[Clinicopathological and genetic characteristics of congenital cystic adenomatoid malformation of lung and its associated lung cancer in adults].

Objective: To investigate the clinicopathological features and genetic characteristics of congenital cystic adenomatoid malformation (CCAM) of lung and CCAM associated lung cancer in adults. Methods: A total of 13 cases of CCAM of lung in adults, diagnosed from June 2015 to May 2023, were collected from the Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. Their histopathological features were correlated with probable development into lung cancer. Next-generation sequencing was performed on the benign and malignant areas of all cases. Results: The pathological classification of all cases were of CCAM of lung type 1. There were 4 male and 9 female cases, age ranged from 18 to 65 years, with a mean age of 41 years. Six cases were accompanied by lung cancer, all of them were mucinous adenocarcinoma. Next-generation sequencing showed no gene mutation in 2 of the 13 cases; KRAS mutations in exon 2 were detected in 7 cases, in which there were 6 cases complicated with lung mucinous adenocarcinoma and no matter in the malignant or benign regions, the same case exhibited the same mutation sites in KRAS gene. Conclusions: CCAM of the lung is a congenital disease, and in adults, type 1 is most commonly found in the pathological classification, and it is often accompanied by cancer. Gene mutations are frequently detected in CCAM of the lung, KRAS being the most recurrent mutation which may play an important role in the carcinogenesis.

[Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations].

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

[Clinicopathological and genetic characteristics of bronchial sialadenoma papilliferum: report of four cases].

Objective: To investigate the clinicopathological, immunophenotypic, and molecular genetic features of bronchial sialadenoma papilliferum (BSP). Methods: Four cases of BSP collected at the Shanghai Pulmonary Hospital from May 2018 to June 2021 were retrieved and analyzed. These cases were evaluated for their clinical, histological, immunohistochemical (IHC) and genomic features. The patients were followed up and relevant literature was reviewed. Results: All four patients were male, aged from 55 to 75 years (mean 62 years), with tumor diameter of 6 to 21 mm (mean 13.5 mm), and lesions were located in the left lower lobe (n=2), right lower lobe (n=1), and trachea (n=1). They were characterized by a combination of surface exophytic endobronchial papillary proliferation and an endophytic two-cell layered ductal structure. IHC staining showed that CK7 and EMA were strongly positive in ductal epithelium; p63, p40, CK5/6 were positive in ductal and papillary basal cells; SOX10 was positive in ductal epithelium and basal cells; S-100 was positive in basal cells and ductal epithelium in two cases. Next generation sequencing showed that two cases harbored BRAF V600E mutation. Conclusions: BSP is an extremely rare primary lung tumor arising from the salivary gland under bronchial mucosa. The primary treatment choice of this tumor is complete surgical resection. The diagnosis and differential diagnosis of this tumor depend on classic histomorphologic and IHC features, and BRAF V600E gene mutation can be detected.

[Pathological assessment of non-small cell lung cancer resection specimens after neoadjuvant therapy].

Objective: To pathologically evaluate the surgically resected specimens of three different therapies (neoadjuvant chemotherapy, neoadjuvant targeted therapy and neoadjuvant immunotherapy combined with chemotherapy) for non-small cell lung cancer. Methods: One-hundred and thirteen cases of post neoadjuvant therapy non-small cell lung cancer specimens were collected at Tongji University Affiliated Shanghai Pulmonary Hospital from January 2000 to March 2020. There were ninty patients receiving neoadjuvant chemotherapy (chemotherapy group;26 cases of adenocarcinoma and 64 cases of squamous cell carcinoma), 13 patients receiving neoadjuvant targeted therapy (targeted group;13 cases of adenocarcinoma) and 10 patients receiving neoadjuvant immunotherapy combined with chemotherapy (immune combined chemotherapy group;4 cases of adenocarcinoma and 6 cases of squamous cell carcinoma). They were evaluated for histologic tumor regression responses (necrosis, inflammatory cell infiltration, cholesterol crystal deposition, foam cell infiltration, reactive granuloma and interstitial collagenous formation) and pathological responses [main pathological response (MPR) and complete pathological response (PCR)]. Results: Chemotherapy group, targeted group and immune combined chemotherapy group all showed degenerative changes in residual tumor cells, increased atypia, various degrees of necrosis, foam cell aggregation, cholesterol cleft, inflammatory cell infiltration, and reactive granuloma in the tumor bed. Histologic characteristics of tumor regression reaction were not different between these three groups (P>0.05); the highest percentage of necrosis in the targeted group and immune combined chemotherapy group was only 10% and 20%, respectively, while that in the chemotherapy group was as high as 80%. One case of adenocarcinoma in immune combined chemotherapy group had tumor regression bed. The MPR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 35% (9/26) and 64% (41/64), respectively; the MPR ratio of targeted group was 2/13; the MPR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinoma in immune combined chemotherapy group were 2/4 and 2/6, respectively. The PCR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 11% (3/26) and 3% (2/64), respectively; the PCR ratio of targeted group was 0/13; the PCR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinomain immune combined chemotherapy group were 0/4 and 1/6, respectively. Conclusions: Different neoadjuvant therapy may cause various histopathological changes in non-small cell lung cancer: more necrosis is noted in the chemotherapy group and regression bed frequently appears in the immune combined chemotherapy group. In the immune combined chemotherapy group, there are significant lymphoplasmacytic infiltration and lymphoid follicle formation in the lung parenchyma beside the tumor bed.

