Search

Abstract This study evaluates the diagnostic efficacy of automated machine learning (AutoGluon) with automated feature engineering and selection (autofeat), focusing on clinical manifestations, and a model integrating both clinical manifestations and CT findings in adult patients with ambiguous computed tomography (CT) results for acute appendicitis (AA). This evaluation was compared with conventional single machine learning models such as logistic regression(LR) and established scoring systems such as the Adult Appendicitis Score(AAS) to address the gap in diagnostic approaches for uncertain AA cases. In this retrospective analysis of 303 adult patients with indeterminate CT findings, the cohort was divided into appendicitis (n = 115) and non-appendicitis (n = 188) groups. AutoGluon and autofeat were used for AA prediction. The AutoGluon-clinical model relied solely on clinical data, whereas the AutoGluon-clinical-CT model included both clinical and CT data. The area under the receiver operating characteristic curve (AUROC) and other metrics for the test dataset, namely accuracy, sensitivity, specificity, PPV, NPV, and F1 score, were used to compare AutoGluon models with single machine learning models and the AAS. The single ML models in this study were LR, LASSO regression, ridge regression, support vector machine, decision tree, random forest, and extreme gradient boosting. Feature importance values were extracted using the “feature_importance” attribute from AutoGluon. The AutoGluon-clinical model demonstrated an AUROC of 0.785 (95% CI 0.691–0.890), and the ridge regression model with only clinical data revealed an AUROC of 0.755 (95% CI 0.649–0.861). The AutoGluon-clinical-CT model (AUROC 0.886 with 95% CI 0.820–0.951) performed better than the ridge model using clinical and CT data (AUROC 0.852 with 95% CI 0.774–0.930, p = 0.029). A new feature, exp(-(duration from pain to CT)3 + rebound tenderness), was identified (importance = 0.049, p = 0.001). AutoML (AutoGluon) and autoFE (autofeat) enhanced the diagnosis of uncertain AA cases, particularly when combining CT and clinical findings. This study suggests the potential of integrating AutoML and autoFE in clinical settings to improve diagnostic strategies and patient outcomes and make more efficient use of healthcare resources. Moreover, this research supports further exploration of machine learning in diagnostic processes.

This study evaluates the diagnostic efficacy of automated machine learning (AutoGluon) with automated feature engineering and selection (autofeat), focusing on clinical manifestations, and a model integrating both clinical manifestations and CT findings in adult patients with ambiguous computed tomography (CT) results for acute appendicitis (AA). This evaluation was compared with conventional single machine learning models such as logistic regression(LR) and established scoring systems such as the Adult Appendicitis Score(AAS) to address the gap in diagnostic approaches for uncertain AA cases. In this retrospective analysis of 303 adult patients with indeterminate CT findings, the cohort was divided into appendicitis (n = 115) and non-appendicitis (n = 188) groups. AutoGluon and autofeat were used for AA prediction. The AutoGluon-clinical model relied solely on clinical data, whereas the AutoGluon-clinical-CT model included both clinical and CT data. The area under the receiver operating characteristic curve (AUROC) and other metrics for the test dataset, namely accuracy, sensitivity, specificity, PPV, NPV, and F1 score, were used to compare AutoGluon models with single machine learning models and the AAS. The single ML models in this study were LR, LASSO regression, ridge regression, support vector machine, decision tree, random forest, and extreme gradient boosting. Feature importance values were extracted using the “feature_importance” attribute from AutoGluon. The AutoGluon-clinical model demonstrated an AUROC of 0.785 (95% CI 0.691–0.890), and the ridge regression model with only clinical data revealed an AUROC of 0.755 (95% CI 0.649–0.861). The AutoGluon-clinical-CT model (AUROC 0.886 with 95% CI 0.820–0.951) performed better than the ridge model using clinical and CT data (AUROC 0.852 with 95% CI 0.774–0.930, p = 0.029). A new feature, exp(-(duration from pain to CT)3 + rebound tenderness), was identified (importance = 0.049, p = 0.001). AutoML (AutoGluon) and autoFE (autofeat) enhanced the diagnosis of uncertain AA cases, particularly when combining CT and clinical findings. This study suggests the potential of integrating AutoML and autoFE in clinical settings to improve diagnostic strategies and patient outcomes and make more efficient use of healthcare resources. Moreover, this research supports further exploration of machine learning in diagnostic processes. [ABSTRACT FROM AUTHOR]

Background: Histopathological examination is adequate for the diagnosis of most cutaneous melanocytic neoplasms. However, there is a subset that is either difficult to definitively diagnose or would have diagnostic disagreement upon review by multiple dermatopathologists if a more exhaustive review was performed. Methods: Melanocytic lesions underwent an independent, blinded diagnostic histopathological review of hematoxylin and eosin‐stained sections. Each lesion was reviewed by three to six dermatopathologists and categorized as benign, malignant, or unknown malignant potential (UMP). Diagnoses were grouped as concordant (all the same designation); opposing (received benign and malignant designations); majority (single designation with the highest number of diagnoses, no benign/malignant opposing designations); and non‐definitive (equal number of non‐opposing designations [i.e., benign/UMP or malignant/UMP]). Lesions with equivocal designations (concordant or majority UMP, opposing, majority, and non‐definitive) were utilized in a patient treatment model of projected surgical treatment discrepancies. Results: In total, 3317 cases were reviewed, and 23.8% of lesions received equivocal diagnoses. Of these, 7.3% were majority benign, 4.8% were majority malignant, 2.7% were majority UMP, 0.5% were concordant UMP, 6.9% were opposing, and 1.6% were non‐definitive. Patient treatment models of those with equivocal lesions (n = 788) revealed a potential of overall surgical treatment variations ranging from 18% to 72%, with the highest variation amongst lesions with opposing, non‐definitive, or majority UMP (40%–72%) diagnoses. Conclusion: Histopathologic review in this large cohort demonstrated substantial diagnostic variation, with 23.8% of cases receiving equivocal diagnoses. We identified diagnostic ambiguity even in lesions where a definitive diagnosis was previously rendered by a single real‐world dermatopathologist. The combined clinical impact of diagnostic discordance or a final diagnosis of UMP is highlighted by high diagnosis‐dependent treatment variation in the patient treatment model, which could be underreported in a real‐world setting, where review by more than one to two dermatopathologists is relatively rare. [ABSTRACT FROM AUTHOR]

