Benign but fatal: management of endotracheal Rosai-Dorfman disease with acute onset.

Rosai-Dorfman disease (RDD) is a non-malignant condition mainly manifesting as a proliferation of histiocytes in lymph nodes. Endotracheal RDD (ERDD) with an acute onset presentation is extremely rare. There are few case reports of ERDD mainly concerning its pathology, diagnostics and bronchoscopic treatment, without providing sufficient clinical information from a comprehensive perspective. As a novel and challenging technique, tracheal resection and reconstruction (TRR) with spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS) has been reported as feasible and safe in highly selected patients, but few centres have shared their experience with this approach. This case-based discussion includes not only practical issues in the management of a life-threatening ERDD patient, but also specialists' views on the management of acute obstructive airway, and the surgeons' reflection on TRR with SV-VATS.

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.

Silva cumulative score and its relationship with prognosis in Endocervical adenocarcinoma.

BACKGROUND: The Silva system has been demonstrated to have a good predictive value of lymph node metastasis (LNM) in endocervical adenocarcinoma (EAC). Tumours were classified based on the highest identified pattern of invasion in this system, this may not exactly reflect the true situation when it presents with a "mixed pattern" in some cases. Recent study has shown that patients with lymphovascular invasion (LVI) have worse prognosis in EAC. Here we design a Silva cumulative score (SCS) system which also combined the LVI status to explore its prognostic role in EAC patients. METHODS: A total of 120 patients with EAC were included in this study. Clinicopathological characteristics were retrospectively retrieved from the medical records and follow-up data were obtained. The clinicopathological information included age at diagnosis, depth of invasion (DOI), LNM, LVI, Silva classification, and SCS. SCS is a classification system based on the sum score of different Silva pattern which is founded on morphological phenomena. The relationships between the pathological characteristics and prognoses were analyzed. RESULTS: According to the Silva system, 11 (9.2%), 22 (18.3%) and 87 (72.5%) patients had patterns A, B, and C, respectively. Patients with pattern C had the highest incidence of LVI and LNM (p < 0.05). Although the Kaplan-Meier curves demonstrated that survival decreased with increasing Silva classification for A-C cancers, there was no statistically significant difference [disease-free survival (DFS): p = 0.181; overall survival (OS): p = 0.205]. There were 45 cases presented as mixed-type of Silva patterns. According to the SCS, 23 cases (19.2%) were rated as grade I, 31 cases (25.8%) as grade II and 66 (55.0%) cases as grade III. Patients with SCS grade III had the highest incidence of LVI and LNM (p < 0.05). Kaplan-Meier analysis revealed that patients with higher SCS had significantly shorter DFS and OS than those with lower SCS (p < 0.05). High SCS was an independent predictor of poorer OS and DFS (p < 0.05) in patients with EAC. CONCLUSIONS: The application of the Silva system could effectively predict the LNM of patients and may be helpful in selecting an appropriate surgical procedure. The SCS system we designed showed a good predictive value for DFS and OS in EAC.

microRNA-200c-3p suppresses proliferation and invasion of nephroblastoma cells by targeting EP300 and inactivating the AKT/FOXO1/p27 pathway.

miR-200c-3p is aberrantly expressed in numerous cancers, but its underlying mechanisms in nephroblastoma are unknown. In our study, the differentially regulated miRNAs between the nephroblastoma tissues and adjacent non-neoplastic renal tissues were screened based on microarray analysis. The miR-200c-3p expression in nephroblastoma tissues and cells was detected by qRT-PCR. Then, the effects of miR-200c-3p mimic or inhibitor on cell proliferation, invasion, and migration were evaluated by CCK-8 assay, plate colony formation assay, soft agar assay, Transwell, and wound-healing assay in SK-NEP-1 and G401 cells. Afterward, the target gene of miR-200c-3p was predicted by TarBase, miRTarBase, miRDB softwares, and then verified by dual-luciferase reporter gene assay. The in vivo effects of miR-200c-3p on pathological changes and tumor volume were investigated in tumor xenograft mice by H&E staining and in vivo fluorescence imaging. ChIP assay was used to evaluate the relationship between histone acetyltransferase E1A-binding protein p300 (EP300) and P27, and the relationship of the role of miR-200c-3p in nephroblastoma and the AKT/FOXO1/p27 signaling pathways was evaluated by western blotting. Our study shows that miR-200c-3p was downregulated in nephroblastoma tissues and cells, and EP300 was a target gene of miR-200c-3p. Furthermore, miR-200c-3p mimic decreased cell proliferation and inhibited cell migration and invasion in nephroblastoma. Mechanistically, miR-200c-3p could inhibit p-AKT activity and enhance p-FOXO1 and p27 expression. Notably, the transcription factor P27 could bind to the EP300 promoter. This study demonstrates a new approach to treat nephroblastoma.

