WHO Classification System Research Articles

Emerging therapies for pancreas neuroendocrine cancers.

Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors can be functional, i.e., hormone secreting tumors, e.g., insulinoma, gastrinoma or VIPoma, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNET's, usually present later either incidentally or due to tumor bulk symptoms. The recent WHO classification system in 2010 classified PNET's into different stages and grades depending on the mitotic activity and Ki-67 labeling index. PNET's have a broad range of prognoses depending on the histologic grade, differentiation and biologic behavior. Computerized tomographic scanning (CT), magnetic resonance imaging (MRI) and octreoscan are imaging tools used to diagnose PNET, in addition to a confirmatory tissue diagnosis with immunohistochemical stains, typically obtained by either cytologic or histologic assessment. Symptomatic advanced PNET's can be treated with a long-acting somatostatin analogue for those tumors with somatostatin receptor positivity and which may also have antiproliferative activity. Another treatment modality is peptide receptor radionucleotide therapy (PRRT) in somatostatin receptor-positive tumors, albeit as yet with limited availability in the United States. Systemic therapies with combination cytotoxic agents e.g., streptozocin, anthracyclines, and capecitabine and temozolomide, all have established activity in PNET's. Biologic agents targeting the VEGF and mTOR signaling pathways, e.g., sunitinib, bevacizumab or everolimus are becoming integrated as treatments for PNET's. Poorly differentiated, high grade PNETs with a very high mitotic rate are treated with platinum-based chemotherapy regimens similar to treatment paradigms for small cell carcinoma of the lung. For liver confined or predominant disease, strategies such as cytoreductive surgery, hepatic artery embolization or radioembolization are treatment modalities to effect locoregional tumor control. The next generation of studies in PNET will help define optimal sequencing strategies of available therapies and also will attempt to use biomarker-guided approaches to select therapies.

Clinicopathological Analysis of Patients with Non-muscle-invasive Bladder Cancer: Prognostic Value and Clinical Reliability of the 2004 WHO Classification System

The aim of this study was to clarify the prognostic value and clinical reliability of the 2004 World Health Organization classification system of non-muscle-invasive bladder cancer. Between January 1995 and November 2010, 153 patients were diagnosed with non-muscle-invasive bladder cancer. We used a substage system that discerns T1-microinvasive (T1m, 42 patients) and T1-extensive-invasive (T1e, 37 patients) cancers. There were 2 (1.3%), 89 (58.2%) and 62 (40.5%) cases of Grade 1-3 urothelial carcinoma, respectively, on the basis of the 1973 World Health Organization classification system. Of these, 37 (24.2%) and 116 (75.8%) were graded as low and high on the basis of the 2004 World Health Organization classification system. All of the cases with progression (15 patients) were diagnosed as high grade at the time of primary transurethral resection of the bladder tumor. Based on the Kaplan-Meier analysis, the 2004 World Health Organization classification system accurately predicted tumor recurrence (P = 0.029) and progression (P = 0.031). The 5-year recurrence-free survival rates in patients with low-grade and high-grade tumors were 68.7 and 47.1%, and the 5-year progression-free survival rates were 100 and 89.0%, respectively. In the high-grade T1 cases, the substage (T1m or T1e) was a significant predictor of tumor recurrence (P = 0.001) and progression (P = 0.020). The 2004 World Health Organization classification system accurately predicts the risk of recurrence in primary non-muscle-invasive bladder cancer cases and has the same accuracy when predicting the risk of progression as the 1973 World Health Organization classification. Furthermore, the substaging system for high-grade T1 tumors is useful in predicting both recurrence and progression.

