Cutaneous Malignant Melanoma

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Cutaneous Malignant Melanoma

• Maria M. Dennison, M.D.
• Vice-President and Medical Director
• RGA International Division
• 21st Congress of the International Committee for
  Life, Disability, and Health Assurance Medicine
• Venice-Italy
• April 2004

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Overview

• Statistics
• Risk Factors
• Precursor-Atypical Mole Syndrome
• New AJCC Staging
• Sentinel Lymph Node Dissection

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STATISTICS

• Lifetime risk of melanoma- 1 in 75
• versus 1 in 1500 in the 1930s
• 5 year Survival Rate - 90
• versus 40 in the 1940s
• Demographics-median age of 40
• Incidence rate varies by country
• Incidence - increasing 5 per year
• Death Rate - increasing 2 per year

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Adopted from Rigel et al, NYU Melanoma
Cooperative Group 2000
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Etiologies

• Immunosuppression
• - defective DNA repair
• - systemic immune alteration (HIV)
  
• Ultraviolet (UV) radiation/sunlight
• Moles
• Family History

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Risk Factors and Sunlight

• Blond or red hair
• Marked freckling of upper back
• 3 or more blistering sunburns prior to age 20
• 3 or more years in an outdoor summer job
• Presence of actinic keratosis
• Malignant melanoma in a first-degree relative

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Sid Seagull-Slip! Slap! Slop!
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Pigmented Nevi

• Sporadic moles
• Early childhood
• 10-45 in number
• lt5 mm
• Few with atypia

• Atypical Moles
• Teens to 20s
• gt100 in number
• 5-8 mm
• Many with atypia

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Benign Pigmented Lesions

• Simple Lentigo
• Junctional Nevus
• Compound Nevus
• Intradermal Nevus
• Seborrheic Keratosis
• Solar Lentigo
• Single atypical mole

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Precursor and Marker

• Dysplastic Nevi/Atypical Moles
• -total number of moles (gt100)
• -number of atypical moles
• -number of family members with AM
• -personal melanoma history

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Grading the Risk of Atypical Mole Syndrome

• A - atypical moles
• - no family history
• B - atypical moles
• - family history of atypical moles
• C - atypical moles
• - personal history of melanoma
• - no family history

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Grading the Risk of Atypical Mole Syndrome
(continued)

• D1 - atypical moles
• - family history melanoma in 1 relative
• D2 - atypical moles
• - family history melanoma in gt1 relative

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Familial Atypical Mole and Melanoma Syndrome
(FAMMS)

• 1 or more 1st or 2nd degree relative with
  melanoma
• Large number of melanocytic nevi
• Atypia
• Specific histological criteria
• Asymmetry
• Subepidermal fibroplasia
• Lentiginous melanocytic hyperplasia

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Clinical Features
ASYMMETRY
COLOR
BORDER
DIAMETER
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Subtypes of Invasive MM

• Superficial Spreading (SSMM)
• - accounts for 70 of melanomas
• - radial growth phase
• -arises in pre-existing nevi
• - multicolored
• Nodular (includes amelanotic melanoma)
• - accounts for 15
• - vertical/ invasive growth phase
• -arises de novo
• - blue-black coloration

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Old Staging System

• 1 - Thin or Intermediate, Node Negative
• 2 - Thick, Node Negative
• 3 -Any thickness, node positive
• 4 - Distant Metastasis

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Journal of Clinical Oncology, Vol 19, No 16
(August 15), 2001
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AJCC Survival Data (1997)

• Tumor thickness
• New tumor cut-off points
• Presence of Ulceration
• Local Recurrence, Satellite and
• In-Transit Metastases
• Number (not size) of positive nodes
• Elevated LDH

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New Criteria for Stages 1 2

• Tumor thickness
• Breslows Scale
• Thin (lt 1 mm)
• Intermediate (1-4 mm)
• Thick (gt4 mm)
• Ulceration
• a no ulceration
• b ulceration present

