Transcript Melanoma Tutorial - Medical Student LC

Melanoma Tutorial
Quick Review and Q/A
Melanoma Tutorial
Quick Review and Q/A
• 46 WF presents to your office with an
“irritating” mole (nevus) on her left leg.
Quick Review
What is your approach?
• Hx, Px, possible biopsy
• Hx
– CC: “irritating mole on left leg”
– HPI:
» Possible symptoms of the lesion (bleeding, itchiness,
tenderness)
» Duration of lesion (1 month, 1 year, 10 years)
» Changes in lesion (shape, border, color, diameter)
» Previous biopsies, treatments or diagnoses of this lesion
» Previous biopsies, treatments or diagnoses of other lesions
» Other dermatological diseases
» Risk factors: Fitzpatrick skin type, life time sun exposure,
tanning bed use, sun burns, number of nevi (moles),
hair/eye color, freckles, ethnicity (i.e. Irish) Family Hx for
skin cancers such as melanoma
Quick Review
Physical Exam
• Evaluate “irritating lesion” (ABCD method)
– A = Asymmetry (shape: is the lesion circular?)
– B = Border (is the border smooth or irregular?)
– C = Color (solid brown, various shades, black,
red, blue?)
– D = Diameter (> than the diameter of a pencil?)
• Head-to-toe Dermatological Exam including
scalp, mucus membranes, hands and feet and
genitalia if appropriate (melanomas have been
found along the vaginal wall)
• Palpate regional lymph nodes
Quick Review
If you are still concerned about the
lesion - biopsy
• Histological review is the gold-standard for
diagnosing skin lesions
• Biopsy methods include: shave, punch and
excisional.
• Pathologist reviews specimen and provides report
often with diagnosis and recommendations. For
example, if the melanoma reaches the border of the
specimen, wider excision is advised.
• Possible diagnoses include: Skin cancer
(melanoma, basal cell carcinoma, squamous cell
carcinoma), Spitz nevus, actinic keratosis, etc.
Quick Review
This case, the biopsy indicates
melanoma – next step?
• Wider excision and reconstruction
• Sentinel node biopsy to identify lymph
node status
• Possible metastases? Review Hx, Px,
Diagnostic Tests such as CXR, CT, liver
function tests
• Follow-up for melanoma recurrence and
dermatological exams
Quick Review
If metastatic – treatment?
• Lymph nodes – lymphadenectomy,
possible chemo
• Lung, liver mets – chemotherapy
• Chemotherapy not as effective in treating
metastatic melanoma as it is other
cancers.
• 5-year survival with mets is extremely poor
Quick Review
What is a melanoma?
• A melanoma is a cancer derived from
melanocytes
• Melanocytes are pigment (melanin)
producing cells found along the basal layer
of the epidermis.
• A melanoma may or may not arise from a
preexisting pigmented lesion (i.e. nevus)
Q/A
Is melanoma a serious cancer?
• Melanomas are not the most common
form of skin cancer; however,
• Melanomas are the most serious form of
skin cancer because:
• Higher probability of metastasis
• Higher risk of morbidity and mortality
• Metastases are difficult to treat and prognosis is
extremely poor
Q/A
How common is melanoma in
Canada?
• The incidence of melanoma is increasing
at ridiculous rates amongst white
populations throughout the world.
• The rate of annual increase of melanoma
is nearly greater than all other cancers in
Canada including breast, lung, prostate.
• In Canada, NS has one of the highest age
standardized incidence rates of
melanoma
Q/A
Is everyone at risk for developing a
melanoma?
• Everyone is at risk of developing
melanoma; however the likelihood is
variable and depends on a number of
factors:
– Risk increases with age
– Risk is greater in Caucasian populations and
certain ethnicities
– Risk is directly related to life time exposure of
UV radiation
Q/A
Who treats patients with
melanoma?
• The treatment of melanoma is often a
multidisciplinary approach and includes
one or some of the following:
– Family Physician
– Dermatologist
– Plastic Surgeon
– General Surgeon
– Oncologists (surgical, medical)
– Pathologists
Q/A
What are the different types of
melanoma?
