In this chapter the more important ocular tumours will be considered. There are a con- siderable number of other rare tumours and the interested student should refer to one of the more specialised and comprehensive textbooks of ophthalmology for further reading.
The Globe
Expanding tumours in the eye present diagnos- tic problems because it is not usually possible to biopsy them.
Choroidal Melanoma
The most common primary intraocular tumour is the malignant melanoma of the choroid. In white people, the tumour has an incidence of one in 2500 and the average age at presentation is 50 years. The incidence rises with age with a peak at 70 years. However, it is important to appre- ciate that no age is exempt because choroidal melanomas have been reported in children as young as three years. It is extremely rare in black people. It differs from melanoma of the skin in that it grows more slowly and metastasises late.
Most choroidal melanomas are thought to orig- inate from choroidal nevi, which are present in up to 10% of the population. At first, it is seen as a raised pigmented oval area, which can be any- where in the fundus (Figure 15.1). It is usually brown in colour although it can be amelanotic (or greyish). As the tumour enlarges there might
be an associated exudative retinal detachment or, less often, secondary glaucoma. Other asso- ciated features might include choroidal haemor- rhage and serial photography might be needed to confirm the growth. The usual presentation is with decreased vision or a visual field defect.
Diagnosis is confirmed with careful clinical examination, including indirect ophthalmo- scopy and slit-lamp biomicroscopy (contact lens or volk lens examination), fluorescein angiography, ultrasonography and transvitreal fine-needle aspiration in equivocal cases. The most common site for metastases is the liver, so abdominal ultrasound, serum liver function tests, and chest X-ray should be performed at regular intervals. The appearance of liver metas- tases can be delayed for several years and can occur even if the eye has been removed, sig- nifying micrometastases at the time of presen- tation. Approximately 40% of patients develop liver metastases within ten years of the initial diagnosis, while the estimated five-year mortal- ity rate for treated medium-size melanomas is between 15% and 23%. The differential diagno- sis of choroidal melanoma includes retinal detachment, metastatic choroidal tumours, wet macular degeneration, large choroidal nevi, choroidal haemangioma or choroidal effusion.
Historically, treatment involved enucleation (removal of the globe); today, however, many alternative eye-sparing treatments are available, partly dependent on the size and local spread of the tumour. Options include radiotherapy (external plaque, proton beam or helium ion),
15
Tumours of the Eye and Adnexae
121
laser photocoagulation for small lesions, local resection and transpupillary thermotherapy.
Untreated, the tumour can extend into the orbit and provide an unpleasant problem for the patient.
Choroidal Metastases
These make up the most common intraocular tumours in adults. Although lesions can be demonstrated in at least 1–2.5% of patients with carcinomas, many cases remain asymptomatic unless the macula is involved. In males, the most common primary tumour is found in the lung and in females, it is the breast. The metastatic tumours are usually treated with external beam radiotherapy.
Retinoblastoma
This is a rare tumour of childhood, which arises not from the choroid but, as its name suggests, from the retina. It is, however, the commonest
primary intraocular tumour in children, with an incidence of one in 15,000 live births. It shows certain rather strange and unusual features. It is not usually present from birth, but occurs most frequently in infancy to age three years (although it can occur in older patients); it is either inherited as an autosomal dominant trait or can be sporadic in nature. Approximately 40% of cases are considered to be inherited. In one-third of inherited cases it appears in both eyes. A change in the RB1 gene on chromosome 13 is found in the inherited cases. Initially, it can be seen in an individual, suspected on account of the family history, as a small white, raised mass. Examination under anaesthesia is essen- tial in such cases because the tumour might be in the extreme periphery of the fundus. A larger tumour can present as a white mass in the pupil (“leucocoria”) and such an appearance in infancy demands immediate referral to an ophthalmologist (Figure 15.2). Other presenting features include strabismus, secondary glau- coma, proptosis or intraocular inflammatory signs. Computed tomography (CT) scanning and ultrasound might show a calcified intra- ocular mass. Extension tends to occur locally along the optic nerve and enucleation is often life saving. Until recently, enucleation was the treatment of choice and cure rates of 90–95%
were achieved. Nowadays, eye-sparing therapy is preferred, in an attempt at avoiding the physical and psychological trauma involved in enucleating a young child. Alternative treat- ment options include initial systemic tumour chemoreduction with carboplatin-based regi- mens, followed by external beam radiotherapy, plaque radiotherapy, cryotherapy or laser pho- tocoagulation. Genetic counselling is essential for these patients in order to prevent the increasing incidence of the tumours, which will result from effective medical treatment.
Melanoma of the Iris
This rare iris tumour usually presents as a sol- itary iris nodule, which might or might not be pigmented. It can cause distortion of the pupil, which can be an early warning sign. Other fea- tures that can point to the diagnosis are local- ised lens opacity, iris neovascularisation and elevation of intraocular pressure. Melanoma of the iris is extremely slow growing and probably much less malignant than choroidal melanoma, Figure 15.1. Choroidal melanoma poorly pigmented (amelan-
otic) melanoma a fundus photograph. b Bisected eye showing pigmented and nonpigmented portions of melanoma in same eye (with acknowledgement to Mr A. Foss).
a
b
with a survival rate of at least 95% at five years.
Treatment is usually in the form of a sector or total iridectomy.
The Eyelids
Benign Tumours
Meibomian Cysts (Chalazion)
This is the commonest eyelid lump in all ages.
It is caused by blockage of the meibomian gland orifice such that the secretions accumulate. A granulomatous inflammation is set up, which results in a painless, round, firm, slowly growing lump in the tarsal plate (Figure 15.3).The cyst can become infected, when it becomes red hot and painful. Treatment is by incision and curettage.
Molluscum Contagiosum
This is caused by a viral infection and is most commonly seen in children. The lesions consist of several pale, waxy, umbilicated nodules on the eyelids and face. Similar lesions can be located on the trunk. The eyelid lesions shed viral par- ticles, which produce a chronic conjunctivitis and less often superficial keratitis. The lesions might disappear in about six months, but can need curettage or cautery.
Papilloma
This is the name used to describe a rather common virus-induced nodule or filiform wart often seen on the lid margin.
Seborrhoeic Keratosis
This is common in the elderly and consists of slow-growing, sessile, greasy lesions of the eyelid. They are usually brown and friable.
Senile Keratosis
Senile keratosis consists of multiple, flat, scaly lesions, which can occasionally undergo trans- formation into a squamous cell carcinoma.
Xanthelasma
These are slightly elevated lesions consisting of lipid deposits usually on the medial aspect of the eyelids. They can be associated with hyper- lipidaemia, especially in the younger patient.
Keratoacanthoma
This is an example of a lesion that grows rapidly, too rapidly for a neoplasm, over a period of a few weeks and then resolves spontaneously (Figure 15.4). It usually starts as a red papule, which grows quickly into a nodule with a keratin-filled crater. The lesion can resemble a basal cell carcinoma. Small lumps on the eyelids should be removed and biopsied. Larger lumps can be biopsied by taking a small segment from them before total excision if this proves neces- sary. Special care should be taken with the exci- sion of any lesion on the eyelid in view of the risk of causing distortion of the lid margin or exposure keratitis.
Figure 15.2. Retinoblastoma: leucocoria.
Figure 15.3. Chalazion.
Kaposi Sarcoma
This is a well-known association with acquired immune deficiency syndrome (AIDS). The lesions consist of purple nodules on the eyelid and similar lesions in the lower conjunctival fornix composed of proliferating endothelial and spindle-shaped cells. Inflammatory cells might also be present with vascular channels without endothelial cell lining. Human herpes virus 8 is thought to be important in the patho- genesis of these lesions.
Benign Vascular Tumours of the Eyelids
These fall into three types: capillary haeman- gioma of the newborn (strawberry naevus), cavernous haemangioma and telangiectatic haemangioma.
Capillary Haemangioma of the Newborn (Strawberry Naevus)
This is usually seen before the age of six months, and nearly all examples regress spontaneously, usually in few months and by the age of five years.
Tumours appear as red, slightly raised marks on the skin. Even extensive tumours of this kind can show a dramatic improvement over several years and conservative management is usually indi- cated unless the tumour is associated with a fold of skin that occludes the eye, causing amblyopia.
Larger tumours can produce orbital enlarge- ment. If treatment is required, intralesional steroid injections have proved beneficial.
Cavernous Haemangioma
These tumours lie more deeply in the skin and appear as a bluish swelling in the lid, which expands when the child cries. These lesions can also disappear spontaneously or, if persistent, they can be treated by freezing.
Telangiectatic Haemangioma
Also known as the port wine stain or naevus flammeus, this tumour tends to be distributed over the area supplied by one or more of the branches of the fifth cranial nerve and usually remains throughout life as a dark red dis- colouration in the skin (Figure 15.5). The importance of this particular appearance is its association with secondary glaucoma and hae- mangioma of the meninges. The latter produces calcification and a characteristic X-ray appear- ance. The combination of lesions is known as the Sturge–Weber syndrome. There can be hypertrophy of the affected area of the face, leading to asymmetry.
Malignant Tumours of the Eyelids
Basal Cell Carcinoma
This is the most common malignant tumour of the eyelid in adults (80–90% of cases). Patho- Figure 15.4. Keratoacanthoma (with acknowledgement to
Mr A. Sadiq).
Figure 15.5. Port wine stain (naevus flammeus).
genesis is related to exposure to ultraviolet light, hence it most frequently involves the lower lid and medial canthus. The tumour begins as a small insignificant nodule, which turns into a small crater-like lesion with a slightly raised, pearly-coloured edge with fine dilated blood vessels on its surface (Figure 15.6). Although the tumour rarely metastasises, it is locally invasive, and, therefore, early diagnosis and treatment is important. In the early stages, it is a simple matter to remove the lesion and confirm the diagnosis by biopsy, but if left the tumour tends to spread into surrounding structures and into the underlying bone and orbit (Figure 15.7).
Treatment depends on the size, extent and loca- tion of the tumour. Usually, surgical excision with wide margins is the technique of choice, either by a simple excisional biopsy or by the more complex Mohs’ procedure. The more extensive, neglected basal cell carcinomata are treated by radical surgery, cryotherapy or palliative radiotherapy.
Squamous Cell Carcinoma
Squamous cell carcinoma is the second most common malignant eyelid lesion and cons- titutes 5–10% of cases. It occurs most commonly in the elderly and is related to sunlight exp- osure. The tumour can initially resemble a basal cell carcinoma, although the edges are usually not rolled. Spread tends to occur to the local lymph nodes (preauricular for the upper lid and submandibular for the lower lid). Treatment is
similar to a basal cell carcinoma. Sebaceous Gland Carcinoma
This uncommon tumour constitutes 1–3% of malignant eyelid tumours (higher in Asians). It arises from the meibomian glands in the tarsal plate. It appears as a discrete, firm nodule, which often presents as a “recurrent chalazion”, thereby delaying diagnosis. Treatment involves wide excision with or without radiotherapy. Mortality ranges from 6% to 30%, depending on site, size, symptom duration and histological classification.
Melanoma of the Eyelid
Malignant melanoma of the eyelids is similar to malignant melanoma elsewhere, appearing as a raised, often shiny, black lump. It metastasises at an early stage and the prognosis does not seem to be altered by excision.
Figure 15.6. Early basal cell carcinoma of medial canthus.
Figure 15.7. Extensive basal cell carcinoma involving the orbit and extending across the nose to the opposite side. a Clinical photograph; b computerised tomography scan.
a
b
The Conjunctiva
Benign Lesions
Benign Pigmented Lesions of the Conjunctiva
Conjunctival epithelial melanosis occurs in approximately 90% of black people and 10%
of white people, and is noticeable in early life.
The lesions are flat, brownish patches scattered throughout the conjunctiva, but might be more noticeable at the limbus (Figure 15.8). Usually, they do not grow. Other pigmented lesions, for example the benign naevus, require closer attention and specialist evaluation.
Nonpigmented Lesions
Pingueculum is a common mass lesion of the conjunctiva. It is seen as a yellowish nodule usually on the medial interpalpebral fissure. It is a fibrovascular degeneration and is seen in all climates.
Pterygium is a growth of abnormal fibrovas- cular tissue extending from the conjunctiva over the cornea (Figure 15.9). It is thought to result from to chronic irritation from dust and solar radiation. It is more common in hot climates and individuals who work out of doors. Recur- rent inflammation of the pterygium is often self-limiting but responds to a short course of topical steroids. If it extends over the visual axis of the cornea it can cause visual impairment and, therefore, surgical excision might be required, although regrowth occurs in a large proportion of patients.
Malignant Lesions
Melanoma of the Conjunctiva
Malignant melanomata can occur on the conjunctiva (Figure 15.10) but they should not be confused with the relatively common benign conjunctival naevus. The latter is a slightly raised pigment-stippled lesion often seen at the limbus on the temporal side. Closer examination with the hand lens or microscope reveals one or two minute cysts. It is generally accepted that these benign lesions should be excised and biopsied if they become irritable or sometimes simply on cosmetic grounds, but they rarely become malignant. The treatment of conjunctival malignant melanoma involves wide surgical excision with adjuvant cryother- apy or radiotherapy. The five-year survival rate is approximately 85%.
Figure 15.10. Melanoma of conjunctiva.
Figure 15.8. Conjunctival melanosis.
Figure 15.9. Pterygium.
The Orbit (see Table 15.1)
Lacrimal Gland and Sac Tumours
Lacrimal gland tumours can either be inflam- matory, mixed cell tumours or adenocarcino- mas. They present with proptosis or a mass in the outer part of the eyelid superotemporal orbit. Lacrimal sac tumours are less common and present with sac swelling. Benign lesions and infections need to be excluded.
Dermoid Cyst
This cystic swelling is usually seen at the level of the eyebrow in the upper outer part of the orbit.
It is smooth and fluctuant and often fixed to bone.
Sometimes a deeper part of the cyst can occupy a cavity in the bone and a computed tomography (CT) scan is advisable when this is suspected.
Rupture of the cyst can lead to profound orbital inflammation. Excision on cosmetic grounds and for diagnosis is usually indicated.
