Pulmonary Lymphoepithelioma-like Carcinoma Disguised as Squamous Cell Carcinoma

Lymphoepithelioma-like carcinoma (LELC) of lung is a rare distinct subtype accounting for 0.9% of all lung cancers. LELC has been described in the nasopharynx, stomach, thymus, liver, cervix, salivary glands, and urinary bladder, and it primarily affects young, nonsmokers of Asian ancestry.1Yener N.A. Balikci A. Cubuk R. Midi A. Orki A. Eren Topkaya A. Primary lymphoepithelioma-like carcinoma of the lung: report of a rare case and review of the literature.Turk Patoloji Derg. 2012; 28: 286-289PubMed Google Scholar LELC is characterized by diffuse lymphocytic infiltrate and the presence of Epstein-Barr virus (EBV) in tumor cells.2Travis W.D. Brambilla E. Burke A. Marx A. Nicholson A.G. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. IARC, Lyon, France2015Google Scholar A 52-year-old Asian woman, a lifetime nonsmoker, presented with persistent cough. Imaging revealed a 4 × 4.2-cm lobulated mass in her left lower lobe lung, abutting the lateral aspect of the descending thoracic aorta. Core needle biopsy revealed poorly differentiated squamous cell carcinoma. The results of metastatic work-up were negative, and the patient underwent a video-assisted thoracoscopic left lower lung lobectomy, which revealed 4.5 × 4.4 × 3.5-cm mass. Five lymph nodes were sampled and were negative for malignancy. Lobectomy specimen showed a well-demarcated tumor with solid growth of tumor cells. These solid nests comprised cells with vesicular nuclei, prominent nucleoli, mild to moderate cytoplasm, indistinct cell borders, and tumor nests infiltrated by small lymphocytes. Epstein-Barr encoding region in situ hybridization demonstrated strong, diffuse labeling of tumor cells only. The combination of the morphologic findings of the tumor cells and Epstein-Barr encoding region in situ hybridization positivity confirmed LELC. Programmed death ligand 1 testing revealed 90% expression. Tumor tissue was negative for EGFR, ALK receptor tyrosine kinase gene (ALK), ROS1, and BRAF mutations. The patient's disease was staged as T2aN0M0 (stage IB by AJCC 7th edition and stage 2A by AJCC 8th edition). The patient would have been a candidate for adjuvant chemotherapy if this were true squamous cell carcinoma; however, given the excellent prognosis with this histologic type, she was not offered adjuvant therapy and has remained free of disease at 17 months. LELC was first described in 1987 by Begin et al. as a type of large-cell carcinoma, and approximately 200 cases of LELC of the lung have been reported so far.1Yener N.A. Balikci A. Cubuk R. Midi A. Orki A. Eren Topkaya A. Primary lymphoepithelioma-like carcinoma of the lung: report of a rare case and review of the literature.Turk Patoloji Derg. 2012; 28: 286-289PubMed Google Scholar Common clinical presentations include dry cough, hemoptysis, chest pain, weight loss, and fever; however, as many as one-third of patients may be discovered incidentally. Pulmonary LELCs often occur peripherally as a solitary lesion but can sometimes have endobronchial involvement.2Travis W.D. Brambilla E. Burke A. Marx A. Nicholson A.G. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. IARC, Lyon, France2015Google Scholar LELC is morphologically similar to undifferentiated nasopharyngeal carcinoma. Epstein-Barr virus encoded RNA 1 has been isolated from malignant tumor cells with prominent nucleoli amid a lymphoid-rich stroma. Tumor cells often express latent membrane protein 1 and BCL2 apoptosis regulator, along with CD8-positive T lymphocytes, which suggests a role of Epstein-Barr virus in pathogenesis. There is a low prevalence of EGFR mutations in pulmonary LELCs, and they are often associated with high programmed death ligand 1 expression.2Travis W.D. Brambilla E. Burke A. Marx A. Nicholson A.G. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. IARC, Lyon, France2015Google Scholar There are limited data regarding outcomes, but two small retrospective analyses have shown that LELCs generally have more favorable outcomes when compared with other NSCLCs. The 5-year progression-free survival and overall survival rates in one study were 53% and 80%, respectively.3Mok F.S.T. Osh C. Aty C. et al.Treatment outcomes of primary pulmonary lymphoepithelioma-like carcinoma: a series of 22 patients and treatment strategy review.Hong Kong Journal of Radiology. 2013; 16: 270-277Crossref Scopus (3) Google Scholar In another study, the 5-year overall survival rate was 62%, which contrasts with the rate of 17.7% for all lung cancers.4Liang Y. Liang W. Yujia Z. et al.Primary pulmonary lymphoepithelioma-like carcinoma: fifty-two patients with long-term follow-up.Cancer. 2012; 118: 4748-4758Crossref PubMed Scopus (105) Google Scholar Chemotherapeutic agents with activity against LELC include platinums, taxanes, pemetrexed, gemcitabine, 5-fluorouracil, and vinorelbine. There is also some suggestion that these tumors are more chemosensitive than other NSCLCs.5Chan A.T. Teo P.M. Lam K.C. et al.Multimodality treatment of primary lymphoepithelioma-like carcinoma of the lung.Cancer. 1998; 83: 925-929Crossref PubMed Scopus (55) Google Scholar It is imperative to the establish correct diagnosis of this rare histologic type with an experienced pathologist for recommending appropriate management, avoiding overtreatment, and counseling the patient on prognosis.