Lymphoepithelioma-like carcinoma of the skin: New case of an exceedingly rare primary skin tumor
Dermatopathology Section, Department of Cellular Pathology, PathLinks Pathology Services, Lincoln County Hospital, Lincoln, United Kingdom. email@example.com
Lymphoepithelioma-like carcinoma of the skin (LE-lCS) is a very rare, primary skin neoplasm of uncertain origin. The tumor reveals striking morphological similarity to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma). However, the primary skin tumors have never been associated with Epstein-Barr virus (EBV), in contrast to those at some extracutaneous sites. Since the first description by Swanson et al. in 1988, only 46 cases have been documented over the last 20 years. This case report presents an 89-year-old woman with a 0.5cm plaque-like, discolored lesion on her left cheek of one-month duration. The patient underwent surgical excision and is disease free one year later. The histopathological, immunohistochemical and EBV in situ hybridization features are described. The clinical and pathological differential diagnosis is discussed. This case supports the contention that LE-lCS is not associated with EBV.
An 89-year-old woman presented to our outpatient clinic with a month-long history of a 0.5cm plaque-like, indolent brown lesion on the left cheek. There was no ulceration. Centrally there was a 0.3cm beige papule with pearly appearance. The epidermis overlying the papule was thinned and stretched. No telangiectatic vessels were evident. No local/cervical lymphadenopathy was detected. The plaque was excised after a clinical diagnosis of nodular basal cell carcinoma. After surgical excision the patient was free of recurrent tumor or local or distant metastatic spread during a follow-up period of one year.
Microscopic examination revealed a nodular, well-defined intradermal tumor with expansive borders without epidermal infiltration (Fig. 1). The epidermal surface showed no ulceration or evidence of dysplasia. The tumor was composed of atypical, epitheloid neoplastic cells arranged in a syncitial growth pattern with indistinct cell margins, surrounded by a dense, mostly lymphocytic infiltrate resembling a germinal centre (Figs. 2 & 3). The tumor cells were round to polygonal with eosinophilic cytoplasm and large vesicular nuclei and prominent nucleoli (Fig. 4). Mitoses were readily identified.
Neoplastic epithelioid cells showed expression of cytokeratins (AE 1/AE3) and epithelial membrane antigen (EMA), confirming epithelial differentiation (Figs. 5 & 6). Surrounding lymphocytic infiltrate was positive for CD20 and CD3 (Figs. 7 & 8). The tumor was negative for synaptophisin, chromogranin, cytokeratin (CK) 20 and TTF1. EBV-associated antibodies including anti EBV, EBNA & ZEBRA were negative. In situ hybridization for EBV-encoded RNA for detection of active and latent infection (Lytic & EBER PNA probes) were negative.
Microscopic findings along with the tumor's immunoprofile were consistent with a lymphoepithelioma-like carcinoma of the skin. The main differential diagnosis, a metastasis of lymphoepithelioma of the nasopharynx or other site, was ruled out by normal head and body CT scans and a thorough ear-nose-throat examination including biopsies.
The first case of LE-lCS was documented by Swanson et al. in 1988 ; since then an additional 46 cases have been reported. Similar tumors have been reported in a variety of sites including nasopharynx, salivary glands, lung, thymus, stomach, cervix, and urinary bladder [4, 5, 6, 7].
Lymphoepithelioma-like carcinoma of the skin is a very rare primary skin tumor of uncertain histogenesis. Adnexal and epidermal origins have been proposed based on eccrine and trichilemmal differentiation [8, 9, 10] and the rare presence of epithelial dysplasia and epidermal involvement [11, 12].
It is usually a plaque-like, firm, variously-colored, facial or neck nodule affecting approximately equally females and males in their seventies. Lymphoepithelioma-like carcinoma of the skin is microscopically distinct from other primary skin tumors showing well-circumscribed lobules or nests of large, cohesive, epithelioid cells closely associated with a dense, mixed T and B lymphocytic infiltrate. The epithelioid component has no connection with the epidermis; the cells display poorly defined eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli and increased mitotic activity, including atypical mitotic figures.
The main differential diagnosis includes undifferentiated nasopharyngeal carcinoma or metastatic lymphoepithelioma-like carcinoma from other sites, poorly differentiated squamous cell carcinoma, melanoma, lymphoma, and cutaneous lymphadenoma. Detection of EBV and clinical work-up for primary lymphoepithelioma-like carcinoma (LE-lC) in other organs may help in differentiating primary skin tumors from metastases. While undifferentiated nasopharyngeal carcinoma and some LE-lC of the other sites are associated with EBV , the skin tumors have never been reactive for EBV-encoded RNA . Poorly differentiated squamous cell carcinoma with a marked lymphocytic host response usually reveals an epidermal origin and epithelial dysplasia. Merkel cell carcinoma displays characteristic CK20 positivity and staining for neuroendocrine markers. Melanoma and lymphoma show different immunoprofiles including positivity for S100 and lymphoid markers, respectively. Cutaneous lymphadenoma is a benign tumor with no cytological atypia or mitoses, showing peripheral palisading of the epithelial nests.
The association of LE-lC and EBV varies in different organs and locations. EBV is definitively associated with the tumors in only 4 sites: lung, thymus, salivary glands, and stomach .
The association of EBV with LE-lC is restricted to Asian patients with tumors of the salivary glands and lung, whereas gastric and thymic tumors related to EBV are independent of race. However, LE-lCS apparently has no relationship to EBV .
Whenever possible the treatment of choice for LE-lCS is complete surgical excision . Radiotherapy is also a useful modality for the treatment of lymphoepitheliomas in patients with incomplete surgical excision .
Lymphoepithelioma-like carcinoma of the skin has a relatively good prognosis with low metastatic potential. Among all reported cases, 78 percent of patients were free of disease after treatment. An additional ten percent of patients had a local recurrence and only 2 patients developed lymph node metastases with a fatal outcome [1, 17].
In conclusion, LE-lCS is an exceedingly rare, but distinct pathological entity of unclear histogenesis. Immunohistochemistry, in situ hybridization, and clinical work-up including head and body CT scans and thorough ENT examination, are important for the confirmation of the diagnosis and subsequent treatment. Despite its similarity to lymphoepithelioma a conservative surgical approach is advised [9, 13, 15]. Furthermore this case supports the lack of a relationship between EBV and lymphoepithelioma-like carcinoma of the skin; this is in keeping with the other reported cases of this primary skin tumor.
Acknowledgement: I want to thank Mr. Reed for his help in polishing this article.
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