原发性肺淋巴上皮瘤样癌8例临床分析

BACKGROUND AND OBJECTIVE: Lymphoepithelioma-like carcinoma, an uncommon epithelial tumor, is mostly originated form the nasopharynx and also occurs in foregut-derived organs, such as lung, stomach, salivary gland, and thymus. Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype accounting for around 0.9% of non-small cell lung cancer (NSCLC). We aimed to evaluate clinicopathological features, treatment modalities, and prognosis of PPLELC. METHODS: In the current study, a retrospective analysis on 8 patients diagnosed with PPLELC at Hunan Cancer Hospital between October 2013 and June 2016 was conducted with respect to their clinical characteristics and outcomes, in order to deeply investigate this rare subtype of lung cancer. RESULTS: In all 8 patients, 62.5% (5/8) were female, and the median age was 51.5 years (range 41 years-64 years). The majority (87.5%) were never smokers and 50.0% were asymptomatic at diagnosis. About 37.5% presented with stage I disease, 50.0% had stage Ⅲ disease and 12.5% had stage Ⅳ disease. Histologically, the tumor morphology was indistinguishable from undifferentiated carcinoma of the nasopharynx and were characterized by poorly differentiated tumor cells with large vesicular nuclei and prominent nucleoli showing syncytial growth patterns and accompanied by heavy lymphocytic infiltration. The tumor cells were presented as positive for P63 (100.0%, 6/6), CK5/6 (100.0%, 5/5), CK (100.0%, 5/5). The expression of programmed cell death ligand 1 (PD-L1) in 8 patients was detected. When membranous staining was present in ≥5% of the cells, it was defined as PD-L1 positive. The PD-L1 expression frequency was 50.0% (4/8), and the tumor proportion score (TPS) fluctuated between 20.0% and 70.0%. Epidermal growth factor receptor(EGFR) mutations were detected in 3 cases and all tested samples were wild type; moreover, ALK rearrangement was negative in 2 patients with available data. KRAS, B-raf, C-kit, HER2, VEGFR1 and VEGFR2 were detected in 1 case. The results showed that KRAS was wild type, B-raf and C-kit mutation was negative, and HER2, VEGFR1 and VEGFR2 were moderately expressed. All patients underwent surgery with or without adjuvant therapy. Among these patients, 5 patients received adjuvant chemotherapy, including 2 patients with stage Ib disease, 2 patients with stage Ⅲa disease and 1 patient with stage Ⅳ disease. 1 patient with stage Ⅲa disease received adjuvant chemotherapy and radiotherapy and 1 patient with stage Ⅲa disease received neoadjuvant chemotherapy. All patients survived until the deadline for follow-up. The median survival time of all LELC patients is 57 months. The 3- and 5-year overall survival (OS) rates of LELC patients were 87.5% and 50.0%, disease-free survival (DFS) rates were 87.5% and 50.0%, respectively. CONCLUSION: PPLELC is uncommon but distinct subtype of NSCLC with unique clinicopathologic characteristics that tends to affect young nonsmoking patients, without significant predilection for sex and with strong association with Epstein-Barr virus (EBV) infection. Histology and immunohistochemistry are the main diagnostic methods. Rare or no driver gene mutations were found in the common oncogenes such as EGFR mutations and ALK gene rearrangement, implying that the mutagenesis of these genes was not involved in the tumorigenesis of PPLELC. PD-1 and PD-L1 may be potential therapeutic targets for PPLELC. The patients are diagnosed at an earlier stage and have a better prognosis than those with other non-small cell lung cancer. No standardized treatment regimens currently exist for this rare tumor. The mainstay of treatment for early-stage disease is curative surgical resection, whereas multimodality treatment (surgery, chemotherapy, radiotherapy) has been adopted in advanced or metastatic diseases. Due to its low incidence, further research is needed to determine its biological characteristics and optimal treatment options.