الفهرس 
Skin Structure and FunctionOnly 14 pages are availabe for public view
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Abstract
Summary
elanoma 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 acrallentiginous.
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 most important Cell signaling pathways in melanoma are MAPK (RAS/RAF/MEK/MAPK) pathway which
is prolifrative signal and PI3K/AKT/mTOR which is antiapoptotic
pathway.
The most definitive therapeutic intervention in the
management of malignant melanoma is primary surgical
excision. Most patients with primary tumors of less than 1 mm
thickness have a low risk of locoregional or systemic spread.
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.Other immunotherapeutic agents currently being
tested are antibodies that interfere with the PD-1 (programed
death-1) and PD-L1 (PD-1 ligand)