine, has been used as an antileukemic, anti-inflammatory, and immunosuppressive agent to treat many debilitating skin diseases such as atopic dermatitis, autoimmune bullous disease, chronic actinic dermatitis, erythema multiforme, lichen planus, and pityriasis rubra pilaris. However, serious adverse drug reactions (ADRs) may occur, which necessitate drug discontinuation and may result in fatality. The common ADRs include myelosuppression (neutropenia or leukopenia), gastrointestinal adverse effect (nausea/diarrhea), pancreatitis, and hepatotoxicity. The incidence is estimated to be 15–28% in patients with inflammatory bowel diseases (IBD), mainly Crohn\'s disease. In a survey conducted in England, dermatologists reported that 29.1% of their patients experienced ADRs. There are relatively few safety data of azathioprine in Asian dermatology patients.