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Cardiac undifferentiated pleomorphic sarcoma (UPS) is a rare malignancy. Several studies have revealed frequent MDM2, CDK4, PDFGRA, and KIT amplifications and CDKN2A and CDKN2B deletions. Cases lacking the above copy number alterations may harbor alternative driver mutations; however, little is known about such occurrences. This study was conducted to gain further insights into the molecular features of cardiac UPS using targeted sequencing of 560 cancer-related genes, and fluorescence in situ hybridization and immunohistochemistry of MDM2, CDK4, CDKN2A, TP53, and RB1 in 9 cardiac UPS cases. TP53 mutation or CDKN2A deletion was found in cases lacking MDM2 amplification. Further, p53 overexpression was detected in the case with TP53 mutation, while p16 expression was completely lost in the case with CDKN2A homozygous deletion. p16 overexpression was found in cases with MDM2 and CDK4 amplification but without CDKN2A deletion. Immunohistochemistry of MDM2, CDK4, p53, and p16 is expected to be preliminarily used for gene status analysis. As cardiac UPS and intimal sarcomas are merging into a single spectrum, mutation data for 3 cardiac UPS and 9 intimal sarcomas from the literature, as well as data for 5 cardiac UPS in our study were evaluated, and known recurrently mutated cancer driver genes, including PDGFRB, TP53, ALK, PTCH1, RET, ERBB4, JAK3, GATA1, PIK3CG, and RARA, were identified. Several new potentially actionable mutations, including those in RARA, ALK, PTCH1, RET, ROS1, ABL1, and MET, were also found. These findings improve the molecular understanding of this rare malignancy and are expected to provide a basis for developing precision therapeutics for cardiac UPS and intimal sarcomas.

Triple-negative breast cancer (TNBC) is a common hypotype of breast cancer. Circular RNAs (circRNAs) are burgeoning serve as vital controllers in numerous tumors. Nevertheless, the expression and regulatory mode of circRNAs in TNBC are still indistinct. This paper aimed to reveal the function and molecular mechanism of circular RNA dehydrodolichyl diphosphate synthase (circDHDDS) in TNBC.The contents of circDHDDS, DHDDS mRNA, microRNA-362-3p (miR-362-3p) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were executed to assess cell proliferation. The flow cytometry assay was utilized to detect cell apoptosis. The transwell assay and tube formation assay were applied to measure cell migration, invasion and angiogenesis. The targeted relationships of miR-362-3p and circDHDDS or DDX5 were forecasted and detected by dual-luciferase reporter assay. The in vivo test was implemented to confirm the effect of circDHDDS.The contents of circDHDDS and DDX5 were increased, and miR-362-3p level was decreased in TNBC. CircDHDDS deficiency reserved cell proliferation, migration, invasion and angiogenesis, while facilitated cell apoptosis in TNBC cells. Furthermore, miR-362-3p was validated to exert a tumor repressive effect in TNBC cells by suppressing DDX5. Moreover, DDX5 could regulate the development of TNBC. The experimental data exposed that levels of miR-362-3p presented noteworthy negative correlation with circDHDDS and DDX5, while circDHDDS and DDX5 exhibited significant positive correlation. In mechanism, circDHDDS bound to miR-362-3p to modulate DDX5 expression. In addition, circDHDDS knock-down also attenuated tumor growth.CircDHDDS expedited TNBC by swelling DDX5 via adapting miR-362-3p.

Objective Because of their rarity, it is not known whether isocitrate dehydrogenase 2 (IDH2) mutations are related to olfactory neuroblastoma. We investigated relationships between IDH2 mutations, clinicopathological parameters, and prognosis for olfactory neuroblastoma to establish a molecular classification based on IDH2 mutations. Materials and methods An 82-patient cohort was retrospectively screened by immunohistochemistry using a mutation-specific IDH2 antibody and by real-time PCR for IDH2 mutations. We also determined immunohistochemically the expression of chromogranin A, synaptophysin, neuron-specific enolase, CD56, S100, and Ki67. Results The two methods for detection of IDH2 mutations had high consistency. Mutation of IDH2 detected by real-time PCR was correlated with higher Kadish stage, Hyams grade, and Ki67 proliferation index. Mutation of IDH2 was negatively correlated with expression of chromogranin A, synaptophysin, CD56, and S100. Kaplan-Meier analysis showed that an IDH2 mutation, high Hyams grade, and Ki67 index were associated with poor overall survival. Hyams grade and IDH2 mutation were independent prognostic factors in multivariable analysis. Conclusions Immunohistochemistry was a reliable method to assess the mutation status of IDH2. Tumors with IDH2 mutations represented a distinct subset with aggressive behavior and poor prognosis. The gene status of IDH2 can be a major molecular classification criterion in olfactory neuroblastoma.

Background As a rare salivary gland malignancy, clear cell carcinoma (CCC) is easily misdiagnosed. This study identified the features that allow better recognition of the clinicopathological and molecular characteristics and the prognosis of CCC, focusing on high-grade transformation (HGT) in this tumor and cases arising in uncommon sites. Methods Clinicopathological and follow-up data for 10 CCC samples were retrieved. Immunohistochemical (IHC) staining was performed, and fluorescence in situ hybridization (FISH) was used to detect EWSR1 gene rearrangements, EWSR1–ATF1 gene fusions, and MAML2 gene rearrangements. Results Histologically, typical CCCs comprised bland polygonal or round cells with clear cytoplasm. In contrast with typical CCCs, HGT tumor cells exhibited nuclear pleomorphism, high nuclear-to-cytoplasmic ratios, high mitotic activity, and necrosis. Rare morphologic features such as pseudopapillae, gland-like spaces, and entrapped ducts were also observed. Occasionally, tumors involving the oral cavity might arise from the overlying epithelium of the mucosal surface. Immunohistochemically, all the cases expressed p63, p40, and CK5/6, while myoepithelial-related markers were uniformly negative in all cases. HGT exhibited a wild type p53 expression pattern. FISH demonstrated EWSR1 rearrangement (10/10) and EWSR1–ATF1 fusion (4/5); however, MAML2 remained intact (0/3). Conclusions CCCs with HGT or occurring in uncommon sites are extremely rare. Combining morphology based IHC and molecular detection provided reliable evidence that the HGT component represented a transformation of CCC rather than the coexistence of another tumor and helped differentiating CCCs in uncommon sites from their mimics, avoiding potential misdiagnosis and inappropriate therapy. The overall prognosis for CCCs is good, except for the HGT cases, which needed continued treatment.

Purpose: Prostatic ductal adenocarcinoma (PDA) is recognized as an advanced stage cancer and is often observed in conjunction with acinar adenocarcinoma, with abundant cytoplasm arranged in a papillary pattern. When compared with acinar adenocarcinoma, it is characterized by an increased biochemical recurrence rate and unusual metastasis sites. The purpose of the present study was to further elucidate the genomic alterations associated with PDA. Methods: Whole-exome sequencing (WES) and linkage analyses were performed on genomic DNA isolated from formalin-fixed, paraffin-embedded (FFPE) samples obtained from eleven PDA tumors and paired benign tissues. The profiles of somatic mutations, indels as well as copy-number alterations were confirmed in PDA patients. The clonal evolution patterns of the eleven PDA cases were compared with the data obtained from the Cancer Genome Atlas (TCGA) for eight primary prostatic acinar adenocarcinoma patients. Results: The same somatic changes were observed in PDA as in advanced and/or metastatic acinar adenocarcinomas. For example, the mutations of a known prostate cancer driver gene CDKN1A, were the most significant events among 17% of tumors. In addition to the known amplification of chromosomes 1q, 4p, 8q, and 14q, the copy number of several large regions also increased significantly. The origin of PDA was heterogeneous: some patients (e.g. P5) were consistent with the monoclonal model, while others (e.g. P7) were polyclonal. Conclusions: PDA and acinar adenocarcinomas of prostate with high Gleason score have similar mutational profiles. The somatic mutations in PDA may be the reason for its invasive biological behavior.

Sinonasal mucosal melanoma (SNMM) is a rare tumour with a poor prognosis. The purpose of this study was to identify independent predictors of outcome in SNMM and to examine the expression of PD-L1 and the relationship between expression and clinicopathological characteristics.A total of 117 patients with SNMM were reviewed in the Department of Pathology of Beijing Tongren Hospital (115 cases) and Beijing Chuiyangliu Hospital (2 cases) from June 2007 to June 2018. We evaluated the expression of PD-L1 in SNMM and investigated whether there was an association between the expression of the marker and clinicopathological characteristics.Sex, age, side, location, size, histological type, melanin particles, nuclear fission and tumour infiltrating lymphocytes (TILs) were not significantly related to survival. The median survival times at the T3, T4a, and T4b stages were 23, 19, and 6 months, respectively. The difference between overall survival (OS) and AJCC stages was statistically significant. The tumour cells (TCs) were PD-L1 positive in 14/117 (12.0%) cases, and tumour-associated immune cells (ICs) were PD-L1 positive in 23/117 (19.7%) cases. A statistically significant correlation was observed between the positive expression rate of PD-L1 in ICs and TILs grading; however, there was no significant correlation between the positive expression rate of PD-L1 in TCs and TILs grading.The AJCC stages were the only independent predictors of survival. There was no correlation between the positive expression rate of PD-L1 and OS. A statistically significant correlation was observed between the positive expression rate of PD-L1 in ICs and TILs grading.

