(8 a-b) fenske - cutaneous oncology - melanoma 2018.ppt€¦ · 11/05/2018 · lentigo maligna...

Dermatology for the Non-DermatologistMay 30 – June 3, 2018

Neil Alan Fenske, MDCutaneous Oncology - NMSC 1

Neil Alan Fenske, MD, FACP

MINI-SYMPOSIUM

Cutaneous Oncology-Melanoma

•Recognizing Melanoma – It Saves Lives!

•You’ve Diagnosed Melanoma – Now What?

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 malesLowest: Young black females

Hall 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 Predictions

178,560 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




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 Predictions

What 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




MELANOMA 5 Year Survival Predictions By Race


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


• Signs & Symptoms: Pruritus

Pain

Bleeding

Ulceration


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;33:1000-7²Friedman R NYU personal communicationj




• 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


• 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!)


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


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: MonitoringTotal 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!





• Beware: If asymmetry, poor circumscription, variegate color esp. if pigment spreads beyond scar!

Melanoma

Biopsy site



• 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 amelanoticmelanoma

• 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 frommalignant 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!




Attempt complete removal, by deep “scallop” technique 2mm margins -----------------provides dermatopathologist better assessment of entire lesion & growth pattern


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 definedby 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 considerations²For 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




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-upGuidelines 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!


Melanoma: Staging Work-up GuidelinesAsymptomatic 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”

(8 a-b) fenske - cutaneous oncology - melanoma 2018.ppt€¦ · 11/05/2018 · lentigo maligna...

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