Abstract Biren Parikh Introduction Hormonal status and HER2 expression are valuable biomarkers and dictate the management of the patients diagnosed with invasive breast cancer (IBC). It is crucial to identify the patients who truly respond to anti-HER2 targeted therapy. Updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines has recommended certain modifications in HER2 interpretation by fluorescence in situ hybridization (FISH) with concomitant immunohistochemistry (IHC). Objectives We aimed to evaluate HER2 FISH interpretation in IBC with equivocal IHC results as per 2018 ASCO/CAP recommendations and compare FISH results with hormonal receptor status. Materials and Methods FISH results of 502 cases of IBC with equivocal IHC report between January 2016 to January 2022 were reviewed retrospectively. FISH results were categorized according to ASCO/CAP guidelines 2018 into five respective groups. Results FISH testing in IHC equivocal cases showed 219 (43.6%) cases were classic amplified (positive) belonged to group 1, 217(43.2%) cases were classic nonamplified (negative) fell into group 5, 39 (7.8%) and 02 (0.4%) patients were in group 2 (negative) and group 3 (positive), and 25 (5.0%) cases were in group 4 (negative). About 52.1 and 49.3% of cases with estrogen receptor and progesterone receptor positivity were reported as HER2 positive. Among 502 cases, 25 equivocal cases according to the 2013 guidelines were redefined as HER2 negative and 02 (0.4%) cases reported positive were classified negative as per updated 2018 guidelines. Conclusion Revised 2018 guidelines is helpful in accurate identification of HER2 status and in avoiding targeted therapy in unwarranted cases. Updated 2018 guidelines has removed equivocal HER2-FISH category that has eliminated management dilemma in these cases. Only long-term clinical follow-up will establish the validity of the updated guidelines.

Dilated cardiomyopathy (DCM) is common in Great Danes (GDs) but screening for this condition can be challenging. We hypothesised that cardiac troponin-I (cTnI) concentration is elevated in GDs with DCM and/or ventricular arrhythmias (VAs), and is associated with reduced survival time in GDs. One hundred and twenty-four client-owned GDs assigned echocardiographically as normal (n = 53), equivocal (n = 37), preclinical DCM (n = 21), or clinical DCM (n = 13). A retrospective epidemiological study. Echocardiographic diagnosis, VAs, and contemporaneous cTnI concentrations were recorded. Diagnostic accuracy and cTnI cut-offs were determined with receiver operating characteristic analyses. Effects of the cTnI concentration and disease status on survival and cause of death were explored. Median cTnI was greater in clinical DCM (0.6 ng/mL [25th–75th percentiles: 0.41–1.71 ng/mL]) and GDs with VAs (0.5 ng/mL [0.27–0.80 ng/mL], P<0.001). Elevated cTnI detected these dogs with good accuracy (area under the curve: 0.78–0.85; cut-offs 0.199–0.34 ng/mL). Thirty-eight GDs (30.6%) suffered a cardiac death (CD); GDs suffering CD (0.25 ng/mL [0.21–0.53 ng/mL]) and specifically sudden cardiac death (SCD) (0.51 ng/mL [0.23–0.72 ng/mL]) had higher cTnI than GDs dying of other causes (0.20 ng/mL [0.14–0.35 ng/mL]; P<0.001). Elevated cTnI (>0.199 ng/mL) was associated with shorter long-term survival (1.25 years) and increased risk of SCD. Great Danes with VAs had shorter survival times (0.97 years). A cardiac troponin-I concentration is a useful adjunctive screening tool. Elevated cTnI is a negative prognostic indicator. [ABSTRACT FROM AUTHOR]

Automated amyloid-PET image classification can support clinical assessment and increase diagnostic confidence. Three automated approaches using global cut-points derived from Receiver Operating Characteristic (ROC) analysis, machine learning (ML) algorithms with regional SUVr values, and deep learning (DL) network with 3D image input were compared under various conditions: number of training data, radiotracers, and cohorts. 276 [11C]PiB and 209 [18F]AV45 PET images from ADNI database and our local cohort were used. Global mean and maximum SUVr cut-points were derived using ROC analysis. 68 ML models were built using regional SUVr values and one DL network was trained with classifications of two visual assessments – manufacturer's recommendations (gray-scale) and with visually guided reference region scaling (rainbow-scale). ML-based classification achieved similarly high accuracy as ROC classification, but had better convergence between training and unseen data, with a smaller number of training data. Naïve Bayes performed the best overall among the 68 ML algorithms. Classification with maximum SUVr cut-points yielded higher accuracy than with mean SUVr cut-points, particularly for cohorts showing more focal uptake. DL networks can support the classification of definite cases accurately but performed poorly for equivocal cases. Rainbow-scale standardized image intensity scaling and improved inter-rater agreement. Gray-scale detects focal accumulation better, thus classifying more amyloid-positive scans. All three approaches generally achieved higher accuracy when trained with rainbow-scale classification. ML yielded similarly high accuracy as ROC, but with better convergence between training and unseen data, and further work may lead to even more accurate ML methods. [ABSTRACT FROM AUTHOR]