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.

Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study.

BACKGROUND: Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent. METHODS: Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically. RESULTS: The study participants had a mean age of 59 years (range, 35-81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P <  0.001), necrotic/tumor debris (31 of 42; 73.8%; P <  0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P <  0.001), desmoplasia (35 of 41; 85.4%; P <  0.001), and grade 3 nuclei (12 of 14; 85.7%; P <  0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS. CONCLUSIONS: Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning.

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.

Bcl-2 family in non-small cell lung cancer: its prognostic and therapeutic implications.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Despite significant advances in its research of tumor biology and therapy, the prognosis for this neoplasm has still remained poor. The great majority of anticancer agents, regardless of their mechanisms of action, exert their lethal actions on cancer cells by inducing apoptosis following drug-induced cellular damage. Many reported studies have evaluated the prognostic and therapeutic implications of apoptosis in lung cancer, but their exact clinical value has remained unclear. Therefore more prospective studies are currently required to further validate apoptosis as prognostic and predictive biomarkers in lung cancer patients. The current study reviewed the studies on the prognostic and predictive significances of Bcl-2 family proteins in NSCLC. We also discussed potential treatment strategies which could target apoptotic proteins in lung carcinoma cells. Exception for Bcl-2 itself, studies of the prognostic significance of other Bcl-2 family proteins is markedly limited. The abundance of literature suggests that targeting apoptosis in NSCLC is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies, and new biomarkers are needed.

MET gene copy number gain is an independent poor prognostic marker in Korean stage I lung adenocarcinomas.

BACKGROUND: MET gene copy number gain (CNG) and protein overexpression have been reported in lung cancer, but the clinical implications in early stage adenocarcinoma remain unclear. METHODS: We investigated MET gene copy number and protein expression in 141 cases of surgically resected stage I pulmonary adenocarcinoma. MET gene CNG was determined by silver in situ hybridization, and MET protein expression was assessed by immunohistochemistry. The correlation between MET gene CNG/protein expression and clinicopathologic parameters and prognostic significance was analyzed. RESULTS: MET gene CNG was found in 24.1% (34 of 141) of the cases and was associated with larger tumor size, pleural invasion, and lymphatic vessel invasion. MET gene CNG was inversely correlated with the presence of lepidic subtype (r = -0.17, p = 0.045) and was not associated with EGFR, KRAS mutation, or ALK gene rearrangement. In addition, MET gene CNG was significantly associated with shorter disease-free survival (DFS) (49 vs. 75 months; p < 0.001) and shorter overall survival (OS) (65 vs. 78 months; p = 0.01). Multivariate analysis confirmed that MET gene CNG was significantly associated with poorer DFS [p < 0.001; hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.2-13.9] but was not significantly associated with OS. MET overexpression was observed in 71.3% of cases (97 of 136), but it was not correlated with gene CNG. CONCLUSIONS: MET gene CNG is an independent poor prognostic factor in patients with stage I lung adenocarcinoma. It is associated with aggressive pathologic features and is inversely correlated with the presence of lepidic subtype.

Cytoplasmic YAP expression is associated with prolonged survival in patients with lung adenocarcinomas and epidermal growth factor receptor tyrosine kinase inhibitor treatment.

BACKGROUND: Yes-associated protein (YAP) has been reported to be associated with the prognosis of various cancers and also to affect epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) activity in ovarian cancer cell lines. However, few studies have evaluated YAP protein expression in lung cancer, and the results have lacked consistency. METHODS: YAP expression was evaluated in a total of 205 curatively resected lung adenocarcinomas and 36 cases of EGFR-mutated TKI-treated patients. Correlations between the expression of YAP and clinicopathologic features, response to EGFR-TKI treatment, and prognostic significance were analyzed. RESULTS: High cytoplasmic YAP expression was positively correlated with the clinicopathologic parameters that have been associated with favorable prognosis. Multivariate analysis revealed that high cytoplasmic YAP expression was an independent prognostic factor in lung adenocarcinomas (progression-free survival: hazard ratio [HR] 0.659; 95 % confidence interval [CI] 0.431-1.010; p = 0.050; overall survival: HR, 0.474; 95 % CI 0.263-0.854; p = 0.013) and EGFR-TKI-treated patients with EGFR mutation (progression-free survival: HR, 0.346; 95 % CI 0.146-0.818; p = 0.016; overall survival: HR, 0.291; 95 % CI 0.125-0.676; p = 0.004). CONCLUSIONS: High cytoplasmic YAP expression predicted a good clinical outcome for patients with lung adenocarcinoma and in EGFR-TKI-treated patients. Therefore, YAP may play a role in EGFR-TKI-treated lung cancer, and YAP targeting may enhance therapeutic effects in combination with other cancer drugs.

