Ann Thorac Surg 2003;76:603-605
© 2003 The Society of Thoracic Surgeons
Case report
Primary lymphoepithelioma of the esophagus
Freddy Angulo-Pernett, MDa,
W. Roy Smythe, MDa*
a Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
Accepted for publication January 1, 2003.
* Address reprint requests to Dr Smythe, Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 445, Houston, TX 77030, USA
e-mail: rsmythe{at}mdanderson.org
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Abstract
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A case of primary lymphoepithelioma of the esophagus is presented in an Arabic female patient. This very rare Epstein-Barr virus infection-related malignancy has previously been reported only in patients from Japan. The tumor exhibited classic histologic and immunohistochemical features of lymphoepithelioma, and was successfully treated with neoadjuvant chemotherapy and irradiation followed by surgical resection.
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Introduction
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Lymphoepithelioma is a distinctive tumor type characterized by anaplastic epithelial derived cells surrounded by T lymphocytes [1]. The most common site for this malignancy is the pharynx, where it is termed undifferentiated nasopharyngeal carcinoma (UNPC). Lymphoepithelioma has primarily been described in foregut derivative tissues (stomach, lung, and thymus) and less frequently in other areas. An association between Epstein-Barr virus (EBV) and this malignancy has been firmly established, but this finding is usually restricted to those tumors found in foregut derived areas [2]. Fewer than five reports of true primary lymphoepithelioma of the esophagus have been published in the world’s literature, and all thus far in patients from Japan [3–5]. We present a case of primary lymphoepithelioma of the esophagus arising in a patient of Arabic descent.
A 64-year-old woman, native to the United Arab Emirates, reported a 4-year history of intermittent dysphagia. The patient also reported nausea, vomiting, and a 10-pound weight loss. Her past medical history was significant for hypothyroidism, hypertension, and migraine. The patient denied tobacco or alcohol use or any unusual exposure history. An esophagogastroduodenoscopy with biopsy was performed. At 27 cm, a polypoid, exophytic nonobstructing tumor mass was noted. Distally, there was an extensive area of Barrett’s mucosa, with islands of squamous mucosa. Endoscopic ultrasound suggested a T3N0 mol/L0 tumor. Computed tomography of the chest, abdomen, and pelvis revealed no evidence of tumor, adenopathy, or metastasis. Magnetic resonance imaging of the brain was negative. Barium contrast illustrated a 5.0 x 1.5 cm polypoid mass in the midthoracic esophagus. Although an outside biopsy had been interpreted as squamous cell carcinoma, histopathologic examination of the repeat biopsy specimen revealed an undifferentiated carcinoma consistent with lymphoepithelioma, with islands of epithelial tumor cells surrounded by lymphocytes (Fig 1).
Immunohistochemical analysis of sections demonstrated expression of EBV-encoded latent membrane protein 1 (LMP-1; Fig 2).
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Fig 1. Low magnification histopathology of the tumor revealing normal mucosa of the esophagus, as well as tumor. Arrows indicate islands of epithelial tumor cells that are surrounded by lymphocytes. (NM = normal mucosa; Tu = tumor).
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Fig 2. Histomicrograph demonstrating positive nuclear latent membrane protein-1 (LMP-1) staining in epithelial cells of tumor. Dark nuclei (arrows) are immunohistochemically positive for the LMP-1 Epstein-Barr virus antigen.
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The patient was initially treated with chemoradiation therapy including 5-fluorouracil, cisplatin and 50.4-Gy external beam radiation. Three weeks following completion of radiotherapy, an esophagogastroduodenoscopy with ultrasound of the esophagus was performed, which revealed a 0.5-cm diameter polypoid lesion remaining at 27 cm. Six weeks following radiotherapy, the patient underwent a transhiatal esophagectomy with cervical esophagogastric anastamosis. There was no evidence of tumor at preoperative esophagoscopy, and both the procedure and postoperative recovery were uneventful. Final pathologic examination demonstrated a complete pathologic response, with only hemosiderin and inflammation in the esophageal wall. Regional lymph nodes did not contain tumor. The patient is alive and well without evidence of recurrence at 24-months postsurgical resection.
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Comment
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Lymphoepithelioma is a tumor histologically identical to UNPC carcinoma occurring outside the nasopharynx. Due to a lack of differentiation these tumors have been frequently mistaken morphologically for either melanoma or lymphoma. Epstein-Barr virus has been known to be associated with malignancy dating back to the demonstration of herpes virus in cultured cell lines derived from patients with Burkitt’s lymphoma [6]. In recent years a number of other malignancies, such as UNPC, AIDS and transplant immunosuppression associated lymphoma, lymphoepithelioma, gastric adenocarcinomas, and Hodgkin’s tumors have been reported to have an EBV association. Interestingly, there is an unexplained strong clustering of EBV-related malignancies in Africa, Southeast Asia, and among the Eskimo population in the northwest North American continent [1, 2]. The association between lymphoepithelioma and EBV was initially suspected on the basis of positive serologic studies, and later confirmed by detection of EBV genomes in UNPC biopsies. Epstein-Barr virus sequences are limited to the epithelial tumor cells rather than the infiltrating lymphocytes, as is noted with transplant-related immunoproliferative disorder where the tumor cells result from EBV initiated clonal lymphocyte proliferation [7].
It is known that the EBV nuclear antigen 1 (EBNA1) protein interacts with viral DNA allowing it to be maintained in human cells as an episome. A second related protein, EBV nuclear antigen 2 (EBNA2) upregulates expression other viral proteins, including EBV LMP-1. Latent membrane protein-1 acts as an oncogene, and experimental expression of this protein leads to the development of lymphoma. The oncogenic potential of LMP-1 may be related to an ability to activate NF-
B, a known pro-survival transcription factor [8]. Current standard detection methods for EBV in human cells include use of immunohistochemical detection of LMP-1, as was noted in our patient, as well as EBV RNA in situ hybridization [2].
Compared with other tumor types of the same clinical stage, patients with gastric and lung lymphoepithelioma have been reported to have a better prognosis [9–11]. In addition, one group from Japan, when publishing results of all patients surviving 10 years following resection of esophageal carcinoma (10/150), reported that 2 of 10 patients were lymphoepithelioma—a significant overrepresentation [5]. The more favorable prognosis for lymphoepithelioma has been related to the infiltrating lymphocyte population, which is primarily made up of cytotoxic T cells specifically reactive to the adjacent epithelial cells that contain EBV sequences. By convention it is generally accepted that multimodality therapy, including surgical resection, is most effective for these tumors regardless of location, but the small numbers of cases extant has precluded a comparison between individual treatments.
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References
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- Weiss L.M., Gaffey M.J., Shibata D. Lymphoepithelioma-like carcinoma and its relationship to Epstein-Barr Virus. Am J Clin Pathol 1991;96:156-158.[Medline]
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- Epstein M.A., Achong B.G., Barr Y.M. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1964;1:702-703.[Medline]
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Abstract
Introduction
