World Health Organization Tumor Research Articles

Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor.

The World Health Organization's tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RT-qPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Neuroimaging of pediatric tumors of the sellar region-A review in light of the 2021 WHO classification of tumors of the central nervous system.

Sellar/suprasellar tumors comprise about 10% of all pediatric Central Nervous System (CNS) tumors and include a wide variety of entities, with different cellular origins and distinctive histological and radiological findings, demanding customized neuroimaging protocols for appropriate diagnosis and management. The 5th edition of the World Health Organization (WHO) classification of CNS tumors unprecedently incorporated both histologic and molecular alterations into a common diagnostic framework, with a great impact in tumor classification and grading. Based on the current understanding of the clinical, molecular, and morphological features of CNS neoplasms, there have been additions of new tumor types and modifications of existing ones in the latest WHO tumor classification. In the specific case of sellar/suprasellar tumors, changes include for example separation of adamantinomatous and papillary craniopharyngiomas, now classified as distinct tumor types. Nevertheless, although the current molecular landscape is the fundamental driving force to the new WHO CNS tumor classification, the imaging profile of sellar/suprasellar tumors remains largely unexplored, particularly in the pediatric population. In this review, we aim to provide an essential pathological update to better understand the way sellar/suprasellar tumors are currently classified, with a focus on the pediatric population. Furthermore, we intend to present the neuroimaging features that may assist in the differential diagnosis, surgical planning, adjuvant/neoadjuvant therapy, and follow-up of this group of tumors in children.

Apparent diffusion coefficient values effectively predict cell proliferation and determine oligodendroglioma grade

This study aims to evaluate the value of conventional magnetic resonance imaging (MRI) features and apparent diffusion coefficient (ADC) values in differentiating oligodendroglioma of various grades and explore the correlation between ADC and Ki-67. The preoperative MRI data of 99 patients with World Health Organization (WHO) grades 2 (n = 42) and 3 (n = 57) oligodendroglioma confirmed by surgery and pathology were retrospectively analyzed. Conventional MRI features, ADCmean, ADCmin, and normalized ADC (nADC) were compared between the two groups. A receiver operating characteristic curve was used to evaluate each parameter's diagnostic efficacy in differentiating the two tumor types. Each tumor's Ki-67 proliferation index was also measured to explore its relationship with the ADC value. Compared with WHO2 grade tumors, WHO3 grade tumors had a larger maximum diameter and more significant cystic degeneration/necrosis, edema, and moderate/severe enhancement (all P < 0.05). The ADCmin, ADCmean, and nADC values of the WHO3 and WHO2 grade tumors were significantly different, and the ADCmin value most accurately distinguished the two tumor types, yielding an area under the curve value of 0.980. When 0.96 × 10-3 mm2/s was used as the differential diagnosis threshold, the sensitivity, specificity, and accuracy of the two groups were 100%, 93.00%, and 96.96%, respectively. The ADCmin (r = -0.596), ADCmean (r = - 0.590), nADC (r = - 0.577), and Ki-67 proliferation index values had significantly negative correlations (all P < 0.05). Conventional MRI features and ADC values are beneficial in the noninvasive prediction of the WHO grade and tumor proliferation rate of oligodendroglioma.

Determining venous thromboembolism risk in patients with adult-type diffuse glioma

AbstractVenous thromboembolism (VTE) is a life-threating condition that is common in patients with adult-type diffuse gliomas, yet thromboprophylaxis is controversial because of possible intracerebral hemorrhage. Effective VTE prediction models exist for other cancers, but not glioma. Our objective was to develop a VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers. We analyzed preoperative arterial blood, tumor tissue, and clinical-pathologic data (including next-generation sequencing data) from 258 patients with newly diagnosed World Health Organization (WHO) grade 2 to 4 adult-type diffuse gliomas. Forty-six (17.8%) experienced VTE. Tumor expression of tissue factor (TF) and podoplanin (PDPN) each positively correlated with VTE, although only circulating TF and D-dimers, not circulating PDPN, correlated with VTE risk. Gliomas with mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2 (IDHmut) caused fewer VTEs; multivariable analysis suggested that this is due to IDHmut suppression of TF, not PDPN. In a predictive time-to-event model, the following predicted increased VTE risk in newly diagnosed patients with glioma: (1) history of VTE; (2) hypertension; (3) asthma; (4) white blood cell count; (5) WHO tumor grade; (6) patient age; and (7) body mass index. Conversely, IDHmut, hypothyroidism, and MGMT promoter methylation predicted reduced VTE risk. These 10 variables were used to create a web-based VTE prediction tool that was validated in 2 separate cohorts of patients with adult-type diffuse glioma from other institutions. This study extends our understanding of the VTE landscape in these tumors and provides evidence-based guidance for clinicians to mitigate VTE risk in patients with glioma.

