no slide title · mini-symposium cutaneous oncology ... department of dermatology & cutaneous...
TRANSCRIPT
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Neil Alan Fenske, MD, FACP
MINI-SYMPOSIUM
Cutaneous Oncology-Melanoma
•Recognizing Melanoma – It Saves Lives!
•You’ve Diagnosed Melanoma – Now What?
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Neil Alan Fenske MD, FACPProfessor & Endowed Chair
Department of Dermatology & Cutaneous SurgeryProfessor
Department of Cell Biology & Pathology
Department of Oncologic Sciences
University of South Florida Morsani College of Medicine
Senior Member
Cutaneous Oncology Program
Moffitt Cancer Center
Tampa, Florida
CUTANEOUS ONCOLOGY: MELANOMA
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Recognizing Melanoma-It Saves Lives!
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Melanoma: A Mysterious Disease!
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Melanoma: Metastasis Does Occur!
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Melanoma: Lifetime Risk
Lifetime Risk of an American Developing Invasive Melanoma
Rigel DS et al. J Am Acad Dermatol 1996;34:839-47
Highest: Old white males
Lowest: Young black femalesHall HI et al.J Am Acad Dermatol 1999;40:35-42
ACS: 2017 1 in <50 ( ~2.4% overall lifetime risk)
Males: 1 in 33
Females: 1 in 52
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Melanoma Risk: Racial & Ethnic Groups
• White Americans have the highest risk of developing melanoma in both men & women
• Lifetime risk for an American
1 in 40 for white Americans (~2%) ♂ > ♀
1 in 1,000 for African Americans (~0.1%)
1 in 700 for Asian/Pacific Islanders (~0.15%)
1 in 200 for Hispanic/Latinos (~0.5%)
• A person’s specific risk may vary, depending on his or her individual risk factors
American Cancer Society 2017
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From Siegel, et al. Cancer Statistics, 2018.
CA Cancer J Clin 2018;68:7-30
Ten Leading Cancer Types for the Estimated New Cancer Cases by Sex, 2018
#5
#6
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Annual Age-Adjusted Cancer Incidence Rates for Selected Cancers by Sex, 1975 to 2014
From Siegel, et al. Cancer Statistics, 2018.
CA Cancer J Clin 2018;68:7-30
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Incidence Trends for Melanoma by Age and Sex, 1992 to 2012
From Siegel, et al. Cancer Statistics, 2016.
CA Cancer J Clin 2016;66:6-30
(Not updated in 2017 or 2018)
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MELANOMA
2018 ACS Incidence Predictions178,560 new cases of melanoma in the US predicted for 2018
91,270 invasive melanoma cases
7,940 cases predicted for Florida*
87,290 melanoma in situ cases
9,320 deaths predicted for 2018
* Second-most cases of any state in the US after California,
(9,830); New York third (4,920); Texas fourth (4,440)
Siegel et al, CA Cancer J Clin 2018;68:7-30
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MELANOMA
2018 Predictions vs 2017
More new cases, but fewer deaths predicted for 2018
91,270 invasive cases + 4,160
74,680 melanoma in situ cases +12,610
7,940 cases predicted for Florida + 330
9,320 deaths predicted for 2018 * - 410
(+): Increase compared to 2017 predictions
(-): Decrease compared to 2017 predictions
* Down 810 (8.0%) from 2016 peak of 10,130 deaths
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MELANOMA
Incidence Predictions
Adolescents and Young AdultsCancers in adolescents (aged 15 to 19 years) differ somewhat from those in children in terms of type and distribution. For example, brain and other nervous system tumors (21%) (more than one-half [58%] of which are benign/borderline malignant) and lymphoma (20%) are equally common, and there are almost twice as many cases of Hodgkin lymphoma as non-Hodgkin lymphoma. Leukemia is third (13%), followed by germ cell and gonadal tumors (11%) and thyroid carcinoma (11%).
