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 PhasesHorizontal (radial): more indolent, typically cured by surgical incision

aloneVertical: have increased metastatic potential; vertical growth phase

melanomas may arise from radial growth phase or de novo, nodular melanoma have most vertical phase

PathophysiologyFive 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 1-2 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 Excisional Margins

Approximate 5 year survival In situ 0.5-1 cm

<1 mm95-100% <1.0mm 1 cm

1 - 2 mm80-96% 1.1-2mm 1-2 cm

2.1 - 4 mm60-75% >2.0 2 cm

>4 mm50%

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

StagingStage 0: Melanoma in Situ (Clark Level I), 99.9% SurvivalStage 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