Melanoma
David A . Jansen
Chief Division Plastic Surgery
Tulane University
CC: “I have a lesion on my leg”
• HPI: 25 yo Irish male who presented to
clinic with a lesion on his leg. Pt stated he
wasn’t sure how long it has been there
“probably a couple of months.” He
reported it getting bigger and changing
color since he first noticed it. It also had
developed an ulcer associated with it.
History
• PMH: multiple blistering sunburns as a
teenager
• PSH: RIH repair as child
• Allergies: PCN
• Meds: none
• Social: Lifeguard, EtOH occasional,
Tobacco denies, illicit +THC
• FH: mother: melanoma, HTN
PE
•
•
•
•
•
•
Gen: A & O x3, NAD
HEENT: PERRL, EOMI, MMM
NECK: no lymphadenopathy
Lungs: CTAB
CV: S1S2 no mrg, no edema
ABD: +BS, soft, NT, ND, no rebound, no
guarding
• Ext: warm, dry, 2+radial pulses
• Neuro: CN II-XII intact
• Skin:
PE
Labs
•
•
•
•
•
•
•
•
•
•
WBC: 8.6
HBG: 14.5
HCT: 43.2
PLT: 285
Na: 140
K+: 4.3
Cl: 102
CO2: 25
BUN: 16
Cr: 0.7
Differential Diagnosis?
What to do next?
Biopsy Results
• Superficial spreading melanoma
• Breslow Depth: 2.5mm
• Ulceration present
Now What?
Surgery
• WLE with 2 cm margins and SLNB
• Results: negative margins, SLNB neg
Melanoma
Facts
• Most commonly diagnosed malignant tumors in US are
cutaneous neoplasms
• Most common skin cancers Basal CellCancer,
Squamous Cell Cancer, and Melanoma
• Melanoma accounts for 4% of skin cancer diagnosis
• 75% of skin cancer deaths
• 48,000 melanoma related deaths occur worldwide per
year
• Incidence of melanoma in Caucasians has tripled
between 1980 and 2003
• 5th most common cancer in males, 7th in females
• Most common on women on their legs; and males on
their back
Epidemiology
•
Life time risk: 1 in 39
Caucasian males, 1 in 58
Caucasian females
• Incidence rates
increasing most rapidly in
older people
• Overall trend is increased
diagnosis at earlier stage
• Mortality has declined for
those 20 to 44 and
increased in men over
age 65
Risk Factors
• UV light: strongest association for intermittent exposure
and sunburn in adolescence and childhood
– an analysis of more than 20 epidemiological studies indicates
that people who begin using tanning devices before age 30 are
75% more likely to develop melanoma.
• Phenotypic traits: fair complexion, inability to tan,
blue/green eyes, blonde/red hair, freckling
• Familial: 10%, multiple genes involved, ex: xeroderma
pigmentosa (AR), Familial atypical multiple-mole
melanoma syndrome (CDKN2)
• Atypical nevi: 3 to 20 fold increase risk, ex: giant
congenital nevus, greater than 100 nevi
• Immunosuppression
Classification
• Superficial spreading: is the
most common of the
melanomas (70%). It usually
occurs in middle age, but may
occur in younger people. It can
assume many shapes, and
have a variety of colors,
though there is usually a
reddish hue
• Lentigo maligna (10-15%):
usually occurs in older people
(>6th decade) and occurs in
chronically sun exposed areas,
most commonly on the face.
Hutchinson Freckle This type
carries the best prognosis
Classification
• Acral-lentiginous
melanoma (5%) is most
frequent in blacks and
Asians. The most
common site is the
plantar surface of the
foot; may be subungual
• Nodular melanoma
(15%)most often occurs
in middle age and is more
frequent in males. It is
usually dome shaped and
may ulcerate. Typically
carries the worst
prognosis
Classification
• Desmoplastic: frequently mistaken for a
scar; pale and fleshy
• In-transit metastases: lesions in the skin
greater than 2 cm from primary lesion,
arise from cells in lymphatics; poor
prognosis
Growth Phases
Horizontal (radial): more indolent, typically cured by surgical incision
alone
Vertical: have increased metastatic potential; vertical growth phase
melanomas may arise from radial growth phase or de novo,
nodular melanoma have most vertical phase
Pathophysiology
Five stages of tumor progression have been suggested:
–
–
–
–
–
Benign melanocytic nevi
Melanocytic nevi with architectural and cytologic atypia (dysplastic
nevi)
Primary malignant melanoma, radial growth phase
Primary malignant melanoma, vertical growth phase
Metastatic malignant melanoma
Clinical Diagnosis
• A: asymmetry- one half of lesion doesn’t match
the other
• B: border irregularity-ragged, notched, fuzzy
• C: color-not uniform
• D: diameter- greater than 6 mm
• E: enlargement/evolution
• Nodular
– Elevated
– Firm
– growing
Diagnosis
• Histopathology necessary for diagnosis
– Melanoma markers: S-100, Melan-A, HMB-45
• Initial biopsy: excisional biopsy preferred with 12 mm of normal appearing skin, orient the
incision along langer’s line of stress, or parallel
to long axis of extremity
• Larger lesions: punch or incisional biopsy, not as
accurate because the thickest part of the lesion
may not be the part sampled.
