Chapter 3
Tumors of the Eyelids
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The eyelids are a highly specialized region of the ocular adnexa consisting of multiple tissue types, all having the potential to give rise to a spectrum of benign and malignant lesions. Accurate identification and classification of these lesions is important for proper care and management.

Tumors of the eyelids can be classified based on origin such as tumors of the epidermis/dermis, tumors of melanocytic origin, and those of glandular, neural, vascular, metastatic, xanthomatous, histiocytic, and inflammatory origin. In this chapter we discuss the various eyelid tumors based on their site of origin.

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Eyelid papilloma is a common benign growth arising from the periocular skin in older individuals. It is a flesh colored, pedunculated or sessile lesion with a corrugated or cerebriform surface (Fig. 1).1 Clinically it can simulate other benign and malignant lesions such as verruca vulgaris, seborrheic keratosis, inverted follicular keratosis, fibroma, and squamous call carcinoma. The majority of eyelid papillomas can be observed unless they cause mechanical disruption of eyelid function or are cosmetically disfiguring, in which case they can be completely excised. If a papilloma becomes irritated or painful excision is warranted.

Fig. 1 A cerebriform papilloma on the lower eyelid of a patient who was enucleated for retinoblastoma.


Seborrheic keratosis is a pigmented cutaneous lesion that can occur throughout the skin in older individuals but can develop in the eyelid area. This raised lesion can be smooth or verrucous, with varied pigmentation, size, and distribution (Fig. 2).2 It can be mistaken for cutaneous melanoma because of its pigmented appearance. It is managed with observation or surgical excision.3

Fig. 2 Seborrheic keratosis of the lower lateral eyelid.


Keratoacanthoma is a relatively rapidly growing skin lesion that can occur on the face and eyelids. Classically, it appears as a nodular mass with a central keratin-filled crater (Fig. 3). It generally develops on the skin but has been rarely recognized on mucous membranes including conjunctiva.4–9 It typically has a rapid onset over a few months and then regresses over a period of months. Clinically, it resembles noduloulcerative basal cell carcinoma or squamous cell carcinoma and may be difficult to differentiate from these lesions. Multiple keratoacanthomas occur in Ferguson-Smith syndrome and Muir-Torre syndrome. These syndromes can be associated with systemic neoplasms, particularly of the gastrointestinal system.4,10,11 Keratoacanthoma can be managed by observation, but has the potential to grow rapidly and be locally destructive or indistinguishable from true malignancy. For these reasons early complete excision is diagnostic and curative. For larger lesions or those involving critical structures, incisional biopsy can be preformed to exclude carcinoma, knowing that sampling error may occur. Other treatments such as cryotherapy, radiotherapy, and intralesional chemotherapy have been used, however, surgical excision is preferred when possible.5

Fig. 3 Keratoacanthoma with a central crater.


Inverted follicular keratosis, also known as basosquamous-cell acanthoma because of its lack of hair follicle involvement histopathologically, is a papillomatous skin nodule that occurs commonly on the face and eyelid margin in middle-aged adults.12 It is usually a solitary lesion that is more common in males and develops over a period of months. It can appear as a nodule at the eyelid margin often with a crusted surface. Control of these lesions is obtained with complete surgical excision. It is now believed to be an abortive variant of irritated seborrheic keratosis.12


Pseudocarcinomatous hyperplasia is a benign condition that simulates an eyelid malignancy. This lesion progresses quickly over a period of weeks and frequently is nodular with a crusted or ulcerated surface. It is usually idiopathic or can be a reactive phenomenon related to previous surgery, trauma, medication, adjacent carcinoma, or mycotic infections.13 Surgical excision is warranted to rule out malignancy.


Epidermal inclusion cyst is a slow-growing, firm, smooth, keratin-filled cystic lesion commonly found on both the upper and lower eyelids. This subcutaneous lesion arises spontaneously from pilar cysts or from trauma. Multiple epidermal inclusion cysts have been described in Torre's syndrome and Gardner's syndrome where they are associated with certain systemic malignancies.11,14 Care should be taken to remove the entire cyst to minimize the chance for recurrence.