Background: Equivocal and indeterminate breast lesions which are detected on sonomammography should be further evaluated by either biopsy or follow-up. Contrast-enhanced digital mammography can act as a problem-solving tool to avoid biopsies of some problematic breast lesions and help clinicians to take a proper decision about these lesions in the same setting. Objective: This study aimed to evaluate the complementary role of contrast-enhanced digital mammography (CEDM) to characterize indeterminate and equivocal breast lesions detected on sonomammography and its role to downgrade or upgrade the final BI-RADS category of these lesions. Patients and Methods: This prospective study included 35 females with mean age of 48.26 years. Ladies were referred from the clinic for screening mammograms during the period from august 2020 to September 2021. Results: Contrast-enhanced digital mammography showed higher specificity (86.4%), PPV (80.0%), NPV (95.0%), and accuracy (88.6%). While sonomammography revealed specificity of 63.6%, PPV of 60.0%, NPV of 93.3%, and accuracy of 74.29%. However, both showed a comparable sensitivity of about 92.3%. Fourteen lesions (40%) were downgraded by CEDM and proved to be benign lesions and five lesions (14.2%) were upgraded and proved to be malignant lesions. Conclusion: Contrast-enhanced digital mammography is a promising technique in the characterization of equivocal and indeterminate breast lesions (BI-RADS 3 and 4). It can be utilized to help in the final assessment of these findings in the same setting and offer assistance in avoiding biopsies in numerous patients with more prominent specificity and precision than sonomammography. [ABSTRACT FROM AUTHOR]

The American Society of Clinical Oncology and College of American Pathologists guidelines for HER2 testing in breast cancer (BC) have been updated with more stringent criteria regarding immunohistochemistry (IHC) 2 + interpretation. The aim of our study was to determine HER2 status in IHC 2 + cases based on 2013 and 2018 guidelines and to investigate specific histologic characteristics that might predict HER2 status in tumors with equivocal IHC staining. Two hundred eighty BC cases reported as IHC 2 + and 24 cases reported as non-IHC 2 + were reviewed with 12 histologic characteristics. Of the IHC 2 + cases based on 2013 guideline, 21% were reclassified to IHC 1 + when applying the 2018 guidelines. Consequently, it led to an 8% increase of HER2 amplification rate in 2018 IHC 2 + group. Seven characteristics were significantly associated with prediction of HER2 amplification in IHC 2 + BCs, including high tumor-infiltrating lymphocytes (TILs), distinct cellular membrane, no apical snout, large nuclear size, nuclear size variation, high nuclear grade, and tubule formation < 10%. Using these criteria, the presence of four or more characteristics significantly indicates HER2 amplification. Moreover, four characteristics among them, including high TILs, distinct cellular membrane, nuclear size variation, and high nuclear grade, were also associated with HER2 amplification in non-IHC 2 + cases, demonstrating their predictive value as complements to IHC. In conclusion, we provide specific morphologic features that will improve pathologist performance in identifying more HER2-positive BCs. We further suggest an algorithm for trastuzumab therapy decisions using a combination of histomorphologic evaluation and the updated 2018 guidelines. [ABSTRACT FROM AUTHOR]

Abstract Background Assessing the extent of disease in newly diagnosed prostate cancer (PC) patients is crucial for tailoring an appropriate treatment approach. Prostate-specific membrane antigen (PSMA)–targeted positron emission tomography/computed tomography (PET/CT) reportedly has greater accuracy than conventional imaging for staging PC. As with any imaging modality, pitfalls and nonspecific findings do occur. The PSMA reporting and data system (PSMA-RADS) version 1.0 offers structured interpretation of PSMA-targeted studies and classifies lesions by likelihood of clinical significance. The aim of this retrospective study was to evaluate the clinical significance of equivocal bone findings on staging PSMA-targeted imaging, as defined by PSMA-RADS version 1.0, in the preoperative setting. Fifteen of 406 consecutive patients staged by PET/CT prior to radical prostatectomy had equivocal bone lesions. The scans were retrospectively scored with the PSMA-RADS version 1.0 system, blinded to disease course and follow-up data. Postoperative persistence of prostate-specific antigen levels supported by imaging and histological findings was used as the reference standard for the true significance of equivocal imaging findings. Results Thirteen of the 15 patients had an overall PSMA-RADS score of 3B, of whom only two had true metastatic disease. The remaining patients had scores of 4 (n = 1) or 5 (n = 1), all confirmed as true positive prostate-related malignant lesions. A per-lesion analysis identified 29 bone lesions, of which 27 were scored PSMA-RADS 3B, and only three of them were true metastases. Thus, debatable lesions proved to have no clinical significance in 84.6% of cases, and only 11% of equivocal PSMA-RADS 3B bone lesions were true positive. Conclusions In intermediate and high-risk patients staged prior to radical prostatectomy, the majority of PSMA-RADS 3B lesions are of no clinical relevance. Bone lesions judged as being highly suspicious for metastases (PSMA-RADS 4/5) were all validated as true positives.

In 2018, the American Society of Clinical Oncology/College of American Pathologists revised the criteria for HER2 immunohistochemistry (IHC) equivocal (2+) classification in their updated guideline. We reviewed invasive breast cancer specimens originally classified as equivocal (2+) under the 2018 guideline that underwent HER2 fluorescence in situ hybridization (FISH) testing from August 2018 to August 2019 at our Canadian reference hospital to investigate cases with ambiguous staining patterns between the 1+ and 2+ definitions. Demographics, pathologic features, and pre-analytic conditions were recorded. The H&E and corresponding HER2 IHC slides were reviewed to confirm tumor type and grade, and classify as HER2 indeterminate, 0, 1+, 2+, or "Intermediate" (staining features between the 1+ and 2+ classifications). FISH testing was performed on 289 cases and 273 met inclusion criteria. The FISH-amplified rate was 12.1%. Upon IHC review, 44.7% (122/273) of cases were reclassified as Intermediate. These cases had incomplete staining with moderate intensity (43/122, 35.3%) and/or <10% complete weak or moderate staining (102/122, 83.6%). Intermediate cases had a significantly lower frequency of amplified FISH results than 2+ cases (p < 0.0001), with only four (3.3%) FISH positive and two (1.6%) FISH heterogeneous. Our study highlights the ambiguity in the current guideline for classifying some HER2 IHC patterns. As the rate of gene amplification in these cases was low (4.9%), we recommend adhering to the 2018 HER2 2+ criteria for reflex FISH testing. However, cases with <10% moderate complete staining and certain heterogeneous patterns warrant special consideration. Further descriptive clarification of 1+ criteria is needed. [ABSTRACT FROM AUTHOR]

