Sebaceous Carcinoma of the Ocular Region: A Review

doi:10.1016/j.survophthal.2004.12.008

Survey of Ophthalmology

Volume 50, Issue 2, March–April 2005, Pages 103-122

https://doi.org/10.1016/j.survophthal.2004.12.008 Get rights and content

Abstract

Sebaceous carcinoma of the ocular region is a malignant neoplasm that is being recognized more frequently and managed by innovative techniques of local resection, cryotherapy, topical chemotherapy, and radiotherapy, resulting in improved visual and systemic prognosis.

Introduction

Sebaceous carcinoma is an important malignant neoplasm that occurs most often in the periorbital area, usually in the eyelid.9, 10, 25, 28, 33, 56, 60, 91, 92, 98, 103, 129, 133 It can exhibit aggressive local behavior and can metastasize to regional lymph nodes and distant organs. Historically, this neoplasm was notorious for masquerading as other benign and less malignant lesions, resulting in delays in diagnosis and relatively high morbidity and mortality. Hence, the ophthalmologist should be cognizant of the clinical features and current therapy of periorbital sebaceous carcinoma. In recent years, greater awareness of this neoplasm has resulted in earlier diagnosis and has provided the opportunity for less aggressive therapy. Even though ophthalmologists have become more familiar with the clinical variations of periorbital sebaceous carcinoma, we have observed that serious delays in diagnosis are still common. This review provides an update on sebaceous carcinoma of the ocular region, with emphasis on current options in management.

Sebaceous glands are generally associated with hair follicles and, hence, are most abundant in skin where more hair is present. They are characterized by holocrine secretion in which the entire cell is desquamated into the lumen and secreted through a duct to the skin surface. Even though cells within sebaceous glands demonstrate a high mitotic activity, the development of malignant sebaceous neoplasms is uncommon.⁵⁶

The terms sebaceous carcinoma, sebaceous gland carcinoma, and sebaceous cell carcinoma and meibomian gland carcinoma have all been used in the literature to describe the malignant neoplasm discussed in this review. In speaking with several ophthalmic pathologists, we found that there is no general agreement on terminology. However, in most recent articles, the term sebaceous carcinoma has been employed and most ophthalmic pathologists seem to prefer that term. Hence, the term sebaceous carcinoma is used in this article.

Sebaceous carcinoma is a malignant neoplasm that originates from cells that comprise sebaceous glands.9, 10, 25, 28, 33, 56, 60, 91, 92, 103, 129, 133 There is an unusual abundance of sebaceous glands in the ocular region, particularly in the tarsus (Meibomian glands) and in association with the cilia (Zeis glands). The caruncle is also endowed with sebaceous glands that are associated with fine lanugo hairs of that structure. Sebaceous glands are also present in the eyebrow region. Therefore, all of these periorbital sites are capable of spawning sebaceous neoplasms.⁵⁶

A historical review of periorbital sebaceous carcinoma was provided by Kass and Hornblass in 1989.⁶⁰ Based on their review, the first case may have been reported by Thiersch in 1865 and another case was reported by Baldauf in 1870. However, Allaire is generally credited with reporting the first reasonably well-documented case in 1891.⁶⁰ There were several subsequent reports including one by Hagedoorn, who recognized the aggressive nature and metastatic potential of this neoplasm.⁴³

Most of our modern understanding of eyelid sebaceous carcinoma was initiated by the review of Straatsma in 1956, who reported 16 cases in which he clarified the origin and clinical behavior of this neoplasm.¹⁴³ Subsequently, other publications contributed to our understanding of this neoplasm.9, 10, 18, 26, 28, 91, 92, 95, 103, 129, 145, 147, 155, 168

Although sebaceous carcinoma has a marked tendency to arise in the ocular region, particularly in the eyelids, it does occur in other locations.3, 5, 6, 7, 100, 158 It is estimated that approximately 25% of sebaceous carcinomas occur in extraorbital sites, about 70% of which are in the head and neck region.¹⁵⁸ The parotid gland is the most common extraorbital origin and accounts for almost 30% of all cases.¹⁵⁸ In that location, the tumor may arise either from pleuripotential cells with capacity for sebaceous differentiation or from ectopic sebaceous cells that are displaced in the parotid gland during embryologic development. An incomplete list of other reported sites of origin include the submandibular gland, chest, extremities, great toe, sole of the foot, penis, external auditory canal, and anterior neck region.5, 90, 101 The demographics, clinical course, pathology, management, and prognosis are similar for extraorbital and periorbital sebaceous carcinoma.

Section snippets

Incidence

About 5–10% of all skin malignancies occur on the eyelid and basal cell carcinoma is the most common malignant eyelid tumor.²⁴ Although the incidence varies from series to series, in the United States it is generally acknowledged that basal cell carcinoma accounts for about 90% of malignant eyelid tumors, sebaceous carcinoma for about 5%, squamous cell carcinoma for about 4%, and others, including melanoma, for only about 1%.