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Basal cell carcinoma of the skin is the most common malignancy in Caucasians.15 It arises from the basal layer of the epidermis and locally invades surrounding tissues. Although basal cell carcinoma rarely metastasizes, it can be quite invasive and destructive. Basal cell carcinoma commonly affects the periocular skin, comprising 80% to 90% of all eyelid malignancies.16,17 The incidence of eyelid basal cell carcinomas is 14 per 100,000 population per year in white Americans and higher rates have been observed in other countries.18–21 Basal cell carcinoma typically occurs in older men and woman above the age of 50 and tends to affect individuals with fair complexion (blonde or red hair with blue or green eyes). Risk factors associated with development of basal cell carcinoma include ultraviolet radiation exposure, fair skin, sunburn during childhood, arsenic exposure, immunosuppression, previous basal cell carcinoma, and family history of skin cancer.

Basal cell carcinoma can be categorized into two basic types, the noduloulcerative and morpheaform, or sclerosing, variant. The noduloulcerative variant is the most common and accounts for 75% of basal cell carcinomas.18 It is a raised, firm, slow-growing, pearly or flesh-colored lesion. It typically shows telangiectatic vessels or ulceration, and usually demonstrates loss of overlying cilia (Fig. 4). The lower eyelid is most frequently involved, followed by the medial canthus, upper eyelid and lateral canthus. The morpheaform variant is typically diffuse, light colored, and relatively flat with indistinct borders (Fig. 5). This variant is more aggressive and invasive despite being less obvious, and it is more likely to show recurrence (Fig. 6).22,23 Other variants of basal cell carcinoma include pigmented, superficial, and cystic types.

Fig. 4 Nodular basal cell carcinoma with rolled edges.

Fig. 5 Morpheaform basal cell carcinoma involving the entire lower eyelid showing a thickened lower eyelid and loss of cilia.

Fig. 6 Another morpheaform basal cell carcinoma involving the lower eyelid demonstrating its poorly defined margins.

Systemic conditions associated basal cell carcinoma includes Gorlin-Goltz syndrome, xeroderma pigmentosum, nevus sebaceous of Jadassohn, and Bazex syndrome. Gorlin-Goltz syndrome is an autosomal dominant condition associated with multiple basal cell carcinomas that occur at an early age. Other findings include odontogenic keratocysts, palmer dyskeratosis, and bifid ribs.24 Xeroderma pigmentosum is an autosomal recessive condition associated with multiple skin carcinomas including basal cell carcinoma, squamous cell carcinoma, and melanoma. It is a result of a dysfunction in the DNA repair mechanism leaving individuals highly susceptible to ultraviolet radiation.24 Nevus sebaceous of Jadassohn is a sporadic condition that can be part of the organoid nevus syndrome. Cutaneous nevus sebaceous is a thickened greasy cutaneous plaque with an 8% to 14% chance of developing basal cell carcinoma and other adnexal neoplasms (Fig. 7).25 Bazex syndrome is an autosomal dominant condition characterized by multiple basal cell carcinomas in younger individuals.26 Associated findings include hypertrichosis, milia, hypohydrosis, and “ice-pick marks” on the extremities. Multiple basal cell carcinomas or occurrence at a young age should raise suspicion for associated syndromes.

Fig. 7 Nevus sebaceous of Jadassohn located below the lateral eyebrow. Note the small cutaneous horn arising from it.

Surgical management of primary lesions with wide margins and frozen section control or Mohs surgery is the preferred method of treatment and offers the lowest rates of recurrence.21,22 Most lesions can be removed and closed primarily. However, larger lesions may require reconstruction with grafts or flaps. Advanced lesions with extensive orbital invasion may require exenteration. Cryotherapy has been used in selected cases with reported success in treating small lesions.27 Radiotherapy has been used as a supplemental treatment in advanced cases.


Invasive squamous cell carcinoma or squamous cell carcinoma in situ (Bowen's disease) accounts for approximately 2% to 9% of eyelid malignancies.28–30 Lesions are typically seen in older individuals and have a predilection for Caucasian males, with a history of excessive exposure to ultraviolet radiation. Clinical presentation is variable but most lesions have associated skin damage or actinic keratosis (Fig. 8). The lower eyelid is affected more frequently and the lesion can involve the eyelid margin. It appears as a nodule or plaque with crusting and telangietatic vessels and rolled edges. Squamous cell carcinoma is locally invasive and can rarely metastasize to regional and distant lymph nodes. It is more commonly seen in immunocompromised patients.

Fig. 8 Squamous cell carcinoma involving the eyelids and face. This former lifeguard has had multiple surgeries for removal of squamous cell carcinomas from his face and eyelids.

