Melanoma

Benign features

• Absence of mitotic activity
• No intradermal migration
• No nuclear enlargement or pleomorphism
• Melanin in superficial layers but not deep layers

Conjunctival melanoma

• Premalignant lesions:

  • Primary acquired melanosis with atypia (75% of melanomas): conjunctival intraepithelial melanocytic neoplasia

    • Diffuse flat areas of pigmentation
    • PAM without atypia does not progress to melanoma

  • Pre-existing naevus (20%)

  • De novo: rare

• Raised pigmented of fleshy conjunctival lesion

• Metastasizes to lymph nodes, brain and other organs

• >5mm thickness and forniceal/palpebral or caruncular lesions carry worse prognosis

• 10% mortality at 5 years, 25% mortality at 10 years

Uveal melanoma

• Arise from the melanocytes

• Associated genes:

  • BAP1: most associated with metastasis and mortality
  • SF3B1 and EIF1AX: associated with better prognosis
  • GNAQ and GNA11: no effect on prognosis

• Relative incidence

  • Iris 8%: slow-growing, nodular tumours. Can cause secondary glaucoma
  • CB 12%
  • Choroid 80%

• Unilateral

• Majority are amelanotic

• Mushroom shaped classically due to subretinal spread after breaching Bruch’s membrane, but may be ovoid or nodular

• Ocular and oculodermal melanocytosis are associated with increased rate of uveal melanoma (1 in 400 in Caucasians). Due to excessive melanocytes

  • Slate-grey or bluish hyperpigmentation of the sclera (scleral involvement raises risk of glaucoma)
  • Bluish discoloration of periocular skin in the V1 or V2 dermatome
  • Naevus of Ota: both ocular and periorbital skin discolouration (typically unilateral)

• Complications

  • Exudative retinal detachment
  • Angle closure
  • Neovascular glaucoma (vasoformative factor production)
  • Spontaneous necrosis with symptoms of endophthalmitis
  • Proptosis

• Histology

  • Callender classification system but can only be used after enucleation

    • Spindle A: cigar-like shaped, slender nucleus, fine chromatin, indistinct nucleolus
    • Spindle B: plumper nucleus and more distinct nucleolus
    • Epithelioid: larger with more pleomorphism. 75% mortality at 15 years
    • Mixed: majority. 50% mortality at 15 years
    • Patterns can be assessed using periodic acid-Schiff stain

  • ISDNA (inverse standard deviation of nucleoli area): newer classification system

• Macroscopic features

  • Collar studding
  • Orbital spread
  • Subretinal fluid/secondary exudative detachment
  • Orange pigment: lipofuscin
  • Choroidal folds
  • Mushroom-shaped breaks through Bruch’s

• Metastatic spread most common to the liver and then to lungs

  • Work-up should include
    • LFTs
    • Liver/abdominal ultrasound
    • Chest X-ray
    • Consideration of CT/MRI of chest and abdomen

• Management principles

  • MDT approach

  • Large tumours (>15mm)

    • Enucleation

  • Medium tumours (10-15mm)

    • Plaque radiotherapy
    • Enucleation

  • Small tumours (<10mm)

    • Observation eg. if at macula
    • Laser photocoagulation
    • Plaque radiotherapy

• Prognostic parameters

  • Age

  • Male gender (poorer prognosis)

  • Size (larger basal diameter)

  • Location: CB tumours carry worse prognosis (ie. more anterior location)

  • Cell type: epithelioid type carry worse prognosis

    • Epithelioid: 35% 15-year survival
    • Spindle: 75% at 15 years

  • Closed loop vascular patterns (vasculogenic mimicry patterns) on PAS stain carry worse prognosis

  • Cytogenetics: loss of chromosome 3 heterozygosity (ie. monosomy 3); additional copies of 8q

  • (Chromosome 6p gain is associated with better prognosis)

  • Extrascleral extension leads to metastasis via the vortex veins tributaries

• Risk factors for systemic metastases in choroidal melanomas

  • Posterior margin adjacent to disc
  • Documented growth
  • Thickness at least 1.1mm or larger

• Choroidal melanomas spread to the orbital via scleral emissary channels

• Risk factors for malignancy in choroidal naevi (To Find Small Ocular Melanomas Using Helpful Hints Daily)

  • Thickness >2mm
  • Fluid: subretinal fluid
  • Symptoms
  • Orange pigment (lipofuscin)
  • Margin within 3mm of disc
  • UltrasoundHollowness
  • Halo absent
  • Drusen absent

Eyelid melanoma

• Tumour thickness is the most important prognostic indicator

  • Breslow depth is the thickness from the epithelial surface to the deepest point
    • Melanoma in situ
    • Stage 1: thin/early melanoma (<0.8mm depth)
    • Stage 2: intermediate (0.8-4mm depth). Lymph node biopsy is indicated
    • Stage 2 (still): thick melanoma (>4mm). <50% 5 year survival
    • Stage 3: advanced (spread beyond the original tumour site)

• Lentigo maligna is the most common type of melanoma (90%)

• Nodular melanoma is the next most common (10%) [cp. With cutaneous melanoma for which superficial spreading type is most common. In cutaneous melanoma, the subtype does not affect prognosis]

Choroidal mass: differential

• Tumour

  • Choroidal melanoma
  • Metastasis
  • Naevus
  • Haemangioma
  • CHRPE
  • Melanocytoma of optic disc
  • Retinoblastoma

• Other

  • RD
  • Disciform scar
  • Exudative maculopathy/retinopathy eg. Coats
  • Posterior scleritis