2. Out line
• Definition
• Epidemeology
• Etiology and pathogenesis
• Diagnosis
• Clinical-Histopathologic Subtypes
• Clinical course and prognosis
• Management
3. DEFINITION
• Melanoma (a word derived from the greek melas [dark] and oma
[tumor]) is a malignant tumor arising from melanocytic cells and
hence can occur anywhere where these cells are found.
• The most frequent type is cutaneous melanoma but melanomas
develop also at the mucosal, the uveal, or even the meningeal
membrane.
• melanoma has the ability to metastasize to any organ, including the
brain and heart.
4. EPIDEMIOLOGY
• incidence of melanoma has increased significantly worldwide over
the last several decades.
• There is a low annual incidence in the whole world population of 3.0
new cases per 100,000 population.
• The highest incidence of melanoma is reported for Australia/New
Zealand with about population,
followed by Northern Europe and Northern America.
• The median age at diagnosis is 57 years, and the median age at death
is 67 years.
5. • Males are approximately 1.5 times more likely to develop melanoma
than females.
• White people have a 10-fold greater risk of developing cutaneous
melanoma than black people, Asian people, or Hispanic people.
• White and black people have a similar risk of developing plantar
melanoma.
• Noncutaneous melanomas (e.g., mucosal) are more common in non
white populations.
6. ETIOLOGY AND PATHOGENESIS
There are several risk factors for melanoma, with sun exposure and genetics being the 2 most important
ones.
• Personal history of atypical moles
• family history of melanoma
• greater than 75-100 moles
• Previous nonmelanoma skin cancer
• Congenital nevus (giant, .20 cm)
• History of melanoma
• Immunosuppression
• Chronic tanning with UVA (PUVA treatments [>250] for psoriasis)
• Repeated blistering sunburns
• Freckling
• Fair skin, inability to tan
• Red or blond hair
8. SUN EXPOSURE
• Ultraviolet (UV) exposure, is a major environmental cause of
melanoma, especially in high-risk populations.
• However, certainly not all melanomas are sun related.
• History of sunburns is an important risk factor, the more sunburns in
a lifetime, the higher the melanoma risk.
• One blistering sunburn in childhood more than doubles a person’s
chances of developing melanoma later in life.
9. • Intermittently exposed skin areas have the highest rates of developing
melanoma in younger persons.
• In men, the trunk, particularly the upper back, is the most common site for
melanoma.
• In women, the lower legs, followed by the trunk, are the most common sites.
• In older persons, there is a greater incidence of melanomas located on
chronically exposed areas with maximal cumulative sun exposure.
• The face is the most common location for melanoma in older persons, with
the addition of the neck, scalp, and ears as well, in older men.
10. • Individuals with recreational and vacation sun exposure who
experience acute episodic exposures to sunlight may be at greater
risk than those with constant occupational sun exposure.
• Continuous UV radiation exposure, either in adult life or during
adolescence, seems to play a protective role in melanoma risk.
• Those with outdoor occupations have been found to have a lower risk
of acquiring melanoma.
11. PUVA and Risk of Melanoma
• Oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is
effective therapy for psoriasis and other skin conditions.
• It is carcinogenic. An increased risk of melanoma is observed
beginning 15 years after first exposure to oral methoxsalen (psoralen)
and ultraviolet A radiation (PUVA).
12. Sunscreen Effectiveness
• Melanoma may be preventable by regular sunscreen use in adults.
• Sunscreen use may give people a false sense of security and
encourage excessive exposure.
• Wearing hats and protective clothing and avoiding sunbathing are
more protective than using chemical sunscreens.
13. SKIN PHENOTYPE
• Fitzpatrick skin phototype I–II
are phenotypic features
associated with an increased risk
of melanoma of 2- to 3-fold.
• Melanoma occurs much less
frequently in Type V–VI skin,
suggesting that skin pigment
plays a protective role.
14. MELANOCYTIC NEVI
• Nevi, or moles, are benign tumors composed of nevus cells that are derived
from melanocytes.
• There is an increased risk of melanoma associated with nevi, both in a
quantitative (ie, number of nevi) and qualitative (ie, typical vs atypical nevi)
manner.
