Sebaceous carcinoma, also known as sebaceous gland carcinoma (SGc), sebaceous cell carcinoma, and meibomian gland carcinoma, is an uncommon malignant cutaneous (skin) tumor. Most are typically about 1.4 cm at presentation. SGc originates from sebaceous glands in the skin and, therefore, may originate anywhere in the body where these glands are found. SGc can be divided into 2 types: periocular and extraocular. The periocular region is rich in sebaceous glands, making it a common site of origin. The cause of these lesions in the vast majority of cases is unknown. Occasional cases may be associated with Muir-Torre syndrome. SGc accounts for approximately 0.7% of all skin cancers, and the incidence of SGc is highest in Caucasian, Asian, and Indian populations. Due to the rarity of this tumor and variability in clinical and histological presentation, SGc is often misdiagnosed as an inflammatory condition or a more common neoplasm. SGc is commonly treated with wide local excision or Mohs micrographic surgery, and the relative survival rates at 5 and 10 years are 92.72 and 86.98%, respectively.
Epidemiology SGc accounts for approximately 0.7% of all skin cancers and 0.2 to 4.6% of all malignant cutaneous neoplasms. Notable risk factors include age, gender, and race. Over 98% of SGc occur in patients over the age of 40. The mean age of diagnosis for periocular and extraocular SGc is around 67 years. Periocular SGc tends to be more common in women, while extraocular SGc tends to be more common in men. SGc is extraordinarily rare in children, with only a few cases reported. There is a higher incidence of SGc in Caucasians, Asians, and Indians. While SGc affects Caucasians over 80% of the time, SGc tends to be more prevalent in the Eastern versus Western Hemisphere, contributing to 33% of eyelid malignancies in China versus 1–5.5% in Caucasians. The higher incidence of SGc in Asian populations may be due to the lower incidence of other eyelid tumors or genetic.
Presentation Sebaceous carcinoma is a neoplastic growth of sebaceous glands. It is predominantly seen in the head and neck region, given the high density of sebaceous glands in this region. The periocular region, which includes the meibomian, Zeis, and sebaceous glands of the caruncle and eyelid, is the most common site accounting for up to 75% of SGc. Meibomian glands are a type of sebaceous gland that lines the upper and lower eyelids and do not contain a follicle. The glands of Zeis contain the individual eyelash. The upper eyelid contains more meibomian glands than the lower eyelid, and consequently, SGc is 2-3 times more common in the upper eyelid. Periocular SGc most commonly presents as a yellow, hard, painless, subcutaneous nodule or papule, which may rapidly enlarge, and may be confused with chalazion, blepharitis, conjunctivitis, or other inflammatory conditions of the eye. Extraocular SGc accounts for approximately 25% of all SGc. commonly presents as a painless, red and brown or red and yellow, ulcerated papule on the head or neck and may mimic nonmelanoma skin cancers, molluscum contagiosum, adnexal neoplasms, or pyogenic granuloma. The mean lesion size of periocular and extraocular SGc is approximately 1.4 cm.
Pathophysiology SGc arises from the adnexal epithelium of sebaceous glands, most commonly the Meibomian glands or glands of Zeis. On histology, there are irregular lobules of different sizes with undifferentiated cells and distinct sebaceous cells with a foamy cytoplasm. The pathogenesis of SGc remains poorly understood. The majority of SGc are solitary and sporadic and believed to be associated with such factors as ultraviolet exposure, radiotherapy, and immunosuppression. Other SGc including those occurring outside of the head and neck region and the presentation of multiple at a time are believed to be associated with genetic defects including defects in mismatch repair genes, Muir–Torre syndrome (MTS), and familial retinoblastoma. The observation of extraocular SGc arising from Bowen disease or actinic keratosis and the predisposition of SGc to arise in sun-exposed areas suggest a role for ultraviolet exposure or intraepidermal neoplasia in the pathogenesis of some SGc in sun-exposed areas. While there are markedly increased rates of cutaneous neoplasms in solid organ transplant recipients, there is evidence to suggest that solid organ transplantation may increase the risk of SGc up to 90 times. Others have observed a significantly increased risk of SGc in patients with AIDS, suggesting some role for immunosuppression. Reports have also shown the onset of SGc within the field of irradiation for patients undergoing radiotherapy for retinoblastoma, eczema, or cosmetic epilation. There are cases reported of SGc arising from nevus sebaceus. MTS is an autosomal dominant cancer syndrome characterized by multiple sebaceous and visceral neoplasms, the most common being colorectal adenocarcinoma. MTS results from defects in DNA mismatch repair genes, MLH1, MSH2, and MSH6, leading to a buildup of unstable microsatellite sequences and replication errors predisposing to various malignancies. Patients with MTS may present with numerous sebaceous tumors at a younger age (mean age of 53 years) and in atypical locations, including extraocular. The incidence of MTS in patients with sebaceous neoplasms is as high as 14 to 50%. Besides mutations in mismatch repair genes, Wnt/beta-catenin signaling is known to be altered and plays a significant role in the development of sebaceous tumors. Altered expression of beta-catenin, p21, sonic hedgehog signaling (Shh), and E-cadherin has been associated with invasion, metastasis, and poor clinical outcomes. More recently, mutations in tumor suppressor genes including p53 and Rb have been associated with the development of sporadic SGc as well as SGc in MTS patients with intact mismatch repair and subsets of younger patients presenting with SGc harboring transcriptionally active high-risk human papillomavirus (HPV).
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