• Different types of melanomas can often be distinguished
by their clinical appearance; however, a microscopic
analysis can clearly identify the following types:
– Melanoma in situ
» Not yet invasive
– Superficial spreading melanoma
SSM
» Any site
– Nodular melanoma
» Any site
– Lentigo melanoma
NM
» Face
– Acral melanoma
» Sole, palms, mucous membranes
LM
Q/A
How does a melanoma develop?
• Melanomas are skin tumors and have a similar
pathophysiology as other cancers
• There is a disruption in the melanocyte life cycle
(cell division, growth and death)
– Genetic transformations in the melanocyte include
• Expression of proto-oncogenes
• Defect or loss of tumor suppressor genes
– This leads to uncontrolled cellular division, poor
cellular differentiation and a decrease in apoptosis
– Angiogenesis and invasion progress with melanomas
as they do other cancers
Q/A
Where do melanomas develop?
• Melanomas can develop anywhere in the body
were there are melanocytes
– Retina
– Cutaneous (including scalp, ears, hands and feet,
genitalia)
– Certain mucosa including vaginal
• Cutaneous melanomas are the most common
and certain types of melanoma are found more
common in some areas
• The most common site of melanomas in males
and females is the trunk and extremities,
respectively.
Q/A
What is the natural history of a
melanoma?
• Melanomas grow both in radial and vertical panes.
• Melanomas grow in size both “above and below” the
skin.
• Skin layers from superficial to deep are: epidermis,
papillary dermis, reticular dermis and subcutaneous
tissue).
• Further invasion into the deeper layers of the skin
increases the likelihood of metastasis.
• Metastases is malignant growth outside original location
including other areas of skin, lymph nodes or distant
organs.
• Melanomas left untreated are likely to become
metastatic,
Q/A
What are the clinical features of a
melanoma?
• Melanomas are usually asymptomatic (i.e.
not tender, ulcerated or itchy)
• People present with concerned lesions if
they are in a cosmetic area or if they have
notice change in the lesion
• Lesions may have been present for years
• Lesions suspicious for melanoma have
unusual characteristics in shape, border,
color and diameter (ABCD)
Q/A
How does ABCDE define a
melanoma?
• A = Asymmetry
» Cancerous growth does not usually result in a perfect
circular shape, compared to a normal nevus.
• B = Border
» The border is also irregular, such as the NS coastline
• C = Color
» Color is often variable including multiple shades of brown
as well as black, red, and blue. Non-pigmented
melanomas are also possible.
• D = Diameter
» Usually > 6mm
• E = Evolving
» How quickly the lesion changes over time
Q/A
Does a positive family history of
melanoma put a patient at risk?
• As with all diseases a positive family
history increases the clinician’s suspicion.
• Certain ethnicities such as Irish and
Scottish have a higher incidence of
melanoma
• Genes responsible for melanoma
development are being researched.
Q/A
What are the risk factors for
developing a melanoma?
• Accumulated exposure to UV radiation
• People are exposed to the majority of life-time UV radiation
before the age of 21.
• Exposure includes time spent in direct sunlight during sport,
occupation and leisure activities
• Both UVA and UVB, artificial and natural UV radiation
accumulate to cause DNA damage.
• Thus the incidence of melanoma increases with age
• Ethnicity
• Irish and Scottish descents
• Individuals with fair skin, multiple freckles and likely to burn
are at an increased risk of melanoma.
• Previous melanoma
Q/A
What are the Fitzpatrick skin
types?
•
•
•
•
•
•
Type I (very white or freckled) - Always burn
Type II (white) - Usually burn
Type III (white to olive) - Sometimes burn
Type IV (brown) - Rarely burn
Type V (dark brown) - Very rarely burn
Type VI (black) - Never burn
What type are YOU?
Q/A
If I am concerned that a patient’s
skin lesion is a melanoma what do
I do?
• Referral: Clinician’s with the most experience in
assessing patients with melanoma are the most
likely to make the correct clinical diagnosis
• Diagnosis: Gold Standard method is a
microscopic examination of the specimen. A
section of the specimen (biopsy) can be
removed from the skin and sent to a pathologist
• The location of the lesion may warrant the need
for a plastics or general surgeon to remove the
lesion.