• Adults with more than 100 clinically typical-appearing nevi, children with
more than 50 typical-appearing nevi, and any patient with atypical nevi are at
risk.
15. Incidence and Evolution
• Moles are so common that they appear on virtually every person.
• They are present in 1% of newborns and increase in incidence
throughout infancy and childhood.
• The incidence peaks in the fourth to fifth decades.
• Nevi then diminish in number with advancing age.
16. • Size and pigmentation may increase at puberty and during pregnancy.
• There is a strong correlation between sun exposure and the number
of nevi.
• Nevi may occur any where on the cutaneous surface.
• Acquired nevi on the buttocks or female breast are unusual.
17. Nevi versus Melanoma
• Each individual nevus tends to remain uniform in color and shape.
• Melanomas vary in shape, color, and surface characteristics.
• Early melanomas may appear quite uniform.
18. Atypical Nevi
• also referred to as dysplastic nevi or Clark nevi,
• They sometimes have a “fried egg” appearance with a central darker
bump and a surrounding lighter colored spot.
• Dysplastic nevi differ from commonly acquired nevi by
1. beginning to appear near puberty instead of in childhood and
2. continuing to develop past the fourth decade.
19. The clinical diagnosis of atypical melanocytic nevi is established when
at least three of the following characteristics are present:
• Diameter greater than 5 mm
• Ill-defined borders
• Irregular margin
• Varying shades in the lesion
• Presence of papular and macular components
20.
21. FAMILY HISTORY
• Patients with familial melanoma are estimated to account for approximately
5% to 12% of all patients with melanoma.
• Having one first-degree relative with melanoma doubles the risk of
melanoma, whereas having 3 or more first-degree relatives with melanoma
increases the risk 35- to 70-fold.
• Patients with familial melanoma typically have earlier-onset melanoma and
multiple primaries as well as atypical nevi.
• In addition, patients with familial melanoma have an increased risk of internal
cancers, such as pancreatic cancer or CNS tumors.
22. DIAGNOSIS
PHYSICAL EXAMINATION
• Clinical diagnosis of melanoma can be made in about 80% to 90% of cases.
• ABCDs of Malignant Melanoma Recognition (Does not apply to
nodular or desmoplastic melanoma.)
• A = asymmetry (one half is not identical to the other half),
• B = border (irregular, notched, scalloped, ragged, or poorly defined borders as
opposed to smooth and straight edges),
• C = color (having varying shades from one area to another),
• D = diameter (ie, greater than 5 mm), and
• E = evolution (changes in the lesion over time).
• Lesions having these characteristics may potentially represent melanoma.
23. • Another diagnostic aid that is useful in detecting melanoma is the
“ugly duckling” sign.
• A pigmented lesion that is different from other pigmented lesions
on a particular individual should be approached with a high index
of suspicion.
• Changes in shape and color are important early signs and should
always arouse suspicion.
• Ulceration and bleeding are late signs.
24.
25. Characteristics of Benign Moles
• Circumferential enlargement occurs in common nevi of children.
• Have a more uniform tan, brown, or black color.
• The border is regular and the lesion is roughly symmetric.
• Most acquired benign moles are 6 mm or less in diameter and appear
early in life.
26. Recent Change in a Mole
• The patient’s description of a change in a mole may be the earliest
sign of melanoma.
• Changing color, increasing diameter, height, or asymmetry of borders;
or changing surface characteristics as well as pruritus, pain, bleeding,
ulceration, or tenderness all suggest evolution into melanoma.
27. DERMOSCOPY
• Dermoscopy is a noninvasive
technique in which a handheld
device is used to examine a lesion
through a film of liquid (eg,
immersion oil), using nonpolarized
light (contact dermoscopy), or the
lesion is examined under polarized
light without a contact medium
(noncontact dermoscopy).
28. HISTOLOGY
• The histologic diagnosis is based on the assessment of a constellation of
findings, including both architectural and cytologic features.
• The major features of melanoma include
• asymmetry,
• poor circumscription
• large size (>5 to 6 mm).
