Objective:To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) .Methods:A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate.Results:Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ 2=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery ( P<0.05). Multivariate model results showed that positive expression of BAP1 protein ( HR=3.75, 95% CI: 2.23-6.30, P<0.001) and age ≥57 years ( HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion:Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.

Objective:To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) .Methods:A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate.Results:Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ 2=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery ( P<0.05). Multivariate model results showed that positive expression of BAP1 protein ( HR=3.75, 95% CI: 2.23-6.30, P<0.001) and age ≥57 years ( HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion:Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.

Objective:To establish a speech recognition system based on adaptive technology and to evaluate its value in pathological grossing processes.Methods:A total of 600 tissue specimens were collected at the Zhejiang Provincial People's Hospital affiliated to Hangzhou Medical College between October 1, 2020 and December 31, 2020. A speech recognition system based on adaptive technology was used in the pathological grossing processes, and the pathological examination reports were generated and extracted.Results:The speech recognition system based on adaptive technology showed a good recognition rate (overall recognition rate = 77.87%) and helped achieve rapid input and output of pathological examination data.Conclusions:The speech recognition system can reduce the labor costs, improve the work efficiency of pathologists and increase the quality of medical services, which may be valuable for building next-generation smart hospitals.

Objective:To find clues potentially valuable for fighting against infection with human respiratory syncytial virus (HRSV), the differentially expressed genes in HEp-2 cells infected with HRSV were analyzed.Methods:Gene expression profiles of HEp-2 cells infected with HRSV were collected from the public gene expression omnibus (GEO) database. The differentially expressed genes following HRSV infection at each time point of 4, 8, 12, and 15 hours were found using R language. The differentially expressed genes were analyzed by gene ontology (GO), KEGG pathway and protein-protein interaction network (PPI). Genes with relatively high protein interaction in PPI were randomly selected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) verification at the transcription level from HEp-2 cells after HRSV infection at 4 hours.Results:A total of 101 differentially expressed genes were determined, including 92 upregulated genes and 9 downregulated genes. Function enrichment analysis revealed that HRSV infection could cause significant changes in multiple signaling pathways such as immune response in HEp-2 cells. The results of qRT-PCR were consistent with the trend of transcriptome data.Conclusions:The differentially expressed genes and the change of signaling pathways in HRSV-infected HEp-2 cells is of great significance to the studies on pathogenic mechanism and prevention of HRSV infection.

Objective:To develop a convolutional neural network based model for assisting pathological diagnoses on thyroid liquid-based cytology specimens.Methods:Seven-hundred thyroid TCT slides were collected, scanned for whole slide imaging (WSI), and divided into training and test sets after labeling the correct diagnosis (benign versus malignant). The extracted regions of interest after noise filtering were cropped into pieces of 512 × 512 patch on 10 × and 40 × magnifications, respectively. A classification model was constructed using deeply learning algorithms, and applied to the training set, then automatically tuned in the test set. After data enhancement and parameters optimization, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the model were calculated. Results The training set with 560 WSI contained 4 926 cell clusters (11 164 patches), while the test set with 140 WSI contained 977 cell clusters (1 402 patches). YOLO network was selected to establish a detection model, and ResNet50 was used as a classification model. With 40 epochs training, results from 10× magnifications showed an accuracy of 90.01%, sensitivity of 89.31%, specificity of 92.51%, positive predictive value of 97.70% and negative predictive value of 70.82%. The area under curve was 0.97. The average diagnostic time was less than 1 second. Although the model for data of 40× magnifications was very sensitive (98.72%), but its specificity was poor, suggesting that the model was more reliable at 10× magnification. Conclusions:The performance of a deep-learning based model is equivalent to pathologists′ diagnostic performance, but its efficiency is far beyond. The model can greatly improve consistency and efficiency, and reduce the missed diagnosis rate. In the future, larger studies should have more morphology diversity, improve model′s accuracy and eventually develop a model for direct clinical use.

