Primary pulmonary lymphoepithelioma-like carcinoma is characterized by high PD-L1 expression,but low tumor mutation burden

Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer (NSCLC). There are few reported studies on the relationship between programmed death ligand-1 (PD-L1) expression and genomics features of this distinct NSCLC subtype. Our study aimed to investigate the expression levels of PD-L1 to determine their clinical value and to identify genetic alterations in PLELC. Fifty-nine PLELC patients, whose clinical information and pathology results were available, were included in this study. Immunohistochemical analysis of PD-L1 was performed in all cases. Specimens of 37 PLELCs and 3 metastatic nasopharyngeal carcinomas (NPCs) of the lung, resected within the previous 3 years, were chosen for mutation analysis, using next-generation sequencing of 425 genes. PLELC patients in the present study were mainly non-smoking females, with a high frequency of PD-L1 positivity in their tumors. Positivity rates were 96.6 %, 91.5 %, 83.1 %, and 61.0 % at tumor proportion scores (TPSs)≥ 1%, 5%, 10 %, and 50 %, respectively. Moreover, we observed that PD-L1 expression was higher in specimens stored for ≤ 3 years and in tumor cells with vesicular nucleus morphology at a TPS ≥ 50 %. Mutation analysis suggested a relatively high frequency of TP53 mutations and MCL1 copy number variation, but low tumor mutation burden (TMB) (ranging from 0 to 6.9, median of 1.1 mutation per megabase) and similarity of gene alteration with NPCs. However, no specific germline mutation was detected in PLELC patients. Additionally, survival analysis showed that patients in the early stages (stage I and II) had higher progression-free survival rates (P = 0.035) and those with tumors containing obvious stroma fibrosis tended to have worse prognosis (P = 0.008). However only stage was shown to be the independent prognostic factor (P = 0.008, HR=4.807, 95 %CI:1.508−15.323).PLELC is a subtype of lung cancer with distinct clinicopathological and genetic features, especially characterized by high PD-L1 expression and low TMB.     

Primary epithelial tumors of the lacrimal gland; a retrospective analysis of 22 patients

This study analyzed the clinical and histopathological aspects, treatment and prognosis of 22 patients with primary epithelial tumors of the lacrimal gland treated in a single institution over 25 years. 191 lacrimal gland lesions retrieved from the archives of the Department of Pathology, Erasmus University Medical Center, were retrospectively reviewed. The clinical and surgical pathology files of 22 primary epithelial neoplasms (16 benign; 6 malignant tumors) were studied. All benign tumors were pleomorphic adenomas; 50% of the malignant neoplasms were adenoid cystic carcinomas. The mean time from complaint to diagnosis was 3 years for benign tumors and 6 months for malignancies. Most benign tumors were treated by local excision; no recurrences occurred. Treatment of malignant tumors varied but generally involved extensive surgery with postoperative radiotherapy. 50% of these patients showed regional and/or distant metastasis. 33% of patients with malignancy died of their disease. Most primary epithelial tumors of the lacrimal gland are pleomorphic adenomas. They have a long duration of symptoms before diagnosis, are treated by limited surgery and recur infrequently. Malignant tumors have a short duration of symptoms, are sometimes mistaken for inflammatory disease, and are, even in case of aggressive surgery, characterized by a high rate of local recurrence and metastasis.     

Genetic Profiling of Cell-Free DNA From Pleural Effusion in Advanced Lung Cancer as a Surrogate for Tumor Tissue and Revealed Additional Clinical Actionable Targets

BackgroundPleural effusion (PE) has been one of the promising sources of liquid biopsy in advanced lung cancer patients. However, its clinical utility is not widely accepted due to the lack of full estimation of its potential versus routine clinical samples.MethodA total of 164 advanced lung cancer patients were enrolled with 164 matched tumor tissue and PE-cfDNA, 153 accompanied plasma and 63 ¹PE-sDNA.ResultPE-cfDNA displayed significantly higher median mutant allele frequency and an overall mutation concordance rate of 65% to tissue, which was higher than PE-sDNA (43%) and plasma-cfDNA (43%). The discrepancies between PE-cfDNA and tumor tissue were high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients were identified with actionable mutations in PE-cfDNA and four patients benefited from PE-cfDNA-guided targeted. Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients compared to tumor tissue alone. Our finding highlighted the importance of PE-cfDNA in the optimal selection of patients for targeted therapy.ConclusionThe PE-cfDNA-based liquid biopsy displays better performance in the characterization of gene alterations than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which might be important for selecting patients for better treatment management.     

Mutations of genes including DNMT3A detected by next-generation sequencing in thyroid cancer

More than 90% of thyroid cancer belongs to the papillary and follicular thyroid carcinomas based on pathological subtypes. Papillary and follicular thyroid carcinoma are generally associated with a good prognosis. In contrast, other pathological subtypes such as poorly-differentiated and anaplastic thyroid carcinoma (PDTC and ATC) have a poor clinical outcome with a short life expectancy. To identify the genetic variations and biomarkers that may potentially distinguish the aggressive form of thyroid cancer, we performed a retrospective analysis of the formalin-fixed paraffin-embedded tumor samples from 50 patients who mainly displayed aggressive thyroid cancer using next-generation sequencing of 416 solid tumor-related genes. We adopted extensive bioinformatic analysis to vigorously remove germline single-nucleotide polymorphism and systematic sequencing errors, and report here that mutation in DNMT3A gene was significantly enriched in patients with PDTC or ATC.