Clinical benefit of neoadjuvant immunotherapy in resectable esophageal squamous cell carcinoma (ESCC). remains unclear. This study evaluated the efficacy and safety of the programmed death 1 (PD-1) inhibitor tislelizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable ESCC.Treatment-naïve patients were enrolled and eligible patients received 3 cycles of neoadjuvant therapy with tislelizumab, carboplatin, and nab-paclitaxel. The primary endpoint was surgery patients major pathological response (MPR). Subgroup analysis was stratified by tumor downstaging, circumferential resection margin (CRM), PD-ligand 1 (PD-L1) expression, and tumor mutation burden (TMB). Safety was assessed by adverse events (AEs) and postoperative complications.Between September 2020 and March 2021, 45 patients were enrolled. Thirty-six (80.0%) of 45 patients underwent surgery, and 29 (80.5%) underwent successful R0 resection. MPR and pathological complete response (pCR) for surgery patients were 72.0% and 50.0%, respectively. Intention to treatment (ITT) patients MPR and PCR were 57.5% and 40%. Downgrading occurred in 75% of 36 patients. MPR and pCR were identified to be associated with tumor downstaging and CRM but not PD-L1 expression or TMB. TPS levels in MPR and pCR group were significantly higher than that in Non-MPR and Non-pCR group, respectively. Treatment-related AEs of grade 3-4 and immune-related AEs occurred in 42.2% and 22.2% of 45 patients, respectively, and postoperative complications occurred in 77.8% of 36 patients. No treatment-related surgical delay or death occurred. No associations between gene mutation and pathological efficacy were observed.Tislelizumab plus chemotherapy as neoadjuvant therapy demonstrates promising antitumor activity for resectable ESCC with high rates of MPR, pCR, and R0 resection, as well as acceptable tolerability.

Background. Receptor for advanced glycation end products (RAGE) is implicated in tumor biology. Released high mobility group box protein 1 (HMGB1) ligand binding to RAGE receptor in tumor cells promotes tumor progression. The mechanisms of HMGB1-RAGE signaling in M2 macrophages involved in lymphangiogenesis in laryngeal carcinoma remain poorly understood. Here, we assessed the effect of HMGB1-RAGE signaling on M2 macrophages in lymphangiogenesis. Methods. HMGB1, CD163, and D2-40 in laryngeal squamous cell carcinoma (LSCC, n = 123 ), laryngeal precursor lesions (LPLs, n = 102 ), and vocal polyp (VP, n = 55 ) were analyzed by immunohistochemistry. THP-1 cell-expressed RAGE gene was knocked down and then polarized to M0 macrophages and M2 macrophages. IL-23, TNF-α, TGF-β, and IL-10 were measured by ELISA; IL-1β, IL-12, IL-10, and CCL-13 were evaluated by RT-qPCR, and CD206, CD163, and RAGE were evaluated by western blot to evaluate whether classical M2 macrophages were obtained. Conditioned media from RAGE+/- M0 macrophages and RAGE+/- M2 macrophages incubated in the presence or absence of HMGB1, anti-Toll-like receptor (TLR)2, anti-TLR4 antibodies, and anti-VEGF-C antibodies were collected separately for human dermal lymphatic endothelial cells (HDLEC) for proliferation, migration, lymphangiogenesis assay, and VEGF-C concentration analysis. Results. HMGB1 and M2 macrophage densities were increased in LSCC ( P < 0.01 ). HMGB1 and M2 macrophage densities were significantly correlated with lymphatic vessel density (LVD) in LSCC ( P < 0.01 ). The HMGB1 overexpression and higher M2 macrophage density were involved in lymph node metastasis ( P < 0.01 ) and poor prognosis ( P < 0.05 ). In vitro, conditioned medium from HMGB1-stimulated RAGE+ M2 macrophages activated lymphangiogenesis by upregulating the VEGF compared to controls ( P < 0.05 ). On the contrary, RAGE knockdown obviously decreased the corresponding effects of HMGB1-preconditioned M2 macrophages upon HDLEC ( P < 0.05 ). HMGB1-TLR pathway does not significantly increase HDLEC proliferation, migration, and lymphangiogenesis on M2 macrophages. Conclusions. HMGB1 promotes lymphangiogenesis by activation of RAGE on M2 macrophages. Targeting RAGE may provide an effective therapeutic strategy against M2 macrophages in LSCC patients with lymph node metastasis.

Nonalcoholic steatohepatitis (NASH) has the potential to progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Upregulation of sonic hedgehog (Shh) has been documented in development of NASH through sustained cell stress. At the same time, transforming growth factor-β1 (TGF-β1), which is a central element in fibrogenic reactions in various diseases and sites, has been reported to be associated with hepatic inflammation and fibrotic reaction. To explore crosstalk between Shh and TGF-β1 in the development and progression of NASH, we investigated the expression of both these proteins in 135 human specimens of NASH, 35 fatty liver specimens, 35 specimens of alcoholic steatohepatitis with immunohistochemistry. Shh protein was expressed in the cytoplasm of ballooned hepatocytes with an ubiquitin-like pattern. In addition, a few scattered apoptotic hepatocytes in the inflammatory foci showed homogeneous cytoplasmic Shh expression. TGF-β1 protein was observed mainly in the activated hepatic stellate cells (HSCs) which were located in the inflammatory foci surrounding ballooned hepatocytes. Moreover, the mRNA levels of both Shh and TGF-β1 in the liver biopsy specimens from NASH patients was significantly increased compared with those in fatty liver patients. Statistically, there was a significant association of the expressions of Shh and TGF-β1 proteins in NASH (r=0.6, P

Traditional histological grading for predicting adenoid cystic carcinoma (ACC) outcomes is challenging and unreliable. We explored the relationship between dominant cell type (DCT) and outcomes for ACC of the head and neck to develop a new approach to predicting prognosis. Clinicopathological data were obtained from a retrospective cohort of 167 patients with primary ACC of the head and neck. Using immunohistochemistry markers to determine DCT, tumors were subclassified into three distinct subtypes, epithelial-predominant (E-ACC), myoepithelial-predominant (M-ACC), and conventional (C-ACC). Differences in clinicopathological parameters and clinical outcomes among these subtypes were then analyzed. Compared to that of M-ACC and C-ACC, E-ACC exhibited more aggressive clinicopathological features with predominantly solid components, high-grade transformation, lymphovascular invasion, tumor necrosis (TN), Ki-67 ≥ 30%, and advanced stage of disease. Both E-ACC and M-ACC could present as solid morphological forms, but E-ACC had a significantly worse prognosis than M-ACC. DCT, TN, and disease stage were independent predictors of recurrence-free survival. DCT, TN, age ≥ 50 years, and disease stage were independent predictors for overall survival. In conclusion, DCT was an independent prognostic indicator for both recurrence-free and overall survival for ACC. Our results provide a new approach to predicting prognosis in ACC and a strong pathological basis for clinically optimizing treatment.

Background The diagnosis of microinvasive laryngeal squamous cell carcinoma (LSCC) is not always straightforward and sometimes can be very challenge in daily clinical practice. The focus lies in the confirmation of microinvasion. Cancer-associated fibroblasts (CAFs), as the major element of reactive tumor stroma, are believed to participate actively in the growth and invasion of tumor cells. Objectives To evaluate the diagnostic role of α-smooth muscle actin (α-SMA) labelling CAFs in microinvasive LSCC. Methods A total of 81 laryngeal biopsy specimens were retrieved, including 41 cases of microinvasive LSCC with depth of invasion no more than 3 mm, 20 laryngeal squamous intraepithelial lesion (SIL), and 20 benign pseudoepitheliomatous hyperplasia (PEH). All cases were stained for immunohistochemistry, using antibody against the α-SMA antigen. The correlation between the presence of CAFs in microinvasive LSCC and tumor histological characteristics was investigated. Results Immunoreactivity of α-SMA was detected in twenty-nine microinvasive LSCC (29/41, 71%), while no reactivity was observed in laryngeal SIL (0/20, 0%), and rarely in PEH (2/20, 10%). The α-SMA expression pattern in stroma of microinvasive LSCC was significantly different from that of SIL (χ2 = 26.966, p = 0.000) and PEH (χ2 = 19.838, p = 0.000). In addition, there seemed to be a certain correlation between the histological characteristics of microinvasive LSCC and the presence of interstitial CAFs. Conclusions This study highlights the practical role of utilizing α-SMA in the pathological diagnosis of microinvasive LSCC, with emphasis on variable histomorphologic features of microinvasive LSCC.