Skin Melanoma accounts for 4% of the cancers in adolescents
Siegel et al, CA Cancer J Clin 2018;68:7-30
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MELANOMA
Future Incidence Predictions
Comparing predictions in US for 2015 to 2020 & beyond
• 2020: 111,000 invasive cases +37,130 (50%↑)
• 2030: 151,000 invasive cases +77,130 (>2x ↑)
By 2030, melanoma will be the fifth most common cancer in the
US behind breast (294,000), prostate (228,000), lung (225,000),
and thyroid (183,000)
+ = increase compared to 2015 predictions
Rahib et al, Cancer Res 2014;74:2913-21 Siegel et al, CA Cancer J Clin 2015;65:5-29
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MELANOMA
Future Incidence PredictionsWhat do they mean for us?
• Potentially dramatic increases in the number of new cases over
the next 15 years – a doubling of cases nationwide
• Most will likely have localized disease, & occur increasingly in
an elderly population, but probably many more pediatric cases
as well
• Patients with metastatic melanoma will live longer & require
more follow-up due to new treatments
• We will need to be prepared for more volume & more survivors
than ever before!
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MELANOMA
Stage At Diagnosis By Race
Siegel et al, CA Cancer J Clin 2018;68:7-30
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MELANOMA
5 Year Survival Predictions By Race
Siegel et al, CA Cancer J Clin 2018;68:7-30
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Melanoma: Value of Early Diagnosis
Melanoma 5 year survival
All cases 92%
Localized 98%
Lymph nodes 62%
Metastatic 16%
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Melanoma: General
TRENDS IN SURVIVAL
92%!
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Melanoma: Site Predilection• Most common sites based on sex
Men: upper back>chest Women: lower legs>back
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• Greater near equator (except ocular)
• Uncommon in African Americans
• Common in xeroderma pigmentosum
• Induced in mice (carcinogen + UVL)
• Rare doubly clothed areas
• Periodic intense exposure (SSM, NM)
• Chronic cumulative exposure (LMM)
Melanoma: Relationship to UVL
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Melanoma: Risk Factors
• # of moles (>50) & size (> 5mm)
• # of atypical moles (>5)
• Congenital moles
• Personal Hx of dysplastic nevi &/or melanoma
• Family Hx melanoma
• Dysplastic nevus syndrome
• Genetic markers (e.g. CDNK2A mutations)
• DNA repair defects (e.g. xeroderma pigmentosa)
• Immunosupppression
• Ultraviolet exposure
• Childhood sunburns
• Intermittent sun burning in unacclimatized fair skin
• Equatorial latitude
• Fair skin (types I-II)
• High socioeconomic status
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Melanoma: Characteristics
• ABCD & E’s of Melanoma:
A = Asymmetry
B = Border irregularity
C = Color variegation
D = Diameter > 6 mm
E = Evolution
Friedman RJ et al. Cancer J Clin 1985; 35:130-151
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Melanoma: Characteristics
• Signs & Symptoms:
Pruritus
Pain
Bleeding
Ulceration
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Melanoma: Characteristics
Flag sign
Plus variations of brown & black
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• Lentigo maligna 5%
• Superficial spreading 70%
• Nodular 15%
• Acral & rare vareities 10%
Melanoma: Clinical Varieties
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Melanoma: Biphasic Growth Pattern
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• Incidence: 5%
• Median age: 70
• Growth:
Primarily radial, very slow
• Location:
Face, neck, arms, hands
• Exposure:
Chronic cumulative
Melanoma: Clinical VarietiesLentigo Maligna Melanoma
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• Incidence: 70%
• Median age: 50
• Growth:
Primarily radial, slow
Many arise in nevi
• Location:
Males: trunk
Females: legs
• Exposure:
Periodic intense
Melanoma: Clinical VarietiesSuperficial Spreading Melanoma
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Melanoma: Clinical Varieties Nodular Melanoma
• Incidence: 15%
• Median age: 50
• Growth:
Primarily vertical, rapid
• Location:
Males: trunk
Females: legs
• Exposure:
Periodic intense
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Melanoma: Clinical Varieties Acral Lentiginous Melanoma
• Incidence: 10%
Principal melanoma in
African Americans and
Asians
• Median age: 65
• Growth:
Primarily radial, slow
• Location:
Palms/soles, subungual
• Exposure:
None
Hutchinson’s sign
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Melanoma: Rare Clinical VarietiesAmelanotic Melanoma