Multicenter Institutional Experience of Surgically Resected Thymic Epithelial Tumors (TETs): An Observational Report on Behalf of F.O.N.I.C.A.P. (Forza Operativa Nazionale Interdisciplinare Contro il Cancro del Polmone)

This multicenter analysis evaluated patient outcome and clinical pathologic features of thymic epithelial tumors after complete surgical resection and adjuvant treatment. Histologic classification and clinical staging were performed according to WHO classification and Masaoka staging system, respectively. We analyzed 62 patients, 20 (32%) of whom had myasthenia at diagnosis. Clinical and pathologic staging was as follows: 31 (50%) and 30 (48%) patients had stage I disease, 19 (30%) and 22 (35%) stage II, 5 (8%) and 3 (6%) stage III, 2 (4%) and 2 (3%) stage IVa, and 5 (8%) and 5 (8%) stage IVb, respectively. Histologic examination revealed 11 (19%) type A tumors, 19 (30%) type AB tumors, 7 (12%) type B1 tumors, 11 (17%) type B2 tumors, 11 (17%) type B3 tumors, and 3 (5%) type C tumors. Adjuvant therapies comprised chemotherapy in 3 (5%) patients and radiotherapy in 16 (26%) patients. Median follow-up was 71 months (range 1-145). DFS and OS at 48, 60, and 72 months were 89 and 89%, 86 and 97%, and 95% and 92%, respectively. Myasthenia at the onset of disease (P=0.18 for DFS; P=0.97) and tumor size>5 cm (P=0.94 for DFS; P=0.56) were not prognostic factors. TETs are rare and indolent tumors. Complete surgical resection followed by adjuvant therapies, such as chemotherapy and/or radiotherapy, in patients at risk of recurrence show very good DFS and OS results, even in cases with radically resected pleural-pulmonary metastases.

Is Pregnancy Associated with Severe Dengue? A Review of Data from the Rio de Janeiro Surveillance Information System

BackgroundDengue is a reportable disease in Brazil; however, pregnancy has been included in the application form of the Brazilian notification information system only after 2006. To estimate the severity of maternal dengue infection, the available data that were compiled from January 2007 to December 2008 by the official surveillance information system of the city of Rio de Janeiro were reviewed.Methods and Principal FindingsDuring the study period, 151,604 cases of suspected dengue infection were reported. Five hundred sixty-one women in their reproductive age (15–49 years) presented with dengue infection; 99 (18.1%) pregnant and 447 (81.9%) non-pregnant women were analyzed. Dengue cases were categorized using the 1997 WHO classification system, and DHF/DSS were considered severe disease. The Mann-Whitney test was used to compare maternal age, according to gestational period, and severity of disease. A chi-square test was utilized to evaluate the differences in the proportion of dengue severity between pregnant and non-pregnant women. Univariate analysis was performed to compare outcome variables (severe dengue and non-severe dengue) and explanatory variables (pregnancy, gestational age and trimester) using the Wald test. A multivariate analysis was performed to assess the independence of statistically significant variables in the univariate analysis. A p-value<0.05 was considered statistically significant.A higher percentage of severe dengue infection among pregnant women was found, p = 0.0001. Final analysis demonstrated that pregnant women are 3.4 times more prone to developing severe dengue (OR: 3.38; CI: 2.10–5.42). Mortality among pregnant women was superior to non-pregnant women.ConclusionPregnant women have an increased risk of developing severe dengue infection and dying of dengue.

Expression and clinical significance of the proliferation marker minichromosome maintenance protein 2 (Mcm2) in diffuse astrocytomas WHO grade II

BackgroundThe WHO classification system for astrocytomas is not considered optimal, mainly because of the subjective assessment of the histopathological features. Few prognostic variables have been found that stratify the risk of clinical progression in patients with grade II astrocytoma. For that reason there is a continuous search for biomarkers that can improve the histopathological diagnosis and prognostication of these tumours.AimThis study was designed to investigate the prognostic significance of the proliferative marker Mcm2 (minichromosome maintenance protein 2) in diffuse astrocytomas WHO grade II and correlate the findings with histopathology, mitoses, and Ki67/MIB-1 immunostaining.Method61 patients with histologically verified grade II astrocytoma (WHO 2007) were investigated. Paraffin sections were immunostained with anti-Mcm2, and the Mcm2 proliferative index (PI) was determined as the percentage of immunoreactive tumour cell nuclei.ResultsMcm2 PI was not associated with any histopathological features but correlated significantly with mitotic count and Ki67/MIB-1 PI (p<0.05). In the survival analyses Mcm2 showed trends to poorer survival, however, statistical significance was not achieved in the univariate analyses (p>0.05).ConclusionsIn our hands Mcm2 immunostaining has no advantage over Ki67/MIB-1 in the evaluation of grade II astrocytomas. Larger studies are needed to fully clarify the prognostic role of this biomarker.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1715002791944037

