Cancer, Skin cancer, Diseases of skin, oncology

1. Shyala Chand

2. • Melanoma is a malignant neoplasm of pigment-forming
cells: Melanocytes.
• Melanoma accounts for only about 1% of skin cancers
but causes a large majority of skin cancer deaths (60%
mortality of all skin cancers)
• The incidence of malignant melanoma in white
populations generally increases with decreasing latitude,
with the highest recorded incidence occurring in
Australia, where the annual rates are 10 and over 20
times the rates in Europe for women and men
respectively.

3. • Incidence of malignant melanoma has increased 3–6%
over the last few decades, making this one of the fastest
growing cancers worldwide.
• Use of tanning beds, especially in female adolescents
increases melanoma risk by 75%.
• Slight male dominance.

5. • Sun exposure (UVB) in involved in the causation of more
than 80% of cutaneous melanomas.
• UV radiation also promotes the production of growth
factors from keratinocytes and suppresses T cell-
mediated cutaneous immune defences.
• Stimulation of melanin production by UV radiation
produces reactive oxygen species of melanin that cause
DNA damage and suppress apoptotic mechanisms.
• Melanoma forms as the result of accumulated
abnormalities in genetic pathways within the melanocyte
that promote cell proliferation and prevent normal
pathways of cell death in response to DNA damage

6. • Head & neck – 25%
• Trunk – 25%
• Lower limb – 25%
• Upper limb – 11%
• Common sites:
Males: trunk (post)
Females: leg

8. • Around 2% of all melanomas are inherited.
CDKN2A (tumor suppressor gene encoding p16)
CDK4 (oncogene)
• Patients with a mutated CDKN2A gene have 70% chance
of developing melanoma and 17% chance of developing
pancreatic cancer.
• Normal fxn: CDK4 acts as a proto oncogene that
promotes progression from G1 to S phase of cell cycle
allowing proliferation where as p16 inhibits CDK4 action
arresting cell division.
• 25-60% of melanoma patients have inactivated p16.

9. BRAF
• Around 40-60% of melanomas have
BRAF mutations.
• Is a proto oncogene encoding a serine/
threonine protein kinase that promotes
cell growth & proliferation via MAPK
pathway.
• Gain of function mutation leads to
uncontrolled cell proliferation.
• Most common mutation is V600E
missense mutation (accounts for 90%
BRAF mutations).
• BRAF is NOT involved in initiation of
melanoma.
• Associated in mutations of vertical phase
and metastasized melanomas ; is a prime
target for anti melanoma therapeutics.

10. NRAS
• NRAS mutations account for 15-20% of melanoma
cases.
• Also part of MAPK pathway with BRAF (rarely present
together in same patient)
• Mutations result in thick vertical growth and promote
transition of primary melanoma into metastatic variant.
• NRAS alterations are more common in sun exposed
areas.

12. Superficial Spreading Melanoma
• The most common type of melanoma,
representing about 70% of all cases.
• Appears as a flat or barely raised lesion,
often with irregular borders and variations in
colour.
• These melanoma lesions most commonly
appear on the trunks of men, the legs of
women, and the upper back of both sexes.
• These lesions are diagnosed most
frequently in patients between the ages of
30 and 50. About half of these melanomas
occur in pre-existing moles.

13. Nodular Melanoma
• Appears as a blue-black, dome-
shaped nodule although 5% of the
time the lesions are pink or red.
• Found most often on the trunk, the
head, or the neck, and represents
10% to 15% of all melanomas.
• More common in men than women.
• Nodular melanoma invades more
deeply earlier and therefore often
presents with a greater depth of
invasion.
• Most aggressive form. Frequently
associated with a
poorer prognosis than other
melanomas.

14. Amelanotic melanoma
• Non pigmented and clinically appears as pink or flesh
coloured lesions. Often mimic basal or squamous cell
carcinoma.
• Occurs most commonly in the setting of the nodular
melanoma subtype or melanoma metastasis to skin.
• Poorly differentiated cancer cells are unable to produce
melanin pigment.

15. Lentigo Maligna Melanoma (Melanoma in
situ)
• Melanoma typically takes many years to
develop. Comes from a pre-
existing lentigo, rather than a mole. Only
about 5% of all melanoma cases
are lentigo maligna melanoma
• It occurs most often in older adults,
usually on the face and other chronically
sun-exposed areas.
• Development of lentigo maligna
melanoma is more influenced by chronic
sun exposure.
• These melanomas are generally large,
flat, tan-colored lesions containing
differing shades of brown, or as in other
melanomas, black, blue, red, grey, or
white.

16. Acral Lentiginous Melanoma
• Typically appears on the palms, soles, or under the nails.
• Less than 5% of all melanomas, most common
melanoma in African-Americans and Asians/ Pacific
Islanders.
• Melanomas look like bruises or injuries to the palms,
soles, or nail beds therefore not diagnosed early.

17. Mucosal Melanoma
• rare form of melanoma that occurs on
mucosal surfaces of the body.
• These mucosal surfaces line the sinuses,
nasal passages, oral cavity, vagina, anus,
and other areas.
Ocular Melanoma
• relatively uncommon, accounting for only
3% of all melanoma cases.
• ocular melanoma is the most common type
of primary intraocular cancer in adults
• also called uveal melanoma

18. • Clark’s
Classification

19. • Breslow Scale – measures thickness used in TNM
staging( for prognosis)

20. • TNM Staging

21. • Total body-skin examination using dermascope.
• Lymph node examination.
• Complete excisional biopsy with 2 mm clearance
margins.
• Family/ clinical history.

24. • Depends on stage of progression and differentiation of
tumor.
• Levels of differentiation:

25. Early stage: wide local excision

26. • Advanced stage: wide local excision, sentinel node
biopsy, chemotherapy, lymphadenectomy.

27. • Metastatic stage: Chemotherapy, Immunotherapy

28. • Signal transduction inhibitor therapy: Signal transduction
inhibitors block signals that are passed from one molecule to
another inside a cell. Blocking these signals may kill cancer
cells.
Eg. Vemurafenib, dabrafenib, trametinib, and cobimetinib are
signal transduction inhibitors used to treat some patients with
advanced melanoma or tumors that cannot be removed by
surgery. Vemurafenib and dabrafenib block the activity of
proteins made by mutant BRAF genes. Trametinib and
cobimetinib affect the growth and survival of cancer cells.
• Oncolytic virus therapy: A type of targeted therapy that is
used in the treatment of melanoma. Oncolytic virus therapy
uses a virus that infects and breaks down cancer cells but not
normal cells. Radiation therapy or chemotherapy may be given
after oncolytic virus therapy to kill more cancer cells.

29. • Angiogenesis inhibitors: A type of targeted therapy that
is being studied in the treatment of melanoma.
Angiogenesis inhibitors block the growth of new blood
vessels. In cancer treatment, they may be given to
prevent the growth of new blood vessels that tumors
need to grow.

30. • Seek the shade, especially between 10 AM and 4 PM.
• Do not burn.
• Avoid tanning and never use UV tanning beds.
• Cover up with clothing, including a broad-brimmed hat
and UV-blocking sunglasses.
• Use a broad spectrum (UVA/UVB) sunscreen with an
SPF of 15 or higher every day
• Keep newborns out of the sun. Sunscreens should be
used on babies over the age of six months.
• Examine skin head-to-toe every month.
• See physician every year for a professional skin exam.