Melanoma

Meku Damtie (M.D.)

July 18, 2006

 Introduction
Melanocytes – Derived from neural crest cells; during

embryogenesis migrate to the basal layer of

epidermis, hair follicles, retina & uveal tract,

Leptomeninges, inner ear and ectodermal mucous

membrane

Melanocyte number is the same among sexes and races

 Different pigmentation is related melanosome

size

 Sun exposure, MSH, ACTH, estrogen and

progesterone stimulate melanin production

 Melanin absorbs radiant energy from the sun

 Introduction
• Melanocytes normally lie as individual clear cells in the junctional zone ( basal layer
of the epidermis )

• May be increased in number to produce benign pigmented lesions

Congenital nevus – may be large at birth
-- Grow in synchrony with the child

Acquired nevus (common mole)  collection of melanocytes in the

epidermis (junctional), dermis (intradermal), in both (compound)
-- Appear in crops, most reach only 3-4mm in diam.
-- Average number of 20-30-in the 3 rd decade

Dysplastic nevus – Arise after puberty

-- Grow to 7mm or more, irregular border & pigmentation
-- Histological atypical melanocytes

• In a Freckle  normal number of melanocytes produce excess pigment

• Lentigo  increased number of discrete melanocytes

• Melanoma  Arises as a result of malignant transformation of melanocytes

 More than 90% occur in the skin
 Epidemiology
• Melanoma – 4-5% of skin cancers: but accounts for 77% skin cancer deaths

• Age – melanoma affects a broad range of age groups; peaks in 4th-5th decade

• Gender -- male to female = 1.2;1.0

• Race uncommon in black individuals

 Annual age adjusted incidence of blacks is only 0.9% of whites
 Presentation in blacks is different and more deadlier

• Incidence rate increasing more than any other cancer ( 6%/ year in USA)
Australia and Israel have the highest incidence  40/100,000/year
 Decreased ozone layer
 Increased recreational sun exposure

• Survival rate is improving – early Dx, surgical techniques, adjuvant Rx

91% in USA, 81% in Europe, 40% in developing countries
 Malignant Skin Tumor in Sidamo
Lindtjorn B. 1980 Ethiop. Med. J.
• 101 patients (73 male; 28 female) biopsy proven skin
malignant tumors
58 (57.4%) had squamous cell ca
28 (60.9%) developed over a chronic ulcer
30 (29.7%) had melanoma
15 male and 15 female
Site 2 on face; 2 on arm; 1 on leg;
25 (83%) on the foot (plantar)
7 (6.9%) had Kaposi sarcoma
6 (5.9%) had basal cell ca
 Etiologic /Risk Factors
• Sun exposure during childhood & adolescence

UV-B radiation, low latitude, number of blistering sun burns

• Personal characteristics

Blue eyes, blond/red hair, pale complexion

Skin reaction to sun light ---easily sunburned

Freckling

Benign and/ or dysplastic melanocytic nevi – number has better correlation than size

Immunosuppressive states

• Family history  in 5-10% of patients

• Trauma -- ? In Africans
 Clinical Features
• Most occur as a solitary pigmented lesion with ABCDs
May be difficult to appreciate in black skin

• Most arise de novo; 10-50% of cases may arise from pre-existing nevi

• 5% amelonocytic

• 3-5% present with metastatic disease without evidence of primary lesion

 Regressed or undocumented excision of primary lesion

Glasgow 7-point check list for a pigmented lesion

Major Features Minor Features

change in size diameter >7mm

irregular shape inflammation
irregular color oozing
change in sensation
The ABCDs for identifying early Melanoma from a benign mole
 Classification
• Melanomas are classified into 4 major types based on growth pattern 

superficial spreading melanoma (SSM), nodular melanoma (NM), lentigo

maligna melanoma (LMM) and acral lentiginous melanoma (ALM)

SSM, LMM and ALM have junctional component  initially Radial Growth Phase

Vertical Growth Phase -- Appears in time

-- Associated with both invasive features and metastatic
capability
NM is subjunctional and has vertical growth phase from the beginning

