Eye (2013) 27, 199–207 & 2013 Macmillan Publishers Limited All rights reserved 0950-222X/13 www.nature.com/eye Oculoplastic aspects C Rene CAMBRIDGE OPHTHALMOLOGICAL SYMPOSIUM of ocular oncology Abstract represents a significant proportion of the oculoplastic surgeon’s workload. In this review, It is estimated that 5–10% of all cutaneous the features of periocular skin cancer are malignancies involve the periocular region presented together with a discussion of the and management of periocular skin cancers treatment modalities. account for a significant proportion of the oculoplastic surgeon’s workload. Epithelial tumours are most frequently encountered, Diagnosing malignant eyelid disease including basal cell carcinoma, squamous cell carcinoma, and sebaceous gland Although malignant eyelid disease is usually carcinoma, in decreasing order of frequency. easy to diagnose on the basis of the history and Non-epithelial tumours, such as cutaneous clinical signs identified on careful examination melanoma and Merkel cell carcinoma, rarely (Table 1), differentiating between benign and involve the ocular adnexae. Although malignant periocular skin lesions can be non-surgical treatments for periocular challenging because malignant lesions malignancies are gaining in popularity, occasionally masquerade as benign pathology. surgery remains the main treatment modality For instance, a cystic basal cell carcinoma (BCC) 4,5 and has as its main aims tumour clearance, can resemble a hidrocystoma or sebaceous restoration of the eyelid function, protection gland carcinoma (SGC) classically mimics a 6,7 of the ocular surface, and achieving a good chalazion. Conversely, a benign lesion such as cosmetic outcome. The purpose of this article a pigmented hidrocystoma may be mistaken for 8 is to review the management of malignant a malignant melanoma. Therefore, an eyelid periocular tumours, with particular emphasis biopsy is often required to make the correct on surgical management. diagnosis. For small lesions, excision biopsy Eye (2013) 27, 199–207; doi:10.1038/eye.2012.243; with a suitable margin might be appropriate, published online 30 November 2012 but larger lesions require an incisional biopsy. Punch biopsy is a simple technique, which has a Keywords: eyelid neoplasms; cryotherapy; role in the diagnosis and management of periocular skin tumours.9–11 Department of radiotherapy; Mohs surgery; reconstruction Ophthalmology, Cambridge University Hospitals NHS Malignant eyelid tumours Foundation Trust, Cambridge, UK Most malignant periocular tumours derive from epithelial cells (Table 2) and non-epithelial Correspondence: C Rene, Department of Introduction malignant eyelid tumours are fairly rare. Ophthalmology, Skin malignancies account for nearly one-third Therefore, the discussion that follows focusses Addenbrooke’s Hospital, of all newly diagnosed cancers,1 and it is mostly on the epithelial tumours, except for Cambridge University estimated that about 5–10% of them occur in the malignant melanoma. Hospitals NHS Foundation periocular region.2 Furthermore, periocular skin Trust, Hills Road, Cambridge, CB2 0QQ, UK 4 cancers account for 90% of ophthalmic Tel: þ 44 (0)1223 216500; 3 Basal cell carcinoma (BCC) tumours. Therefore, it is essential that all Fax: þ 44 (0)1223 217968. ophthalmologists are able to recognize the BCC accounts for the vast majority of periocular E-mail: cornelius.rene@ features of malignant periocular skin cancer and tumours (90–95%).12 They derive from the basal addenbrookes.nhs.uk be aware of the treatment modalities. Although layer of the epidermis, have ultraviolet (UV) non-surgical treatments for periocular skin light exposure as an important aetiological Received: 10 October 2012 Accepted in revised form: cancers are gaining in popularity, surgery factor and occur almost exclusively in fair- 11 October 2012 13,14 remains the main modality of treatment and the skinned patients. The mean age of incidence Published online: surgical management of periocular skin cancer is in the seventh decade, with a slight male 30 November 2012 Periocular oncology C Rene 200 preponderance, but they are increasingly seen in younger surface telangiectasia (Figure 1a). With progression they age groups because of excessive sun exposure or UV usually ulcerate with resultant bleeding and crust light from sun beds.15,16 The lower lid is the commonest formation (Figure 1b), or they may undergo cystic location, followed by the medial canthus, with the upper degeneration (Figure 1c). In contrast to nodular BCCs, lid rarely involved.2,12 morpheaform (or morpheic) BCCs have poorly defined On the basis of their clinical appearance BCCs can be margins (Figure 1d). Occasionally BCCs are pigmented classified into several clinical subtypes (Table 