I have a problem with my foot.
A 57 y.o. woman from Bosnia presents with a problem with her foot.
This patient has melanoma metastatic to the second toe. She is being scheduled for an amputation.
Melanoma is not a new disease. In the 1960’s nine Peruvian mummies; 2400 years old were found to have melanotic deposits in the skin. Rene Laennec was the first to describe the disease in 1804.
Melanoma caused 55,000 deaths in 2012 with Australia and New Zealand being the countries with the highest incidence.Exposure of melanocytes whether in a mole(25% of cases ) or in the skin is thought to cause malignant transformation. It has a higher incidence in airline pilots and crew because of exposure to UV light.
Spread of melanoma is related to the depth of the initial lesion. When the tumor is in the epidermis and 1 mm in depth, it can be completely cured by excision. As it begins to grow vertically, it enters the papillary dermis and begins to spread through lymphatics.
By stage III metastasis has occurred and the melanoma becomes “incurable” however recent advances have improved survival .
About 60% of melanomas contain a B-Raf mutation andinhibitors of this mutation like vemurafenib have been used for treatment since 2011.
Recently pembrolizumab has been used for metastatic melanoma. It works by unleashing an immune response against the cancer cells. Melanoma can “hide” from the immune system by expressing a protein called PD-1 (programmed death-1)which turns off the immune response butpembrolizumab targets PD-1 which allows the immune system to attack the cancer. 30% of melanomas have PD-1 . The most famous recent successful treatment of a PD-1 positive melanoma was Jimmie Carter.
Clinical Trials.gov NCT01295827 Study of Pembrolizumab MK-3475 in participants with progressive locally advanced or metastatic carcinoma or non small cell lung Ca Po7990/MK3475-001 Keynote-001
Sanlorenzo, m Wehner M, Linos E, Kornak J et al. The risk of melanoma in airline pilots and cabin crew JAMA dermatology 2014.1077.
Chapman P, Hauschild A, Robert C. et al. 2011 Improved survivalwith vemurafenib in melanoma with BRAF V600Emutation NEJM 364(26) 2507-2516.
Urteaga P. {acl G 1966 “On the Antiquity of Melanoma” Cancer 19(5): 607-10.