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Lymphoepithelioma-like carcinoma (LELC) of the skin is a rare malignant epithelial neoplasm, which resembles histologically the nasopharyngeal neoplasm of the same name.1,2 Similar tumours have been reported at a variety of sites including salivary gland, tonsil, thymus, stomach, and uterus. Those involving the skin usually present as a papulonodular lesion on the head or neck of patients above 50 years of age. Only one case originating in the eyelid has been previously described.3 We describe a further two cases and discuss the differential diagnosis.
A 79 year old man presented with a fusiform swelling occupying the medial half of his right lower lid (fig 1A). This had developed 8 months previously and was gradually increasing in size. An ectropion repair had been performed on this lid 7 years before presentation. The patient underwent excision of the lesion with reconstruction of the lid using a pedicle flap. The excised lesion was submitted for histopathological examination.
The patient had a medical history of carcinoma in situ of the right vocal cord, which was treated with laser excision in 2000 with no recurrence on follow up.
A 67 year old man presented with a subcutaneous cystic lesion at the margin of the lower eyelid. This had been present for 8 months and was gradually increasing in size. A clinical diagnosis of sebaceous cyst was considered. The lesion was excised and submitted for histopathological examination.
Histopathological examination of both lesions showed a relatively well circumscribed lesion situated within the dermis with no connection with the overlying epidermis (fig 1B). The lesions consisted of clusters of malignant epithelial cells with vesicular nuclei and large nucleoli (fig 1C). Foci suggestive of hair follicle differentiation were identified in case 2 (fig 1D). These clusters of malignant epithelial cells were surrounded by a mixed reactive inflammatory cell infiltrate composed predominantly of lymphocytes and plasma cells. Eosinophils and polymorphs were also identified in the inflammatory infiltrate from case 2.
In both cases immunohistochemical staining showed strong positivity for cytokeratins and epithelial membrane antigen in the islands of malignant epithelial cells. Immunohistochemical staining for Epstein-Barr virus was negative.
LELC, first described in 1988 by Swanson et al,1 is a rare cutaneous neoplasm that usually presents as a cutaneous nodule of short duration covered by an intact epidermis. The clinical diagnosis is often non-specific such as “lump” or “cyst.” In contrast, the microscopic appearances, as described above, are distinctive.
The histogenesis of LELC is uncertain. Most authors support an adnexal origin.1,4 This is suggested by the tumour location within the dermis and the absence of a connection with the overlying epidermis. This is further supported by the identification of areas of adnexal differentiation in some tumours, as in case 2.4 Conversely, cases displaying dysplasia in the overlying epidermis have been reported and this is suggestive of epidermal origin for LELC.5
Metastatic disease within the eyelid from underlying primary nasopharyngeal carcinoma (NPC) must be excluded before diagnosing LELC of the skin. The first patient had a history of carcinoma in situ of the larynx. The histology of this was reviewed and confirmed as squamous cell carcinoma in situ without evidence of invasion and there has been no evidence of recurrence on regular follow up. Furthermore, the surface epithelial cells of the laryngeal lesion were morphologically unlike the clusters of malignant epithelial cells seen in the LELC of the eyelid. Both patients also underwent endoscopy of the nasopharynx and no tumour or other abnormalities were identified.
NPC has a strong association with Epstein-Barr virus (EBV) infection. LELC at other sites has rarely been shown to have this association. Similar to those previously reported in the skin, EBV was not identified in either of our cases.6 Other differential diagnoses include anaplastic lymphoma, poorly differentiated squamous cell carcinoma, sebaceous carcinoma, melanoma, Merkel cell tumour, and cutaneous lymphadenoma.7 These can usually be discriminated from LELC with immunohistochemistry.
In the small number of cases reported so far, LELC appears to be of low malignant potential with a tendency towards local recurrence but a very low metastatic potential.1,2,4,5 Both cases presented have shown no sign of recurrence to date. LELC is a rare but distinctive malignant neoplasm that should be considered in the differential diagnosis of cyst like or nodular lesions of the eyelid.