The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma.

BACKGROUND: The classification of thymomas is based on the morphology of epithelial tumor cells and the proportion of lymphocytes. Type A thymomas are composed of the spindle or oval tumor epithelial cells. Tumor cells of B thymomas are epithelioid-shaped with increasing atypia. Type AB thymomas have the features of epithelial tumor cells of A and B thymomas. The diagnosis can be difficult because of the complex morphology. Some novel thymic epithelial markers have been reported in several preclinical studies, but they have not been applied to clinical practice. Here, we investigated the expression of 3 cortical and 3 medullary markers, which are thymoproteasome-specific subunit ß5t (ß5t), thymus-specific serine protease 16 (PRSS16), cathepsin V, autoimmune regulator (AIRE), CD40 and claudin-4. METHODS: Immunohistochemistry was used to analyze 53 cases of thymomas and thymic squamous cell carcinomas (TSCC), aiming to explore the expression of cortical and medullary epithelial markers and their correlation with histological classification, Masaoka-Koga stage, and prognosis. RESULTS: Our results found that for cortical epithelial markers the expression of ß5t, PRSS16, and cathepsin V was higher in type AB and B thymomas than in micronodular thymoma with lymphoid stroma (MNT), and we observed a dramatic increase of ß5t and PRSS16 expression in type AB compared to type A thymomas. In medullary epithelial markers, the expression of AIRE was higher in type A than in B3 thymomas. CD40 and ß5t expression were associated with the Masaoka-Koga stage. High cathepsin V expression was related to a good prognosis and a longer progression-free survival. CONCLUSION: This is the first comprehensive analysis of the role of thymic cortical and medullary epithelial markers as biomarkers for differential diagnosis and prognosis in thymic tumors. Thymic medullary epithelial immunophenotype was found to exhibit in type A, MNT, and TSCC. Type B thymomas primarily exhibited a cortical epithelial immunophenotype. Type AB thymomas showed cortical, medullary, or mixed corticomedullary epithelial immunophenotype. Our results demonstrated that thymic cortical and medullary epithelial markers including ß5t, PRSS16, cathepsin V, and AIRE could be used as ancillary markers in the diagnosis and prognosis of thymic epithelial tumors.

PD-L1 expression and immune stromal features in HPV-independent cervical adenocarcinoma.

AIMS: Human papilloma virus (HPV)-independent cervical adenocarcinoma (CA) is usually diagnosed at an advanced stage, while the therapeutic options are limited. Therefore, effective treatment options are required. The programmed cell death 1 (PD-1) inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical squamous cell carcinoma expressing PD-ligand 1 (PD-L1). However, no data regarding PD-L1 expression in HPV-independent CA are available. Thus, we evaluated the association between PD-L1 expression and the clinicopathological characteristics and survival of patients with HPV-independent CA. METHODS: We evaluated PD-L1, mismatch repair (MMR) protein expression and the immune stromal features of 44 patients with HPV-independent CA. PD-L1 expression was defined as a combined positive score (CPS) ≥1 and a tumour proportion score (TPS) ≥1%. RESULTS: PD-L1 expression was observed in 14 cases (31.8%) with CPS ≥1 and 12 cases (27.3%) with TPS ≥1%. PD-L1 expression, based on either the CPS or the TPS, was associated with a high tumour-infiltrating lymphocyte percentage (CPS = P < 0.001; TPS = P < 0.001). Patients with a PD-L1 CPS ≥1 showed worse progression-free survival and overall survival than PD-L1-negative patients (P = 0.004 and P = 0.023, respectively). Forty-two cases demonstrated intact MMR expression and two cases demonstrated loss of MSH2/MSH6. CONCLUSIONS: Our data demonstrated that PD-L1 was expressed in HPV-independent CA, especially in clear cell carcinoma, and that PD-L1 expression is a negative prognostic marker. Our data support the role of PD-L1 in HPV-independent CA and its potential as an immunotherapeutic target.

Clinicopathologic Features and Genetic Alterations in Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma of the Lung: Long-Term Follow-Up Study of 121 Asian Patients.

