Woman referred for growing eyelid lesion

The patient reported a 6-month history of an enlarging cluster of bumps on her left upper eyelid.

Jeffrey Chang

Vivek Chaturvedi

A 64-year-old woman was referred to our practice after noticing a cluster of bumps on her left upper eyelid that had been growing in size over 6 months. No pain, bleeding or discharge was noted, and there was no history of similar lesions.

History

Her medical history was notable for chronic obstructive pulmonary disease. She had a 20 pack-year history of cigarette smoking but had stopped smoking 5 years before presentation. She worked as an accounting clerk.

Examination

On exam, the patient’s vision without correction was 20/25 in the right eye and 20/25 in the left eye. Her IOP, ocular motility and pupillary exam were within normal limits. External examination of the eyelids revealed a lesion involving the left upper lid margin (Figure 1) extending from the lid margin into the palpebral conjunctiva. The lesion was yellow in color and had an irregular, clustered appearance (Figure 2). Significant eyelash loss was noted. A slit lamp examination and dilated fundus examination were within normal limits aside from mild nuclear cataracts.

Figure 1. External photograph of both eyes. Images: Witkin AJ, Laver NMV and Kapadia M

Figure 2. External photograph of the left eye, with eversion of the upper eyelid.

What is your diagnosis?

Eyelid lesion

The differential diagnosis for this condition is short and includes chalazion, sebaceous hyperplasia, basal cell carcinoma, squamous cell carcinoma and sebaceous cell carcinoma.

Differential diagnosis

A chalazion is a focal inflammation of the eyelid, formed due to obstruction of the meibomian glands. A focal “head” may be whitish in color, but chalazia are typically not yellow in color. Chalazia are almost never associated with loss of eyelashes. Any chronic chalazion in an older person should raise suspicion for sebaceous cell carcinoma.

Sebaceous hyperplasia usually presents as multiple yellow papules on the skin and may be found on the eyelid. Multiple sebaceous adenomas and hyperplasias on a patient may raise the suspicion of Muir-Torre syndrome, an autosomal dominant form of hereditary non-polyposis colon cancer, which is associated with an increased risk of visceral cancers.

Basal cell carcinoma is the most common malignancy of the eyelid, accounting for approximately 90% of eyelid malignancies in the United States. It is most commonly found on the lower eyelid, followed by the medial canthus, upper eyelid and lateral canthus. Basal cell carcinoma is classically described as a pearly nodule associated with telangiectasias and central ulceration. However, superficial spreading or sclerosing forms of the tumor may demonstrate less typical findings.

Squamous cell carcinoma of the eyelid is much less common than basal cell carcinoma and represents approximately 5% of eyelid malignancies. Squamous cell carcinoma may appear scaly on examination but often demonstrates similar findings to basal cell carcinomas.

Sebaceous cell carcinoma represents less than 1% of eyelid malignancies in the United States. It is found on the eyelid more frequently than anywhere else in the body. The average age of presentation is approximately 70 years, with women more commonly affected than men. Unlike basal cell carcinoma and squamous cell carcinoma, sebaceous carcinoma most commonly affects the upper eyelid, likely due to a higher number of meibomian glands in this location. Sebaceous cell carcinoma is known for its ability to masquerade as other diseases, such as chalazion or blepharitis, due to its common superficial pagetoid spread through the conjunctiva.

Sebaceous carcinoma is a feared disease due to higher rates of recurrence, local spread and metastasis compared with most other eyelid malignancies. Studies have shown local recurrence rates ranging from 10% to 35%, with metastasis in 15% to 25% of patients. The 5-year mortality rate for patients with metastatic disease was found to be as high as 25% to 40%. Recent studies have shown a dramatic decline in rates of metastasis, perhaps due to increased awareness of this disease and earlier treatment. Currently, overall 5-year mortality from sebaceous cell carcinoma may be as low as 6%.

