[Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder].

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34ßE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.

[Application and Progress of Convolutional Neural Network-based Pathological Diagnosis of Gastric Cancer].

The incidence of gastric cancer is the highest among all kinds of malignant tumors in China. Because gastric cancer is very hard to identify in its early stage, the early diagnosis rate of gastric cancer in China is relatively low. At present, the pathological diagnosis of gastric cancer mainly depends on the diagnosis of pathologists. However, the gradual improvement of people's living standards and the growing demand for medical and health care have exacerbated the shortage of medical resources, which has become a even more serious problem. Therefore, there is an urgent need for new technologies to help deal with this challenge. In recent years, with the rapid development of artificial intelligence (AI) and digital pathology, AI-aided pathological diagnosis based on convolutional neural network (CNN) as the core technology is showing promises for improving the diagnostic efficiency of gastric cancer. It is also of great significance for the early diagnosis and treatment of the disease and the reduction of its high incidence and mortality. We herein summarize the application and progress of deep-learning CNN in pathological diagnosis of gastric cancer, as well as the existing problems and prospects of future development.

Blood Oxygenation Level-dependent Magnetic Resonance Imaging of Breast Cancer: Correlation with Carbonic Anhydrase IX and Vascular Endothelial Growth Factor.

BACKGROUND: Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is a functional MRI technique which involves using the paramagnetic properties of deoxyhemoglobin to image the local tissue oxygen concentration. The purpose of this study was to investigate whether BOLD-MRI could evaluate hypoxia and angiogenesis of breast invasive ductal carcinoma (IDC). METHODS: Ninety-eight female patients with IDC were retrospectively included in this research. All patients underwent breast BOLD-MRI at 3.0 T before surgery. R2* values of BOLD-MRI were measured. The expression of carbonic anhydrase IX (CA IX) and vascular endothelial growth factor (VEGF) was analyzed by immunohistochemistry. Spearman's correlation analysis was used to correlate R2* value with CA IX and VEGF levels. RESULTS: Heterogeneous intensity on BOLD-MRI images was the main finding of IDCs. The mean R2* value was 52.8 ± 18.6 Hz. The R2* values in patients with axillary lymph node metastasis were significantly higher than the R2* values in patients without axillary lymph node metastasis (t = 2.882, P= 0.005). R2* values increased with CA IX level and positively correlated with the level of CA IX (r = 0.616, P< 0.001); however, R2* value had no significantly correlation with the level of VEGF (r = 0.110, P= 0.281). CONCLUSION: BOLD-MRI could noninvasively evaluate chronic hypoxia of IDC, but not angiogenesis.

Diagnostic value of medical thoracoscopy in malignant pleural effusion induced by non-Hodgkin's lymphoma.

Malignant pleural effusion (MPE) appears in up to 20% of patients with non-Hodgkin's lymphoma (NHL). The present study aimed to assess the efficacy of medical thoracoscopy (MT) in the diagnosis of patients with MPE induced by NHL. Between July 2005 and June 2014, 833 patients with pleural effusions of unknown etiology underwent MT in Beijing Chaoyang Hospital (Beijing, China), where diagnostic thoracocentesis or/and blind pleural biopsy had failed to yield an answer. Demographic, radiographic, thoracoscopic, histological and immunophenotyping data of 10 NHL patients with MPE were then retrospectively analyzed. Under medical thoracoscopy, pleural nodules (in n=6 patients), hyperemia (n=5), plaque-like lesions (n=4), pleural thickening (n=3), cellulose (n=3), ulcer (n=2), adhesion (n=2), and scattered hemorrhagic spots (n=1) were observed on the surface of parietal pleura. Histopathological and immunohistochemical analysis of pleural biopsy samples led to a correct diagnosis of B-cell NHL in 7 patients and T-lymphoblastic NHL in 2 patients. Data from the present study demonstrated that pleural biopsy through MT achieved a definite diagnosis of NHL in 9 out of 10 (90%) patients with MPE induced by NHL. Therefore, MT is a useful method for diagnosing MPE induced by NHL.

Multiple cavernous hemangiomas of the lung.

We present a rare case of multiple cavernous hemangiomas. A 19-year-old girl was seen with dyspnea and fatigue. Thoracic computed tomography showed multiple nodule shadows scattered in the lung. Lung biopsy was carried out. Postoperative histopathologic study identified the nodules as pulmonary cavernous hemangiomas.

Short-hairpin RNA-mediated MTA2 silencing inhibits human breast cancer cell line MDA-MB231 proliferation and metastasis.

OBJECTIVE: To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis. METHODS: A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis. RESULTS: After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression. CONCLUSIONS: For the first time to our knowledge we showed that MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. The role of MTA2 in breast cancer growth and metastasis might be linked with regulation of matrix metalloproteinase and apoptosis.

