الفهرس 
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Abstract
Melanoma is a malignant tumor arising from melanocytes. The most common localization of the tumor is the skin, which includes about 95% of cases. But melanomas can be observed in other locations such as the mucosal membranes of gastrointestinal tract and genitourinary system or in the eye.
The incidence of melanoma varies in different populations and depends on some biological, lifestyle and/or environmental factors. There are four main histological patterns of melanoma, superficial spreading, nodular, lentigo maligna, and acral lentiginous.
Various assistive optical devices like dermoscopy are becoming part of routine clinical practice. Imaging studies like CT and MRI are very important in stage III and IV disease to role out distant metastases.
The risk of lymph nodal involvement correlates with thickness of the primary lesion and presence of ulceration. The removal of the regional lymph nodes was believed to have the potential to cure patients with clinically occult lymph nodes.
This belief led to the practice of routine elective lymph node dissection (ELND) in all patients who were deemed to have a high risk of regional spread. The ELND is now replased by sentinel lymph node biopsy (SLN) for high risk patient and should be considered routine in this subset.
The risk of recurrence of melanoma is substantial in deeply invasive primary melanoma and when lymph nodes are involved at diagnosis. The only adjuvant therapy for high risk melanoma approved by the Food and Drug Administration (FDA) is interferon Alfa.
Melanoma is widely believed to be a radioresistant tumor. The concept of radioresistance of melanoma has been interpreted to mean that radiation therapy is not useful for the treatment of melanoma, a perception that is incorrect. Radiation therapy has been successfully used for primary treatment of ocular melanoma and lentigo maligna melanoma.
The prognosis of a patient with stage IV metastatic malignant melanoma in the 21st century remains poor. Despite decades of research efforts, the median survival time of a patient with disseminated melanoma is less than 9 months with a less than 5% probability of survival beyond 5 years of diagnosis.
Dacarbazine, the first drug approved for the treatment of stage IV melanoma. BRAFV600E inhibitor, Vemurafenib, which was approved by the FDA in 2011 as a therapeutic option for treatment of unresectable metastatic melanoma improve the progression free survival. Also Dabrafenib was approved by the US FDA in May 2013 as a new treatment standard for patients with unresectable or metastatic melanoma with a BRAFV600E mutation.
Other new target therapies include MEK inhibitors like Trametinib which was also approved by FDA in May 2013, c- KIT inhibitors like Imatinib and mTOR inhibitors like Temsirolimus and Everolimus.
The combination of target therapies is now under investigation particularity so the combination of BRAF (Dabrafenib) and MEK (Trametinib) inhibitors. Ipilimumab a monoclonal antibody to the T-lymphocyte associated antigen 4 (CTLA-4) was approved by the US FDA in March 2011 and it is currently implemented as a treatment option for patients with stage III and IV metastatic melanoma.