The incidence of myelodysplastic syndromes in Western Greece is increasing

Descriptive epidemiology of the myelodysplastic syndromes (MDS) is always interesting and may reveal time-dependent and geographical variations, as well as occupational exposure. Epidemiological data in Greece are not available by now. We have collected and analyzed medical records of all patients with a documented diagnosis of MDS, performed by an expert hematologist and/or hematopathologist, in the geographical area of Western Greece, during the 20-year period, defined between 1990 and 2009. We have then calculated and described demographic and clinical features of the diagnosed MDS patient population, and assessed the incidence and prevalence rates of MDS in Western Greece, during the above-mentioned period. A total of 855 patients with newly diagnosed MDS have been identified. Refractory anemia was the most common subtype in both FAB and WHO classification systems and in both genders. Del-5q and RARS were more commonly encountered among females, and the dysplastic subtype of chronic myelomonocytic leukemia among males. Trisomy 8 was the most common single cytogenetic abnormality. The crude mean annual incidence rate of MDS was 6.0 per 100,000 inhabitants aged ≥15 years old (all subtypes according to FAB), and it was 4.8 per 100,000 when CMML and RAEB-T were excluded. Crude incidence rate was higher in rural than in urban areas, but this finding was not confirmed after age standardization. Age-standardized mean annual incidence rate in men was 7.9/100,000 and in women 3.4/100,000. A continuously increasing incidence rate of MDS has been observed throughout the study period.

The First Keystone Symposia Conference on Pulmonary Vascular Disease and Right Ventricular Dysfunction: Current Concepts and Future Therapies

The First Keystone Symposia Conference on Pulmonary Vascular Disease and Right Ventricular Dysfunction: Current Concepts and Future Therapies

Clinicopathological features of colorectal neuroendocrine neoplasms and prognostic significance of WHO staging system

To investigate the clinicopathological characteristics of colorectal neuroendocrine neoplasms (NENs) and the prognostic significance of the new WHO classification and staging system about gastroenteropancreatic NENs. The clinical and pathological records were reviewed in 73 patients with colorectal NENs (carcinoids). All slides were retrieved and reviewed, immunohistochemical staining (EnVision method) was performed and follow-up information retrieved. Forty-one men and thirty-two women were included with a median age of 53 years (19 - 79 years). The location of the primary tumors in 65 patients was within 10 cm from the anorectal line. In 45 cases, the tumor diameter was ≤ 1 cm (no metastasis occurred); in 11 cases, the tumor diameter was > 1 cm but ≤ 2 cm (two patients had metastatic tumors); in 17 cases, the tumor diameter was > 2 cm (12 patients had metastatic tumors). The metastatic rate was significantly correlated with tumor size (P = 0.000). All tumors were immunoreactivity for synaptophysin and/or chromogranin A. According to the criteria of WHO classification and staging system about gastroenteropancreatic NENs, there were 65 cases of neuroendocrine tumors, including 51 cases of grade 1 (G1), 14 cases of grade 2 (G2), 4 cases of neuroendocrine carcinoma (G3) and 4 cases of mixed adenoneuroendocrine carcinoma. Following-up data showed that of the 34 patients with G1 tumor, there were no tumor-related death, but two patients showed metastases, and the remaining patients were disease free for 6 to 179 months. Of the 12 patients with G2 tumors, five developed metastasis, there were two tumor-related deaths, and the nine surviving patients were alive for 17 to 118 months. Of the four G3 patients, all developed metastasis and there were three tumor-related deaths. Of the four mixed adenoneuroendocrine carcinoma there were two tumor-related deaths. The difference of metastatic rate, tumor-related mortality, and overall survival among different grading groups in this series was statistically significant (P = 0.000). Colorectal neuroendocrine neoplasm is a group of tumors with distinct prognostic difference, and most of these tumors show an indolent clinical behavior. There is a good correlation between the new WHO classification and staging system of gastroenteropancreatic NENs and their clinical behaviors.