Objective: To investigate the molecular genetic and clinicopathologic characteristics, immunophenotypes, diagnostic and differential diagnostic features of myxoid angiomatoid fibrous histiocytoma (MAFH). Methods: Three cases of MAFH were collected from the archives of Zhejiang Provincial People′s Hospital between January 2015 to August 2018. The clinical and radiologic features, histomorphology, immunohistochemistry, molecular genetics and prognosis were analyzed. Results: Patients consisted of 2 women and 1 man aged 37 years, 46 years, and 57 years, respectively. The clinical manifestations of 3 patients were presented as a painless, slowly-enlarged mass with a duration ranging of 2 weeks, 2 months and 50 years. These tumors were located at the deep somatic soft tissue of extremities or limbs (right hip, left forearm, left wrist, respectively) and 2 were preoperatively considered as ganglion cyst or giant cell tumor of tendon sheath by imaging examinations. The diameter of circumscribed mass lesion was ranged from 3.0 to 7.5 cm, which exhibited a gray white to tan and gelatinous cut surface. Extensive hemorrhage and cystic changes were observed in 2 cases. Under low magnification, all tumors showed a dense fibrous pseudo-capsule with a peritumoral lymphoplasmacytic cuff and a multi-nodular growth pattern. Blood-filled cystic spaces were observed in 2 tumors. The myxoid stroma occupied 60.0%, 80.0% and 90.0% area of the entire tumor, respectively. Within the myxoid areas, tumor cells were oval to stellate and arranged in cord-like, microcystic and reticular growth patterns. Transitions of myxoid tumor components to more solid areas with typical histology of angiomatoid fibrous histiocytoma (AFH) were observed at least focally in all the three cases. The tumor cells exhibited minimal atypia and scarce mitoses (1 to 2/50 HPF) without necrosis, and prominently focal intracytoplasmic vacuoles were identified in one case. The results of immunohistochemistry staining showed that, 2/3 cases focally expressed desmin, 2/3 focally expressed epithelial membrane antigen (EMA), and 1/3 focally expressed CD99. The positive index of Ki67 was approximately 1% to 5%. Fluorescence in situ hybridization analysis showed that EWSR1 gene rearrangement occurred in all of the three cases. During the period of follow-up, one case showed local recurrence at 15 months, one case showed postoperative recurrence at 24 months, and the recurrent tumor slowly grew for 120 months until the second resection, without recurrence at the following 2 months. The left case showed a disease-free survival at 32 months. Conclusions MAFH is a rare subtype of AFH with a low-grade behavior and may lead to diagnostic confusions. Carefully searching for the typical AFH histomorphology and combining with EWSR1 gene rearrangement test can help to distinguish MAFH from other mimickers.

Objective: To detect the clinicopathological features, immunophenotype, diagnosis, and differential diagnosis of composite pheochromocytoma(CP). Methods: Five cases of CP were collected at Zhejiang Provincial People′s Hospital from January 2011 to January 2019. The clinical, radiological, histologic, immunohistochemical and outcome data were analyzed; the diagnosis and differential diagnosis were discussed. Results: The patients′ age range was 52-68 years (mean 59 years, median 54 years), There were 4 males and 1 female, and the male to female ratio was 4∶1. Tumor size was 3-4 cm (mean 3.6 cm, median 3.5 cm). The most common clinical manifestation was adrenal mass. Histologically, the classical feature was two distinct morphologic components, one with tumor cells arranged in irregular nests, and with fine granular and basophilic oramphophilic cytoplasm; the other was composed of scattered ganglion cells in the background of Schwann cells organized in interwoven bundles. The components of pheochromocytoma expressed PHOX2B(5/5), synaptophysin (5/5), CgA (5/5), the sustentacular cells expressed S-100 protein; the components of ganglioneuroma expressed S-100 protein (5/5), NF (5/5), the ganglion cells were weakly positive for PHOX2B, synaptophysin and CgA. All the cases were surgically resected and all patients were free of recurrence at follow-up. Conclusions CP is rare adrenal tumor, and it has typical histologic features but no specific clinical manifestations. Attention should be paid to its characteristic histomorphology with the use of PHOX2B, CgA, synaptophysin and S-100 protein immunohistochemistry that is helpful for its diagnosis.

Objective:To investigate the clinicopathological features,diagnosis and differential diagnosis of renal angiomyolipoma with epithelial cysts(AMLEC).Methods:Four cases of renal AMLEC diagnosed between January 2014 and June 2019 at the Department of Pathology,Zhejiang Provincial People′s Hospital were subjected to clinicopathological, histological and immunohistochemistry analyses along with a literature review.Results:All the four patients were females and aged from 19 to 52 years (mean 34.5 years). Three cases were accidentally discovered by physical examination, and the medical history was 1 to 6 years. The preoperative imaging Bosniak classification was grade Ⅲ in 3 and grade Ⅳ in 1 case. The maximum diameter of the tumor ranged from 2.5 to 9.0 cm (average 5.0 cm). Histologically, all of the 4 tumors showed three histological components: (1) simple epithelial cysts lined by a layer of cuboidal/low-columnar to occasionally, hobnailcells; (2) a thin, compact subepithelial "cambium-like" layer of cellular, mullerian-like short spindle cell stromas with prominent admixedchronic inflammation; (3) a outermost layer of thick, long-fascicles of smooth muscle-like stromas, often surrounded by dysplastic, tortuous thick-walled blood vessels. There was often a prominent lymphatic channel network in the smooth muscle component forming slit like branched and curvilinear spaces. None of the 4 tumors had fat content.Immunohistochemically, the epithelial cells lining the cysts strongly expressed PAX8 and CK7. The subepithelial "cambium-like" stromas strongly expressed melanocytic markers (HMB45, Melan A, Cathspin K, MiTF) and mullerian markers (ER,PR,CD10), and were negative for smooth-muscle markers(SMA,desmin,calponin). The outermost layer of smooth muscle-like stromas strongly expressed smooth-muscle markers, and were only focally positive for melanocytic and mullerian markers. Follow-up information was obtained in 3 cases, among which no evidence of tumor recurrence or metastasis was found at 3, 5, and 66 months of follow-up, respectively.Conclusions:Renal AMLEC is a rare histological subtype of angiomyolipoma with benign biological behavior, and has characteristic histological and immunophenotypic characteristics.Pathologists should be familiar with the clinicopathological appearances of AMLEC and include it in the differential diagnostic spectrums of renal tumors with biphasic epithelial and mesenchymal features.

