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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

nodular melanoma

A superficial spreading melanoma

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

An acral lentiginous melanoma of the sole of the foot

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

Locally recurrent malignant melanoma

Morbidity of isolated limb perfusion

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

Bibliography

Ball A S  Thomas J.  Surgical management of malignant melanoma.  Brit Med Bull 1995; 5I:  584-608.

Bishop J A.  Melanoma.  Hosp Med 2000;  61:  103-107.

Hall P N,  Javid M,  de Takats P G.  Therapeutic trends in cutaneous melanoma.  Hosp Med 1999:  60:  39-43

Krementz E T et al.  Regional chemotherapy for melanoma.  Ann Surg 1994;  220:  520-535

Mackie R M.  Clinical recognition of early invasive malignant melanoma.  Br Med J 1990;  301: 1005-6

Neades G T et al.   Safe margins in the excision of primary cutaneous melanoma.  Br J Surg 1993;  80:  731-733

O'Rourke M G E  Bourke C.  Recommended width of excision for primary malignant melanoma.  World J Surg 1995;  19:  343-345

Scott R N  McKay A J.  Elective lymph node dissection in the management of malignant melanoma.  Br J Surg 1993;  80:  284-288.

Soong S-J.  Predicting survival and recurrence in localised melanoma:  A multivariate approach.  World J Surg 1992;  16:  191-195

Soutar D S.  The surgical management of cutaneous malignant melanoma.  In: eds Johnson C D  Taylor I.  Recent advances in Surgery 19. Churchill Livingstone, London 1996. p215 - 234.

Stone C A  Goodacre T E.  Surgical management of regional lymph nodes in primary cutaneous malignant melanoma.  Br J Surg 1995; 82: 1015 - 1022.

Tsao H,  Atkins M B,  Sober A J.  Management of cutaneous melanoma.  N Engl J Med 2004;  351:  998-1012

Thomas J M,  Newton-Bishop J,  A'Hern R et al.  Excision margins in high-risk malignant melanoma.  N Engl J Med 2004;  350:  757-766.

 

 
 

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