Purpose To analyze retrospectively the clinicopahological characteristics and immuophenotype in 120 cases of pulmonary selerosing hemangioma ( PSH) . Methods Data of 120 cases of PSH were collected and reviewed, including gross features and frozen diagnosis, histopathological features, morphology in HE and immunohistochemical characteristics of tumor cells. Results PSH pres-ents a well-circumscribed mass with a sense of expansion after cutting, which showed a solid, grey to tan-yellow surface with foci of haemorrhage. Two kinds of tumor cells and four typical patterns with mixed forms, are often shown under light microscope (92/120, 76. 67%). Focal accumulation of histocytes and scattered mast cells were noted in some cases (83/120, 69. 17%). Both surface cells and round cells were TTF-1 and EMA positive. Surface cells expressed SP-A, CK and NapsinA. Round cells expressed vimentin. Conclusion Gross features and typical“two cell types, four patterns” contribute to PSH diagnosis. Meanwhile, foal accumulation of foam histocytes and scattered mast cells show a clue to PSH diagnosis and differential diagnosis.

The mechanism of irritable bowel syndrome (IBS) is still incompletely understood in the world although large amount of investigations have been carried out on it. There are many studies on the pathophysiology of IBS in China, which has huge amount of population suffering from IBS with special ethnicity and culture, including Mainland China, Hong Kong and Taiwan. We collected the literatures to show the results and discuss whether there were any differences in the pathophysiologic findings between China and other countries, whether there were any differences among different subtypes and how the pathophysiology correlated with the manifestations of patients. Gene polymorphism, disturbances of gastrointestinal motility, visceral hypersensitivity, intestinal infection and inflammation, psychological disturbances, food hypersensitivity and intolerance, and altered gut microflora were reviewed in this paper. Some conflicting outcomes between China and other countries were noted although most of them were similar.
China ; Food Hypersensitivity ; Gastrointestinal Motility ; Hong Kong ; Humans ; Hypersensitivity ; Inflammation ; Irritable Bowel Syndrome ; Stress, Psychological ; Taiwan

Objective: To compare droplet digital PCR (ddPCR) and Super-amplification refractory mutation system (ARMS) in the detection of T790M mutation of epidermal growth factor receptor (EGFR) in the plasma of non-small cell lung cancer patients who had developed resistance to EGFR tyrosine kinase inhibitor (TKI) , and to investigate the clinical application of ddPCR. Methods: Plasma samples were collected from non-small cell lung cancer patients who had acquired EGFR-TKI resistance at Shanghai Pulmonary Hospital, Tongji University, from May 2017 to November 2017. Extracted ctDNA was analyzed by ddPCR and Super-ARMS to evaluate the T790M mutation status of EGFR gene. Results: A total of 37 patients with activating EGFR mutation that acquired resistance to EGFR-TKI were selected in the study, including 17 male and 20 female with a median age of 64 years (range 40-83 years). Before TKI treatment, all the patients harbored EGFR inhibitor sensitive mutations but without T790M mutation. After acquiring resistance to EGFR-TKI treatment, the T790M mutation rate detectable by ddPCR was 45.9% (17/37). In contrast, the mutation rate of T790M detectable by Super-ARMS was 35.1% (13/37, P<0.05). For the 13 positive cases detected by Super-ARMS (ΔCt<8), they were all positive by ddPCR assay; Among the 10 negative cases detected by Super-ARMS (ΔCt≥8), there were 3 cases positive by ddPCR assay. For patients without ΔCt by Super-ARMS assay, there was one weak positive case detectable by ddPCR assay. Among 17 EGFR T790M positive patients, 9 received EGFR inhibitor Osimertinib treatment, and 7 of them had good therapeutic response after the treatment. Conclusions While a significant correlation between the two methods is shown. ddPCR is more sensitive than Super-ARMS in the detection of EGFR T790M mutation, indicating that it is a better method in guiding target drug therapy of non-small cell lung cancer patients after acquiring the resistance to EGFR-TKI.