• Nests of melanocytes in the lower epidermis and dermis tend to vary in size and
shape, and to become confluent.
• lack of maturation of nests with descent into the dermis.
• single melanocytes dominate over nests
• presence of melanocytes above the basal layer (pagetoid spread)
29. LABORATORY TESTING
• minor role in the diagnosis of melanoma,
• lactate dehydrogenase (LDH)
• non specific
• S100B
• more specific than LDH
• lacks sensitivity
• monitored in clinical followup
• ? Other tumor markers under investigation
• melanoma-inhibiting activity (MIA),
• tumor-associated antigen 90 immune complex (TA90IC), and
• YKL-40 are
30. IMAGING
Regional skin and lymph node ultrasound
• Skin and lymph node ultrasonography is perhaps the most sensitive
noninvasive method to detect small nodal metastases and is much
more sensitive than clinical examination.
• Lymph node metastases are characterized by a ballooned shape, loss
of central echo, and peripheral perfusion.
31. TOMOGRAPHY
• CT scan, MRI and PET scan can be justified in high-risk melanomas (>4
mm Breslow thickness), as the risk for hematologic spread increases.
32. SENTINEL LYMPH NODE BIOPSY (SLNB)
• SLNB is a powerful staging and prognostic tool which may be used to
detect occult micrometastases in regional lymph nodes.
• SLNB is far more sensitive and accurate at detecting microscopic
metastases than PET scan, CT scans, or ultrasonographic imaging
combined with lymph node fine-needle aspiration.
33.
34. Clinical-Histopathologic Subtypes
SUPERFICIAL SPREADING MELANOMA (SSM)
• SSM is the most common subtype, accounting for approximately 70% of
all cutaneous melanomas.
• It is diagnosed most commonly on intermittently sun exposed areas,
most frequently the lower extremity of women, and the upper back of
men.
• SSM is the subtype of melanoma most commonly associated with
preexisting nevi.
• The history of SSM is often of a lesion slowly changing over months to
years. It may be mistaken for an atypical nevus or seborrheic keratosis.
35.
36. NODULAR MELANOMA (NM)
• NM is the second most common melanoma subtype and accounts for
approximately 15% to 30% of all melanomas.
• The trunk is the most common site.
• NM is remarkable for rapid evolution, often arising over several weeks to
months.
• NM more often lacks an apparent radial growth phase.
• It is more common for NM to begin de novo than to arise in a preexisting
nevus.
• Amelanotic lesions may be mistaken for basal cell carcinoma, pyogenic
granuloma, or hemangioma, whereas pigmented lesions may be mistaken for
blue nevi or pigmented basal cell carcinomas.
37.
38. LENTIGO MALIGNA (LM) AND LENTIGO MALIGNA MELANOMA (LMM)
• LM is a melanoma in situ with a prolonged radial growth phase that
eventually becomes invasive and is then called LMM.
• LM and LMM are diagnosed most commonly in the seventh to eighth
decades in an older population than other types of melanoma—
uncommon before the age 40.
• The most common location is on the chronically sun-exposed area face,
on the cheeks and nose in particular; the neck, scalp, and ears in men.
• Its pathogenesis is thought to be related to cumulative sun exposure
rather than intermittent e
39.
40. ACRAL LENTIGINOUS MELANOMA (ALM)
• ALM constitutes only 2% to 8% of melanomas in whites but represents the most
common form in darker-pigmented individuals (60% to 72% in African
Americans and 29% to 46% in Asians).
• diagnosed more often in an older population, with the median age of onset of 65.
• The most common site for ALM is the sole, with the palm and subungual
locations.
• Often ALM are misdiagnosed first as a plantar wart or hematoma.
• ALM is not thought to be associated with sun exposure.
41.
42. DESMOPLASTIC MELANOMA (DM)
• DM most commonly develops in the sixth or seventh decade on sun-
exposed head and neck regions.
• The lesions typically have a firm, sclerotic, or indurated quality, and
one-half are amelanotic.
• Approximately half of the lesions arise in association with the LM
histologic subtype.
• DMs reveal a high mutation burden most likely induced by UV
radiation.
43.