The incidence of sebaceous carcinoma shows a puzzling variation

Demographics and Risk Factors

Some relative risk factors for periocular sebaceous carcinoma include older patient age, female sex, race, prior irradiation, systemic associations, prolonged use of diuretics, and immunosuppression.

Ocular Origins

As mentioned earlier, the periorbital area is particularly well-endowed with sebaceous glands any of which can spawn sebaceous carcinoma. The clinical features of sebaceous carcinoma that develops from these specific glands are discussed in the subsequent section.

Clinical Features

Historically, sebaceous carcinoma of the eyelid is notorious for masquerading as a more common benign condition (“masquerade syndrome”), often resulting in a long delay before the correct diagnosis is made (Brownstein S, Gariepy EL, Codere F: Sebaceous carcinoma masquerading as a chalazion. Ophthalmic Practice 5:123–6, 1987).4, 10, 15, 28, 86, 103, 129, 157 Such a delay in diagnosis can increase the chance of local recurrence, metastasis, and death. Consequently, ophthalmologists,

Clinical Differential Diagnosis

Because sebaceous carcinoma can resemble a number of inflammatory and neoplastic conditions, it is important for the clinician to be familiar with the clinical variations of sebaceous carcinoma and the simulating conditions. As mentioned earlier, confusion with benign conditions such as chalazion and blepharoconjunctivitis has led to the term “masquerade syndrome” to characterize this lesion.15, 37, 42, 161

Methods of Spread

One of the more clinically challenging aspects of sebaceous carcinoma is its ability to extend beyond its original site to affect other structures. This can occur in the form of direct local extension, regional metastasis, or distant metastasis.

Pathology

Another challenging problem related to sebaceous carcinoma is the difficulty often encountered in histopathologic diagnosis of this neoplasm. Because the tumor usually occurs in the ocular area, specimens are often sent to ophthalmic pathologists who are more accustomed to seeing this uncommon tumor. General pathologists, particularly those in community hospitals, are unlikely to see a case during their entire career. Hence, it has often been misdiagnosed as squamous cell carcinoma, basal cell

Histopathologic Differential Diagnosis

As mentioned earlier, the histopathologic diagnosis of sebaceous carcinoma can be challenging and it is often misdiagnosed as other neoplasms, particularly squamous cell carcinoma or basal cell carcinoma. However, based on the typical histopathologic features of these entities and the aforementioned histochemical and immunohistochemical reactions, the diagnosis can generally be established. The following represents some of the light microscopic features that serve to differentiate them.

Pathogenesis

Most sebaceous carcinomas appear to arise de novo, and not from a pre-existing sebaceous adenoma, sebaceous hyperplasia, or sebaceous (organoid) nevus. Other factors that may be pathogenically related, like irradiation, immunosuppression, and use of diuretics, have already been discussed.

Studies have shown that there may be a relationship of sebaceous carcinoma and human papillomavirus (HPV). A report of 21 tumors from Japan revealed that 13 tumors (62%) were positive for HPV DNA using in-situ

Diagnostic Techniques

The diagnostic methods and management of sebaceous carcinoma necessarily overlap, but they are discussed separately here for simplification. The diagnosis of periorbital sebaceous carcinoma (as well as other eyelid neoplasms) necessitates a high index of suspicion based on clinical findings, followed by excisional or incisional biopsy, and histopathologic confirmation of the diagnosis. If an incisional biopsy is done to establish a diagnosis, it is generally preferable to perform a full

Management

The following information related to management is derived from personal experience of the authors combined with a review of the literature, and may not necessarily reflect the experience or views of others who manage sebaceous carcinoma.

The first step in management of a patient with periorbital sebaceous carcinoma is to establish the diagnosis and determine the extent of the disease as quickly and as accurately as possible. This requires a comprehensive clinical evaluation of the eyelid,

Prognosis

The visual prognosis for patients with periorbital sebaceous carcinoma varies with the extent of the disease and the type of treatment employed. The systemic prognosis varies with several factors. In an earlier series of 88 cases submitted to the AFIP, Boniuk and Zimmerman reported 30% mortality.¹⁰ Doxanas and Green reported an 18% tumor-related mortality in their series of 40 patients.²⁸ Rao and associates reported 104 cases with greater than 5-year follow-up data.¹⁰³ Of those, 23 patients

Summary and Conclusions

Sebaceous carcinoma is a malignant neoplasm that develops most often in the eyelids, usually from the meibomian glands of the tarsus. It has a tendency to be exhibit diffuse, invasive growth in the eyelid and conjunctiva, and can metastasize to regional lymph nodes and distant organs. Historically, this neoplasm is notorious for masquerading as inflammatory disease or other tumors, resulting in delays in diagnosis and higher morbidity and mortality. In recent years, however, greater awareness

Method of Literature Search

Literature selection for this review was based on a Medline database search (1966–2004), using the terms eyelid, conjunctiva, tumor, sebaceous carcinoma, and sebaceous gland carcinoma. To supplement this, the medical librarians at Wills Eye Hospital, Thomas Jefferson University, conducted a similar computerized search on the same subjects. Pertinent articles from the English-language literature were primarily selected. Additionally, relevant references contained within those articles were

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