Sebaceous Carcinoma : 42946-PD / 108343


Learning Objectives:

  • To review the pathophysiology and clinical features of sebaceous carcinoma
  • To review management options for sebaceous carcinoma
  • To review the statistical concept of rank correlation

Course Credit:

2 hours



An 80 year old male presents to clinic with a “bump” on his right upper eyelid.  He says it has been present for approximately one year, and although not particularly bothersome to him he feels it may be enlarging.  His medical and ocular history are otherwise unremarkable.  On exam, a yellowish lesion is observed on the nasal aspect of the right upper lid, extending onto the palpebral conjunctiva (see image).  The lesion is nontender and is fixed to the underlying tarsus.  There are no palpable lymph nodes in the head or neck.

What is the most likely diagnosis?

INCORRECT - a chalazion is a benign lesion of the eyelid occurring as a result of blockage to a meibomian gland or gland of Zeis. Although sebaceous carcinoma and chalazion are often confused, the lesion shown does not resemble a typical chalazion, and has features suggestive of a more sinister process.
Basal cell carcinoma
INCORRECT - basal cell carcinoma is the most common form of eyelid malignancy. Although it may be considered in the differential diagnosis of such a lesion, the yellowish color and extension onto the palpebral conjunctiva are more suggestive of the (rarer) sebaceous carcinoma.
Sebaceous hyperplasia
INCORRECT - sebaceous hyperplasia is a relatively common condition that presents as yellowish or skin-coloured papules, most often on the face as opposed to eyelids. The loss of cilia and extension onto the palpebral conjunctiva should prompt suspicion for an eyelid malignancy.
Sebaceous carcinoma



Sebaceous carcinoma (also known as sebaceous gland carcinoma or sebaceous cell carcinoma) is an uncommon malignancy that is most often found in the periorbital area, especially the eyelids.1  It accounts for less than 1% of all eyelid tumors, but is the second most common malignancy of the eyelids behind only basal cell carcinoma (90%).  It accounts for roughly 5% of such lesions (squamous cell carcinoma accounts for 4% and other lesions such as melanoma for the remaining 1%).2   Sebaceous carcinoma commonly masquerades as benign conditions such as chalazion, making it is notoriously difficult to diagnose.  Such diagnostic delay can often lead to poor outcome.  The tumor can be aggressive in nature, causing both local invasion as well as metastatic disease.


Sebaceous carcinoma is mostly a disease of elderly individuals, diagnosed at a mean age of 68.43 and rare before the age of 60.1  It can occasionally by seen in younger individuals, most of whom have had previous irradiation to the eyelid area.  It is also more common in females.




Sebaceous glands are glands in the skin that secrete sebum, an oily substance functioning to lubricate the skin and hair.  Sebaceous glands are located on most of the body (apart from the palms and soles) but are found in the greatest numbers on the face and scalp.  Histologically they are unilobar or multilobar and attach to hair follicles with ducts through which sebum flows.  When associated with a hair follicle the entire complex is often referred to as a pilosebaceous unit.


Sebaceous glands are found in greatest abundance on the eyelids.  Meibomian glands are a special type of sebaceous glands not associated with a hair follicle (the ducts terminate in sweat pores)- they secrete a form of sebum known as meibum which functions to slow evaporation of tears.  The glands of Zeis are unilobar sebaceous glands at the eyelid margin which are associated with the eyelashes (most styes originate from the glands of Zeis).  The caruncle also contains sebaceous glands associated with fine lanugo hairs.  The eyebrows contain a significant number of sebaceous glands as well.1



Several different lesions may arise from sebaceous glands, including:

