Classification and Reliability of Lumbar Facet Cysts Grading Scales.

BACKGROUND: The presence of symptomatic lumbar facet cysts has been associated with segmental instability. Given this association, decompression versus decompression with fusion is a frequently debated topic. Multiple grading scales have been devised to identify patients at high risk for development of cyst recurrence; however, there exists no external evaluation of these scales. METHODS: A retrospective review of 54 patients undergoing initial treatment for lumbar synovial cysts at a single institution over the past 12 years was conducted. Surgical treatment consisted of decompression with cystectomy without fusion. Patients were assessed and classified according to the NeuroSpine Surgery Research Group (NSURG) and Rosenstock Classification systems. Five neurosurgeons reviewed the preoperative magnetic resonance images, and results were classified. Interrater reliability was assessed using both Gwet's AC1 coefficient and Krippendorff's alpha. A 1-way analysis of variance was used to evaluate predictive ability of both classification systems. RESULTS: In total, of the 54 patients who underwent decompression, 7 had cyst recurrence. Overall cyst recurrence was most common in NSURG grade 2 cysts (3/12, 25%) followed by grade 1 cysts (4/27, 14.8%). Of the NSURG grade 3 and 4 patients, none had cyst recurrence. In the Rosenstock grades the most common recurrence was in grade 3 cysts (1/4, 25%) followed by grade 1 cysts (5/26, 19.2%). Interrater reliability demonstrated good reproducibility on Gwet's AC1 and Krippendorff's alpha on both grading scales. Neither score was predictive of cyst recurrence (P > 0.05). CONCLUSIONS: The Rosenstock and NeuroSpine scores demonstrate good overall interrater reliability but are inconsistent in their ability to predict recurrence of lumbar facet cysts.

Combining weakly and strongly supervised learning improves strong supervision in Gleason pattern classification.

BACKGROUND: One challenge to train deep convolutional neural network (CNNs) models with whole slide images (WSIs) is providing the required large number of costly, manually annotated image regions. Strategies to alleviate the scarcity of annotated data include: using transfer learning, data augmentation and training the models with less expensive image-level annotations (weakly-supervised learning). However, it is not clear how to combine the use of transfer learning in a CNN model when different data sources are available for training or how to leverage from the combination of large amounts of weakly annotated images with a set of local region annotations. This paper aims to evaluate CNN training strategies based on transfer learning to leverage the combination of weak and strong annotations in heterogeneous data sources. The trade-off between classification performance and annotation effort is explored by evaluating a CNN that learns from strong labels (region annotations) and is later fine-tuned on a dataset with less expensive weak (image-level) labels. RESULTS: As expected, the model performance on strongly annotated data steadily increases as the percentage of strong annotations that are used increases, reaching a performance comparable to pathologists ([Formula: see text]). Nevertheless, the performance sharply decreases when applied for the WSI classification scenario with [Formula: see text]. Moreover, it only provides a lower performance regardless of the number of annotations used. The model performance increases when fine-tuning the model for the task of Gleason scoring with the weak WSI labels [Formula: see text]. CONCLUSION: Combining weak and strong supervision improves strong supervision in classification of Gleason patterns using tissue microarrays (TMA) and WSI regions. Our results contribute very good strategies for training CNN models combining few annotated data and heterogeneous data sources. The performance increases in the controlled TMA scenario with the number of annotations used to train the model. Nevertheless, the performance is hindered when the trained TMA model is applied directly to the more challenging WSI classification problem. This demonstrates that a good pre-trained model for prostate cancer TMA image classification may lead to the best downstream model if fine-tuned on the WSI target dataset. We have made available the source code repository for reproducing the experiments in the paper: https://github.com/ilmaro8/Digital_Pathology_Transfer_Learning.

Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers.