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.

Objective To investigate the clinicopathological features and epidermal growth factor receptor ( EGFR ) gene mutation of primary pulmonary mucoepidermoid carcinoma ( PMC ).Methods Fifth-five cases of PMC were included in the study;their clinicopathological, immunohistochemical features were evaluated, and in 31 cases, paraffin embedded specimens were subjected to mutation analysis of exons 18, 19,20 and 21 of the EGFR gene by ARMS method.Results There were 32 females and 23 males.The patients′age ranged from 11 to 68 years( mean 36 years).The tumor size ranged from 0.7 to 5.5 cm( mean 2.4 cm).The tumors were located in the segmental bronchus and upper segmental bronchus.The tumors were well-demarcated, had no obvious capsules, and protruded into the bronchial lumen.Microscopically, there were three types of tumor cells including squamous cells, mucin-producing cells and intermediate cells.Fifty-three cases were low grade, two were high grade and both showed lymph node metastases.Immunohistochemically the tumor cells were uniformly negative for TTF1, Napsin A and ALK ( Ventana D5F3) in all 55 cases.The tumor cells were positive for CK7, and some squamous and intermediate cells were positive for p63 and CK5/6 in all 55 cases;whereas they were positive for p40 in 53 cases.The mucin-producing cells were negative for CK5/6, p63 and p40, but were positive for PAS in all 55 cases.The Ki-67 positive rate was <10%in the low grade PMC, and was about 80%-90%in the high grade cases.Follow-up information was available in 37 patients, with no recurrence or death.There were no EGFR gene mutations in all 31 patients of PMC.Conclusions PMC is a rare malignant salivary gland-type tumor occurring mainly in the central trachea of young patients.Most PMCs are low grade with good prognosis.The rate of lymph node metastasis of high grade PMC is high.Diagnosing PMC in small biopsies could be problematic.The lack of TTF1 expression is helpful to differentiate from other primary lung cancers.There is no EGFR gene mutation in PMC.