[Research advances in the v-raf murine sarcoma viral oncogene homolog gene mutation in ameloblastoma].

V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a pro-oncogene, which is one member of the RAF family. Mutated BRAF is found in approximately 8% of human tumors. BRAF gene mutations lead to continuous activation of the mitogen-activatd protein kinase (MAPK) pathway, which resulting in abnormal cell proliferation and tumorigenesis. In recent years, recurrent MAPK signaling mutations were identified in ameloblastoma, among which BRAF-V600E is the most prominent type. This provides new strategies for the targeted treatment of ameloblastoma. This paper reviewed the latest advances in BRAF gene mutation associated with ameloblastoma and its potential clinical significance.

[Clinicopathologic features and genetic profile of the redefined large cell lung carcinoma].

Objective: To investigate the clinicopathologic features and genetic profile of large cell lung carcinoma (LCC) redefined by new classification. Methods: Basing on 2015 WHO classification criteria in redefining large cell lung carcinoma, the expression of specific markers (TTF1, Napsin A, p40, CK5/6, CK, vimentin and ZEB1) was detected by immunohistochemistry and D-PAS staining in 303 surgically-removed lung specimens previously diagnosed as large cell lung carcinoma. The clinicopathologic and genetic characteristics (including EGFR, KRAS, BRAF, ALK and ROS1 gene mutation) were analyzed. Results: Based on the new definition of LCC, 116 cases (116/303, 38.3%) of LCC formerly diagnosed were reclassified as solid adenocarcinoma, 49 cases (49/303, 16.2%) as squamous cell carcinoma, 6 cases (6/303, 2.0%) as adenosquamous carcinoma, 22 cases (22/303, 7.3%) as spindle cell carcinoma and only 110 cases (110/303, 36.3%) as large cell carcinoma. Redefined LCCs were characterized as middle-age (range 40-80), male (102/110, 92.7%) and smoking patients (64/110, 58.2%) with intermediate-advanced stage. Among 110 cases, 9 cases with EGFR mutation and 10 cases with KRAS mutation and 1 case with ALK fusion were found. No BRAF and ROS1 alterations were identified. Conclusions: According to the new classification, LCCs formerly diagnosed are mostly reclassified as adenocarcinoma and non-keratinizing squamous cell carcinoma. The newly defined LCC may significantly benefit from clinical therapy.

Significance of lipopolysaccharide detection in children with pulmonary infections.

