Introduction:
Carcinoma is a tumor originating from putative epithelial cells whose genome gets altered or damaged, causing the cells to undergo transformation and show unusual malignant properties. Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rarely seen, unique tumor and a sub-type of non-small-cell-lung carcinoma (NSCLC). It is frequently misinterpreted or misdiagnosed as squamous carcinoma. It is seen in around one percent of all NSCLC-affected individuals and usually affects young, nonsmoking people.
What Is Carcinoma?
Carcinoma is a tumor originating from putative epithelial cells whose genome gets altered or damaged, causing the cells to undergo transformation and show unusual malignant properties. Frequently affected by carcinomas are lung, breast, prostate, bladder, etc. It can be diagnosed with the help of a biopsy in which a tissue is extracted from the suspected part of the body and examined further. For its treatment, options like chemotherapy, radiation, surgery, targeted cancer therapy, biologic therapy, etc., are preferred alone or in combination with certain medications. The good part about this tumor is the affected patients are diagnosed at an earlier stage and have shown a better prognosis than those with other non-small cell lung cancers.
What Is Pulmonary Lymphoepithelioma-Like Carcinoma?
Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rarely seen, unique tumor and a sub-type of non-small-cell- lung- carcinoma (NSCLC). It is frequently misinterpreted or misdiagnosed as squamous carcinoma. It is seen to occur in association with Epstein-Barr virus (EBV) infection, which is not reported very clearly and not well understood. It is seen in around one percent of all NSCLC-affected individuals, frequently young, nonsmoking, Asian populations. Its clinical and radiographical manifestations are not pathognomonic. The tumor has unique pathologic features that distinguish it from those of undifferentiated nasopharyngeal carcinoma, termed carcinoma of the nasopharynx. It is characterized by ill-differentiated tumor cells with large vesicular nuclei and prominent nucleoli, which are nests-like or diffuse sheets that present a syncytial growth pattern. The presence of the Epstein-Barr virus in the tumor cells is very crucial for its identification. The differential diagnoses comprise lymphoepithelioma-like carcinoma from other sites and pulmonary involvement of lymphoma. EGFR mutations and ALK rearrangements are not frequently observed in lymphoepithelioma-like carcinoma, in contrast to programmed death ligand-1 expression, which is shown in a majority of cases.
What Are the Clinical Features of Pulmonary Lymphoepithelioma Carcinoma?
The clinical features of pulmonary lymphoepithelioma-like carcinoma (PLELC) are:
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It is rarely seen.
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Its prevalence is seen in the non-smoking male population.
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It is seen to affect the lungs.
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It is usually found in the periphery or subpleural lung and is not related to the bronchus.
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Cough and hemoptysis are primarily seen in affected individuals.
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Chest pain is observed.
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Its prevalence can be seen in both males and females.
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It is a solitary, round to ovoid, nonencapsulated, and well-circumscribed nodule.
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The age of affected individuals lies between 35 to 85 years, and the mean age lies between 51 and 57 years.
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Frequently noted symptoms include cough with or without hemoptysis.
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Most patients are asymptomatic while diagnosing.
Some other clinical features seen are chest pain, weight loss, exertional dyspnea, night sweats, joint pain, fever, and pleural effusion.
How Is Pulmonary Lymphoepithelioma Carcinoma Diagnosed?
The histopathological manifestations of PPLELC closely resemble those of nasopharyngeal carcinoma. A distinguishing feature of PPLELC is the presence of a large number of tumor-infiltrating lymphocytes in the tumor background and positivity for EBER. However, in biopsy specimens, these characteristics might not be clear because of the small sample size. In a research study, it was identified that common immune markers for PPLELC, such as P40, P64, and CK5/6, resemble those seen in SCC, leading to a potential risk of misdiagnosis. In a reported case, a patient underwent a lung biopsy, which yielded a small gray-white tissue sample of about 0.59 inches. The immune markers observed were: CD56(-), CK8/18(+), CgA(-), Ki-67 (+, 30%), P40(+), Syn(-), and TTF-1(-).
Due to the limited amount of biopsied tissue, the typical microscopic characteristics of PPLELC were not observed, and the immune markers appeared to align with SCC, resulting in a misdiagnosis. However, during surgical treatment, a larger specimen was obtained, and the postoperative pathological examination revealed a significant number of tumor-infiltrating lymphocytes. The immune markers observed were CK5/6(+), CK8/18(+), Ki-67(+,60%), P40(+), and TTF-1(-). Additionally, the in-situ hybridization examination suggested EBER(+). These findings led to the correct diagnosis of lymphoepitheliomatous carcinoma ultimately. It is observed that EBER, a crucial diagnostic test that differentiates SCC from PPLELC, is affordable, making it accessible to a huge population of patients.
How Is Pulmonary Lymphoepithelioma Carcinoma Managed?
The treatment approach for PPLELC currently lacks unified guidelines, and there are no specific National Comprehensive Cancer Network guidelines for its management. However, radical surgery is usually considered the primary treatment method. In a study conducted on 52 PPLELC patients who had radical surgery alone, only six experienced relapses, with recurrence developing between 10.6 and 41.
Overall, the prognosis of PLELC remains favorable. Nowadays, it is believed that early-stage patients frequently do not require postoperative adjuvant therapy, while chemotherapy can extend the overall survival of advanced-stage patients. Some of the best options for treatment are:
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Platinum-based dual-drug combination chemotherapy is frequently chosen as the first-line treatment for advanced PPLELC in clinical practice.
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Surgery is the main treatment strategy for early and operable stage pulmonary LELC.
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Pulmonary lymphoepithelioma-like carcinoma (PLELC) is more sensitive to chemoradiotherapy than adenocarcinoma or squamous cell carcinoma.
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In comparison with adenocarcinoma or squamous cell carcinoma, the prognosis of PLELC is better.
Conclusion:
PPLELC is a rare subtype of lung cancer that is frequently misdiagnosed with squamous cell carcinoma because of its microscopic look and immune markers closely resembling those of SCC. As of now, there are no standardized treatment options for PPLELC. Surgical intervention is a frequently chosen treatment approach, and patients might benefit from postoperative adjuvant chemotherapy. Patients who possess stage III-N2 PLELC have a favorable prognosis, with radiotherapy playing an important role in treatment. Both definitive chemoradiotherapy and radical surgery followed by chemoradiotherapy demonstrate favorable efficacy and manageable toxicity.
