Alloys ; Cobalt ; Humans ; Lung ; pathology ; Lung Diseases ; diagnosis ; pathology ; Tungsten

Objective: To investigate the expression of BRD4 in squamous cell carcinoma (SCC) tissues and cells, and the effects of its expression on cell proliferation and invasion ability. Methods: Immunohistochemistry was used to detect BRD4 protein expression in SCC tissues and paired normal esophageal squamous epithelial tissues. The expression of BRD4 protein was detected in different SCC cell lines and normal esophageal squamous epithelial cells by Western blot. BRD4 siRNA and control siRNA were used to transfect SCC Eca109 cells, and experiments were divided into three groups: untreated group, control siRNA group and BRD4 siRNA group. Western blot was employed to investigate the expression of BRD4 protein in the three groups of SCC Eca109 cells. CCK-8 kit was utilized to detect cell proliferation ability, and Transwell chamber was used to examine cell invasion ability. Finally, Western blot was used to detect the expression of MMP2 and MMP9 proteins. Results: The positive rate of BRD4 protein expression in SCC tissues was significantly higher than that of normal squamous epithelial tissues. The expression of BRD4 protein in 4 SCC cell lines was higher than that in normal esophageal cell Het-1A. BRD4 siRNA obviously downregulated the expression of BRD4 protein in Eca109 cells, and its downregulation contributed to the suppression of cell proliferation and invasion ability in Eca109 cells (all P<0.05), coupled with the decreases of MMP2 and MMP9 proteins. Conclusion BRD4 may be closely associated with the proliferation and invasion of SCC, and it thus may be a potential therapeutic target for SCC.

Objective:To investigate the clinicopathologic features and prognosis of mediastinal T lymphoblastic lymphoma/leukemia (T-LBL/ALL).Methods:Sixty-one patients with mediastinal T-LBL/ALL diagnosed at First Affiliated Hospital of Zhengzhou University from August 1, 2011 to December 31, 2018 were enrolled. Their clinical, pathological, imaging features and prognosis were retrospectively analyzed.Results:Of the 61 patients with mediastinal T-LBL/ALL, 46 were male and 15 were female, with a male to female ratio of approximately 3∶1, aged 5 to 71 years (median 24 years, average of 24.5 years). Radiological findings were mediastinal soft tissue masses (58 cases) or mediastinal multiple enlarged lymph nodes (1 case). The tumor had a diameter of 4.9 to 18.3?cm in size, and data of 2 cases was unavailable. The patient′s main symptoms were superior vena cava syndrome (cough, dyspnea, facial or neck edema), shortness of breath and chest pain, while about 1/3 of patients developed B symptoms (high fever, night sweats or significant weight loss). All 61 cases were biopsy specimens, and 2 of the tumors were later resected. Histopathologic examination showed that the thymic tissue epithelial network structure was destroyed or completely disappeared. A large number of lymphocytoid tumor cells were diffusely infiltrative, with infiltration into adipose tissue, starry sky phenomenon, linear-like arrangement, interstitial collagen hyperplasia and tumor cell extrusion. Focal tumor necrosis was present in some cases. Tumor cells were overall small to medium in size. They had little cytoplasm, slightly distorted, round or oval-shaped nuclei, fine chromatin, and innocuous/small nucleoli. Immunohistochemical studies showed that the tumor cells expressed CD7 (100%, 33/33), TDT (93.4%, 57/61), CD99 (83.3%, 25/30), CD1a (4/7), CD10 (8/18), CD34 (13.2%, 5/38), but did not express B cell markers (CD20 and PAX5) or granulocyte monocyte marker (MPO). The Ki-67 proliferation index was usually greater than 50%. One case was tested for TCR clonal rearrangement, which was positive. Several hemotherapy regiments were used. Hyper-CVAD (cyclophosphamide, vindesine, dexamethasone, and epirubicin) were most frequently administrated (60.4%, 32/53), followed by BFM-90 (50.9%, 27/53). Some patients were treated with the above two and other treatment options. Follow-up data were available in 55 of the 61 patients, and 26 patients (47.3%) survived. The average five-year survival rate was 50.6%. The patient′s prognosis was not significantly related to the International Prognostic Index, age of onset, gender, or tumor size.Conclusions:The mediastinal T-LBL/ALL is rare, and most of its specimens are needle biopsies. The histological morphology is often difficult to interpret, while the addition of clinical features and immunohistochemistry may help. The combination of CKpan, TDT, CD99, CD7, CD3, PAX5, CD34, CD10, and Ki-67 immunohistochemicl studies may assist in diagnosis of the most cases.

