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Sebaceous Carcinoma

Sebaceous carcinoma (SGc), also known as sebaceous gland carcinoma, sebaceous cell carcinoma, and meibomian gland carcinoma, is an uncommon malignant cutaneous tumour originating from sebaceous glands.

These glands are located throughout the body, thus SGc may arise anywhere. It is most common in the periocular region due to the high density of sebaceous glands. SGc accounts for approximately 0.7% of all skin cancers and is frequently misdiagnosed due to its rarity and variable presentation.

Treatment commonly involves wide local excision or Mohs micrographic surgery.

Micrograph of a sebaceous carcinoma (left of image) metastatic to the parotid gland (right of image). H&E stain.
Micrograph of a sebaceous carcinoma (left of image) metastatic to the parotid gland (right of image). H&E stain.

Epidemiology

SGc represents about 0.7% of all skin cancers and 0.2 to 4.6% of all malignant cutaneous neoplasms. It mainly affects individuals over 40 years of age, with a mean diagnosis age of 67 years. Periocular SGc is more common in women, whereas extraocular SGc is more common in men. SGc is rare in children and more prevalent in Caucasians, Asians, and Indians. Notably, it contributes to 33% of eyelid malignancies in China compared to 1–5.5% in Caucasians.

Presentation

Sebaceous carcinoma is most frequently found in the head and neck region. The periocular region, which includes the meibomian, Zeis, and sebaceous glands of the caruncle and eyelid, accounts for up to 75% of SGc cases. Periocular SGc typically presents as a yellow, hard, painless nodule or papule that may be mistaken for inflammatory conditions like chalazion or conjunctivitis.

Extraocular SGc, comprising about 25% of all SGc, usually presents as a painless, red and brown or red and yellow, ulcerated papule on the head or neck, potentially mimicking nonmelanoma skin cancers or benign lesions like molluscum contagiosum.

Pathophysiology

SGc arises from the adnexal epithelium of sebaceous glands, particularly the Meibomian glands or glands of Zeis. Histologically, it features irregular lobules with undifferentiated cells and distinct sebaceous cells with a foamy cytoplasm. The pathogenesis is poorly understood, with factors like ultraviolet exposure, radiotherapy, and immunosuppression potentially playing roles. Genetic defects, including Muir–Torre syndrome (MTS), are also implicated.

Diagnosis

Due to the variable clinical and histological appearance, SGc is often misdiagnosed. Full thickness biopsy with microscopic examination is essential for definitive diagnosis. Map biopsies may be required in cases exhibiting pagetoid spread. Histopathological markers and immunohistochemical stains, such as epithelial membrane antigen (EMA) and cytokeratin-7 (CK-7), aid in differentiating SGc from other lesions.

Morphology

Histopathologically, SGc is classified based on cytoarchitecture, cytology, and growth pattern, with the lobular variant being most common. Well- and moderately differentiated tumours exhibit vacuolisation within the cytoplasm.

Immunohistochemistry

Tumour cells in SGc stain positive with EMA, CK-7, Ber-EP4, adipophilin, perilipin, and androgen receptor (AR), and negative for carcinoembryonic antigen (CEA) and S100 protein. Immunohistochemistry can also screen for MTS by identifying the absence of staining for DNA mismatch repair proteins.

Staging

Periocular SGc is staged according to the American Joint Committee on Cancer (AJCC) staging system for eyelid carcinoma. Sentinel lymph node biopsy (SLNB) is recommended for periocular SGc stage T2c or higher to assess regional metastasis.

Treatment

Local SGc is primarily managed with surgical resection, including wide local excision and Mohs micrographic surgery (MMS), which offers precise tumour removal and lower recurrence rates.

Surgical Resection

MMS is preferred over wide local excision due to its accuracy and lower recurrence rates, especially in cosmetically sensitive areas.

Radiation Therapy

Radiotherapy is not recommended as primary therapy due to higher recurrence rates and potential adverse effects. It is reserved for patients unable to undergo surgery.

Chemotherapy

Chemotherapy is not indicated for local disease but may be considered for advanced tumours or metastatic disease.

Adjuvant Radiation Therapy

Adjuvant radiation therapy may be used for locally advanced tumours or those with positive margins, although data on its efficacy is limited.

Prognosis

Survival rates are higher for ocular versus extraocular tumours and localised versus regional disease. The relative survival rates at 5 and 10 years are 92.72% and 86.98%, respectively. The rate of metastasis is approximately 4.4% for periocular SGc and 1.4% for extraocular SGc. Early recognition and improved treatment modalities have contributed to better prognosis over time.


Self-assessment MCQs (single best answer)

What is sebaceous carcinoma (SGc)?



In which region of the body is sebaceous carcinoma most frequently found?



What is the mean age of diagnosis for sebaceous carcinoma?



Which gender is more commonly affected by periocular sebaceous carcinoma?



What is the most common histopathological variant of sebaceous carcinoma?



Which immunohistochemical stain is positive in sebaceous carcinoma cells?



What is the primary treatment for local sebaceous carcinoma?



Which syndrome is associated with sebaceous carcinoma?



What is the recommended staging system for periocular sebaceous carcinoma?



What is the relative 5-year survival rate for sebaceous carcinoma?



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