Sebaceous Carcinoma (Eyelid)

Sebaceous carcinoma is a malignant tumour of the sebaceous glands (meibomian glands, glands of Zeis, caruncle and brow).

• Accounts for about 1 to 5 percent of eyelid malignancies in Western series and up to 30 percent in Asian series.
• Occurs mostly in women aged 60 to 80 years. Upper lid is involved about twice as often as lower lid, because it has more meibomian glands.
• Risk factors: prior head and neck radiotherapy, immunosuppression, Muir-Torre syndrome (sebaceous tumours plus visceral cancers, mismatch repair gene mutations).
• Known as the great masquerader: it mimics chronic blepharitis, recurrent chalazion and chronic conjunctivitis, delaying diagnosis by 1 to 3 years on average.
• Regional lymph node metastasis in about 20 to 30 percent and distant spread in 5 to 15 percent; mortality 6 to 30 percent, higher with delayed diagnosis.

• Firm, painless, yellowish nodule within the tarsus, often mistaken for a chalazion that recurs after curettage.
• Diffuse thickening of the lid margin with loss of lashes (madarosis), lid margin distortion, and chronic unilateral blepharoconjunctivitis not responding to treatment.
• Pagetoid spread: intraepithelial migration of tumour cells into the conjunctiva, producing a diffuse thickened, hyperaemic conjunctiva and punctate keratopathy, with skip lesions.
• Ulceration, bleeding, and yellow crusting. Orbital extension leads to proptosis.
• Preauricular or submandibular lymphadenopathy in advanced disease.

• High index of suspicion in any adult over 50 with a recurrent chalazion or unilateral chronic blepharitis.
• Full thickness wedge biopsy or incisional biopsy for histology with fat stain (oil red O on frozen tissue, because lipid is lost in routine processing). Immunostains: EMA, adipophilin, androgen receptor positive; BerEP4 negative.
• Map biopsies of the bulbar and tarsal conjunctiva (four quadrant plus areas of abnormality) to detect pagetoid spread.
• Imaging: MRI orbits and face for orbital or perineural spread; ultrasound of parotid and cervical nodes; CT chest, abdomen if nodes are positive.
• Muir-Torre: immunohistochemistry for MSH2 and MSH6 in the tumour, followed by genetic testing and colonoscopy for family members.
• Staging by tumour size, nodal and distant disease; sentinel node biopsy considered for tumours larger than 10 mm.

• Wide surgical excision with margin control (Mohs or frozen section), 5 to 6 mm margins, then lid reconstruction (Hughes flap, Cutler-Beard flap, Mustardé flap, tarsoconjunctival grafts).
• Conjunctival pagetoid disease: topical mitomycin C 0.04 percent four times daily for 1 week on and 1 week off, repeated for 3 to 4 cycles, plus cryotherapy to involved areas at surgery. Orbital exenteration for orbital invasion or diffuse conjunctival involvement not controlled otherwise.
• Radiotherapy (45 to 60 Gy in fractions) for non-surgical candidates and as adjuvant therapy for positive margins or perineural invasion.
• Nodal disease: parotidectomy and neck dissection with adjuvant radiotherapy.
• Metastatic disease: platinum based chemotherapy (cisplatin 75 mg/m2 with 5-fluorouracil 1000 mg/m2/day for 4 days every 3 weeks), and immune checkpoint inhibitors (for example pembrolizumab 200 mg every 3 weeks) are used in selected cases.
• Follow up every 3 to 4 months for 2 years, then every 6 months to 5 years, with nodal examination.