[Intraductal carcinomas of the salivary glands: a clinicopathological and molecular genetic analysis of twenty-seven cases].

Objective: To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands. Methods: Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People's Hospital and two cases from Department of Pathology, Henan Provincial People's Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed. Results: There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption. Conclusions: IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.

[Primary synovial sarcoma of lung: a clinicopathological analysis of 12 cases].

Objective: To investigate the clinicopathological features, immunophenotype, molecular features and differential diagnosis of primary synovial sarcoma of the lung (PSSL). Methods: Twelve cases of PSSL were collected at Henan Provincial People's Hospital, during May 2010 and April 2021, and their clinicopathological parameters were summarized. SS18-SSX, H3K27Me3, and SOX2 were added to the original immunomarkers to evaluate their diagnostic value for PSSL. Results: The age of 12 patients when diagnosed ranged from 32 to 75 years (mean of 50 years). There were 7 males and 5 females, 2 left lung cases and 10 right lung cases. Of the 6 patients who underwent surgical resection, five cases were confined to lung tissue (T1), one case had mediastinal invasion (T3), two cases had regional lymph node metastasis (N1), and none had distal metastasis. Microscopically, 11 cases showed monophasic spindle cell type and one case showed biphasic type composed of mainly epithelial cells consisting of cuboidal to columnar cells with glandular and cribriform structures. It was difficult to make the diagnosis by using the biopsy specimens. Immunohistochemistry (IHC) showed CKpan expression in 8 of 12 cases; EMA expression in 11 of 12 case; TLE1 expression in 8 of 12 cases; S-100 protein expression in two of 12 cases; various expression of bcl-2 and vimentin in 12 cases, but no expression of SOX10 and CD34 in all the cases. The Ki-67 index was 15%-30%. The expression of SS18-SSX fusion antibody was diffusely and strongly positive in all 12 cases. SOX2 was partially or diffusely expressed in 8 of 12 cases, with strong expression in the epithelial component. H3K27Me3 was absent in 3 of 12 cases. SS18 gene translocation was confirmed by fluorescence in situ hybridization (FISH) test in all 12 samples. Six cases underwent surgery and postoperative chemotherapy, while the other six cases had chemotherapy alone. Ten patients were followed up after 9-114 months, with an average of 41 months and a median of 26 months. Five patients survived and five died of the disease within two years. Conclusions: PSSL is rare and has a broad morphological spectrum. IHC and molecular tests are needed for definitive diagnosis. Compared with current commonly used IHC markers, SS18-SSX fusion antibody has better sensitivity to PSSL, which could be used as an alternative for FISH, reverse transcription-polymerase chain reaction or next generation sequencing in the diagnosis of PSSL.

[Primary adrenal NK/T cell lymphoma: a clinicopathologic analysis of six cases].

Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.

[Fibrous hamartoma of infancy: a clinicopathological and molecular genetic analysis of 33 cases].

Objective: To investigate the clinicopathological features, immunophenotypic and molecular genetic characteristics and differential diagnosis of fibrous hamartoma of infancy (FHI). Methods: Thirty-three cases of surgically removed FHI were collected from the Department of Pathology, Henan Provincial People's Hospital from October 2011 to December 2020, the clinical and pathologic data with follow-up were collected and analyzed. Next-generation sequencing (NGS) and quantitative real time polymerase chain reaction (q-PCR) were used to study the molecular genetics. Results: The FHI cases occurred in 21 males and 12 females (mean age 16.7 months, range 6 months to 6 years). The sites included trunk (n=21), limb (n=11), and neck (n=1). All patients had painless solitary superficial soft tissue masses, the size was 1.5-9.0 cm (mean 3.8 cm). Microscopically, they were composed of mature adipose tissue, fibroblast/myofibroblast bundle and primitive mesenchymal cells in different proportions; giant cell fibroblastoma-like areas were seen in 14 cases. Immunohistochemistry showed variable expression of EGFR in the spindle cells and primitive mesenchymal components. In most cases, the spindle cells were positive for CD34 and SMA; giant cell fibroblastoma-like areas were strongly positive for CD34; and S-100 protein was expressed by adipocytes in all cases. Ki-67 labeling index ranged 1%-5%. There were recurrent somatic EGFR exon 20 insertion/duplication mutations in six cases tested by NGS, and there were three different mutation types: p.Asn771_His773dupAsnProHis, p.Pro772_His773insProProHis, and p.His773_Val774insThrHis. All the above 6 and another 15 tested cases showed EGFR exon 20 insertion/duplication mutations by q-PCR. Conclusions: FHI is a rare benign fibroblast/myofibroblast tumor. The characteristic histologic feature is organoid triphasic morphology, and the molecular feature is somatic mutation of EGFR exon 20 (insertion/duplication).

