Pigmented eyelid skin lesions are those that display hues of brown, black or blue, or may be mistaken for brown or black lesions.
The pigmentation of skin lesions is caused by:
Melanin, blood, and exogenous pigment (eg, tattoo)
It is imperative to monitor any changes in size, shape or color of these lesions as they may indicate eyelid skin cancer. Early detection and treatment can save cosmetic appearance, vision, and lives.
The eyelids often are affected by a variety of lesions. Most eyelid lesions are of benign origin, but some eyelid lesions may be malignant.
Malignant melanomas are responsible for only 1% of all eyelid lesions. The importance of this lies in the fact that, although only 3% of all skin cancers are melanomas, more than two thirds of all deaths from skin cancer are attributable to malignant melanoma. Therefore, it is important to recognize benign and malignant lesions of the eyelid, especially when pigmented. See the images below.
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Lentigo maligna or superficial spreading melanoma of the eyelid. Courtesy of Joel Sugar, MD.
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Focal melanoma of the upper lid in a patient with history of prior excised conjunctival melanoma. Courtesy of M Duffy, MD, PhD.
Suspicious eyelid lesions, particularly when they are pigmented, need to be removed for purposes of a biopsy. Although a pigmented eyelid lesion may appear benign, it is wise to obtain a specimen for pathological examination because of the associated risk for mortality associated with malignant melanoma. Eyelid lesions in patients aged 76 or older are more likely to be malignant.[1]
Pigmented lesions in infants and small children are more commonly benign and related to inflammation and may pose a significant risk of vision problems. This is particularly true with capillary hemangiomas, cavernous hemangiomas, and giant hairy nevi. Pigmented lesions in infants and children also may be associated with pathology in contiguous structures or associated with systemic disease. These lesions should alert the ophthalmologist that further investigation may be needed. This is particularly true with such lesions as cavernous hemangioma, lymphangioma, and juvenile xanthogranuloma.
The frequency of pigmented lesions of the eyelid varies according to the lesion type and patient characteristics. Certain lesions are seen only in infants and small children, whereas others are seen only in elderly persons (seborrheic keratosis). Environmental characteristics play a role, with the frequency of benign and malignant eyelid lesions increasing in areas closer to the equator. In a major study of removed eyelid growths, 59% were of epidermal origin, 1.5% were malignant, and 6% were premalignant (eg, actinic keratosis or Bowen's disease). Among the malignant growths, the majority (95%) were basal cell carcinoma and a minority (5%) were squamous cell carcinoma. In another significant study of eyelid tumors, 85.7% were benign, 1.1% premalignant, and 13.1% malignant growths. More than half (56.5%) of malignant tumors were basal cell carcinomas, 34.6% were sebaceous carcinomas, 3.8% were squamous cell carcinomas, and 1.7% were lymphoma or plasmacytoma.[2, 3]
Pigment-producing cells derive embryologically from the neural crest. These cells are destined to reside in the basal cell layer of the epidermis. Melanocytes are melanin-producing cells found in the basal cell layer of the epidermis. Nevus cells are incompletely differentiated melanocytes that are found in clumps in the epidermis or the dermis. Nevus cells may or may not produce pigment and, therefore, can be classified as melanotic or amelanotic.
Nevi (moles) can be congenital or acquired. Congenital nevi acquire pigmentation at puberty, at which time they slowly migrate from the epidermis to the dermis.[4] Coincident with this descent, nevi become less active and, therefore, less capable of converting into a malignant lesion. The most active nevus is the junctional nevus. This resides at the epidermal/dermal border and is the most likely of all nevi to convert to a melanoma. As nevi descend further into the dermis (compound and intradermal nevi), they become relatively inactive and, thus, incapable of malignant transformation.
Melanomas arise from epidermal melanocytes and represent less than 1% of all eyelid tumors. It can occur in 1 of the 3 following forms: superficial spreading malignant melanoma, lentigo maligna melanoma, and nodular melanoma. Lentigo maligna is the premalignant form of lentigo maligna melanoma. This is found on the face of elderly patients and is related to exposure to the sun. Once this lesion penetrates into the dermis, it is classified as a lentigo maligna melanoma. Lentigo maligna melanoma is responsible for 90% of all head and neck tumors.
Melanocytes produce melanin and are derived from neural crest cells. Pigmented lesions of the eyelids arise from 1 of 3 types of melanocytes, as follows: (1) epidermal or dendritic melanocytes, (2) nevus cells or nevocytes, and (3) dermal or fusiform melanocytes.