The Clinical Significance of Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Predicting Distant Recurrence in Thymoma

AimsThymomas sometimes require treatment for various recurrence patterns, despite their relatively good survival rates after resection. We focused on their maximum standardised uptake value (SUVmax) on preoperative 18F-fluorodeoxyglucose positron emission tomography as a tumour recurrence predictor in completely resected thymomas. Those with a high SUVmax might be at an increased recurrence risk, irrespective of tumour size. We categorised cases into axes (tumour size and SUVmax) and determined whether cluster analysis predicts recurrence patterns and freedom from recurrence (FFR). Materials and methodsOf the 115 patients who underwent primary surgery for thymoma between 2005 and 2018, 66 were evaluated. According to the Masaoka stage and World Health Organization (WHO) histological type, all histological diagnoses were obtained after resection. All recurrences were diagnosed using computed tomography and categorised into three patterns: distant, local and regional recurrences. A multiple regression analysis was carried out to identify predictors for each recurrence pattern. Cluster analysis was carried out based on tumour size and SUVmax. The FFR rate was evaluated. ResultsAll patients with preoperative SUVmax <3.4 were free from recurrence regardless of Masaoka stage, WHO histological classification and tumour size. Multiple regression analysis revealed that the SUVmax was the only significant predictor for distant recurrence. All cases were divided into three clusters. Cluster 3, with average tumour size and a high SUVmax, showed a higher risk of distant recurrence rate (60%) and a significantly lower FFR rate (P = 0.003). ConclusionsThe preoperative positron emission tomography/computed tomography SUVmax could be a useful thymoma recurrence predictor, especially for distant recurrences. In addition, cluster analysis revealed that cases with average tumour sizes and extremely high SUVmax were identified to have a higher recurrence risk and a significantly lower FFR rate than those in other clusters. Even after complete resection, such cases should be closely followed-up and screened for distant recurrence.

Frontiers in Breast Pathology.

Frontiers in Breast Pathology.

18 F-FET PET maximum standard uptake value and WHO tumour classification grade in glioma.

In the area of oncology, molecular imaging techniques are becoming increasingly utilised. In neuro-oncology imaging, 18 Fluoro-O-(2) fluoroethyl-L-tyrosine (18 F-FET) is one of the molecular tracers used in positron-emission tomography (PET). Here, we investigated the correlation between maximum standard uptake value (SUV) of 18 F-FET PET and histologically determined World Health Organization (WHO) grade in glioma. This was a retrospective review of all 18 F-FET PET studies conducted between August 2014 and August 2019. Review was conducted to identify imaging studies performed on patients who had a glioma with histopathology results from surgical resection or biopsy available. A total of 31 18 F-FET PET studies of histologically confirmed glioma were included. WHO grades ranged from II-IV. A positive correlation between maximum SUV uptake on 18 F-FET PET and WHO grade was observed. There was a correlation identified between WHO glioma grade and maximum SUV on 18 F-FET PET. Further studies are recommended to explore this relationship.

Risk factors for lymph node metastasis in rectal neuroendocrine tumors: A recursive partitioning analysis based on multicenter data.

