Man presents with rapidly growing eyelid lesion

Exam findings include a raised palpebral conjunctival lesion with an irregular surface and a symblepharon.

Issue: December 10, 2016

ByMitesh K. Kapadia, MD, PhD

ByMelina I. Morkin, MD

A 52-year-old Latin-American man was referred to the Oculoplastics service at the New England Eye Center for evaluation of presumed pyogenic granuloma. The patient reported a history of a rapidly growing “stye” in his left lower eyelid for the prior 2 weeks. He denied any associated pain, erythema or discharge. Medical history was positive only for diet-controlled diabetes. He denied any history of malignancy or sexually transmitted infections such as HIV. Ocular history was unremarkable, including any history of trauma or surgery to the eyelid. He was not taking any medications. The patient also denied any history of smoking, intravenous drug use or high-risk sexual activity. He worked as a driver.

Examination

Best corrected visual acuity was 20/25 in both eyes. The pupils were briskly reactive to light with no relative afferent pupillary defect in either eye, and IOP was 15 mm Hg in each eye. Extraocular muscle movements were fully intact, and confrontational visual fields were full in both eyes.

Figure 1. Photograph of external exam showing a raised left inferior eyelid with intact overlying skin that is mildly erythematous (a). Photograph of left lower eyelid upon eversion reveals an elevated growth on the medial palpebral conjunctiva that extends laterally and causes traction on the bulbar conjunctiva (b). Inferotemporal cystic-appearing bulbar conjunctival elevations are also noted.

External examination of the eyelids revealed a non-tender, elevated left lower eyelid with mild erythema but no ulceration (Figure 1a). Marginal reflex distance-2 was found to be 4 mm in the left eye compared with 6 mm in the right eye, indicating a relatively narrow left vertical interpalpebral fissure. Upon eversion of the left lower eyelid, a 7 mm × 9 mm raised, irregular, mildly vascularized conjunctival lesion was noted, measuring approximately 17 mm horizontally in its deeper tarsal portion (Figure 1b). Irregularities in palpation of the orbital fat suggested extension of the lesion into the orbit with no gross proptosis. There was a symblepharon as well as cystic-appearing elevated lesions on the inferotemporal bulbar conjunctiva. External examination was negative for any palpable lymph nodes.

What is your diagnosis?

See answer on next page.

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Rapidly growing conjunctival lesion

Given the presence of an invasive tarsal conjunctival mass, highest on the differential was squamous cell carcinoma. A pyogenic granuloma can develop very rapidly as a red and pedunculated growth over an area of chalazion or prior surgery or trauma. Squamous papilloma typically presents as a fleshy, exophytic growth in the lower fornix and can be more extensive in patients with compromised immune status. Palpebral melanomas are less common than bulbar melanomas, and pigmentation in these is variable. Interestingly, 25% of conjunctival melanomas are amelanotic, which could lead to a similar appearance. Sebaceous carcinoma can masquerade as a chalazion and classically has a white/yellow tinge and nodularity. Lymphoma, although less likely, can also present in the inferior fornix as a salmon pink, sessile mass, which is unilateral in 80% of the cases. The patient denied any history of trauma or surgery that could lead to abnormal scarring. Kaposi sarcoma, which typically presents on the skin as a purplish nodule, can also be found on the conjunctiva as a reddish, highly vascular, nodular subconjunctival lesion, usually in the inferior fornix.

Workup and management

Although the actual duration of the lesion was unclear, it had a highly suspicious appearance with seemingly rapid growth. Therefore, the patient underwent a diagnostic incisional biopsy on the day of presentation, which confirmed the presence of an invasive squamous cell carcinoma extending to the edges of the biopsy. An orbital CT was then ordered to rule out orbital extension. Prominence of the inferomedial periorbital soft tissues was noted, with potential extension into the inferior fornix, although there was no clear deep orbital spread (Figure 2). A neck CT was negative for lymphadenopathy.

Figure 2. Axial (a) and sagittal cuts (b) of orbital CT with contrast showing a rather localized hyperdense prominence in the left lower eyelid, inferomedial to the globe, which seems to extend deep into the fornix and possibly the anterior orbit.