GRP-131 Patient Safety – Analysing Medication-Related Adverse Events

BackgroundMedication-related adverse events (AEs) lead to increased morbidity, mortality and costs. In Denmark, frontline personnel in hospitals and in the primary care sector are obligated to report adverse events to...

Identifying Informational Needs of Pathologists in the Diagnosis of Myelodysplastic Syndromes (MDS)

AbstractAbstract 4242MDS are a heterogeneous group of hematopoietic stem cell disorders whose incidence appears to be increasing. Establishing the diagnosis of MDS requires careful morphologic review of the peripheral blood, bone marrow (BM) aspirate and biopsy and correlation with clinical findings. The role of the pathologist in the diagnosis of MDS is vital. The purpose of this study was to describe current practice patterns and barriers facing both general pathologists and hematopathologists regarding the diagnosis of MDS and to identify areas for continuing education for all pathologists who diagnose MDS. Methods:The study used several methods to collect data including literature review, nominal group technique focus groups, and a case based survey. The survey was distributed during March and April 2012 via fax and email to 5,490 general pathologists and hematopathologists practicing in the US. Responses were received from 233 general pathologists and hematopathologists, of which 130 completed the survey. A final sample of 72 general pathologists and 53 hematopathologists were used in the analysis, giving a response rate of 2.3%. Respondents to the survey were given a small remuneration for their time. Results:As expected, experience with MDS was higher in hematopathologists than general pathologists. Hematopathologists evaluated an average of nine BM aspirates and biopsies per week, whereas general pathologists evaluated an average of 2 per week. Confidence in aspects of MDS diagnosis was also higher among hematopathologists, with 76% being very confident in their ability to classify and report MDS (vs. 33% of general pathologists) and 79% very confident in distinguishing MDS from other hematopoietic disorders (vs. 39% of general pathologists).Regarding general practice patterns, the majority of both groups requires and reviews clinical data for every hematology case (77% hematopathologists, 79% general pathologists). Both groups cited poor quality bone marrow specimens as a much more significant barrier than lack of clinical information or access to technology (fig 1). Only a subset of both groups reported having standardized protocols in their institution for the diagnosis and work-up of MDS (36% hematopathologists and 32% general pathologists). The hematopathologists more frequently had a checklist in place for clinicians to ensure that sufficient and appropriate samples are collected at the time of bone marrow biopsy (62% versus 39% for general pathologists). Most general pathologists (63%) and hematopathologists (55%) do not use the International Prognostic Scoring System (IPSS). Accordingly, most are not aware of the components that comprise the IPSS.The case based survey showed some practice similarities and differences between the groups. The vast majority of both hematopathologists and general pathologists use the current WHO (2008) classification system (96% hematopathologists and 92% general pathologists). The most obvious difference between the groups was in ordering FISH testing for possible MDS. Among those who selected FISH in the hematopathology group, greater than 90% selected probes for chromosomes 5, 7, 8 and 20. There was greater variability in the probes ordered by general pathologists. Most notably chromosome 8 was selected by 58% of general pathologists and BCR-ABL was selected by 29% of general pathologists (vs. 8% in the hematopathologists group). Conclusion:The results of the study suggest there are continuing education opportunities for these pathologists to ensure more standardized diagnostic evaluation for MDS. The need for more standardized protocols for the work-up of patients for MDS was voiced by both general pathologists and hematopathologists. Pathologists may also benefit from more clinically oriented continuing education, to include topics such as the International Prognostic Scoring System (IPSS) and other validated prognostic classification systems. [Display omitted] Disclosures:Sagatys:CE Outcomes, LLC: Consultancy. Berger:Celgene Corporation: Celgene Stock Other, Employment. Merwin:Patti Merwin: Company Stock Other, Employment. Sugrue:Celgene Corporation: Employment, Equity Ownership.