The well-differentiated rectal neuroendocrine tumors (RNETs) can also have lymph node metastasis (LNM). Large multicenter data were reviewed to explore the risk factors for LNM in RNETs. Further, we developed a model to predict the risk of LNM in RNETs. In total, 223 patients with RNETs from the Fujian Medical University Union Hospital, the First Affiliated Hospital of Fujian Medical University, and the First Affiliated Hospital of Xiamen University were retrospectively enrolled. Logistic regression analysis was performed to study the factors affecting LNM, and recursive partitioning analysis (RPA) was performed to stratify the risk of LNM. Among the 223 patients diagnosed with RNETs, the incidence of LNM was 10.8%. Univariate and multivariate regression analyses revealed that tumor size, World Health Organization (WHO) grade, and depth of tumor invasion were independent risk factors for LNM (p < 0.05). The area under the curve was 0.948 (95% confidence interval: 0.890-1.000). Furthermore, the incidence of LNM in patients divided into low- and high-risk groups according to RPA was 1.1% and 56.4%, respectively. Compared with tumor size, the depth of tumor invasion and WHO grade are more important factors in predicting LNM. Then, we developed a model based on RPA to predict the risk of LNM in RNETs and identify patients who are suitable for local resection.

The overriding role of surgery and tumor grade for long-term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population-based cohort study.

BackgroundGastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) comprise a heterogeneous disease group. Factors that affect long‐term survival remain uncertain. Complete population‐representative cohorts with long‐term follow‐up are scarce.AimTo evaluate factors of importance for the long‐term survival.Methods and resultsAn Observational population‐based study on consecutive GEP‐NEN patients diagnosed from 2003 to 2013, managed according to national guidelines. Univariable and multivariable survival analyses were performed to evaluate overall survival (OS) and to identify independent prognostic factors. One hundred ninety eligible patients (males, 58.9%) (median age, 60.0 years; range, 10.0–94.2 years) were included. The small bowel, appendix, and pancreas were the most common tumor locations. The World Health Organization (WHO) tumor grade 1–3 distributions varied according to the primary location and disease stage. Primary surgery with curative intent was performed in 66% of the patients. The median OS of the study population was 183 months with 5‐ and 10‐year OS rates of 66% and 57%, respectively. Only age, WHO tumor grade, and primary surgical treatment were independent prognostic factors for OS.ConclusionThe outcomes of GEP‐NEN patients are related to several factors including age and primary surgical treatment. WHO tumor grading, based on the established criteria, should be routine in clinical practice. This may improve clinical decision‐making and allow the comparison of outcomes among different centers.

Morphology Matters: A Critical Reappraisal of the Clinical Relevance of Morphologic Criteria From the 2019 WHO Classification in a Large Colorectal Cancer Cohort Comprising 1004 Cases.

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly have an independent impact on patient prognosis. We reclassified a large single-center cohort of 1004 CRCs spanning 2 decades for adjusted WHO grade (low vs. high), tumor budding (Bd1/Bd2/Bd3), and CRC subtype (adenocarcinoma not otherwise specified, micropapillary, mucinous, serrated, medullary, adenoma-like, signet-ring cell, mixed adenoneuroendocrine carcinoma/neuroendocrine carcinoma, undifferentiated) according to the criteria of the 2019 WHO classification. We investigated the interaction of these parameters, their connection to stage/microsatellite status, and their significance for patient survival in the different subgroups. Specific subtypes other than adenocarcinoma not otherwise specified represented one third of all CRCs and were unevenly distributed throughout stage and microsatellite subgroups. Subtypes, WHO grade and tumor budding profoundly impacted all survival parameters (P<0.001 for all analyses), with CRC subtypes and tumor budding-but not WHO grade-being stage-independent prognosticators for all survival comparisons. WHO grade had very limited prognostic value in CRC subtypes, while tumor budding retained its strong prognostic impact in most scenarios. Accurate delineation of CRC subtypes introduced in the 2019 WHO classification provides strong stage-independent prognostic information, arguing that they should be considered in pathology reports and in clinical trials. Of the morphology-based grading schemes included in the 2019 WHO, tumor budding outperforms WHO grade.