Cavernous Haemangioma
This is the commonest primary neoplasm of the orbit in adults. It is benign. It is unusual for surgery to be necessary in such cases. It is usually located within the muscle cone, and gives rise to axial proptosis.
Glioma of the Optic Nerve
This rare tumour causes progressive proptosis and optic atrophy but it can be slow growing.
There is an association with Von Reckling- hausen’s disease (neurofibromatosis type 1) and the presence of pigmented patches in the skin should make one suspect this. Treatment by
surgical resection and/or radiotherapy is indi- cated if intracranial spread is documented.
Rhabdomyosarcoma
This rare but highly malignant orbital tumour is seen in children. Its growth is so rapid that it may be misdiagnosed as orbital cellulitis. If a correct diagnosis is made at an early stage, there is some hope of reaching a cure by combining radiotherapy and chemotherapy. The tumour is thought to arise from striated muscle and the histological diagnosis is confirmed by finding striation in the tumour cells. It is usually located in the superonasal orbit.
Metastatic Tumours and Tumours from Neighbouring Sites
A wide variety of tumours can invade the orbit and produce proptosis and often diplopia. Lym- phoma is one example. It can present as an iso- lated lesion or in association with Hodgkin’s disease or leukaemia. Examples of local spread from adjacent structures include carcinoma of the nasopharynx, carcinoma of the lacrimal gland and meningioma. In children, orbital metastases arise most commonly from neuro- blastoma and Ewing’s sarcoma. In the adult, the commonest primary sites are bronchus, breast, prostate and kidneys.
“Pseudotumour” (Idiopathic Orbital Inflammatory Disease)
This is an inflammatory swelling in the orbit of unknown cause, which can present with pain, proptosis and diplopia. A mass might be palpa- ble in the orbit and biopsy reveals nonspecific inflammatory tissue consisting mainly of lym- phocytes. Diagnosis can eventually be made by exclusion of other causes of proptosis. In severe cases, a course of systemic steroids and/or radiotherapy is usually effective.
Exophthalmos and Proptosis
Both these terms mean forward protrusion of the eyes but traditionally exophthalmos refers to the bilateral globe protrusion in thyroid disease. Proptosis refers to unilateral forward Table 15.1. Primary orbital tumours.
Vascular Capillary haemangioma
Cavernous haemangioma Lymphangioma
Neural Optic nerve glioma
Meningioma Neurofibromatoma Lacrimal gland
Lymphoproliferative Rhabdomyosarcoma Histiocytosis
displacement of the globe from whatever cause.
In practice, the terms tend to be used rather loosely and are now almost synonymous.
Causes of Proptosis (see Table 15.2)
When one eye seems to bulge forward, the doctor might have a serious problem on his hands and the following likely causes should be considered:
• Pseudoproptosis. An apparent bulging forward of the eye occurs if the eye is too big, as in unilateral high myopia, or if the other eye is sunken following a blow-out fracture of the maxilla (orbital floor).
These need to be distinguished from a true proptosis.
• Thyrotoxicosis. This is the commonest cause of unilateral or bilateral proptosis;
diagnosis is achieved from the history, examination and tests of thyroid function (Figure 15.11).
• Infection. Orbital cellulitis, usually from neighbouring sinuses, requires urgent otorhinological opinion.
• Trauma. Proptosis can occur as a result of retro-orbital haemorrhage. Diagnosis should be possible from the patient’s history.
• Haemangioma. This can expand after bending down or crying.Ultrasound and CT scanning can confirm the diagnosis. Occa- sionally, angiography might be required.
• Pseudotumour. Biopsy should be carried out if possible, and other causes excluded.
• Mucocele of sinuses. Diagnose by X-ray or CT scan.
• Lymphoproliferative disease. A biopsy, full blood count and sternal marrow puncture should be carried out.
• Others. There are a large number of pos- sible but rare causes of proptosis.
Assessment of Proptosis
In the clinic, proptosis is best assessed by stand- ing behind the seated patient and asking him to look down. The position of each globe in rel- ation to the lids and face can be best seen by this means. Proptosis can be measured by means of an exophthalmometer. A number of such instruments are on the market and they depend on measuring the distance from the rim of the outer margin of the orbit to the level of the anterior part of the cornea. These measure- ments are not always accurate (especially for the novice) but best results are achieved by ensuring that they are made by the same person, using the same instrument on each occasion for a given patient.
Once thyroid disease and trauma have been excluded, the patient would require further investigations including systemic examination, full blood picture, orbital ultrasound, CT scan, magnetic resonance imaging (MRI) scan, possibly carotid angiography and sometimes orbital biopsy.
Figure 15.11. Proptosis: dysthyroid disease.
Table 15.2. Causes of proptosis.
• Endocrine
• Vascular abnormalities
• Inflammatory disorders
• Primary orbital tumours
• Metastases
