Clinicopathologic Report
May 2001

Primary Intraepithelial Sebaceous Gland Carcinoma of the Palpebral Conjunctiva

Author Affiliations

From the Oncology Service (Drs Honavar, C. L. Shields, J. A. Shields, and Demirci), Oculoplastics Service (Dr Maus), and Department of Pathology(Dr Eagle), Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pa; and Oncology Service, L.V. Prasad Eye Institute, Hyderabad, India (Dr Honavar).




Copyright 2001 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2001

Arch Ophthalmol. 2001;119(5):764-767. doi:10.1001/archopht.119.5.764

Sebaceous gland carcinoma usually arises from meibomian or Zeis glands deep within the eyelid, but it can rarely arise within the conjunctival epithelium without a deep component. We describe a woman with a history of chronic blepharoconjunctivitis unresponsive to topical medications. Examination disclosed confluent papillary hypertrophy of the upper palpebral conjunctiva and deposits of white flaky material. Tarsoconjunctival punch biopsy revealed intraepithelial sebaceous gland carcinoma. Management consisted of frozen section–controlled complete tumor excision with removal of the entire posterior lamella of the right upper eyelid, cryotherapy to the margins, and reconstruction. Histopathologic analysis confirmed primary sebaceous gland carcinoma localized to the conjunctival epithelium without involvement of underlying meibomian or Zeis glands or the caruncle. Patients with unexplained chronic unilateral blepharoconjunctivitis or papillary hypertrophy of the palpebral conjunctiva should be considered for biopsy to rule out neoplasia, even when there is no sign of an underlying eyelid mass.

Sebaceous gland carcinoma of the ocular adnexa is a relatively rare tumor that arises from the meibomian glands, Zeis glands, or sebaceous glands in the caruncle or eyebrow.17 It is estimated that this cancer represents 1% to 6% of all eyelid malignant neoplasms.4 The clinical presentation of sebaceous gland carcinoma depends on its site of origin. Sebaceous gland carcinoma of meibomian gland origin usually presents as a slowly enlarging, deep tarsal mass that may simulate a chalazion.4 The Zeis gland tumor appears as a well-circumscribed mass near the eyelid margin.3 Some patients have unilateral chronic blepharoconjunctivitis before the tumor is clinically obvious, leading to delay in diagnosis.8 Patients with this presentation generally manifest conjunctival intraepithelial invasion of sebaceous gland carcinoma (pagetoid spread) from a primary focus of tumor in the meibomian or Zeis glands.4,8 Sebaceous gland carcinoma confined to and presumably arising primarily within the conjunctival epithelium without underlying glandular or invasive component is uncommon.810 Herein, we describe one such case with supportive histopathologic findings.


A 33-year-old white woman developed contact lens intolerance, conjunctival hyperemia, and irritation in her right eye for 1 year. She had been treated with topical medications for chronic blepharoconjunctivitis without relief. Her only medical problem was idiopathic thrombocytopenic purpura, treated with varying doses of oral corticosteroids for 14 years. There was no history of radiotherapy to the face or systemic malignancy. On examination, her visual acuity was 20/20 OU. The left eye was unremarkable. The right eye revealed diffuse hyperemic papillary hypertrophy of the entire upper palpebral conjunctiva and scattered deposits of white flaky material (Figure 1A). There was no evident eyelid mass or madarosis. Minimal bulbar conjunctival congestion and diffuse superficial punctate keratopathy were noted. There was no obvious involvement of the bulbar or inferior palpebral conjunctiva. The clinical differential diagnosis included squamous or sebaceous neoplasia of the conjunctiva as well as atypical conjunctival infection. A deep tarsoconjunctival punch biopsy revealed purely intraepithelial sebaceous gland carcinoma without an underlying tarsal component. Map biopsy specimens from 9 other sites on the bulbar and lower palpebral conjunctiva were negative for malignancy. The tumor management involved complete excision of all sebaceous units of the upper eyelid using frozen section–controlled excision of the entire posterior lamella including the eyelid margin (Figure 1B) and cryotherapy to the margins. The defect was reconstructed with a free tarsoconjunctival graft from the opposite upper eyelid. Healing was excellent and all permanent margins were free of tumor. The patient was free of tumor recurrence 1 year after the surgery.

Figure 1.
Image not available

A, Conjunctival primary intraepithelial sebaceous gland carcinoma manifesting as diffuse papillary hypertrophy of the upper palpebral conjunctiva. B, An intraoperative photograph showing the entire tarsus and the palpebral conjunctiva up to the superior fornix being excised. Margins were uninvolved by frozen section biopsy examination.

The surgical specimen was received as a single piece of fresh unfixed tissue. A segment of the specimen was submitted for frozen sections and staining for the lipid with oil-red-O stain. The remainder of the specimen was fixed in formalin, sectioned perpendicular to the lid margin in a bread-loaf fashion, and submitted for routine light microscopy. The palpebral conjunctiva was thickened and replaced by tumor cells that had pleomorphic and hyperchromatic nuclei, focally vacuolated cytoplasm, and prominent mitotic activity (Figure 2A-B). The cells stained positively with oil-red-O confirming the presence of intracytoplasmic lipid (Figure 2C). Immunohistochemical analysis showed that the cells were strongly immunoreactive for BRST-2, focally positive for cytokeratin marker CAM 5.2, and minimally immunoreactive for epithelial membrane antigen, consistent with the diagnosis of sebaceous gland carcinoma. Step sections showed that the tumor was confined to the palpebral conjunctiva without deep involvement of the meibomian glands or Zeis glands. The margins of the excised area processed for frozen sections were negative for tumor. The final diagnosis was primary intraepithelial sebaceous gland carcinoma of the palpebral conjunctiva.

