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Melanoma
Edward Buckingham, M.D.
Combined Plastics ConferenceSeptember 6, 2000
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Melanoma - Outline
General statistics and development Risk factors and patient assessement
Pathology and prognosis Work-up and staging
Surgical treatment
Lymph node controversy/sentinel node
Adjuvant therapy
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Melanoma - Data
Incidence increase fastest Mortality increase 2nd only to lung
5th most prevalent, incidence 7%/yearincrease
5% skin cancer, 75% skin cancer death
1/75 in 2000, 1/1500 in 1935
20% H&N, 51% facial, 26% scalp, 16%
neck, 9% ear
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Development of Nevi
Melanocytes dendritic, neural crest, basal cell layer
synthesis of melanin
1/10 to keratinocytes
hyperplasia- tanning/lentigines, increased ratio
Nevus transformation poorly understood
dendritic- rounded
no longer lentigionous pattern- nests
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Development of Nevi
Junctional nevi nests along dermal-epidermal junction
Compound nevi
invade dermis, first as nests then cords and
single cells
Dermal nevi junctional component lost
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Evolution of Nevi
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Melanocyte Hyperplasia
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Junctional Nevi
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Compound Nevi
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Dermal Nevi
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Developement of Melanoma
Questionable benign melanocytes
progressive hyperplasia/dysplasia
Radial growth
in epidermis, lines of radii, no expansive nests
or nodules slow unrestricted , no metastatic potential
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Development of Melanoma
Vertical growth vertically into dermis
expansive and coalescent nests and nodules
metastatic potential dermal lymphatic and
vascular invasion
Growth patterns biphasic- slow radial months to years- rapid
vertical growth
monophasic- rapid vertical growth only
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Evolution of Melanoma
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Dysplastic Nevi
border melanocytic nevi and malignantmelanoma
clinical resembles malignant melanoma
lentiginous compound nevus, prominent
bridging across rete ridges
aberrant in inter-rete spaces lamellar fibrosis of papillary dermis,
variable lymphoid response
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Dysplastic Nevi
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Dysplastic Nevi
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Types of Melanoma
Acral lentiginous Mucosal melanoma
Superfical spreading melanoma
Lentigo maligna melanoma
Nodular melanoma
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Superficial spreading
most common head and neck, 50% 4th to 5th decade
clinical mixture of brown/tan, pink/white
irregular borders, biphasic growth
irregular nests in epidermis
underlying lymphoid infiltrate
enlarged nests and single cells in all
epidermal layers
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Superficial spreading
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Lentigo maligna
20% of head and neck longest radial growth phase >15 yrs
elderly sun exposed areas
clinical dark, irregular ink spot
contiguous lintiginous proliferation,
dyshesive, variable shape, atrophicepidermis, infundibular basal cell layer of
hair follicles
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Lentigo maligna
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Nodular melanoma
30% of head and neck 5th decade
aggressive monophasic growth
sun-exposed and nonexposed areas
well circumscribed blue/black or nodular
with involution in irregular plaque
downward tumorigenic growth, expand
papillary dermis into reticular dermis
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Nodular melanoma
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Mucosal melanoma
8% head and neck histologic staging little use
local control predicts survival
neck dissection for clinical N+
XRT for histo N+
adjuvant interferon alpha 2-b
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Risk factors
Type I or II skin atypical and congenital nevi
actinic skin changes
history of melanoma
family history of melanoma, atypical nevi
history of significant sun exposure
(blistering)
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Clinical
early, increase in size, change in shape orcolor of pigmented lesion
most common symptom pruritis
late, tenderness, bleeding, ulceration
ABCDEs (asymmetry, border, color,
diameter, elevation, surrounding tissue) Epiluminescence microscopy (ELM)
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Biopsy
excisional biopsy or saucerization if small incisional if large
Depth of biopsy must be to sub-Q fat
if melanoma a second excision must be
performed
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Pathology
diagnosis, tumor thickness in millimeters,margins
histologic subtype, anatomic site, Clark
level, mitotic rate, growth phase, ulceration,regression, lymphocytes, angiolymphatic
spread, neurotropism, microsatellitosis,
precursor lesion
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Prognosis Breslow (thickness in millimeters) strongest
predictor
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Prognosis
Clark level less predictive, thin skin useful
