ObjectiveTo investigate the continuous pathological features of biopsy specimens from five cases of small bowel allotransplantation (SBT) in order to provide more reliable information for the diagnosis and treatment of acute rejection (AR) in SBT.Methods324 biopsy specimens of intestinal mucosa after SBT from 5 patients were collected and studied by histology,histochemistry and electron microscopy.ResultsIn the early stage after operation (0～3 months),AR IND-1 grade was diagnosed for four times on 3 of 5 patients.During 3-6 months,AR IND-1 grade for three times was diagnosed in 2 cases,and AR 2 grade for two times during 7 ～ 12 months. All the patients suffered ischemia reperfusion injury, lymphatic vessel reconstruction and AR.Conclusion The pathological examination of biopsy specimens of intestinal mucosa is still the most reliable detecting method to diagnose AR,and continuous observation may play an important role to monitor the occurrence,development,and treatment response of AR. The final diagnosis of AR depends on structure of intestinal mucosa,crypt epithelium injury and inflammatory cells infiltration. The communication among the pathologist and surgeon is the best way to reduce misdiagnoses.Ultrastructural examination is used to verify the pathogenic microorganism.

Purpose To investigate the clinicopathologic features, diagnosis and differential diagnosis of ovarian juvenile granulosa cell tumor (JGCT).Methods The history records, pathologic features and immunophenotype of 8 cases of JGCT were retrospectively evaluated and their prognosis was achieved by follow-up.Results The age of patients ranged from 6～21 years old,with an average age of 15.1 years.The main clinical manifestations included an abdominal mass, ascites and isosexual pseudoprecocity. Cut surface of the tumor was typically solid with cysts formed. The histopathological changes displayed solid nests, diffuse sheet, multiple round or ovoid follicles in variable size.Macrofollicles could be seen in some cases.The follicular pattern consisted of small cystic cavities containing eosinophilic secretions. The tumor cells were round or polygonal, medium in size. The tumor cells had abundant pale or slightly eosinophilic cytoplasm, round nuclei with fine chromatin. Nuclear grooves were inconspicuous.Mitosis figures could be found. Immunohistochemical results showed that the tumor cells expressed inhibin-α,CD99,vimentin; while Melan-A,calretinin and S-100 were positive staining in part of the cases.CKpan,EMA,PLAP,Syn and CgA were negative in all the cases.Conclusions Ovarian juvenile granulosa cell tumor is a rather rare, low malignant tumor with good prognosis. Its diagnosis depends on the histologic and immunohistochemical findings and clinical features. Its differential diagnosis includes adult granulose cell tumor, hypercalcaemic type small cell carcinoma, carcinoid and dysgerminoma.

Objective: To improve the limitation and stability of tissue processing on mucosa from small intestine transplantation and to provide better evidence of pathological diagnosis for the acute rejection on small intestine transplantation. Method:92 samples of mucosa from small intestine transplantation were reviewed.There were three methods of tissue processing (ultrasonic wave and microwave as well as routine) were adopted.The results were analyzed with statistical methods. Results: Among 18 samples processed by the method of ultrasonic wave,4 samples were A grade (22.22%). Among 50 samples processed by the method of microwave,30 samples were A grade (60.00%). Among 24 samples processed by the method of routine,13 samples were A grade (54.17%).The Chi Square Test suggested that there was statistic difference among three processing methods. Conclusions: Microwave is the best method of tissue processing on mucosa of small intestine transplantation and for the diagnosis acute rejection.