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Eyelid nevus is a common benign growth of melanocytic origin that can be acquired or congenital. Acquired nevi can be classified as junctional (involving the base of the epidermis), dermal (involving only the dermis) or compound (involving both dermis and epidermis). An acquired nevus generally becomes apparent between the ages of 5 and 10 years as a small, flat, lightly pigmented lesion. With time, slow enlargement can occur as cells migrate into the dermis. Later in life, the nevus resides completely in the dermis where neuronization and desmoplasia can occur. These stages can be observed clinically (Fig. 9).

Fig. 9 Acquired eyelid nevus on the upper eyelid.

A congenital nevus is present at birth and can involve both upper and lower eyelids at a site where it divides embryologically (“kissing nevus”; Fig. 10). Nevi have a low potential to develop into melanoma and should be observed and excised if suspicious. Based on an analysis of nearly 340,000 patients, the lifetime risk for a cutaneous nevus to change into melanoma is approximately 1 in 3000 in men and 1 in 10,000 in woman.31,32

Fig. 10 Congenital eyelid nevus in a young girl involving upper and lower eyelid (kissing nevus).


Oculodermal melanocytosis, or nevus of Ota, is a congenital condition in which flat pigmentation involves the periocular skin, uveal tissue, and occasionally meninges, and oral mucosa. This condition is typically unilateral but can occur bilaterally. The dermal component rarely gives rise to melanoma, however, uveal involvement carries an increased risk for malignancy and these patients should be monitored annually for uveal melanoma (Fig. 11).33

Fig. 11 Oculodermal melanocytosis or nevus of Ota. Note the scleral pigmentation as well as dermal pigmentation of the upper and lower lateral eyelid.


Melanoma accounts for approximately 1% of malignant tumors of the eyelid. Similar to elsewhere on the skin eyelid melanoma can be divided into four types: nodular melanoma, superficial spreading melanoma, lentigo maligna melanoma, and acral lentiginous melanoma (Fig. 12).31 All but the latter occur on the eyelids. Management and prognosis are similar to melanoma elsewhere on the skin with the exception that the recommended surgical margins usually cannot be obtained because of the surrounding ocular structures. Sentinel lymph node biopsy can also be advised in these cases.

Fig. 12 Lightly pigmented melanoma of the lower eyelid, note the loss of cilia centrally.


Sebaceous carcinoma of the eyelid usually arises from Meibomian glands of the tarsus of the upper eyelid and less commonly the lower eyelid. It can also arise from the Zeis glands associated with the cilia and the sebaceous glands of the caruncle. Sebaceous gland carcinoma is a rare, potentially fatal malignancy that comprises 5% of malignant eyelid tumors. It typically affects older individuals, women more than men, with a higher incidence in Asians, where it comprises 30% to 40% of eyelid malignancies.34–36 Sebaceous carcinoma has also been reported in younger individuals who are immunosupressed or who have received radiation treatment.37

Clinically, sebaceous carcinoma can resemble indolent inflammatory conditions such as blepharitis or chalazion leading to a delay in diagnosis. Rates of misdiagnosis have been reported as high as 50%.38 Sebaceous carcinoma can assume a solitary nodular, diffuse or multicentric growth pattern. The lesion typically present as a painless nodule or thickening of the eyelid, occasionally yellow in color with loss of overlying cilia (Fig. 13). Pagetoid spread can lead to diffuse involvement of the conjunctiva and cornea (Figs. 14 and 15). Local invasion of deeper structures occurs in 6% to 17% and metastasis to the preauricular or submandibular lymph nodes occurs in 18% to 28% of cases.34,36 Management of sebaceous gland carcinoma must be individualized, depending on the extent of the disease. Staging map biopsies followed by surgical excision with frozen-section control or Mohs surgery can be performed. Cryotherapy, topical chemotherapy, and radiotherapy have also been used as adjuncts to surgery.39 Exenteration is occasionally necessary for control of advanced cases especially those with pagetoid disease or orbital invasion.36

Fig. 13 Sebaceous gland carcinoma, note the nodular involvement of the upper eyelid.

Fig. 14 Sebaceous gland carcinoma showing pagetoid involvement of the conjunctiva.

Fig. 15 Sebaceous gland carcinoma, note the diffuse involvement of the lower eyelid and conjunctiva.

