Sebaceous carcinoma is a rare malignant tumor of the sebaceous gland. These tumors are most frequently seen on the eyelids. They are most commonly found as solitary tumors but may be seen as a part of the Muir-Torre syndrome. The Muir-Torre syndrome is caused by a genetic abnormality in the tumor suppressor genes MSH2 and MLH1 and is associated with multiple sebaceous tumors, both benign and malignant. The syndrome is also associated with a high incidence of internal gastrointestinal and genitourinary malignancies.
Clinical Findings: These tumors are most commonly found on the eyelid skin and the eyelid margin. The reason is that the periocular skin contains many types of modified sebaceous glands, including the meibomian glands and the glands of Zeis. Many other, less common modified sebaceous glands exist, including the caruncle glands and the multiple sebaceous glands associated with the hairs of the periocular skin. It is believed that most sebaceous carcinomas arise from the meibomian glands, with the glands of Zeis the second most common site of origin. The meibomian glands are modified sebaceous glands that are located within the tarsal plate of the upper and lower eyelid.
Sebaceous carcinoma has been reported to occur in all areas of the body, but the vast majority occur on the eyelids, with the next most common area being the rest of the head and neck region, probably because the density of sebaceous glands is higher in these regions. The tumors typically start as small subcutaneous nodules or thickenings of the skin. They are initially asymptomatic and can be mistaken for a stye or chalazion. The tumor almost always has a slight yellowish coloration, which, together with the characteristic peri- ocular location, can help with the diagnosis. The major differentiating factor is that these other two inflammatory processes are very acute in onset, are painful, and resolve within a few weeks. Sebaceous carcinoma is a slow-growing tumor that persists and continues to enlarge, eventually causing erosions and ulceration. Once this occurs, the tumor becomes painful and can easily bleed with superficial trauma. The clinical differential diagnosis is often between sebaceous carcinoma and a basal cell carcinoma or squamous cell carcinoma.
Sebaceous carcinomas occur with a higher incidence in the older female population. There is a predilection for Caucasians and for patients receiving chronic immunosuppressive therapy. Patients with the Muir-Torre syndrome are at dramatically higher risk for seba- ceous carcinoma compared with age-matched controls. Previous radiation therapy for the treatment of facial or ocular tumors has also been shown to be a predisposing factor for the development of sebaceous carcinoma.
As the tumors enlarge, they exhibit an aggressive local growth pattern. They can rapidly enlarge and metastasize to regional lymph node basins.
Pathogenesis: Solitary sebaceous carcinomas arise from sebaceous glands, but the exact pathomechanism is not understood. Many risk factors have been determined, but how these translate into tumor development is still being studied. More is known about the sebaceous tumors associated with the Muir-Torre syndrome. This syndrome is caused by a genetic defect in the mismatch repair genes. The syndrome is inherited in an autosomal dominant fashion. The genes that are abnormal in this syndrome are responsible for microsatellite instability within the cells of the sebaceous carcinomas and may lead directly to malignant transformation of the benign sebaceous gland.
Histology: These tumors are derived from sebaceous glands and show a high degree of infiltrative growth. The tumor deeply invades the subcutaneous tissue; in the periocular area, it often invades the underlying muscle tissue. The lesions are poorly circumscribed, and mitoses are frequently seen. The tumor cells are large basaloid cells that show areas of mature sebocyte differentiation and areas that are poorly differentiated.
Treatment: The tumors are locally aggressive and have a high rate of regional lymph node metastasis. The treatment of choice is surgical removal, either with Mohs micrographic surgery or with a wide local excision, making sure to get clear tumor margins. These tumors have a high risk of recurrence, and clinical follow-up is required. The use of postoperative radiotherapy is warranted in specific cases. Patients with metastatic disease may benefit from a combination of radiotherapy and systemic chemotherapy.