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New Stages I and 2

• IA - to 1 mm without ulceration (T1a)
• IB - to 1 mm with ulceration, level IV, V (T1b)
• - 1.01-2 mm without ulceration (T2a)
• IIA - 1.01-2 mm with ulceration (T2b)
• - 2.01-4 mm without ulceration (T3a)
• IIB - 2.01-4 mm with ulceration (T3b)
• - gt4.01 mm without ulceration (T4a)
• IIC - gt4.01 mm with ulceration (T4b)

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Surgical Treatment For Primary Tumor

• Surgical Excision with Narrow Margins
• Thin - 1 cm. margin
• Intermediate - 2 cm. margin

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10 Year Survival Rates New Stages 1 and 2
Balch et al
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Patterns of Progression

• Thin melanomas have a low risk of recurrent
  disease but the risk increases slightly over time
• Intermediate thickness melanomas have a relative
  constant risk of recurrent disease and death
• Thick melanomas and Stage 3 and 4 have the
  greatest risk of recurrence/death in first few
  years after initial diagnosis, but show a
  reduction in future risk over time.

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PATHOLOGY REPORT

• Thickness
• Degree of Ulceration
• Level of Invasion
• Growth Pattern
• Margin Status
• Tumor Infiltrating Lymphocytes (TIL)
• Regression

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Other Adverse Prognostic Factors

• Anatomic site-scalp, trunk,
• hands and feet, nail
  bed
• mucosa
• Age-older, especially gt age 60
• Gender-male
• Pregnancy is not an adverse factor per se

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Metastasizing Thin Melanomas

• 15 thin melanomas (lt 1mm) spread to the lymph
  nodes or distant sites
• Increased risks male
• gt age 45
• Breslow gt0.75 mm
• All 3 factors 20 risk of recurrence
• Histological features included extensive
  regression

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New Regional Stage 3

• Micrometastases (a)
• Macrometastases (b)
• Satellite or In-transit Lesions
• Number of Regional Lymph Nodes
• 1 (N1) with a 10 year survival40
• 2-3 (N2) with a 10 year survival26
• 4 (N3) with a 10 year survival15

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Sentinel Lymph Node (SLN)

• 1st node in lymphatic basin that drains the
  lesion is most at risk for metastatic disease
• Histology of SLN is representative of the entire
  lymph node basin
• 15-26 of SLN are tumor positive requiring
  extensive nodal dissection

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Lymphatic Mapping

• Pre-op mapping of lymph basin with cutaneous
  lymphoscintigraphy
• Intra-operative SLN identification rate 98
• - Isosulfan blue dye and
• - Technetium-labeled radioisotope detected with
  hand-held gamma probe
• SLN dissection
• Immunohistology of serial sections
• - PCR identifies tyrosine-messenger RNA

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Predictors of Positive SLN

• Tumor thickness
• lt 1 mm (Stage IA) 4-8
• 1-2 mm (Stage IB) 10-20
• 2-4 mm (Stage IIA) 20-35
• gt 4 mm (IIB IIC) 35-55
• Truncal location
• Tumor ulceration

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New Stage 4 Metastases

• Site of Distant Metastases
• a Skin or Subcutaneous
• b Lung
• c Viscera such as brain, bone, liver
• Lactate Dehydrogenase (LDH)

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New Stages 3 and 4

• IIIA 1-3 microscopic lymph node
• and/or in- transit mets
• without ulceration
• IIIB 1-3 micro lymph node with ulceration
• 1-3 macro lymph nodes without
  ulceration
• IIIC 1-3 lymph nodes macro lymph nodes
• with ulceration
• gt 4 lymph nodes
• IV - systemic metastasis both non-visceral and
  
• visceral

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New Melanoma Staging System
Balch et al
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Summary Points

• Atypical moles in the clinical setting of many
  moles are associated with an increased risk of
  malignant melanoma.
• Tumor thickness, i.e. Breslows scale, is the
  most reliable prognostic variable.
• Histologic ulceration adversely affects
  prognosis.

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Summary Points (continued)

• Nodal tumor burden, the number of diseased lymph
  nodes, also adversely affects prognosis
• Sentinel lymph node dissection is a new modality
  that identifies regional spread of tumor, and
  aids in the identification of micrometastasis.