Feline mammary tumors: Comparison of histological classifications and prognostic factors in a 3-year survival study (Part I).

The aims of this study were to stratify the risk of recurrence based on the Masaoka-Koga stage and World Health Organization (WHO) classification systems after R0-resection for thymic epithelial tumors (TETs). A retrospective analysis was conducted on 479 patients who underwent surgery between Jan 1994 and Feb 2014 for TETs. The study group comprised 251 males and 228 females, with a median age of 52 years (range, 15-84 years). Of the 479 patients, 406 (84.8%) patients underwent R0-resection. Recurrence after R0-resection occurred in 32 patients during a median follow-up of 53 months (range, 2-227 months). A multivariate analysis revealed that the preoperative treatment including chemotherapy (P=0.036), Masaoka-Koga stage (P=0.011) and the WHO classification (P=0.001) were predictors for recurrence after R0-resection. Patients were stratified into four risk groups using a potential model incorporating both the Masaoka-Koga stage and WHO classifications. Group 1 comprised WHO types A/AB/B1 in stage I/II; Group 2 comprised WHO type A/AB/B1 in stage III or WHO type B2/B3 in stage I/II or WHO type C in stage I; Group 3 comprised Type B2/B3/C in stage III, or WHO type C in stage II/III; and Group 4 comprised WHO type B2/B3/C in stage IV. The 5-year freedom-from-recurrence (FFR) rates were 99.4% for group 1, 84.7% for group 2, 63.7% for group 3, and less than 44.4% for group 4 (P<0.001). In group 3, the rate of locoregional recurrence of patients treated with postoperative radiation therapy was lower than patients treated without postoperative radiation therapy (P=0.032). A risk model incorporating both Masaoka-Koga stage and WHO classification systems may provide multi-faceted information about recurrence and adjuvant treatment after R0-resection of TETs.

The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives.

We performed an immunohistochemical study with monoclonal antibodies to Ki-67 antigen and p53 protein on 45 cases of thymic epithelial tumors classified according to the recent World Health Organization (WHO) classification system to evaluate whether there is correlation between the expression of these markers and prognosis, histologic subtype, and myasthenia gravis (MG). We also correlated histologic subtype with sex, age, MG, and survival. Ki-67 and p53 labeling indices (LIs) were expressed as a percentage of positive nuclear immunostaining by counting 1,000 epithelial tumor cells. Statistically significant differences were found between Ki-67 LI and survival (p = 0.007), whereas the prognostic implication of p53 could not be demonstrated, although there appeared a trend that patients with tumors of higher LIs had worse survival. Significant correlations were also found between Ki-67 (p < 0.0005) and p53 (p < 0.0005) LIs and histologic subtypes. No correlation was found between these parameters and MG. Histologic subtypes of the WHO classification also correlated with survival (p = 0.01), whereas no correlation was found with sex, age, and MG. In conclusion, our results indicate that the proliferative activity, assessed by Ki-67 LI, and the histologic pattern, according to WHO classification system, seems to represent reliable parameters in the prognosis of thymic epithelial tumors.

BackgroundDengue disease severity is usually classified using criteria set up by the World Health Organization (WHO). We aimed to assess the diagnostic accuracy of the WHO classification system and modifications to this system, and evaluated their potential practical usefulness.MethodsPatients, admitted consecutively to the hospital with severe dengue, were classified using the WHO classification system and modifications to this system. Treating physicians were asked to classify patients immediately after discharge. We calculated the sensitivity of the various classification systems for the detection of shock and the agreement between the various classification systems and the treating physician's classification.ResultsOf 152 patients with confirmed dengue, sixty-six (43%) had evidence of circulatory failure. The WHO classification system had a sensitivity of 86% (95%CI 76–94) for the detection of patients with shock. All modifications to the WHO classification system had a higher sensitivity than the WHO classification system (sensitivity ranging from 88% to 99%). The WHO classification system was in only modest agreement with the intuitive classification by treating physicians whereas several modified classification systems were in good agreement.ConclusionThe use of the WHO classification system to classify dengue disease severity is to be questioned, because it is not accurate in correctly classifying dengue disease severity and it lacks sufficient agreement with clinical practice.

Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

Acute Myeloid Leukemia (AML) is a heterogeneous malignancy driven by over 200 different cytogenetic abnormalities, giving rise to eight different subtypes, each identified as having a unique prognostic outcome and response to treatment. The World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia describes specific subtypes and is widely used to treat and diagnose AML. However, the current WHO classification system is based primarily on treatment outcomes for adult patients. In recent years, the incorporation of genetic and molecular testing has aided in the identification of several distinct subtypes that are not yet recognized by the WHO classification system. One key genomic driver in some cases of AML is the internal tandem duplication (ITD) within the gene that codes for the FMS-like tyrosine kinase receptor-3 (FLT3). Pediatric AML patients with FLT3-ITD consistently have high relapse rates and low overall survival rates, which may be improved by intensifying and specifying treatment regimens. Despite increasing research showing the prognostic significance of FLT3-ITD AML and development of FLT3 inhibitors, this cytogenetically unique form of AML with a distinctly poor prognosis in children is not mentioned in the current WHO classification. The authors suggest the need for inclusion of FLT3-ITD as a distinct entity in the WHO classification due to its prognostic effect in pediatric AML in particular. Though advancements have been made in the understanding and treatment of FLT3-ITD AML, the application of current and future research will be limited without the inclusion of FLT3-ITD as a distinct entity.

Application of the WHO reporting system for soft tissue cytopathology with assessment of risk of malignancy: a retrospective study

Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria

Does the prewash total motile sperm count (TMSC) have a better predictive value for spontaneous ongoing pregnancy (SOP) than the World Health Organization (WHO) classification system? The prewash TMSC shows a better correlation with the spontaneous ongoing pregnancy rate (SOPR) than the WHO 2010 classification system. According to the WHO classification system, an abnormal semen analysis can be diagnosed as oligozoospermia, astenozoospermia, teratozoospermia or combinations of these and azoospermia. This classification is based on the fifth percentile cut-off values of a cohort of 1953 men with proven fertility. Although this classification suggests accuracy, the relevance for the prognosis of an infertile couple and the choice of treatment is questionable. The TMSC is obtained by multiplying the sample volume by the density and the percentage of A and B motility spermatozoa. We analyzed data from a longitudinal cohort study among unselected infertile couples who were referred to three Dutch hospitals between January 2002 and December 2006. Of the total cohort of 2476 infertile couples, only the couples with either male infertility as a single diagnosis or unexplained infertility were included (n = 1177) with a follow-up period of 3 years. In all couples a semen analysis was performed. Based on the best semen analysis if more tests were performed, couples were grouped according to the WHO classification system and the TMSC range, as described in the Dutch national guidelines for male infertility. The primary outcome measure was the SOPR, which occurred before, during or after treatments, including expectant management, intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection. After adjustment for the confounding factors (female and male age, duration and type of infertility and result of the postcoital test) the odd ratios (ORs) for risk of SOP for each WHO and TMSC group were calculated. The couples with unexplained infertility were used as reference. A total of 514 couples did and 663 couples did not achieve a SOP. All WHO groups have a lower SOPR compared with the unexplained group (ORs varying from 0.136 to 0.397). Comparing the couples within the abnormal WHO groups, there are no significant differences in SOPR, except when oligoasthenoteratozoospermia is compared with asthenozoospermia [OR 0.501 (95% CI 0.311-0.809)] and teratozoospermia [OR 0.499 (95% CI: 0.252-0.988)], and oligoasthenozoospermia is compared with asthenozoospermia [OR 0.572 (95% CI: 0.373-0.877)]. All TMSC groups have a significantly lower SOPR compared with the unexplained group (ORs varying from 0.171 to 0.461). Couples with a TMSC of <1 × 10(6) and 1-5 × 10(6) have significantly lower SOPR compared with couples with a TMSC of 5-10 × 10(6) [respectively, OR 0.371 (95% CI: 0.215-0.64) and OR 0.505 (95% CI: 0.307-0.832)]. To include all SOPs during the follow-up period of 3 years, couples were not censured at the start of treatment. Roughly, three prognostic groups can be discerned: couples with a TMSC <5, couples with a TMSC between 5 and 20 and couples with a TMSC of more than 20 × 10(6) spermatozoa. We suggest using TMSC as the method of choice to express severity of male infertility. None.

Classification and scoring systems in myelodysplastic syndromes: A retrospective analysis of 311 patients

The World Health Organization (WHO) classification system for central nervous system (CNS) tumors provides a distinct framework for differentiating these tumors from other types. Notably, gliomas are the most common and clinically significant primary brain tumors. The 2021 update of the WHO classification system (WHO CNS5), building upon the 2016 edition, integrates molecular genetics with histopathological insights to enhance diagnostic precision. This update advocates a multi-layered diagnostic strategy, combining histopathology, WHO grading, and molecular genetics into a unified diagnosis, thus refining the basis for clinical research, trials, and therapeutic interventions. In WHO CNS5, gliomas are categorized into three main groups based on IDH mutation and 1p/19q codeletion status: Diffuse astrocytoma with IDH-mutant, oligodendroglioma with IDH-mutant and 1p/19q-codeletion, and glioblastoma with IDH-wildtype. The diagnostic criteria for adult diffuse gliomas include detailed descriptions of the updated classification, focusing on the molecular markers and histopathological characteristics.

