Lymphoepitheliomalike Carcinoma of the Orbit

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 perineural invasion.

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.

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.

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: besmaeli@mdanderson.org).