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Melanoma: Rare Clinical VarietiesDesmoplastic Melanoma
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Moles as Precursor Lesions of Melanoma
• Reports of association between 10% - 50%
• Skender-Kalnenas¹ et al studied 289 cases MM
51% associated with a nevus
– 56% atypical (dysplastic)
– 41% common acquired
– 3% congenital
• Friedman studied 612 cases MM
35% associated with a nevus
– 86% atypical (dysplastic)
– 14% common acquired
– <1% congenital
¹ Skender-Kalnenas TM et al. J Am Acad Dermatol 1995;33:1000-7
²Friedman R NYU personal communicationj
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Moles as Precursor Lesions of Melanoma
• Acquired (common) nevi associated with increased risk for melanoma if numerous
80% of all patients have up to 50 nevi
Risk likely increases with > 50 lesions
Nevi on unusual sites (buttocks, feet, ant. scalp) may be precursors
• Atypical nevi are both a “marker” for increased risk for melanoma (on normal skin) & are precursor lesions (low individual risk)
Risk related to total number nevi (common & atypical)
Risk related to personal & family Hx for MM
Prophylactic removal therefore will not prevent development MM
Kanzler MH et al. J Am Acad Dermatol 2001;45:260-276
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Moles as Precursor Lesions of Melanoma
• Congenital nevi can be precursor lesions (1-2.5% newborns)
Histologic growth pattern best indicator (risk if involvement of deep dermis)
Small size (<1.5 cm) --------------------low risk (observation)
Intermediate size (1.5 cm-20 cm) –- intermediate risk (biopsy to assess for depth)
Large size (>20 cm) -------------------- high risk (“wait & watch” not acceptable!)
Kanzler MH et al. J Am Acad Dermatol 2001;45:260-276
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Atypical Moles (AM)
• Synonym: Dysplastic, Clark’s nevi
• Occur in < 10% of American Caucasians
• Sporadic or familial
• Single or multiple
• Cutaneous marker identifying individuals at increased risk
for melanoma
• Risk affected by personal and/or family history of melanoma
Slade J et al. J Am Acad Dermatol 1995; 32:479-94
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Atypical (Dysplastic) Moles
COMMON NEVUS ATYPICAL MOLE
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Atypical (Dysplastic) Moles
COMMON MOLES ATYPICAL MOLES
Distribution Usually sun-exposed areas Unusual areas (buttocks, breast, scalp)
Number 55% adults 10-15 lesions > 2mm;
10-20% > 50 nevi; ~20% none
One to many; AMS (frequently > 50)
Heterogeneous appearance
Behavior Appear after 6-12 months of life;
↑ in size & # childhood/puberty;
Few to 4th decade-then disappear
Appear near puberty;
Dynamic: ↑ or ↓ in atypicality adulthood;
New lesions throughout life
Size Usually < 5 mm Usually > 5mm
Shape &
contour
Round, symmetric, uniform;
Distinct border;
Macular or papular appearance
Irregular with indistinct border;
Macular “shoulder”& slightly papular
“fried egg” for size; Mammillated
Color Uniform: tan to dark brown Variable: tan to dark brown, reddish hue
Kanzler MH et al. J Am Acad Dermatol 2001;45:260-276
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Atypical Mole Syndrome (AMS)
• No universally accepted definition
• Several variants all possessing atypical moles
• Syndrome synonyms: Dysplastic nevus, B-K mole, FAM-M, FAMMM, Clark’s nevus and “classic” atypical mole syndrome (CAMS)
• A spectrum of phenotypic expressions:
Lowest risk: patient with one AM & no personal or family history of MM
Highest risk: patient with multiple AM and/or MM & some or all kindred with AM & at least two of whom have MM (FAMMM syndrome)
Slade J et al. J Am Acad Dermatol 1995; 32:479-94
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Familial Atypical Mole and Melanoma Syndrome (FAM-M)
• NIH Consensus Conference definition:
Patient has a large number of melanocytic nevi, often
more than 50, several clinically atypical (AM) & many
variable in size
Patient has history of melanoma in one or more first- or
second-degree relatives
AM display distinctive histopathologic features
• Lifetime risk of developing melanoma approaches 82% in
patients with AM & 2 or more first-degree relatives with
melanoma
NIH Consensus Conference in JAMA 1992; 263:1314-1319
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Atypical Mole Syndrome
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Atypical Mole Syndrome: Relative Risk Kraemer Classification
Kraemer KH & Greene MH: Dermatol Clin 1985;3:225-37
Familial & Sporadic Precursors of Cutaneous Melanoma
RISK 300X!!!
