Parvesh Konda

Introduction and Epidemiology

Sebaceous cell carcinoma is a rare cancer of sebaceous glands that most commonly affects the eyelids (75%). The approximate global incidence rate varies between 1 to 3 people per one million person-years. There were just over 700 diagnoses in England between 1999 and 2008 (1). Due to similar presentations, sebaceous carcinoma can sometimes be misdiagnosed as a chalazion, hordeolum, basal cell carcinoma or blepharoconjunctivitis – causing delays in diagnosis and treatment.

Risk Factors

Risk factors for sebaceous carcinoma are numerous. The most common association is Muir Torre syndrome – an autosomal dominant variant of hereditary non-polyposis colorectal carcinoma causing defects in mismatch repair genes. Other risk factors include: a history of ionising radiation exposure (e.g. for retinoblastoma) (2), benign adenomas of sebaceous glands, older age and immunosuppression (3).

Presentation

Usually, sebaceous carcinoma presents as a firm painless lump on the eyelid. Another presentation is eyelid thickening with associated chronic blepharoconjunctivitis (3). The presentation can easily be mistaken for chalazion or blepharitis. A case series by Shields et al. describes that only 32% of cases of sebaceous carcinoma were initially clinically diagnosed as sebaceous carcinoma (4). Other misdiagnoses in this case series included: blepharoconjunctivitis (25%), chalazion (20%), basal cell carcinoma (BCC) (13%) and squamous cell carcinoma (SCC) in 10% (4). This study highlights the difficulty in accurate diagnosis of this condition and the need for a high degree of suspicion in non-resolving chalazion or blepharitis. Sebaceous carcinoma typically affects older adults, but non-syndromic cases have been reported in teenagers and young adults (5, 6).

Diagnosis

The gold standard methods of diagnosis are by biopsy and histological examination. Features of sebaceous carcinoma under microscopy can assist in the diagnosis: the tumour may invade the subcutis, and there may be a pagetoid (upward spread) invasion of the epidermis. Necrosis may also be seen. Special cells within sebaceous glands called sebocytes may be observed to contain a characteristic multivacuolated cytoplasm. Further analysis through immunohistochemistry is often needed to assist in diagnosis- e.g. through the identification of epithelial membrane antigen (EMA) and CK7 (8). Plaza et al. carried out a detailed immunohistochemical (IHC) analysis of sebaceous carcinoma in comparison to SCC and BCC and found that adipophilin may represent a sensitive and reliable marker for diagnosis of SC and can help to differentiate it from some of its imitators (9). Luo et al. have described the use of a deep-learning approach to automate the differential diagnosis of sebaceous carcinoma vs BCC – offering a method that may improve diagnostic accuracy (10).

Novel methods in assisting the diagnosis of the condition have been explored. Non-invasive meibography describes the use of an infrared filter and charge-coupled device camera to visualise meibomian glands (7). Nemoto et al. demonstrated that sebaceous carcinomas exhibit higher reflectivity for the tumour mass surrounded by a region of lower reflectivity in comparison to a chalazion which generally demonstrates lower reflectivity and more sharply defined borders. This study was limited to a small sample size of 5 individuals with chalazion and 3 with sebaceous carcinoma therefore further studies are needed to explore the utility of this method.

Management

The management is dependent on the features of the tumour. Complete examination of the eye including assessment of proptosis, globe displacement and pupil abnormalities is recommended. In addition, examination of the local lymph nodes assesses for local lymphatic spread (11).

Staging uses the TNM system. T2c or higher tumours may be considered for a CT scan of the tumour and local lymphatics. In addition, fine needle aspiration may be used for the assessment of lymphatic spread.

Screening for Muir-Torre syndrome is recommended in patients with extraocular sebaceous carcinoma and a Mayo MTS risk score of 2 or over or patients with MMR-deficient sebaceous carcinoma before 50 (12).

Treatment of local tumours uses surgical techniques such as complete circumferential peripheral and deep margin assessment (CCPDMA), Mohs micrographic surgery or Wide Local Excision (with 1cm margins to the fascial plane) when the former methods are not available.