BACKGROUND: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are both small tumors with good prognosis after surgical resection, and most of them present as ground glass opacities (GGOs) on computed tomography (CT) screening. However, the differences in clinicopathologic features and genetic alterations between AIS and MIA are poorly elaborated, and few studies have evaluated the prognosis of MIA with different invasive components. Meanwhile, the histological features of lung lesions presenting as unchanged pure GGOs are barely understood. METHODS: Clinicopathologic features and genetic alterations of AIS (n = 59) and MIA (n = 62) presenting as GGOs were analyzed. Long-term preoperative observation (ranging from 2 to 1967 days) and postoperative follow-up (ranging from 0 to 92 months) was conducted. RESULTS: The tumor size and consolidation/tumor ratio were significantly larger in the MIA cohort than those in the AIS cohort both on CT and microscopy images. Immunohistochemically, the expression of p53, Ki67, and cyclin D1 was higher in MIA than in AIS. The EGFR mutation rate was significantly higher in MIA, while other genetic alterations showed no differences. Six MIA cases showed recurrence or metachronous adenocarcinoma and all the cases with a predominant micropapillary invasive pattern demonstrated this feature. CONCLUSIONS: The current CT measurements may be helpful in distinguishing AIS from MIA, but show limited utility in predicting the histology of unchanged pure GGOs. The invasive pattern may have an influence on the postoperative process of MIA; therefore, further studies are needed to evaluate the current diagnostic criteria and treatment strategy for MIA.

Comprehensive analysis of spread through air spaces in lung adenocarcinoma and squamous cell carcinoma using the 8th edition AJCC/UICC staging system.

BACKGROUND: This study aimed to comprehensively investigate the effect of spread through air spaces (STAS) on clinicopathologic features, molecular characteristics, immunohistochemical expression, and prognosis in lung adenocarcinomas (ADC) and squamous cell carcinomas (SQCC) based on the 8th edition AJCC/UICC staging system. METHODS: In total, 303 ADC and 121 SQCC cases were assessed retrospectively. Immunohistochemical staining was performed for E-cadherin, vimentin, Ki67, survivin, Bcl-2, and Bim. Correlations between STAS and other parameters were analyzed statistically. RESULTS: STAS was observed in 183 (60.4%) ADC and 39 (32.2%) SQCC cases. In ADC, the presence of STAS was associated with wild-type EGFR, ALK and ROS1 rearrangements, low E-cadherin expression, and high vimentin and Ki67 expression. In SQCC, STAS was associated with low E-cadherin expression and high vimentin and survivin expression. Based on univariate analysis, STAS was associated with significantly shorter disease-free survival (DFS) and overall survival (OS) in ADC. In SQCC, STAS tended to be associated with shorter OS. By multivariate analysis, STAS was an independent poor prognostic factor in ADC for DFS but not OS. Stratified analysis showed that STAS was correlated with shorter DFS for stage I, II, IA, IB, and IIA ADC based on univariate analysis and was an independent risk factor for DFS in stage I ADC cases based on multivariate analysis. CONCLUSIONS: Our findings revealed that STAS is an independent negative prognostic factor for stage I ADC using the new 8th edition AJCC/UICC staging system. Stage I patients with STAS should be followed up more closely and might need different treatment strategies.

Proscillaridin A induces apoptosis, inhibits STAT3 activation and augments doxorubicin toxicity in prostate cancer cells.

Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSN-A in various cancers including prostate cancer remain largely unexplored. In the present study, we have shown that PSN-A inhibits proliferation and induces apoptosis in prostate cancer cells in a dose-dependent manner. Further mechanistic study have shown that anticancer activity of PSN-A in prostate cancer cells is associated with ROS generation, Bcl-2 family proteins modulation, mitochondrial membrane potential disruption and ultimately activation of caspase-3 and cleavage of PARP. Moreover, we found that PSN-A inhibits JAK2/STAT3 signaling and augments doxorubicin toxicity in prostate cancer cells. Of note, LNCaP cells were found to be more sensitive to PSN-A treatment as compared to DU145 cells. Taken together, the data provided first evidence of the anticancer activity and possible molecular mechanism of PSN-A in prostate cancer. Further study is needed to develop PSN-A into a potential lead compound for the treatment of prostate cancer.

Malignant Mixed Epithelial and Stromal Tumor of the Kidney: Report of a Carcinosarcoma Case and an Updated Literature Review.

Mixed epithelial and stromal tumors of the kidney (MESTK) are rare and recently defined entities that comprise both epithelial and stromal cells. MESTK is mostly benign; however, to date, 18 borderline or malignant cases have been reported. In this study, we report a case of carcinosarcoma exhibiting a large carcinoma and small sarcoma component, and review the relevant literature. The patient was a 59-year-old woman who presented with a large mass in the left kidney having solid and focal cystic components. The patient underwent left radical nephrectomy. The tumor was gray-white and solid-cystic, with a relatively clear boundary. Microscopically, the tumor revealed benign and malignant components. The benign component consisted of multiple tubules, variable-sized cysts lined with benign epithelium, and hyalinized stroma. The malignant component was composed of predominantly small cell neuroendocrine carcinoma and a small quantity of adenocarcinoma, squamous cell carcinoma, and sarcoma. Finally, a diagnosis of the malignant MESTK was made. Certain cases of borderline or malignant transformation of MESTK have been published, so it is important to enhance findings made by other studies.

