## 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 (&lt;10mm)
        - Observation eg. if at macula
        - Laser photocoagulation
        - Plaque radiotherapy

<HotTopic>
<p className='font-semibold'>Collaborative Ocular Melanoma Study</p>

- Pre-enucleation radiotherapy did not improve survival

- Small melanomas have 1% mortality at 15 years and observation does not increase mortality

- Plaque radiotherapy was equal to enucleation for medium sized tumours

</HotTopic>

- 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)
    - **T**hickness >2mm
    - **F**luid: subretinal fluid
    - **S**ymptoms
    - **O**range pigment (lipofuscin)
    - **M**argin within 3mm of disc
    - **U**ltrasound**H**ollowness
    - **H**alo absent
    - **D**rusen 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 (&lt;0.8mm depth)
        - Stage 2: intermediate (0.8-4mm depth). Lymph node biopsy is indicated
        - Stage 2 (still): thick melanoma (>4mm). &lt;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

Tumours, masses and neoplasia

Melanoma

Intro

FRCOphth Part 2 Study Notes

Tumours overview

Uveitis

Uveitis background

Anterior uveitis

Intermediate uveitis

Uveitis in JIA

Uveitis with JIA

Retinal vasculitis

Sarcoidosis

Behcet's disease

Toxoplasmosis

Strabismus

Overview

Viral uveitis

Esotropia

Fungal uveitis

Mycobacterial uveitis

Adnexal masses

Exotropia

Spirochaetal uveitis (including Syphilis)

Nematode uveitis

Retinoblastoma

Retinoblastoma (for Part 2)

Incomitent

Voyt-Koyanagi-Harada syndrome

Conjunctival intraepithelial neoplasia

Vertical deviations

Orbit and ocular adnexae

Orbit

Sympathetic ophthalmia

AV Malformations and hamartomas

Arteriovenous malformations and hamartomas

Restriction syndromes

Paediatrics

Leucocoria

Congenital Cataract

Paediatric Glaucoma

Retinopathy of prematurity

Retinopathy of Prematurity

ROP-like disorders

Congenital nasolacrimal duct obstruction

White dot syndromes

Aniridia: Short Arm 11 Deletion (11p13)

Choristomas

Management Of Amblyopia

Alphabet patterns

Iris Nodules

Scleritis

Meningioma

Strabismus surgery

Optic nerve glioma

Lymphoma

Extraocular Muscles

Rhabdomyosarcoma

Idiopathic orbital inflammation

Orbital neuroblastoma

Anterior Persistent Foetal Vasculature

Lacrimal system

Metastatic lesions

Surgical Retina

Retinal Detachment

Vitreoretinal Interface And Macular Hole

Epiretinal Membrane

Medical Retina

Diabetic Eye Disease

Orbital Blood Vessels

Retinal Vascular Disease

Macular Degeneration

Central Serous Chorioretinopathy (CSCR)

Sickle Cell Retinopathy

Retinitis Pigmentosa

Albinism

Retinal Telangiectasias

Miscellaneous Retinopathies

Atropine And Myopia Progression

Pharmacology

Side Effects Of Systemic Drugs

Foetal Alcohol Syndrome

Neuro-ophthalmology

Optic Neuropathy

Papilloedema

Idiopathic Intracranial Hypertension

Chiasmal Disorders

Retrochiasmal Disorders

Migraine

Paranasal Sinuses

Supranuclear Motility Disorders

Third Nerve Palsies

Fourth Nerve Palsies

Sixth Nerve Palsies

Seventh Nerve Palsies

Anisocoria

Myasthenia Gravis

Myopathies

Blepharospasm

Functional Visual Loss

Lacrimal Glands

Phakomatoses

Developmental diseases

Tear Film

Eyelids

Blinking

Lid Malpositions

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Pigmented Conjunctival Lesions

Squamous Cell Carcinoma Of The Conjunctiva

Ocular Cicatricial Pemphigoid

Cornea

Corneal Structure And Development