Pathological characteristics of recurrent glioma and its prognosis analysis

Objective To explore the pathological characteristics of recurrent glioma and its relationship with the patient′s prognosis. Methods A retrospective analysis was conducted on the clinical data of 54 patients with recurrent glioma treated at Neurosurgery Department, Sun Yat-sen University Cancer Center from August 2002 to December 2016. All patients underwent a second operation of tumor resection and postoperative pathological examinations including the World Health Organization (WHO) classification of the tumor, Ki-67 index, O6-methylguanine-DNA-methyltransferase (MGMT) status and isocitrate dehydrogenase 1 (IDH1) status. The histopathological features of recurrent samples were classified according to presence of necrosis and tumor cells as well as activity of tumor cells. The overall survival (OS) of patients was analyzed using the Kaplan-Meier method. The univariate and multivariate Cox regression analysis was further conducted to determine the clinical factors affecting OS in patients with recurrent glioma. Results Pathological test results in 54 patients were as follows: (1) In terms of WHO grade, there were 6 cases of grade Ⅱ(11.1%), 14 cases of grade Ⅲ(25.9%), 30 cases of grade Ⅳ(55.6%), and 4 cases (7.4%) without tumor cells. Compared with the first operation, there was no change in the WHO grade in 32 patients (59.2%), 7 (13.0%) had lower WHO tumor grades and 15 (27.8%) had higher grades; (2) In terms of Ki-67 index, out of 32 cases undergoing two times of testing, 15 cases had decreased Ki-67 index, 14 had increased Ki-67 index, and 3 cases had unchanged index; (3) In terms of IDH1 status, out of 29 cases undergoing two times of relevant tests, 9 cases were mutant and 20 were wild type; (4) In terms of MGMT status: out of 8 cases undergoing two times of relevant tests, 6 cases consisting of 3 cases with positive expression and 3 cases with negative expression had no change, and the remaining 2 changed from positive expression in the first test to negative expression in the second test; (5) In terms of pathological classification, 4 cases were necrosis type, 20 were mixed type, and 30 were active type. The follow-up time of 54 patients was 16.1±3.2 months (1.3-160.3 months). The Kaplan-Meier analysis showed a median OS of 14.4 months in 54 patients. The result of multivariate Cox regression analysis showed that high WHO grade of recurrence tumor (HR=2.80, 95% CI: 1.42-5.53, P<0.01) and absence of postoperative radiotherapy (HR=4.05, 95% CI: 1.41-11.64, P=0.01) were independent risk factors affecting OS in patients with recurrent glioma. Conclusions This preliminary study has suggested that recurrent gliomas might have changed pathological results revealed post re-surgery, and low WHO tumor grade and postoperative radiotherapy seem to be predictive factors of better prognosis. Key words: Glioma; Recurrence; Pathology; Prognosis

Opa-Interacting Protein 5 Expression in Human Glioma Tissues Is Essential to the Biological Function of U251 Human Malignant Glioma Cells.

Opa-interacting protein 5 (OIP5) is a member of the cancer-testis antigen (CTA) family that elicits a spontaneous antitumor immune response. The failure of current immunotherapies for glioma has prompted the search for novel biomarkers that may be utilized as therapeutic targets. This study aimed to investigate whether OIP5 serves as a target for malignant glioma immunotherapy. Glioma specimens from 53 adult patients were evaluated for OIP5 expression by immunohistochemical (IHC) staining, and the correlation of OIP5 expression with World Health Organization (WHO) tumor grade was analyzed. Endogenous expression of OIP5 in glioma cell lines was determined via real-time polymerase chain reaction (RT-PCR). Using lentiviral siOIP5, the effect of OIP5 gene knockdown on proliferation, cell cycle, and apoptosis in U251 glioma cells was studied. The results show that OIP5 is overexpressed in glioma tissues and is correlated with WHO tumor grade (P < 0.001). However, OIP5 protein expression is barely detectable in normal adult brain tissues. MTT assays and analysis using the Celigo Imaging Cytometry System reveal that the silencing of OIP5 inhibits U251 cell growth. Cell cycle assays and Annexin V staining show that OIP5 silencing disrupts the balance of the cell cycle and increases U251 cell death. These results indicate that OIP5 is upregulated in malignant glioma specimens but barely detected in normal brain tissues. OIP5 knockdown inhibits the biological function of glioma cells, reinforcing that OIP5 may serve as an immunotherapeutic target for malignant glioma.