[Diagnostic value of combined application of GATA3, SOX10 and p16 in triple negative breast carcinomas].

Objective: To investigate the expression of GATA3, SOX10, and p16 in triple-negative breast cancer (TNBC) and analyze their significance and correlation with clinicopathology. Methods: The expressions of GATA3, SOX10 and p16 in 53 cases of TNBC and 50 cases of non-TNBC were detected by immunohistochemical staining. Results: GATA3 and SOX10 were positive in 58.5%(31/53) and 75.5%(40/53) of TNBC, respectively. The expression of SOX10 was significantly higher than that in non-TNBC (P<0.05). SOX10 was positive in 17 of the 22 cases that lacked GATA3 expression (77.3%). The expression of p16 was significantly higher in the TNBC, and the co-expression with SOX10 was significantly increased (P<0.05). The sensitivity, specificity, and AUC under the ROC curve of SOX10 were higher than those of GATA3. The sensitivity of SOX10 was higher than that of p16, but the specificity was lower than that of p16. The AUC of SOX10 was higher than that of p16. AUC of combined detection of GATA3 and SOX10, SOX10 and p16 were higher than that of each antibody alone (P<0.05). The expression of GATA3, SOX10, and p16 had no significant correlation with age, tumor size, and lymph node metastasis. The expression of SOX10 and p16 in grade 3 and basal-like TNBC increased significantly, and their co-expression increased. Conclusions: The expressions of SOX10 and p16 in TNBC are significantly increased. SOX10 is a reliable marker for the diagnosis of TNBC and a supplement to GATA3. Whether p16 is a marker related to the prognosis of TNBC remains to be further studied.

[Expression of CD200 and INSM1 in gastrointestinal and pancreatic neuroendocrine neoplasms and its diagnostic values].

Objective: To investigate the expression and diagnostic values of CD200 and insulinoma associated protein 1 (INSM1) in gastrointestinal and pancreatic neuroendocrine neoplasm (GIP-NEN). Methods: The expression of CD200, INSM1, Syn and CgA was detected in 69 cases of GIP-NEN, 66 cases of gastrointestinal and pancreatic non-neuroendocrine neoplasm (GIP-nonNEN) and 16 cases of metastatic neuroendocrine neoplasm by immunohistochemistry, to compare the values of CD200, INSM1, Syn, CgA and their combinations in diagnosing GIP-NEN. Receiver operating characteristics (ROC) curve was used. Results: The immunoreactivity of CD200 was present in the cytoplasma and/or membrane of the neoplasms cells, the positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of CD200 for diagnosing GIP-NEN were 95.7% and 78.8%, respectively. There was significant difference of the positive rates of CD200 between neuroendocrine tumor and neuroendocrine carcinoma (P=0.05). The immunoreactivity of INSM1 was present in the nuclei of neoplasms cells. The positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of INSM1 for diagnosis of GIP-NEN were 85.5% and 95.5%, respectively. There were also significantly different positive rates of INSM1 between neuroendocrine tumor and neuroendocrine carcinoma, as well as between G1 and G3 neuroendocrine tumors (P<0.05). There was no difference in the area under ROC curve (AUC) of single stain of CD200, INSM1, Syn or CgA (0.857, 0.907, 0.890 and 0.833, respectively, P>0.05). The sensitivity of combined CD200+INSM1 stains for diagnosing GIP-NEN was significantly higher than that of Syn+CgA (85.5% vs. 63.8%, P<0.05). The AUC of two combinations were 0.962 and 0.925, respectively, which were not statistically different (P>0.05). Conclusions: CD200 and INSM1 are two novel markers of neuroendocrine neoplasm, which aid to diagnosis for GIP-NEN and exclude its mimickers. They are associated with tumor grades. Combining both as an immunohistochemical panel shows high sensitivity and specificity. Thus, the combined panel can be utilized as useful supplement for Syn and CgA.

[MicroRNA-140-5p suppresses cell proliferation and invasion in esophageal squamous cell carcinoma by targeting Glut1].

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.

Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1, by X.-L. Cui, X.-D. Wang, S.-K. Lin, C.-M. Miao, M. Wu, J.-G. Wei, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8449-8455-DOI: 10.26355/eurrev_201910_19157-PMID: 31646575" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19157.