Objectives The MeltPro MTB assays for detection of resistance to antituberculosis (TB) drugs perform well in genotypic drug susceptibility testing (DST) of clinical samples, but their effectiveness with formalin-fixed, paraffin-embedded (FFPE) tissues is unknown. Methods FFPE tissues were obtained from 334 patients with TB. Susceptibility to rifampicin (RIF), isoniazid (INH), and fluoroquinolones was examined using the MeltPro MTB assays, with Xpert MTB/RIF (Xpert) and/or phenotypic DST (pDST) results as references. Samples with discordant results were analyzed by multiplex polymerase chain reaction–targeted amplicon sequencing (MTA-seq). Results With pDST as the reference, the MeltPro MTB assays sensitivity for RIF, INH, levofloxacin (LVX), and moxifloxacin (MXF) was 95.00%, 96.00%, 100%, and 100%, respectively, and the specificity was 95.15%, 95.92%, 94.69%, and 89.92%, respectively. Concordance was 99.08% between the MeltPro MTB and Xpert (κ = 0.956) for RIF and 95.12% (κ = 0.834), 95.93% (κ = 0.880), 95.12% (κ = 0.744), and 90.24% (κ = 0.367) between the MeltPro MTB and pDST for RIF, INH, LVX, and MXF, respectively. MTA-seq confirmed the discordancy between the MeltPro MTB and pDST for 26 (89.66%) of 29 samples. Conclusions The MeltPro MTB assays rapidly and efficiently predict Mycobacterium tuberculosis resistance to the main first- and second-line anti-TB drugs in FFPE tissues.

Background The prognostic factors and survival difference between inverted papilloma (IP)-associated sinonasal squamous cell carcinoma (SCC) and de novo SCC are unclear. Objective This study aimed to compare the clinical features and oncologic outcomes in patients with IP-associated SCC and de novo SCC; and additionally, to analyze the prognostic factors of the two types of SCCs. Methods Data from 173 SCC patients treated for IP-associated SCC (n = 89) and de novo SCC (n = 84), were reviewed retrospectively for demographic features, tumor characteristics, treatment modality, and clinical outcomes. 5-year overall survival (OS) and disease free survival (DFS) was analyzed using the Kaplan-Meier method, and Cox proportional hazards model was used to analyze factors influencing prognosis. Results A higher proportion of IP-associated SCC occurred in frontal and sphenoid sinus compared to de novo SCC. The two groups demonstrated similar 5-year OS and DFS (5-year OS: 63.3% and 55.4%, DFS: 45.4% and 50.1%, respectively). The metachronous tumor had a relatively better prognosis outcome than synchronous tumor and de novo SCC (5-year OS: 73.1%, 54.5% and 55.4%, respectively). Both groups showed similar loco-regional recurrence rates ( p > 0.05); however, de novo SCC tumors demonstrated an increased incidence of distant metastasis. Multivariate analysis indicated that age >70 years, advanced tumor stage and surgical margin were independent predictive factors for the risk of mortality (HR 2.047, 1.581 and 1.931, respectively). Conclusion IP-associated SCCs have an aggressive loco-regional tendency, whereas de novo SCCs have a higher aggressive distant metastatic propensity. Age, tumor stage and surgical positive margin are key factors for poor prognosis and should be routinely taken into consideration during treatment planning and subsequent surveillance.

Objective To investigate the role of human papillomavirus (HPV) in laryngeal squamous cell carcinoma (LSCC) and analyse the relationship between HPV and the expression of cell cycle-related proteins. Design The study consisted of LSCC between 2005 and 2011 in Tongren Hospital. Clinical data such as age, sex, smoking/alcohol consumption, and TNM stage were collected. HPV DNA and cell cycle-related proteins were assessed in terms of clinical features. Setting Single-centre study. Participants A total of 332 LSCC patients were included in the study. Main outcome measures The presence of genotype-specific HPV DNA was evaluated using PCR-RDB in formalin-fixed paraffin-embedded tissues. All samples were also evaluated for p16INK4A , p21WAF1/CIP1 , P53, Cyclin D1, and Ki67 immunohistochemical staining by tissue microarray. Results HPV DNA was detected in 45 of 332 (13.55%) patients with LSCC, with HPV-16 being the predominant genotype. The presence of HPV-16 DNA was significantly associated with basaloid squamous cell carcinoma and cystic lymph node metastasis (P 0.05). Conclusion HPV DNA was detected in 13.55% patients with LSCC, with HPV-16 being the predominant genotype and it was correlated with p16INK4A and manifested a higher Ki-67 labelling index and p21WAF1/CIP1 expression than HPV-16-negative tumours.

Background Myxoid liposarcoma has a distinct migration aptitude; however, pancreatic metastasis is rare. Case presentation We report on the case of a 40-year-old female patient who suffered solitary pancreatic metastasis of myxoid liposarcoma and had a right thigh myxoid liposarcoma radical resection 5 years ago. The patient underwent a medial pancreatectomy and pancreaticojejunostomy for solitary pancreatic metastasis of myxoid liposarcoma. After 12 months of disease-free survival, the patient underwent an extended radical resection for the recurrence of the right thigh primary myxoid liposarcoma and received postoperative radiotherapy. Currently, the disease-free survival time after the last operation has been 22 months. Conclusions We reviewed the relevant literature and suggest that radical surgery might result in a good prognosis for patients with solitary pancreatic metastasis of myxoid liposarcoma.

Solute carrier family 7, membrane 11 (SLC7A11) or (xCT) is a component of the cysteine-glutamate transporter, which plays a critical role in glutathione homeostasis which is important to protect cells from oxidative stress. SLC7A11 is distributed in various tissues and participates in the occurrence of a number of diseases, particularly in the pathogenesis of malignant tumors, but its role in laryngeal cancer development has not yet been clearly defined. The objective of the present study was to investigate the role of SLC7A11 in laryngeal squamous cell carcinoma (LSCC). We conducted immunohistochemistry and RT-PCR to evaluate the protein and mRNA levels of SLC7A11 in LSCC and in control tissues, respectively. The knockdown experiments were conducted with SLC7A11 short hairpin RNA (shRNA) lentivirus, and the protein and mRNA levels of SLC7A11 were assessed by RT-PCR and western blotting. The functional study of SLC7A11 in vitro was conducted by MTT assay, and the effects on the cell cycle were detected using flow cytometry. Immunohistochemical results revealed that the expression levels of SLC7A11, Ki-67 and p53 in LSCC tissues were higher than those in laryngeal dysplasia tissues. The Spearman rank correlation analysis revealed that the expression of SLC7A11 was positively correlated with the expression of p53 and Ki-67. Cox regression analysis and Kaplan-Meier plots confirmed that the expression levels of SLC7A11 were a prognostic factor for overall survival (OS) rates and postoperative recurrence of LSCC. Moreover, the functional study of SLC7A11 in vitro revealed that knockdown of SLC7A11 using shRNA inhibited cell proliferation by inducing cell cycle arrest at the G1 phase. Immunohistochemical and RT-PCR results and knockdown experiments of SLC7A11 revealed that SLC7A11 was involved in the progression of LSCC, and may provide clinical information for the evaluation of OS rates and postoperative recurrence of LSCC. Collectively, these observations suggest that SLC7A11 may be a vital biomarker for the diagnosis and prognosis in human LSCC, and targeting SLC7A11 appears to be a potentially significant method for LSCC treatment.

Objective The clinicopathological significance of Mucin5AC (MUC5AC) in lung adenocarcinoma with mucin production is still unclear. This study aimed to explore MUC5AC expression in lung adenocarcinoma with mucin production and its correlation with histological subtypes, common driver mutations and its impact on prognosis. Methods MUC5AC and thyroid transcription factor 1 immunohistochemistry was performed on surgical samples from 90 patients with lung adenocarcinoma with mucin production. Common driver mutations including EGFR and KRAS mutations and ALK rearrangement were detected by established methods. Results MUC5AC was significantly associated with lymphovascular invasion (P = 0.023) and tumors with intra-cytoplasmic mucin (P Conclusions The clinicopathological features of non-pure mucinous subtype of lung adenocarcinoma with mucin production were distinct and should be distinguished from pure mucinous subtype. MUC5AC was associated with poor prognosis and could be a potential therapeutic target for this distinct type of lung adenocarcinoma that has few effective treatments.