3), the (Figure 1e) or have a linear morphology. commonest of which is the nodular BCC,2,12 which The clinical behaviour of BCCs is largely determined presents as a well circumscribed, pearly lump with by their histological subtype (Table 4). In a study of 1039 BCCs, Sexton et al17 found that aggressive histological subtypes like micronodular, infiltrative, and morpheaform BCCs had a higher incidence of positive Table 1 Clinical features of malignant eyelid disease tumour margins (18.6, 26.5, and 33.3%, respectively) after Loss of lashes excision compared with nodular and superficial BCCs, Distortion of eyelid margin which were fully excised in 490% of cases. Pearly appearance (BCC) Telangiectasia The poor prognostic factors for BCC, in addition to Ulceration histopathological subtype, are summarized in Table 5. Induration Medial canthal tumours have a tendency to invade Eyelid cicatrization and secondary ectropion/retraction deeply and may involve the orbit early. Similarly, lateral Increasing pigmentation, especially of recent onset canthal tumours have a tendency to involve the lateral conjunctival fornix and lateral orbit. BCCs recurring after radiotherapy are more difficult to diagnose because the Table 2 Classification of malignant eyelid tumours tissue changes induced by radiation are very similar to Epithelial Non-epithelial those induced by the tumour. Therefore, these tumours present late and are more difficult to manage.12 BCC Malignant melanoma SCC Merkel cell tumour Sebaceous gland carcinoma Kaposi sarcoma (SGC) Table 4 Histological subtypes of BCC Metastases Nodular Lymphoma Morpheaform Microcystic adnexal Infiltrative carcinoma Superficial spreading Malignant sweat gland Micronodular tumours Mixed Table 5 Poor prognostic factors for BCC Table 3 Clinical varieties of BCC Aggressive histopathological subtype Nodular Medial canthus Nodulo-ulcerative Lateral canthus Morpheaform Large tumour Cystic Indistinct borders Pigmented Recurrent or incompletely excised tumour Linear Previous radiotherapy Figure 1 Morphological varieties of BCC. (a) Nodular, (b) noduloulcerative, (c) cystic, (d) extensive morpheaform BCC with ulceration and orbital invasion, and (e) pigmented BCC in lash line with adjacent pigmented intradermal naevus on lid margin. Eye Periocular oncology C Rene 201 Squamous cell carcinoma (SCC) area, including the caruncle. SGC is a very aggressive tumour, which metastasizes early and is often fatal. The SCC (Figure 2) accounts for about 2–5% of malignant incidence increases with age and peaks in the seventh to eyelid tumours.12 Like BCC, the lower lid is most eighth decades.6,7,19 A recent retrospective review from a frequently involved, UV light is implicated in its large US-based population registry confirmed that SGC causation and the incidence peaks in fair-skinned accounted for a higher proportion of malignant skin patients in their seventh decade, with a slight male tumours in Asian/Pacific Islander patients, but preponderance. They may derive from actinic keratosis concluded that this is due to a relative lack of other skin or Bowen’s disease and the risk increases after prolonged tumours rather than an inherent risk of developing SGC immunosuppression, previous radiotherapy and in in that subgroup compared with whites, as previously patients with xeroderma pigmentosum. As SCCs arise thought.19 The tumour may be multicentric and diffuse from keratinocytes in the epidermis, hyperkeratosis or involvement of the eyelids and conjunctiva can occur cutaneous horn formation are common features. Faustina because of pagetoid spread.6,7,12 It is renowned for et al18 found that the rate of metastasis to regional nodes masquerading as a wide variety of benign conditions, the could be as high as 24% with distant metastases and commonest of which are a chalazion (Figure 3) or chronic perineural invasion occurring less frequently. Poor blepharoconjunctivits.6,7,12 Other modes of presentation prognostic factors include poorly differentiated tumours, include a papilloma, trichiasis, conjunctival cicatrization, large tumour size, and perineural invasion. marginal keratitis, and corneal vascularization. Occasionally, it can also mimic other malignant pathology such as BCC and SCC.6 With such diverse Sebaceous gland carcinoma (SGC) presentation, SGC is often misdiagnosed and the This rare tumour, which arises from sebaceous glands, diagnostic delay is responsible for significant morbidity has a predilection for the head and neck, especially the and high mortality rate.6,7,12,19 Therefore, one should meibomian glands in the upper lid.6,7,19 However, it can maintain a high index of suspicion and a low threshold involve any of the sebaceous glands in the periocular for full thickness eyelid biopsy in an elderly patient