Breslow Depth
• Total vertical height of lesion
• Used to predict prognosis and determines
excisional margins
Breslow Thickness
Approximate 5 year survival
<1 mm95-100%
1 - 2 mm80-96%
2.1 - 4 mm60-75%
>4 mm50%
Excisional Margins
In situ
<1.0mm
1.1-2mm
>2.0
0.5-1 cm
1 cm
1-2 cm
2 cm
Clark’s Level
•
•
•
•
•
•
•
describes the level of anatomical
invasion of the melanoma in the
skin
Five anatomical levels, and higher
levels have worsening prognostic
implications
1. Melanoma confined to the
epidermis
2. Invasion into the papillary
dermis
3. Invasion to the junction of the
papillary and reticular dermis
4. Invasion into the reticular
dermis
5. Invasion into the subcutaneous
fat
Prognosis
•
•
•
•
•
•
•
•
Tumor thickness in millimeters
depth related to skin structures (Clark level)
type of melanoma
presence of ulceration
presence of lymphatic/perineural invasion
presence of tumor-infiltrating lymphocytes
presence of satellite lesions
presence of regional or distant metastasis
Surgery
• Wide local excision based on Breslow depth
• Sentinel lymph node biopsy should be preformed on all
patients with a Breslow depth of 1mm or greater
• A Breslow depth of 0.75-1.0mm may be considered for
SNLB based on presence of ulceration, high mitotic rate
• Use both isosulfan blue and radiolabeled colloid for
SLNB
• If the sentinel lymph node is negative there is a 96%
chance that the rest of the nodes are negative
• If positive, a regional lymphadenectomy is indicated, and
consider additional metastasis
Adjuvant Therapy
• Interferon-alpha2b: improve disease free and overall
survival rates in pts with stage IIb or III disease
• IL-2 for stage IV disease
• Ipilimumab: increase in median survival from 6.4 to 10
months in patients with advanced melanomas treated
with the monoclonal antibody, versus an experimental
vaccine
• Vaccine trials for local 1.5-4mm
• Radiation: typically used for palliation of bone pain or
brain metastasis, may reduce rate of local reoccurance
but not survival
• Chemotherapy: not very useful, reports of isolated
hyperthermic limb perfusion to treat in transit metastasis
of extremities using TNF
Staging Work-Up
• Potential to metastasize to any organ: skin,
subcutaneous tissue, lung, liver, brain, bone
• All stages typically get LDH and CXR
• LDH tests are often used to screen for
metastases, although many patients with
metastases (even end-stage) have a normal
LDH; extraordinarily high LDH often indicates
metastatic spread of the disease to the liver
• Typically preformed for stage III and IV
– CT
– PET
– MRI brain
Staging
Stage 0: Melanoma in Situ (Clark Level I), 99.9% Survival
Stage I/II: Invasive Melanoma, 85-99% Survival
-T1a: Less than 1.00 mm primary tumor thickness, w/o Ulceration and
mitosis < 1/mm2
-T1b: Less than 1.00 mm primary tumor thickness, w/Ulceration or mitoses
≥ 1/mm2
-T2a: 1.00-2.00 mm primary tumor thickness, w/o Ulceration
Stage II: High Risk Melanoma, 40-85% Survival
-T2b: 1.00-2.00 mm primary tumor thickness, w/ Ulceration
-T3a: 2.00-4.00 mm primary tumor thickness, w/o Ulceration
-T3b: 2.00-4.00 mm primary tumor thickness, w/ Ulceration
-T4a: 4.00 mm or greater primary tumor thickness w/o Ulceration
-T4b: 4.00 mm or greater primary tumor thickness w/ Ulceration
Stage III: Regional Metastasis, 25-60% Survival
-N1: Single Positive Lymph Node
-N2: 2-3 Positive Lymph Nodes OR Regional Skin/In-Transit Metastasis
-N3: 4 Positive Lymph Nodes OR Lymph Node and Regional Skin/In Transit
Metastases
Stage IV: Distant Metastasis, 9-15% Survival
-M1a: Distant Skin Metastasis, Normal LDH
-M1b: Lung Metastasis, Normal LDH
-M1c: Other Distant Metastasis OR Any Distant Metastasis with Elevated
LDH
Surveillance
• Primary objective to identify potentially curable
locoregional recurrences and second primary
cancers
• Stage I and II: most locoregional reoccurrences
• Stage III: systemic recurrences more common
• Most reoccurrences caught by PE
• Stage IA recommend detailed medical history
and PE every 6 to 12 months
• Stage IB to III history and PE every 3 to 6
months for 3 years, every 4 to 12 mo for 2 years
• Order additional studies based on symptoms
Resources
• Greenfield’s Surgery
• The Washington Manuel of Surgery