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MALIGNANT MELANOMA

Overview

  • Relatively uncommon, therefore all suspicious lesions should be referred under 2-week rule to local screening services

    • A new mole appearing after the onset of puberty which is changing in shape, colour or size

    • A long-standing mole which is changing in shape, colour or size

    • Any mole which has three or more colours or has lost its symmetry

    • A mole which is itching or bleeding

    • Any new persistent skin lesion especially if growing, if pigmented or vascular in appearance, and if the diagnosis is not clear

    • A new pigmented line in a nail especially where there is associated damage to the nail

    • A lesion growing under a nail

  • ​Early recognition of melanoma presents the best opportunity for cure

  • Risk factors:

    • UV exposure​

    • Age

    • Previous melanoma

    • Immunosuppression

    • Family history

    • Fitzpatrick skin type and hair colour

    • Predisposing conditions

      • Atypical mole syndrome​

      • Dysplastic naevus​​

      • Congenital naevus

      • Xeroderma pigmentosum

      • Lentigo maligna

Overview

Histological subtypes

  • Superficial spreading melanoma

    • Most common​

    • Long horizontal growth phase before vertical growth

    • Flat junctional naevus, asymmetrical borders, colour variegation

  • Nodular melanoma​

    • Aggressive​

    • Typically arises de novo in normal skin 

    • Dome shaped with sharp demarcation

  • Lentigo maligna melanoma​​

    • Least aggressive​

    • Related to sub exposure

    • Displays vertical growth phase as opposed to just radial growth phase of precursor lesion (lentigo maligna)

  • Acral lentiginous melanoma​

    • Usually on palms, soles of feet, subungual or sun-protected areas​

    • Usually flat with irregular border and multiple colour shades

  • Desmoplastic melanoma​

    • Propensity for perineural invasion​

    • High rate of regional lymph node spread

  • Amelanotic melanoma​

    • No pigment by light microscopy​

    • Diagnosis by immunohistochemistry​

Histological subtypes

Staging

  • TNM staging in accordance to American Joint Committee on Cancer (AJCC) 8th edition

  • Breslow thickness - tumour thickness in millimetres from stratum granulosum

  • Ulceration of the primary tumour upstages the disease to the next T substage

  • Mitotic rate ≥ 1 per squared mm is independently associated with worse disease-specific survival

  • T-stage

    • Tx - Primary tumour thickness cannot be assessed​

    • T0 - No evidence of primary tumour

    • Tis - Melanoma in situ

    • T1

      • T1a - <0.8mm without ulceration​

      • T1b - <0.8mm with ulceration or 0.8-1.0 mm with or without ulceration

    • T2

      • T2a - >1.0-2.0mm​ without ulceration

      • T2b - >1.0-2.0mm with ulceration

    • T3​

      • T3a - >2.0-4.0mm without ulceration​

      • T3b - >2.0-4.0mm with ulceration

    • T4​

      • T4a - >4.0mm without ulceration​

      • T4b - >4.0mm with ulceration

  • N-stage​​

    • Nx - Regional nodes not assessed​

    • N0 - No regional metastases detected

    • N1

      • N1a - 1 clinically occult (detected by sentinel lymph node biopsy)​

      • N1b - 1 clinically detected

      • N1c - No regional lymph node disease, with presence of in-transit, satellite and/or microsatellite metastases

    • N2​

      • N2a - 2-3 clinically occult​

      • N2b - 2-3 involved nodes, at least one of which was clinically detected

      • N2c - 1 clinically occult or clinically detected, with presence of in-transit, satellite and/or microsatellite metastases

    • N3​

      • N3a - ​≥4 clinically occult​

      • N3b - ≥4 involved nodes, at least one of which was clinically detected or the presence of any number of matted nodes

      • N3c - ≥2 clinically occult or clinically detected and/or presence of any number of matted nodes, with presence of in-transit, satellite and/or microsatellite metastases

  • M-stage

    • M0 - No evidence of distant metastasis​

    • M1 - Evidence of distant metastasis

      • M1a

        • M1a(0) - Distant metastasis to skin, soft tissue including muscle, and/ or nonregional lymph node​, LDH not elevated

        • M1a(1) - Distant metastasis to skin, soft tissue including muscle, and/ or nonregional lymph node​, LDH elevated

      • M1b

        • M1b(0) - Distant metastasis to lung with or without M1a sites of disease​, LDH not elevated

        • M1b(1) - Distant metastasis to lung with or without M1a sites of disease​, LDH elevated

      • M1c​

        • M1c(0) - ​Distant metastasis to non-CNS visceral sites with or without M1a or M1b sites of disease​, LDH not elevated

        • M1c(1) - Distant metastasis to non-CNS visceral sites with or without M1a or M1b sites of disease​, LDH elevated

      • M1d​

        • M1d(0) - Distant metastasis to CNS with or without M1a, M1b or M1c sites of disease​, LDH not elevated

        • M1d(1) - Distant metastasis to CNS with or without M1a, M1b or M1c sites of disease​, LDH elevated

  • AJCC prognostic stage group​​

    • 0 - Tis N0 M0​

    • IA - T1a-T1b N0 M0

    • IB - T2a N0 M0

    • IIA - T2b-T3a N0 M0

    • IIB - T3b-T4a N0 M0

    • IIC - T4b N0 M0

    • IIIA - T1a/b-T2a N1a/N2a M0

    • IIIB - T0 N1b/N1c M0, T1a/b-T2a N1b/c or N2b M0, or T2b/T3a N1a-N2b M0

    • IIIC - T1a-T3a N2c N3a/b/c M0, T3b/T4a ≥N1 M0, or T4b N1a-N2c M0

    • IV - Any T Any N M1

Staging

Investigations

  • Excision biopsy with 2mm margins with cuff of fat

    • Pathological evaluate for Breslow thickness​, ulceration, mitotic rate, deep and peripheral margins, microsatellites

  • Imaging​

    • Stages I and II - CT, PET/CT, MRI generally not recommended​

    • Stage III - CT chest/abdomen/pelvis, CT/MRI brain with or without PET/CT​

Investigations

Management

  • Wide local excision (WLE) of primary tumour

    • Reduce local recurrence

    • Depth of excision to but not including next fascial layer

    • Margins​​

      • In situ - 5mm​ margin

      • <1mm - 1cm​ margin

      • ≥1mm - 2cm margin

  • Sentinel lymph node biopsy​​

    • Staging procedure​, not therapeutic treatment

    • Performed in conjunction with WLE of primary tumour

    • Indicated for stage IB melanoma

  • Lymph node dissection

    • No role ​​for elective lymph node dissection in negative SLNB

    • Therapeutic lymph node dissection in positive SLNB did not improve melanoma-specific survival (MSLT-II trial)

    • Therapeutic lymph node dissection indicated in patients not suitable for immunotherapy, who cannot attend for follow-ups (usually for geographical reasons)

  • Immunotherapy​

    • Rapidly advancing adjuvant treatment option​

    • Ipilimumab - monoclonal antibody directed to CTLA-4 receptor

    • ​Vemurafenib - BRAF kinase inhibitor​

    • Imatinib - for tumours with c-KIT mutation

Management
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