Proteomic signatures associated with clinical measures of more aggressive cancers could yield molecular clues as to disease drivers. Here, utilizing the Clinical Proteomic Tumor Analysis Consortium (CPTAC) mass-spectrometry-based proteomics datasets, we defined differentially expressed proteins and mRNAs associated with higher grade or higher stage, for each of seven cancer types (breast, colon, lung adenocarcinoma, clear cell renal, ovarian, uterine, and pediatric glioma), representing 794 patients. Widespread differential patterns of total proteins and phosphoproteins involved some common patterns shared between different cancer types. More proteins were associated with higher grade than higher stage. Most proteomic signatures predicted patient survival in independent transcriptomic datasets. The proteomic grade signatures, in particular, involved DNA copy number alterations. Pathways of interest were enriched within the grade-associated proteins across multiple cancer types, including pathways of altered metabolism, Warburg-like effects, and translation factors. Proteomic grade correlations identified protein kinases having functional impact in vitro in uterine endometrial cancer cells, including MAP3K2, MASTL, and TTK. The protein-level grade and stage associations for all proteins profiled-along with corresponding information on phosphorylation, pathways, mRNA expression, and copy alterations-represent a resource for identifying new potential targets. Proteomic analyses are often concordant with corresponding transcriptomic analyses, but with notable exceptions.

Intraoperative and early postoperative complications in postchemotherapy retroperitoneal lymphadenectomy among patients with germ cell tumors using validated grading classifications.

BACKGROUND: Postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an essential, yet potentially morbid, therapy for the management of patients with advanced germ cell tumors. In the current study, the authors sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAEs) and early postoperative complications. METHODS: Between 2000 and 2018, all patients who underwent PC-RPLND were analyzed for iAEs and early postoperative complications using the Kaafarani and Clavien-Dindo classifications, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. RESULTS: Of the 453 patients identified, 115 patients (25%) and 252 patients (56%), respectively, experienced an iAE and postoperative complication. Major iAEs (grade ≥3) were observed in 15 patients (3%) and major postoperative complications (grade ≥3) were noted in 80 patients (18%). The most common iAE was vascular injury (112 of 132 events; 85%), which occurred in 92 patients (20%), and the most frequent postoperative complication was ileus, which occurred in 121 patients (27%). Original and postchemotherapy retroperitoneal mass size, nonretroperitoneal metastases, intermediate and/or poor International Germ Cell Cancer Collaborative Group classification, previous RPLND, elevated tumor markers at the time of RPLND, and anticipated adjuvant surgical procedures increased the risk of both iAEs and postoperative complications. Patients who experienced an iAE were significantly more likely to experience a postoperative complication (odds ratio, 2.50; 95% confidence interval, 1.58-3.97 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the first analysis of PC-RPLND using validated classifications for both iAEs and postoperative complications, advanced disease and surgical complexity significantly increased the risks of major iAEs and postoperative complications. Standardized reporting of adverse perioperative events allows providers and patients to appreciate the consequences of PC-RPLND during counseling and decision making.

Prognostic value of the 2017 World Health Organization Classification System for gastric neuroendocrine tumors: A single-center experience.

BACKGROUND/AIMS: Gastric neuroendocrine tumors (G-NETs) are rare tumors, but their incidence is gradually increasing. Despite the existence of many classification systems, determining prognosis and planning treatment in patients with G-NETs remains a clinical challenge. In this study, the prognostic value of the World Health Organization (WHO) 2017 grading system and the effect of surgery on survival in low grade neuroendocrine tumors were investigated. MATERIALS AND METHODS: G-NETs who were diagnosed between January 2000 and May 2017 were included in the study. Patients' demographic characteristics, treatment details, and survival data were obtained from medical charts. Pathological samples were re-classified according to the WHO 2017 grading system. RESULTS: Of the total 94 evaluated patients, 50 (53.2%) were classified with G1 NETs, 37(39.4%) with G2 NETs, 4(4.2%) with well-differentiated G3 NETs, and the remaining 3 patients with poorly differentiated G3 neuroendocrine carcinoma (NEC). The median follow-up time was 83.2 months. There was a statistically significant difference in 5-year progression free survival (PFS) between G1 tumors (100%) and G2 tumors (76%) (p<0.001). However, there was no statistically significant deference in 5-year overall survival rate (OS) for G1 (97%) and G2 (82%) tumors (p=0.141). When G2 and G1 NETs were compared according to their surgical approach, radical surgery was more frequently performed in patients with G2 tumors (p<0.001). However, radical surgery did not improve PFS in G1 and G2 NETs. CONCLUSION: The WHO 2017 NET classification system may have low prognostic value for determining the prognosis of patients with G1 and G2 tumors. Radical surgery for G1 and G2 NETs did not improve PFS in our study.

Histological type and typing of breast carcinomas and the WHO classification changes over time.

The World Health Organization's new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast carcinomas which is still principally based on histological features and follows the traditions of histological typing. It gives a subjective and critical view on the WHO classifications and their changes over time, and describes the changes related to some of the most common or challenging breast carcinomas: in situ carcinomas, invasive breast carcinomas of no special type, lobular, cribriform, tubular, mucinous, papillary, metaplastic carcinomas and carcinomas with medullary pattern and those with apocrine differentiation are discussed in more details. Although the 5th edition of the classification is not perfect, it has advantages which are mentioned along with problematic issues of classifications.

[Grading of prostate cancer. For a more precise prognosis]. / Gradación del cáncer de próstata. Hacia una mayor precisión pronóstica.

The simplification of the Gleason grading system, together with the reclassification of some of its patterns, has improved correlation with the clinical reality of prostate cancer, whilst maintaining the basic principles established fifty years ago. The subsequent grouping of the patterns into five degrees has allowed a more rational unification and enhanced the physician/patient communication. However, a greater precision in the assessment of the prognosis for each patient is still necessary and, to this end, elements that allow greater discrimination are continually being sought. The purpose of this brief review is to discuss the value and possible future incorporation in international recommendations of the percentage of pattern 4, the quantification of the cribriform pattern, the detection of intraductal carcinoma, the regrouping of some 'scores' and the possible stratification of the grade group 1.

Histological intralesional heterogeneity of actinic keratoses relates to field cancerization.

BACKGROUND/OBJECTIVES: Histological heterogeneity within distinct actinic keratosis (AK) lesions has been described and might serve as an additional feature of AKs. We aimed to investigate and quantify the histological heterogeneity of AKs regarding different grading systems. METHODS AND MATERIAL: We assessed the histology of 3 mm biopsies of AK lesions located on the scalp or face. We documented basal proliferation (PRO I-III), histological grade (AK I-III) and determined the overall classification of each lesion. RESULTS: Of the 305 lesions included, 48 (15.7 %) lesions were classified as AK I, 152 (49.8 %) as AK II and 105 (34.4 %) as AK III. 33 AKs (10.8 %) showed no basal proliferation, 94 (30.8 %) were graded as PRO I, 99 (32.5 %) as PRO II and 79 (25.9 %) as PRO III. One histological grade and basal growth pattern per lesion was observed in 94 (30.8 %) and 104 (34.1 %) cases respectively, two grades in 170 (55.7 %) and 168 (55.1 %) cases, and three grades in 41 (13.4 %) and 33 (10.8 %) cases (Chi-squared test, p < 0.0001). CONCLUSIONS: By analogy with the clinical heterogeneity of field cancerization, AKs show a high histological grade heterogeneity even within small lesions. Variations in AK grading reflect the heterogeneity of the cancerization field and might serve as additional feature.

Reproducibility and Prognostic Performance of the 1973 and 2004 World Health Organization Classifications for Grade in Non-muscle-invasive Bladder Cancer: A Multicenter Study in 328 Bladder Tumors.

