Malignant melanoma

Epidemiology

Incidence of melanoma is doubling every 10 years
40 per 100,000/ year in Queensland, Australia
4 per 100,000/ year in Scotland
Overall 1000 deaths / year in United Kingdom
Education increasing the number of thin tumours detected
Number of thick tumours detected annually remains constant

Risk factors

Giant melanocytic naevus
Total number of naevi
Dysplastic naevus syndrome
History of recurrent sunburn
10% autosomal dominant with reduced penetrance

Clinical features

Major Sign

Change in size
Change in shape
Change in colour
Diameter more than 7 mm

Minor signs

Inflammation
Bleeding
Sensory changes

Early detection

Lesion unlikely to be a melanoma without at least one major sign
Educational efforts at early detection are proving successful
Need to assess
- A = Asymmetry
- B = Border irregularity
- C = Colour variegation
- D = Diameter

Pathology

60% arise in pre-existing naevi
Have initial radial and then vertical growth phase
Determines growth characteristics of the tumour

Superficial spreading melanoma (65%)

Occurs in middle age
Female : male ratio 2:1
Commonest sites - lower leg in women and trunk in men
Usually slightly elevated lesion with variable colour

Nodular melanoma (27%)

Aggressive tumour
Occurs in younger age group
Female : male ratio 1:2
Early vertical growth phase
Usually uniform colour, early ulceration and bleeding

Lentigo maligna melanoma (7%)

Least malignant
Usually found on face of elderly
Long radial growth phase
Presents as flat light brown macule

Acral lentiginous melanoma (1%)

Aggressive tumour
Commonest type found in negros and orientals
Occurs on soles of feet and palms of hand
Subungual melanomas included in this group

Intransit metastases

Uncommon. Seen in <2% tumours
Appear as intracutaneous metastases or 'satellites'
Those within 2 cm of primary classified as part of it
Usually associated with regional lymphadenopathy

Lymph node metastases

Commonest metastatic presentation
Reduces survival by 50%
70 - 80% patients with regional lymphadenopathy have distant disease

Tumour thickness

Tumour thickness most important prognostic factor for local, distant recurrence and survival
Five year survival related to Breslow thickness:
- <0.75 mm = 95-99%
- 0.76-1.49 mm = 80-90%
- 1.5-3.99 mm = 60-75%
- >4.0 mm = <50%
With regional lymphadenopathy 10-year survival is less than 10%
No internationally agreed classification of definition of thin, intermediate and thick tumours
Review of trials and comparison of trials difficult

Melanoma surgery

Resection margins

Until recently history rather than controlled trials have dictated practice
Handley (1907)
- Hunterian Lecture based on one case.
- Recommended 5 cm margin
Butterworth and Klaude (1934)
- Found microscopic lymphatic invasion to 3 cm
- Recommended 5 cm resection margins
Olson (1966)
- Trial of resection 1 cm vs. 3 cm resection margins
- Identical local recurrence rate but still recommended 5 cm margin !
WHO Melanoma Group (1990)
- Randomised controlled trial of 1 cm vs. 3 cm resection margins
- Resection margins did not influence survival
Generally accepted resection margins based on clinical appearance are:
- Impalpable lesions - 1 cm margin
- Palpable lesion - 2 cm margin
- Nodular lesion - 3 cm margin

Regional lymphadenectomy

20% clinically palpable nodes are histologically negative
20% palpably normal nodes have occult metastases
Therapeutic lymph node dissection provides regional control and prognostic information
No improvement in survival
For tumours <0.75 mm thick - 90% cured by local excision alone
For tumours >4.0 mm thick - 70% have distant metastases at presentation
For these two groups lymphadenectomy provides no added survival benefit
Lymphadenectomy for 'intermediate' thickness tumours controversial

Morbidity of lymphadenectomy

Lymphoedema (26%)
Seroma ( 23%)
'Functional deficit' (8%)
Wound Infection (5%)
Persistent pain (5%)

Adjuvant Therapy

Patients at high risk of recurrence should be considered for systemic adjuvant therapy
Patients include those with:
- Primary tumour > 4 mm thick
- Resectable positive locoregional lymph nodes
No standard adjuvant therapy exists
Interferon a2b has shown promising results
Shown to increase disease-free and overall survival

Isolated limb perfusion

Intra-arterial chemotherapy
Commonly used agents - melphalan +/- TNF-alpha
Used with hyperoxygenation
Hyperthermia with a temperature of 41-42 °C
Perfusion generally last about 1 hour
Usually combined with lymphadenectomy

Indications

Intransit metastases
Irresectable local recurrence
Adjuvant therapy for poor prognosis tumours
Palliation to maintain limb function

Morbidity of isolated limb perfusion

Mortality (2%)
Limb oedema (76%)
Persistent pain ( 60%)
Neuropathy (25%)
Venous thrombosis (10%)
Septicaemia & thrombocytopenia (3%)

Bibliography

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