Eyelid melanoma shares similarities with cutaneous melanoma and has similar risk factors such as excessive sun exposure, dysplastic nevi, personal history of melanoma, older age, and Fitzpatrick skin types I-II. Additionally, there are systemic conditions that may increase the likelihood of developing eyelid melanoma, including familial atypical multiple mole melanoma syndrome, familial melanoma, and xeroderma pigmentosum.[1, 3]
A careful history is important when a patient presents with a pigmented lesion of the eyelid. A patient should be asked when the lesion was first noticed; whether it was present at birth; if it has changed in size, shape, or color; and whether there are any associated symptoms, such as discharge, irritation, or bleeding. Benign lesions tend to maintain a uniform appearance, while malignant melanomas tend to be asymmetric, have irregular borders, and often are associated with changes in color. This has been taught to medical students as the ABCs of melanoma.[5]
Benign lesions
Freckles: These lesions are small (1-3 mm in diameter) tan-to-brown macules originating from epidermal melanocytes. They occur more commonly in light-skinned individuals and darken with sun exposure. These lesions reflect melanocyte overactivity, not proliferation.
Lentigo simplex: These lesions arise from epidermal melanocytes and may appear on skin and mucous membranes as brown macules. They usually appear in childhood, are unaffected by sun exposure, and are associated with Peutz-Jeghers syndrome.
Solar lentigo: These tan-to-brown macules are found commonly in sun-exposed areas of older individuals and in patients with xeroderma pigmentosum. Lesions usually have irregular borders and slowly increase in size.
Melasma: Melasma is a skin condition that is characterized by the development of irregularly shaped skin areas containing varying shades of brown pigmentation. It most commonly occurs on the sides of the face, the forehead, the upper lip, the chin, and the sides of the neck. Frequently, melasma is associated with pregnancy or the use of oral contraceptives, but melasma can occur in men. Most pregnancy-associated cases fade away following delivery, eventually clearing within a few months.
Melanocytic nevus: They frequently occur on the eyelid skin and on the eyelid margins. The clinical appearance often is predictive of histologic type (see Histologic Findings). Lesions typically present in childhood as small, flat tan macules that increase in size. As the lesion increases in diameter, a nest of cells drops off into the dermis; then, a compound nevus is formed. They are elevated slightly and pigmented. Intradermal nevus are dome-shaped, pedunculated, or papillomatous and usually are less pigmented or amelanotic.
Congenital melanocytic nevus: These lesions occur in 1% of newborns and may be single or multiple and usually are deeply pigmented. Their border is irregular, and the surface may be covered with hair. The challenges of management of facial congenital melanocytic nevi (CMN) are the balance of the risk of malignant transformation, surgical management, and long-term evaluation of functional and cosmetic outcomes.[6]
Spindle-epithelioid cell nevus: Also termed juvenile melanoma or Spitz nevus, spindle-epithelioid cell nevus is a pink-to-orange dome-shaped nodule occurring in children and young adults.
Balloon cell nevus: They are lightly pigmented, elevated lesions that usually are less than 5 mm in diameter. No clinical features are used to make the differential diagnosis with the other nevocellular nevi.
Nevus of Ota: These nevi are blue-to-purple lesions with mottled discoloration of the skin in the distribution of the ophthalmic and maxillary divisions of the trigeminal nerve. Nevus of Ota frequently is associated with ipsilateral ocular melanocytosis involving the conjunctiva, sclera, and uveal tract.
Blue nevus: These nevi are solitary, blue nodules that are less than 1 cm in diameter.
Malignant lesions
Cutaneous malignant melanoma: Lentigo maligna is a tan or brown macular lesion with irregular borders and is the premalignant stage of lentigo maligna melanoma.[7] Superficial spreading melanomas present as a brown, irregularly shaped macule. Nodular melanomas typically are dark brown or black nodules or plaques (rare on eyelids). See the image below.
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Lentigo maligna or superficial spreading melanoma of the eyelid. Courtesy of Joel Sugar, MD.
Basal cell carcinoma are pigmented about 5% of the time; 13 (5.06%) of 257 cases were found to have pigment in a recent study by Kirzhner and Jakobiec.[8]
Any pigmented lesion that shows growth is suggestive of malignancy, and a biopsy should be performed. Particular characteristics that are suggestive of malignant transformation are irregular borders, changes in color, asymmetry, ulceration, or bleeding.
Pigmented lesions in childhood that cause disruption of images to the retina and are amblyogenic should be treated surgically.
