Dr Omar Mostafa¹* & Dr Kusy Suleiman²*,
Dr Yusuf Abdallah³

1. Foundation Year 1 Doctor, Acute Medical Unit, Walsall Manor Hospital. ^{Contact author}
2. Academic Foundation Year 2 Doctor, Ophthalmology Department, Sandwell & West Birmingham NHS Trust. ^{Contact author}
3. Ophthalmology ST1 Doctor, Heartlands Hospital, University Hospital Birmingham. ^{Contact author}

* Joint first authors

Key Words: Choroidal, Melanoma, Cancer, Management, Prognosis

Key Points

• Choroidal Melanoma is rare but, life-threatening.
• Choroidal Melanoma commonly presents asymptomatically.
• Once the melanoma is spread, the clinical prognosis becomes poor.
• A high index of suspicion should be sought with any pigmented ocular lesion to exclude malignancy.

Abstract

Pigmented fundus lesions on fundoscopic examination are not an uncommon finding. Pigmented tumoral lesions can arise from the retinal epithelium or choroidal melanocytes causing a spectrum of disorders, ranging from choroidal naevus and foreign bodies to the rarer choroidal melanoma. As choroidal melanoma is the most common primary malignant intraocular tumour, this educational review aims to provide a structured overview of this topic to students and junior doctors, to help establish an understanding of such a rare but life-threatening condition. This will also provide the reader with an insight on referral guidelines in the United Kingdom, a brief overview of various treatments, and factors that affect patient’s prognosis.

Introduction

The term ‘melanoma’ is derived from the Latin word ‘Melan’ which means dark pigment. In medicine, the term is used to describe cancerous tumours that commonly affect the skin, rich in melanin-producing melanocytes, and have the potential to invade nearby structures (1).

In the context of the eye, ocular melanoma is a rare form of ocular cancer, but also the most common primary tumour of the eye (2). Most of the primary melanocytic tumours arise from the uvea which consists of the iris, choroid and ciliary body, whilst the rest arises from the conjunctiva. The most common subtype of uveal melanoma is choroidal melanoma, occurring in about 90% of uveal melanoma cases (2).

Epidemiology

Intraocular melanomas share similar epidemiology with cutaneous melanomas; most cases (up to 98%) occur in Caucasians (3), with incidence rates occurring 8-10 times higher in Caucasians compared with Blacks(4).

Incidence of intraocular melanoma appears to increase with age, peaking around the age of 55, with an age range between 50 to 80 years (4).

Risk Factors

Several factors contribute to choroidal melanomas (2). Since the tumours arise from the choroidal layer of the uvea, they can occur due to:

1. Pre-existing melanocytic naevus or congenital ocular melanocytosis (5,6)
2. De-novo growth (sporadic)

De-novo growth is thought to be due to several risk factors, including fair skin, light colour of the iris and sunlight (UV) exposure (7).

Presentation

Symptomology depends on the stage of the tumour, but it is often asymptomatic; it is more likely to be detected incidentally on examination. One study found that as much as up to 30% of confirmed cases presented without any symptoms! (8).

Those presenting with symptoms may complain of Blurred vision, loss of visual field, floaters/flashes, and irritation (8). Those symptoms may be explained by the classic shape of the tumour, seen on examination; it usually presents as a “mushroom-like” shape as it breaks through Bruch’s membrane (the innermost layer of the choroid), which disturbs the retinal layers – resulting in those symptoms (9).

Some tumours may appear amelanotic (without pigmentation) which are more difficult to spot. They can also be very aggressive, causing local bleeding and protrusion of the eyeball (proptosis), whilst others may metastasise causing constitutional symptoms like weight loss and fatigue (10).

Differentials

There are a few conditions that may overlap with the fundoscopic presentation of choroidal melanoma (See figure set 1). Some of these include the pre-disposing congenital conditions mentioned previously, such as (10):

1. Naevus
2. Congenital Ocular Melanocytosis
3. Secondary metastasis
4. Retinoblastoma (the commonest cause of childhood white pupil)
5. Cavernous Haemangioma (blood vessels malformations)
6. Foreign body

Investigations

Although primarily a clinical diagnosis, various investigations allow assessment of the disease nature and burden (11), such as Ultrasound (US), Computerised-Tomography (CT), Magnetic Resonance (MR) and Fine-Needle Aspiration Biopsy (FNAB).

The specialist can order those investigations to support in making an accurate staging and assess for metastases. This allows the tumour to be staged according to the T (tumour) N (node) M (metastases) system (12).

Referral

In the United Kingdom, national guidelines denote that suspected cancer cases must be referred to an appropriate specialist via the urgent 2-week-wait (2WW) pathway, and the same applies to ocular melanomas (13). In turn, those patients will then be managed in one of the specialist ocular oncology centres.

As with other cancers, a multidisciplinary team (MDT) should be involved early on for shared decision making. The team usually involves an ocular oncologist, histopathologist or radiologist and a clinical nurse specialist. If the disease more advanced, more specialists can be involved.

Management

Management of ocular melanomas can be divided into two main categories: non-surgical or medical management, and surgical (13).

The choice of treatment depends on several factors, including patient choice, staging of the tumour and suitability of the patient.

• Non-surgical options
  • These include the use of radiotherapy and phototherapy. Both techniques are often reserved for patients that are unfit for surgery, to control the tumour growth.
• Surgical options
  • Depending on the size and location, tumours can be simply excised but in more advanced cases it may involve the whole eye (Enucleation) or removal of the eye plus all content within the orbit (Exenteration).
• Metastasis
  • Metastatic disease will require palliative control with systemic chemotherapies. Surgical interventions will be aimed at symptomatic control.
  • The most common site of metastases is the liver, which occurs in up to 50% of cases (15).

 Due to the risk of recurrence, these patients require lifelong follow-up.

Prognosis

The prognosis depends on several factors including tumour pathology, metastases, and patient’s demographics (16). Poorer prognosis is associated with tumours of greater thickness, genetic mutations, and extra-ocular spread. One study (17) yielded that median survival after liver metastasis is very poor; about 4 – 6 months.

It is important to note that not every patient will want to know their prognosis, as some may want to avoid the extra psychological burden. However, prognosis allows patients to be categorized based on the risk of progression and metastasis, and therefore patients can be enrolled into randomized studies to evaluate therapies used, enhancing future care for choroidal melanoma.

Conclusion

Choroidal melanoma is a rare manifestation of malignant melanoma that can primarily arise from melanocytes at the choroid of the retina, or secondarily to skin metastases. It can present asymptomatically with a high risk of pre-existing subclinical metastatic spread, but the local mass effect may cause loss of vision. Although diagnosed clinically, imaging is important to assess the spread of the tumour. As with other cancers, an urgent referral is necessary, and an MDT approach is required to determine management. Patient follow-up is lifelong. Due to the implications, clinicians are recommended to refer any pigmented lesions on the ocular surface or intraocular to rule out malignancy.

References

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