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Syringomas are small, benign, tan, eccrine sweat gland tumors that occur mostly in young women on the lower eyelids and cheeks. It is often multiple and can manifest as a dominant trait. Observation or excision is warranted for these lesions (Fig. 16).

Fig. 16 Syringomas involving the bridge of the nose.


Eccrine acrospiroma is a benign lesion that arises from eccrine sweat glands. It can occur anywhere on the skin and can involve the face and eyelids. It is generally a solitary, rather fast-growing, flesh-colored nodule deep to the epidermis. It is often solid but can have a cystic component. Complete surgical excision offers excellent tumor control.


Eccrine hidrocystoma arises from ducts of eccrine sweat glands, occur most commonly on the eyelid and its margin. It is usually clear or bluish in color, smooth, and can enlarge with sweating (Fig. 17). Multiple lesions are common and they can be observed or excised.

Fig. 17 Eccrine hidrocystoma of the upper eyelid.


Apocrine hidrocystoma on the eyelid arises from the glands of Moll at the eyelid margin. It is usually a solitary cysts with a bluish hue from iron in the cyst wall (Fig. 18).40

Fig. 18 Apocrine hidrocystoma. Note the bluish hue of this large lesion.


Syringocystadenoma papilliferum is a rare benign lesion arising from apocrine glands or within a nevus sebaceous of Jadassohn.41 It often assumes a plaque-like or papillary configuration with a corrugated or ulcerative surface. Clinically, it can resemble basal cell carcinoma or keratoacanthoma and complete surgical excision is necessary.


Pleomorphic adenoma more often occurs in the lacrimal or salivary glands but can arise from apocrine glands of the eyelid. These solitary solid nodules are clinically indistinct and diagnosis is usually made histopathologically.42


Rarely the eyelid can give rise to malignant sweat gland tumors. They include mucinous sweat gland carcinoma, and apocrine gland adenocarcinoma. Complete excision with frozen section control or Mohs surgery is advised.

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Trichoepithelioma is a benign tumor that arises from hair follicles and involves the eyelids and face. Lesions can be solitarily or multiple as in Brooke's tumor. Brooke's tumor is an autosomal dominant condition associated with multiple trichoepitheliomas usually on the face.43


Trichilemmoma arises from the trichilemma of the hair follicle and produces a benign nodular tumor with an irregular surface on the eyelid margin or eyebrow in older adults. Lesions are usually solitary but multiple lesions occur occasionally as a marker for Cowden's disease, which has associated systemic findings.44


Pilomatrixoma, or benign calcifying epithelioma of Malherbe, develops from hair matrix cells and involves the eyebrows more often than the eyelids in children and young adults. It appears usually in the first decade of life as a reddish blue mass fixed to the skin, originating at eyelid margin or brow at the base of a hair follicle.45 Excision is warranted.

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Neurofibroma is a subcutaneous nodule comprised of neurons, fibroblasts, and Schwann cells and is divided into three types including localized, solitary and plexiform. The plexiform neurofibroma and multiple localized type are commonly seen in patients with neurofibromatosis whereas the solitary type can occur in normal individuals (Figs. 19 and 20).46

Fig. 19 Multiple neurofibromas in the periocular region in a patient with NF1 also note the lisch nodules on the iris.

Fig. 20 Plexiform neurofibroma in a young girl. Note the diffuse involvment of the right eyelid and face.


Neurilemoma (schwannoma) arises from peripheral nerves and occasionally can involve the eyelids.47 It can occur as an isolated lesion or in patients with neurofibromatosis type 1. Lesions are firm, yellow, painless nodules and are best managed with complete excision.


Merkel cell carcinoma is a rare, aggressive tumor that arises from specialized neuroendocrine cells (Merkel cells) found in the skin. It can occur on the eyelid in elderly individuals as a painless enlarging red nodule with telangietatic vessels. These lesions have a relatively high recurrence and metastatic rate. Management with wide surgical margins and frozen section control is the treatment of choice. Adjuvant radiation and lymph node dissection is considered after excision (Fig. 21).48–50

Fig. 21 Merkel cell carcinoma of the upper eyelid.

