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Review Article

Sebaceous gland carcinoma of the eyelid

Upender K. Wali, Abdullah Al-Mujaini
Department of Ophthalmology, College of Medicine and Health Science, Sultan Qaboos University, Muscat, Sultanate of Oman

Sebaceous gland carcinoma, commonly arises in the

periocular area, is an uncommon condition. It represents
15.5% of eyelid malignancies and is considered to be
the third most common eyelid malignancy after basal
cell and squamous cell carcinomas, although few reports
placed this tumor as second most common after basal
cell carcinoma. It usually affects elderly women and
characterized by high rate of local recurrence, regional,
and distant metastases. A delay in diagnosis, which
can be attributed primarily to ability of this tumor to
masquerade as more benign conditions, often leads to

inappropriate management with increased morbidity

and mortality rates. In this study, the authors discuss
key elements of the primary disease and therapeutic
options available to treat such devastating problem.
Keywords: Mohs, nodular, pagetoid, sebaceous gland
carcinoma
Oman Journal of Ophthalmology, 2010; 3(3):117-121
DOI: 10.4103/0974-620X.71885

www.ojoonline.org

Introduction

development of multiple primaries.

Sebaceous gland tumor of the eyelids may arise from the meibomian
glands, glands of Zeis or glands associated with the caruncle.[1] They
are included in the list of tumors of the epidermal appendages, socalled adnexal skin structures. Sebaceous gland carcinoma (SGC)
might be the second most common lid malignancy after basal cell
carcinoma (BCC). Its multifocal origin and pagetoid spread give
it an unique place among eyelid malignancies.

On one hand it can mimic as benign lesion as blepharoconjunctivitis,

whereas on the other extreme it can have widespread local and
fatal distant metastases. Immunohistochemistry, molecular
biology, and electron microscopy have greatly improved the
diagnosis, management, and prognosis of SGCs overall. Surgery,
chemotherapy, and radiotherapy all contribute to the treatment
of SGC.

Sebaceous glands are located in the periocular skin, caruncle, and

eyebrow skin follicles. The tumor is a very rare, slow growing, and
commonly found in elderly population with female predisposition.
Mean age at diagnosis is mid-sixties; however, the tumor has
been reported in children as young as 3.5 years old.[2] It is rare
in Caucasians and common in oriental Asiatics. The reported
incidence of SGC varies from 0.5 to 5% of all lid carcinomas in
USA and 28% in China.[3,4] SGC most commonly arises from the
meibomian glands anterior to the gray line, occasionally from the
glands of Zeis or Moll, and from sebaceous glands in caruncle;
however, the cell of origin may not be certain in 5060% of
cases.[5] In contrast to basal cell carcinoma (BCC) or squamous
cell carcinoma (SCC), SGC is two to three times more common
in upper eyelid due to more number of meibomian glands
there.[3,6] Five percent cases may have simultaneous involvement
of both eyelids due to intraepithelial spread and/or spontaneous

The literature was reviewed using online searches of PubMed

(19852010), OVID, and Google Scholar. The search strategy
included MeSH and natural language terms using the keywords
mentioned. Reference lists in retrieved articles, and textbooks,
were also searched for relevant references.

Relevant Anatomy
With its two parts; the epithelial or epidermis and the cutaneous
or dermis, the skin of the eyelid is the thinnest in the body.
Anatomically, the eyelid can be divided into two lamellae. The
anterior lamella contains skin, orbicularis muscle, eyelashes, and
their follicles whereas the posterior lamella has mucocutaneous
junction, meibomian gland orifices, and tarsal plate.
The dermis contains sebaceous glands which are found in the

Copyright: 2010 Wali UK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Correspondence:
Dr. Abdullah Al-Mujaini, Department of Ophthalmology, Sultan Qaboos University Hospital, 123 Al Khod, Muscat, Sultanate of Oman. E-mail: mujainisqu@hotmail.com

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Wali and Al-Mujaini: Sebaceous gland carcinoma of the eyelid

tarsal plate, caruncle, and eye brow. There are approximately 25
such oil producing sebaceous glands in the upper tarsal plate and
20 in the lower. Glands of Zeis are small, modified, sebaceous
secreting glands that open into the hair follicles at the base of the
eyelashes.

Pathophysiology
Two important features differentiate sebaceous carcinoma from
other periocular malignancies. First, unlike single origin of other
tumors, sebaceous carcinoma appears to arise from multifocal
origins. Second, unlike radial spread of basal cell and SCCs,
SGC tends to spread superficially in a pattern known as pagetoid
spread.[7,8] This spread may lead to the erroneous histologic
diagnosis of epithelial dysplasia or carcinoma in situ.
Immunohistopathology shows that the cells occur in irregular
lobular masses with distinctive invasiveness. The cytoplasm is
pale, foamy, and vacuolated [Figure 1]. This feature of foamy
cytoplasm is seen only in sebaceous carcinoma. The nuclei are
hyperchromatic, and the cells stain positive for lipid such as oil red
O stain. The ultrastructural features of SGC include desmosoes,
tonofilaments, and intracytoplasmic nonmembrane bound lipid.
Occasionally bizarre and atypical tripolar mitotic cells may be
seen. Immunohistochemical reaction aids in the diagnosis of
SGC. Molecular biology of SGC suggests dysplasia if there is no
expression of p53 or invasiveness, if there is hyperexpression of
p53.