Objective:To investigate the diagnostic features of pulmonary sclerosing pneumocytoma (PSP) in needle biopsy specimens so as to improve the preoperative diagnostic accuracy and to prevent misdiagnoses.Methods:A total of 79 needle biopsy cases confirmed as PSP in surgical resection specimens were collected in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2015 to January 2023. A retrospective analysis was conducted to investigate the clinical, pathological, and immunohistochemical characteristics of PSP.Results:Among the 79 cases, there were 8 males and 71 females, with an age range of 14 to 67 years (median 47 years). Among the 79 needle biopsy cases of PSP, 5 cases were initially misdiagnosed as adenocarcinoma and 1 as carcinoid preoperatively, while the remaining 73 cases were correctly diagnosed. 84.8% (67/79) of the PSP presented with well-defined, homogeneous, solitary solid tumors on chest imaging. Morphologically, 26.6% (21/79) of the PSP mainly showed a single histological component, 67.1% (53/79) contained two histological components, and 6.3% (5/79) contained three histological components. There were no cases containing all four histological components simultaneously. The tumor was composed of cuboidal cells on the surface and round cells in the stroma and lacked significant cytological atypia and mitotic figures. Some cases exhibited variations in histology and cellular morphology, such as glandular spaces (58.2%, 46/79), sclerotic papillae (46.8%, 37/79), hypercellularity (16.5%, 13/79), and cytological atypia (24.1%, 19/79). Immunophenotyping indicated that both tumor cell types expressed TTF1, EMA and β-catenin, while surface cells expressed pan-cytokeratin and Napsin A, and stromal cells expressed vimentin. In some cases, ER and PR were also expressed.Conclusions:When diagnosing PSP in needle biopsy specimens, the key to avoiding misdiagnosis is recognizing the presence of dual-cell populations within the tumor. The useful clues include presence of cellular papillae, mild cellular atypia, morphological diversity, interstitial foam-like cell aggregates, and prominent background hemorrhage and sclerosis. The characteristic immunophenotype and middle-aged female predilection are also helpful for the diagnosis of PSP.

Background and objective Besides epidermal growth factor receptor (EGFR) mutation, the non-small cell lung cancer (NSCLC) of anaplastic lymphoma kinase (ALK) rearrangement becomes another important clinical subtype. A speciifc and high-sensitive and economical detection way is convenience for identiifcation of ALK positive NSCLC quickly and accurately. So the objective of our research is to detect ALK rearrangement in 172 cases of NSCLC by using enhancing immunohistochemical way (ventana-IHC, V-IHC). Methods ALK rearrangement in 172 NSCLC samples was detected by us-ing V-IHC, and positive staining cases were further veriifed by lfuorescence in situ hybridization (FISH). Results Among 172 NSCLC cases, there were 12 positive staining. hTe positive results were conifrmed by FISH and 11 cases were FISH positive. hTe overall concordance between V-IHC and FISH is 91.7%(11/12). Conclusion hTe V-IHC method is a reliable method for ALK arrangement and could be used in clinical screen and diagnosis.

Objective: To compare the clinical effects between minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) assisted by Microendoscopic discectomy (MED) and Quadrant for the treatment of degenerative lumbar spinal stenosis (DLSS). Methods: All of 59 patients suffered from DLSS treated surgically from May 2015 to October 2017 were reviewed. According to the surgery method, all cases were divided into MED group (27 cases) and Quadrant channel group (32 cases). All patients were followed up for an average of 18.5 months (11-29 months). Comparison was made on the operative time, intraoperative blood loss, postoperative drainage, postoperative time in bed, postoperative creatine kinase (CK), fusion rate and the degree of muscle fibrosis shown in MRI, as well as visual analogue scale (VAS)score and Oswestry dysfunction index (ODI) score in two groups. Results: The duration of operation in MED group was significantly longer than that in Quadrant group (161.7±22.4 min vs. 145.6±19.4 min, t=4.541, P<0. 01), but less intraoperative blood loss (138.1±26.9 ml vs. 155.6±21.5 ml, t=-2.724, P< 0. 01) and shorter time in bed after surgery (2.3±0.7 d vs. 3.5±1.1 d, t=-4.564, P<0.01). Compared with Quadrant group, CK levels were risen slightly on the first and third postoperative day (P<0.01). CK on the fifth postoperative day in both groups returned to normal. VAS score of lower back pain in MED group was lower than that in Quadrant group on the third day and twelfth month after operation (P<0.05). After 3 months, there was no significant difference in VAS score and ODI between the two groups (P>0.05). ODI was lower in MED group than that in Quadrant group after 6 months and 12 months.The fusion rate was88.9%(24/27) in MED group and 93.8%(30/32) in Quadrant channel group. There was no statistical difference in fusion rate of two groups. 10 patients in MED group and 12 patients in Quadrant group underwent MRI examination of lumbar spine one year after operation. The ratio of postoperative and preoperative atrophy of multiplex muscle area was measured. Muscle atrophy of lower back muscle was lighter in MED group (0.12±0.05 vs. 0.22±0.04, t=-2.428, P<0.05). For intraoperative and postoperative complications, 1 case of dural sac rupture occurred in both groups. Gelatin sponge immediately with fibrin glue was used for plugging up, no postoperative cerebrospinal fluid leakage was found. In Quadrant channel group, 1 case had less blood supply of skin incision edges and epidermal necrosis while the other case had fat liquefaction. Conclusion Compared with the aid of Quadrant, MIS-TLIF assisted with MED had less blood loss, less trauma and faster recovery and could reduce the incidence of postoperative incision complication.