Figure 3. A supraciliary incision was performed on the upper eyelid to spare the skin and along the inferior orbital rim to completely remove the inferior eyelid where the tumor was located (a). The incision was carried down to the level of the periosteum, which was detached along with the periorbita (b). The orbital contents were excised from the orbital apex (c). A split-thickness skin graft was used to line the orbital cavity (d).

Figure 4. Sagittal view of the formalin-fixed exenterated orbit. The lesion displays a round white homogeneous configuration measuring 1 cm × 0.9 cm and growing from the palpebral conjunctiva deeper into the lower fornix (a). A localized area of increased basophilic hypercellularity extending 0.7 cm into the orbit is noted (H&E, 1×) (b). Multiple nests of moderately differentiated non-keratinizing squamous cells invade the dermis (H&E, 10×). Note the presence of intercellular bridges (inset, 20×) (c).

Given the suspected orbital extension of a fast-growing squamous cell carcinoma, orbital exenteration surgery was recommended in this patient. Lower eyelid removal followed by radiation to the orbit and treatment of the bulbar conjunctiva was also offered as an alternative, but the patient decided to proceed with orbital exenteration surgery.

An orbital exenteration was performed, sparing the skin of the upper eyelid with a supraciliary incision, followed by placement of a 0.015 inch split-thickness skin graft harvested from the anterior thigh (Figures 3a to 3d). Macroscopically, a non-pigmented round mass was identified in the palpebral conjunctiva and inferior fornix (Figure 4a). With H&E staining, the hypercellular predominantly basophilic tumor was considered to extend 0.7 cm into the anterior orbit (Figure 4b). Fortunately, the eyelid skin, orbital tissues and optic nerve margins were negative for malignancy, and there was no evidence of perineural or lymphovascular extension. Histologically, strands and nests of non-keratinizing, moderately differentiated squamous cells with intercellular bridges were observed (Figure 4c).

Discussion

Squamous cell carcinoma of the eyelid usually arises as a cutaneous malignancy, with an incidence of 0.09 to 2.4 cases per 100,000 habitants. Predisposing factors include UV light exposure, HPV and HIV infection, older age, male gender, light skin complexion and heavy cigarette smoking. A systemic condition that leads to the development of cutaneous squamous cell carcinoma is xeroderma pigmentosum, which is a hereditary deficiency of the nucleotide excision repair enzyme that normally restores damaged DNA. Immunosuppression is another risk factor for the development of cutaneous squamous cell carcinoma.

Conversely, squamous cell carcinoma of the palpebral conjunctiva is exceedingly rare, with fewer than 15 cases found in the literature. A single case of bilateral palpebral squamous cell carcinoma has also been reported. The association between HPV and periocular tumors has been controversial, with studies producing conflicting results.

Although usually silent, palpebral squamous cell carcinomas can elevate and ulcerate the skin, or also mimic conjunctivitis or a chalazion. On exam, an indurated mass should be palpable. As the tumor invades the orbit or bone, globe displacement and limitations of extraocular muscle movements can be seen, as well as optic neuropathy and cranial nerve palsies in advanced cases with orbital apex and cavernous sinus spread.

Treatment options depend on the size and location of the tumor and are limited by the cosmetic and functional significance of the eyelid. Mitomycin C, 5-fluorouracil, interferon and cryotherapy are used topically for intraepithelial, noninvasive conjunctival lesions. Wide local excision remains the primary surgical approach, with cases of orbital invasion often requiring orbital exenteration surgery. Radiotherapy is a useful adjunctive treatment for advanced cases, especially when perineural or lymphatic spread is seen on pathology, or when an incomplete surgical resection was performed.

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Exenteration can be total, eyelid-sparing or combined with orbitectomy, depending on the extension, behavior and location of the tumor. Split-thickness skin grafts are usually placed after exenteration to line the orbital cavity. These are often harvested from the anterior or lateral thigh with a commercially available dermatome.

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For more information:
Melina I. Morkin, MD, Mitesh K. Kapadia, MD, PhD, and Nora V. Laver, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
Edited by Jessica Moon, MD, and Emily C. Wright, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.