Clinical Features
SGC has a tendency to invade the periocular region. Upper eyelid
is most commonly involved followed by the lower eyelid and the
caruncle.[9]

hallmark of this tumor. It is one of the most dangerous eyelid

tumors due to; a) the tumor masquerading as inflammatory
conditions such as blepharo-conjunctivitis, chalazion or superior
limbic keratoconjunctivitis,[10-12] or as other ocular tumors like
BCC or SCC, with a result that the correct diagnosis is often
delayed until metastasis has occurred, b) the incidence of
metastasis is high (41%),[3,5,7] c) delineation of tumor margins,
even with excellent paraffin-embedded sections is difficult due
to either intraepithelial pagetoid spread and/or multicentric
pattern,[5,6,8,13-15] and d) the histological diagnosis may be incorrect
if lipid stains (oil-red-O) are not used on properly prepared tissues.
In general, there are two main pathological presentations of the
SGC - nodular and spreading.

The Nodular Form

In over 50% cases, SGC may present as a pseudochalazion or a
chronic blepharoconjunctivitis.[10-12,16,17] The nodular form is a
discrete, hard, immobile nodule commonly located in upper tarsal
plate [Figure 2]. It is yellowish due to lipid. Any chalazion of
unusual consistency or its recurrence after incision and curettage
more than three times should undergo full thickness resection and
histological examination. Occasionally, it may have a multicentric
origin.
The spreading variety of SGC occurs in pagetoid form with diffuse
intraepithelial infiltration of the lid skin.[8,11,13] This causes diffuse
thickening of lid margin, loss of eyelashes, and resembles chronic
blepharoconjunctivitis. The pagetoid spread may involve both
eyelids and conjunctival epithelium.[13]

It bears no characteristic clinical appearance, but pagetoid

infiltration of conjunctival epithelium or skin epidermis is a

An unusual variant of SGC may present as MuirTorre syndrome

which is characterized by squamous differentiation of the tumor,
multiple sebaceous adenomas or carcinomas in the skin, and
visceral malignancies.

Figure 1: Malignant cells with vaculated cytoplasm (V), mitotic figures (M), and areas
of necrosis (N) (H & E, 60)

Figure 2: Clinical presentation showing large mass of the right upper eyelid

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Wali and Al-Mujaini: Sebaceous gland carcinoma of the eyelid

SGC is important to know because it is a notorious diagnostic
pitfall for the clinician as well as the pathologist. It is the
pagetoid spread or the dermal infiltration of the tumor that may
confuse both the clinician and the pathologist. The clinician may
misdiagnose SGC as blepharoconjunctivitis, and the pathologist as
dysplasia. Accurate diagnosis and treatment of SGC are important
because this tumor is the most aggressive of the epithelial tumors
of the eyelid. Any unilateral blepharoconjunctivitis with loss of
eyelashes, thickening of the lid margin and that fails to respond
to the treatment should be biopsied, so should be any suspicious
area of conjunctiva or the limbus.
Sebaceous gland hyperplasia constitutes 8% of caruncular
growths. SGC of caruncle may involve mucous membrane graft of
the defect after excision of the tumor.
The systemic extension of the tumor can occur by continuous
growth, lymphatic spread, or hematogenous spread. The
most common sites of spread are orbit, preauricular and/or
submandibulr nodes, and parotid gland. The less common sites
of extension include cervical nodes, lung, pleura, liver, brain,
pericardium, lips, ethmoid sinus, or skull.[3,5,6,18,19]

Diagnosis
Diagnosis is frequently difficult due to two main reasons; (1) in
early stages the external signs are quite subtle, resembling a benign
lesion such as a chalazion or chronic blepharoconjunctivitis and
(2) the presence of yellowish material within the tumor gives it
resemblance to SCC.
Thus, due to high index of suspicion, it becomes mandatory to
include SGC in the differential diagnosis of most eyelid masses
and recurrent, nonresponding eyelid inflammatory conditions.
A delay in clinical diagnosis of SGC can be attributed primarily to its
ability to masquerade as more common benign eyelid conditions.
This often leads to delayed management with increased morbidity
and mortality rates.[20] The actual reported sebaceous carcinomarelated mortality is about 6%.[7]

Occasionally, SGC may diffusely infiltrate conjunctival epithelium.

This may resemble lesions such as chronic blepharoconjunctivitis,
superior limbal keratoconjunctivitis or cicatricial pemphigoid,
and BCC. The tumor may mimick chronic inflammation and even
grow bacteria on repeated cultures but does not improve with
antibiotics. Conjunctival scrapping may reveal the underlying
SGC pathology. Due to such mimicking, SGC is one of the forms
of masquerade syndromes. Diffuse intraepithelial sebaceous
carcinoma closely resembles SGC in its rarity and indolent course;
however, the former is not an obvious primary tumor of the eyelid
and may not require exenteration. Papilloma simulates SGC and
sometimes may be differentiated only by histology.