Eyelid skin, although thinner, is continuous with and, therefore, histologically identical to skin in other parts of the body. The dermis contains a collagen matrix with vascular channels and dermal appendages. The epidermis contains a basal cell layer where melanocytes reside. The eyelid margin is continuous with the palpebral conjunctiva.
Pigmented lesions can arise on the eyelid or eyelid margin. Margin tumors should arouse the suspicion of a conjunctival neoplasm. The propensity of pigmented lesions to arise on the eyelid is related to the actinic exposure of the area.
A medical background involving a history of skin cancer, UV exposure, and non-healing or recurrent cutaneous lesions ought to raise concerns regarding periorbital skin malignancy.
Examination under magnification with a slit-lamp or dermatoscope is useful for accurately characterizing the lesion. Measure each suspicious lesion in millimeters in both vertical and horizontal dimensions. Palpate the edges of the lesion to determine if it is involved or fixed to deeper tissues.
Eversion of the lower lid and double-eversion of the upper lid are crucial for determining the involvement of the conjunctiva and fornices.[9]
During the evaluation of a potentially malignant pigmented eyelid lesion, the following should be noted:
Color
Diameter
Shape and border
The appearance of telangiectasic vessels
Madarosis
Ulceration
Poliosis
Local lymph node exam
Local invasion to lacrimal drainage system, ocular surface and orbit
Freckles: These demonstrate hyperpigmentation on the basal layer of the epidermis.
Lentigo simplex: These lesions show hyperpigmentation on the basal layer of the epidermis with an increased number of melanocytes.
Solar lentigo: See lentigo simplex.
Melanocytic nevi: These lesions can be classified histologically as junctional, compound, or intradermal. Junctional lesions show nests of nevus cells in the epidermis at the dermal-epidermal junction. Compound nevus is when the nests of nevus cells are dropping off into the dermis, and, on intradermal lesions, the remaining epithelial nests migrate into the dermis.
Congenital melanotic nevi: Many lesions contain features of compound nevi with nevus cells in the dermis and the dermal-epidermal junction.
Spindle-epithelioid cell nevus: Compound nevi with spindle or epithelioid cells are present throughout the epidermis and dermis. Mitotic figures and nuclear atypia are present. Histologic differentiation from malignant melanoma may be difficult to make.
Balloon cell nevus: Lesions contain balloon cells, with small pyknotic nuclei and granular or vacuolated cytoplasm.
Nevus of Ota: Pigmented dendritic melanocytes are present throughout the dermis.
Blue nevus: Pigmented dendritic melanocytes and macrophages are scattered throughout the dermis with fibrous tissue adjacent.
Malignant melanoma: Lentigo melanoma is characterized by hyperplasia of atypical melanocytes throughout the basal cell layer. Superficial spread melanoma is typified by atypical melanocytes that occur in nests throughout all levels of epidermis. In nodular melanoma, dermal invasion is always present, and it exhibits large anaplastic epithelioid cells.
Tumor depth has been the hallmark of staging in cutaneous malignant melanoma. As described by Breslow,[10] melanomas measuring 0.76 mm or less carry a 5-year survival rate of 100%, whereas those invading greater than 1.5 mm are associated with a 5-year survival rate of 50-60%.
In 2021, the most extensive analysis of eyelid skin melanoma was published. The study revealed a 5-year overall survival rate of 88.6% for melanoma in situ and 77.1% for invasive melanoma. Furthermore, the researchers identified that being aged ≥75 years at diagnosis, T4 staging, lymph node involvement, and the nodular melanoma histologic subtype were indicative of poor survival.[11]
The benign pigmented lesions of the eyelids do not require any medical therapy. However, any benign lesion that affects vision should be excised with primary reconstruction. Vision can be affected in various ways, most commonly by a mechanical blepharoptosis (with occlusion of the visual axis) or by induction of astigmatism. In the first 10 years of life, this can lead to amblyopia and permanent reduction of vision if not treated in a timely fashion. Malignant lesions require surgical excision.
For patients with primary periocular basal cell carcinoma, Moesen et al found that cryotherapy using a nitrous oxide probe has certain advantages over surgical removal of tumors in the periocular region, but careful follow-up is advisable.[12]
Surgical therapy may be performed for cosmetic reasons or suspicion of malignancy in benign pigmented lesions.
The procedure of choice for treatment of cutaneous malignant melanoma of the eyelid is wide surgical excision with 1 cm of skin margins confirmed by histology. Regional lymph node dissection should be performed for tumors greater than 1.5 mm in depth and/or for tumors that show evidence of vascular or lymphatic spread.