Association Between CD133, CD44, and Nestin Expression and Prognostic Factors in High-Grade Meningioma

Meningioma is the most common primary brain tumor. It is graded as I, II, or III based on the World Health Organization (WHO) classification of central nervous system tumors. Meningiomas, especially those classified as grade II-III, have an aggressive history and a high recurrence rate. Cancer stem cells (CSCs) represent a small subset of tumor cells and are considered to be involved in tumor initiation, growth, and/or recurrence. To date, the CSCs of meningioma have not been well established. We assessed 51 grade II/III meningiomas using immunohistochemistry to determine if a correlation exists with the prognosis by investigating CD133, CD44, and nestin expression as possible CSC markers and age, gender, initial WHO tumor grade, Simpson grade, and the use of adjuvant radiation therapy. The median overall survival was 7.1 years, and the median progression-free survival (PFS) was 1.8 years. Univariate analysis using Cox proportional hazards regression revealed a negative correlation between CD133 and nestin expression and PFS (P= 0.0176 and P= 0.0138, respectively), and high expression of CD44 demonstrated a tendency toward a shorter PFS (P= 0.0563), as did the initial WHO grade and Simpson grade found at the initial operation (P= 0.0166 and P 0.0333, respectively). Multivariate analysis showed relevance between CD133 and nestin expression and PFS. CD133 and nestin expression, initial WHO grade and Simpson grade were associated with PFS in patients with grade II/III meningioma. These findings might suggest that these molecules are representative of CSCs in meningioma regarding the aspect of clinical course.

Predictors of recurrence and postoperative outcomes in patients with non-skull base meningiomas based on modern neurosurgical standards

Abstract Background Advances in neurosurgical techniques and neuroimaging resolution questions the modern-day reliability of the Simpson grade for predicting meningioma recurrence. Therefore, we evaluated the reliability of predictors for recurrence and outcomes in detail in patients with non-skull base meningiomas (NSBMs). Methods We retrospectively analyzed data from consecutive 175 NSBMs underwent surgical resection. We performed Kaplan–Meier analyses of recurrence-free survival (RFS) according to Simpson and World Health Organization (WHO) grades. Predictors of RFS and clinical deterioration were estimated by univariate and multivariate analyses. Correlation between the Simpson grade and change in Karnofsky Performance Scale scores was assessed by Fisher's exact test. Results Log-rank tests revealed significant correlations of both the Simpson and WHO grades with RFS for the overall cohort, convexity, and falx/tentorium meningioma. Unlike patients undergoing Simpson grade I and II resections, RFS in patients with WHO grade I and II/III tumors differed significantly from the early postoperative stage. Multivariate analysis identified tumor size, Simpson grade, and MIB-1 labeling index as significant predictors of RFS. Clinical deterioration was more frequent among patients undergoing less aggressive resection. Tumor location was the only significant predictor of clinical deterioration. Conclusions Our findings indicate that tumor size, Simpson and WHO grades, and MIB-1 labeling index are significant predictors of NSBM recurrence. Moreover, the risk of recurrence markedly decreases within the follow-up duration of 80 months. Aggressive resection appears to minimize the risk of recurrence without evidence of clinical deterioration. Follow-up schedules should be based on the WHO grade and extent of resection.

Spheno-Orbital Meningiomas: An Analysis Based on World Health Organization Classification and Ki-67 Proliferative Index.

