Anterior segment
tumours

Referral priority: Low or urgent

All patients suspected of having malignant tumours in the anterior segments of the eye must be promptly referred to an ophthalmologist or a hospital following local guidelines. However, patients diagnosed with conjunctival naevi and benign lesions should only be monitored without requiring immediate referral.

Click on one of the cards below to read more about the specific eye condition.

Written by
Marko Lukic
Edited by
Svein Tindlund and Jon Gjelle
Published
June 2023
Sections
01
Introduction

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02
Symptoms

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03
Clinical features

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04
Diagnostics

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05
Management and treatment

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06
References

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Atlas overview
Sections
01 Introduction
01

Introduction

There are various tumours of anterior eye segments. They are of different origins and may be either benign or malignant. This chapter will focus on conjunctival melanocytic tumours, conjunctival intraepithelial neoplasia, lymphoma of the conjunctiva, and iris melanoma.

Conjunctival naevus, primary acquired melanosis (PAM), and conjunctival melanoma are tumours within the conjunctival melanocytic tumours group.(1)

Conjunctival nevi are the most common melanocytic conjunctival tumours. They are more common in Caucasians and appear within the first two decades of life. They are typically located in the interpalpebral conjunctiva near the limbus and rarely involve the cornea. The risk of transformation into conjunctival melanoma is 1%.(2) Conjunctival naevi can be classified into junctional, subepithelial, and compound. Compound ones are the most common ones. The naevi may have the presence of cysts which is visible on a slit lamp. They are most common in people with brown irises.3 Changes in tumour colour were detected in 13%, and a change in tumour size was detected in 8%.(3)

Primary acquired melanosis is an uncommon unilateral condition that typically affects middle-aged Caucasians. The proliferation of conjunctival epithelial melanocytes characterizes the lesion. Based on histology, it may be PAM without melanocytic cellular atypia and PAM with melanocytic cellular atypia.4 The latter has a 50% chance of developing into conjunctival melanoma.(4,5)

Conjunctival melanoma accounts for about 2% of all ocular malignancies.(4) The histological findings are like cutaneous melanoma. 71% of conjunctival melanomas were associated with PAM with atypia, and 17% arose from a nevus. De novo conjunctival melanoma is sporadic. Conjunctival melanoma usually affects white individuals with a median age of 62 years. Shields et al. reported that the tumour was most found in the bulbar conjunctiva (72%), caruncle (15%), or plica semilunaris (11%). Rarely was the tumour found in the fornix (1%), tarsal conjunctiva (1%), or within the cornea (<1%).(5)

Conjunctival intraepithelial neoplasia is an uncommon, slowly progressive unilateral disease. Risk factors include ultraviolet light exposure, HPV infection, AIDS, and xeroderma pigmentosum.(4,6) The histological spectrum includes conjunctival epithelial dysplasia, carcinoma-in-situ, and squamous cell carcinoma. Clinical differentiation between these three conditions is not reliable. The conjunctival invasive squamous cell carcinoma incidence varies from 0.02 to 3.5 per 100,000. It is more common in men (75%) and elderly patients (75%>60 years old). Conjunctival invasive squamous cell carcinoma most commonly begins at the limbus (75%).(6,7)

Lymphomas are malignant neoplasms derived from monoclonal proliferations of B or T lymphocytes. Conjunctival lymphomas comprise about ¼ of all ocular adnexal lymphomas, with nearly all (98%) of B-cell lineage arising from mucosa-associated lymphoid tissue (MALT). They arise from three clinical settings; de novo and extension from orbital lymphoma may be associated with systemic lymphoma. It is mostly presented in elderly patients, and it may be bilateral.(4,8)

Iris melanoma is the most common primary neoplasm of the iris and accounts for approximately 5% of all uveal melanomas. The average age of involvement lies within the 5th decade. Although there is no gender preference, iris melanomas occur more frequently in Caucasians with light-coloured iris.(4,9,10) Most iris melanomas have low-grade malignancy.

02

Symptoms

Patients with conjunctival melanocytic lesions (naevi, PAM, and melanoma) are usually asymptomatic. In most cases, they visit an eye care specialist when they notice a change in colour or size of the lesion, or those lesions are recognized during a regular eye examination.

Patients with conjunctival intraepithelial neoplasia and conjunctival lymphoma may represent eye irritation and discomfort. Some of them notice conjunctival mass. The conjunctival lymphoma may represent chemosis, epiphora, dry eyes, and ptosis.

