Tumours overview

• 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

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