BACKGROUND: Histologic grade is an important prognosticator in patients with non-muscle-invasive bladder cancer (NMIBC). Currently, 2 classifications for grade are widely used; the World Health Organization (WHO) 1973 and the WHO 2004. We compare inter-observer variability of both classifications and investigate which histologic criteria cause this variability. Furthermore, the prognostic value of both classifications was assessed. PATIENTS AND METHODS: Three pathologists reviewed 328 bladder tissue samples of 232 patients with NMIBC in a blinded manner. WHO 1973 grade, WHO 2004 grade, histologic criteria of both classifications, and T-category were evaluated. Reproducibility was analyzed using the weighted Fleiss κ, association between criteria scores and grade with the χ2 test, and time-to-recurrence and time-to-progression with the log-rank test and Cox regression. RESULTS: Reproducibility of both classifications was poor. The WHO 2004 showed better reproducibility (κ = 0.35; 95% confidence interval (CI), 0.29-0.42) compared with the WHO 1973 as a 3-tiered (κ = 0.24; 95% CI, 0.19-0.28), but not as a 2-tiered (G1 + G2 vs. G3) classification (κ = 0.36; 95% CI, 0.29-0.42). Reproducibility of individual criteria was poor (κ range, -0.05 to 0.25). All criteria were associated with grade (P < .05). After a median follow-up of 60 months, 33 of 232 and 112 of 232 patients developed progression and recurrence, respectively. In 1 out of the 3 pathologists, progression was predicted by both the WHO 1973 grade and the WHO 2004 grade in multivariable analysis. Recurrence was not predicted by grade (multivariable). CONCLUSIONS: Reproducibility of the WHO 2004 and WHO 1973 classification for grade are poor. Scoring of individual criteria is poorly reproducible, suggesting that descriptions of these criteria for grade are not specific. The prognostic value of both the WHO 1973 and the WHO 2004 differ per pathologist.

The new Epstein gleason score classification significantly reduces upgrading in prostate cancer patients.

PURPOSE: To evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates. MATERIALS AND METHODS: Between 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value. RESULTS: The five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p = .001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p = .267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007). CONCLUSIONS: The new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management.

Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance.

OBJECTIVE: To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS). MATERIALS AND METHODS: Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling. RESULTS: Out of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years. CONCLUSION: Absence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS.

Validation of the 2015 prostate cancer grade groups for predicting long-term oncologic outcomes in a shared equal-access health system.

BACKGROUND: A 5-tier prognostic grade group (GG) system was enacted to simplify the risk stratification of patients with prostate cancer in which Gleason scores of ≤6, 3 + 4, 4 + 3, 8, and 9 or 10 are considered GG 1 through 5, respectively. The authors investigated the utility of biopsy GG for predicting long-term oncologic outcomes after radical prostatectomy in an equal-access health system. METHODS: Men who underwent prostatectomy at 1 of 6 Veterans Affairs hospitals in the Shared Equal Access Regional Cancer Hospital database between 2005 and 2015 were reviewed. The prognostic ability of biopsy GG was examined using Cox models. Interactions between GG and race also were tested. RESULTS: In total, 2509 men were identified who had data available on biopsy Gleason scores, covariates, and follow-up. The cohort included men with GG 1 (909 patients; 36.2%), GG 2 (813 patients; 32.4%), GG 3 (398 patients; 15.9%), GG 4 (279 patients; 11.1%), and GG 5 (110 patients; 4.4%) prostate cancer. The cohort included 1002 African American men (41%). The median follow-up was 60 months (interquartile range, 33-90 months). Higher GG was associated with higher clinical stage, older age, more recent surgery, and surgical center (P < .001) as well as increased biochemical recurrence, secondary therapy, castration-resistant prostate cancer, metastases, and prostate cancer-specific mortality (all P < .001). There were no significant interactions with race in predicting measured outcomes. CONCLUSIONS: The 5-tier GG system predicted multiple long-term endpoints after radical prostatectomy in an equal-access health system. The predictive value was consistent across races. Cancer 2017;123:4122-4129. © 2017 American Cancer Society.

Space-Occupying Tumor Bed Cysts as a Complication of Modern Treatment for High-Grade Glioma.