44. MUCOSAL MELANOMA
• Melanoma can infrequently (1.3% of melanomas) arise on mucosal
surfaces on the head and neck (conjunctival, intranasal, sinus, and oral
cavities), genital, anorectal, or even urethral mucosa.
• As most of these lesions present initially with a radial growth phase
manifesting a macular pigmentation.
• Melanomas on vulva and vagina account for about 50% of the mucosal
melanomas among women.
• In both genders, the nasal cavity was otherwise the most frequent
location for mucosal melanomas.
46. NEVOID MELANOMA
• histologically resemble benign nevi by their symmetry and apparent
maturation with descent in the dermis, thus with greater potential for
misdiagnosis.
• Clues to their histologic diagnosis include marked hyperchromasia of
the nuclei of the tumor cells, the presence of mitoses, and expansive
growth of the dermal cells.
• Clinically, this may correspond to a tan papule or nodule, more often
>1 cm in diameter on a young adult.
48. SPITZOID MELANOMA
• Spitzoid melanoma is a subtype of melanoma that clinically and
histologically resembles a Spitz nevus, but tends to be larger and have
asymmetry and irregular coloration.
• Features that favor the diagnosis of a Spitzoid melanoma over a
benign Spitz nevus are large size (greater than 1 cm in greatest
dimension); lesions with a thick invasive component (>2 mm Breslow
thickness);
49.
50. UVEAL MELANOMAS
• Uveal melanomas account for about 5% of all melanomas and develop mainly
in the choroid, followed by ciliary body and iris of the eye.
• Nevertheless, uveal melanoma is the most common primary intraocular
malignancy.
• The median age at diagnosis is 58 years.
• Risk factors include the presence of a choroidal nevus, a nevus of Ota, and
dysplastic nevus syndrome.
• There is an 8 times higher incidence rate in whites as compared to the black
population.
• Clinically most patients present with painless loss or distortion of vision or the
tumor is diagnosed in asymptomatic patients in routine ophthalmic screening.
53. • Melanoma can progress to different stages of the disease.
1. STAGES I AND II MELANOMA
• In general, the 5- to 10-year survival for patients with localized thin
primary melanoma <1mm in Breslow depth is more than 90%.
54. 2. STAGE III MELANOMA
• range from patients with microscopic nodal disease (IIIA) to patients
with bulky clinical nodes or in-transit metastases (IIIC).
• The general overall 5-year survival range of 38% to 78%.
55. 3. STAGE IV MELANOMA
• Melanoma is known for its propensity to metasasize to virtually any
organ and also for its highly variable clinical course.
• The most common visceral sites are the lungs (18%-36%), liver (14%-
20%), brain (12%-20%), bone (11%-17%), and GI tract (1%-7%).
• Once metastases to distant sites have been detected, median survival
without any treatment is approximately 6 to 9 months.
56. Metastatic melanoma of unknown primary(MUP)
• MUP is defined as the presence of histologically confirmed melanoma
in a lymph node, visceral site, or distant skin/subcutaneous tissues
without a history or evidence of a primary cutaneous, mucosal, or
ocular melanoma.
• This situation occurs in 2% to 5% of all cases of melanoma.
• Approximately 60% of these involve the lymph nodes and might have
developed from nodal nevi.
58. • The number of lymph nodes involved (independent of tumor deposit
size) is the most significant risk factor in patients with stage III
melanoma.
• Prognostic factors in distance metastasis are site of metastasis,
number of metastatic sites and surgical resectability.
60. Adjuvant treatment
• Interferon-α
• Two different dosage regimens were routinely used:
• high-dose (HDI) and low-dose interferon (LDI) treatment.
• The high-dose regimen consists of 20 million units per square meter of body
surface area per day given intravenously 5 days a week for 4 weeks (induction
phase), followed by 10 million units per square meter per day given
subcutaneously 3 times a week for 48 weeks (maintenance phase).
• The low-dose regimen uses 3 million units 3 times a week given
subcutaneously for 1.5 years.
61. • Immune checkpoint blocker
• For patients with stage III disease, treatment with the anti-CTLA-4 antibody
ipilimumab is used.
• Adjuvant radiotherapy