Our understanding of the exact molecular and genetic alterations responsible for the evolution of the diverse diseases included under the myelodysplastic and myeloproliferative disorders lags behind that of the acute leukemias and CML. However, progress is being made, and new tests for molecular markers (increased PRV-1/CD177, decreased Mpl expression) are being developed. While in the past, treatment for both groups of diseases was primarily supportive, an improved understanding of the underlying pathobiology has led to new treatments with promising preliminary results. The laboratory's role in the diagnosis, prognosis, and determination of efficacy of treatment will continue to expand as new tests become available.

To explain the new changes in pathologic diagnoses of biphenotypic primary liver cancer (PLC) according to the updated 2019 World Health Organization (WHO) classification and how it impacts Liver Imaging Reporting and Data System (LI-RADS) classification using gadoxetic acid-enhanced MRI (Gd-EOB-MRI). We retrospectively included 209 patients with pathologically proven biphenotypic PLCs according to the 2010 WHO classification who had undergone preoperative Gd-EOB-MRI between January 2009 and December 2018. Imaging analysis including LI-RADS classification and pathologic review including the proportion of tumor components were performed. Frequencies of each diagnosis and subtype according to the 2010 and 2019 WHO classifications were compared, and changes in LI-RADS classification were evaluated. Univariable and multivariable analysis were performed to determine significant tumor component for LI-RADS classification. Of the 209 biphenotypic PLCs of the 2010 WHO classification, 177 (84.7%) were diagnosed as bipheonotypic PLCs, 25 (12.0%) as hepatocellular carcinomas (HCCs), and 7 (3.3%) as cholangiocarcinomas (CCAs) using the 2019 WHO classification. Of the 177 biphenotypic PLCs, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. There were no significant differences in the proportion of LR-5 and LR-M categories between the WHO 2010 and 2019 classifications (p = 0.941). Proportion of HCC component was the only independent factor for LI-RADS classification (adjusted odds ratio, 1.02; p < 0.001). According to the 2019 WHO classification, 15% of biphenotypic PLCs from the 2010 WHO classification were re-diagnosed as HCCs or CCAs, and a substantial proportion of biphenotypic PLCs of the 2019 WHO classification could be categorized as LR-4 or LR-5 on Gd-EOB-MRI. • Among 209 diagnosed biphenotypic PLCs according to the 2010 WHO classification, 177 (84.7%) lesions were reclassified as bipheonotypic PLCs, 25 (12.0%) as HCCs, and 7 (3.3%) as CCAs using the 2019 WHO classification. • Of the 177 biphenotypic PLCs at the 2019 WHO classification, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. • LI-RADS classification relied on the proportion of HCC component (adjusted odds ratio,1.02; p < 0.001).

Recent updating of the World Health Organization (WHO) classification of central nervous system (CNS) tumors in 2016 demonstrates the first organized effort to restructure brain tumor classification by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS tumor diagnostic criteria also attempt to reduce interobserver variability of histological interpretation and provide more accurate stratification related to clinical outcome. As an example, diffuse gliomas (WHO grades II–IV) are now molecularly stratified based upon isocitrate dehydrogenase 1 or 2 (IDH) mutational status, with gliomas of WHO grades II and III being substratified according to 1p/19q codeletion status. For now, grading of diffuse gliomas is still dependent upon histological parameters. Independent of WHO classification criteria, multidimensional scaling analysis of molecular signatures for diffuse gliomas from The Cancer Genome Atlas (TCGA) has identified distinct molecular subgroups, and allows for their visualization in 2-dimensional (2D) space. Using the web-based platform Oncoscape as a tool, we applied multidimensional scaling-derived molecular groups to the 2D visualization of the 2016 WHO classification of diffuse gliomas. Here we show that molecular multidimensional scaling of TCGA data provides 2D clustering that represents the 2016 WHO classification of diffuse gliomas. Additionally, we used this platform to successfully identify and define novel copy-number alteration-based molecular subtypes, which are independent of WHO grading, as well as predictive of clinical outcome. The prognostic utility of these molecular subtypes was further validated using an independent data set of the German Glioma Network prospective glioblastoma patient cohort.

Retrospective Analysis of Patients with Refractory Cytopenia with Unilineage Dysplasia.