Surgical excision always should be performed with attention placed toward obtaining clean surgical margins. At the present time, 2 forms of analysis currently are performed to obtain this goal, as follows: frozen sectioning and Mohs micrographic surgery. Mohs surgery is a specialized technique and is not offered in many rural areas. Although both modalities achieve the same endpoint, it has been postulated that Mohs surgery provides a more definitive result. This does not mean that frozen section analysis is in any way inadequate or inferior, as frozen section analysis does yield excellent results. At the current time, surgeon preference dictates pathological processing. If possible, frozen sections of pigmented malignant lesions should be confirmed with permanent sections of margins. Any suspicion of a positive margin with a pigmented malignancy should prompt reoperation with a new biopsy or a wider excision.
A retrospective survey of the members of the American Society of Ophthalmic Plastic and Reconstructive Surgery and the European Society of Ophthalmic Plastic and Reconstructive Surgery by Esmaeli and colleagues yielded 44 cases.[13]
According to this study, Breslow thickness is an important prognostic indicator for eyelid skin melanomas. A 5-mm margin of excision may be adequate for thin melanomas of the periocular skin, but because of the small number of patients in this series who had >5-mm margins, a definitive comparison of outcome with larger margins of excision cannot be made. For melanomas >/=2 mm, wider margins of excision may be prudent, and careful surveillance for local and regional recurrence is indicated..[13]
Laser can be used for certain eyelid pigmented lesions; a recent study has shown a case of bilateral uveitis after intense pulsed light therapy for eyelid pigmented lesions.[14]
In general, biopsy should precede all extensive tumor resections, even if the clinical diagnosis seems apparent. There is debate as to the danger of incising into a melanoma for biopsy. Biopsies of pigmented lesions that are highly suggestive of malignancy probably should be a complete excision (excisional vs incisional) and clear margins confirmed on permanent section from the primary excision.
A metastatic evaluation is recommended for patients who have malignant lesions.
Benign lesions should be observed. Epithelial lesions that display painless growth, irregular borders, ulceration, induration, or telangiectasia should raise suspicion of malignancy. Signs that show malignant change in pigmented lesions include irregular borders, asymmetric shape, color change or presence of multiple colors, recent changes, or diameter greater than 5 mm. As with all malignant lesions of the eyelid, madarosis (loss of eyelash cilia) and meibomian gland destruction also should increase suspicion significantly.
Benign lesions rarely have malignant transformation; therefore, a biopsy or excision should be performed on lesions suggestive of malignancy that demonstrate irregular growth or appearance.[15]
Nevus of Ota can present with malignant degeneration with the choroid at the site of involvement. Periodic fundus examination and follow-up care for glaucoma are recommended.
Metastasis is linked to the depth of invasion from malignant melanoma.
Iatrogenic complications from periocular surgery and radiotherapy carry a number of risks.These include:
Lagophthalmos
Symblepharon
Eyelid retraction
Ptosis
Ectropion
Entropion
Trichiasis
Dry eye syndrome from exposure, aqueous deficiency, or evaporation
Most benign lesions have an excellent prognosis. The treatment varies according to site, diagnosis, and systemic evolution. The prognosis and metastatic potential from melanoma are related to the depth of invasion, as described by Breslow.[10]
The current literature is not extensive enough to draw any conclusions regarding definitive treatment of malignant melanoma of the eyelid. At the current time, treatment of eyelid melanoma is extrapolated from data reported on melanoma treatment in other areas of the body. Further studies are warranted.
Donny W Suh, MD, MBA, FAAP, FACS, Professor, Department of Ophthalmology, Chief of Pediatric Ophthalmology and Adult Strabismus, Medical Director of Eye-Mobile, Gavin Herbert Eye Institute, UC Irvine Health, University of California, Irvine, School of Medicine; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Chief Medical Officer, Suh Precision Syringe, LLC; Medical Staff, Children’s Hospital of Orange County
Disclosure: Nothing to disclose.
Coauthor(s)
Christine Hakimeh, MD, Fellow in Pediatric Ophthalmology, UCI Health Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine
Disclosure: Nothing to disclose.
Kourosh Shahraki, MD, Postdoctoral Research Fellow, Department of Ophthalmology, University of California, Irvine, School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Chief Editor
Hampton Roy, Sr, MD, † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Mounir Bashour, MD, PhD, CM, FRCSC, FACS, Assistant Professor of Ophthalmology, McGill University Faculty of Medicine; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD
Disclosure: Nothing to disclose.
Roger Bassin, MD, Clinical Instructor, Department of Ophthalmology, University of Illinois at Chicago
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