Background This study examines the effects of tanshinone IIA (TIIA) on epithelial–mesenchymal transition (EMT) in tracheal transplantation and the ability of TIIA to inhibit tracheal narrowing after tracheal transplantation. Mechanisms that may be involved in this process are also explored. Methods Human bronchial epithelial cells were treated in vitro with TGF-β1 for 72 h. The cells were pretreated with TIIA (40 μg/mL) or DMSO for 2 h before TGF-β1 stimulation. For the in vivo experiments, tracheas (5-6 rings) from Wistar rats were orthotopically transplanted into Sprague–Dawley rats. The experimental group received multiple infusions of sodium TIIA sulfonate (25 mg/kg, qd, intraperitoneally). The control group received infusions of the same volume of saline. Allografts were harvested at 3, 7, 10, 14, 35, and 90 d after transplantation and were examined for tracheal narrowing. Tracheal tissue samples and human bronchial epithelial cell were then subjected to further tests. Results In the in vitro assay, epithelial cadherin expression was decreased after TGF-β1 stimulation, whereas α-smooth muscle actin and vimentin expression levels were increased. The expression levels of ZEB1 and Snail1 were also increased. These changes in expression were partially reversed by treatment with TIIA. In the in vivo assay, TIIA alleviated tracheal stenosis after tracheal allograft transplantation in rats and mitigated EMT by inhibiting the Smad signaling pathway and the expression of the transcription factors ZEB1 and Snail1. Conclusions Our research suggests that TIIA reduces tracheal narrowing after tracheal transplantation by suppressing TGF-β1–dependent EMT.

BACKGROUND Class III β-tubulin (βIII-tubulin) has been reported to express at the invasive margin of colorectal cancer. The present study aimed to investigate the clinical implication of βIII-tubulin expression at the invasive margin of colorectal cancer. MATERIAL AND METHODS We recruited 111 patients with surgically resected colorectal carcinoma for bIII-tubulin expression analysis. The cases with bIII-tubulin-positive tumor cells found only in the invasive front tumor area were assigned to the invasive front group, while the remaining cases were all assigned to the non-invasive front group. Clinical analysis of βIII-tubulin and other clinical data was performed. RESULTS The positive staining rates and staining intensity of bIII-tubulin were significantly different between the invasive and non-invasive front groups (p=0.001 and p=0.006), and there was a significant difference in tumor differentiation between the 2 groups (p=0.032). In the non-invasive front group, staining intensity of bIII-tubulin was significantly associated with positive staining rates and lymphatic metastasis (p

Rationale Oncocytic Schneiderian papillomas (OSP) are an uncommon type of sinonasal papillomas that arise from the Schneiderian epithelium, accounting for only 6% of all sinonasal papillomas. Malignancies arising in OSP are rare and are almost always described as in situ or invasive squamous cell carcinoma, although mucoepidermoid, small cell carcinoma and sinonasal undifferentiated carcinoma have also been reported. To our knowledge, only 18 such instances have been reported in the medical literature. Patient concerns Here, we report the case of an 81-year-old man presenting with a left sinonasal neoplasm, who had undergone 4 operations. The first postoperative pathology revealed a benign nasal polyp. The following several postoperative pathology revealed a novel, human papillomavirus-negative adenocarcinoma with increasing malignant features with each recurrence arising in an OSP. In addition, the most recent recurrences were associated with metastasis of cervical lymph nodes. And after the operation, the patient refused adjuvant radiotherapy. On 6-month follow-up after the last operation, the patient developed an in situ tumor recurrence 1 month after the fourth operation and refused to undergo surgery again. Diagnosis Immunohistochemistry for Ki67, CK7, CK5/6, P53, and P63 showed a progression of malignancy. HPV assay presented the 21 most prevalent HPV types were negative. In addition, KRAS gene exon 2 G12C presented mutation in the OSP-associated adenocarcinoma. Interventions During the whole course of the patient's disease, we performed four nasal endoscopic operations. And after the last operation, the patient refused adjuvant radiotherapy and KRAS-targeted therapy. Outcomes We are the first to describe adenocarcinoma arising in an OSP. To our surprise, from the first benign neoplasm to the second OSP-associated adenocarcinoma, it went through a long period of 10 years. However, after the adenocarcinogenesis, the differentiation of tumor became worse with the shorter interval of each recurrence. Lessons Therefore, for elderly patients with unilateral nasal polyps, long-term follow-up is necessary. Once OSP turns into malignant, radical resection should be performed as much as possible to reduce the irritability of tumors.

Aims Concomitant occurrence of Mikulicz's disease (MD) and immunoglobulin (Ig)G4-related chronic rhinosinusitis (IgG4-related CRS) is extremely rare. We evaluated the clinicopathological features of MD patients with concomitant IgG4-related CRS (CRS-MD). Methods and results Twelve CRS-MD patients were evaluated clinically and biopsy samples were taken from the lacrimal/salivary glands (n = 12) and nasal mucosa (n = 7) for assessment of IgG4-positive cells, using immunohistochemical techniques. Similarly, nine MD patients and 10 patients with common CRS were evaluated as controls. CRS-MD patients had higher serum IgG and IgG4 concentrations than MD patients (P

To investigate the relationship of prognostic nutritional index (PNI) with clinicopathological factors and the clinical significance of PNI in predicting the survival in patients with advanced gastric cancer.Clinicopathological and follow-up data of 1150 patients with advanced gastric cancer who underwent radical gastrectomy from January 2007 to December 2010 at the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital were analyzed retrospectively. The PNI value was calculated [PNI=absolute value of lymphocyte(10Of 1150 cases, 846 were males and 304 were females with an average age of 62 (24 to 88) years. The average maximum diameter of tumor was 5.4(1.0 to 20.0) cm. Tumor of 159 cases located in the gastric fundus, 221 cases in the gastric body, 705 cases in the gastric antrum and 65 cases in the whole stomach. Well differentiated tumors were found in 198 cases and poorly differentiated tumors in 952 cases. As for depth of tumor invasion, 165 cases were T2, 343 cases were T3 and 642 cases were T4. According to TNM stage, 53 cases were stage I(, 397 cases were stage II( and 700 cases were stage III(. The average lymph node metastasis rate was 25.0%, meanwhile lymph node metastasis was N0 in 296 cases, N1 in 246 cases, N2 in 277 cases and N3 in 331 cases. Blood examination showed hemoglobin ≤130 g/L in 544 cases and130 g/L in 606 cases; carcinoembryonic antigen ≤5 μg/L in 903 cases and5 μg /L in 247 cases; carbohydrate antigen 19-9 ≤37 kU/L in 927 cases and37 kU/L in 223 cases. In whole patients, the mean value of PNI was 51.81(24.5 to 80.4), PNI ≤51.81 group had 563 cases, and PNI51.81 group had 587 cases. Between PNI ≤51.81 group and PNI51.81 group, age (χAlthough the PNI is not an independent risk factor of overall survival in patients with advanced gastric cancer, it is still an indicator of survival in patients with gastric cancer. Improving preoperative nutritional status in patients with gastric cancer may contribute to a better prognosis.

Objectives To evaluate CD163+ tumor-associated macrophages (TAMs), Ki-67, and cyclin D1 to differentiate laryngeal dysplasia in the 2017 World Health Organization classification. Methods Immunohistochemistry for CD163, Ki-67, and cyclin D1 was performed using paraffin-embedded specimens. CD163+ TAMs infiltrating the epithelium were estimated. Ki-67 and cyclin D1 were evaluated in four parts of the epithelium-basal, parabasal, middle third, and upper third layers. Results In total, 133 specimens were analyzed, including low-grade dysplasia (n = 31), high-grade dysplasia (n = 49), carcinoma in situ (n = 23), and normal mucosa (n = 30). CD163+ TAMs infiltrating the epithelium were significantly higher in high-grade dysplasia than in low-grade dysplasia. In the basal layer, Ki-67+ and cyclin D1+ cells were overexpressed in high-grade dysplasia (P < .0001). The area under the curve was 0.958 for Ki-67 and 0.909 for CD163+ TAMs (P < .0001). Conclusions CD163+ TAMs infiltrating the epithelium and Ki-67 overexpression in the basal layer may serve as biomarkers to differentiate low-grade dysplasia from high-grade dysplasia of the larynx. A symmetric proliferative pattern was observed during laryngeal carcinogenesis following Ki-67 overexpression.

