Eyelid Papilloma

Etiology

Papilloma etiology depends on the type of epithelial proliferation. Squamous papillomas and seborrheic keratosis are idiopathic benign cellular proliferations. There is no known definitive cause of these lesions. However, malignant skin lesions that can look like papillomas are often associated with chronic UV exposure and sun-damaged skin. Verruca vulgaris is caused by human papillomavirus type 6 or 11.

Epidemiology

One study found that, overall, epidermal tumors make up the majority of eyelid tumors. One study found seborrheic keratosis to be the most frequently encountered lesion, followed by squamous cell papilloma.[4] Another study, however, reported that squamous papillomas are the most common benign epithelial tumor of the eyelid.[1] Seborrheic keratosis is typically found in middle-aged or older adult patients. Squamous papillomas do not have a strong predilection for a particular race or sex. These papillomas tend to become more frequent with age, but they can occur at any age.

Histopathology

Seborrheic keratosis displays hyperkeratosis, acanthosis, and some degree of papillomatosis on histological preparation. By definition, the squamous cells comprising the lesion do not exhibit dysplasia. One characteristic finding in some seborrheic keratosis is the pseudo-horn cysts. These are circular collections of surface keratin in the acanthotic epithelium of the seborrheic keratosis lesion.

Squamous papillomas display benign squamous epithelium with variable acanthosis and hyperkeratosis, and focal parakeratosis, overlying a fibrovascular core. These have occasionally been shown to exhibit features of chronic inflammation.[1] Pseudoepitheliomatous hyperplasia demonstrates invasive, elongated processes of hyperplastic epithelium and often contains inflammatory cells; however, features of malignancy, eg, dysplasia and atypical mitoses, are absent.[1] Inverted follicular keratoses display endophytic proliferation of basal and squamous elements. Pigmentation, acantholysis, and chronic inflammation can occur in these lesions.[1]

History and Physical

Clinical History

When evaluating a skin lesion on the eyelid, the following questions are important to ask the patient:

• How long has the lesion been present?
• Have you noticed the lesion changing color, size, or shape?
• Does the lesion cause pain or irritation?
• Has the lesion bled or drained any fluid or purulent material?
• Do you have any other similar skin lesions on other parts of your body?
• Have you had a similar lesion in the past on the eyelid?
• Do you have a history of skin cancer? 

When patients present with eyelid papillomas, they typically have been present for months to years. These lesions do not grow rapidly, and patients do not notice changes in their character over time. Occasionally, the patient can feel the papilloma from the weight of the eyelid, or the lesion may become mildly inflamed, but chronic or severe inflammation is uncharacteristic of a papilloma. Papillomas do not bleed or drain purulent material unless the patient picks at the lesion and it subsequently becomes infected. A history of skin cancer in a patient should prompt the clinician to monitor the lesion more closely for suspicious characteristics.

Physical Examination

When performing the physical exam, clinicians should perform the following evaluations: 

• Examine the surrounding skin for additional skin lesions.
• Feel facial/neck lymph nodes to assess for lymphadenopathy.
• Using the slit lamp, examine the lesion for the destruction of nearby tissues (skin ulceration, destruction of Meibomian glands, or eyelash loss (madarosis). Note any telangiectasia of the lesion, whitening of nearby eyelashes (poliosis), and destruction of Meibomian glands. Evert eyelids to look for disruption of the palpebral conjunctiva.

The following physical exam findings for papillomas vary slightly by type:

• Squamous papilloma: This is a soft, flesh-colored lesion that is generally smooth, round, or pedunculated.
• Seborrheic keratosis: Classically has a “stuck on” appearance and can have varying degrees of pigmentation. Lesions tend to range from pink or flesh-colored to dark brown. These lesions are well-circumscribed and usually slightly elevated.
• Pseudoepitheliomatous hyperplasia: These lesions are often reactive processes in response to trauma, wounds, burns, and pharmaceutical agents that can appear similar to basal cell or squamous cell carcinoma. These lesions are usually elevated on the skin with an irregular surface and occasionally ulceration or crusting.[1]
• Inverted follicular keratosis: This is normally a solitary lesion affecting the eyelid margin. Inverted follicular keratosis may or may not be pigmented and has been described as either nodular or papillary in appearance.[1]
• Verruca vulgaris: Flesh-colored skin growth. The superior portion of the lesion can have very tiny, fingerlike projections that are sometimes visible without magnification.