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• Controversial
Aggressive biopsies vs observation?
Excisional vs scallop biopsies (if indicated)?
• Excision (if biopsy positive)
All lesions or only those with severe atypia?
What about lesions with moderate atypia?
Conventional vs deep scallop?
1mm vs 2mm margins?
• Dermatopathologist
What are their skill sets?
Do they “over read” atypia?
Do they make “recommendations” to excise?
Management of “Atypical /Dysplastic Nevi”
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Atypical Mole Syndrome: Monitoring
Total body photography
Probably better for common mole monitoring--lesions not dynamic
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• Blue nevus
• Spitz nevus
• Halo nevus
• “Recurrent” (post-biopsy) nevus
Melanoma Mimickers: Melanocytic Nevi
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Melanoma Mimickers: Blue nevus
• Benign, gray to blue tumor
with melanin deep in dermis
• Spindle & cellular variants
• Most common on head,
neck & back of hand
• Cellular variant rare risk of
transformation to
melanoma (Excise)
Spindle
Cellular
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Melanoma Mimickers: Spitz nevus
• Reddish papule or
nodule in children or
young adult
• Common on head
and neck
• Mimics melanoma
histologically
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Spitz Nevus – Pearl Alert
Beware the adult with a diagnosis of Spitz Nevus!
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Melanoma Mimickers: Halo nevus
• Surrounded by ring of
hypo- or de-pigmentation
• Immunologic reaction to
abnormal nevus
• Common in teenagers
• Associated vitiligo
• Rarely a marker for
melanoma (esp adults)
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Halo Nevus – Pearl Alert
• Beware the adult with a diagnosis of Halo Nevus!
• Perform full skin & eye exam to “look for the melanoma”
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Melanoma Mimickers: Recurrent Nevus
(Pseudomelanoma)
• Recurrence of benign
nevus at site of
incomplete removal
• Residual melanocytes
become hyperactive
producing irregular
pigmentation confined
to scar!
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Melanoma Mimickers: Recurrent Nevus
(Pseudomelanoma)
• Recurrence of benign
nevus at site of
incomplete removal
• Beware: If asymmetry,
poor circumscription,
variegate color esp. if
pigment spreads beyond
scar!
Melanoma
Biopsy site
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Melanoma Mimickers: Recurrent Nevus
(Pseudomelanoma)
• Recurrence of benign
nevus at site of
incomplete removal
• Beware: If asymmetry,
poor circumscription,
variegate color esp. if
pigment spreads
beyond scar!
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Pearl Alert
Beware the lesion that stands out from the rest or
stands alone
The Ugly Duckling!
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Melanoma Mimickers: Non-Melanocytic Nevi
• Seborrheic keratosis
• Solar lentigo
• Lentigo simplex
• Becker’s nevus
• Vascular tumors
• Dermatofibroma
• Pigmented basal cell carcinoma
• Tattoo
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Melanoma Mimickers: Seborrheic keratosis
• Greasy, verrucous keratotic
plaque with “stuck on”
appearance
• Some very black &/or
smooth mimicking
melanoma (BIOPSY)
• When inflamed, mimics
melanoma (BIOPSY!)
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Pearl Alert
Use “scrape test” for
seborrheic keratoses
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Melanoma Mimickers: Solar lentigo
• Present in 90% by age 60
• Uniform, dark brown irregular
macules, frequently clustered
• Sun-exposed sites
• Do not fade in winter
• Mimic lentigo maligna
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Melanoma Mimickers: Lentigo Simplex
• Uniform light brown to black
macule
• Anywhere on body
including mucosa (lips,
genitalia) and nail beds
• Not associated with sun
exposure
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Melanoma Mimickers: Becker’s Nevus
• Unilateral
• Common on shoulders of
young males
• Hypertrichosis common later
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Melanoma Mimickers: Cherry Hemangioma
• Bright red dome-shaped papule
• Some bluish
• Often many lesions
• Associated seborrheic keratoses
• Trunk & proximal extremities
• May bleed mimicking
amelanotic melanoma
• May become infarcted mimicking
melanoma
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Melanoma Mimickers: Pyogenic Granuloma
• Solitary rapidly growing red
friable polyp
• Finger, face and lips on children
and young adults
• Gingiva of pregnant women
• May bleed & mimic amelanotic
melanoma
• ALWAYS BIOPSY!