Effect of Embelin on TRAIL receptor 2 mAb-induced apoptosis of TRAIL-resistant A549 non-small cell lung cancer cells.

INTRODUCTION: Some non-small cell lung cancer (NSCLC) tumor cells are insensitive to tumor necrosis factor- related apoptosis-inducing ligand (TRAIL) -based therapy. This study was conducted to examine the effect of embelin on the sensitivity of the A549 NSCLC cell line to TRAIL receptor2 (TRAILR2) monoclonal antibodies and to investigate the potential mechanisms. MATERIALS AND METHODS: A549 cells were treated with embelin, TRAILR2 mAb or a combination of both. Cell viability was measured using ATPlite assay and apoptosis rates were determined by flow cytometry with AnnexinV-FITC and propidium iodide staining, with the expression levels of proteins analyzed by Western blotting. RESULTS: The cell survival rate of separate treatments with 100 ng/ml TRAILR2 antibody or 25 uM embelin were 81.5±1.57% and 61.7±2.84%, respectively. Their combined use markedly decreased cell viability in A549 cells to 28.1±1.97% (P<0.05). The general caspase inhibitor Z-VAD- FMK could inhibit the embelin-enhanced sensitivity of A549 cells to TRAILR2 mAb (75.97±3.17%)(P<0.05). Both flow cytometry and cell morphological analysis showed that embelin was able to increase TRAIL-induced apoptosis in A549 cells. Combined treatment with embelin and TRAILR2 mAb augmented the activation of initiator caspases and effector caspase. In addition, A549 cells showed increasing levels of TRAILR2 protein and decreasing levels of Bcl-2, survivin and c-FLIP following the treatment with embelin+TRAILR2 mAb. CONCLUSIONS: Embelin could enhance TRAIL-induced apoptosis in A549 cells. The synergistic effect of the combination treatment might be due to modulation of multiple components in the TRAIL receptor-mediated apoptotic signaling pathway, including TRAILR2, XIAP, survivin, Bcl-2 and c-FLIP.

[Expression of glucose transporter protein 1 and desmin in reactive mesothelial hyperplasia and epithelioid malignant mesothelioma].

OBJECTIVE: To investigate the expression of glucose transporter protein 1 (GLUT-1) and desmin in benign and malignant mesothelial lesions, including reactive mesothelial hyperplasia (RMH), epithelioid malignant mesothelioma (EMM) and metastatic adenocarcinoma (MAC). METHODS: One hundred and forty two pleural biopsy specimens were collected in this study, including 58 cases of RMH, 53 cases of EMM and 31 cases of MAC. Immunohistochemical EliVision method was performed to detect GLUT-1 and desmin expression. RESULTS: The positive rates for GLUT-1 in RMH, EMM and MAC were 13.8% (8/58) , 81.1% (43/53) and 77.4% (24/31) , respectively, with statistically significant differences between RMH and others (both P < 0.01). The positive rates for desmin in RMH, EMM and MAC were 77.6% (45/58) , 9.4% (5/53) and 0 (0/31) , respectively, with statistically significant difference between RMH and others (both P < 0.01). The combined expression pattern of positive GLUT-1 and negative desmin was found in 1 (1.7%, 1/58) RMH cases, 41 (77.4%, 41/53) EMM cases and 24 (77.4%, 24/31) MAC cases, with statistically significant difference between RMH and others (both P < 0.01). CONCLUSIONS: GLUT-1 and desmin may be used as immunohistochemical markers in separating RMH from EMM. Combined application of two antibodies may improve the specificity.

Evaluation of ALK rearrangement in Chinese non-small cell lung cancer using FISH, immunohistochemistry, and real-time quantitative RT- PCR on paraffin-embedded tissues.

Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor. Accurate identification of patients with ALK-positive non-small cell lung cancer (NSCLC) is essential for the clinical application of ALK-targeted therapy. However, assessing EML4-ALK rearrangement in NSCLC remains challenging in routine pathology practice. The aim of this study was to compare the diagnostic accuracy of FISH, immunohistochemistry (IHC), and real-time quantitative RT-PCR (QPCR) methodologies for detection of EML4-ALK rearrangement in NSCLC and to appraise immunohistochemistry as a pre-screening tool. In this study, a total of 473 paraffin-embedded NSCLC samples from surgical resections and biopsies were analyzed by IHC with ALK antibody. ALK rearrangement was further confirmed by FISH and QPCR. ALK protein expression was detected in twenty patients (20/473, 4.2%). Of the 20 ALK-positive cases by IHC, 15 cases were further confirmed as ALK rearrangement by FISH, and 5 cases were not interpretable. Also, we evaluated 13 out of the 20 IHC-positive tissues by QPCR in additional to FISH, and found that 9 cases were positive and 2 cases were equivocal, whereas 2 cases were negative although they were positive by both IHC and FISH. The ALK status was concordant in 5 out of 8 cases that were interpretable by three methods. Additionally, none of the 110 IHC-negative cases with adenocarcinoma histology showed ALK rearrangements by FISH. Histologically, almost all the ALK-rearranged cases were adenocarcinoma, except that one case was sarcomatoid carcinoma. A solid signet-ring cell pattern or mucinous cribriform pattern was presented at least focally in all ALK-positive tumors. In conclusion, our findings suggested that ALK rearrangement was associated with ALK protein expression. The conventional IHC assay is a valuable tool for the pre-screening of patients with ALK rearrangement in clinical practice and a combination of FISH and QPCR is required for further confirmation.

[Clinicopathological characteristics and prognosis of malignant pleural mesothelioma].

OBJECTIVE: To investigate the clinicopathological characteristics and prognosis of malignant pleural mesothelioma. METHODS: Thirty patients with malignant pleural mesothelioma diagnosed between January 2006 and June 2012 in our hospital were studied retrospectively. Clinical manifestations, radiological characteristics, endoscopic features, histopathology, and survival status were analyzed. RESULTS: There were 15 males and 15 females, with a median age of 58 years. The commonest clinical symptoms were dyspnea on exertion (26 cases), followed by chest pain (15 cases). The main radiological manifestations were small to large amount of pleural effusions (28 cases), often accompanied by pleural thickening and/or pleural nodules.Of the 30 cases, 25 were diagnosed through medical thoracoscopy and 1 through surgical thoracoscopy. Thoracic lesions manifested as nodules of diffuse distribution on the diaphragmatic pleura and parietal pleura.Some pleural surface was covered with lesions like white tiles.Histopathological examination showed epithelial type in 24 cases, sarcomatoid type in 5 and biphasic type in 1 case.Immonohistological examination showed that the positive rates of calretinin, MC, D2∼40 were 27, 25 and 19 cases respectively.Fifteen patients received chemotherapy, 2 underwent pleurectomy, and 8 were treated with best supportive care. Twenty-four patients were followed for 1 month to 6 years, and 6 patients were lost.Overall survival time was 1-54 months. Those who survived longer than 24 months received chemotherapy with pemetrexed and cisplatin/carboplatin or pleurectomy. CONCLUSIONS: Clinical manifestations of malignant pleural mesotheliome were nonspecific, medical thoracoscopy can make early diagnosis. The pathological diagnosis of malignant pleural mesothelioma was based on immunohistochemical examination, calretinin, MC and D2-40 had positive diagnostic value. Malignant pleural mesothelioma had poor prognosis, chemotherapy with pemetrexed and cisplatin/carboplatin could prolong the survival time of the patients.

[Clinicopathologic features of micropapillary variant of pure mucinous carcinoma of breast].

OBJECTIVE: To study the clinicopathologic features of pure mucinous carcinomas of the breast with diffuse micropapillary pattern. METHODS: Twenty-six cases of micropapillary variant of pure mucinous carcinoma of the breast were retrospectively reviewed by light microscopy, immunohistochemistry and clinical data analyses. RESULTS: The age of 26 female patients ranged from 30 to 77 years old, of which 12 cases with clinical details available were mean 54 years old. The tumor diameter ranged from 0.8 to 9.0 cm (mean 3.2 cm). Ipsilateral axillary nodal metastases were identified in 3 cases. Cutaneous involvement was also found in 2 cases. The tumor cells showed the similar architectural arrangement as in invasive micropapillary carcinoma, with peripheral borders of the cell clusters highlighted by epithelial membrane antigen. Various amount of mucin occupied the retraction spaces around the tumor cells. Compared with conventional pure mucinous carcinoma of the breast, mucinous carcinomas with micropapillary pattern showed different nuclear grades (19 cases of grade I, 2 cases of grade II, 5 cases of grade III). The micropapillary cell clusters varied in size (22 cases of big micropapillary and 4 cases of small). Intraductal carcinoma was observed in 12 cases. Calcification and psammoma bodies were observed in 8 cases. Immunophenotyping, the tumor cells were with higher expression of hormone receptors, but HER2 were negative. Ki-67 positive index was 1% ∼ 70%. Neuroendocrine differentiation was observed in 6 cases. CONCLUSIONS: The micropapillary variant of pure mucinous carcinoma of the breast, which mainly occurs in younger women, may carry the similar propensity for angioinvasion and nodal metastasis as infiltrating micropapillary carcinoma at least in cases with high nuclear grade. This morphologic subtype needs to be distinguished from conventional pure mucinous carcinoma of the breast and treated properly.

Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema.

BACKGROUND: The condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema (CPFE). CPFE has distinct clinical characteristics compared with emphysema alone (EA) and idiopathic pulmonary fibrosis (IPF) without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF. METHODS: Fraction exhaled nitric oxide (Fe,NO) and differential cell counts, the concentrations of monokine induced by interferon gamma (MIG/CXCL9), interferon-inducible protein 10 (IP-10/CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11) were measured in induced sputum obtained from subjects with CPFE (n = 22), EA (n = 22), IPF (n = 14), and healthy volunteers (HV, n = 12). In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects. RESULTS: The CPFE group had higher alveolar NO than subjects in the EA and HV groups (P = 0.009, P = 0.001, respectively) but not than the IPF group (P > 0.05). Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group (P = 0.001, P = 0.008). In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants (P = 0.003, P = 0.004). Immunoreactivity for inducible nitric oxide synthase (iNOS) was higher in the CPFE group than in the EA group (P = 0.018, P = 0.006, respectively). CONCLUSIONS: The pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophil cell infiltration and high NOS expression in alveolar macrophage might participate in this pathogenesis.

Clinical features and imaging findings in pulmonary capillary hemangiomatosis: report of two cases and a pooled analysis.

BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a rare disease and no Chinese case has been reported yet. The disease is often misdiagnosed and its clinical characteristics are incompletely described. The aim of this study was to describe two Chinese cases and to clarify the clinical and radiographic parameters of patients with PCH. METHODS: Two PCH cases were presented and other cases were searched from the English literature. All available clinical and radiographic data were collected from 62 literature reported PCH cases. A pooled analysis of total 64 cases was made. RESULTS: Dyspnea and hemoptysis were the most common clinical symptoms of PCH. Pulmonary hypertension (PH) was found in 78% of the reported cases. PCH typically showed characteristic diffuse or patchy ground-glass opacities (GGOs) and/or multiple ill-defined centrilobular nodules in the computed tomography. CONCLUSIONS: The diagnosis of PCH requires a high clinical suspicion. However, both clinical presentations and radiographic studies often provide clues to the diagnosis, which may prompt early lung biopsy for a definite diagnosis.

[Pulmonary capillary hemangiomatosis: a clinicopathologic analysis of 2 cases with review of literature].

OBJECTIVE: To investigate the clinicopathologic features of pulmonary capillary hemangiomatosis (PCH). METHODS: The clinical and pathologic profiles of 2 PCH cases were evaluated. Immunohistochemical study (EnVision method) was performed on fixed tissues. The biologic behavior was analyzed with follow-up data. RESULTS: The main presenting symptom was dyspnea. Chest radiography of the two cases depicted diffuse, ground-glass nodules, accompanied by enlarged central pulmonary arteries. Microscopically, the most distinctive feature was proliferation of capillary channels within pulmonary interstitium and alveolar walls, accompanied by muscularization of arterioles. Immunohistochemical study showed an abundance of mast cells in the lesion, and staining for platelet-derived growth factor receptor-beta (PDGFR-ß) localized to vascular smooth muscles surrounding the proliferating capillaries and the mast cells. The index of Ki-67 was less than 1 percent and the p53 was negative. CONCLUSIONS: PCH is a rare vascular proliferative disease of yang patients. Increased number of mast cell and the up-regulation of PDGFR-ß may suggest mechanism for PCH. The clinical and radiologic diagnosis of PCH can be very difficult, and the histological examination is regarded as the most reliable means to establish the diagnosis. Pathologists should improve their knowledge on PCH.

Extensively infiltrating colon adenocarcinoma similar to Crohn's disease: a case report.

A 38-year-old Chinese man presenting with chronic diarrhea and secondary incomplete intestinal obstruction was hospitalized in April 2010. Electronic colonoscopy and barium enema examination initially showed longitudinal scar-like strictures and cobblestone appearance in the colon that was similar to those in Crohn's disease. After subtotal colectomy and partial intestinal resection, the pathological examination indicated colon adenocarcinoma that diffusely infiltrated along the colon longitudinal axis rather than the initial diagnosis of Crohn's disease. Pathological examination revealed colon adenocarcinoma with excessive desmoplastic reaction and infiltrating cancer cells along the colon longitudinal axis that may have accounted for the morphological similarities to Crohn's disease in this case. The findings in the present case suggest that colon carcinoma should be considered when Crohn's disease-like findings are encountered, not only in individuals with concurrent cancer in other sites, but also in patients with a long history of gastrointestinal symptoms such as chronic diarrhea or abdominal pain.