Evaluation

Documenting the lesion with a photo allows for comparison of the size and appearance of the lesion over time. Measuring the size of the lesion at each visit can confirm that the lesion is growing over time.. If the lesion displays any characteristics that are concerning for malignancy, consider performing a biopsy. Typically, an incisional biopsy is performed in these cases.[5]

Treatment / Management

Lesions identified as eyelid papillomas can be observed. If the papilloma is causing irritation or is cosmetically unacceptable for the patient, it can be removed. Most papillomas can be removed with a bedside shave excision. Verruca vulgaris typically responds better to cryotherapy. Other modalities utilized to remove these types of lesions include radiofrequency and plasma exeresis.[6][7][5]

One study reported successful treatment of a large eyelid papilloma with intralesional interferon. A larger study of 64 patients with eyelid papilloma-like lesions found that radiofrequency lesion removal was safe and effective. In this study, 72% of the lesions treated were squamous papillomas.

Papilloma Excision Technique

The following steps are recommended when performing papilloma excision. First, topical tetracaine should be instilled in the ipsilateral eye to minimize irritation from the cleaning solution. Clean the papilloma and surrounding eyelid tissue with full-strength povidone-iodine solution, then place a small sterile drape with a fenestration to isolate the lesion.

Then inject 1 mL to 2 mL of lidocaine with epinephrine directly beneath the papilloma, using the minimal volume necessary to ensure patient comfort. Using 0.5 mm forceps, gently grasp and elevate the lesion while excising it with a 15-blade or iris scissors. Begin at the base to ensure complete removal without extending into deeper tissues. Achieve hemostasis with a handheld cautery device as needed. The residual defect generally remains small and does not require suturing to approximate the skin. Prescribe an antibiotic, eg, erythromycin ophthalmic ointment, applied 3 to 4 times daily for 1 to 2 weeks until healing occurs to reduce infection risk. Send the excised tissue for pathologic evaluation when any suspicious features are present.[6][8][9](B2)

Differential Diagnosis

Several benign and malignant eyelid lesions can resemble an eyelid papilloma and should be included in the differential diagnosis during evaluation, eg, chalazion/hordeolum, epidermal inclusion cyst, molluscum contagiosum, xanthelasma, squamous cell carcinoma, nevus, actinic keratosis, basal cell carcinoma, and sebaceous gland carcinoma.[10] Careful clinical examination and, when necessary, histopathologic analysis are important to ensure accurate diagnosis and appropriate management.

One common benign condition that may be mistaken for an eyelid papilloma is seborrheic keratosis, which presents as a well-demarcated, waxy, “stuck-on” lesion that can develop on the eyelids. Verruca vulgaris (common wart) may also appear similar, as this lesion presents with a rough, papillomatous surface due to human papillomavirus infection. Skin tags (acrochordons) are another benign lesion that can occur on the eyelids and present as soft, pedunculated growths. Although typically harmless, they may clinically resemble small papillomas.

Malignant lesions must also be considered, particularly because the eyelid is a common site for skin cancer. Basal cell carcinoma, the most common malignant eyelid tumor, may initially present as a small, nodular lesion with pearly borders and telangiectasia, sometimes mimicking benign growths. Squamous cell carcinoma can present as a scaly, ulcerated lesion and may occasionally resemble papillomatous growths in early stages. Sebaceous gland carcinoma, though less common, is an aggressive eyelid malignancy that may masquerade as a benign lesion or chronic inflammatory condition.

Because these conditions can have overlapping clinical features, lesions that demonstrate rapid growth, irregular borders, ulceration, bleeding, lash loss, or persistent recurrence should be evaluated carefully. When diagnostic uncertainty exists, biopsy and histopathologic examination are recommended to confirm the diagnosis and rule out malignancy. Accurate differentiation among these conditions is essential to ensure appropriate treatment and favorable patient outcomes.

Prognosis

The prognosis for eyelid papillomas is excellent, as these lesions are benign epithelial proliferations that rarely lead to significant complications. Most eyelid papillomas remain stable over time and do not undergo malignant transformation.[11] When treatment is desired due to cosmetic concerns, irritation, or diagnostic uncertainty, simple excision or minor procedural removal is typically curative. Recurrence after complete removal is uncommon but may occur if the lesion is incompletely excised.

Complications

Complications are rare but may include local irritation, bleeding, or infection following removal procedures. In most cases, patients experience good cosmetic outcomes when lesions are treated appropriately. The most important prognostic consideration is ensuring accurate differentiation from malignant eyelid tumors, eg, basal cell carcinoma or squamous cell carcinoma, which may initially resemble benign papillomas. Prompt evaluation of suspicious or changing lesions enables early diagnosis and treatment, contributing to favorable long-term outcomes and the preservation of eyelid function and appearance.