The minichromosomal maintenance (MCM) proteins are involved in the initiation and DNA replication. The role of MCM4 remains to be elucidated. The purpose of this study was to investigate the effects of MCM4 in laryngeal squamous cell carcinoma (LSCC) cell growth and apoptosis.LSCC cell line UMSCC 5 was used in this study. The small interfering RNA (siRNA) of MCM 4 gene was used to identify the effects of MCM4 on the proliferation and apoptosis using methylimidazole tetrazolium (MTT) assay and flow-cytometry, respectively. Confirmed LSCC and adjacent non-tumor tissues were collected from 34 patients who were willing to participate in the study, from 2010 through 2015, from 163 patients undergoing treatment in the Department of Otorhinolaryngology/Head and Neck Surgery of Beijing Tongren Hospital in Capital Medical University of P.R. China. Immunohistochemical staining of MCM4 expression in the resected tissues was performed to analyze the correlation between its expression and the clinicopathological characteristics.The results showed that siRNA of MCM4 could significantly inhibit LSCC cell line UMSCC 5 proliferation and induce apoptosis. MCM4 mRNA was higher expressed in carcinoma tissues than in adjacent normal tissues. MCM4 expression was correlated with male gender, smoking history and poor differentiation.We noticed a significant role for MCM4 overexpression in human LSCC tissues and their corresponding adjacent non-neoplastic tissues and found that siRNA of MCM4 can significantly decrease the proliferation of cancer cells. It is suggested that MCM4 profiling could potentially be used to predict response to treatment and prognosis in LSCC.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The five-year survival rate of HNSCC has not improved even with major technological advancements in surgery and chemotherapy. Currently, docetaxel, cisplatin, and 5-fluoruracil (TPF) treatment has been the most popular chemotherapy method for HNSCC; but only a small percentage of HNSCC patients exhibit a good response to TPF treatment. Unfortunately, at present, no reasonably effective prediction model exists to assist clinicians with patient treatment. For this reason, patients have no other alternative but to risk neoadjuvant chemotherapy in order to determine their response to TPF. In this study, we analyzed the gene expression profile in TPF-sensitive and non-sensitive patient samples. We identified a gene expression signature between these two groups. We further chose 10 genes and trained a support vector machine (SVM) model. This model has 88.3% sensitivity and 88.9% specificity to predict the response to TPF treatment in our patients. In addition, four more TPF responsive and four more TPF non-sensitive patient samples were used for further validation. This SVM model has been proven to achieve approximately 75.0% sensitivity and 100% specificity to predict TPF response in new patients. This suggests that our 10-genes SVM prediction model has the potential to assist clinicians to personalize treatment for HNSCC patients.

This study was to analyze the dys-regulation of microRNA-10a-5p and microRNA-34c-5p and their correlations with clinicopathological characteristics of laryngeal epithelial premalignant lesions (LEPL). Quantitative real-time polymerase chain reaction was performed to detect the expression of microRNA-10a-5p and microRNA-34c-5p in 94 cases of LEPL and 47 controls. Retrospective follow-up data of all patients were collected and the correlation between the dys-regulation of microRNA-10a-5p/microRNA-34c-5p and clinicopathological characteristics was examined by linear regression analysis. Expression of microRNA-10a-5p was down-regulated in LEPL, showing statistical difference between low-risk lesion group and high-risk lesion group, while microRNA-34c-5p expression was up-regulated gradually in LEPL groups and dropped suddenly in squamous cell carcinoma group. In addition, the differential expression of microRNA-10a-5p is profiled with either LEPL grade or gender, showing a linear correlation; and microRNA-34c-5p expression is correlated with alcohol consumption in LEPL patients (P < 0.05). The dys-regulation of microRNA-10a-5p and microRNA-34c-5p in LEPL and their correlations with clinicopathological characteristics might provide important theoretical and experimental basis for LEPL classification and the two microRNAs can serve as more valuable markers in diagnosis and clinical management of LEPL.

Inflammatory myofibroblastic tumor (IMT) is rare in nasal cavity and paranasal sinus. The aim of this study was to describe the clinicopathological features of sinonasal IMT and analyze the relationship between the clinicopathological features and the prognosis. A retrospective study of 25 IMT patients between 2001 and 2012 was performed. Data on clinical features, treatment, and follow-up were recorded. The histological characters were observed. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan-Meier method. Clinically, the most common symptoms were nasal obstruction, facial pain, and toothache. Twenty patients received follow-ups 6-120 months after initial diagnosis. Fifteen (75 %) developed recurrence 1 or more times. One patient had left cervical lymph node metastasis (5 %). Five patients died of the tumor (25 %). Histologically, the IMTs composed of bland spindle cells admixed with a prominent infiltrate of plasma cells and lymphocytes and showed obvious atypia in recurrent cases. Histology with necrosis, mitosis (≥1/10 HPF), ganglion-like cells, histological pattern I or II and relapse (≥4 times) was significantly associated with poor OS and EFS. IMT of the nasal cavity and paranasal sinuses exhibits relatively bland histologic appearances, but can shows strongly aggressive behavior and relatively poor outcomes. Multiple relapse, necrosis, frequent mitosis, the presence of ganglion-like cells, and histological pattern might be associated with poor clinical outcomes.

These results provided a battery of genes relating to TPF chemotherapeutic sensitivity and might act as molecular targets in laryngeal squamous cell carcinoma (LSCC) treatment. Moreover, these candidate biomarkers could contribute to LSCC individualized treatment.To screen out a set of candidate genes which could help to determine whether patients with LSCC could benefit from TPF induction chemotherapy.Gene-expression profiles in seven TPF-sensitive patients were compared to four resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line UMSCC5 after TPF treatment were observed by qRT-PCR.Through microarray analysis, 1546 differently expressed genes were identified, of which 769 were up-regulated in TPF chemotherapy-responsive tissues, whereas 777 were down-regulated. Gene ontology (GO) analysis suggested these genes participating in physiological processes including cell differentiation, metabolism, signal transduction, and cellular component organization. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that Wnt and p53 signaling pathways occupied important roles in TPF chemotherapeutic sensitivity. Moreover, in vitro cell culture experiments revealed the expression alternations of Mapk10, Jun, Vegfb, Pik3r5, Pld1, Tek, Itga6 exposed to TPF treatment by qRT-PCR, whilst providing an insight into the mechanism underlying TPF chemotherapeutic response in LSCC.

Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the expression pattern and function of lncRNAs in laryngeal squamous cell carcinoma (LSCC) are still unclear. To investigate the aberrantly expressed lncRNAs and mRNAs in advanced LSCC, we screened lncRNA and mRNA expression profiles in 9 pairs of primary Stage IVA LSCC tissues and adjacent non-neoplastic tissues by lncRNA and mRNA integrated microarrays. Gene Ontology and pathway analysis were performed to find out the significant function and pathway of the differentially expressed mRNAs, gene-gene functional interaction network and ceRNA network were constructed to select core mRNAs, and lncRNA-mRNA expression correlation network was built to identify the interactions between lncRNA and mRNA. qRT-PCR was performed to further validate the expressions of selected lncRNAs and mRNAs in advanced LSCC. We found 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs. The mRNAs ITGB1, HIF1A, and DDIT4 were selected as core mRNAs, which are mainly involved in biological processes, such as matrix organization, cell cycle, adhesion, and metabolic pathway. LncRNA-mRNA expression correlation network showed LncRNA NR_027340, MIR31HG were positively correlated with ITGB1, HIF1A respectively. LncRNA SOX2-OT was negatively correlated with DDIT4. qRT-PCR further validated the expression of these lncRNAs and mRNAs. The work provides convincing evidence that the identified lncRNAs and mRNAs are potential biomarkers in advanced LSCC for further future studies.

The present study indicates that miR-21 is involved in progression from normal to pre-malignant laryngeal lesions (PLLs) and from PLLs to laryngeal squamous cell carcinoma (LSCC). Furthermore, normalized PCR results for miR-21 might be used to discriminate between normal and ordinary hyperplasia before the emergence of dysplasias and pre-malignant lesions with malignant potential.To investigate a sensitive marker that contributes to progression from normal tissue to PLLs and from PLLs to LSCC.In 116 PLLs and LSCC patients and 19 without dysplasia matched sets of tissue and plasma samples from Beijing Tongren Hospital, miR-21 was analysed by droplet digital PCR and quantitative real-time polymerase chain reaction based on paraffin-embedded tumour tissue and plasma.Compared with controls, miR-21 levels in tissue and plasma were significantly higher for both PLL and LSCC groups (for both groups vs controls: p 0.0001 for tissue; p 0.05 for plasma). Areas under receiver-operating curves (AUC) for tissue miR-21 were PLL group vs controls: 0.9026 and LSCC group vs controls: 0.8681. For plasma miR-21, AUCs were PLL group vs controls: 0.7355 and LSCC group vs control: 0.6723.

Studies from different countries showed variations of genetic changes and association with Chlamydia psittaci in ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 38 ocular adnexal MALT lymphoma cases from Northern China were studied. Genetic abnormalities were investigated in 28 cases by interphase FISH. C. psittaci and other infectious agents that are commonly-associated with chronic eye disease were screened in 38 cases by PCR. Genetic abnormalities were detected in 60.7% of cases. Among them, only one showed a break-apart of the IgH gene and all others showed numerical abnormalities, including trisomy 18 in 7 cases (25%), 3 copies of BCL6 gene in 12 cases (43%), and 3 copies of C-MYC gene in 2 cases (7%). C. pneumoniae was positive in two cases (5.3%), and C. psittaci, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were not detected in any cases. In conclusion, numerical abnormalities are frequent and the chromosomal translocations commonly associated with MALT lymphomas are rare in ocular adnexal MALT lymphoma of Northern China. C. psittaci and other infectious agents are not associated with ocular adnexal MALT lymphoma in these patients.