OBJECTIVE: The present study aimed to observe the alterations of lipopolysaccharide (LPS) and some other laboratory indexes in children suffering from pulmonary infections, and to investigate the condition of Gram-negative bacterial infection. PATIENTS AND METHODS: All the patients received routine blood test, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), Mycoplasma pneumoniae antibody IgM (MP-IgM), LPS, blood culture and chest X-ray examination. The clinical data was collected followed by induction arrangement and statistical analysis. RESULTS: In terms of the rate of abnormity in peripheral white blood cell count and positive rate of blood CRP, no significant difference was found between children with pulmonary infections and the healthy individual in the control group (p > 0.05). The positive rates of blood MP-IgM were 33.33% and 32.26% in children with different progressive stages of pulmonary infections, which were significantly lower than those in the control group (62.96%) (p < 0.05). The positive rates of blood LPS in the observation group were higher than those in the control group, especially for those children at progressive stages within one week; and the difference between them was significant (p < 0.05). With regard to blood bacterial culture, the positive rates were 9.52% and 29.03% for children in progressive stages within one week and over one week in the observation group, respectively; the latter was significantly higher than that in the control group (p < 0.05). The result of the correlation analysis suggested a weak correlation between the positive rate of increased blood LPS in the observation group and that in blood bacterial culture (χ2 = 6.61, p < 0.05; Pearson's contingency coefficient C = 0.34). However, there was no significant correlation between the positive rate of increased blood LPS and peripheral blood white cell count, CRP, or MP-IgM (p > 0.05). CONCLUSIONS: Endotoxemia is often accompanied by pulmonary infections, and gram-negative bacterium is a common pathogenic bacterium in children with different progressive stages of pneumonia.

Epstein-Barr virus serology and gastric cancer incidence and survival.

Among 185 cases of gastric cancer and 200 controls in Linxian, China, Epstein-Barr virus (EBV) seropositivity was not associated with increased risk of gastric cancer. High EBV nuclear antigen titres were associated with longer survival in cardia cancer cases, possibly due to chance.

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers.

We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. The distribution of serum 25(OH)D was calculated using the known sampling weights. For the cohort as a whole, the 25th, 50th, and 75th percentile concentrations of 25(OH)-vitamin D were 19.6, 31.9, and 48.7 nmol l(-1), respectively, and we found that higher serum 25(OH)D concentrations were associated with monotonically increasing risk of ESCC in men, but not in women. Comparing men in the fourth quartile of serum 25(OH)D concentrations to those in the first, we found a hazard ratio (HR) (95% confidence interval (CI)) of 1.77 (1.16-2.70), P trend=0.0033. The same comparison in women had a HR (95% CI) of 1.06 (0.71-1.59), P trend=0.70. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result.

Multiphoton route to ZnO nanowire lasers.

With intense femtosecond laser excitation, multiphoton absorption-induced stimulated emission and laser emission in ZnO bulk crystal and nanowires have been demonstrated at room temperature. UV-stimulated emission peaks appeared in both bulk crystal and nanowires when the excitation exceeded certain thresholds, and a sharp lasing peak with a linewidth of ~0.5 nm was observed from ZnO nanowires. The emission properties were attributed to the band-edge emission of the recombination of carriers excited by two- and three-photon absorption processes in the wide-bandgap semiconductor.

Risk factors for oesophageal squamous dysplasia in adult inhabitants of a high risk region of China.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) is a common cancer worldwide and has a very high mortality rate. Squamous dysplasia is the precursor lesion for OSCC and it can be seen during routine endoscopy with Lugol's iodine staining. We aimed to examine the risk factors for squamous dysplasia and determine if a risk model could be constructed which would be useful in selecting apparently healthy subjects for endoscopic screening in a high risk population in Linzhou, People's Republic of China. SUBJECTS AND METHODS: In this cross sectional study, 724 adult volunteers aged 40-65 years were enrolled. All subjects completed a questionnaire regarding potential environmental exposures, received physical and dental examinations, and underwent upper endoscopy with Lugol's iodine staining and biopsy. Subjects were categorised as having or not having histologically proven squamous dysplasia/early cancer. Risk factors for dysplasia were examined using univariate and multivariate logistic regression. The utility of the final multivariate model as a screening tool was assessed using a receiver operating characteristics curve. RESULTS: We found that 230 of 720 subjects (32%) with complete data had prevalent squamous dysplasia. In the final multivariate model, more household members (odds ratio (OR) 1.12/member (95% confidence interval (CI) 0.99, 1.25)), a family history of cancer (OR 1.57 (95% CI 1.13-2.18)), higher systolic blood pressure OR 1.11/10 mm Hg (95% CI 1.03-1.19)), heating the home without a chimney (OR 2.22 (95% CI 1.27-3.86)), and having lost more but not all of your teeth (OR 1.91 for 12-31 teeth lost (95% CI 1.17-3.15)) were associated with higher odds of having dysplasia. Higher household income (OR 0.96/100 RMB (95% CI 0.91-1.00)) was associated with a lower odds of having dysplasia. Although we found several statistically significant associations, the final model had little ability to accurately predict dysplasia status, with maximum simultaneous sensitivity and specificity values of 57% and 54%, respectively. CONCLUSIONS: We found that risk factors for dysplasia were similar to those previously identified as risk factors for OSCC in this population. The final model did a poor job of identifying subjects who had squamous dysplasia. Other methods will need to be developed to triage individuals to endoscopy in this high risk population.

Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) has a very poor prognosis, which is largely due to late diagnosis. Successful early detection strategies will require identification of clinically relevant precursor lesions that can be targets for screening and treatment. AIMS: To identify the clinically relevant histological precursors of OSCC. SUBJECTS: A cohort of 682 endoscoped patients from a high risk rural population in Linxian, China. METHODS: Subjects were endoscoped and biopsied at baseline and followed for 13.5 years. We estimated the relative risk of developing OSCC for each of the initial histological diagnoses using Cox proportional hazards regression models. RESULTS: A total of 114 (16.7%) patients developed OSCC during the follow up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for incidence of this tumour, by initial histological diagnosis, were: normal 1.0 (reference), oesophagitis 0.8 (0.2-3.2), basal cell hyperplasia 1.9 (0.8-4.5), mild dysplasia 2.9 (1.6-5.2), moderate dysplasia 9.8 (5.3-18.3), severe dysplasia 28.3 (15.3-52.3), and carcinoma in situ 34.4 (16.6-71.4). CONCLUSIONS: In this study, squamous dysplasia and carcinoma in situ were the only histological lesions associated with a significantly increased risk of developing OSCC within 13.5 years after endoscopy. There was no evidence that oesophagitis predisposed to this tumour. Increasing grades of dysplasia were strongly associated with increasing risk, indicating that the histological grading was clinically meaningful. The follow up experience of severe dysplasia and carcinoma in situ was equivalent, suggesting that this distinction is not clinically relevant. Documenting these precursor lesions of OSCC should assist in the development of effective prevention, early detection, and treatment strategies for this disease.

Sphingolipids as biomarkers of fumonisin exposure and risk of esophageal squamous cell carcinoma in china.

OBJECTIVE: Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case-control study to examine the relationship between serum sphingolipids and ESCC incidence. METHODS: Cases and controls were selected from a large prospective trial conducted in Linxian, People's Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up: 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline. RESULTS: No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/ sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use. and alcohol use. CONCLUSION: Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC.

Prospective study of tooth loss and incident esophageal and gastric cancers in China.

OBJECTIVE: To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study. METHODS: Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases. RESULTS: Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1-1.6) in the esophagus, 1.3 (1.0-1.6) in the gastric cardia, and 1.8 (1.1-3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort. CONCLUSIONS: In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines.

A cross-sectional study of human serum sphingolipids, diet and physiologic parameters.

Sphinganine and sphingosine, the two sphingoid base backbones of sphingolipids, are highly bioactive compounds that are of increasing interest to nutritionists because they occur in food and their metabolism can be altered by fungal toxins that contaminate some foods. Nonetheless, no studies of diet and sphinganine or sphingosine concentrations in serum have yet been reported. Here we describe a cross-sectional study of 265 residents of Linxian, People's Republic of China, which examines potential demographic, physiologic and dietary correlates of serum sphinganine and sphingosine in this population. Median concentrations of serum sphinganine and sphingosine were compared among strata for 29 different variables. For sphinganine, no significant differences were found. For sphingosine, significant differences were seen among strata of age, menstruation status, serum cholesterol, carotenoids, retinol, tocopherols, fresh and dried vegetable and fresh fruit consumption. Using multivariate linear regression with stepwise selection, we found that the significant predictors for serum sphingosine included total tocopherols, age, serum selenium and retinol, with a final R(2) = 0.22; for sphinganine, tooth loss was the sole correlate, with R(2) = 0.015. Analyses using ranked sphingolipid data or principal components analysis, to simplify the food variables, did not materially alter these results. This study represents the largest report of human serum sphingolipid concentrations to date and provides insight into potential explanatory variables that can be incorporated into future studies.