Most patients with iris melanoma are symptomatic. They may notice a growing iris mass. Those patients with circumscribed iris melanoma or diffuse iris masses may represent heterochromia, uveitis, cataract, and glaucoma.

03

Clinical features

Conjunctival naevi

They represent solitary, sharply demarcated, flat, slightly elevated, pigmented bulbar lesions. The naevi are most often located in the juxta limbal area. The extent of pigmentation is variable (some may be non-pigmented). Cystic spaces are often. The second most common location of the naevi is the plica and caruncle.

Any unusual site like palpebral or fornical conjunctiva and any sudden increase in growth or pigmentation should be suspected of potential malignancy!

Primary acquired melanosis (PAM)

The PAM without atypia can present at any age, whilst the PAM with atypia is usually seen after the age of 45 years. It represents irregular, unifocal, or multifocal areas of flat, brown pigmentation, which may involve any part of the conjunctiva. It may expand or stay stable for a long period. Clinically, it is impossible to distinguish PAM without and with atypia (only histologically). However, any sudden appearance of one or more modules in otherwise flat lesions is a sign of malignant transformation.

Image 1. Diffuse primary acquired melanosis.

Conjunctival melanoma

Conjunctival melanoma mostly appears in the sixth decade. Those patients with dysplastic naevus syndrome may develop conjunctival melanoma earlier. A common site of conjunctival melanoma is a limbus, represented as a black or grey nodule with feeder’s vessels. Amelanotic conjunctival melanomas are smooth and appear as a fish-flesh.

Image 2. Conjunctival melanoma – affects the bulbar conjunctiva, fornix, and tarsal conjunctiva.
Image 3. Conjunctival amelanotic melanoma *Courtesy of prof N. Vukojevic, Ophthalmology Clinic, University Hospital Zagreb

Conjunctival intraepithelial neoplasia and squamous cell carcinoma

The conjunctival intraepithelial neoplasia (CIN) is a squamous neoplasia confined to the conjunctival epithelium that sometimes transgresses the basement membrane but strictly does not have the potential to metastasize, unlike invasive squamous carcinoma. Conjunctival intraepithelial neoplasia could be a fleshy, sessile, or minimally elevated lesion frequently appearing perilimbal in the interpalpebral zone or less commonly in the inferior fornix or palpebral conjunctiva. CIN can extend into the adjacent corneal epithelium. It appears like a grey superficial opacity that can be avascular or have fine vascularization.

Conjunctival invasive squamous cell carcinoma cannot be differentiated clinically from CIN. It frequently occurs in the interpalpebral region of Caucasian elderly or immunosuppressed patients. The lesion can be a sessile, gelatinous, circumscribed, or papillomatous mass with leukoplakia. Some lesions are diffuse, flat, and poorly delineated, which can be confused with chronic conjunctivitis, scleritis, or pagetoid invasion of sebaceous carcinoma.

Conjunctival lymphoma

They represent slowly growing, mobile, salmon-pink, or flesh-coloured infiltrate in the fornices or epibulbar surface. Very rarely, they may be diffuse lesions that mimic chronic conjunctivitis.

Iris melanoma

Several clinical variations include circumscribed, diffuse, and tapioca iris melanoma. Circumscribed iris melanomas appear as a variably pigmented, well-defined mass in the iris stroma and are more commonly found in the inferior half of the iris. The degree of pigmentation can vary, as well as the shape. Some are small and flat, and others are elevated and dome-shaped.

Image 4. Iris melanoma
Image 4. Iris melanoma – note nodular bump in the inferior iris (white arrow) *Courtesy of prof N. Vukojevic, Ophthalmology Clinic, University Hospital Zagreb

Diffuse iris melanomas present progressive iris discolouration with the disappearance of iris crypts and pigment accumulation in the anterior chamber. They may give rise to ipsilateral hyperchromic heterochromia. These can be misdiagnosed as pigmentary glaucoma or pigment dispersion syndrome.

Tapioca melanoma is a variant of iris melanoma with multiple amelanotic nodules on the surface, giving the appearance of tapioca pudding.(11)

Iris melanomas may represent pupillary distortion, ectropion uveae, and glaucoma. Features associated with malignancy include prominent vascularity, rapid growth, diffuse spread, and seeding.

04

Diagnostics

Colour photography is vital for further monitoring conjunctival/iris lesions.

Ultrasound biomicroscopy is useful in iris melanomas where shape and size are well-established.

Biopsy (incisional and excisional) and histopathology are most important in accurately diagnosing conjunctival lesions.

