History
A recurrent eyelid tumor in a 69-year-old woman treated by orbital exenteration.
Diagnosis
Sebaceous carcinoma with infiltration of the orbit
Histopathology
The section comes from the lateral orbit and shows a moderately differentiated carcinoma in the orbital soft
tissue and upper eyelid. The tumor is composed of cells with large vesicular nuclei and abundant foamy
cytoplasm. Abnormal mitotic figures are seen. The cells are arranged in lobules and nests of different
sizes, many of the larger ones exhibiting central necrosis. Some lobules appear to contain acini. In areas
the tumor cells are smaller and less cohesive with hyperchromatic nuclei and eosinophilic cytoplasm.
Discussion
Sebaceous carcinoma, although an infrequent neoplasm, usually occurs in the periocular region, particularly
the upper eyelid. It may also arise in the lower eyelid, the medial canthus and bridge of nose, the eyebrow
and the caruncle and some tumors may be multicentric. Occasional cases have been described arising within a
pleomorphic adenoma of the lacrimal gland.1 The tumor may present as a mass (43%), a recurrent chalazion
(20%) or a persistent unilateral blepharoconjunctivitis (30%)2 and the mean age of presentation is in the
seventh decade, with women slightly outnumbering men.3,4 Some patients, 28% of those in the series of
Wolfe et al,4 have a history of radiation exposure 5 and the tumor has been described as a second
malignancy in survivors of retinoblastoma therapy, particularly those that received radiation treatment.6-8
Sebaceous carcinoma has a lobular growth pattern that mimics normal sebaceous gland architecture, with
increased cytoplasmic lipid towards the centre of the neoplastic lobule. Occasional acinar structures may
be seen within the lobules but on electron microscopy these do not appear to be true acini. The presence of
lipid may be confirmed by histochemistry and ultrastructural examination reveals vacuoles of different sizes
that lack a limiting membrane.4 The ducts of normal sebaceous glands display squamous differentiation
and keratinization and the tumor may resemble a squamous cell carcinoma. Poorly differentiated sebaceous
carcinoma may resemble a basal cell carcinoma or may grow in an "Indian file".
Within the eyelid the tumor usually arises from the Meibomian glands of the tarsus or the glands of Zeis
associated with the lashes. Often the precise origin cannot be determined. In up to 80% of cases the
neoplasm spreads into the overlying epidermis or conjunctival epithelium either as single cells or small
clusters ("Pagetoid" spread) or as carcinoma-in-situ.4 This intraepithelial spread is often associated
with degeneration and acantholysis of the epithelium and may be accompanied by a marked inflammatory
response that manifests clinically as chronic blepharoconjunctivitis, a so-called "masquerade syndrome".9,10
Margo et al 11 have reported the case of a 67-year-old woman with a 10-year history of unilateral
blepharoconjunctivitis treated with topical steroids whose underlying sebaceous carcinoma only became
apparent when a nodule developed in the inferior bulbar conjunctiva. Although there is disagreement over
the prognostic significance of intra-epithelial extension,2,3,4 the management implications are clear.
Wide margins of excision are required because of the possibility of "skip lesions" and diffuse extension is
an indication for orbital exenteration.2 In advanced cases the tumor metastasises by lymphatic and blood
vessels to the regional (pre-auricular and cervical) lymph nodes, the lungs and the liver. Vascular
permeation is an indicator of poor prognosis.3
Orbital exenteration involves removal of the eye, the orbital soft tissues, the optic nerve and the eyelids
and is usually performed to achieve complete extirpation of a malignant tumor.12 Depending on the type
and extent of the tumor the orbital bone may also be removed, including the anterior skull base. Whenever
possible, and particularly in young people, the eylids are conserved. Most exenterations are performed for
secondary infiltration of the orbit by basal cell carcinoma, squamous cell carcinoma of sinonasal origin, or
malignant melanoma of either conjunctival or choroidal origin.12,13 After the orbital contents have been
removed the surgeon should be encouraged to submit a separate biopsy from the orbital apex to assess the
possibility of intracranial extension. Exenteration is not always curative, particularly with adenoid
cystic carcinoma of lacrimal gland, but the rate of recurrence within the orbit following the procedure is
low (7%).12 After exenteration the orbit may be allowed to heal by spontaneous granulation. This takes
several months and may be complicated by a sino-orbital fistula in as many as 68% of cases if bone is
removed. Alternatively, the socket may be lined with a skin graft or a muscle flap.12
The Muir-Torre Syndrome is an association of sebaceous neoplasms of the skin with visceral malignancies.
Sebaceous adenoma, epithelioma and carcinoma have all been described in the syndrome; sebaceous hyperplasia
may also occur but this lesion is relatively common in the general population.14 Although most of the
sebaceous neoplasms are situated in the head and neck region, few involve the eyelid and the presence of a
benign sebaceous neoplasm in the eyelid is more likely to be an indicator of the syndrome than is a
sebaceous carcinoma.15 Conjunctival sebaceous neoplasms may be associated with this syndrome16 but
also occur independently17
Chalazion
A chalazion is a granulomatous inflammatory response to sebum extruded from obstructed Meibomian glands.
Like sebaceous carcinoma it is more common in the upper lid. It presents as an acutely painful, inflamed
mass on either the cutaneous or conjunctival surface of the lid. Chalazia may be multiple and recurrent
chalazia must be submitted for pathological examination to exclude sebaceous carcinoma.
The histological appearance varies with the duration of the lesion. In the acute phase a localized or
diffuse granulomatous response is accompanied by a mixed inflammatory infiltrate. Round spaces from which
lipid has been dissolved may be seen within granulomata and often a fringe of neutrophils is seen around the
spaces. Some granulomata may show central necrosis with suppuration and caseous necrosis may occasionally
be observed. A variety of conditions may produce granulomatous inflammation of the eyelids, including
sarcoidosis, tuberculosis, histoplasmosis, foreign body implantation, heavy infestation with Demodex and
acne rosacea. The presence of lipid spaces and neutrophils in the granulomata substantiates a diagnosis of
chalazion but, in the absence of these findings, histochemical stains for microorganisms are warranted.
A resolving chalazion is characterised by empty, irregular spaces and a lymphohistiocytic infiltrate in the
surrounding scar tissue. If the fibrotic reaction is prominent and small granulomata persist, the diagnosis
of sarcoidosis should be considered. Involutional atrophy of the Meibomian glands is frequently accompanied
by a lipogranulomatous reponse and deposition of loose connective tissue within the tarsus.
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