Lymphoepitheliomalike carcinoma (LELC) of the skin is an uncommon cutaneous
malignancy with the potential for distant metastasis.1
We describe a patient with LELC of the mid forehead and an asymptomatic orbital
mass, which when biopsied proved to be a lymphoepitheliomalike carcinoma (LELC).
A 45-year-old man was referred to the Ophthalmology Clinic at the University
of Texas M. D. Anderson Cancer Center, Houston, for the evaluation of an asymptomatic
right-sided orbital mass that had been identified on recent magnetic resonance
imaging (MRI) scans. The patient denied any orbital symptoms or signs except
for numbness and paresthesia in the area of the right-sided supraorbital notch,
which had been present for at least 2 years. He had a history of a skin nodule
on his mid forehead, of which a biopsy specimen had been taken at another
institution and diagnosed as LELC of the skin. Subsequently, 2 wide-local
excisions with positive margins were performed on the nodule, and biopsy specimens
of the skin overlying the supraorbital notch revealed lymphoepithelioma with
The ophthalmologic examination results revealed a best-corrected visual
acuity of 20/70 OD and 20/15 OS; the visual acuity had been stable in the
right eye since a scleral buckle procedure for retinal detachment was performed
approximately 18 years prior to this presentation. The external examination
revealed quiet globes; the Hertel exophthalmometry measurement was 19 mm in
each eye. Results of the extraocular motility examination were normal. The
pupils were equal, round, and reactive to light with no afferent pupillary
defect. The confrontation visual fields were normal in the left eye, but superior
and temporal field defects were found in the right eye; it was not clear whether
the field deficit was new or due to the previous retinal detachment in the
right eye. The slitlamp examination and applanation tonometry measurements
were normal in both eyes. A dilated fundus examination revealed a 0.4 cup-disc
ratio in the right eye and a 0.2 cup-disc ratio in the left eye. There was
evidence of a scleral buckle band with an attached retina in the right eye;
there were no choroidal striae.
High-resolution MRI scans of the orbits were obtained with conventional
pulse sequences. They revealed a multilocular cystlike mass in the medial
aspect of the right orbit (Figure 1).
Other imaging features included fluid-fluid layers within the lesion and peripheral
enhancement. A computed tomography scan of the head and neck area that was
obtained 6 weeks prior to the MRI scan did not show an orbital mass.
A, An axial T1-weighted magnetic
resonance imaging (MRI) scan, tailored to the orbits, reveals a multilobular,
slightly hyperintense lesion in the upper medial aspect of the right orbit
(arrows). B, An axial T2-weighted MRI scan demonstrates a cystlike appearance,
with a fluid-fluid layer (arrows) best seen in the anterior component of the
tumor. C, An axial postcontrast fat-suppressed T1-weighted image shows peripheral
enhancement and a lack of central enhancement.
An orbital biopsy of the mass was performed through a modified Lynch
incision (superonasal orbitotomy).2 The
cystic mass was identified in the superonasal orbit, approximately 25 mm posterior
to the anterior lacrimal crest. The mass extended posteriorly toward the superior
orbital fissure, and there was no clearly defined capsule. Partial excision
of the mass was performed, and the frozen-section diagnosis was consistent
with poorly differentiated LELC. The patient underwent concurrent chemoradiotherapy,
consisting of 2 cycles of cisplatin followed by 3 cycles of cisplatin and
5-fluorouracil; external beam radiotherapy was administered in 33 fractions,
at a total dose of 6600 rad (66 Gy).
The material from the forehead lesion that was provided by another institution
consisted of a skin ellipse containing a dense, nodular infiltrate of the
deep dermis (Figure 2A). Islands
of large cytologically malignant cells with polygonal, pleomorphic nuclei
and prominent nucleoli were identified (Figure
2B). These islands were surrounded by a very dense lymphocytic infiltrate.
A, Deep nodular infiltrate (hematoxylin-eosin,
original magnification ×4). B, Island of atypical cells (pleomorphic
nuclei with prominent nucleoli) surrounded by small lymphocytes (original
magnification ×40). C, Immunohistochemical study performed in the orbital
lesion, which shows positive expression of cytokeratin (anti-cytokeratin stains:
AE1/AE3, CAM 5.2, Zym 5.2, MNF 116; amino-ethylcarbazole, original magnification
The surgical specimen from the orbital biopsy performed at M. D. Anderson
Cancer Center consisted of multiple fragments of pink, firm tissue with a
combined measurement of 1 × 0.6 × 0.4 cm. The specimen was routinely
processed, and additional slides were analyzed by a standard immunohistochemical
method. Histologically, there was an infiltrate very similar to that seen
in the outside material. An immunohistochemical study showed expression of
cytokeratin (Figure 2C), which confirmed
the epithelial nature of the malignant cells. This constellation of histologic
features is indicative of LELC. Standard in situ hybridization studies failed
to reveal evidence of infection by Epstein-Barr virus.