Objective:To investigate the clinicopathological features of pulmonary epithelioid hemangioendothelioma (PEHE).Methods:Eighteen cases of PEHE were collected from August 2011 to December 2018 at the First Affiliated Hospital of Zhengzhou University. All cases were retrospectively studied by hematoxylin and eosin staining and immunohistochemistry (IHC). The clinicopathological features were reviewed; the status of CAMTA1 and TFE3 gene was analyzed and patients′ outcome was followed up.Results:Of the 18 cases, there were 11 males and 7 females with a male to female ratio of 1.6 to 1.0. The patients′ age ranged from 36 to 68 years (mean 52 years). Twelve cases (12/18) showed a single nodule and six cases (6/18) showed multiple bilateral nodules. Seven cases (7/18) involved other organs besides lung. Seventeen (17/18) patients presented with respiratory symptoms and one patient (1/18) presented with abdominal pain. Grossly, the tumors were greyish-white nodules with indistinct borders. Microscopically the tumor cells were epithelioid and arranged in strands and nests, and cytoplasmic vacuoles were commonly noted. The stroma was myxochondroid or hyaline. By IHC, the tumor cells were positive for CD31(18/18), CD34 (16/18), ERG (18/18) and Fli-1 (18/18); CKpan was focally positive in 5 cases (5/18). TFE3 was positive in 3 cases (3/18), and Ki-67 index ranged from 5% to 30%. FISH analysis showed seventeen cases (17/18) had CAMAT1 rearrangement, one case had TFE3 rearrangement displaying a split signal. Eight patients (8/18) had surgical excision, three patients (3/18) had surgery and chemotherapy, and seven patients (7/18) had chemotherapy only. Four patients (4/18) died of the disease.Conclusions:Patients with PEHE have non-specific symptoms, and correct diagnosis depends on pathologic biopsy and the exclusion of other tumors with epithelioid morphology. Some patients with PEHE have poor prognosis, particularly in those who have multiple nodules, peripheral invasion or metastasis.

Objective:To investigate the expression of microRNA-140-5p (miR-140-5p) in esophageal squamous cell carcinoma (ESCC) and its role in cell proliferation and invasion of ESCC.Methods:Real-time quantitative PCR (qPCR) was used to detect the expression levels of miR-140-5p in ESCC tissues and cells. Negative control and miR-140-5p mimic were transfected into Eca109 and KYSE70 cells. CCK-8 kit and Transwell assay were employed to examine the changes of cell proliferation and invasion ability after transfection, respectively. The dual-luciferase reporter assay was used to assess the interaction of miR-140-5p with Glut1. Western blot was utilized to detect the Glut1 protein expression after transfection.Results:Analysis of the related GEO datasets revealed that the expression of miR-140-5p in ESCC tissues was significantly lower than that in normal tissues ( P<0.01). The qPCR testing demonstrated that the expression of miR-140-5p in ESCC tissues and cells was markedly lower than that in normal tissues and normal esophageal epithelial cell Het-1A ( P<0.01). The miR-140-5p expression was closely associated with tumor differentiation, TNM staging and lymph node metastasis in ESCC patients. The survival rate of ESCC patients with high miR-140-5p level was higher than those with low miR-140-5p level ( P<0.05). Besides, addition of miR-140-5p mimic significantly upregulated the expression of miR-140-5p in Eca109 and KYSE70 cells, and suppressed cell proliferation and invasion in Eca109 and KYSE70 cells. The dual-luciferase reporter assay showed that Glut1 was a direct target of miR-140-5p in ESCC cells, and its expression was upregulated in ESCC tissues. Glut1 expression was inversely associated with miR-140-5p expression in ESCC tissues. MiR-140-5p mimic dramatically inhibited the expression of Glut1 in Eca109 and KYSE70 cells. Conclusions:MiR-140-5p plays an essential role in ESCC development and progression. Targeting at miR-140-5p/Glut1 may be a novel therapeutic strategy for ESCC patients.

