no slide title · mini-symposium cutaneous oncology ... department of dermatology & cutaneous...

Neil Alan Fenske, MD, FACP

MINI-SYMPOSIUM

Cutaneous Oncology-Melanoma

•Recognizing Melanoma – It Saves Lives!

•You’ve Diagnosed Melanoma – Now What?

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

Recognizing Melanoma-It Saves Lives!

Melanoma: A Mysterious Disease!

Melanoma: Metastasis Does Occur!

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

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

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

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

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)

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

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

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

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

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!

MELANOMA

Stage At Diagnosis By Race

Siegel et al, CA Cancer J Clin 2018;68:7-30

MELANOMA

5 Year Survival Predictions By Race

Siegel et al, CA Cancer J Clin 2018;68:7-30

Melanoma: Value of Early Diagnosis

Melanoma 5 year survival

All cases 92%

Localized 98%

Lymph nodes 62%

Metastatic 16%

Melanoma: General

TRENDS IN SURVIVAL

92%!

Melanoma: Site Predilection• Most common sites based on sex

Men: upper back>chest Women: lower legs>back

• 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

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

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

Melanoma: Characteristics

• Signs & Symptoms:

Pruritus

Pain

Bleeding

Ulceration

Melanoma: Characteristics

Flag sign

Plus variations of brown & black

• Lentigo maligna 5%

• Superficial spreading 70%

• Nodular 15%

• Acral & rare vareities 10%

Melanoma: Clinical Varieties

Melanoma: Biphasic Growth Pattern

• Incidence: 5%

• Median age: 70

• Growth:

Primarily radial, very slow

• Location:

Face, neck, arms, hands

• Exposure:

Chronic cumulative

Melanoma: Clinical VarietiesLentigo Maligna Melanoma

• 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

Melanoma: Clinical Varieties Nodular Melanoma

• Incidence: 15%

• Median age: 50

• Growth:

Primarily vertical, rapid

• Location:

Males: trunk

Females: legs

• Exposure:

Periodic intense

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

Melanoma: Rare Clinical VarietiesAmelanotic Melanoma

Melanoma: Rare Clinical VarietiesDesmoplastic Melanoma

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

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

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

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

Atypical (Dysplastic) Moles

COMMON NEVUS ATYPICAL MOLE

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

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

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

Atypical Mole Syndrome

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!!!

• 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”

Atypical Mole Syndrome: Monitoring

Total body photography

Probably better for common mole monitoring--lesions not dynamic

• Blue nevus

• Spitz nevus

• Halo nevus

• “Recurrent” (post-biopsy) nevus

Melanoma Mimickers: Melanocytic Nevi

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

Melanoma Mimickers: Spitz nevus

• Reddish papule or

nodule in children or

young adult

• Common on head

and neck

• Mimics melanoma

histologically

Spitz Nevus – Pearl Alert

Beware the adult with a diagnosis of Spitz Nevus!

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)

Halo Nevus – Pearl Alert

• Beware the adult with a diagnosis of Halo Nevus!

• Perform full skin & eye exam to “look for the melanoma”

Melanoma Mimickers: Recurrent Nevus

(Pseudomelanoma)

• Recurrence of benign

nevus at site of

incomplete removal

• Residual melanocytes

become hyperactive

producing irregular

pigmentation confined

to scar!

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

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!

Pearl Alert

Beware the lesion that stands out from the rest or

stands alone

The Ugly Duckling!

Melanoma Mimickers: Non-Melanocytic Nevi

• Seborrheic keratosis

• Solar lentigo

• Lentigo simplex

• Becker’s nevus

• Vascular tumors

• Dermatofibroma

• Pigmented basal cell carcinoma

• Tattoo

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!)

Pearl Alert

Use “scrape test” for

seborrheic keratoses

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

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

Melanoma Mimickers: Becker’s Nevus

• Unilateral

• Common on shoulders of

young males

• Hypertrichosis common later

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

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!

Melanoma Mimickers: Venus Lake

• Common on ears & lips

• Actinically damaged skin

• Blanches with diascopy

Melanoma Mimickers: Dermatofibroma

• Firm reddish-brown

papule

• Arms & Legs

• Exhibit “Dimple” sign

• Mimics desmoplastic

melanoma-history is

everything!

Melanoma Mimickers: Pigmented BCC

• Pearly, translucent

border when surface

stretched

• Specks of pigment

• Slightly more

common in Hispanics

Melanoma Mimickers: Tattoo Pigment

History is the key

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

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!

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!

Melanoma: Biopsy Technique

Attempt complete removal,

by deep “scallop” technique

2mm margins -----------------

provides dermatopathologist

better assessment of entire

lesion & growth pattern

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

Pearl Alert

Exception: May

need several

biopsies if lesion is

large and ill-defined

& excision not

feasible

Clark Breslow

Melanoma: Microstaging

Pathology Report - What’s Important

• Tumor thickness (Breslow)

• Ulceration

• Mitoses

• Margin involvement

You’ve Diagnosed Melanoma-

Now What?

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

• 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

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

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%)

Sentinel Node Hypothesis

• Conclusion: If sentinel

node is tumor free, the

remaining lymphatic

basin will also be tumor

free

Sentinel Lymph Node BiopsyClinical Example

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

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

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

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)

)

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

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)

• 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”

Arrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrgh!

YMKG

Gasparilla