05

Management and treatment

Conjunctival melanocytic tumours
Conjunctival naevi should be well photographed and monitored only. In case of any change in growth or pigment, it may be excised.

Lesions suspicious of PAM should be carefully biopsied. The PAM without atypia requires no treatment, whilst PAM with atypia should be treated. Smaller lesions should be excised, and larger lesions can be treated with mitomycin C or cryotherapy.

The primary treatment of conjunctival melanoma is the excision of the entire tumour with wide surgical margins of 3-5mm. A “no touch” technique should also be used, not touching any cancerous cells with surgical instruments, which could also spread cells. If the tumour invades the sclera, part of the sclera should also be removed. Cryotherapy can be used as adjuvant therapy for excision. Lesions thicker than 2 mm requires lymph node biopsy. Metastatic conjunctival melanoma can be treated with BRAF inhibitors and KIT inhibitors.

Conjunctival intraepithelial neoplasia
Both CIN and conjunctival squamous cell carcinoma are surgically treated using the “no touch” technique to avoid the potential risk of seeding. This technique incorporates large macroscopically tumour-free margins (at least 4 mm) in a single piece to increase the likelihood of clear margins. Cryotherapy is then applied to the conjunctival and limbal margins depending on the size of the wound defect, and the conjunctiva is either closed primarily or with a graft (amniotic membrane or auto conjunctival graft). Topical chemotherapy (MMC and 5-FU) is often used as adjuvant therapy to surgical excision. Enucleation or orbital exenteration is reserved for cases with intraocular or periocular invasion.

Treatment for conjunctival lymphoma is multidisciplinary, with ophthalmologists, haematologists, and radiotherapists ranging from surgical resection, cryotherapy, radiotherapy, systemic chemotherapy, or targeted anti-B-cell therapy.

Iris melanoma
Small lesions with no growth could be carefully watched and well documented. Worrisome features are documented growth, surface nodularity, a height greater than 2mm, prominent vascularity, and associated hyphema. Those lesions require treatment, and among treatment options are brachytherapy, excisional biopsy (iridectomy with anterior cyclectomy if needed), and enucleation. Enucleation is reserved for a diffuse involvement of the iris and angle structures or the development of complications like glaucoma that are not amenable to non-invasive methods.

Patients with conjunctival tumours should be treated by experienced and trained physicians.

06

References

1 https://eyewiki.aao.org/Conjunctival_Melanocytic_Tumors

2 Gerner N, Nørregaard JC, Jensen OA, Prause JU. Conjunctival naevi in Denmark 1960–1980: A 21‐year follow‐up study. Acta Ophthalmologica Scandinavica. 1996 Aug;74(4):334-7.

3 Shields CL, Fasiudden A, Mashayekhi A, Shields JA. Conjunctival nevi: clinical features and natural course in 410 consecutive patients. Archives of ophthalmology. 2004 Feb 1;122(2):167-75.

4 Kanski, J. and Bowling, B., 2016. Kanski’s Clinical Ophthalmology. [Edinburgh]: Elsevier.

5 Folberg R, McLean IW, Zimmerman LE. Malignant melanoma of the conjunctiva. Human pathology. 1985 Feb 1;16(2):136-43.

6 Shields CL, Chien JL, Surakiatchanukul T, Sioufi K, Lally SE, Shields JA. Conjunctival tumours: a review of clinical features, risks, biomarkers, and outcomes—The 2017 J. Donald M. Gass Lecture. The Asia-Pacific Journal of Ophthalmology. 2017 Mar 1;6(2):109-20.

7 https://eyewiki.aao.org/Conjunctival_Epithelium_Neoplasms#:~:text=The%20conjunctival%20papilloma%20is%20an%20elevated%20lesion%2C%20that%20usually%20has,bulbar%20conjunctiva%20or%20the%20caruncle.

8 https://eyewiki.aao.org/Conjunctival_Lymphoma#:~:text=Conjunctival%20lymphomas%20make%20up%20about,B%20cell%20(3%25)%20lymphoma.

9 https://eyewiki.aao.org/Iris_Melanoma

10 Shields CL, Shields JA, Materin M, Gershenbaum E, Singh AD, Smith A. Iris melanoma: risk factors for metastasis in 169 consecutive patients. Ophthalmology. 2001 Jan 1;108(1):172-8.

11 Reese AB, Mund ML, Iwamoto T. Tapioca melanoma of the iris: Part 1. Clinical and light microscopy studies. American Journal of Ophthalmology. 1972 Nov 1;74(5):840-50.