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Congenital capillary hemangioma is a common benign tumor that occurs shortly after birth.51 Lesions can occur superficially or deep to the epidermis. Superficial lesions involving the eyelids are soft and red with sharp margins. Capillary hemangioma typically enlarges within the first 2 to 6 months after diagnosis and then undergoes spontaneous regression over the following years (Fig. 22). Lesions may be amblyogenic by obstruction of the visual axis or induced astigmatism depending on the extent of eyelid involvement. Most lesions can be managed with observation and preventive measures for amblyopia. Intralesional or systemic corticosteroids have been used to hasten spontaneous regression and surgery is rarely necessary.52,53 Deep capillary hemangiomas appear as a bluish subcutaneous mass that can involve the orbit and cause compression and displacement of the globe (Fig. 23).

Fig. 22 Superficial congenital capillary hemangioma of the upper eyelid in a young boy.

Fig. 23 Deep capillary hemangioma of the upper eyelid.


Acquired capillary hemangioma or cutaneous pyogenic granuloma is an acquired red vascular nodule that occurs in adults in the periocular region. It has no malignant potential and can be safely observed (Fig. 24).

Fig. 24 Acquired capillary hemangioma.


Nevus flammeus or port-wine stain is a congenital vascular malformation, often associated with Sturge-Weber syndrome (Fig. 25). These lesions are usually observed but can be treated with pulsed-dye laser.54

Fig. 25 Nevus flamus in a young man with Sturge Webber Syndrome.


Kaposi's sarcoma is a malignant vascular tumor more commonly seen in immunosupressed patients with acquired immunodeficiency syndrome but also occur in older individuals of European descent.55,56 These lesions appear nodular or diffuse, red or purple, and can be solitary or multifocal. Management consists of systemic chemotherapy or local radiation.


Metastatic lesions to the eyelids are relatively rare.57 Lesions appear as solitary nodules that can resemble a chalazion. In contrast to chalazion, they tend to enlarge and can ulcerate. Biopsy of the lesion can confirm the diagnosis and help guide systemic therapy.

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Xanthelasma is a yellowish cutaneous plaque found in the periocular area in middle-aged and elderly individuals. It is composed of lipid-containing cells and is usually found in the upper eyelid bilaterally (Fig. 26). Management consists of observation and systemic lipid evaluation. Xanthelasma is sometimes seen in patients with Erdheim-Chester disease58 and necrobiotic xanthogranuloma.

Fig. 26 Bilateral xanthelasma of the upper eyelids.


Juvenile xanthogranuloma is a cutaneous inflammatory condition that can affect the eyelids, orbit, iris and conjunctiva as small, flesh colored nodules. Lesions usually spontaneously resolve, however systemic corticosteroids have been used to promote resolution of persistent nodules.


Molluscum contagiosum is a pox viral infection that is usually seen in young children and immunosupressed adults. Multiple umbilicated lesions occur on the eyelids and can produce a follicular conjunctivitis. Treatment includes observation or removal of the lesions by eviseration of their contents.


Chalazion is a common lipogranulomatous reaction to an obstructed Meibomian gland. Some malignancies can mimic their benign appearance. Management includes warm compresses, topical antibiotics, and occasionally incision and drainage. Recurrent or persistent lesions should be biopsied to exclude malignancy.

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Management of patients with cutaneous lesions in the periocular region should include thorough clinical history and examination, photographic documentation, and formation of a differential diagnosis followed by testing or biopsy and administration of the appropriate treatment. Considerations in treatment must include how therapy will affect the function of the eyelid and how diagnostic procedures will affect control of the disease. Incisional biopsies are a useful method for confirming or excluding a diagnosis, however, in certain cancers this technique may be detrimental and cause dissemination of the tumor. Excisional biopsy avoids this complication and should be used when appropriate. In situations when incisional biopsy is appropriate, adequate sample should be obtained in a representative portion of the lesion with a margin of normal surrounding tissue when possible. Techniques for excisional biopsies of eyelid lesions should use frozen section control or Mohs surgery if the clinical margins are indistinct or the presumed diagnosis warrants. Small lesions can be excised using anatomic knowledge of the anterior and posterior lamella. Limited excision of tumors allows for ease of surgical repair. For large lesions involving both anterior and posterior lamella, full-thickness resection with pentagonal wedge resection is a useful technique (Fig. 27A to 27C). Extensive lesions require complete eyelid removal or exenteration.

Fig. 27 Full thickness resection of a lower eyelid basal cell carcinoma. A,The planed pentagonal incision is marked with a marking pen. B,The lesion is resected. C, The eyelid one week after reconstruction using Tenzel flap closure.

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In summary, there are numerous benign and malignant tumors that can involve the eyelid. Clinical recognition and proper diagnosis and management are important for best patient care.
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