  • Acne: acne vulgaris is a common skin disease characterized by areas of skin with seborrhoea (scaly red skin), comedones, papules, pustules, nodules, and scarring.  It develops primarily as a result of excess sebum production from sebaceous glands.
  • Sebaceous cyst: a cyst resulting from a blocked sebaceous gland.
  • Sebaceous hyperplasia:  sebaceous hyperplasia involves enlargement of sebaceous glands, and is seen as yellowish or skin-coloured papules that are found most commonly on the face.  They occur at a high prevalence in the general population and are also seen with Muir-Torre syndrome (see below).4, 5  Risk factors including older age, renal transplantation, and chronic immunosuppression.4, 5  It does not have malignant potential, and is not a precursor to sebaceous carcinoma.4, 5  Treatment is for cosmetic reasons only.
  • Nevus sebaceous of Jadassohn: nevus sebaceous of Jadassohn (NSJ) is a benign lesion occurring most commonly on the scalp and face that is a hamartoma with epidermal, follicular, sebaceous, and apocrine elements.4, 5   Such lesions may be at a small risk of malignant transformation, however early excision is controversial.    They may be caused by maternal transmission of human papillomavirus (HPV).
  • Sebaceous adenoma: sebaceous adenoma is a benign neoplasm of sebaceous origin.4, 5  It is similar to sebaceous hyperplasia but exhibits expansion of basaloid cells beyond the normal 1-2 cell layers.  They are characterized by smooth, well circumscribed, speckled yellow papules mostly seen in older individuals.4, 5   Occasionally the lesions may cause bleeding, ulceration, and pain.  It is also associated with Muir-Torre syndrome.  Treatment involves excision, however there is thought to be no malignant potential from the lesions.
  • Seboacanthoma: a seboacanthoma is a subtype of sebaceous adenoma that resembles a keratoacanthoma but is composed of sebaceous lobules.  They are rare and usually only seen with Muir-Torre syndrome.4, 5
  • Sebaceoma: a sebaceoma (sebaceous epithelioma) is another benign tumor associated with Muir-Torre syndrome that is characterized as a yellowish papule with rolled borders.4, 5  Treatment is with excision, as the lesions commonly cause bleeding and ulceration.4, 5


A sebaceous carcinoma is the most worrisome lesion arising from a sebaceous gland.  Most arise de novo and not from pre-existing sebaceous lesions as previously mentioned.1  In the periorbital area they may originate from the meibomian glands (most commonly), glands of Zeis, or sebaceous glands of the caruncle or eyebrow.6  Rarely it has been reported to originate from the lacrimal gland.2   However it should be noted that often the site of origin is difficult to determine.7  The periocular area is the most common location for sebaceous carcinoma.


There are some unique aspects to the pathophysiology of sebaceous carcinoma.  Firstly, approximately 18% of cases are multicentric in nature, which has important implications for management.2  Secondly, approximately 50% of cases exhibit pagetoid invasion of the epithelium, in which tumor cells infiltrate the epithelium and may spread to involve large areas of the conjunctiva or eyelid skin.8  Pagetoid invasion can often mimic squamous cell carcinoma in situ.1


In general, like with other cancers, three patterns of growth may be seen with sebaceous carcinoma:

  • Local infiltration: sebaceous carcinoma can be locally invasive to structures such as the eyelid skin, conjunctiva, cornea, and orbit.  This is often due to pagetoid invasion of the epithelium.  Rarely local invasion may occur into the lacrimal drainage system or even the cranial cavity.2 
  • Regional metastasis: the most common method of metastasis with sebaceous carcinoma is through lymphatic channels to regional lymph nodes.1  In the past nodal metastasis was reported to occur in 30% of patients but is now less common secondary to earlier recognition.  Typically tumors from the upper eyelids tend to metastasize to preauricular and parotid nodes (the most common sites of metastasis), while tumors of the lower eyelids often metastasize to submandibular and cervical nodes.1  The estimated rate of nodal metastasis is 8-28%.9-11
  • Distant metastasis: distant metastasis may occur in advanced cases secondary to hematogenous spread.  Organs typically involved include the lung, liver, bone, and brain.1  Occasionally distant metastasis occurs before regional lymph node involvement.12

Presentation and course


Sebaceous carcinoma can present in a variety of ways, often similar to other benign conditions, making diagnosis difficult for the clinician.  The most common way the condition presents is as a solitary eyelid nodule.  It is most often painless, firm, and subcutaneous, resembling a chalazion.1  In fact, lipids present in the tumor may incite a foreign body giant cell reaction to further simulate a chalazion.1  Initially the nodule is deep to the dermis and fixed to the tarsus, with overlying skin smooth and mobile.1  As the lesion enlarges to involve the epidermis it may develop yellowish coloration due to the presence of lipids. 