Background: Assessing the extent of disease in newly diagnosed prostate cancer (PC) patients is crucial for tailoring an appropriate treatment approach. Prostate-specific membrane antigen (PSMA)–targeted positron emission tomography/computed tomography (PET/CT) reportedly has greater accuracy than conventional imaging for staging PC. As with any imaging modality, pitfalls and nonspecific findings do occur. The PSMA reporting and data system (PSMA-RADS) version 1.0 offers structured interpretation of PSMA-targeted studies and classifies lesions by likelihood of clinical significance. The aim of this retrospective study was to evaluate the clinical significance of equivocal bone findings on staging PSMA-targeted imaging, as defined by PSMA-RADS version 1.0, in the preoperative setting. Fifteen of 406 consecutive patients staged by PET/CT prior to radical prostatectomy had equivocal bone lesions. The scans were retrospectively scored with the PSMA-RADS version 1.0 system, blinded to disease course and follow-up data. Postoperative persistence of prostate-specific antigen levels supported by imaging and histological findings was used as the reference standard for the true significance of equivocal imaging findings. Results: Thirteen of the 15 patients had an overall PSMA-RADS score of 3B, of whom only two had true metastatic disease. The remaining patients had scores of 4 (n = 1) or 5 (n = 1), all confirmed as true positive prostate-related malignant lesions. A per-lesion analysis identified 29 bone lesions, of which 27 were scored PSMA-RADS 3B, and only three of them were true metastases. Thus, debatable lesions proved to have no clinical significance in 84.6% of cases, and only 11% of equivocal PSMA-RADS 3B bone lesions were true positive. Conclusions: In intermediate and high-risk patients staged prior to radical prostatectomy, the majority of PSMA-RADS 3B lesions are of no clinical relevance. Bone lesions judged as being highly suspicious for metastases (PSMA-RADS 4/5) were all validated as true positives. [ABSTRACT FROM AUTHOR]

Purpose: For breast cancer, accurately illustrating HER2 characteristics is a critical precondition for evaluating the prognosis and predicting the efficacy of anti-HER2 therapy. Our purpose was to expose HER2 mRNA expression through an in situ hybridization assay (RNAscope), to aid the identification of HER2 status in breast cancers with a previously controversial classification for patients suffering from a HER2 IHC2+ and HER2/CEP17 ≥2.0 and a

Purpose: For breast cancer, accurately illustrating HER2 characteristics is a critical precondition for evaluating the prognosis and predicting the efficacy of anti-HER2 therapy. Our purpose was to expose HER2 mRNA expression through an in situ hybridization assay (RNAscope), to aid the identification of HER2 status in breast cancers with a previously controversial classification for patients suffering from a HER2 IHC2+ and HER2/CEP17 ≥2.0 and a <4.0 mean HER2 gene copy number/cell (entitled FISH group 2 by update 2018 HER2 testing guideline). Methods: A total of 8,983 cases of breast cancer with a known HER2 status detected by initial IHC, and a necessary reflex FISH assay for those with IHC2+, were retrospectively analyzed. Then, 41 cases of HER2 IHC2+ in the FISH group 2 were collected and a RNAscope was performed. Results: The incidence of breast cancers with IHC2+ and in the FISH group 2 was 0.46% (41/8,983) in our single-institutional study cohort. In most of the cases (27/41, 65.9%), low levels of HER2 mRNA expression (score 1 and 2 by RNAscope) were demonstrated. Only one case (1/41, 2.4%) of high-level HER2 mRNA expression (score 4 by RNAscope), harboring a FISH HER2/CEP17 ratio of 2.06 and an average HER2 copy number of 3.70, was revealed. One case with the highest FISH HER2/CEP17 ratio of 3.90, showed the lowest level of HER2 mRNA expression (score 1 by RNAscope). Two cases with the same highest average HER2 signals/cell (3.95) by FISH possessed score 3 and score 2 with RNAscope, respectively. No cases with a score of 0 by RNAscope occurred in our sample. In the majority of cases (35/41, 85.4%), hypodisomy of chromosome 17 (average CEP17 signals/cell ≤1.75) was observed. There was no significant relationship between the mRNA expression and FISH results (average HER2 signals/cell, average CEP17 copy number, or HER2/CEP17 ratio) and clinicopathological features (ER and PR statuses, Ki 67 index, tumor size, and lymph node metastasis) in our population. Conclusion: HER2 mRNA overexpression was not a feature in our group of patients. Based on our data, breast cancers with HER2 IHC2+ and in FISH group 2 support a categorization of HER2 negative. [ABSTRACT FROM AUTHOR]

Copyright of Hipogrifo: revista de literatura y cultura del siglo de oro is the property of Hipogrifo: revista de literatura y cultura del siglo de oro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objective:Determination of HER2 gene is crucial in breast carcinoma management and prognosis, as HER2 alterations are linked to a shorter disease-free period, overall survival and resistance to tamoxifen anti-estrogen therapy and other chemotherapy regimens, regardless of the nodal or hormone receptor status. This study aimed to estimate HER2 gene status of infiltrative mammary cancer cases with immunohistochemically equivocal (2+) score using Silver DNA in Situ Hybridization(SISH) technique and to investigate its association with clinicopathological variables. Methods: The study included 52 formalin-fixed paraffin embedded tissue blocks from female patients with invasive breast carcinoma with score of 2+ (equivocal) HER2 immunohistochemistry. All cases were studied by silver DNA in situ hybridization technique (SISH) for the determination of the amplified HER2 DNA. Results: TheSISH technique showed that HER2 gene was not amplified in 33 cases out of 52 (63.5%); while the rest of 19 cases (36.5%) revealed amplified gene status.According to age, HER2 gene status reported non-significant difference in the age groups between cases with amplified and non-amplified gene status (P=0.173). There was a significant negative association between positive Estrogen (ER) and Progesterone (PR) status and HER2 gene amplification (P= 0.002 and 0.017, respectively). Conclusion: More than half of breast carcinoma cases with equivocal HER2 immunoreactivity showed non-amplified gene status; this needs to be considered by oncologists in their management planning of breast cancer. Amplified HER2 gene is significantly associated with negative ER and PR status that affects patients’ management protocols and future outcome of the disease.