Alteration of the E-cadherin/ß-catenin complex predicts poor response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation alone may be insufficient to predict clinical outcomes in the response to EGFR-tyrosine kinase inhibitor (TKI) therapy. The secondary mutation T790 M and MET amplification are mechanisms of acquired resistance to EGFR-TKI in approximately 50 % of patients, but the remaining mechanisms are unknown. METHODS: Eight metastatic lesions and specimens from 41 non-small cell lung carcinoma (NSCLC) patients harbouring activating EGFR mutations who underwent surgical resection and EGFR-TKI therapy were available. Immunohistochemistry was used to evaluate E-cadherin, ß-catenin, and PTEN. Chromogenic in situ hybridisation and silver-enhanced in situ hybridisation were used to evaluate EGFR and MET amplification. RESULTS: Patients with E-cadherin/ß-catenin alteration showed a poor objective response rate (ORR) (p = 0.005) and shorter overall survival (p = 0.059). Additionally, ß-catenin alteration was associated with a poor ORR (p = 0.012). Of the metastatic tumours, three cases (37.5 %) showed the acquisition of altered E-cadherin/ß-catenin and PTEN loss and two cases (25 %) demonstrated MET/EGFR amplification. CONCLUSIONS: Altered E-cadherin/ß-catenin expression in NSCLC harbouring EGFR mutations was associated with a poor response to EGFR-TKI. During metastatic progression, changes in E-cadherin/ß-catenin were found. These results may suggest that E-cadherin/ß-catenin alteration is related to poor TKI response and resistance.

Discordance between anaplastic lymphoma kinase status in primary non-small-cell lung cancers and their corresponding metastases.

AIMS: The anaplastic lymphoma kinase gene (ALK) has attracted considerable attention as a potential molecular target in non-small-cell lung cancer (NSCLC). However, it is unclear whether ALK alterations are acquired during the metastatic progression of NSCLC. METHODS AND RESULTS: ALK status and ALK expression were evaluated in a series of 67 primary NSCLCs and their corresponding metastatic lesions using fluorescence in-situ hybridization and immunohistochemistry. ALK rearrangement was detected in 7.5% (5/67) of the primary tumours and in 9.0% (6/67) of the metastases (P < 0.001). ALK copy number gain (CNG) was detected in 1.5% (1/67) of the primary tumours and in 35.8% (24/67) of the metastases. Whereas ALK rearrangement was detected only in adenocarcinomas, CNG was identified in various histological subtypes of NSCLC. ALK expression was detected in 11.9% (8/67) of the primary tumours and in 25.4% (17/67) of the metastatic lesions. CONCLUSIONS: ALK alteration and ALK expression can be acquired during metastatic progression in NSCLC, and ALK CNG is associated with ALK expression.

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.

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.

YAP increases response to Trastuzumab in HER2-positive Breast Cancer by enhancing P73-induced apoptosis.

The role of the Yes-associated protein (YAP) in oncogenesis and progression of breast cancer remains controversial. Meanwhile, development of therapeutic resistance to trastuzumab, a common breast cancer treatment administered after chemotherapy, is a significant challenge in the treatment of HER2-positive breast cancer. We, therefore, analyzed the role of YAP in trastuzumab resistance in HER2-positive-breast carcinoma cells in vitro and evaluated the status of YAP and related proteins in patient-derived breast carcinoma tissues by immunohistochemistry. YAP expression was observed in both BT474-TS (trastuzumab-sensitive) and BT474-TR (trastuzumab-resistant) cells. Treatment with trastuzumab increased expression of nuclear-YAP (N-YAP) in BT474-TS cells, whereas BT474-TR cells showed a decrease in N-YAP expression following trastuzumab treatment. YAP silencing significantly reduced trastuzumab-induced inhibitory effects in BT474-TS cells. YAP-silenced cells also showed decreased apoptosis and significantly lower p73 levels following trastuzumab treatment. Combined protein kinase B (AKT) inhibitor-trastuzumab treatment significantly inhibited BT474-TR cell proliferation, resulting in increased N-YAP and p73 expression, as well as apoptosis. In both paclitaxel, doxorubicin and cyclophosphamide (TAC)-treated, and docetaxel, carboplatin, and trastuzumab (TCbH)-treated groups; the pathological complete response (pCR) ratios were inversely correlated with p-AKT status in biopsy specimens, while YAP and p73 status were positively correlated with the pCR ratio in the biopsy specimens of the TCbH group. Our results show that YAP is involved in trastuzumab resistance in HER2-positive breast carcinoma cells and that YAP and AKT may be developed as prognostic markers of neoadjuvant trastuzumab therapy in patients with HER2-positive breast cancer.