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Melanoma Mimickers: Venus Lake
• Common on ears & lips
• Actinically damaged skin
• Blanches with diascopy
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Melanoma Mimickers: Dermatofibroma
• Firm reddish-brown
papule
• Arms & Legs
• Exhibit “Dimple” sign
• Mimics desmoplastic
melanoma-history is
everything!
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Melanoma Mimickers: Pigmented BCC
• Pearly, translucent
border when surface
stretched
• Specks of pigment
• Slightly more
common in Hispanics
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Melanoma Mimickers: Tattoo Pigment
History is the key
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Dermatoscope
• A hand-held microscope that provides
detailed visualization of the structures
of the epidermis, the dermal –
epidermal junction, and the papillary
dermis not visible to the naked eye.
• Powerful tool to aid the diagnosis of
early melanomas
• Helps differentiate benign from
malignant pigmented and non-
pigmented lesions of the skin
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Pigmented Lesions:
When Should You Perform A Biopsy?
• Onset after age 40
• Irregular border
• Asymmetry
• Irregular pigment esp. black
• Colors of “American flag”
• Change in size
• Pain, irritation, pruritus
• Bleeding, crusting “Infection”
• When you don’t know what it is!
• INTUITION!
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Melanoma: Biopsy Technique
• Goal is complete removal for thorough
histological evaluation & microstaging
If high index of suspicion
– Excisional biopsy whenever possible
– Punch biopsy of the darkest & thickest
area if too large or excision not feasible
If low index of suspicion
– Deep “scallop” or “saucerization”, not
tangential or “shave”
– Incumbent on provider to get below lesion!
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Melanoma: Biopsy Technique
Attempt complete removal,
by deep “scallop” technique
2mm margins -----------------
provides dermatopathologist
better assessment of entire
lesion & growth pattern
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Melanoma: Biopsy Technique
Exception: Punch biopsy
can be used to take a
portion of a large lesion or
a very small lesion (in
effect an excision) if
clinically conventional
excision not feasible
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Pearl Alert
Exception: May
need several
biopsies if lesion is
large and ill-defined
& excision not
feasible
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Clark Breslow
Melanoma: Microstaging
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Pathology Report - What’s Important
• Tumor thickness (Breslow)
• Ulceration
• Mitoses
• Margin involvement
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You’ve Diagnosed Melanoma-
Now What?
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Initial Diagnostic Work-Up
• Validate Adequate Biopsy (Need
to be below the base of the lesion-
for prognostic purposes; however
doesn’t affect ultimate outcome!)
• Full Skin Exam
• Complete ROS
• Palpation of lymph node basins
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• The extent of the staging work-up & treatment should be defined
by the extent of local & regional disease
• Focus on meaningful assessment of primary & nodal disease
Primary lesion:
Thin or thick
Regional nodal involvement:
Microscopic or macroscopic
Surgical Therapy of MelanomaIndividualized treatment
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Disease-free survival stratified by SLN status
Gershenwald et al. J Clin Oncol 1999
SLN status is the most
powerful independent
prognostic factor
predicting survival;
individualizing treatment
Reasons to Perform SLNB Improved Staging & Prognosis
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Sentinel Node Hypothesis
• Concept:
Melanoma metastasis
proceeds in an orderly
manner via lymphatics
The sentinel node reflects
status of the remaining
lymphatic basin
“Skip metastases” rarely occur
(<3%)
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Sentinel Node Hypothesis
• Conclusion: If sentinel
node is tumor free, the
remaining lymphatic
basin will also be tumor
free
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Sentinel Lymph Node BiopsyClinical Example
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Surgical Therapy of MelanomaIndividualized treatment
TUMOR THICKNESS SURGERY
In Situ 0.5-1.0 cm margins; No SLNB²
≤1.0 mm 1.0 cm margins; No SLNB³
1.01-2.0 mm 1.0-2.0 cm margins; SLNB
> 2.0 mm 2.0 cm margins; SLNB
+ lymph nodes (Including + SLNB) Complete lymph node dissection
Surgical Guidelines¹
¹Margins can be modified to accommodate anatomic/functional considerations
²For large MMIS, Lentigo maligna type, margins > .5 cm may be necessary to clear:
(consider topical Imiquimod or radiotherapy if + margins and inoperable)
³Consider SLNB selected patients (.76-1.0 mm) e.g. young & high risk histology
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Melanoma: Staging Work-upWhy important?