• Rare types; desmoplastic melanoma, verrucous melanoma

Superficial spreading melanoma
Has an extended radial growth phase

Most common type 60-70%

usually arises from a pre-existing dysplastic nevus

Any site, but common on back of men and legs of

women

Any age after puberty

Lesion is usually flat, become irregular & elevated in

later stages
• ALM -- soles, palms, the digits, subungual/
periungual and mucosal surfaces
 2-8% in whites; 35-60% in blacks
 Early progression to NM
 More aggressive with poor prognosis
 May be misdiagnosed as infection or trauma

Amelanocyti subungual melanoma

Nodular melanoma  15-30% of cases
Characterized by vertical growth only
may not show ABCDs
Elevation & Evolving important
Arise de novo
Discrete nodule, with dark black pigmentation
Middle age: Males > Females

Amelanotic NM
Lentigo maligna melanoma 4-10%
Arise from in-situ melanoma (LM) on sun
damaged skin  face, neck, dorsum of hand
Older people; Females > males
Indolent course; better prognosis
 Diagnosis
• Clinical
• Definitive Dx can only be made after Bx
• Any lesion suspected should be biopsied
• Excisional Bx recommended  full thickness skin with
subcutaneous tissue; 2mm normal skin margin
• Incisional & punch Bx  reserved where skin removal is
critical
• Imaging studies  CXR
 Other imaging studies are indicated if there is
Sn / Sx of distant metastases
• DDX Benign pigmented lesions
Pyogenic granulomas
Pigmented SCC &BCC most BCC in blacks are pigmented
 Staging & Prognosis
The revised AJCC TNM Classification of 2002

• Primary Tumor  `Length by width` not well correlated with Px

Micro staging; Breslow depth ( for thin melanomas < 1mm: Clark's
level)
Ulceration; presence/Absence

• Regional L.node Involvement

Microscopic or Macroscopic
Number of involved L.nodes

• Distant metastases
Site
LDH level
Other prognostic factors  age > 65yrs; anatomic location BANS area;
Male sex; Angiolymphatic invasion
Micro staging of primary tumor
 Treatment of Cutaneous Melanomas
Excision of the Primary Lesion
• William Norris described WLE in 1857
• Excision should include the subcutaneous tissue
• Limited excision  30 to 60% local recurrence
rate
• Handley in 1907 recommended a 2.5cm margin
after mic examination from autopsy
• Later, the recommended surgical margin
increased to 5cm to include possible
microsatelites
Prospective, randomized studies to determine margin of excision

1.France, 5cm Vs 2cm margin in 319 patients, with melanomas ≤2mm thick

Result  no difference in local recurrence or survival rate

2.Intergroup melanoma committee,2cm vs 4cm margins in 468 patients,1-4mm thick

 no Statistically significant diferrerence: same 10 yr survival rate

 need of skin grafts; 46% in 4cms and 11% in2cms

3.Swedish melanoma study group,2cm vs 5cm margins in 989 patients,0.8-2mm

 Local recurrence in 1% of patients equally distributed b/n the two groups

4. WHO melanoma group 1cm Vs 3cm margin in 612 patients with melanomas <2mm thick
No local recurrence in thinner than 1mm thick melanomas

2.7% local recurrence with melanomas 1.1 – 2 mm thick with 1cm margin; no
recurrence in 3cm margin

 Updated after 15 yrs; no difference in overall survival and disease- free survival for the
two groups
• Current recommendation
Less than 1mm thick  1cm margin

1- 4mm thick  2cm margin

Greater than 4mm thick  at least 2cm margin

 Significant reduction in expense and morbidity associated with

skin graft

• For subungual & digit melanomas  amputation proximal to IP joint

or the digit
Hyperthermic Isolation Limb Perfusion
High dose Melphalan  >80% response
with TNF-alpha > 90% regression
• Ocular melanoma  Accounts for 4% melanomas
Generally has no lymphatic access
Has unique propensity to metastasize hematogenously
Rx  Eye sparing or enucleating
• Melanoma of the anus and vulva
Rx  WLE + inguinal LND
APR and radical vulvoctomy  not associated with improved survival
• Adjuvant Rx
High dose IFN alpha-2b for 1yr is indicated for stage III
melanoma
 Management of regional lymph
nodes
• Clinically enlarged L.nodes  5% of patients at presentation
 Confirm by FNAC