DNMT3A mutations in De Novo Myelodysplastic Syndrome: Distinct Clinico-Biological Features and Prognostic Relevance

AbstractAbstract 3799 Background and PurposeMutations of the DNMT3A gene, which encodes the enzyme DNA methyltransferase 3A, were identified in patients with myeloid malignancies and are associated with poor prognosis in primary AML patients. However, the clinical and prognostic implications of these mutations in myelodysplastic syndrome (MDS) remain to be determined. Methods and MaterialsA total of 328 de novo MDS patients diagnosed according to French-American-British (FAB) criteria at the National Taiwan University Hospital who had cryopreserved bone marrow cells for study were recruited into mutational analyses. Mutations in DNMT3A gene at exon 2–23 were analyzed by polymerase chain reaction and direct sequencing. The results were correlated with clinical features, cytogenetics, gene mutations and treatment outcomes. ResultsAmong the 328 patients, 115 patients (35.0%) had refractory anemia (RA), 19 (5.8%) had RA with ring sideroblasts (RARS), 122 (37.2%) had RA with excess blasts (RAEB), 35 (10.7%) had RAEB in transformation (RAEBT), and 37 (11.3 %) had chronic myelomonocytic leukemia (CMMoL). DNMT3A mutations at 20 different positions were identified in 33 patients, including thirteen missense mutations, two nonsense mutations and five frame-shift mutations. Among these 33 patients, 31 had single mutation of DNMT3A, and the other 2 patients had double mutations. The most common mutation was R882H (n = 8), followed by R882C (n = 7), Y735C (n=2), and R720H (n=2). All other mutations were detected in only one patient each. Totally, DNMT3A mutations were identified in 33 (10.1%) of 328 patients diagnosed according to the FAB classification and in 25 (9.8%) of 256 diagnosed according to 2008 WHO classification.DNMT3A-mutated patients were older (median age, 74 years vs. 66 years, P=0.048) and had higher platelet counts at diagnosis than DNMT3A-wild patients (median, 123.5×103/μL vs. 73 ×103/μL, P=0.016). According to FAB classification, patients with RARS had the highest incidence (26.3%) of DNMT3A mutations, followed by RAEBT (14.3%), RAEB (11.5%), and CMMoL (8.1%), whereas those with RA had the lowest incidence (5.2%, P=0.035). Chromosome data were available in 308 patients (93.9%) at diagnosis and clonal chromosomal abnormalities were detected in 155 patients (50.3%). There was no difference in the distribution of 2008 WHO classification, karyotype and international prognostic scoring system (IPSS) between patients with and without DNMT3A mutations.To investigate the association of gene mutations in the pathogenesis of MDS, a mutational screening of 10 other genes was also performed. Among the 33 patients with DNMT3A mutations, 16 patients (48.5%) showed additional molecular abnormalities at diagnosis, including seven with concurrent IDH1/IDH2 mutations, seven ASXL1 mutations, five AML1/RUNX1 mutations, two MLL-PTD, two RAS mutations and one JAK2 mutation. Eight of these 16 patients (50%) had two other concurrent mutations, and the others had one additional mutation. It's clear that DNMT3A mutation was closely interacted with IDH mutation in MDS (IDH mutation occurring in 21.2% of DNMT3A-mutated patients vs. 3.4% in DNMT3A-wild ones, P=0.001).With a median follow-up of 57.6 months (range, 0.1–250.7 months), there was no significant difference in overall survival (OS) between patients with and without DNMT3A mutation by either FAB or 2008 WHO classifications (median, 22.5 months vs. 30.9 months, P=0.669 and 25.2 months vs. 34.9 months, P=0.538, respectively) as well as in the rate of acute transformation. However, among the subgroup of patients with RA by FAB classification or refractory cytopenia with unilineage dysplasia by 2008 WHO classification, DNMT3A-mutated patients had significantly shorter OS than DNMT3A-wild patients (median, 28.3 months vs. 39.8 months, P<0.001 and 23.8 months vs. 40.3 months, P=0.026, respectively). Further, DNMT3A mutation is an independent poor prognostic factor in these two subgroups. ConclusionOur findings provided evidence that DNMT3A mutations could be detected in a substantial portion of de novo MDS patients. DNMT3A mutations are associated with distinct clinical and biological features and poor prognosis in selected groups of patients. Disclosures:No relevant conflicts of interest to declare.