To study the clinicopathologic characteristics of IgG4-related sialodacryoadenitis and chronic rhinosinusitis (CRS).A total of 13 patients (patient group) were evaluated clinically and biopsy specimens from the lacrimal/salivary glands (n=12) and nasal mucosa (n=8) were reviewed and immunohistochemistry was performed to assess IgG-and IgG4-positive cells. Similarly, nine patients with IgG4-related sialodacryoadenitis without CRS and 10 patients with common CRS were included as controls.There were 8 male patients and 5 female patients. The age of patients ranged from 32 to 71 years (mean 50.2 years). The patient group had higher serum IgG4 concentration than that of the control group (P0.05). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis were prominent in lacrimal/salivary glands in both groups; however the magnitude of IgG4-positive plasmacytic infiltration in the patient group was significantly higher than that of the control group (P0.05). Similarly, evaluation of nasal mucosa revealed greater lymphocytic and plasmacytic infiltration, and lymphoid follicle formation, together with significantly higher amount of IgG4-positive plasma cell infiltration in the patient group compared to the common CRS group (P0.05).IgG4-related disease (IgG4-RD) simultaneously involving lacrimal/salivary glands and nasal cavity/paranasal sinuses is rare and characterized by a combination of IgG4-positive plasma cell infiltration involving lacrimal/salivary glands and nasal mucosa along with an increased serum level of IgG4. As a systemic disease, early and accurate diagnosis is therefore of great importance, and unnecessary surgery should be avoided.

To investigate the clinical and pathologic features of middle ear adenoma (MEA).Eight cases of MEA were collected from Beijing Tongren Hospital, Capital Medical University between 2004 and 2014, and immunohistochemical staining was performed.The patients included five women and three men (mean age, 37.5 years; median 37 years; range, 21-51 years). All patients had unilateral lesions. Five MEA occurred on the left side, and three on the right. In seven patients the MEA was primary, and they presented with hearing loss (6 cases), tinnitus (5 cases), sense of ear blockage (3 cases), otalgia (1 case) and facial nerve paralysis (1 case). The remaining patient had recurrent MEA, and presented with otorrhea, aural fullness and tinnitus. Histologically, the tumor cells were arranged in a variety of patterns, including solid sheets, nests, glands, ribbons or trabeculae. Glandular structures were prominent in one case only. Immunohistochemically, the tumor cells were diffusely positive for keratin (8/8) and vimentin (8/8), and focally positive for CK 7(8/8) and CK5/6(8/8). CK7 and CK5/6 were predominantly positive in tumor cells with glandular growth pattern; CK7 was positive in the luminal cells while CK5/6 was positive in the abluminal cells. Both were also expressed focally in scattered tumor cells with non-glandular pattern. The tumor cells were also diffusely positive for synaptophysin(8/8), diffusely but weakly positive for NSE (5/8), and were diffusely or focally positive for chromogranin A (4/8). Both S-100 protein and calponin were negative in all cases. The proliferation rate was low, about 1%-2%. Six cases were followed up for one year and three months to ten years and six months, with an average follow-up period of four years and two months. Two patients developed recurrence, but there were no regional or distant metastases.Diagnosis of MEA requires pathologic confirmation since the clinical symptoms are non-specific. MEA can show a variety of histologic patterns, and should be distinguished from other space-occupying lesions at this site. Immunohistochemical staining has greatly contributed to the diagnosis and differential diagnosis of MEA. The prognosis of this tumor is good. Patients with MEA require long-term follow-up for recurrences.

Background Fascin,an actin binding protein,usually expressed at a low level in normal epithelium,but is significantly increased in transformed epithelial cells and several common carcinomas.In this study,we examined the expression of fascin by immunohistochemistry in sinonasal epithelium with chronic inflammation (control group),exophytic papilloma (EP),inverted papilloma (IP) with dysplasia and cancerated IP (including carcinoma in situ and invasive squamous cell carcinoma,SCC),and furthermore investigated the relationship between fascin expression and formation of malignant IP. Methods Fascin expression was immunohistochemically detected using monoclonal antibody against fascin in 86 paraffin embedded tissues,including 10 cases of sinonasal mucosa with chronic inflammation,10 of EP,45 of IP with dysplasia (45 cases were divided into three groups:IP with mild dysplasia,IP with moderate dysplasia,and IP with severe dysplasia,15 cases each),and 21 of cancerated IP. Results The level of fascin expression was significantly higher in the neoplastic tissue than that in control group.Fascin expression increased gradually with the progression from sinonasal epithelium with chronic inflammation,IP with mild dysplasia,IP with moderate dysplasia,IP with severe dysplasia,to cancerated IP,and significant difference of fascin expression was observed between any two groups of the five. Conclusion Precancerous lesions of IP exhibit elevated levels of fascin that may be associated with carcinogenesis of IP.Fascin may play a role in the formation of IP and EP. Chin Med J 2007;120(5):375-379

To explore the expressions of the cytokeratin 7 (CK7), cytokeratin 20 (CK20), SOX10 and cadual type homeobox transcription factor 2 (CDX2) in primary adenocarcinoma of the sinonasal tract, and evaluate their diagnostic values.A total of 41 paraffin-embeded specimens of primary adenocarcinoma of the sinonasal tract treated in Beijing Tongren Hospital of Capital Medical University were selected from May 2002 to January 2015. All cases were confirmed by histology and clinical data, including 12 cases of non-intestinal sinonasal adenocarcinomas (non-ITACs), 10 cases of intestinal sinonasal adenocarcinomas (ITACs) and 19 cases of salivary gland-type adenocarcinomas (including 12 cases of adenoid cystic carcinomas, 3 cases of polymorphous low grade adenocarcinomas, 2 cases of mucinous adenocarcinomas and 2 cases of acinar cell carcinomas). Expressions of CK7, CK20, SOX10 and CDX2 were assessed by immunohistochemistry staining method.Nuclear staining for CDX2 was identified in all the ITACs,including diffuse nuclear staining in 8 cases and partial nuclear staining in 2 cases. Cytoplasmic staining for CK20 was identified in 9 cases of ITACs, and partial cytoplasmic staining was found in 1 case of non-ITACs, while CK20 was negative in all other adenocarcinomas.Seven cases of ITACs were negative for CK7, while CK7 was positive in all other adenocarcinomas. CK7, but not CDX2 and CK20, was expressed in normal sinonasal epithelium. SOX10 was negative in 10 cases of ITACs and 2 cases of non-ITACs, and positive in all other adenocarcinomas. The sensitivity of CK7-, CK20+, SOX10- and CDX2+ in primary ITACs of the sinonasal tract were 70.0%, 90.0%, 100%, 100%, respectively, and the specificity were 100%, 96.8%, 93.5%, 100%, respectively.Expressions of CK7-, CK20+, SOX10- and CDX2+ have high sensitivity and specificity in ITACs and can be used as a reliable diagnostic marker for primary intestinal-type adenocarcinoma of the sinonasal tract. Additionally, diagnostic value of CDX2 in primary intestinal-type adenocarcinoma of the sinonasal tract is superior to CK20, CK7 and SOX10.

To investigate the relationship between ALDH1A1 expression and lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC).One hundred and fifty-three paraffin-embedded specimens of PTC treated in the Beijing Tongren Hospital of Capital Medical University were selected from January 2006 to December 2013. The expression of ALDH1A1 was detected in both tumor tissues and adjacent non-tumor tissues by immunohistochemistry and several clinicopathological parameters (size, bilaterality, multifocality, tumor border and extrathyroidal extensions) were assessed by HE staining. The correlation of ALDH1A1 expression with LNM was analyzed.In 153 cases of PTC, there were 82 cases with LNM, 126 cases with high ALDH1A1 expression in tumor tissues, and 112 cases with high ALDH1A1 expression in adjacent non-tumor tissues. On univariate analysis, patient age45 years, tumor size of 10 mm or more, invasive tumor border, and high ALDH1A1 expression in tumor tissues predicted LNM in PTC (P0.05), whereas gender, bilaterality, multifocality, extra-thyroidal extensions and high ALDH1A1 expression in adjacent non-tumor border did not (P0.05). On multivariate analysis, invasive tumor border, high ALDH1A1 expression in tumor tissues were found to be independent predictive factors for LNM in PTC (P0.05). After a follow-up of 42 months (median time), four patients developed locoregional recurrences, but no distance recurrence or disease related death were seen in 82 patients of follow up. The estimated 5-year locoregional recurrence was 4.88%. Of these four logcoregional recurrences, three involved lymph nodes and one involved the remaining thyroid. The ALDH1A1 expression in tumor tissues was high in all of recurrence cases.High ALDH1A1 expression in tumor tissues is correlated with lymph node metastasis in PTC and may be used as an independent predictive factor of LNM, and may improve treatment and follow-up strategies for PTC.

