Eyelid Papilloma

The term "papilloma" derives from the Latin word "papilla," meaning nipple, reflecting the growth's nipple-like or protruding appearance on the skin or mucous membranes. It also is associated with the human papillomavirus (HPV), a group of viruses known to cause wart-like growths on the skin and mucous membranes, highlighting the etymological and clinical link between the term "papilloma" and the virus. An eyelid papilloma is the most common benign epidermal tumor. Lesions usually are papillomatous, that is, of smooth, rounded, or pedunculated elevation.[2, 3, 4, 5, 6]  The lesion that most commonly fits this description is a benign squamous papilloma. However, it is possible that other benign or malignant eyelid lesions, including squamous cell carcinoma, may take on a similar appearance.

The majority of eyelid tumors primarily stem from the cutaneous origins. Delving further into this classification, the most prevalent eyelid tumors can be categorized into 2 subgroups: epithelial and melanocytic tumors, both of which are mostly of epidermal origin. The precise etiology of squamous cell papilloma (SCP) remains a topic of debate among medical professionals, as it is yet to be universally confirmed. Despite this uncertainty, a few prime culprits have been consistently highlighted in the literature. Notably, both mechanical and chemical irritations are implicated as potential triggers, along with infections by certain strains of the human papillomavirus (HPV). The involvement of HPV in the pathogenesis of SCP is particularly noteworthy. HPV6 and HPV11 stand out as the 2 most frequently associated genotypes with SCPs. However, it's crucial to mention that while the high-risk HPV16 and 18 have been identified in SCPs, their prevalence is significantly lower compared to HPV6 and HPV11.[6]

Frequency

International

Squamous papilloma represents the most common benign lesion of the eyelid. Results of a retrospective analysis of eyelid tumors showed that epidermal tumors are the most common eyelid tumors, with papilloma being the most common. Eyelid papilloma represents 10-26% of all eyelid tumors based on thousands of cases of eyelid tumors from around the world.[2, 3, 4, 5]  In a single study in Turkey, eyelid papilloma was the second most common after Seborrheic Keratosis.

Race

No known differences in race presentation or frequency exist.

Sex

No difference in occurrence exists between the sexes.

Age

Frequency increases steadily with age, but they may occur at any age and are typically occur in middle-aged or older adults.

Prognosis is excellent. However, the lesions can recur in the same or different location.

Warn patients to protect their skin from the sun's damaging influence, with hats, sunglasses, and protective lotions, and to minimize exposure to the sun. See a medical practitioner if any new lesions appear.

When evaluating patients with eyelid lesions, a meticulous history is essential. It’s important to ask about the timeline of the lesion's appearance, growth, and presence of any accompanying changes. Has the lesion been stable, or has there been rapid growth over a short period? Inquiries should be made regarding associated symptoms such as itching, irritation, pain, or discharge. Changes in vision or ocular discomfort, although not directly indicative of papilloma, can provide valuable context. Additionally, it’s important to identify risk factors, including any previous skin lesions or history of HPV-related conditions. Lastly, a thorough medical history, including medications, allergies, and systemic conditions, can offer insights into the patient's overall health and other potential causes or risk factors for the lesion. In addition to general questions about past medical history and family history, document the following:

• Determine how long the lesion has been present.

• Determine if the lesion has grown (eg, rapidly, slowly).

• Determine if the lesion has changed in any way (eg, color, bleeding, ulceration).

• Ask the patient if any similar lesions have occurred before anywhere on the patient's body.

• Ask the patient if a malignant skin lesion has occurred before.

General inspection

During the clinical examination of a patient with an eyelid lesion, careful external examination is required. It’s important to the size, shape, color, and location of the lesion in relation to the eyelid margin and surrounding structures. Additionally, it's essential to assess the functionality of the eyelid, noting any lagophthalmos, entropion, or ectropion that might be secondary to the lesion's presence. Examination of regional lymph nodes, especially the preauricular and submandibular nodes, can be crucial in identifying any signs of regional spread, particularly in suspicious or malignant-looking lesions. Evaluating the integrity of the patient's visual field, ocular motility, and other adjacent ocular structures ensures a holistic understanding of the lesion's impact.

Slit lamp examination

The use of bright lighting, and often a magnifying loupe or slit-lamp biomicroscopy, can provide detailed insights into the lesion's surface characteristics, vascular pattern, and any ulceration or scaling. Palpation of the lesion can offer information regarding its consistency, mobility, and tenderness.

Assess for telangiectasias on nodular tumors, loss of eyelashes (madarosis), or whitening of eyelashes (poliosis) in the region of the tumor, and inspect the meibomian orifices to determine whether they have been destroyed. Ulceration and inflammation with distortion of the eyelid anatomy, abnormal color, texture, or persistent bleeding suggest malignancy.

Cutaneous papilloma has been associated with human papilloma virus infections.[6]

Eyelid papillomas, while benign in nature, can lead to a range of complications. Large eyelid papillomas have the potential to mechanically impair eyelid movement. This disturbance can disrupt the protective mechanisms of the eyelid, compromise the ocular surface and potentially lead to dryness or exposure-related issues. Large lesions can grow over visual axis impairing patients’ vision. In addition, lesions can be irritating or itchy to patients. Eyelid papillomas can result in significant cosmetic concerns for patients. This aesthetic disturbance can impact patients’ confidence and quality of life.  It's essential for clinicians to recognize and address these potential complications to ensure comprehensive patient care.