Ubiquitin C-terminal hydrolase-L1 expression in non-small-cell lung cancer and its association with clinicopathological features and prognosis.

UbiquitinC-terminal hydrolase-L1 (UCH-L1) is a cysteine hydrolase. It functions as a ubiquitin hydrolase, stabilizes the ubiquitin monomer, and affects cell division through cell cycle protein deubiquitination. Abnormal UCH-L1 expression is closely related to the occurrence and development of several tumors. Although some in vitro studies have demonstrated the significance of UCH-L1 in non-small-cell lung cancer (NSCLC), only few clinical studies have focused on the UCH-L1 expression in NSCLC, and the results are controversial and non-uniform. We investigated the UCH-L1 expression in 401 cases of surgically resected NSCLC, including 286 cases of adenocarcinoma (ADC) and 65 cases of squamous cell carcinoma. The associations between the UCH-L1 expression and clinicopathological features, programmed cell death-ligand 1 (PD-L1) expression, and prognostic significance were analyzed. For NSCLC, the UCH-L1 expression is associated with sex, smoking history, tumor size (>3 cm), lymphocyte infiltration, advanced pathological stages, and shortened overall survival (OS; 89.72 vs. 114.55 months; P = 0.005), but not PD-L1 expression. The UCH-L1 expression in ADC is associated with advanced pathological stages, pleural invasion, and shortened OS (90.38 vs. 118.55 months; P = 0.010). Multivariate analysis confirmed that UCH-L1 expression was an independent poor prognostic factor for NSCLC (OS: hazard ratio [HR], 1.854; 95% confidence interval [CI], 1.132-3.038; P = 0.014). Our results suggest that the UCH-L1 expression differs across tumors with different clinicopathological features, and it is related to poor prognosis.

Giant nodular fasciitis originating from the humeral periosteum: A case report.

BACKGROUND: Nodular fasciitis (NF) is a self-limiting tumor that mostly occurs in the subcutaneous superficial fascia. NF originating from the appendicular periosteum is extremely rare. A large NF lesion of periosteal origin can be misdiagnosed as a malignant bone tumor and may cause overtreatment. CASE SUMMARY: A right axillary mass was found in a 46-year-old man and was initially diagnosed intraoperatively as low-grade sarcoma, but later diagnosed as NF after post-resection histopathological evaluation. Furthermore, fluorescence in situ hybridization analysis revealed a USP6 gene rearrangement that confirmed the diagnosis. To the best of our knowledge, this is the first case of NF in the humeral periosteum. CONCLUSION: NF poses a diagnostic challenge as it is often mistaken for sarcoma. Postoperative histopathological examination of whole sections can be combined with immunohistochemical staining and, if necessary, the diagnosis can be confirmed by molecular detection, and thus help avoid overtreatment.

Diagnostic Challenge of Sarcomatoid Variant of ALK-Positive Anaplastic Large Cell Lymphoma: Case Report and Updated Systematic Literature Review.

The sarcomatoid variant of anaplastic large cell lymphoma is an extremely rare histologic pattern of anaplastic large cell lymphoma that consists of spindle-shaped neoplastic cells and is easily misdiagnosed as a soft tissue sarcoma. We report a case of the sarcomatoid variant of anaplastic large cell lymphoma that was initially diagnosed as an inflammatory myofibroblastic tumor in our hospital and as liposarcoma after consultation. This article analyzed the features of this entity by reviewing the literature. Only 15 cases have been reported, most of which were misdiagnosed as sarcoma, sarcomatoid carcinoma, or inflammatory myofibroblastic tumor. Most of the reported cases showed a myxoid stroma, with a variable number of inflammatory cells. The hallmark cells usually can be found by careful evaluation of the slides. Immunohistochemistry including CD30, EMA, and ALK are the most useful for diagnosis. Most are III or IV stage, and have a good prognosis after chemotherapy.

Biomass pyrolysis with alkaline-earth-metal additive for co-production of bio-oil and biochar-based soil amendment.

The alkaline-earth-metal (AEM) has a good performance on modification of both bio-oil and biochar during biomass pyrolysis. In this work, the pyrolysis of rice husk (RH) in the presence of CaO, CaCO3, MgO and MgCO3 was comparatively studied for selecting an appropriate AEM additive to balance the qualities of pyrolytic products. Pyrolysis of RH with the AEM additives could decrease the acids content and increase the hydrocarbons content in bio-oil. Compared with the Ca-additives (i.e., CaO, CaCO3), the Mg-additives (i.e., MgO, MgCO3) were more beneficial for enhancing the hydrocarbons production. The addition of biochar to soil can significantly enhance the water retention. RHC-MgCO3 had a maximum water retention capacity, while RHC-MgO had a minimum water retention capacity due to its lowest specific surface area. Additionally, the Mg-modified biochar had a much higher nutrient (i.e., K+, PO43-) adsorption capacity. In particular, RHC-MgO with a lowest specific surface area had a highest PO43- adsorption capacity, which was evidenced by the adsorption of PO43- onto biochar mainly controlled by the chemisorption process. PO43- adsorbed in the RHC-MgO released rapidly indicating its low PO43- retention capacity. In general, MgCO3 would be an appropriate candidate that is used in pyrolysis of biomass for co-production of bio-oil and biochar composite with high capacities of water/nutrient adsorption and retention for soil amendment.

Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review.

BACKGROUND: Spread through air spaces (STAS) is a spreading phenomenon of lung cancers, which is defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. To date, several articles have reviewed the studies concerning the significance of STAS; however, most articles focused on the prognosis without summarizing the significance of STAS on other aspects. In this review, we comprehensively summarized the current literature related to STAS, so as to explore the clinical significance of STAS from multiple perspectives. MAIN BODY: This section provided a comprehensive overview of the significance of STAS from multiple perspectives and summarized current controversies and challenges in the diagnosis and clinical application. CONCLUSION: STAS is a conspicuous spreading phenomenon of lung cancers indicating worse prognosis; nevertheless, the treatment strategy for patients with STAS remains to be discussed. Further studies are needed to elaborate whether a STAS-positive patient who underwent limited resection needs a second operation or postoperative adjuvant treatment. Meanwhile, the internal mechanism of STAS formation is largely undiscovered. Whether the capability of detachment-migration-reattachment in STAS tumor cells is achieved at the time of primary tumorigenesis or in the progress of tumor development needs to be studied, and the related signal pathways or genetic alterations need to be explored. With this information, it may be possible to improve the prognosis of patients with STAS-positive lung cancers.

Differential Expression of PD-L1 in Central and Peripheral and TTF1-Positive and -Negative Small-Cell Lung Cancer.

Background: Central and peripheral location as well as thyroid transcription factor-I (TTF-1) expression was reported to be associated with different characteristics and prognosis of small-cell lung cancer (SCLC). This study aimed to investigate differential expression of PD-L1 in different SCLC subtypes, and in biopsy and resection specimens. Methods: We retrospectively analyzed 142 SCLC tumor samples using immunohistochemistry to correlate PD-L1 (22C3) expression with clinicopathologic features and survival data. Results: PD-L1 expression was found in 19.7% SCLCs (28/142) and was more frequent in females than in males (32%, 16/50 vs. 13%, 12/92, p = 0.009), in central type than in peripheral type SCLCs (26%, 26/100 vs. 4.8%, 2/42, p = 0.003), and in TTF-1 positive than in negative SCLCs (23.8%, 25/105 vs. 8.1%, 3/37, p = 0.039). PD-L1 expression was associated with vascular (p = 0.001) and lymphatic invasion (p = 0.001). There was no significant difference in PD-L1 expression between biopsy and resection specimens. On univariate analysis, patients with PD-L1 expression had significantly shorter progression-free survival (PFS; p = 0.026) and overall survival (OS; p = 0.012). Multivariate analysis revealed that PD-L1 expression was an independent prognostic factor for OS (HR, 2.317; 95% CI 1.199-4.478; p = 0.012) and PFS (HR, 1.636; 95% CI 0.990-2.703; p = 0.051) in SCLC. Conclusions: PD-L1 expression was more frequent in central type, TTF-1 positive SCLCs, and predicted a poor clinical outcome in these patients. Therefore, tumor location and TTF-1 expression could predict expression status of PD-L1, and could potentially serve as clinical response to immunotherapy.

Pyrolysis and combustion kinetics of lignocellulosic biomass pellets with calcium-rich wastes from agro-forestry residues.

The pyrolysis and combustion kinetics of biomass pellets (i.e., rice husk, herb residue, and wood residue) with the calcium-rich wastes (i.e., CaO, CaCO3, and eggshell) from agro-forestry residues were comparatively studied. During pyrolysis or combustion of biomass, the Ca-rich wastes could slightly influence the decomposition rate in the stage of devolatilization at relatively lower temperatures (e.g., <400 °C). However, the lignin decomposition and the char combustion were obviously influenced by the calcium-based catalysis at higher temperatures (>700 °C). Particularly, the eggshell had a lowest activation energy in the stage of char combustion. The presence of alkali and alkaline-earth metals (AAEMs) in the eggshells might have positive effects on volatile and char combustion. During the combustion, the decomposition temperatures of CaCO3 and eggshell were decreased, thereby favoring to uptake CO2. Furthermore, by identifying the small molecular products, it was found that both CaCO3 and CaO can improve the pyrolysis of RH, but CaCO3 showed better performances, especially on CO2 capture at lower temperatures and on the enhancement of CO production.