Purpose: Human epidermal growth factor receptor 2 (HER2) status is both an independent prognostic factor and a predictive factor for the efficacy of targeted therapy for breast cancer, so it is critical to accurately detect HER2 protein expression and/or gene amplification. According to the recommendations of the 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines for HER2 breast cancer testing, an additional test should be pursued on a different block from the same tumor as one of the options for patients with immunohistochemistry (IHC) 2+ and a HER2/CEP17 ratio of < 2.0 with an average HER2 signals per tumor cell of ≥ 4.0 and < 6.0 by reflex test using dual-probe fluorescence in situ hybridization (FISH) (double-equivocal HER2). Our aim in this study is to explore the consistency of HER2 status between the two blocks. Methods: We retrospectively analyzed 5685 primary invasive breast cancers between April 2015 and January 2019 from Peking Union Medical College Hospital. For cases with double-equivocal HER2 revealed in initial blocks, HER2 gene status was evaluated by FISH in a different block from the same tumor. The FISH score was interpreted according to the 2013 ASCO/CAP guidelines for HER2 testing. Results: In our cohort of 5685 specimens, the overall HER2 IHC3+, 2+, 1+ and 0 cases were 20.5%, 31.8%, 28.3%, and 19.5%, respectively. Then, 13.7%, 66.3%, and 20.0% of HER2 amplification, non-amplification, and equivocation rates were found, respectively, in IHC2+ patients (n = 1777) by reflex FISH assay. For specimens with double-equivocal HER2 (n = 333), HER2 status was assessed in another block from the same tumor by FISH and then the frequency of HER2 positive, negative, and equivocation was estimated at 5.7%, 22.5%, and 71.8%, respectively. Because double-equivocal HER2 cases are classified in the HER2 negative category by the 2018 ASCO/CAP HER2 testing guidelines, only 1.3% (19/1511) of HER2 positive patients were determined through additional HER2 testing in another block from the HER2 negative population. Conclusions: HER2 status in different blocks from the same tumor in primary invasive breast cancer was highly concordant. Our data supported the recommendation of the 2018 ASCO/CAP HER2 testing guidelines in breast cancer to remove the suggestion for additional HER2 testing using another block contained in the previous version. [ABSTRACT FROM AUTHOR]

Copyright of Cahiers Victoriens & Edouardiens is the property of Presses Universitaires de la Mediterranee and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To compare AmnioQuick Duo+ versus the placental α-microglobulin-1 (PAMG-1) test for diagnosis of prolonged premature rupture of membranes (PROM).Methods: A multicenter prospective cohort study included women with suspected PROM at six tertiary institutions in southern Nigeria between January 1 and December 31, 2015. The inclusion criteria were features of PROM lasting at least 24 hours and a pregnancy duration of more than 24 weeks. AmnioQuick Duo+ (Biosynex, Strasbourg, France) and PAMG-1 (AmniSure International, Boston, USA) tests were used to diagnose PROM, which was confirmed after delivery by any two of the following criteria: delivery within 48 hours to 7 days, chorioamnionitis, membranes perceptibly ruptured at delivery, and adverse perinatal outcomes considerably associated with prolonged PROM.Results: Of 100 women assessed for eligibility, 99 were included. Sensitivity, specificity, and accuracy were, respectively, 97.3%, 100%, and 95.9% for AmnioQuick Duo+, and 93.2%, 100%, and 90.4% for PAMG-1. The differences were not significant and the diagnostic discordant rate between the two tests was 3.1%. In equivocal cases (i.e., negative pooling test result), AmnioQuick Duo+ and PAMG-1 performed equally (diagnostic accuracy, 100% vs 97.7%; P>0.99).Conclusion: For diagnosis of PROM, AmnioQuick Duo+ was found to be non-inferior and comparable in accuracy to the PAMG-1 test, with a diagnostic discordance rate of 3.1%. [ABSTRACT FROM AUTHOR]

Purpose: While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Alternative probes may be used in equivocal cases. We present a single community-based institution’s experience in further evaluating these cases.Patients and methods: Between 2014 and 2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA. Of the patients tested by FISH, 505/3908 (12.9%) also had IHC data.Results: Most (73.9%) FISH equivocal cases remained equivocal after IHC testing. However, 50.5% of equivocal cases were classified as HER2 amplified by alternative probes. Most cases were positive by more than one probe: 78% of positive cases by RAI1 and 73.9% by TP53. There was a significant difference between IHC and FISH alternative testing (p < 0.0001) among the equivocal cases by conventional FISH testing, 44% of IHC negative cases became positive while 36% of the positive IHC cases became negative by alternative FISH testing. Available data showed that 41% of patients were treated with palbociclib and were positive by alternative FISH.Conclusion: The prevalence of double HER2 equivocal cases and the discrepancy between IHC and alternative FISH testing suggest that FISH alternative testing using both RAI1 and TP53 probes is necessary for conclusive classification. Because almost half of FISH equivocal cases converted to HER2 amplified upon alternative testing, clinical studies to determine the benefit of anti-HER2 therapy in these patients are urgently needed. [ABSTRACT FROM AUTHOR]

In breast cancer, human epidermal growth factor receptor 2 (HER2) status is determined by immunohistochemistry (IHC) and/or in situ hybridization. Oncotype DX also reports HER2 status by an rt-PCR-based assay. Assay concordance between IHC and fluorescent in situ hybridization (FISH) (including alternative probe HER2 FISH) vs Oncotype DX HER2 rt-PCR has not been described in the post-2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Guideline revision setting. We performed a retrospective review of HER2 equivocal invasive breast carcinoma from 2014 to 2016 with the Oncotype DX HER2 result. Fifteen patients with HER2 equivocal invasive breast cancer had Oncotype DX performed. Of these, 13 underwent alternative probe HER2 FISH yielding 4 negative, 6 equivocal and 3 positive results. All 15 cases were classified as HER2 negative by Oncotype DX rt-PCR, including the three cases which were positive by alternative probe HER2 FISH, yielding a discordance rate for Oncotype DX rt-PCR HER2 of 20% (3/15). All three patients with HER2- positive breast cancer on the basis of alternative probe HER2 FISH received anti- HER2-targeted therapy. Treatment decisions based on HER2 status should utilize the IHC/FISH result as Oncotype DX results may incorrectly disqualify some patients from being eligible for anti-HER2 therapy based on the current 2013 ASCO/CAP HER2 Guidelines. [ABSTRACT FROM AUTHOR]