An eyelid papilloma is a benign epithelial proliferation of the eyelid skin.The majority of eyelid papillomas can be clinically diagnosed based on history and examination. A previous study showed that ophthalmologists can accurately differentiate and diagnose most eyelid lesions based on history and clinical examination alone but histopathologic confirmation is still recommended in most cases. The clinical assessment of eyelid malignancy by ophthalmologists has a sensitivity of 87.5% and a specificity of 81.5% and the histopathological confirmation of suspected malignancy is critical.[7]  Consideration should be given to drawing and photographing any eyelid lesion at initial evaluation (including suspected eyelid papillomas) with high-resolution images both for documentation and follow up to determine change over time.

Ultrasound biomicroscopy (UBM) at 50 MHz has been tried in detecting malignancy of various eyelid lesions and has been shown to have a high sensitivity and a moderate specificity.[8]  Imaging by high-resolution Optical Coherence Tomography (OCT) has not yet been established in routine clinical practice for diseases of the conjunctiva and eyelids. Some eyelid lesions may have orbital involvement and may require additional orbital imaging.

A biopsy of the lesion may be performed, which will provide the definitive diagnosis, as an accurate diagnosis of an eyelid lesion requires histologic examination.

Usually, squamous papillomas are sessile or pedunculated and have a color similar to the surrounding skin. They often are multiple and tend to involve the lid margin. A small keratin crust often can be palpated on the surface (keratotic papilloma). Microscopically, these lesions are composed of fingerlike projections of vascularized connective tissue covered by hyperplastic epithelium (papillae). The epidermis usually is acanthotic, with elongation of the rete ridges, and shows areas of hyperkeratosis and focal parakeratosis.[9]

The advent of artificial intelligence (AI) has brought transformative innovations to the realm of ophthalmology, particularly in the diagnosis and management of eyelid skin lesions. Leveraging vast datasets and machine learning algorithms, AI tools can assist in the rapid and precise identification of various eyelid lesions, ranging from benign papillomas to malignant tumors. These systems analyze features often imperceptible to the human eye, increasing diagnostic accuracy and potentially reducing the need for invasive biopsies. Furthermore, with continuous learning and adaptation, these AI models evolve over time, holding promise for even more accurate and timely interventions in the future.[10]

When addressing eyelid papilloma, the treatment approach hinges on both the presentation and severity of the lesion. Benign papillomas that remain asymptomatic and don't pose significant cosmetic concerns often can be observed without immediate intervention. However, if there's any uncertainty in the clinical diagnosis, early incisional or excisional biopsies are recommended to guide the treatment course. For symptomatic papillomas, safe and straightforward in office excision is standard approach. During these procedures, it's imperative to exercise caution to protect vital ocular and adnexal structures, such as the canthal tendons, lacrimal puncta and canaliculi, lacrimal sac, and the ocular surface. Ensuring their preservation is crucial to prevent postoperative complications and maintain optimal eye function. Complete excision of papilloma is preferred to prevent recurrence and offer the best therapeutic outcome.

Lee et al studied eyelid margin papillomas for which complete excision was cosmetically unacceptable. The study reported a case in which interferon was an effective treatment for a conjunctival papilloma.[11]

The surgical management of benign eyelid tumors is tailored to ensure not only the complete removal of the lesion but also the preservation of the eyelid's functional and aesthetic integrity. Papilloma excision technique is as follows:

1. Preparation: Administer a topical tetracaine drop in the affected eye to prevent irritation from the cleaning agent. Clean the area of the papilloma and the adjacent eyelid tissue using a full-strength povidone-iodine solution. Use a small sterile drape, ideally with a hole cut out, to isolate the lesion.
2. Anesthesia: Inject 1 mL to 2 mL of lidocaine with epinephrine directly underneath the papilloma. Ensure that the quantity of anesthetic used is sufficient to ensure patient comfort.
3. Excision: Grasp and elevate the lesion gently with toothed forceps (Paufique forceps or 0.5mm forceps). Using either a 15-blade, iris or Westcott scissors, excise the papilloma including the base. There's typically no requirement to penetrate deeper tissues.
4. Post-Excision: If any bleeding occurs, gentle pressure or a handheld cautery tool is effective for hemostasis. Given that the resulting defect is generally small, sutures are often unnecessary. Advise patients to apply a prescribed antibiotic, such as erythromycin ophthalmic ointment, on the healing incision three to four times daily for 1 to 2 weeks. This promotes healing and minimizes infection risk.
5. Pathological Consideration: Always consider sending the excised tissue for pathological evaluation, especially in the presence of suspicious features.

Argon laser has been successfully used to treat benign eyelid tumors for upper and lower lids.[12]  More recently, excisional biopsy of eyelid papillomatous lesions using radiofrequency techniques has been successfully described.[13]

Surgical scarring and possibly lid notching are the only likely complications. Usually, the lesions are small and bleeding and infection rarely occur postexcision.

Patients should receive follow-up care as needed, and counseling regarding the possibility of recurrence should be provided.