Radiotherapy may be used as adjuvant therapy or as a primary option when surgery is not feasible, though evidence for its use as monotherapy is mixed. (13, 14).  

Orbital exenteration and chemotherapy may be considerations in extensive disease (15).

Prognosis

The 5-year survival rate is 78% for localized or regional disease and 50% for metastatic disease (16). Prognosis depends on early detection and tumour size, with localised disease having significantly better outcomes compared to metastatic cases. (16).

References

(1) Sebaceous gland carcinoma (Internet). (cited 2025 Jan 28). Available from: https://www.cancerresearchuk.org/about-cancer/skin-cancer/types/sebaceous-gland-carcinoma

(2) Kivelä T, Asko-Seljavaara S, Pihkala U, Hovi L, Heikkonen J. Sebaceous carcinoma of the eyelid associated with retinoblastoma. Ophthalmology. 2001 Jun;108(6):1124–8.

(3) Torres-Laboy P, Schmieder SJ. Sebaceous Carcinoma. In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2025 (cited 2025 Jan 28). Available from: https://www.ncbi.nlm.nih.gov/books/NBK610689/

(4) Shields JA, Demirci H, Marr BP, Eagle RC, Shields CL. Sebaceous carcinoma of the eyelids: personal experience with 60 cases. Ophthalmology. 2004 Dec;111(12):2151–7.

(5) Omura NE, Collison DW, Perry AE, Myers LM. Sebaceous carcinoma in children. J Am Acad Dermatol. 2002 Dec;47(6):950–3.

(6) Keskinaslan I, Pedroli GL, Piffaretti JM, Meyer P, Kunz C, Haefliger IO. Eyelid sebaceous gland carcinoma in a young Caucasian man. Klin Monbl Augenheilkd. 2008 May;225(5):422–3.

(7) Nemoto Y, Arita R, Mizota A, Sasajima Y. Differentiation between chalazion and sebaceous carcinoma by noninvasive meibography. Clin Ophthalmol. 2014 Sep 18;8:1869–75.

(8) Sebaceous carcinoma pathology (Internet). (cited 2025 Jan 28). Available from: https://dermnetnz.org/topics/sebaceous-carcinoma-pathology

(9) Plaza JA, Mackinnon A, Carrillo L, Prieto VG, Sangueza M, Suster S. Role of Immunohistochemistry in the Diagnosis of Sebaceous Carcinoma: A Clinicopathologic and Immunohistochemical Study. The American Journal of Dermatopathology. 2015 Nov;37(11):809.

(10) Luo Y, Zhang J, Yang Y, Rao Y, Chen X, Shi T, et al. Deep learning-based fully automated differential diagnosis of eyelid basal cell and sebaceous carcinoma using whole slide images. Quant Imaging Med Surg. 2022 Aug;12(8):4166–75.

(11) Owen JL, Kibbi N, Worley B, Kelm RC, Wang JV, Barker CA, et al. Sebaceous carcinoma: evidence-based clinical practice guidelines. The Lancet Oncology. 2019 Dec 1;20(12):e699–714.

(12) Roberts ME, Riegert-Johnson DL, Thomas BC, Rumilla KM, Thomas CS, Heckman MG, et al. A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir-Torre variant of Lynch syndrome. Genet Med. 2014 Sep;16(9):711–6

(13) Hata M, Koike I, Omura M, Maegawa J, Ogino I, Inoue T. Noninvasive and curative radiation therapy for sebaceous carcinoma of the eyelid. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):605–11.

(14) Nunery WR, Welsh MG, McCord CD. Recurrence of sebaceous carcinoma of the eyelid after radiation therapy. Am J Ophthalmol. 1983 Jul;96(1):10–5.

(15) Mulay K, Aggarwal E, White VA. Periocular sebaceous gland carcinoma: A comprehensive review. Saudi J Ophthalmol. 2013 Jul;27(3):159–65.

(16) Sargen MR, Starrett GJ, Engels EA, Cahoon EK, Tucker MA, Goldstein AM. Sebaceous carcinoma epidemiology and genetics: Emerging concepts and clinical implications for screening, prevention, and treatment. Clin Cancer Res. 2021 Jan 15;27(2):389–93.