Objectives: To assess the usefulness of serial electrophysiology in Guillain‐Barré syndrome (GBS) in a multicenter setting and the reasons for change in electrodiagnostic subtypes with serial studies. Methods: We retrospectively analysed serial electrophysiology of 51 patients with GBS from 4 European centres. Proportions of subtypes were determined at each timing. Individual case analyses were also performed where diagnostic changes occurred with either criteria, to ascertain if changes were due to disease progression or criteria inadequacy. Results: At first study, comparing old vs new criteria, acute inflammatory demyelinating polyneuropathy (AIDP) was diagnosed in 70.6% vs 51%, axonal GBS in 15.7% vs 39.2%, equivocal forms in 11.8% vs 7.8%. At second study, AIDP was diagnosed in 72.5% vs 52.9%, axonal GBS in 9.8% vs 33.3%, equivocal forms in 15.7% vs 11.7%. Subtype proportions were unchanged, indicating serial studies did not, in the cohort, alter diagnostic rates for each subtype irrespective of criteria used. Individual review of cases where subtype electrodiagnosis changed indicated suboptimal specificity for AIDP/sensitivity for axonal GBS as main cause of diagnostic shifts with old criteria, whereas disease progression explained most changes with new criteria (55.6% vs 81.8%; P = .039). Conclusions: Serial electrophysiology is unhelpful in GBS. Repeat studies cannot represent the gold standard as electrodiagnosis may alter due to disease progression. Changes in electrodiagnosis relate more often to disease progression with new criteria but are more frequently due to suboptimal sensitivity/specificity with old criteria. A single electrophysiological study using the most accurate available criteria appears sufficient in GBS. [ABSTRACT FROM AUTHOR]

This text performs, from the viewpoint by the theory Discourse Analysis (AD), the practice of reading a sentence that was part of the magazine cover IstoÉ, number 2436, dated August 12, 2016, in a matter titled "IT IS TIME TO LEAVE". This magazine, known for always having positioned itself with harsh reviews of the Dilma government, in this edition, contradicting an editorial line and the own call of the matter, stamped the sentence "The crimes against it became evident". We conceiving the language as the materiality of discourse with space for the possible and the impossible that is its own, and taking the sentence as text, we allow ourselves to apprehend effects of this impossible that emerges through the language. IstoÉ, in the perspective of psychoanalysis, produces a flawed act and, in the perspective of AD, a equivocal that is constructed by the language itself, making emerge the impossible of the discourse for the FD that supports the senses of IstoÉ. [ABSTRACT FROM AUTHOR]

• In patients with a prostate imaging reporting and data system 3 lesion, the detection rate of clinically significant prostate cancer (csPCa) is about 17%. Therefore, the management of this patients can be discussed. • Prostate-specific antigen density (PSAD) ≥ 0.15 ng/ml/cm3 and age were independent predictive factors of csPCa and previous negative prostate biopsy (PBx) was negatively associated with csPCa. • Using PSAD alone to select patient to undergo PBx, would omit 71.5% of PBx at the cost of missing 15.0% of csPCa. • Other predictive factors as age and PBx history should also be considered in the discussion with the patient, to avoid several PBx while missing few csPCa. • Combining predictive factors could be an option to avoid unnecessary PBx. Indeed, in patient with PSAD < 0.15 ng/ml/cm3, younger than 65 years old with previous negative PBx, there was no csPCa. While Prostate Imaging Reporting and Data System (PI-RADS) 4 and 5 lesions usually justify prostate biopsy (PBx), the management of a PI-RADS 3 lesion can be discussed. The aim of our study was to determine the optimal prostate-specific antigen density (PSAD) threshold and predictive factors of clinically significant prostate cancer (csPCa) in patients with a PI-RADS 3 lesion on MRI. Using our prospectively maintained database, we conducted a monocentric retrospective study, including all patients with a clinical suspicious of prostate cancer (PCa), all of them had a PI-RADS 3 lesion on the mpMRI prior to PBx. Patients under active surveillance or displaying suspicious digital rectal examination were excluded. Clinically significant (csPCa) was defined as PCa with any ISUP grade group ≥ 2 (Gleason ≥ 3 + 4). We included 158 patients. The detection rate of csPCa was 22.2%. In case of PSAD ≤ 0.15 ng/ml/cm3, PBx would be omitted in 71.5% (113/158) of men at the cost of missing 15.0% (17/113) of csPCa. With a threshold of 0.15 ng/ml/cm3, the sensitivity and the specificity were 0.51 and 0.78 respectively. The positive predictive value was 0.40 and the negative predictive value was 0.85. According to multivariate analysis, age (OR = 1.10, CI95% 1.03–1.19, P = 0.007), and PSAD ≥ 0.15 ng/ml/cm3 (OR = 3.59, CI95% 1.41–9.47, P = 0.008) were independent predictive factors of csPCa. Previous negative PBx was negatively associated with csPCa (OR = 0.24, CI 95% 0.07–0.66, P = 0.01). Our result suggests that the optimal PSAD threshold was 0.15 ng/ml/cm3. However, in this case omitting PBx in 71.5% of cases would be at the cost of missing 15.0% of csPCa. PSAD should not be used alone, other predictive factors as age and PBx history should also be considered in the discussion with the patient, to avoid PBx while missing few csPCa. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: The updated 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing have made some major changes in HER2 fluorescence in situ hybridization (FISH) interpretation criteria with additional FISH equivocal cases. Repeat HER2 testing is recommended after initial HER2 FISH equivocal results; however, little is known about its impact on final HER2 status. The aim of this study is to investigate whether reflex test clarifies HER2 status, and to characterize clinicopathological features of the newly defined HER2 equivocal group. Methods: A total of 886 consecutive cases of primary invasive breast cancer conducted with dual-probe HER2 FISH testing between November 2013 and December 2015 were reviewed. HER2 immunohistochemistry (IHC) and FISH testing were performed on a different tissue block or a new specimen after initial HER2 FISH equivocal results. Results: Compared to 2007 guideline, 85 (9.6%) cases changed their category by using 2013 guideline. The major change of the 85 cases is that 57 (6.4%) cases in HER2 FISH-negative category changed to equivocal, and the equivocal category cases increased from 36 to 67. HER2 FISH equivocal was significantly associated with HER2 IHC equivocal (2+) and chromosome 17 polysomy ( P < 0.01). Repeat testing by IHC and FISH clarified HER2 status in 33 and 42% of HER2 equivocal cases, respectively. Overall 32 (48%) initial HER2 equivocal cases stayed HER2 equivocal after repeat FISH and or IHC testing. These tumors were ER/PR+, with high KI-67 index. Conclusion: New guidelines classify more HER2 FISH equivocal cases. Repeat HER2 testing clarifies HER2 status in about 50% of initial HER2 FISH equivocal cases. In addition, HER2 equivocal cases merit further study as there is limited information about prognosis and optimal treatment strategy for this population. [ABSTRACT FROM AUTHOR]