Objective:To investigate the clinicopathological characteristics and genetic mutations of SMARCA4-deficient lung adenocarcinoma.Methods:From January 2021 to April 2023 in the First Affiliated Hospital of Zhengzhou University, 42 cases of SMARCA4-deficienct lung adenocarcinoma were diagnosed and now analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed. Next-generation sequencing (NGS) was performed to investigate the mutations of related genes.Results:Among the 42 cases, there were 35 biopsy and 7 surgical specimens. There were 38 males and 4 females. The male to female ratio was 9.5∶1.0, with an age range from 42 to 78 years. Thirty-three patients were smokers. Overall, 4 cases (9.5%), 2 cases (4.7%), 18 cases (42.9%) and 18 cases (42.9%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Microscopically, all the cases were non-mucinous adenocarcinoma, without lepidic pattern. The morphology was diverse. Rhabdomyoid cells, tumor giant cells and tumor necrosis were present. Most of the tumor cells had eosinophilic cytoplasm and occasionally clear cytoplasm. Defined cell borders and variable cytoplasmic hyaline secretory globules could be found. Inflammatory cells infiltrated the tumor stroma. Immunohistochemistry showed 29 cases (69.0%, 29/42) expressed TTF1, 10 cases (40.0%, 10/25) expressed Napsin A, and 20 cases (100.0%, 20/20) expressed INI1. Forty cases (95.2%, 40/42) showed BRG1 loss in all tumor cells, while 2 cases (4.8%, 2/42) had partial BRG1 loss. PD-L1 (22C3) was positive in 59.2% of the cases (16/27). NGS revealed mutations in EGFR, ROS1, MET, RET and KRAS. Six cases (6/8) showed SMARCA4 mutation, while some cases were accompanied by mutations of TP53 (7/15), STK11 (4/8), and KEAP1 (1/8). Driver gene mutations were more common in women ( P<0.05). Patients were followed up for 1-25 months. Four patients died and 20 patients′ diseases progressed. Conclusions:SMARCA4-deficient lung adenocarcinoma lacks characteristic morphology. Most of them express TTF1 and harbor driver gene mutations. It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.

Objective To investigate the clinical symptoms, imaging features, pathologic manifestations and diagnosis of tracheobronchopathia osteochondroplastica (TO). Methods The clinical data, imaging and pathologic features and outcome of 18 TO patients diagnosed at the First Affiliated Hospital of Zhengzhou University from August 2011 to August 2018 were collected and analyzed. Results The 18 TO patients included 10 males and 8 females; patients′ age range was 31 to 64 years (mean 52 years). Six patients (6/18) were smokers. The main presenting clinical symptoms included cough in 15 cases, expectoration in eight cases (8/18), hemoptysis in five cases (5/18), chest tightness in four cases, wheezing in three cases and chest pain in two cases. The time interval between the initial symptoms and diagnosis was 1.5 to 360.0 months, and the average time interval was 45.2 months. Blood calcium and phosphorus were normal in 18 patients (18/18). Chest X?ray showed no direct evidence of TO. Six patients (6/18) showed irregular changes in the trachea or bronchial wall by chest CT scan. Three patients (3/18) had mild ventilatory obstruction. TO was classified as: 10 cases (10/18) were scattered type, seven cases (7/18) were diffuse type and one case (1/18) was confluent type. Epithelial squamous metaplasia, submucosal cartilage, submucosal ossification and hematopoietic bone marrow within the ossified areas were the characteristic histopathologic findings of TO. Conclusions TO is a rare benign disorder that shows atypical presentation. CT scan is insensitive, the histopathology shows submucosal cartilage or ossification. TO should be diagnosed by comprehensive consideration of clinical symptoms, imaging and pathology.