UHRF2 mRNA Expression is Low in Malignant Glioma but Silencing Inhibits the Growth of U251 Glioma Cells in vitro

UHRF2 is a member of the ubiquitin plant homeo domain RING finger family, which has been proven to be frequently up-regulated in colorectal cancer cells and play a role as an oncogene in breast cancer cells. However, the role of UHRF2 in glioma cells remains unclear. In this study, we performed real-time quantitative PCR on 32 pathologically confirmed glioma samples (grade I, 4 cases; grade II, 11 cases; grade III, 10 cases; and grade IV, 7 cases; according to the 2007 WHO classification system) and four glioma cell lines (A172, U251, U373, and U87). The expression of UHRF2 mRNA was significantly lower in the grade III and grade IV groups compared with the noncancerous brain tissue group, whereas its expression was high in A172, U251, and U373 glioma cell lines. An in vitro assay was performed to investigate the functions of UHRF2. Using a lentivirus-based RNA interference (RNAi) approach, we down-regulated UHRF2 expression in the U251 glioma cell line. This down- regulation led to the inhibition of cell proliferation, an increase in cell apoptosis, and a change of cell cycle distribution, in which S stage cells decreased and G2/M stage cells increased. Our results suggest that UHRF2 may be closely related to tumorigenesis and the development of gliomas.

Long‐term survival in thymic epithelial tumors: A single‐center experience from China

To evaluate long-term survival in thymic epithelial tumors (TETs), we present our experiences at a single institution in China. We performed a retrospective analysis including 115 patients with TETs from 2001 to 2006. Histological diagnosis was completed based on the new WHO classification system. A univariate and multivariate survival analysis was performed, which included myasthenia gravis (MG), WHO histological type, Masaoka stage, completeness of resection, and adjuvant radiotherapy (RT). WHO histological subtype was closely correlated with that of Masaoka stage. The overall median survival time was 84.4 months and the 7-year survival rate was 78%. In the univariate analysis, three prognostic factors, including WHO histology type, Masaoka stage and complete resection, were statistically significant. In the analysis of the cases with complete resection, adjuvant RT did not show obvious survival benefit. In the multivariate analysis, Masaoka stage was the only independent factor that predicted long-time survival. Thymic carcinoma should be regarded as a different category of the disease due to its aggressive and poorer prognosis. Complete resection of the tumor and Masaoka stage I and II were found to contribute to a better survival. Adjuvant RT is not recommended for patients with complete resection in thymomas.

Expression of c-Jun, p73, Casp9, and N-ras in thymic epithelial tumors: relationship with the current WHO classification systems