Purpose The new ASCO/CAP guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2- FISH, introducing the most controversial change to the HER2-equivocal category. We retrospectively evaluated the impact of AC2013 in a cohort of consecutive invasive breast cancers (IBCs) analyzed with frontline dual-color FISH. Methods 2788 consecutive IBCs were reclassified based on the AC2013 guidelines. Clinico-pathological features of equivocal IBCs were compared with HER2-negative and HER2-positive IBCs. FISH HER2-equivocal cases underwent reflex tests: HER2-IHC, RARA -FISH, and SMS -FISH. Overall and disease-free survivals were evaluated in AC2007 HER2-positive patients treated with trastuzumab and in patients that became eligible for target-therapy according to AC2013. Results Two-hundred HER2-negative cases (7.2%) were classified differently, following AC2013: 0.3% (8/2788) became HER2-positive and 6.9% (192/2788) HER2-equivocal. AC2013, compared with AC2007, significantly increased initial HER2-equivocal cases (6.9%vs1.6%, p < 0.001). AC2013 equivocal-IBCs affected older patients and showed pathological features between HER2-negative and HER2-positive IBCs. After reflex tests, 102 of the 190 equivocal cases (53.7%) were reclassified as HER2-positive, 51 (26.8%) as negative and 37 (19.5%) as equivocal. IHC tested negative in 44.7% of cases, whereas SMS -FISH showed the highest percentage of positive results (45.8%). Clinical outcomes showed no statistically significant differences. Conclusion Overall, 80.5% of FISH-equivocal cases were solved with at least one reflex test and 3.6% of patients became AC2013 HER2-positive, therefore eligible for target-therapy, but showed clinical outcomes similar to HER2-positive patients treated with trastuzumab. Our data belittle the clinical impact of AC2013 HER2-equivocal reclassification; further prospective randomized clinical studies are necessary to support these findings. [ABSTRACT FROM AUTHOR]

Objective To evaluate the significance of routinely reported 'equivocal' lymphovascular invasion ( LVI) in prostatectomy specimens of patients with clinically localized prostate cancer. Materials and Methods Prospectively collected data from men who underwent prostatectomy for clinically localized prostate cancer were retrospectively reviewed. Rates of adverse pathological features and biochemical recurrence ( BCR) were compared between tumours positive, negative or 'equivocal' for LVI. Multivariable Cox regression analysis was performed to identify independent predictors of BCR. Results Of 1 310 consecutive cases, LVI was present definitively in 82 (6.3%) and equivocally in 43 (3.3%) cases. Similar to definitive LVI, equivocal LVI was significantly associated with other adverse pathological features, including advanced stage, higher Gleason grade and positive surgical margins. BCR occurred more frequently in patients with tumours that were equivocal (61%) or positive for LVI (71%) than in patients with negative results (14.7%). In addition, patients with both definitive and equivocal LVI had a significantly shorter BCR-free survival time compared with those with negative LVI. Multivariable Cox regression analysis indicated that the presence of either definitive or equivocal LVI were independent predictors of disease recurrence (hazard ratio [ HR] 3.32, 95% confidence interval [ CI] 2.3-4.8; P <0.001 vs HR 1.66, 95% CI 1.05-2.65; P = 0.032, respectively). Conclusion In this single-institution study, equivocal LVI had a similar association with adverse pathological features and rate of BCR to that of definitive LVI. If our observations are validated in an independent cohort, consideration should be given to the inclusion of equivocal LVI as part of routine pathological reporting. [ABSTRACT FROM AUTHOR]

Background and Objective: Determination of HER2 gene is crucial in breast carcinoma management and prognosis, as HER2 alterations are linked to a shorter disease-free period, overall survival and resistance to tamoxifen anti-estrogen therapy and other chemotherapy regimens, regardless of the nodal or hormone receptor status. This study aimed to estimate HER2 gene status of infiltrative mammary cancer cases with immunohistochemically equivocal (2+) score using Silver DNA in Situ Hybridization (SISH) technique and to investigate its association with clinicopathological variables. Methods: The study included 52 formalin-fixed paraffin embedded tissue blocks from female patients with invasive breast carcinoma with score of 2+ (equivocal) HER2 immunohistochemistry. All cases were studied by silver DNA in situ hybridization technique (SISH) for the determination of the amplified HER2 DNA. Results: The SISH technique showed that HER2 gene was not amplified in 33 cases out of 52 (63.5%); while the rest of 19 cases (36.5%) revealed amplified gene status. According to age, HER2 gene status reported non-significant difference in the age groups between cases with amplified and non-amplified gene status (P=0.173). There was a significant negative association between positive Estrogen (ER) and Progesterone (PR) status and HER2 gene amplification (P= 0.002 and 0.017, respectively). Conclusion: More than half of breast carcinoma cases with equivocal HER2 immunoreactivity showed non-amplified gene status; this needs to be considered by oncologists in their management planning of breast cancer. Amplified HER2 gene is significantly associated with negative ER and PR status that affects patients' management protocols and future outcome of the disease. [ABSTRACT FROM AUTHOR]

Famous Italian singer, Anna Zamperini arrived in Portugal in 1772. She was soon victim of satirical poets who blamed her for being a woman of easy virtue. If this critical appreciation is clearly explained by a certain number of them, it is also enjoyable in ironical poems which ambiguous expression entails a more subtle reading able to spot the equivocal words. The double-edged discourse can be discovered not only in the form but also in the political intention of the poet: the satire, which seems to be a free speech, obeys, as a matter of fact, the Pombal’s ideology with regard to morality and national identity, two close concepts in those days.