Figure 2.
Image not available

A, The excised tarsoconjunctival lamina showing full-thickness replacement of conjunctival epithelium by sebaceous gland carcinoma. Note the absence of deep focus in the meibomian glands or an invasive component (hematoxylin-eosin, original magnification ×20). B, Large anaplastic cells with vacuolated cytoplasm and large vesicular nuclei, diagnostic of sebaceous gland carcinoma (hematoxylin-eosin, original magnification ×200). C, Frozen section of the palpebral conjunctiva showing positive oil-red-O staining indicating the presence of intracellular lipid (oil-red-O, original magnification ×200).


In 1967, Theodore11 and Irvine12 described a "masquerade syndrome" characterized by chronic blepharoconjunctivitis due to an unsuspected conjunctival intraepithelial squamous cell or sebaceous gland carcinoma. Although the originally described neoplasms were squamous cell carcinomas, in retrospect, many of the tumors producing this clinical picture may have been sebaceous gland carcinoma.13,14 Others have also emphasized that tarsoconjunctival inflammation is common in patients with intraepithelial sebaceous gland carcinoma of the conjunctiva.810

Conjunctival intraepithelial sebaceous gland carcinoma typically arises from an underlying primary meibomian or Zeis gland carcinoma that secondarily invades the conjunctival epithelium by a centripetal or radial migration of tumor cells.8 This has been correlated with poor ocular and life prognosis.6,7 Three histopathologic patterns are exhibited by intraepithelial conjunctival sebaceous gland carcinoma—the bowenoid, pagetoid, and papillary types.68 The bowenoid type is characterized by full-thickness replacement of the epithelium by tumor cells that are large and pleomorphic and exhibit prominent mitotic activity. The pagetoid type is characterized by scattered individual tumor cells or nests of tumor cells within the epithelium that are devoid of intercellular bridges. The papillary pattern is rare and manifests with intraepithelial confluent cells resembling carcinoma in situ.8 In our case, the pattern of conjunctival involvement was of the bowenoid type.

It has been estimated that approximately 5% of patients with conjunctival intraepithelial sebaceous gland carcinoma show no detectable eyelid nodule at initial presentation.8 However, this has not been histopathologically proven with step or serial sections in most cases.810 Freeman and associates15 described 2 such cases but the histopathologic evidence was inadequate. Margo and associates9 reported one case of a 65-year-old woman whose exenteration specimen showed intraepithelial sebaceous gland carcinoma involving the inferior tarsal and bulbar conjunctiva, with one small focus of invasive tumor of the bulbar conjunctiva. There was extensive scarring of the tarsus but the meibomian and Zeis glands showed no clear-cut source of tumor. Margo and Grossniklaus10 later reported 2 similar cases in a 58-year-old woman and a 71-year-old man, both treated with orbital exenteration. The meibomian and Zeis glands showed no carcinoma but were completely replaced by lipogranulomatous inflammation. Our case was unique in several respects. The tumor occurred in a young patient aged 33 years who had been receiving oral corticosteroids. Immunosuppression may have contributed to the young age at onset of sebaceous neoplasia, as the patient had no other known predisposition, such as radiation exposure.16 In addition, there was no histopathologic evidence of inflammation, scarring, or tumor in the underlying sebaceous glands. The lack of underlying tarsal tumor on histopathologic examination is extremely unusual and raises speculation as to the source of the malignant cells.

The origin of primary conjunctival intraepithelial sebaceous gland carcinoma without deep involvement has been debated.810 One argument is that the conjunctival epithelium has the potential to spawn sebaceous gland carcinoma.8 From an embryologic point of view, this is understandable, as the sebaceous glands of the tarsus and caruncle arise from invaginations of the embryonic conjunctival epithelium.17 To support this hypothesis, 2 cases of papillomas of the tarsal conjunctival epithelium with focal sebaceous differentiation have been identified.8 Another theory suggests that glandular sebaceous neoplasms could give rise to intraepithelial spread on the ocular surface followed by spontaneous involution of the glandular component, leaving only intraepithelial disease.10 Last, it should be realized that the presence of a focus of microinvasive or deep glandular tumor cannot fully be eliminated, even by step sectioning of the specimen, as the tumor is known to have skip areas.

The optimal method of treating intraepithelial sebaceous gland carcinoma is controversial. Suggested modalities include careful observation, cryotherapy, radiotherapy, complete excision, and orbital exenteration.4,810 We chose complete excision with frozen section control and cryotherapy after map biopsies disclosed no tumor in the remainder of the conjunctiva.

In conclusion, we describe a patient with primary sebaceous gland carcinoma of the conjunctival epithelium without evidence of involvement of the tarsus, Zeis glands, caruncle, or other sites of normal sebaceous glands. Careful follow-up is necessary as the primary tumor site may not yet be evident. Any patient with unexplained asymmetric, chronic blepharoconjunctivitis or papillary hypertrophy of the palpebral conjunctiva should be considered for biopsy to rule out sebaceous gland carcinoma, even in a young patient.

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Article Information

Accepted for publication September 25, 2000.

This work was supported by the Orbis International, New York, NY (Dr Honavar); the Hyderabad Eye Research Foundation, Hyderabad, India (Dr Honavar); Eye Tumor Research Foundation, Philadelphia, Pa (Drs J. A. Shields and C. L. Shields); Paul Kayser International Award of Merit in Retina Research, Houston, Tex (Dr J. A. Shields); and Noel T. and Sara L. Simmons Endowment for Ophthalmic Pathology, Wills Eye Hospital, Philadelphia, Pa (Dr Eagle).

Corresponding author and reprints: Carol L. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107.

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