Objective:To investigate the clinicopathologic features, diagnosis and differential diagnosis of large nested variant of urothelial carcinoma (LNUC) of urinary bladder.Methods:The clinical and pathologic data of five cases of LNUC of urinary bladder diagnosed between January 2014 and December 2018 at the Department of Pathology, Zhejiang Provincial People′s Hospital were analyzed by immunohistochemistry (IHC) and Sanger sequencing. The relevant literature was reviewed.Results:All five patients were male with a mean age of 63 years (range, 48 to 81 years). The mean tumor size was 3.4 cm (range, 1.7 to 4.7 cm). Histologically, the invasive LNUC tumor cells formed medium to large sized nests of varying shapes, from regular round, bulbous, oval to irregularly fused, branched, dumbbell shaped glands, with mild stromal reaction. In all five cases, focal central necrosis and microcystic changes in the tumor nests were identified. Cytologically, the tumor cells were low grade in four cases; the remaining case was overall low grade with focal high grade areas. Mitoses were scarce. All cases possessed surface urothelial tumors, including three low-grade papillary carcinomas, one high-grade papillary carcinoma and one carcinoma in situ. Three of the LNUC were accompanied by small nested variant of urothelial carcinoma and two by conventional high grade invasive urothelial carcinoma. Perineural involvement and angiolymphatic invasion were each noted in four tumors. Radical cystectomy was performed in four cases with TNM stages as followings: pT3aN0M0 in two cases, pT4aN0M0 and pT4aN1M0 in one case each. The remaining case had transurethral bladder resection and was of pT2 stage. By IHC, all five cases were positive for CK7 and p40; four were positive for GATA3; two were positive for CK20; and the mean Ki-67 proliferation index was 18%. TERT promoter mutation status were successfully performed in three cases, with one showing mutation (C228T) and two were wild type. All patients received postoperative chemotherapy. At a follow-up of 2 to 11 months, one patient died of unrelated causes, two patients developed metastases, and two were alive with no evidence of disease.Conclusions:LNUC is a histologic subtype of urothelial carcinoma with deceptively benign features but aggressive behavior, and appreciation of its unique infiltration patterns can aid in diagnosis and differential diagnosis. LNUC tends to coexist with small nested variant of urothelial carcinoma, suggesting these may represent different manifestations of the same urothelial carcinoma subtype.

Objective:To investigate the clinicopathological characteristics, immunophenotypes, and diagnostic and differential diagnostic features of myxoid solitary fibrous tumor (SFT).Methods:Seven cases of myxoid SFT were collected from the archives of Zhejiang Provincial People′s Hospital from January 2014 to December 2019. The clinical features, histomorphology, immunohistochemistry, molecular genetics and prognosis were analyzed and the relevant literature was reviewed.Results:There were three male and four female patients ranging from 32 to 67 years. Locations included the pleura (three cases), pelvic cavity, vagina, parotid gland, and nasal cavity(one each). Tumor size ranged from 2.7 to 13.5 cm. Histologically, all cases were characterized predominantly by the presence of myxoid stroma comprising 55% to 90% of the tumor (mean 72%). The tumors were composed of predominantly stellated, spindled or ovoid cells disposed haphazardly, in loose fascicles, or in anastomosing strands imparting a microcystic/reticular appearance in a extensively myxoid, richly vascularized stroma. Staghorn-shaped branching vessels and thin strands of collagen were commonly seen between tumors cells amidst the myxoid background. These myxoid areas were punctuated by small cellular areas showing diagnostic features of classical SFT, which were present in all seven cases. Areas showing giant cell angifibroma-like change were noted in 2 cases and focal lipomatous metaplasia was identified in 1 case. Atypical features suggestive of aggressive behavior were present in 2 cases and in one of the cases myxoid SFT with high-grade sarcomatous overgrowth was noted. Immunohistochemically, tumor cells in all cases stained positively for STAT6 and CD34. Polymerase chain reaction technique showed in both the examined cases the characteristic NAB2ex4-STAT6ex2 fusion gene. According to the Demicco′s risk assessment model, four cases were classfied as low, one was classified as moderate and 2 was classified as high. Follow-up information was obtained in 4 cases. One tumor recurred 3 times within 48 months after operation, and the other 3 cases had no tumor recurrence and metastasis.Conclusions:Myxoid SFT represents a rare morphologic variant of SFT with biological behaviors ranging from indolent to aggressive. Myxoid SFT should be included in the differential diagnostic spectrums of soft tissue tumors with significantly myxoid change. Carefully searching for the typical SFT histomorphology with the use of immunohistochemistry and if necessary, molecularly testing for NAB2-STAT6 fusion can help to distinguish myxoid SFT from its many mimickers.