• Groups patients into similar
prognostic & management
cohorts
• Guides clinician to counsel
patient regarding prognosis &
treatment
• Groups patients into
homogeneous populations for
clinical trials
Johnson TM et al. Arch Dermatol 2004;140:107-113
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Melanoma: Staging Work-upGeneral Information
• There are no data today that demonstrate any significant difference in overall
survival (OS) between asymptomatic & symptomatic stage IV disease!
• Prognosis is dismal--but some patients may benefit from surgical & / or
systemic intervention--that can lead to significant remission
• Quality of life often worsened by asymptomatic detection of stage IV disease
• Detection of occult regional disease may result in higher survival rates
Stage III survival primarily determined by:
– Number of positive nodes
– The microscopic & macroscopic tumor burden in nodes
– The ulceration status of primary lesion
Status of sentinel node therefore becomes critical
Johnson TM et al. Arch Dermatol 2004;140:107-113
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Melanoma: Staging Work-upGuidelines for Care: General
• Foundation of initial workup is thorough history &
physical exam
Examine the primary site, the regional lymphatic
pathways & lymph node basin(s), remainder of skin &
mucus membranes
ROS should be a melanoma-focused
Stage 0, I, II disease– NO routine blood studies
– NO routine imaging studies unless specific signs/symptoms!
– SLNB stage II and IB >.76mm-1mm (ulceration or mitoses)
)
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Melanoma: Staging Work-up
Guidelines for Care: General
• Imaging & Hematologic Testing—Beneficial? Current screening studies lack both high sensitivity & high specificity
Tests have marginal efficacy & not cost-effective for detecting occult disease
False-positive tests are common (15-20%) – lead to more tests, expense, duress
Tests are indicated if ROS or exam abnormal
Beneficial If abnormal; would preclude more extensive surgery (e.g. CLND if SLN +)
Lymph node sonography & Positron Emission Tomography may be most sensitive non-invasive tests to identify small nodal metastases
However, for asymptomatic patients with clinically localized disease--SLNB is the more sensitive & more specific test to detect sub-clinical nodal disease!
Johnson TM et al. Arch Dermatol 2004;140:107-113
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Melanoma: Staging Work-up Guidelines
Asymptomatic Patients
MELANOMA STATUS NCCN (Version1.2017)
Local disease In Situ (S0) No routine tests
Local disease <1.0 mm (SI) No routine tests
No SLNB*
*Consider SLNB lesion ( 0.75-1.0 mm) if ulceration or mitotic rate > 1/mm²
Local disease ≥1.0 mm (SII) No routine tests
SLNB if clinically neg nodes; if equivocal nodal basin ultrasound with biopsy
of abnormal nodes before SLNB
Regional disease (S III) SLNB +: Consider CT or PET/CT (staging)
Clinically + nodes: Confirm histologically (FNA or core, incisional, or
excisional biopsy)
Baseline CT or PET/CT (staging)
If + inguinofemoral nodes must do pelvic CT
Distant disease (S IV) Confirm histologically (FNA or core, incisional, or excisional biopsy)
Baseline chest/abdominal/pelvic CT with or without PET/CT
Brain MRI or CT with contrast should be performed
Serum LDH (not sensitive marker for metastatic disease-reflects tumor
burden-prognostic value)
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• Routine laboratory tests and imaging studies not
required if melanoma <4 mm
• CXR and LDH optional
• Follow-up for > 4.0 mm or +LN is the same
Baseline LDH, CXR and CT Abdomen
Repeat only if symptomatic
• Full skin exam Q 3 to 6 months
• Patient education on skin and LN self-examination
• Yearly ophthalmologic and gynecologic exams
Malignant Melanoma:Follow-Up “Bottom Line”
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Arrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrgh!
YMKG
Gasparilla