BackgroundTo evaluate the expression and differential significance of c-Jun, p73, Casp-9 and N-ras in thymic epithelial tumors (TETs) with the aim to provide useful information for tumor biology and prospective therapy.MethodsIn this study, we analyzed the expression of four chromosome 1-related genes, namely c-Jun, p73, Casp-9 and N-ras, in 60 cases of thymic epithelial tumors. The tumors included 52 thymomas and 8 thymic carcinomas which were categorized according to the current WHO classification systems.ResultsCompared with the normal thymus tissue, all thymic epithelial tumors demonstrated higher expression of c-Jun and p73. The expression of c-Jun and p73 in type B2, B3 thymoma and thymic carcinomas was similar, and significantly higher than that in all other subtypes of thymomas. Unlike type A thymoma, the expression of Casp-9 was relatively lower in type B thymoma and thymic carcinomas. With respect to the clinical staging systems, c-Jun was more expressed in progressive tumors harboring higher stages. In contrast to c-Jun, p73 and Casp-9, there was no significant aberration with N-ras expression irrespective of either tissue or tumor types.ConclusionsThe overexpression of c-Jun, p73 and Casp-9 in thymic epithelial tumors is closely related with the pathogenesis and biological behavior of the neoplasms. These candidate biomarkers provided useful information for prospective personalized therapy in the clinical management.Additional non-English language abstract language: Chinese背景:评估c-Jun, p73, Casp-9 和 N-ras在胸腺上皮性肿瘤诊断和鉴别诊断中的运用.方法:根据世界卫生组织最新的诊断标准60例胸腺上皮性肿瘤分类,运用Envision法检测c-Jun,p73,Casp-9 和N-ras在不同亚型肿瘤中的表达情况,并结合临床病理学特征进行分析.结果:c-Jun和p73在肿瘤中的表达明显高于正常胸腺组织;c-Jun和p73在B3,B2型胸腺瘤和胸腺癌的表达类似,且表达明显高于其他类型的胸腺肿瘤;Caspase-9在B型胸腺瘤和胸腺癌中的表达相对低于A型胸腺瘤;c-Jun的表达更常见于高级别的胸腺肿瘤.结论:c-Jun,p73和Casp-9在胸腺肿瘤中的表达很好地反映了肿瘤的生物学特点,为胸腺肿瘤的诊断和鉴别诊断提供了较好的理论基础.Virtual Slideshttp://www.diagnosticpathology.diagnomx.eu/vs/1521774814749726

Can molecular markers help with decision making?

WHO classification system remains unsatisfactory due to its lack of reproducibility [1] and lack of precision in terms of prognosis. Tumors that share identical histopathological features can actually represent multiple distinct molecular phenotypes. Several molecular markers provide prognostic information and may help in decision when providing predictive information.

Three-dimensional susceptibility-weighted imaging at 7 T using fractal-based quantitative analysis to grade gliomas

Susceptibility-weighted imaging (SWI) with high- and ultra-high-field magnetic resonance is a very helpful tool for evaluating brain gliomas and intratumoral structures, including microvasculature. Here, we test whether objective quantification of intratumoral SWI patterns by applying fractal analysis can offer reliable indexes capable of differentiating glial tumor grades. Thirty-six patients affected by brain gliomas (grades II-IV, according to the WHO classification system) underwent MRI at 7 T using a SWI protocol. All images were collected and analyzed by applying a computer-aided fractal image analysis, which applies the fractal dimension as a measure of geometrical complexity of intratumoral SWI patterns. The results were subsequently statistically correlated to the histopathological tumor grade. The mean value of the fractal dimension of the intratumoral SWI patterns was 2.086 ± 0.413. We found a trend of higher fractal dimension values in groups of higher histologic grade. The values ranged from a mean value of 1.682 ± 0.278 for grade II gliomas to 2.247 ± 0.358 for grade IV gliomas (p = 0.013); there was an overall statistically significant difference between histopathological groups. The present study confirms that SWI at 7 T is a useful method for detecting intratumoral vascular architecture of brain gliomas and that SWI pattern quantification by means of fractal dimension offers a potential objective morphometric image biomarker of tumor grade.

Dengue in travellers: applicability of the 1975–1997 and the 2009 WHO classification system of dengue fever

The aim of this study was to assess the applicability and benefits of the new WHO dengue fever guidelines in clinical practice, for returning travellers. We compared differences in specificity and sensitivity between the old and the new guidelines for diagnosing dengue and assessed the usefulness in predicting the clinical course of the disease. Also, we investigated whether hypertension, diabetes or allergies, ethnicity or high age influenced the course of disease. In our setting, the old classification, compared with the new, had a marginally higher sensitivity for diagnosing dengue. The new classification had a slightly higher specificity and was less rigid. Patients with dengue who had warning signs as postulated in the new classification were admitted more often than those who had no warning signs (RR, 8.09 [1.80-35.48]). We did not find ethnicity, age, hypertension, diabetes mellitus or allergies to be predictive of the clinical course. In our cohort of returned travellers, the new classification system did not differ in sensitivity and specificity from the old system to a clinically relevant degree. The guidelines did not improve identification of severe disease.