Objective:To investigate the effects of miR-125b on radiosensitivity of cervical cancer cells and its possible downstream mechanism.Methods:The expression of miR-125b and Foxp3 in cervical cancer tissues and cells was detected by RT-qPCR. The HeLa cells were irradiated with 0, 2, 4 and 6 Gy of X-rays. The expression of miR-125b and Foxp3 in each group was detected by RT-qPCR. After downregulation of miR-125b expression and 6 Gy X-ray irradiation, the proliferation ability of HeLa cells was detected by MTT assay, and the expression of Bax and Bcl-2 proteins were detected by Western blot. The relationship between miR-125b and Foxp3 was detected by Targetscan and Dual luciferin reporter assay. After downregulation of Foxp3 expression and 6 Gy X-ray irradiation, the proliferation ability of HeLa cells was detected by MTT assay, and the expression of Bax and Bcl-2 proteins were detected by Western blot. The effects of miR-125b on radiosensitivity of HeLa cells through Foxp3 were detected. After down-regulation of Foxp3, the contents of IL-10 and TGF-β in supernatant were detected by ELISA.Results:The expression of miR-125b in the tissues and cells of cervical cancer was significantly decreased, while the expression of Foxp3 was significantly increased. The expression of miR-125b in HeLa cells was increased after radiation in a dose dependent manner. The expression of Foxp3 in HeLa cells was decreased after radiation in a dose dependent manner. After 6 Gy X-ray irradiation of HeLa cells, down-regulation of miR-125b increased the cell proliferation capacity, significantly reduced the expression of Bax and increased the expression of Bcl-2. miR-125b targets Foxp3 and negatively regulates Foxp3 expression. After 6 Gy X-ray irradiation of HeLa cells, down-regulation of Foxp3 significantly reduced the proliferation capacity of HeLa cells, increased the expression of Bax and decreased the expression of Bcl-2. Overexpression of miR-125b can enhance radiosensitivity of HeLa cells through Foxp3.After 6 Gy X-ray irradiation, down-regulation of Foxp3 reduced the expression of IL-10 and TGF-β in cells.Conclusions:Upregulation of miR-125b enhances the radiosensitivity of cervical cancer cells by targeting and negatively regulating Foxp3, and the mechanism of that may be related to the down-regulation of Foxp3 to reduce the expression of IL-10 and TGF-β in the cells.

OBJECTIVETo investigate the clinicopathological features and prognosis of 22 cases of central neurocytoma (CNC), representing 0.48% of a series of 4 528 patients undergoing biopsy for central nervous system tumors.

METHODSThe histopathological, ultrastructral, immunohistochemical and clinical features of CNC were studied by electron microscopic examination and immunohistochemical stain for Synaptophysin (Syn), neuron special enolase (NSE), Leu-7, glial fibrillary acid protein (GFAP), MBP and proliferating cell nuclear antigen (PCNA).

RESULTSThe age of the cases ranged from 4 to 44 (average 27.9 years) with all tumors localized in the ventricles. In the 18 patients followed up, 14 were alive for 8 months to 14 years and 11 months after the operation, and 4 died. The average survival period was 70.7 months. Histologically, the tumor in all 22 cases had the oligodendroglioma-like pattern with honeycomb appearance and cell-free islands of eosinophilic matrix. Cellular anaplasia, mitosis and necrotic areas were rarely seen in the tumors. Immunohistochemical study demonstrated strong positivity for Syn, NSE and Leu-7, and negative for GFAP and MBP. Ultrastructural features showed presence of round tumor cells with abundant cell processes containing microtubules, neurosecretory granules, clear vesicles and lysosome-like structures.

CONCLUSIONSThe differential diagnosis between CNC and oligodendroglioma could not be established by routine light microscopy. The importance of immunohistochemical and electron microscopic studies for making a correct diagnosis is emphasized. The prognosis of patients is usually favorable, even if the tumor was resected subtotally. The relationship between the presence of anaplastic histological features in CNC and patient outcome remains unclear.

Adolescent ; Adult ; Biomarkers, Tumor ; Brain Neoplasms ; metabolism ; pathology ; physiopathology ; CD57 Antigens ; metabolism ; Child ; Child, Preschool ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Male ; Microscopy, Electron ; methods ; Neurocytoma ; metabolism ; pathology ; physiopathology ; Phosphopyruvate Hydratase ; metabolism ; Prognosis ; Proliferating Cell Nuclear Antigen ; Synaptophysin ; metabolism