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Prognosis
anatomic site, ulceration, gender, histologictype, nodal disease
head and neck- scalp worse
extremity better trunk
women better men
lymph node + Breslow thickness, ulceration, # pos. nodes
Cohen 10 yr survival # nodes positive
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Work-up
H&P
entire skin, inguinal, axillary, supraclavicular,
H&N nodes,especially primary drainage
brain, bone, GI, constitutional symptoms
palpable nodes FNA
Labs and imaging
vary, CXR to routine CT chest and LFT
H&N CT neck routine
If stage III(regional) or IV (distant) - CT head,
chest, abdomen, pelvis
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Work-up
FDG-PET some use in distant disease
sensitivity 17% in study with SLN biopsy
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Staging-Clark
Level I - in situ at basement membrane Level II - through basement membrane
into papillary dermis
Level III - spread to papillary/reticular
interface
Level IV - spread to reticular dermis Level V - sub-Q invasion
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Staging-Breslow
4.00 mm - thick
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Staging
CS/PS (I, II, III) AJCC- Stage I and II - local, III - regional
IV - distant
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AJCC Staging
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Surgical Treatment
Recommended margins vary Rule of thumb
4mm then 3 cm
All depths to underlying muscle fascia
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Nodal Disease
CS-II remove regional lymphaticsdepending on location of primary and
presence of distant metastasis
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CSI- The Debate
Balch study- nonrandomized 5 and 10 yr survival intermediate thickness
(0.76-3.99) doubled with ELND
5 and 10 yr survival for thin (4.0) no change with ELND
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Balch Study
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CSI - The Debate
Four prospective randomized trials Mayo clinic 3 groups stage I (ELND, delayed,
none) no survival difference, increased
complications if none, criticized not looking atsubgroups to benefit
WHO no survival benefit, criticized no
subgroups, largely extremity lesions in females
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CSI - The Debate
Four prospective randomized trials Balch - no overall 5 yr difference, improved in
patients , 60 yrs with ELND, 1-2 mm tumors,
no ulceration, or both benefited, WHO trunk 1.5 mm or more immediate or
delayed no significant survival benefit, however
was between ELND with occult metastasis andlater developers with delayed LND
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The Debate - PRO ELND
sequential dissemination theory 30% stage I & II occult disease
Once palpable 70-80% distant disease, 10 yr
survival 15-25%, 5 yr 1-2 nodes
micrometastasis 65%
Balchs non-randomized study
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The Debate - CON ELND
randomized trials 70% no occult disease
sequential dissemination only theory
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Balchs recommendations
Three groups local, local plus micro, local plus distant
Thin - 95% cure rate no benefit to ELND
Intermediate - 60% regional, 20% distant,
benefit ELND
Thick - >60% regional, >70% distant, nobenefit
Should consider other factors as well
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Sentinel Node Theory
Essence of debate to identify those withoccult metastasis
Morton- first node in group to receive flow
from tumor site
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SLN - procedure
isosulfan blue injection at tumor site, followchannels to node
studies with ELND 80% sensitivity, specificity
99% preoperative lymphscintigraphy, intra-
operative radiolymphoscintigrapy, and
isosulfan blue dye
69.5% SLN excised blue dye, 83.5% hot,
combined success 96%, location matters
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SLN - Utility
prognostic indicator - study SLN statusmost significant indicator of disease-free
and disease-specific survival
pathology H&E, S-100, HMB-45 limited by # sections
reverse transcription with polymerase chain
reaction (RT-PCR)- peripheral blood and
nodes, (mRNA tyrosinase) 29 ELND 38% path
positive, 66% RT-PCR positive
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Adjuvant Therapy
Radiation high dose (400-500 cGy) bulky, residual,
recurrent, unresectable, ill
lentigo maligna 5 yr cure 80% (disfiguring,debilitating location)
adjuvant- trend toward improved regional
control in N+ dissected necks palliate - especially bony mets
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Adjuvant Therapy
Chemotherapy response 25%, durable control 1%
consider in CSI with >1.5 mm, CSII with WLE,
TND no survival advantage demonstrated
single agent dacarbazine (DTIC)
multiple combinations carmustine, cisplatin,
DTIC, tamoxifen
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Adjuvant Therapy
Immunotherapy unusual behavior, no survival benefit
Interferon
ECOG 1684, >4mm or N+, 6.9 yrs high dose
IFN-alpha-2b, improved disease-free and
overall survival approx. 1 yr. 26% dropout rate
toxicity
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Summary
Incidence and deaths on rise Survival rates increasing due to detection
and thorough treatment
Depth and nodal status most important
prognostic indicators
ELND still debated SLD useful
Other modalities therapy further research
Recommended