BACKGROUND: The management of high-grade glioma (HGG) has been affected by recent landmark trials and is now more proactive. More aggressive treatment leads to hospitalization due to side effects, however. Space-occupying tumor bed cysts have been described, but not systematically assessed. We sought to analyze this complication in a contemporary HGG cohort. METHODS: We performed a retrospective review of patients with HGG treated between 2007 and 2013, identified patients with space-occupying tumor bed cysts, and reviewed their hospital notes for relevant variables. Statistical analyses were performed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Tumor bed cysts were found in 12 of 282 patients (4%). The main symptoms were increased intracranial pressure (n = 11), new focal deficits (n = 6), and pseudomeningocele (n = 3), presenting at a median of 19 days since the last resection. Cysts were treated with cystoperitoneal (n = 7) and ventriculoperitoneal (n = 5) shunts, resulting in clinical benefit in 75% of those treated. Intraoperative opening of ventricles is a risk factor, with an OR of 39.339. We propose a classification system comprising 3 cyst types: isolated cyst, cyst with local cerebrospinal fluid (CSF) disturbance, and cyst with global CSF disturbance. CONCLUSIONS: In modern neuro-oncology, the rate of tumor bed cysts complicating HGG management appears stable compared with historical data. Shunt implantation is feasible and effective. We propose a classification system as a common data element for comparison across future studies.

Oncological predictive value of the 2004 World Health Organisation grading classification in primary T1 non-muscle-invasive bladder cancer. A step forward or back?

OBJECTIVE: To compare the clinical reliability of the 1973 and 2004 World Health Organisation (WHO) classification systems in pT1 bladder cancer. PATIENTS AND METHODS: We retrospectively evaluated 291 consecutive patients who had pT1 high grade bladder cancer between 2004 and 2011. All tumours were simultaneously evaluated by a single uro-pathologist as high grade and G2 or G3. All patients underwent a second transurethral resection (TUR) and those confirmed with non-muscle-invasive bladder cancer at second TUR received bacille Calmette-Guérin. Follow-up included urine cytology and cystoscopy 3 months after second TUR and then every 6 months for 5 years. Univariate and multivariate analysis to determine recurrence-free survival (RFS) and progression-free survival (PFS) rates were performed using the Kaplan­Meier method with the log-rank test. RESULTS: G2 tumours were found in 124 (46.6%) and G3 in 142 (53.4%) patients. The mean (median; range) follow-up period was 31.1 (19; 1­93) months. The 5-year RFS rate was 39.1% for the overall high grade population, and 49.1 and 31.8% for G2 and G3 subgroups, respectively. The 5-year PFS was 82% for the overall high grade population and 89 and 73% for G2 and G3 subgroups, respectively. RFS (P < 0.002) and PFS (P < 0.001) rates were significantly different between the G2 and G3 subgroups. In multivariate analysis, only the grade assessed according to the 1973 WHO significantly correlated with both RFS (P = 0.003) and PFS (P < 0.001). CONCLUSION: The results suggest that the 1973 WHO classification system has higher prognostic reliability for patients with T1 disease. If confirmed, these findings should be carefully taken into account when making treatment decisions for patients with T1 bladder cancer.

Molecular classification defines 4 prognostically distinct glioma groups irrespective of diagnosis and grade.

According to World Health Organization criteria, diffuse gliomas are divided into several histological subtypes, including astrocytomas, oligodendrogliomas, and oligoastrocytomas, and 4 malignancy grades (I-IV). Molecular alterations, such as the isocitrate dehydrogenase gene (IDH) mutation or 1p/19q loss, are found in these tumors but are not included in the current classification system. Recently, mutation of α thalassemia/mental retardation syndrome X-linked (ATRX) gene and its loss of expression have been reported in infiltrating gliomas. We evaluated ATRX protein expression in 272 gliomas and its association with molecular and clinical features. Loss of ATRX expression was more common in tumors with an astrocytic component (astrocytomas II/III, 46.4%; oligoastrocytomas, 47.5%) but was uncommon in oligodendrogliomas (7.3%) and glioblastomas (0.9%). In astrocytic tumors, loss of ATRX expression was significantly associated with longer overall survival. Remarkably, on the basis of IDH mutation, 1p/19q codeletion, and ATRX expression, our study defined 4 molecularly and prognostically different groups of gliomas, showing the relevance of ATRX expression as a new marker for refining the molecular classification of gliomas and for distinguishing clinically distinct prognostic subgroups of patients.