RX  Complete regional LND in the absence of distant metastases

For axillary LND it should include level I, II, and III

For inguinal lymphadenectomy, extent of LND is controversial, given the

high rate of complications in deep inguinal LND

 In One study, deep inguinal lymph nodes involved in 43% of patients with
palpable inguinal nodes ~~Advocating complete superficial and deep inguinal
LND
=Others reserve deep inguinal LND for patients with a positive Cloquet`s node
or multiple involved nodes
 Management of the regional lymph node
Patients with no palpable nodal disease
Melanoma<1mm likelihood of nodal disease,<5%
1.01- 2mm 20%
2.01- 4mm 33%
>4mm 40%

 >4mm thick melanomas have >60% distant occult

metastases
 20- 25% of patients who do not have ELND eventually
develops clinically enlarged nodes and needs LND
 Management of regional lymph nodes
• Clinically normal nodes  Mx is controversial
 Snow described complete ELND in 1892

ELND vs Watch and Wait  controversial

Retrospective review compared 10 year survival for patients with localized

( stage I and II ) disease, who had WLE only Vs WLE + ELND
 Survival benefit in patients with melanomas of 0.76 – 4mm
No survival benefit of ELND in thin melanomas ( <0.76mm) and in
thick melanomas ( > 4mm)
Critics  ELND exposes many node negative patients to the morbidity of a LND

Prospective studies showed no significant benefit

The Intergroup Melanoma Surgical Program a significant reduction in mortality with
ELND in patients with non ulcerated melanomas, tumors b/n 1 and 2mm and limb
melanomas
- No improved survival for the majority with clinical negative nodes
 Management of regional lymph nodes

• Sentinel lymph node biopsy (SLNB)

 Morton and et al devised intraoperative lymphatic mapping,
Sentinel lymphadenectomy, and selective complete LND as an
alternative b/c of the controversy of ELND and Delayed dissection
• SLNB has become the standard of care in many major centers
 Pathological status of sentinel L.node determine metastases to
regional L. nodes  Central role in staging
 Survival benefit of SLNB is to be evaluated
• Indication for SLNB  Melanomas 1- 4mm thick
 selectively for thin melanomas
• Positive SLNB  Complete LND
Preoperative dynamic lymphoscyntigraphy
Vital Dye Guidance
Intraoperative Gamma Probe
 Treatment of Advanced Melanoma
• Common sites of metastases
Lns, Skin, Sc tissue = 59% Lungs =36: Liver =20%
Brain =20%; Bone =17%; Gi tract =7%

• Multiple organ met. in 95% Pts dying from melanoma

• Median survival is 6-9 months

• 5 yr survival is 7-19% depending on sites of metastases

• Rx : Surgery for isolated deposits

Solitary lung met. Should be excised  long survival in 33%
Palliative RTX for inoperable cases
Chemotherapy; single agent or combination
Experimental Rx  biochemotherapy, vaccines, gene therapy
High dose IL-2 is accepted by FDA
 Recurrences
• When recurrence occurs it is local in 16%, regional
(lymphatic) in 60% and distant in 24% of the cases
• Local  Within 5 cm of the scar
inadequate excision or out-growth of satellite lesion

• Regional  in-transit, regional L.nodes

• Distant
Good prognosis  wide spread subcutaneous deposits
and pulmonary metastases
Bad prognoses  Other visceral met. brain, liver, gut sub mucosa
 References
• Schwart`s Principles of Surgery 8TH ed.
• Bailey & Love's Short practice of Surgery; 23rd ed.
• Sabiston Text Book of Surgery; 15th ed.
• Clin. Exp.Med(2004) 4:65-77
Review of current state of Rx for primary cutaneous
melanoma
• Lindtjorn B. 1980 Ethiop. Med.J. 18. 159
• Internet revision