Diagnosis and Therapy of Myelodysplastic Syndromes in Germany: A Retrospective Multicenter Analysis

Background: Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell disorders. Patients and Methods: In order to assess current diagnosis and treatment patterns in Germany, the data of 269 patients with MDS from 57 representative centers were analyzed. Results: The most common symptom leading to an initial diagnosis of MDS was anemia (79%). WHO classification, cytogenetic analysis, and IPSS scoring were performed in 92, 67, and 61% of patients, respectively. 5q deletions were identified in 34% of patients whose cytogenetic status was analyzed. Symptomatic anemia was the major trigger for initiating therapy. 49% of patients received supportive care only, and 49% received active therapy (i.e., chemo-, immunomodulatory, or epigenetic therapy), including 5% who received allogeneic transplantation. Of those patients treated with active therapy, approximately half of the higher-risk patients received azacitidine, and approximately half of the lower-risk patients received lenalidomide. Overall, 80% of patients received some form of supportive care, mainly red blood cell transfusions. Conclusion: While the WHO classification system is widely used in clinical practice, karyotyping and IPSS risk assessment do not seem to be common standard. Despite encouraging data on the use of effective and novel drugs, such as lenalidomide and azacitidine in MDS therapies, management of the disease could be further improved by more widespread use of risk stratification of patients using cytogenetics and IPSS assessment.

Prise en charge des méningiomes OMS grade II et III : étude rétrospective monocentrique d’une série chirurgicale de 36 cas

IntroductionAtypical and malignant meningiomas are a rare disease whose histological definition is still recent. Their management is not consensual. The aim of this study was to review the outcome, prognostic factors and the role of complementary therapies. Patients and methodsBetween 1999 and 2007, 36 patients with atypical or malignant meningiomas were managed in our hospital. All surgical specimens were reviewed according to the 2007 WHO classification system. The sex ratio was 1.25 male, the median age was 59 years. The median follow-up was 55 months. Thirty meningiomas were atypical and six were malignant. ResultsFive and 10 years overall survival rate are respectively 72 and 41%, whereas 5 and 10 years progression free survival rate are 61 and 23%. We only identify female sex, age over 70 years and Karnofsky status under 70% as negative prognostic factors. ConclusionAtypical and malignant meningiomas are difficult to manage and have high recurrence and poor survival rates. The prognostic of OMS II meningiomas is heterogeneous. Adjuvant radiation therapy is recommended in case of malignant menigioma or in case of atypical meningioma if incomplete surgical excision is performed.

Endometrial Intraepithelial Neoplasia Terminology in Practice

An alternative WHO classification system for endometrial precancers and hyperplasia separates a lesion called endometrial intraepithelial neoplasia (EIN) from diffuse hormonal effects and cancer, resulting in a 3-category system. EIN is a localized lesion with objective histologic criteria, characterized by monoclonal growth of mutated cells, and associated with a 45-fold elevated cancer risk. This study summarizes our department's experience with EIN diagnoses in the 4 years since conversion to the new terminology. We identified all reports from endometrial samples diagnosed as EIN or including the terms "gland crowding" or "atypia" since conversion and obtained follow-up information from subsequent pathology specimens or clinic notes (82%). The diagnoses were reported by a mixture of pathologists, the majority of whom are not subspecialized to gynecologic pathology and the slides were not reviewed. Overall, 17.1% of women with EIN had carcinoma and 34.9% had either carcinoma or persistent EIN. The proportion of women with EIN or cancer on follow-up did not trend with years since adoption of EIN terminology. The median age at the time of diagnosis was 55 years in an overall population of women who underwent sampling at a median age of 47 years. The median follow-up time was 4 months. All cancers were of endometrioid histology; all but 2 were International Federation of Gynecology and Obstetrics grade 1. In comparison with a previous reproducibility study among expert pathologists on a comparable population from our department, these results for general pathologists show a higher false positive rate for subsequent cancer.