Sebaceous glands are part of epidermal appendages. Neoplasms of the sebaceous glands may be benign, such as sebaceous hyperplasia or sebaceous gland adenomas. The malignant sebaceous gland carcinoma most commonly arises in the periocular area.[1, 2] Fewer than 120 cases of sebaceous cell carcinoma have been reported at extraocular sites. The most common site of origin is the meibomian glands of the eyelids, leading to the term meibomian gland carcinoma.[1] However, this neoplasm can occur in other sebaceous glands, such as in the caruncle, the glands of Zeis, and in the eyebrow. Sebaceous cell carcinoma is a lethal eyelid malignancy and can masquerade as benign conditions. Error or delay in diagnosis is common, and this tumor carries a significant mortality rate with metastasis.
From 2000 through 2016, sebaceous carcinoma had an overall incidence of 2.4 cases per million individuals, with an average of 800 cases per year in the United States. The incidence was higher in males (3.5 cases per million) compared to females (1.7 cases per million) and increased with age, with the highest incidence seen in individuals aged 80 years and older (22.7 cases per million). Additionally, 78% of cases were reported in non-Hispanic Whites, who had approximately four times the incidence rate compared to African Americans.[3]
In a retrospective study, 31 patients were diagnosed with sebaceous cell carcinoma of the ocular adnexa on histopathology. Twenty (65%) of the patients were women and 11 were men. The upper eyelid was involved in 18 patients, the lower eyelid in 10, the upper and lower eyelids in 1, and the caruncle in 2.[4]
Although sebaceous cell carcinomas are more common in elderly patients, they may be seen in younger patients with a history of radiation to the face.
In the periocular area, the most common sites for sebaceous carcinoma typically are the Meibomian glands, which are specialized sebaceous glands. However, tumors also can originate from the Zeiss glands and sebaceous glands in the ocular caruncle.[1]
Sebaceous cell carcinoma may mimic either chalazion or chronic blepharitis.[1] It tends to invade locally, as well as spreading to regional lymph nodes. Sebaceous cell carcinomas may grow in nests with central necrosis. The intraepithelial spread may lead to the erroneous histologic diagnosis of epithelial dysplasia or carcinoma in situ.
Foamy cytoplasm is seen only in sebaceous carcinoma, but it is absent in conjunctival or cutaneous squamous cell carcinoma. It also can histologically mimic basal cell carcinoma, squamous carcinoma, or Merkel cell tumor.
Either fresh tissue or formalin-fixed tissue not exposed to alcohol can be frozen, and positive fat stains, such as oil red O, can confirm the diagnosis of sebaceous carcinoma.
The clinical appearance of sebaceous gland carcinoma is highly variable. They simulate such benign conditions as chalazion, blepharoconjunctivitis, keratitis, and other malignant or benign skin lesions.
Many of the skin tumors have a predilection for the upper eyelid and have a yellowish appearance. Tumors at the eyelid margin commonly cause loss of eyelashes. Classically, this lesion is a firm, painless, indurated mass or ulceration associated with the loss of cilia, in an area that has been treated for recurrent chalazia.
Both the history and the presentation of sebaceous cell carcinoma are variable. Typically, there is an insidious onset of a painless firm eyelid mass. This mass easily can appear clinically as a recurrent or chronic chalazion. Sebaceous cell carcinoma also can mimic unilateral blepharoconjunctivitis, meibomitis, basal or squamous cell carcinoma, conjunctival or corneal carcinoma in situ, orbital inflammation, or superior limbic keratoconjunctivitis.
Sebaceous cell carcinoma is shown in the images below.
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A 63-year-old white man with lower eyelid sebaceous cell carcinoma and lash loss is shown.
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Gross pathology slide of sebaceous cell carcinoma, from same man as seen in image above.
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Microscopic pathology slide of sebaceous cell carcinoma, from same man as seen in images above.
Sebaceous tumors of the eyelid may arise from meibomian glands, Zeis glands, or glands associated with the caruncle.
The meibomian glands originate in the tarsus and number approximately 25 in the upper eyelid and 20 in the lower eyelid. They are oil-producing sebaceous glands. A chalazion is an inflammation caused by obstruction of the meibomian glands and occasionally can be confused with sebaceous cell carcinoma.
Zeis glands are small, modified, sebaceous glands that open into the hair follicles at the base of the eyelashes.
Sebaceous carcinoma is a fast-growing form of skin cancer that has a 5-year survival rate of 78% for localized/regional disease and 50% for metastatic disease. The incidence of this cancer has been on the rise in the United States for many years, but the factors contributing to this increase are not fully understood.[3]
Aside from its aggressive nature, sebaceous carcinoma can lead to substantial treatment-related complications owing to the fact that these tumors primarily develop on the head and neck. Management often involves complex facial reconstruction and radiotherapy, further adding to the potential morbidity associated with the disease.[3]
Obtain a biopsy specimen of the lesion to establish the diagnosis. Numerous sebaceous elements with mitotic figures are observed; the cells may stain positively for fat with oil red O stain. The tumor can be multicentric, and it may grow into nests with central necrosis mimicking comedocarcinoma of the breast. Individual tumor cells may be present in the epithelium in a pattern of intraepithelial spread reminiscent of Paget disease. Therefore, it is recommended to perform multiple conjunctival map biopsies at the time of the initial lesion biopsy to stage the local disease.[1]
It is good clinical practice to obtain a biopsy specimen of any recurrent chalazion or unilateral blepharitis that is resistant to usual treatment. It is also advisable to alert the pathologist to the possible diagnosis and ask for the preferred method of tissue handling. Formalin fixation is fine if the laboratory staff know to avoid alcohol and xylene histoprocessing methods.
The histopathology of sebaceous gland cell carcinoma is dominated by large anaplastic cells with open vesicular nuclei and prominent nuclei set in foamy or frothy cytoplasm. The appearance of the cytoplasm is a result of the presence of lipid vacuoles. A useful histopathologic feature is large nuclear forms, including multinucleated tumor cells and bizarre monstrous cell forms. The spread of the tumor in the form of infiltrating lobules, nests, and cords, as well as superficially within the epithelium, is highly characteristic.
Treatment aims to remove the malignant lesion to prevent local or systemic spread.[5]
The treatment of sebaceous gland carcinoma is adequate surgical excision, with wide surgical margins and fresh frozen section controls to delineate the tumor edges. Lymph node evaluation is necessary to evaluate metastasis.
If diffuse involvement of the upper and lower eyelids is present, exenteration is required. Obtain a biopsy specimen of the areas of reddening of the conjunctiva that are suggestive of sebaceous gland carcinoma at the time of surgery.[3]
Monitoring for additional malignancies or metastatic sites is warranted. A marked increase in head and neck basal cell lesions is found in patients with previous eyelid malignancies. As many as 40% of patients also may have had or may develop other visceral malignancies.
In a retrospective study of 31 patients, as mentioned in Frequency, 23 patients had in situ disease, pagetoid disease, or both. Eight patients reported symptoms for less than 6 months, and 22 patients had symptoms for less than or equal to 12 months before the diagnosis of sebaceous cell carcinoma was made. Local surgical excision of the tumor as initial treatment was performed in 25 patients. Exenteration was the initial surgery performed in 4 patients. Two patients died from metastatic sebaceous cell carcinoma, which is lower than previous reports and may be related to earlier detection or improved surgical excision techniques.[4]
With wide excision and no evidence of metastasis, surgery results in a cure for the malignancies. However, sebaceous lesions have a high incidence of recurrence and metastasis.
The Mohs chemosurgery method commonly is used in facial and periocular nonmelanocytic malignancies.[3] This method allows the focal and complete removal of a tumor with histologically verified margins. However, in diffuse tumors with high recurrence rates, such as sclerosing sweat duct carcinoma, recurrence rates may be as high with the Mohs chemosurgery method as with the traditional methods. In histologically verified sebaceous gland carcinoma, wide complete (ie, full thickness) resection is necessary. Sending additional margins for permanent sections as well as frozen section margins may increase success. Since multiple widespread adnexal biopsies need to be performed, the Mohs chemosurgery method probably is not warranted in most situations of sebaceous cell carcinoma.
Michael L Glassman, MD, Ophthalmic Plastic, Orbital and Reconstructive Surgery, Department of Ophthalmology, Oculoplastic and Orbital Surgery, New York Eye and Ear Infirmary, Manhattan Eye Ear and Throat Hospital
Disclosure: Nothing to disclose.
Specialty Editors
Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Hampton Roy, Sr, MD, † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Mounir Bashour, MD, PhD, CM, FRCSC, FACS, Assistant Professor of Ophthalmology, McGill University Faculty of Medicine; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD
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