Q/A
What types of biopsies are
available?
• Shave:
• Punch:
• Excisional:
Q/A
What are the pathologic features of
a melanoma?
• Cellular atypia: cancerous melanocytes have
atypical cellular features compared to normal
melanocytes, such as:
• Increased nuclear:cytoplasm ratio
• Found migrating in throughout the layers
• Nests: atypical melanocytes are usually found in
nests suggesting uncontrolled growth
• Lymphocytic infiltrate: the presence of immune
cells suggests the attempt of an immune
response to a malignancy
Q/A
What does a pathology report
reveal about a melanoma?
• Macroscopic description of specimen
• Microscopic description providing exact
measurements, cellular observations and
staining results including:
»
»
»
»
Atypia, melanocytic nests, lymphocytic infiltrate
Type of melanoma
Breslow’s depth, Clark’s level
DIAGNOSIS and RECOMMENDATON
Q/A
What is meant by Breslow’s depth
and Clark’s level?
• Breslow’s depth is the most important prognostic factor for a
melanoma. It is the measurement in mm of how much the
melanoma invades the dermis. Thin melanomas have a Breslow’s
depth less than 1mm, thick melanomas invade greater than 4mm.
• Clark’s level is slightly different than Breslow’s depth, it identifies the
deepest layer of the dermis where the melanoma is located:
–
–
–
–
–
Level I: Contained within the epidermis
Level II: Penetration into papillary dermis
Level III: Through papillary dermis to reticular dermis
Level IV: In the reticular dermis
Level V: Into subcutaneous tissue
Clark’s level matters in comparing melanomas of the eyelid to the palm
because of the difference in thickness of certain layers.
Q/A
How likely is it for the melanoma to
recur and what is the
management?
• Local recurrence – within close proximity to
surgical scar from primary melanoma.
• Breslow’s depth is directly associated with risk of
recurrence
• <5% of melanoma patients develop recurrence,
the majority of whom will likely die of this
disease.
• Mgmt: surgical resection with increased margins,
possible systemic treatments (i.e. INF-alpha). Q/A
Where does a melanoma
metastasize too?
• Sites of Metastases:
– Skin/lymph nodes 42%
– Lung 18%
– Liver 14%
– Brain 12%
– Bone 11%
– Intestine 1%
– Other <2%
Q/A
How do I know if the melanoma
has metastasized?
• Hx may indicate symptoms of extended
disease.
• Px should include assessment of the skin,
lymph nodes, respiratory and GI systems.
• Diagnostic tests include sentinel node
biopsy (SNB), CXR, CT, Liver function
tests.
Q/A
What is a sentinel node biopsy
(SNB)?
• A SNB is a procedure performed by some plastic
surgeons and surgical oncologists
• Ink is injected into the site of the melanoma and
migrates up the lymphatic track
• SNB identifies the “draining” lymph nodes most
likely to encounter melanoma metastatic cells
• If the melanoma has spread through the
lymphatic track the SNB should be the first site
of metastases
• A negative SNB often declares no mets at that
time.
Q/A
What are the treatments for a
melanoma case that has not
metastasized?
• Thin melanomas are completely excised
with appropriate “cancer-free margins”
based upon location and depth of
penetration.
• Cases with a melanoma of a Breslow’s
depth >1mm also have a SNB performed
• A negative SNB and no further signs of
mets warrants regular follow up on
excision and then annual skin exams.
Q/A
What are the treatments for a
melanoma case that has
metastasized to lymph nodes?
• If the sentinel node returns with metastatic
melanoma, the remaining lymphatic drainage is
removed.
• Again, the lesion is locally re-excised with
appropriate margins based upon location and
depth of penetration.
• Regular follow-up after surgery is warranted
• Refer to oncologist to discuss patients concerns
and future risks and options with regards to
potential metastasis and medical treatment
Q/A
What are the treatments for a
melanoma case that has
metastasized to other organs?
• Adjuvant Therapy may include immune
modulation with interferon alpha, or
chemotherapies such as DTIC
• There are numerous clinical trials.
• Response rates remain dismal at 10-20%.
• Radiation therapy may be helpful in those
patients requiring palliation.
Q/A