Objective To investigate the effects of lentivirus-mediated RNA interference (RNAi) targeting DNA binding protein A (dbpA) on the proliferation and the biological behavior of colorectal cancer cell line SW620.Methods The experiment was divided into 3 groups:KD group (siRNA-dbpA,lentivirus interference group),CON group (non-specific sequence group) and NC group (blank control group).The lentiviral vector siRNA-dbpA was constructed and verified by PCR and DNA sequencing.SW620 cells were transfected with siRNA-dbpA plasmid,nontargeting siRNA plasmid,or empty plasmid.After 48 h the transfection,the cells were examined for dbpA expression using Western blot.After 72 hrs transfection,flow cytometry was used to detect the cell apoptosis and cell cycle changes.The cell growth inhibition rate was detected by MTT (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay,and then clone formation was detected,and the ability of SW620 cells to form tumors in vivo after dbpA was silenced was studied in nude mice.Results PCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting dbpA gene was successfully inserted into the lentiviral vector.siRNA-dbpA transfection resulted in reduced expression of dbpA in SW620 cells.After transfection,the apoptosis rate of siRNA-dbpA-transfected cells increased to 26.60％ ± 0.38％,significantly higher than that in cells transfected with the nontargeting plasmid or the empty plasmid 12.54％ ± 0.25％ and 4.46％ ± 0.19％,respectively (F =28.159,P ＜0.01).The growth inhibition test indicate that the OD value of the fifth day in siRNA-dbpA group was 0.194 ±0.037,significantly lower than that in the other two groups 0.814 ±0.043 and 1.625 ±0.061,respectively(F =23.214,P ＜ 0.01).The colony formation number is 37 ± 3,64 ± 5and 175 ± 10 respectively,siRNA-dbpA is significantly higher than that in the other two groups(F =40.254,P ＜ 0.01).After the completion of nude mouse transplantation tumor model,through the detection of tumor volume,KD group (group siRNA-dbpA) tumor volume after 14 d and CON and NC group had obvious difference (F =38.256,P ＜ 0.05),and after 21d is more significant difference in tumor size (F =40.241,P ＜ 0.01),can be clearly observed after 35 d KD group (group siRNA-dbpA) growing tumors had differences with the control group (F =30.257,P ＜ 0.05).Conclusion Lentivirus-mediated RNAi targeting dbpA can effectively suppress the expression of dbpA in colorectal tumor in nude mice,it is proved that dbpA silencing has a significant inhibitory effect on the growth of living tumor cells and decrease the proliferation of the colorectal cells.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of primary pleural epithelioid hemangioendothelioma (EHE).Methods:Five cases of pleural EHE diagnosed from 2012 to 2019 in the Shanghai Pulmonary Hospital of Tongji University, China, were collected. They were subjected to review of clinical and image data, reevaluation of histological sections, immunohistochemistry study, clinical follow up and literature review.Results:There were 1 male and 4 females (male to female ratio of 1∶4). The age ranged 19?58 years, with a median age of 52 years. There was no smoking history in all 5 cases. Clinical manifestations included chest distress, chest pain, cough and hemoptysis. CT scan showed pleural effusion, pleural thickening, multiple pleural nodules and pneumothorax. All of the 5 cases were diagnosed based on thoracoscopic biopsies, which were performed for the suspicion of malignancy in 3 cases and for the suspicion of tuberculosis upon the failure of anti-tuberculosis treatment in 2 cases. Histologically, the tumors grew in the mesenchyme, forming cords, nests and solid sheets. The tumor cells were round, oval, short spindle, and polygonal in shape. They were epithelioid and had abundant cytoplasm and prominent nucleoli. Blister cells (vacuoles in cytoplasm) could be seen, and for mednewly-generated vessel lumen. Mucoid degeneration and collagenization were common in the tumor stroma. The positive-stainin grate was 5/5 for vimentin, 5/5 for D2-40, 4/5 for CD31, 4/5 for ERG, 4/5 for CAMTA1, 2/5 for CD34 and 2/5 for CKpan. WT1, calretinin and CK5/6 were all negative. The follow-up time ranged from 4?18 months. During the follow-up, 4 patients were treated with chemotherapy (2 patients died, and 2 survived with tumor), and 1 patient lost to the follow-up.Conclusions:Primary pleural EHE is rare. Its imaging and clinical features are very similar to those of tuberculosis. The correct diagnosis relies on pathological biopsy. Tumor cells are epithelioid. When CD34 is negative and D2-40 is positive, it is easy to be misdiagnosed as malignant mesothelioma. The combination of CD31, ERG and CAMTA1, which have high specificity of EHE, is helpful for the differential diagnosis.

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.

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.

Objective To study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung ( SCLC ).Methods Immunohistochemical study for squamous cell markers (p63, p40 and CK5/6), neuroendocrine markers (chromogranin A, synaptophysin and CD56) and TTF1 was carried out in 283 cases of SCLC.The diagnostic value of these markers was evaluated.Results The expression rate of p63, p40 and CK5/6 were 20.7% (54/261), 7.9% (5/63) and 0.5% (1/221), respectively in the cases of SCLC studied.Amongst the squamous cell markers, CK5/6 had the lowest rate of positivity ( P <0.01 ).On the other hand, chromogranin A, synaptophysin and CD56 were positive in 61.8%( 170/275 ) , 85.5% ( 242/283 ) and 89.2% ( 248/278 ) , respectively.The positivity rate for chromogranin A was lower than that for synaptophysin and CD56 ( P <0.01 ).TTF1 was expressed in 77.2%(217/281).Conclusions p63 and p40 are expressed in a subset of SCLC.In contrast, CK5/6 is rarely positive in SCLC.An immunohistochemical panel of CK5/6, synaptophysin and CD56 is recommended for differential diagnosis of SCLC.