Fungal rhinosinusitis (FRS) is commonly caused by various Aspergillus species (spp) and Mucorales fungi, and the treatment and prognosis of cases differ depending on the causative fungus. The present study describes a novel immunohistochemical method that has high sensitivity and specificity for distinguishing between these two types of fungi in patients with FRS. Three groups were included in the study. Group A included formalin‑fixed paraffin‑embedded blocks of 51 nasal tissue specimens of patients with FRS (27 Aspergillus spp and 24 Mucorales) that were continuously obtained from the Department of Pathology of Tongren Hospital in Beijing as the experimental group and 34 cultures (26 Aspergillus spp and 8 Mucorales) of FRS that were randomly selected from the bacterial laboratory of Tongren Hospital in Beijing to verify the staining results of the paraffin‑embedded blocks. Formalin‑fixed paraffin‑embedded blocks of 10 esophageal cancer specimens were included in Group B as the positive control group. All specimens in Groups A and B were stained with interferon‑γ (IFN‑γ) antibody. Group C consisted of the same specimens as described in Group A, however, when performing the immunohistochemical assay, IFN‑γ antibody was replaced by PBS and this served as the negative control group. The differences in IFN‑γ immunohistochemical staining between Aspergillus spp and Mucorales were analyzed. Staining of IFN‑γ in paraffin‑embedded samples was positive in 92.6% (25/27) of specimens in which Aspergillus spp were the causative pathogen, which was significantly higher compared with specimens in which Mucorales was causative (P

To investigate the expression of microRNA-10a-5p (miR-10a) in laryngeal epithelial premalignant lesions (LEPL) and to analyze the correlations of its dysregulation with clinicopathologic parameters of LEPL.According to the WHO classification (2005), 94 cases of LEPL were grouped into mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD) and carcinoma in situ ( CIS). The expression of miR-10a in 94 cases of LEPL was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and correlated with the clinical and follow-up data of all LEPL patients.miR-10a was down-regulated in LEPL with increasing grade of dysplasia. There was significantly statistical difference between low-risk ( MID + MOD) and high-risk ( SD + CIS) lesion groups (P = 0.03). The linear regression analysis showed that miR-10a was correlated with grade and gender of LEPL (P0.05).Down regulation of miR-10a may be a useful molecular marker for grading of LEPL and diagnosis of early laryngeal cancer.

To identify the type of iron deposition and describe its amount, distribution and associated lesions, in order to support an etiologic diagnosis for hemochromatosis.Hematoxylineosin (HE) stain, reticular fiber stain, Masson's stain and Perl's iron stain were used to assess liver biopsies from 31 patients with hemochromatosis. The Ishak scoring system and Deugnier scoring system were used to assess the histological change in liver and to semi-quantify the excess of hepatic iron. Genetic testing results were received from a portion of the patients and used in analysis.One patient had hereditary (-HFE) hemochromatosis complicated with Gilbert's syndrome, for which the pattern of iron deposition was similar to that of the four patients with Gilbert's syndrome. Iron accumulation appeared as fine granules predominating at the biliary pole of cells and was distributed throughout the lobule with a decreasing gradient spanning from the periportal to centrolobular areas. Mild chronic inflammation was found to be commonly associated with low stage fibrosis.One patient had HFE hemochromatosis complicated with hepatitis B virus infection, and the pattern of iron deposition resembled that in the eight patients with viral hepatitis, wherein the deposition was mainly in the sinusoidal cells and/or portal macrophages. Histological grading and fibrosis staging differed among patients. The five patients with blood disordered showed iron accumulation mainly in the periportal hepatocytes, but mesenchymal iron deposits were also present. The grade of inflammation, as well as of fibrosis,was mild. The five patients with alcoholic disease and the five patients with drug-induced hepatitis showed hepatic iron deposition in swollen or ballooned hepatocytes. The two patients with excessive iron supply showed iron deposition localized within the parenchymal and mesenchymal cells.Etiologic diagnosis of hemochromatosis relies on both the type of iron deposition and the nature of associated lesions. Liver biopsy is necessary for both diagnosis and prognosis.

To investigate the histopathological subjective difference of laryngeal epitheliual premalignant lesions and to analyze the prognosis of every grade of laryngeal epitheliual premalignant lesion.According to 2005 WHO classification system, 237 cases of laryngeal epitheliual premalignant lesions were reviewd by 3 pathologists, meanwhile, the histopathological consistency among 3 pathologists was estimated with κ-statistics method. The Kaplan-Meier survival analysis were performed to assess the prognosis of every grade of laryngeal epitheliual premalignant lesion with follow-up data.There was totally a moderate consistency among 3 pathologists (κ values: 0.598 9), the histopathological difference was mainly between mild dysplasia and moderate dysplasia and between severe dysplasia and carcinoma in situ. The follow-up duration was between 18-120 months, and the median follow-up duration was 38 months. The carcinoma trsnformation rate was 8.44% (20/237) with an average malignant transformation duration of (19.45 ± 7.32) months, which was increased with the degree of dysplasia(mild dysplasia:1.67%, moderate dysplasia:3.57%, severe dysplasia:10.60%, carcinoma in situ:18.18%), no difference could be found between mild and moderate dysplasia, between moderate and severe dysplasia; Moreover, there was no difference between severe dysplasia and carcinoma in situ (P0.05).The histopathological variability brought the uncertainty for classification of laryngeal epitheliual premalignant lesions, which might have an impact on clinical management of laryngeal epitheliual premalignant lesions; there was obvious difference in carcinoma transformation between low-risk and high-risk laryngeal epitheliual premalignant lesions, and more attention on treatment and prognosis assessment should be paid for severe dysplasia as carcinoma in situ.

To study the clinicopathologic characteristics of IgG4-related disease in the orbital and periorbital tissue.The clinical manifestations and pathologic features of 17 cases of IgG4-related disease affecting the orbital and periorbital tissue encountered during the period from 2012 to 2013 were studied.There were 9 male patients and 8 female patients. The age of patients ranged from 11 to 71 years (mean = 48.5 years). The main clinical manifestation was swelling of the eyelids: bilateral in 11 patients and unilateral in 6 patients. The duration of disease ranged from 5 months to 7 years (more than 2 years in 13 cases). Six patients had history of allergic disorders. In addition to orbital/periorbital involvement, the disease also affected salivary gland, lymph node, lung and kidney. The disease relapsed in 9 patients. Amongst the 8 patients treated with steroids, 5 of them achieved complete remission and the remaining 3 patients had partial remission. The IgG4 level of the 17 cases ranged from 1.49 to 14.88 g/L. Histologic examination showed pseudolymphoma pattern in 8 cases, mixed pattern in 8 cases and sclerotic pattern in 1 case. There were various degrees of lymphoplasmacytic infiltrates (with lymphoid follicle formation) and stromal fibrosis. Classical obliterative phlebitis was absent. Tissue eosinophilia was demonstrated in the 17 cases studied. Immunohistochemical study showed the presence of more than 50 IgG4-positive plasma cells per high-power field, with IgG4/IgG plasma cells ratio more than 40%.There are characteristic clinical manifestations, pathologic features and laboratory findings in orbital and periorbital IgG4-related disease. Thorough understanding is important in arriving at a correct diagnosis.

To study the clinicopathological features, immunophenotype, differential diagnosis and prognosis of low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA).The histopathological features and clinical and pathological data of nine cases of LGNPPA were retrospectively analyzed. Immunohistochemistry (Two-step EnVision methods) was used to evaluate the expression of CKpan, vimentin, CK7, CK19, TTF-1 and TG; in situ hybridization was used to detect Epstein-Barr virus mRNA (EBER); and flow-through hybridization was used to evaluate the presence of human papilloma virus (HPV).The mean age for the nine patients (eight males, one female) was 45.3 years (range 23 to 62 years). Microscopically the tumors were characterized by lobulated, papillary and glandular structures with patchy distribution of spindle cells. The papillary interstitial tissue was edematous, myxoid or hyalinized. The tumors were unencapsulated and infiltrated into the surrounding stroma. Four cases displayed transition between normal nasopharyngeal epithelium to neoplastic cells; and one case contained psammoma bodies. Five cases were strongly positive for CKpan, vimentin, CK7, CK19, TTF-1, and were focally positive for EMA and CD117. These five cases were all negative for TG, CK5/6, CK20, S-100 protein, p63, Calponin and SMA. In situ hybridization for EBER and flow-through hybridization for HPV were negative in all five cases. Follow-up data showed no post-operative recurrence of the LGNPPA.LGNPPA is a rare low-grade neoplasm with distinct morphological characteristics. Its diagnosis is primarily based on the site of lesions and the histological features. The diagnosis and differential diagnosis of LGNPPA could be aided by immunohistochemical staining. LGNPPA may originate from nasopharyngeal epithelium; and the prognosis is good with simple and complete resection.

This study was to analyze the interobserver histopathological variability and carcinoma transformation of laryngeal premalignant lesions.A historical cohort study.Department of Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing, China.κ-statistics analysis was performed to estimate interobserver histopathological variability among pathologists by reassessment of 237 cases with laryngeal premalignant lesion according to 2005 WHO classification system. A retrospective follow-up of 237 patients over 8-year duration was carried out, and the carcinoma transformation of laryngeal premalignant lesions was analyzed using Kaplan-Meier survival curve estimation.κ-values of 0.5989 concerning interobserver variability indicated a moderate agreement among 3 pathologists. Major source of intergrade diagnostic disagreement between the original and the consensus diagnoses involved 2 grade pairs, namely, mild and moderate dysplasia, severe dysplasia, and carcinoma in situ. In addition, follow-up study showed that 20 of 237 (8.44%) laryngeal premalignant lesion cases developed into invasive carcinoma. Carcinoma transformation in severe dysplasia group exhibited a similar risk compared to that in carcinoma in situ group (P = .232).Severe dysplasia shows the same carcinoma transformation potential as the carcinoma in situ does. Clinically, more attention to severe dysplasia is needed in comparison with mild and moderate dysplasia.