Objective: To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB. Methods: Immunohistochemical (IHC) EnVision method was used to detect the expression of H3.3 G34W mutant-specific antibody and p63 in 83 GCTBs, 18 aneurysmal bone cysts, 23 chondroblastomas and 28 osteosarcomas diagnosed at Nanjing Jinling Hospital from June 2001 to April 2019. Results: Among the 83 cases of GCTB, 69 cases (69/83, 83.1%) expressed H3.3 G34W. H3.3 G34W expression was found exclusively in the mononuclear cell population with strong and diffuse nuclear staining. H3.3 G34W was expressed in 55 of 57 (96.5%) cases of GCTB in long bones, but only 14 of 26 (53.8%) cases of non-long bone GCTB. All recurrent (9/9)/metastatic GCTB (2/2), post-denosumab GCTB (3/3), primary malignant GCTB (3/3) and secondary malignant GCTB (5/5) also expressed H3.3 G34W. H3.3 G34W was negative in all aneurysmal bone cysts and chondroblastomas. H3.3 G34W was positive in 3 of 28(10.7%) cases of osteosarcomas, and giant cell-rich osteosarcoma(GCRO) was the only histological subtype of osteosarcoma that expressed H3.3 G34W. p63 was expressed in 71.1%(59/83) of GCTB, while the positive rates of p63 in aneurysmal bone cysts,chondroblastomas and osteosarcomas were 3/18, 43.5% (10/23) and 21.4% (6/28) respectively. The sensitivity and specificity of H3.3 G34W mutant-specific antibody in the diagnosis of GCTB were 83.1% and 95.7%. Conclusions H3.3 G34W mutant-specific antibody is a highly sensitive and specific marker for GCTB and helpful for the diagnosis of GCTB and its variants. The limitation of this antibody is that as a mall number of GCTB harbor G34 mutation other than G34W, and thus that cannot be detected. The incidental expression of H3.3 G34W mutant protein in osteosarcoma could be a potential diagnostic dilemma, and the results of H3.3 G34W IHC staining needs careful interpretation.

Objective:To investigate the expression and diagnostic value of SS18-SSX fusion-specific antibody and SSX C-terminal antibody in synovial sarcoma (SS).Methods:Immunohistochemical (IHC) EnVision method was used to detect the expression of SS18-SSX fusion-specific antibody and SSX C-terminal antibody in 51 genetically confirmed cases of SS and 94 non-SS tumors diagnosed at Nanjing Jinling Hospital from August 2013 to December 2020.Results:IHC staining for SS18-SSX fusion-specific antibody revealed strongly diffuse nuclear staining in 48 of 51 (48/51, 94.1%) SS cases, whereas none of the 94 non-SS tumors showed any staining. IHC staining for SSX C-terminal antibody showed strongly diffuse nuclear staining in all 51 (51/51, 100%) SS cases; six of the 94 (6/94, 6.4%) non-SS tumors showed variable staining, including two cases each of leiomyosarcoma and fibrosarcoma, and one case each of malignant peripheral nerve sheath tumor and embryonal rhabdomyosarcoma. The sensitivity and specificity of SS18-SSX fusion-specific antibody in diagnosing SS were 94.1% and 100% and these of SSX C-terminal antibody were 100% and 93.6%, respectively.Conclusions:SS18-SSX fusion-specific antibody and SSX C-terminal antibody are highly sensitive and specific markers for SS. Immunohistochemistry using these antibodies may replace FISH or molecular genetic testing in most cases.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective To study the expression of cadherin 17 ( CDH17 ) in metanephric adenoma ( MA ) , and to explore the value of CDH 17 in the diagnosis of metanephric adenoma.Methods Immunohistochemical EnVision method was used to detect the expression of CDH 17, WT1, CD57, P504S and EMA in 21 cases of MAs, 16 epithelial-predominant Wilms tumors ( e-WT), and 20 solid variant of papillary renal cell carcinomas ( s-PRCC).The expression of CDH17 was also examined in other common renal epithelial tumors , including 10 cases of clear cell renal cell carcinomas ( CCRCC ) , 10 chromophobe renal cell carcinomas ( CHRCC), and 10 oncocytomas.Results Twenty (95.2%) of 21 cases of MAs demonstrated membranous CDH 17 immunoreactivity in all components ( acinar , tubular , and papillary ) , whereas only 1 (1/16) e-WT was positive for CDH17 and all s-PRCCs were negative ( P<0.05).WT1 was negative in s-PRCC and was positive in all cases of e-WT ( 16/16 ) and MA ( 100%,21/21 ).All MAs (100%) were strongly positive for CD57;however, this marker was also positive in 13 (13/16) e-WTs and 9 (45.0%,9/20) s-PRCCs.P504S was strongly positive in all s-PRCCs (100%), but reactivity was seen in 3 (14.3%,3/21) MAs and all e-WTs were negative.The positive rates of EMA in MAs, e-WTs and s-PRCCs were 19.0%(4/21),14/16 and 17/20, respectively.The sensitivity and specificity of CDH17 in the diagnosis of MA were 95% and 97%.CDH17 was negative in all cases of CCRCC , CHRCC and oncocytoma.Conclusions CDH17 is a highly sensitive and specific marker for MA and should be considered in the immunohistochemistry panel for distinguishing MA from its mimics and other common renal epithelial tumors.