The second most common presentation is that of a diffuse pseudoinflammatory pattern that manifests as diffuse unilateral thickening of the eyelid, often resembling blepharitis.  This occurs secondary to pagetoid invasion of the epithelium, most commonly to the forniceal or bulbar conjunctiva and occasionally into the cornea or deeper tissue.1  The conjunctiva may take on a “tigroid” appearance with prominent yellow streaks and papillary hypertrophy.7  In such cases differentiating an inflammatory vs. neoplastic process may be difficult.


Sebaceous carcinoma more frequently affects the upper than lower eyelid (by a factor of approximately 1.7) due to the increased number of meibomian glands in the upper eyelid.23  Simultaneous involvement of the upper and lower eyelids may occur (recall the tumor may be multicentric), and is associated with a poor prognosis.  Associated findings may include pain, extraocular movement restriction, ulceration, and discharge.24  As with other malignant eyelid tumors, loss of cilia and destruction of microarchitecture may occur.1 22  Occasionally rapid progression of the lesion may occur, causing it to assume very large proportions if left untreated.22


It should be noted that there are a vast array of other ways in which sebaceous carcinoma can present to the clinician.  To briefly name a few, these include:

  • Eyelid nodule without attachment to tarsus: especially if the lesion has originated from a gland of Zeis.2
  • Pedunculated lesion
  • Irregular mass with extensive tissue invasion
  • Caruncular thickening: if originating from caruncular sebaceous glands, sebaceous carcinoma may appear as a multinodular yellow thickening resembling a benign lesion such as sebaceous hyperplasia or adenoma.1
  • Eyebrow cyst: simulating epidermal inclusion or sebaceous cyst.1
  • Lacrimal mass: if originating from the lacrimal gland region (rare)

Risk factors


As mentioned previously, sebaceous carcinoma is most common in elderly individuals with most patients being older than 60 at diagnosis.  It is also more common in females.  Other risk factors include:

  • Race: in the Western world sebaceous carcinoma is more common in whites, however overall the condition is seen at a far higher prevalence in Asian countries, particularly China and India.2  In India, sebaceous carcinoma accounts for 30-40% of eyelid malignancies.24  The reasons for this are unclear.
  • Muir-Torre syndrome: Muir-Torre syndrome is an autosomal dominant condition characterized by a greater frequency of several skin lesions including sebaceous adenoma, sebaceous carcinoma, sebaceous epithelioma, and keratocanthoma.25  It also carries an increased risk of internal malignancies including of the gastrointestinal tract (stomach, duodenum colon), breast, and genitourinary tract.1  It is caused by a mutation in DNA mismatch repair genes and is related to the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.  Studies have found a high proportion of patients with sebaceous carcinoma (up to 48%) have a history of systemic malignancies- it is unclear if this is caused by a higher incidence of Muir-Torre syndrome than previously thought.26
  • Previous irradiation: a history of previous irradiation to the eyelid area such as for retinoblastoma or benign conditions (e.g. acne, cutaneous hemangioma, eczema)2 greatly increases the risk for sebaceous carcinoma.  The condition may be seen in teenagers with a history of retinoblastoma treatment as a child.
  • Diuretic use: the relationship between diuretics and risk of sebaceous carcinoma is unclear.  Older studies have suggested an increased risk with such medications, however more recent studies have not supported this claim.8
  • HIV infection: patients infected with HIV have an increased risk of many cancers, including in the periocular area Kaposi’s sarcoma and sebaceous carcinoma.27  This is possibly due to inactivation of p53, a tumor suppressor protein.
  • HPV infection: HPV infection may also increase risk of sebaceous carcinoma (similar to with cervical and rectal cancers).28