Inflammatory myofibroblastic tumor (IMT) of the larynx is an unusual lesion, particularly in the pediatric age group. Laryngeal IMTs in children follow a benign clinical course with reports of only rare recurrences and no metastases. Although anaplastic lymphoma kinase (ALK) has been associated with IMTs, there is only one pediatric laryngeal IMT reported to be ALK-positive with immunohistochemical staining. Here, we present a case of a 10-year-old boy with a laryngeal IMT that recurred four times and was misdiagnosed as recurrent respiratory papillomatosis after the initial three operations. ALK positivity was demonstrated by both immunohistochemical staining and fluorescence in situ hybridization. To the best of our knowledge, this case report is the first to describe a laryngeal IMT that recurred multiple times and was confirmed to be ALK-positive at the molecular level.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a highly malignant carcinoma originating from the midline of the body. This study investigated the clinicopathological significance of NUT rearrangements in poorly differentiated malignant tumors (PDMTs) of the upper-respiratory tract (URT) in China. The clinical and pathological features of 155 PDMTs of the URT were reviewed. Epstein-Barr virus (EBV)-encoded RNA and NUT were investigated by in situ hybridization and immunohistochemistry (IHC), respectively. NUT-positive cases were examined by fluorescence in situ hybridization (FISH) and immunohistochemical staining with a set of cytokeratins (CKs) and neuroendocrine markers. One case was observed by transmission electron microscopy. Four cases of poorly differentiated squamous cell carcinomas and sinonasal undifferentiated carcinomas were diffuse positive for NUT by IHC and also stained for antibodies to CKs and P63 but were negative for neuroendocrine markers. Only 2 of these 4 cases showed rearrangements of the NUT and BRD4 genes by FISH; both these patients died within 12 months. The remaining 2 patients showed no NUT rearrangement by FISH and did not have an aggressive clinical course. NMC is a rare, poorly differentiated carcinoma, which occurs most often in midline organs, and in this first series from China, affected the sinonasal tract of older adults and was not associated with EBV infection. Determination of NUT protein expression and gene rearrangement can allow the differentiation of NMC from other URT PDMTs. The authors suggest that molecular determination of NUT gene rearrangements should therefore represent the gold standard for NMC diagnosis.

Adenoid cystic carcinoma of the external auditory canal is very rare in a child, and has not previously been reported in an individual younger than 18 years. We report an 8-year-old girl with adenoid cystic carcinoma of the external auditory canal associated with cholesteatoma. At the time of diagnosis, the tumor had invaded the surrounding structures and metastasized to the lymph nodes. She underwent palliative surgery and radiotherapy. She subsequently deteriorated and died of her disease 31 months later.

Background Gain of 3q26 is frequently observed in squamous cell carcinomas of mucosal origin, including those originating in the head and neck region. The human telomerase RNA component (hTERC) gene, which is located on chromosome 3q26, encodes for an RNA subunit of telomerase that maintains the length of telomeres through cellular divisions, and is activated in malignant diseases. The present study was designed to detect hTERC amplification in laryngeal lesions and evaluate whether this might serve as a supportive biomarker in histopathological analysis for in the diagnosis of laryngeal lesions. Methods Fluorescent in situ hybridization (FISH) was applied on formalin-fixed paraffin-embedded blocks of 93 laryngeal specimens, including 14 normal epithelium (NE), 15 mild dysplasia (Md), 18 moderate dysplasia (MD), 16 severe dysplasia (SD), 9 carcinoma in situ (CIS), and 21 invasive carcinoma (IC)). Results By histopathologic examination, hTERC amplification rates in NE, Md, MD, SD, CIS and IC cases were 0% (0/14), 13.33% (2/15), 72.22% (13/18), 81.25% (13/16), 100% (9/9) and 100% (21/21), respectively. Amplification of hTERC was significantly associated with histopathologic diagnosis (P < 0.0001). The percentage of hTERC amplification in patients with MD, SD, CIS, and IC was significantly higher than those with NE or Md (P < 0.0001). The number of cells with abnormal signals increased and the abnormal signal patterns were diversified with increasing severity of laryngeal dysplasia (P < 0.0001). Conclusions The hTERC amplification is important in the development of laryngeal squamous cell carcinoma (LSCC). FISH detection of hTERC amplification may provide an effective approach in conjunction with histopathologic evaluation for differential diagnosis of laryngeal lesions. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2226606266791985

Rapid detection and differentiation of Aspergillus and Mucorales species in fungal rhinosinusitis diagnosis are desirable, since the clinical management and prognosis associated with the two taxa are fundamentally different. We describe an assay based on a combination of broad-range PCR amplification and reverse line blot hybridization (PCR/RLB) to detect and differentiate the pathogens causing fungal rhinosinusitis, which include five Aspergillus species ( A. fumigatus , A. flavus , A. niger , A. terreus , and A. nidulans ) and seven Mucorales species ( Mucor heimalis , Mucor racemosus , Mucor cercinelloidea , Rhizopus arrhizus , Rhizopus microsporus , Rhizomucor pusillus , and Absidia corymbifera ). The assay was validated with 98 well-characterized clinical isolates and 41 clinical tissue specimens. PCR/RLB showed high sensitivity and specificity, with 100% correct identifications of 98 clinical isolates and no cross-hybridization between the species-specific probes. Results for five control isolates, Candida albicans , Fusarium solani , Scedosporium apiospermum , Penicillium marneffei , and Exophiala verrucosa , were negative as judged by PCR/RLB. The analytical sensitivity of PCR/RLB was found to be 1.8 × 10 −3 ng/μl by 10-fold serial dilution of Aspergillus genomic DNA. The assay identified 35 of 41 (85.4%) clinical specimens, exhibiting a higher sensitivity than fungal culture (22 of 41; 53.7%) and direct sequencing (18 of 41; 43.9%). PCR/RLB similarly showed high specificity, with correct identification 16 of 18 specimens detected by internal transcribed spacer (ITS) sequencing and 16 of 22 detected by fungal culture, but it also has the additional advantage of being able to detect mixed infection in a single clinical specimen. The PCR/RLB assay thus provides a rapid and reliable option for laboratory diagnosis of fungal rhinosinusitis.

To study the clinicopathologic characteristic of the primary extranodular non Hodgkin's lymphoma in head and neck.Clinical manifestation and the characteristic of clinicopathology of 216 extranodular non-Hodgkin's lymphoma patients in head and neck were analyzed retrospectively.The age of thirty-one to sixty and seventy-one to eighty years old were more common age range in the group of patients. Nasal cavity was the most commonly primary involved site (95 cases, 44.0%), secondly was tonsil (47 cases, 21.8%). The most common histologic subtype was NK/T cell lymphoma, which accounted for 49.5% (107 cases) of cases, secondly was diffuse large B cell lymphoma (DLBCL, 58 cases, 26.7%). The most common histologic subtype in different stach groups respectively is: NK/T cell lymphoma in nasal cavity (74 cases,77.9%), DLBCL in paranasal sinus (6 cases, 50.0%), DLBCL in tonsil (27 cases, 57.4%), NK/T cell lymphoma in nasopharynx (17 cases, 44.7%), and DLBCL in lingual root (5 cases, 45.4%).We conclude that primary extranodular non-Hodgkin's lymphoma is common in head and neck patients. There is characteristic in age, primary involved site and histologic subtype, which is helpful to understand these characteristic for pathologic diagnosis.

To search a method for showing dust granules in phagocytes.The autopsy samples of 10 cases who died of non-pulmonary diseases(group A), 6 cases with silicosis(group B) and 5 cases of dead fetus(group C) were collected. The samples of lung, spleen and lymphnodes were stained by methods of (1)HE staining; (2)Warthin-Starry staining(W-S staining) and modified W-S staining; (3) CD68 (as a first antibody) immunohistochemical staining. The ultrastructure and chemical component of the dust granules in the pulmonary phagocytes(dust cells) of group A(3 cases) and group B(3 cases) were observed and analyzed by transmission electron microscope(TEM) and analytic electron microscope(AEM).In group A and B smaller or minute dust granules which could not be shown by HE staining method were clearly shown by W-S staining and modified W-S staining methods. There were no positive granules found in group C. The CD68 marker of the dust cells was positive. The size, shape, density and chemical elements of the dust granules of group A were different from those of group B under TEM and AEM, excluding bacteria and other intracellular contents.The dust granules in the phagocytes could be shown by W-S staining method, its staining effect for minute dust granules is superior to general HE staining. However, the determination of chemical elements of dusts must depend on AEM.