Diagnosis

In the case described here, the yellow color of the lesion is suggestive of a sebaceous lesion such as sebaceous hyperplasia or sebaceous cell carcinoma, with the loss of eyelashes suggesting a malignant process. A partial thickness biopsy was performed and found to be diagnostic for sebaceous cell carcinoma. However, a full-thickness biopsy is often required to confirm this diagnosis, as the malignancy starts in the meibomian glands in the posterior lamella of the eyelid. The pathologist should be notified of the suspicion for sebaceous cell carcinoma, as useful stains such as oil red O require special tissue processing. The specimen should be sent to a pathologist familiar with sebaceous carcinoma, as the rarity of this disease means that most pathologists will not see a single case in their entire career. Sebaceous carcinoma is often misdiagnosed as squamous cell carcinoma.

Figure 3a. Hematoxylin and eosin stain. Low-magnification shows multiple highly cellular nodules deep to the skin.

Figure 3b. Higher magnification shows multiple cells with vacuolated cytoplasm and multiple mitoses.

A diagnosis of sebaceous cell carcinoma was made based on histopathology (Figures 3a and 3b), and surgical excision of the lesion was planned. Options for surgical excision include excision of the visible lesion with large margins, excision with frozen section controls or orbital exenteration. Conjunctival map biopsies are often performed to look for evidence of pagetoid spread. If diffuse conjunctival involvement is found, cryotherapy or mitomycin C eye drops may be used as adjunctive therapy.

Management

This patient underwent a wedge resection of the upper lid with 5-mm margins and closure of the eyelid defect after a canthotomy and superior cantholysis were performed. A sentinel lymph node (SLN) biopsy was performed simultaneously by an otolaryngologist. SLN biopsy has been studied more extensively in cutaneous melanoma, where there is clearly a worse prognosis with positive SLNs. In cutaneous melanoma, it is still unclear whether there is a survival benefit to performing SLN biopsy. It is postulated that resection of positive SLNs may be therapeutic, as some believe that melanoma spreads locally before metastasizing systemically.

In ocular adnexal tumors (melanoma and sebaceous cell carcinoma), experience with SLN biopsy is limited. The procedure entails injecting radioactive colloid into the subconjunctival space or intradermally around the eyelid lesion at the time of resection. A hand-held gamma probe is then used transcutaneously to identify SLNs in the neck, and lymph nodes are dissected and submitted for histopathologic evaluation.

In summary, a 64-year-old woman with sebaceous cell carcinoma of the upper eyelid was treated with surgical excision of a lesion with large margins as well as sentinel node biopsy. Pathologic analysis showed clear surgical margins of the lid lesion with no pagetoid spread and clear lymph nodes. Map biopsies of the conjunctiva were performed as a separate procedure and were also found to be tumor-free.

References:

• Ho VH, Ross MI, Prieto VG, Khaleeq A, Kim S, Esmaeli B. Sentinel lymph node biopsy for sebaceous cell carcinoma and melanoma of the ocular adnexa. Arch Otolaryngol Head Neck Surg. 2007;133(8):820-826.
• Shields CL, Naseripour M, Shields JA, Eagle RC Jr. Topical mitomycin-C for pagetoid invasion of the conjunctiva by eyelid sebaceous gland carcinoma. Ophthalmology. 2002;109(11):2129-2133.
• Shields JA, Demirci H, Marr BP, Eagle RC Jr, Shields CL. Sebaceous carcinoma of the eyelids: personal experience with 60 cases. Ophthalmology. 2004;111(12):2151-2157.
• Shields JA, Demirci H, Marr BP, Eagle RC Jr, Shields CL. Sebaceous carcinoma of the ocular region: a review. Surv Ophthalmol. 2005;50(2):103-122.
• Shields JA, Demirci H, Marr BP, Eagle RC Jr, Stefanyszyn M, Shields CL. Conjunctival epithelial involvement by eyelid sebaceous carcinoma. The 2003 J. Howard Stokes lecture. Ophthal Plast Reconstr Surg. 2005;21(2):92-96.
• Song A, Carter KD, Syed NA, Song J, Nerad JA. Sebaceous cell carcinoma of the ocular adnexa: clinical presentations, histopathology, and outcomes. Ophthal Plast Reconstr Surg. 2008;24(3):194-200.

• Andre J Witkin, MD, Nora M.V. Laver, MD, and Mitesh Kapadia, MD, can be reached at Tufts Medical Center, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.

• Edited by Jeffrey Chang, MD, and Vivek Chaturvedi, MD. Drs. Chang and Chaturvedi can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.