- Histologically similar tumours may behave differently within the eye, possibly due to it’s immune privileged status
- Neoplasm: proliferation of cells that is progressive, purposeless, independent of the surrounding tissue integrity and continues even after the initial stimulus has ceased
- Malignant tumour (cp benign) are irregular, non-encapsulated, fast-growing and can spread

## Carcinogenesis
- Environmental
    - Chemicals
    - Radiation: directly damages DNA leading to mutation
    - Viruses: conjunctival papillomas are caused by HPV 6 and 11 (16 and 18 are high-risk for carcinoma); EBV contributes to orbital Burkitt’s lymphoma
        - HPV produces the E6 protein which binds to and inactivates p53 leading to uncontrolled DNA replication
        - EBV produces a protein that makes the cell resistant to apoptosis

- Genetic
  - Proto-oncogenes: normal genes that stimulate cell division
  - Tumour suppressor genes: normal genes that inhibit cell division
  - Oncogenes: abnormal/cancerous genes that cause uncontrolled proliferation
  - Loss of both copies of a tumour suppressor gene like Rb is needed for cancer development

## Premalignant states
- Benign tumours: can undergo malignant change possibly after acquiring genetic mutations eg. pleomorphic lacrimal gland adenomas can transform to adenocarcinoma
- Chronic inflammation: chronic lymphocytic infiltrates in the lacrimal gland associated with Sjogren’s syndrome can develop into lymphoma
- Intraepithelial neoplasia (carcinoma in situ): actinic keratosis showed pleomorphism and dysplasia and can become squamous cell carcinoma if they breach the basement membrane

## Ocular oncology referral guidelines
### Who to refer
- Intraocular tumours
    - Any primary intraocular tumour (except for naevi)
    - Any intraocular metastatic tumour if ocular oncology input required
    - Suspected intraocular lymphoma

- Conjunctival and epibulbar tumours
- Conjunctival melanocytic tumours if:
    - Cornea, caruncle or palpebral conjunctiva involved
    - Feeder vessels
    - Nodule with diffuse pigmentation
    - Diameter greater than 3mm, especially in absence of clear cysts

- Suspicious melanocytic choroidal tumours with
    - Any of
        - Thickness >2mm
        - Collar-stud configuration
        - Documented growth

    - Or two of
        - Thickness >1.5mm
        - Orange pigment
        - Serous retinal detachment
        - Symptomatic

- Iris nodules if
    - Diameter >3mm
    - Markedly elevated
    - Secondary glaucoma/cataract
    - Angle involvement

## Benign tumours

- Papilloma: benign tumour of an epithelial surface
    - Eyelids:
        - Basal cell papilloma aka seborrhoeic keratosis
        - Squamous cell papilloma: includes molluscum contagiosum (poxvirus) and viral warts (HPV)
    - Conjunctiva: may be pedunculated or sessile (again, associated with HPV)

- Adenoma: benign tumour of glandular tissue
    - Can arise from eyelid sweat glands, sebaceous glands, meibomian glands
    - Sebaceous adenomas are commonly seen as a yellow mass at the caruncle

### Summary table: adnexal malignancy

<table>
  <thead>
    <tr>
      <th>Adnexal malignancy</th>
      <th></th>
      <th></th>
      <th></th>
    </tr>
    <tr>
      <th></th>
      <th></th>
      <th></th>
      <th></th>
    </tr>
  </thead>
  <tbody>
    <tr>
      <td><strong>Basal cell carcinoma</strong></td>
      <td>Rolled-edge, telangiectasia, central ulcer, plaque</td>
      <td>Nodular: well-defined islands of basal cells with peripheral palisades</td>
      <td>Gorlin-Goltz, Xeroderma pigmentosa, Bazex syndrome, arsenic, Albinism</td>
    </tr>
    <tr>
      <td>Imiquimod: immune response modulator stimulates apoptosis</td>
      <td>Superficial: discontinuous with buds into dermis</td>
      <td>Infiltrative/sclerosing (morphoeic): ill-defined strands of cells</td>
      <td>Micronodular: small collections of cells</td>
    </tr>
    <tr>
      <td><strong>Squamous cell carcinoma</strong></td>
      <td>Fast-growing, nodular ulcer, papillomatous, keratin horn</td>
      <td>Pink cytoplasm, intercellular bridges, keratin pearls.</td>
      <td>Sunlight, immunosuppression, AIDS</td>
    </tr>
    <tr>
      <td>Lymphatic dissemination (pre-auricular and submandibular nodes)</td>
      <td>Spindle cell</td>
        <td></td>
        <td></td>
    </tr>
    <tr>
      <td><strong>Sebaceous cell carcinoma</strong></td>
      <td>Blepharoconjunctivitis, mimics chalazion, BCC and SCC</td>
      <td>Nodular: lobules with foamy/vacuolated cytoplasm</td>
      <td>Muir-Torre syndrome (associated with visceral tumours)</td>
    </tr>
    <tr>
      <td>Oil red O stains lipid red</td>
      <td>Diffuse: pagetoid spread through epithelium</td>
        <td></td>
        <td></td>
    </tr>
    <tr>
      <td><strong>Lacrimal gland neoplasia</strong></td>
      <td>Proptosis, pain, diplopia</td>
      <td>Pleomorphic adenoma: mixed histology, pseudoencapsulated, can transform to carcinoma</td>
      <td>Adenoid cystic: cribiform “Swiss-cheese” appearance (aggressive)</td>
    </tr>
    <tr>
      <td>Mucoepidermoid</td>
      <td></td>
      <td></td>
      <td></td>
    </tr>
    <tr>
<td><strong>Rhabdomyosarcoma</strong></td>
<td>Proptosis, chemosis diplopia</td>
<td>Embryonal: eosinophilic cytoplasm</td>
<td>Alveolar: poor prognosis</td>
</tr>
<tr>
<td>Botyroid</td>
<td></td>
<td></td>
<td></td>
</tr>
</tbody>
</table>



Tumours, masses and neoplasia

Tumours overview

Intro

FRCOphth Part 2 Study Notes

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)

Melanoma

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