To evaluate the clinical behavior of spheno-orbital meningiomas with regard to World Health Organization (WHO) tumor grade and Ki-67, a cellular marker of proliferation. A retrospective review over a 16-year period of the demographic, clinical, radiographic, and surgical data of all patients with spheno-orbital meningioma who underwent surgical resection. Tumor specimens were examined histologically using the current WHO 2016 classification and immunohistochemically using Ki-67/MIB-1 monoclonal antibody. Thirty-eight patients met all inclusion criteria: 78.9% of tumors were WHO grade I with a mean Ki-67 of 3.76, and 93% of patients were clinically stable at last follow up; 10.5% of lesions were WHO grade II (atypical) with a mean Ki-67 of 14.93, and 10.5% of lesions were WHO grade III (anaplastic) with a mean Ki-67 of 58.3. All grade II and III meningiomas exhibited an aggressive clinical course. There were statistically significant correlations between disease clinical progression and WHO tumor grade (p < 0.001), between disease clinical progression and Ki-67 (p < 0.001), and between increasing Ki-67 index and higher WHO grade (p < 0.001). For WHO grade I lesions, a Ki-67 of ≥3.3 correlated with recurrence (p = 0.0256). Overall, disease-specific mortality occurred in 5 (13%) patients. Ki-67 index is a valuable marker to use in conjunction with WHO grade to predict meningioma behavior, particularly in histologically borderline lesions, and possibly to identify a subset of WHO grade I tumors at risk of recurrence. This combination of methods can aid in tailoring treatment and surveillance strategies.

Role of the microRNA 181 family in glioma development.

MicroRNAs (miRNAs) are small, noncoding regulatory RNAs that regulate protein expression by reducing mRNA stability and/or translation, via base pairing with full or partial sequence‑complementary target mRNAs. Recent evidence indicates that miRNAs have roles as tumor suppressors and oncogenes. The members of the miRNA181 (miR181) family have been reported to be downregulated in early stage human glioma, and to be involved in glioma development. The current study demonstrated that all subtypes of the miRNA 181 family were downregulated at stages of human glioma, including miR181a1, a2, b1, b2, c and d. In the present study, the family members were detected by reverse transcription-quantitative polymerase chain reaction in glioma tissues of different stages. miR181c declined the most in the samples from patients with World Health Organization (WHO) gradeI glioma. As glioma development progressed from gradeI to IV, the expression of miRN181 family members continued to decline, with miR181b1 exhibiting the fastest decline rate. Furthermore, a lentivirus was used to overexpress miR181c in primary glioma cells; the result indicated that miR181c overexpression was able to significantly inhibit glioma cell proliferation. Thus, miR181 may be a useful biomarker for human glioma at early stages. Detection of the level of miR181 family members may be a potential method for glioma diagnosis, determining the tumor WHO grade and guiding clinical treatment.

Long term oncological outcome of thymoma and thymic carcinoma - an analysis of 235 cases from a single institution.

Background and objectivesThymoma has a variable long-term oncological outcome after surgical resection. Survival and tumor recurrence were analyzed to determine the predisposing factors for tumor recurrence.MethodsA total of 235 patients who underwent surgery for thymoma or thymic carcinoma from December 1997 to March 2013 were analyzed using Masaoka staging system and World Health Organization (WHO) histological classification. Surgical intervention included extended thymothymectomy via median sternotomy and thymomectomy via thoracotomy/ video-assisted thoracoscopic surgery (VATS).ResultsThe median duration of follow-up was 105 months (12–198 months). Among these 235 patients, recurrence was observed in 25 patients (10.7%). according to Masaoka stage I, IIA, IIB, III, IVA, IVB, recurrence rates were 1/65(1.5%), 8/106(7.5%), 1/32(3.1%), 6/20(30.0%), 8/10(80.0%), 1/1(100.0%), respectively. Disease or treatment-related mortality was observed in 13 patients. Overall survival rate was 94.4%. After univariate analysis, predisposing factors for tumor recurrence included Masaoka stage, WHO histologic type, tumor size, adjuvant therapy and margin status.ConclusionsDue to the indolent behavior of thymoma, tumor recurrence appears to be a better assessment of oncological outcome rather than survival. Factors associated with tumor recurrence include Masaoka stage, WHO histologic type, tumor size, adjuvant therapy and margin status.

Multimodal Imaging of Patients With Gliomas Confirms 11C-MET PET as a Complementary Marker to MRI for Noninvasive Tumor Grading and Intraindividual Follow-Up After Therapy.