Treatment
SGCs are often inadequately treated at first intervention. Different
treatment modalities include local excision, orbital exenteration,
radical neck dissection, radiation, or chemotherapy depending on
the stage of the tumor at the time of presentation. Wide excision at
an early stage is important. Prior to surgical excision, it is important
to examine the patient carefully for evidence of pagetoid spread
or multicentric origin by double eversion of the eyelids, and any
conjunctival alteration such as telangiectasia, papillary change, or
a mass. In such an instance, conjunctival punch biopsies should
be taken in addition to surgical resection of the lid lesion.[21]
Surgical treatment may range from a local excision to orbital
exenteration [Figure 3]. Radical surgical excision with frozen
section control by either a standard method or Mohs micrographic
surgery is the most common and effective method of treatment.
The wound edges should be approximated as far as possible.
Approximately, 30% of SGCs recur after resection.[18,22]
The advantages of Mohs micrographic surgery, in comparison
to a conventional excision of nonmelanotic skin cancer are; (1)
definitive margin excision and (2) minimal loss of surrounding
normal tissue.[23]

Differential Diagnosis
The list for SGC includes; congenital sebaceous gland hyperplasia
which is common on face or scalp or acquired sebaceous gland
hyperplasia which is common on face or forehead. Adenoma
sebaceum of Pringle is another diagnosis to consider. It is found
in tuberous sclerosis and commonly located in the nasolabial fold
and cheek areas. Sebaceous adenoma is common on the eyebrows
and eyelids.
SGC is included in the group of simulating lid lesions (inclusion
cyst, papilloma, senile keratosis, keratoacanthoma, benign
keratosis, dermoid cyst, and amyloidosis).
119

Figure 3: Two weeks after surgical resection of the tumor and reconstruction of the
eyelid

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Wali and Al-Mujaini: Sebaceous gland carcinoma of the eyelid

Few patients with regional nodal metastasis remain alive for long
time, and radical neck dissection for isolated cervical node disease
is often indicated.[6] Local nodal disease without distant metastasis
is treated by radical neck dissection.[7,18,19]

tumors, infiltration into blood vessels and/or lymphatics, orbital

extension, multicentric origin, and finally pagetoid spread.
Tumors less than 6 mm have excellent prognosis. Prognosis of
SGC arising from glands of Zeis is more favorable.

Topical mitomycin C has been tried for pagetoid invasion of the

conjunctiva by eyelid SGC.[24] Cryotherapy is a useful adjunct
to surgery in epibulbar and pagetoid extension of SGC, sparing
exenteration.

It goes beyond doubt that SGC is a great mimicker. On one hand,

it mimics as simple a clinical condition as blepharitis, on the other
hand it may turn out to be a fatal metastatic tumor.

Radiotherapy is usually avoided or may even be contraindicated

because of its adverse side effects such as subsequent conjunctival
keratinization leading to dry eye, lid atrophy, skin necrosis,
lash loss, lid telangiectasia, ectropion, epiphora, keratopathy,
cataract,[25] higher recurrence rate compared to surgery, does
not allow histological confirmation of tumor classification and
eradication and finally recurrences following radiotherapy are
difficult to treat surgically because of poor healing of irradiated
tissues. Most serious radiation-related complications occur in
large tumors of the upper lid.
The reported results of proton electron irradiation in SGC are not
excellent.[22,26] Radiotherapy as a primary form of therapy in SGC
of the eyelid has variable results.[7,26,27] Radiation is mainly reserved
for patients who are not candidates for surgical procedures due to
advanced age or disease, for palliation in widespread disease, and
for patients who refuse exenteration for advanced local disease.
In some cases, wide-field irradiation has either cured the tumor
or produced sufficient shrinkage to allow surgical removal of the
residual mass. As a bias, surgery has been recommended for SGC
confined to the lid, and to limit the use of radiation to diffuse
tumors with orbital or bone involvement. In advanced poorly
differentiated tumors, cure is not affected by either radiotherapy
or orbital exenteration.

References
1.

2.
3.

4.
5.

6.

7.

8.

9.

10.
11.
12.

Prognosis [Table 1]
13.

The overall mortality rate is 510% because of frequent difficulties,

mistakes in diagnosis, and delay in the treatment. The mortality
from metastasis may go up to 25%. The adverse prognostic
features include involvement of upper or both eyelid and tumor
size of 10 mm or more. Others include duration of symptoms
more than 6 months (mortality 38%), poorly differentiated

14.

15.

16.

Table 1: Prognosis of sebaceous gland carcinoma

(SGC) based on clinicopathological tumor
morphology[28]
Well differentiated SGC

Moderately
differentiated
SGC

Poorly
differentiated
SGC

Resemble histogenetic
architecture of the sebaceous
gland lobule (peripheral
stem cell layer and central
sebaceous cells)

Retain lobular
pattern.
Positive
staining
reaction for
fat

Difficult to see or
absent positive
staining reaction
for fat

Oman Journal of Ophthalmology, Vol. 3, No. 3, 2010

17.
18.
19.

20.
21.
22.

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Source of Support: Nil, Conflict of Interest: None declared.

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