Objective To investigate the pathological features of Epstein-Barr virus (EBV)-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (EBVaLELICC), and to improve the understanding of this disease in clinical practice. Methods Clinical and pathological data were collected from one patient with EBVaLELICC, and immunohistochemistry, in situ hybridization, and gene rearrangement test were performed for the paraffin-embedded tissue sample of this patient. The pathological features of this disease were analyzed, and a literature review was performed. Results The female patient, aged 56 years, had the tumor located in the left lateral lobe of the liver, with a clear boundary and a size of 1.8 cm×1.5 cm×1.2 cm. The patient underwent laparoscopic left lateral segment liver resection in Department of Hepatobiliary Surgery. Postoperative pathology showed that tumor cells had a glandular tubular structure, and some cells had an irregular, fused or sieve-like shape, with large nuclei, fine chromatin, small nucleoli, and no mitotic figures; proliferation of lymphocytes and plasma cells was observed with the formation of lymphoid follicles in the stroma. Immunohistochemical staining showed that CK7, CK19, and P53 had an expression rate of 10% in tumor cells, with wild type and a Ki-67 proliferation index of 5%; stromal lymphocytes showed the expression of CD3, CD4, CD8, and CD20, lymphoid follicular germinal center cells showed the expression of BCL-6 and CD10 and had no expression of BCL-2, and plasma cells showed the expression of CD38, Kappa, and Lambda; PD-L1 (22C3) was expressed in both tumor cells and interstitial lymphocytes, with a combined positive score of 30. EBER in situ hybridization assay showed diffuse positivity of tumor cells. Polymerase chain reaction detected multiple clones of lymphocyte immunoglobulin and T cell receptor genes. The patient did not receive any treatment before and after surgery and was alive after 8 months of follow-up, without tumor recurrence or metastasis. Conclusion EBVaLELICC is a rare subtype of cholangiocarcinoma with unique pathological features. Patients can benefit from immunotherapy, and EBVaLELICC tends to have a better prognosis than common cholangiocarcinoma.

Objective:To investigate the value of 18F-FDG PET/CT imaging signs and metabolic parameters in predicting tumor spread through air spaces (STAS) of stage Ⅰ lung adenocarcinoma. Methods:From January 2019 to December 2021, clinical, imaging and metabolic parameters of 381 patients (126 males, 255 females, age (61.2±9.2) years) with stage Ⅰ lung adenocarcinoma were retrospectively analyzed in the Affiliated Hospital of Qingdao University. According to the postoperative pathological results, patients were divided into STAS positive group and STAS negative group. According to the operation time, patients were divided into training set ( n=254) and verification set ( n=127). χ2 test or Mann-Whitney U test was used to compare the differences of different parameters between patients with STAS positive and negative, and binary logistic regression analysis was used to select the predictors of STAS status. The prediction model was established, and ROC curve was used to evaluate the predictive efficacy. Results:There were 49(19.3%, 49/254) patients with STAS positive and 205(80.7%, 205/254) patients with STAS negative in the training set, while those were 35(27.6%, 35/127) and 92(72.4%, 92/127) in the verification set. In the training set, the differences of age ( z=-2.30, P=0.021), type of lesions ( χ2=6.81, P=0.009), spiculation ( χ2=12.64, P<0.001), bronchus truncation ( χ2=6.98, P=0.008), ground glass ribbon sign ( χ2=26.93, P<0.001) and SUV max ( z=-4.62, P<0.001) between the two groups were statistically significant. Multivariate logistic regression analysis showed that age (odds ratio ( OR)=1.048, 95% CI: 1.004-1.094, P=0.032), ground glass ribbon sign ( OR=3.857, 95% CI: 1.693-8.788, P=0.001) and SUV max ( OR=1.133, 95% CI: 1.001-1.282, P=0.049) were independent predictors of STAS status in stage Ⅰ lung adenocarcinoma patients. The logistic regression model was P=1/(1+ e - x), x=-5.292+ 0.480×age (year)+ 1.493×ground glass ribbon sign+ 0.170×SUV max. The AUCs of the model in the training set and verification set were 0.770 and 0.801, with the sensitivity of 81.6%(40/49) and 82.9%(29/35), and the specificity of 69.8%(143/205) and 65.2%(60/92), respectively. Conclusion:Age, ground glass ribbon sign and SUV max have good predictive effects on the occurrence of STAS in stage Ⅰ lung adenocarcinoma.

BackgroundLung cancer is a major health concern worldwide because of its increasing incidence and mortality. This study aimed to clarify the association between mesenchymal-epithelial transition (MET) genomic alterations and clinical characteristics of lung cancer.MethodWe collected data from 5,008 patients with lung cancer diagnosed and treated between January 2017 and July 2021 at the Affiliated Hospital of Qingdao University. Genomic alterations in the MET gene, including the exon 14 skipping mutation and amplification, were detected using amplification refractory mutation system-polymerase chain reaction (2,057 cases) and next-generation sequencing (2,951 cases). Clinical characteristics such as age, sex, tumor location, tumor stage, smoking, pleural invasion, and histology were statistically analyzed for MET exon 14 skipping mutation and amplification. The DNA splicing sites causing the MET exon 14 skipping mutation at the mRNA level were also investigated.ResultsThe incidence of the MET exon 14 skipping mutation was 0.90% (41/4,564) in adenocarcinoma, 1.02% (3/294) in squamous cell carcinoma, and 8.33% (1/12) in sarcomatoid carcinoma specimens. It was more frequently observed in patients over 60 years of age than the MET exon 14 skipping mutation wildtype. The MET exon 14 skipping mutation co-occurred with epidermal growth factor receptor (EGFR) L858R, EGFR 19-Del, and BRAF V600E mutations. At the DNA level, single nucleotide mutation and small fragment deletion (1–38 base pairs) upstream and downstream of MET exon 14 led to MET exon 14 skipping mutation at the mRNA level. MET amplification occurred in 0.78% (21/2,676) adenocarcinoma and 1.07% (2/187) squamous cell carcinoma specimens and was significantly associated with advanced tumor stages (III + IV) compared to the MET amplification wildtype. MET amplification primarily co-occurred with the EGFR mutation.ConclusionsOur study found that MET genomic alterations were statistically related to age and tumor stage and co-existed with mutations of other oncogenic driver genes, such as EGFR and BRAF. Moreover, various splicing site changes at the DNA level led to the exon 14 skipping mutation at the mRNA level. Further studies are required to clarify the association between MET genomic alterations and prognosis.