Grau de malignidade do mastocitoma cutâneo canino quanto a localização segundo as classificações de Patnaik et al. (1984) e Kiupel et al. (2011) / Degree of malignancy of the canine cutaneous mast cell tumor as forlocation according to the classifications of Patnaik et al. (1984) and Kiupel et al. (2011)

Objetivou-se com o presente trabalho coletar dados epidemiológicos relacionados com o mastocitoma canino, além de verificar se há relação entre sua malignidade e localização e, por fim, comparar os métodos de classificação histopatológica segundo Patnaik et al. (1984) e segundo Kiupel et al. (2011). Informações foram coletadas da ficha clínica de 55 cães e 60 fragmentos de pele com mastocitomas foram avaliados histologicamente. Verificou-se que a ocorrência de mastocitoma cutâneo não é influenciada pelo sexo e raça, porém cães sem raça definida e boxers são mais acometidos. Não há uma faixa etária susceptível bem definida, sendo o mastocitoma mais frequente em cães de 8 a 9 anos de idade. A região mais acometida foi a inguinal (50%) e a cabeça a região que apresentou mastocitomas com maior malignidade. Utilizando a classificação de Patnaik et al. (1984) houve diferença significativa entre as classificações histopatológicas de mastocitoma avaliadas por diferentes patologistas, o que não ocorreu utilizando a classificação de Kiupel et al. (2011). Pode-se dizer então que a classificação de Kiupel et al. (2011) gera menor divergência nos diagnósticos, demonstrando-se um método simples e eficaz para a avaliação histopatológica de mastocitoma.

The aim of the present study is to collect epidemiological data related to the canine mastocytoma, to check if there is relationbetween malignancy and its location and, finally, to compare the methods of histopathological classification according to Patnaiket al. (1984) and Kiupel et al. (2011). Informations were collected from the clinical record of 55 dogs and 60 fragments of skinwith a diagnosis of mast cell tumor were evaluated histologically. It was found that the occurrence of cutaneous mast cell tumorsis not influenced by gender and race, but dogs without defined breed and boxers are most affected. There is not a well-definedsusceptible age, but the most mast cell tumors in dogs often 8 to 9 years old. The highest affected region was inguinal (50%) andhead proved a region with higher malignancy. Using the classification Patnaik et al. (1984) there was a significant difference betweenthe histopathological ratings mastocytoma evaluated by different pathologists, which did not occur using the classification Kiupel etal. (2011). It can be said then that the classification Kiupel et al. (2011) generates less divergence in the diagnosis, demonstratinga simple and effective method for histopathological evaluation of mastocytoma.

Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance.

OBJECTIVE: To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS). PATIENTS AND METHODS: Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver-operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan-Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. RESULTS: A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several-fold increase in the risk of disease reclassification (OR 4.3, 95% CI 1.25-14.73). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification. CONCLUSIONS: Free testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.

Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification.

BACKGROUND: It is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs. METHODS: Data of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni- and multivariate analyses. Histopathological findings were re-reviewed by experienced pathologists. NET G1 was defined as mitotic count <2 per 10 high power fields (HPF) and/or ≤2% Ki67 index, and NET G2 as 2-20 mitosis per 10 HPF and/or 3-20% Ki67 index. RESULTS: There were 58 patients with NET G1 and 12 with NET G2. Incidence of recurrence was 11.4%. Univariate analysis demonstrated significant risk factors for recurrence including NET G2 of histological grade (P = 0.0089), male gender (P = 0.0333), tumor size ≥ 20 mm (P = 0.0117), lymph node metastasis (P = 0.0004), liver metastasis (P < 0.0001), lymphatic invasion (P = 0.046), and neural invasion (P = 0.0002). By multivariate analysis, histological grade (hazard ratio; 59.76, P = 0.0022) and neural invasion (hazard ratio; 147.49, P = 0.0016) were significantly associated with recurrence of PNETs. CONCLUSIONS: This study confirmed the prognostic relevance of the new grading classification and that evaluation of perineural invasion and histological grade should be considered as prognostic predictors in well-differentiated PNETs (NET G1 and G2).