The value of combined L-(methyl-[11C]) methionine positron-emitting tomography (MET-PET) and magnetic resonance imaging (MRI) with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET and MRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w]) examinations were performed. The computer software “visualization and analysis framework volume rendering engine (Voreen)” was used for analysis of extent and intersection of tumor compartments. Binary logistic regression models were developed to differentiate between World Health Organization (WHO) tumor types/grades. Tumor sizes as defined by thresholding based on tumor-to-background ratios were significantly different as determined by MET-PET (21.6 ± 36.8 cm3), T1w-Gd-MRI (3.9 ± 7.8 cm3), and FLAIR/T2-MRI (64.8 ± 60.4 cm3; P < .001). The MET-PET visualized tumor activity where MRI parameters were negative: PET positive tumor volume without Gd enhancement was 19.8 ± 35.0 cm3 and without changes in FLAIR/T2 10.3 ± 25.7 cm3. FLAIR/T2-MRI visualized greatest tumor extent with differences to MET-PET being greater in posttherapy (64.6 ± 62.7 cm3) than in newly diagnosed patients (20.5 ± 52.6 cm3). The binary logistic regression model differentiated between WHO tumor types (fibrillary astrocytoma II n = 10 from other gliomas n = 16) with an accuracy of 80.8% in patients at primary diagnosis. Combined PET and MRI improve the evaluation of tumor activity, extent, type/grade prediction, and therapy-induced changes in patients with glioma and serve information highly relevant for diagnosis and management.

Pancreatic neuroendocrine tumour: Correlation of apparent diffusion coefficient or WHO classification with recurrence-free survival

PurposeTo evaluate the correlation between grade of pancreatic neuroendocrine tumours (pNETs) based on the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC), and to assess whether the ADC value and WHO classification can predict recurrence-free survival (RFS) after surgery for pNETs. MethodsThis retrospective study was approved by the Institutional Review Board. The requirement for informed consent was waived. Between March 2009 and November 2014, forty-nine patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for single pNETs were included. Correlations among qualitative MR imaging findings, quantitative ADC values, and WHO classifications were assessed. An ordered logistic regression test was used to control for tumour size as a confounding factor. The association between ADC value (or WHO classification) and RFS was analysed. ResultsAll tumors (n=49) were classified as low- (n=29, grade 1), intermediate- (n=17, grade 2), and high-grade (n=3, grade 3), respectively. The mean ADC of pNETs was moderately negatively correlated with WHO classification before and after adjustment for tumour size (ρ=−0.64, p<0.001 and ρ=−0.55, p=0.001 respectively). RFS was significantly associated with WHO classification (p=0.007), but not with the ADC value (p=0.569). ConclusionThe ADC value of pNETs is moderately correlated with WHO tumour grade, regardless of tumour size. However, the WHO tumour classification of pNET may be more suitable for predicting RFS than the ADC value.

The methylation of a panel of genes differentiates low-grade from high-grade gliomas.

Epigenetic changes play an important role in the pathogenesis of gliomas and have the potential to become clinically useful biomarkers. The aim of this study was the evaluation of the profile of promoter methylation of 13 genes selected based on their anticipated diagnostic and/or prognostic value. Methylation-specific PCR (MSP) was used to assess the methylation status of MGMT, ERCC1, hMLH1, ATM, CDKN2B (p15INK4B), p14ARF, CDKN2A (p16INK4A), RASSF1A, RUNX3, GATA6, NDRG2, PTEN, and RARβ in a subset of 95 gliomas of different grades. Additionally, the methylation status of MGMT and NDRG2 was analyzed using pyrosequencing (PSQ). The results revealed that the methylation index of individual glioma patients correlates with World Health Organization (WHO) tumor grade and patient's age. RASSF1A, RUNX3, GATA6, and MGMT were most frequently methylated, whereas the INK4B-ARF-INK4A locus, PTEN, RARβ, and ATM were methylated to a lesser extent. ERCC1, hMLH1, and NDRG2 were unmethylated. RUNX3 methylation correlated with WHO tumor grade and patient's age. PSQ confirmed significantly higher methylation levels of MGMT and NDRG2 as compared with normal, non-cancerous brain tissue. To conclude, DNA methylation of a whole panel of selected genes can serve as a tool for glioma aggressiveness prediction.