Lymphoepitheliomas are malignant tumors of epithelial origin with various
amounts of reactive lymphocytic infiltrate. Although initially described in
the nasopharynx (World Health Organization type 3 nasopharyngeal carcinoma),3 these tumors have been identified in various locations
throughout the body.4- 8
Lymphoepitheliomalike carcinoma of the skin is a rare cutaneous malignancy
that is probably of adnexal origin.9,10
It is usually a flesh-colored or red, firm nodule or plaque that appears most
often on the face. Since the original description by Swanson et al11 in 1988, at least 21 cases have been described.
The patient described here is slightly younger than most previously reported
patients (older than 50 years) with LELC of the skin.
Lymphoepitheliomalike carcinoma of the skin is microscopically distinct
from other primary cutaneous neoplasms. Although poorly differentiated squamous
cell carcinoma could conceivably be associated with a prominent lymphoid infiltration,
the latter is usually concentrated in the superficial dermis and has connections
with the epidermis. Furthermore, squamous cell carcinoma is usually associated
with at least focal evidence of cytoplasmic keratinization.
Cases of LELC of the skin associated with a metastatic or satellite
lesion in the orbit are extremely rare. The only mention in the literature
is in a study of 1422 orbital tumors analyzed at the eye pathology laboratory
at the Shanghai Medical University, Shanghai, China.12
The authors list an LELC of the skin metastatic to the orbit in one of the
1422 cases reviewed in their article, but no further description of the histologic
findings or the clinical findings is provided.
In the case described here, the orbital mass was an incidental finding
on an MRI scan after the diagnosis of LELC of the forehead skin with perineural
invasion. It is likely that the orbital mass represents a metastatic lesion
secondary to the forehead lesion, though the possibility of a direct extension
into the orbit or a primary orbital tumor with subsequent cutaneous metastasis
cannot be completely ruled out. It is interesting that the radiologic features
of the orbital mass were suggestive of a benign cystic lesion. Although there
were minimal to no orbital signs or visual symptoms of a mass in this patient,
and the radiologic features suggested a benign process, the orbital biopsy
was undertaken to rule out metastasis. Performing the orbital biopsy was a
crucial step, and it changed the staging and treatment of this disease.
This case underscores the importance of a thorough systemic workup for
patients with LELC of the skin. The orbital mass was identified during an
MRI scan of the head and neck, which was obtained to rule out involvement
of the paranasal sinuses or the oropharynx. In general, because of the close
histological similarity to nasopharyngeal lymphoepithelioma, patients with
suspected LELC of the skin should have a thorough otolaryngological examination,
including indirect laryngoscopy, to rule out metastasis to the skin. The differential
diagnosis also includes Merkel cell tumor; lymphoma; pseudolymphoma; and metastatic
lymphoepithelioma from the salivary gland, thymus, cervix, lung, vulva, stomach,
or tonsil. These may be excluded by history, physical examination findings,
and the results of histological studies, including immunohistochemical analysis.
Lymphoma and pseudolymphoma can be excluded because of the expression of lymphoid
markers and the lack of cytokeratin expression. Merkel cell carcinoma is characterized
by malignant epithelial cells with a lesser degree of pleomorphism than is
seen in LELC of the skin; also, the nuclei in Merkel cell carcinoma characteristically
have finely dispersed ("salt-and-pepper") chromatin.
We recommend an imaging study of the head and neck in all patients with
lymphoepithelioma of the periocular skin not only to rule out nasopharyngeal
carcinoma, but also to rule out the possibility of orbital metastasis, as
was the case in this patient.
The association of LELC and the Epstein-Barr virus varies in different
organs and in different geographical regions. The Epstein-Barr virus is definitively
associated with LELC from the stomach, salivary gland, lung, and thymus.13 The association of Epstein-Barr virus with LELC
is restricted to Asian patients with tumors of the salivary gland and lung;
whereas association of Epstein-Barr virus with gastric and thymic LELC is
independent of race. As was the case in our patient, in the skin, there is
no apparent association between LELC and Epstein-Barr virus.14
The treatment of choice for LELC of the skin is complete surgical excision
whenever possible.15 Radiotherapy is also
an effective modality for the treatment of lymphoepitheliomas, particularly
in patients in whom complete surgical excision of the cancer is not possible.16 In the patient whose case we describe, the forehead
lesion had recurred twice and was found to be associated with perineural invasion.
The orbital mass could not be completely excised without total sacrifice of
the intraorbital contents because it extended posteriorly almost to the superior
orbital fissure. External beam radiotherapy was the best treatment option
for this patient with extensive skin, perineural, and orbital lymphoepithelioma.
Corresponding author and reprints: Bita Esmaeli, MD, Ophthalmology
Section, Department of Plastic Surgery, University of Texas M. D. Anderson
Cancer Center, Box 443, 1515 Holcombe Blvd, Houston, TX 77030 (e-mail: email@example.com).
Ahmadi MA, Prieto VG, Clayman GL, Ginsberg LE, Esmaeli B. Lymphoepitheliomalike Carcinoma of the Orbit. Arch Ophthalmol. 2001;119(8):1206-1208. doi: