What Is This White Lesion on the Cheek?

A 66-year-old male patient with a history of hypertension, hypercholesterolemia, and numerous keratinocyte carcinomas presented to the clinic with a skin-colored papule and an adjacent gritty, hyperkeratotic, erythematous papule on the right cheek. The gritty papule was biopsied for concern of squamous cell carcinoma, and pathology revealed a hyperkeratotic actinic keratosis. At the 6-month follow up, the patient reported continued growth of the papule on the right cheek. Clinically, it appeared as a 5-mm, skin-colored papule adjacent to the previous biopsy scar (Figure 1 and Figure 2). A tangential biopsy was performed due to concern for another keratinocyte neoplasm.

What Is The Diagnosis?

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Sebaceous Adenoma

Sebaceous glands are an essential component of the skin that produce a unique combination of lipids, known as sebum, under hormonal influences.^1,2 Most sebaceous glands develop alongside hair follicles and release their contents into the follicular infundibulum via holocrine secretion.^2,3 Free sebaceous glands can be found on the eyelids (meibomian glands); the vermilion of the lips, oral mucosa, and labia minora (Fordyce granules), the areolas (Montgomery tubercles), and the prepuce (Tyson glands).^3-5

Sebaceous hyperplasia is a common condition resulting from sebaceous gland hypertrophy. It primarily affects the middle-aged to older population and is uncommon during childhood and adolescence.⁶ Sebaceous hyperplasia occurs in 1% of the general population; however, its incidence can be as high as 16% in patients on chronic cyclosporine immunosuppression due to its stimulatory effects on undifferentiated sebocytes.^7,8

Sebaceous hyperplasia clinically presents as small, umbilicated, white to yellow papules on the forehead, nose, and cheeks. These lesions are benign, and treatment is considered cosmetic. Histologically, sebaceous hyperplasia presents with increased sebaceous lobules localized superficially in the dermis, surrounding a central pore.⁹

Sebaceous adenomas are true sebaceous neoplasms that present as pink, yellow, or whitish papules or nodules. They have a predilection for the head and neck.¹⁰ Similar to sebaceous hyperplasia, sebaceous adenomas have a higher incidence in patients on chronic cyclosporine immunosuppression, affecting as many as 30% of patients receiving this therapy.^11-13 Histologically, sebaceous adenomas retain a well circumscribed and lobular architecture with mature sebocytes but show connection to the overlying epithelium. The increase in peripheral basaloid germinative cells distinguishes sebaceous adenomas from hyperplasia.¹⁰ Concerning features such as increased mitosis or cytologic atypia are not typically noted.^10,14,15

Sebaceomas display a similar distribution to sebaceous adenomas but are generally larger and more yellow in appearance. On histologic examination, basaloid germinative cells outnumber mature sebocytes and compose greater than 50% of the tumor. Although sebaceomas tend to lose the structured lobular architecture, they remain well circumscribed and symmetric without significant cytologic atypia.¹⁶

Both sebaceous adenomas and sebaceomas are associated with Muir-Torre syndrome, a rare autosomal dominant disease that occurs secondary to deficits in mismatch repair genes, resulting in sebaceous neoplasms and visceral malignancies.^17,18 Screening for Muir-Torre syndrome on biopsy specimens shows loss of expression of MLH1, MSH2, MSH6, and PMS2 in tumors associated with Muir-Torre syndrome but not in sporadically arising tumors.^19,20

Like their nonmalignant counterparts, sebaceous carcinomas are more common in older adults. The periocular type is more common than the extraocular type and is more often associated with Muir-Torre syndrome.²¹ Periocular sebaceous carcinomas are the second most common malignancies in the periocular region after basal cell carcinomas (BCCs).^22,23 They typically present as painless nodules on the upper eyelid and are often mistaken for an inflammatory or infectious process, leading to delayed diagnosis.^24,25 At the time of diagnosis, lymphovascular extension can be observed in up to 20% of cases.²⁶ Histologically, sebaceous carcinomas demonstrate infiltrative growth and invasion into the dermis, subcutis, and even skeletal muscle of the eyelid.¹⁸ Tumor cells often lose evidence of sebaceous differentiation, presenting as pleomorphic cells with high mitotic figures and hyperchromatic nuclei.²⁷

Given their clinical appearance, the most common differential diagnosis for sebaceous adenomas is BCC. Histologically, the foamy cytoplasm of sebaceous tumors can mimic primary clear cell neoplasms of eccrine, melanocytic, keratinocytic, or xanthomatous lesions or metastatic tumors.¹⁸

Surgical excision is considered the appropriate treatment for sebaceous adenomas and sebaceomas. However, given their frequent association with Muir-Torre syndrome, patients diagnosed with sebaceous adenomas or sebaceomas should undergo screening to evaluate the risk of internal malignancies.

Evaluation of the biopsy specimen showed a well-circumscribed tumor composed of mature sebocytes arranged in lobular architecture with an increase in peripheral basaloid cells, suggestive of a sebaceous adenoma (Figure 3 and Figure 4). Tumor involvement extended beyond the deep margins. Results were discussed with the patient, who elected to undergo excisional removal, genetic screening, and routine full body examinations, as recommended.

The sebaceous gland is a vital structure that produces a unique cocktail of lipids essential to the normal function of the skin. With increasing age and hormonal changes, sebaceous glands can undergo hyperplasia, which produces a common but benign lesion that mostly carries cosmetic concerns. True sebaceous neoplasms can arise sporadically but may also be associated with Muir-Torre syndrome and mismatch repair gene deficits. Patients with sebaceous adenomas, sebaceomas, or sebaceous carcinomas should undergo screening tests for Muir-Torre syndrome to determine their risk of visceral malignancies. They should also be followed regularly by a dermatologist.

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22. Xu XL, Li B, Sun XL, et al. Eyelid neoplasms in the Beijing Tongren Eye Centre between 1997 and 2006. Ophthalmic Surg Lasers Imaging. 2008;39(5):367-372. doi:10.3928/15428877-20080901-18

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24. Buitrago W, Joseph AK. Sebaceous carcinoma: the great masquerader: emgerging concepts in diagnosis and treatment. Dermatol Ther. 2008;21(6):459-466. doi:10.1111/j.1529-8019.2008.00247.x

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