Eyelid Papilloma

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Practice Essentials

Eyelid papilloma, commonly referred to as a "skin tag," is a benign growth that can present clinical significance despite its usually innocuous nature.[1] The following is a brief description of eyelid papilloma and its management:

Background

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.

Pathophysiology

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]

Epidemiology

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

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

Patient Education

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.

History

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:

Physical

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.

Causes

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

Complications

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.

Approach Considerations

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.

Imaging Studies

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.

Procedures

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.

Histologic Findings

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]

Other Tests

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]

Approach Considerations

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.

Medical Care

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]

Surgical Care

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]

Complications

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

Long-Term Monitoring

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

Author

Saif Aldeen Saleh Alryalat, MD, Fellow in Neuro-ophthalmology, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Amina I Malik, MD, Associate Professor of Clinical Ophthalmology in Otolaryngology, Director, Ophthalmic Plastic and Reconstructive Surgery, Blanton Eye Institute, Houston Methodist Hospital; Associate Professor of Clinical Ophthalmology, Hospital Institute for Academic Medicine at Houston Methodist; Associate Professor of Ophthalmology, Weill Cornell Medical College

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Horizon Therapeutics .

Andrew G Lee, MD, Chair, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital; Clinical Professor, Associate Program Director, Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch School of Medicine; Clinical Professor, Department of Surgery, Division of Head and Neck Surgery, University of Texas MD Anderson Cancer Center; Professor of Ophthalmology, Neurology, and Neurological Surgery, Weill Medical College of Cornell University; Clinical Associate Professor, University of Buffalo, State University of New York School of Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: AstraZeneca; Bristol Myers Squibb; Horizon<br/>Serve(d) as a speaker or a member of a speakers bureau for: Horizon<br/>Received ownership interest from Credential Protection for other.

Specialty Editors

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD, † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Brian A Phillpotts, MD, Ophthalmologist, St Luke's Cataract and Laser Institute

Disclosure: Nothing to disclose.

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.

References

  1. Cochran ML, Czyz CN. Eyelid Papilloma. StatPearls. 2023 Jan. [View Abstract]
  2. Deprez M, Uffer S. Clinicopathological features of eyelid skin tumors. A retrospective study of 5504 cases and review of literature. Am J Dermatopathol. 2009 May. 31 (3):256-62. [View Abstract]
  3. Bagheri A, Tavakoli M, Kanaani A, Zavareh RB, Esfandiari H, Aletaha M, et al. Eyelid masses: a 10-year survey from a tertiary eye hospital in Tehran. Middle East Afr J Ophthalmol. 2013 Jul-Sep. 20 (3):187-92. [View Abstract]
  4. Yu SS, Zhao Y, Zhao H, Lin JY, Tang X. A retrospective study of 2228 cases with eyelid tumors. Int J Ophthalmol. 2018. 11 (11):1835-1841. [View Abstract]
  5. Gundogan FC, Yolcu U, Tas A, Sahin OF, Uzun S, Cermik H, et al. Eyelid tumors: clinical data from an eye center in Ankara, Turkey. Asian Pac J Cancer Prev. 2015. 16 (10):4265-9. [View Abstract]
  6. Trzcinska A, Zhang W, Gitman M, Westra WH. The Prevalence, Anatomic Distribution and Significance of HPV Genotypes in Head and Neck Squamous Papillomas as Detected by Real-Time PCR and Sanger Sequencing. Head Neck Pathol. 2020 Jun. 14 (2):428-434. [View Abstract]
  7. Margo CE. Eyelid tumors: accuracy of clinical diagnosis. Am J Ophthalmol. 1999 Nov. 128 (5):635-6. [View Abstract]
  8. El-Zawahry MB, Abdel El-Hameed El-Cheweikh HM, Abd-El-Rahman Ramadan S, Ahmed Bassiouny D, Mohamed Fawzy M. Ultrasound biomicroscopy in the diagnosis of skin diseases. Eur J Dermatol. 2007 Nov-Dec. 17 (6):469-75. [View Abstract]
  9. Pe'er J. Pathology of eyelid tumors. Indian J Ophthalmol. 2016 Mar. 64 (3):177-90. [View Abstract]
  10. Escalé-Besa A, Yélamos O, Vidal-Alaball J, Fuster-Casanovas A, Miró Catalina Q, Börve A, et al. Exploring the potential of artificial intelligence in improving skin lesion diagnosis in primary care. Sci Rep. 2023 Mar 15. 13 (1):4293. [View Abstract]
  11. Lee BJ, Nelson CC. Intralesional interferon for extensive squamous papilloma of the eyelid margin. Ophthalmic Plast Reconstr Surg. 2012 Mar-Apr. 28 (2):e47-8. [View Abstract]
  12. Wohlrab TM, Rohrbach JM, Erb C, Schlote T, Knorr M, Thiel HJ. Argon laser therapy of benign tumors of the eyelid. Am J Ophthalmol. 1998 May. 125 (5):693-7. [View Abstract]
  13. Eshraghi B, Torabi HR, Kasaie A, Rajabi MT. The use of a radiofrequency unit for excisional biopsy of eyelid papillomas. Ophthalmic Plast Reconstr Surg. 2010 Nov-Dec. 26 (6):448-9. [View Abstract]
  14. Margo CE. Eyelid tumors: accuracy of clinical diagnosis. Am J Ophthalmol. 1999 Nov. 128(5):635-6. [View Abstract]