Background: Ultrasound (US) is the preferred imaging modality for evaluating suspected pediatric appendicitis. However, borderline appendiceal enlargement or questionable inflammatory changes can confound interpretation and lead to equivocal exams.Objective: The purpose of this study was to determine which findings on equivocal US exams are most predictive of appendicitis.Materials and Methods: All US exams performed for suspected pediatric appendicitis from July 1, 2013, through July 9, 2014, were initially interpreted using a risk-stratified scoring system. Two blinded pediatric radiologists independently reviewed US exams designated as equivocal and recorded the following findings: increased wall thickness, loss of mural stratification, peri-appendiceal fat inflammation, peri-appendiceal fluid, appendicolith and maximum appendiceal diameter. A third pediatric radiologist resolved discrepancies. US features were correlated with the final diagnosis via multivariate analysis.Results: During the study period, 162/3,750 (4.3%) children had US exams initially interpreted as equivocal (mean age 9.8 +/- 3.8 years). Five outpatients were lost to follow-up. Forty-eight of the remaining 157 (30.6%) children had an operative diagnosis of appendicitis. Findings significantly associated with appendicitis were loss of mural stratification (odds ratio [OR] = 6.7, P=0.035), peri-appendiceal fat inflammation (OR = 10.0, P<0.0001) and appendicolith (OR = 15.8, P=0.025). While appendiceal diameter tended to be larger in patients with appendicitis, the difference was not statistically significant.Conclusion: Loss of mural stratification, peri-appendiceal fat inflammation and an appendicolith are significant predictors of appendicitis in children with otherwise equivocal US exams. While maximum appendiceal diameter is not statistically associated with appendicitis in our study, mean appendiceal diameter of 6.7 mm in those without appendicitis suggests that the customary upper normal limit of 6 mm is too sensitive. [ABSTRACT FROM AUTHOR]

Dual-probe fluorescence in situ hybridization (D-FISH) is a widely accepted method to determine the gene amplification status of human epidermal growth factor receptor 2 (Her-2). In 2013, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the guidelines on the Her-2 testing for invasive breast cancer (BCa). The interpretation criteria for D-FISH changed accordingly. In this study, we compared the Her-2 FISH statuses based on the 2013 and 2007 ASCO/CAP guidelines in 1931 cases of BCa with Her-2 D-FISH testing at our hospital. We analyzed the clinicopathologic features of cases with equivocal results by the 2013 ASCO/CAP guidelines. Although the guideline update significantly improved the detection rate of Her-2 amplification, it also significantly increased the rate of equivocal results, posing a dilemma for clinical management. The equivocal results had a good reproducibility. The distribution of D-FISH-equivocal cases did not correlate with Her-2 status by immunohistochemistry, suggesting that Her-2 D-FISH equivocality may not reflect Her-2 overexpression. Compared with Her-2-negative cases by D-FISH, Her-2 D-FISH-equivocal cases had higher Ki67 expression, higher histological grade, more frequent lymph node metastasis, and lower estrogen receptor α expression, indicating a group of BCa with worse prognosis. The clinical significance of Her-2-equivocal results by D-FISH warrants further investigation. [ABSTRACT FROM AUTHOR]

For dual probe HER2 FISH assay, the 2013 CAP/ASCO guideline recommendations lowered the HER2/CEP17 ratio cut off for HER2 amplification to ≥2.0 and introduced an average HER2 copy number criterion for HER2 amplification (≥6.0/cell) and HER2 equivocal categories (≥4 and <6/cell). The HER2/CEP17 equivocal category is eliminated. The aim of this study is to assess the impact of 2013 HER2 FISH testing guideline recommendations update on the assignment of HER2 status with dual probe HER2 FISH assay. Dual probe HER2 FISH assay results on breast cancers from 09/2009 to 07/2015 that underwent reflex HER2 FISH testing after equivocal HER2 (2+) immunohistochemistry (IHC) were reviewed. HER2 copy number, CEP17 signals, and HER2/CEP ratios were noted. HER2 status was assigned as HER2 negative (HER2−), HER2 equivocal (HER2e), and HER2 amplified (HER2+) by applying both 2007 and 2013 CAP/ASCO HER2 FISH guideline recommendations and results were compared. New guidelines reclassified HER2 FISH status in a significant proportion of cases (8.3 %, 69/836; p = .021). There were 22 (2.6 %) more HER2+, 17 (2.1 %) more HER2e, and 39 (4.1 %) fewer HER2− tumors. Change of HER2 status correlated significantly with ≥3 CEP17 signals (38 vs. 2 %; p < .001). The 2013 CAP/ASCO guideline recommendations for HER2 FISH testing by dual probe assay increased the HER2 amplified and HER2 equivocal tumors. Increase in HER2 equivocal tumors would potentially increase the frequency of repeat HER2 testing. Tumors with ≥3 CEP17 signals, so-called chromosome 17 polysomy, are more likely to be impacted and classified as HER2 equivocal. [ABSTRACT FROM AUTHOR]

We analyzed Her2 amplification in breast cancers with equivocal IHC staining to investigate the significance of percentage of Her2 immunostained tumor cells. We especially included the breast cancers with complete/incomplete membrane staining at moderate intensity in less than 10% of the invasive tumor cells. Of 1804 breast cases, 180 had moderate complete/incomplete membrane Her2 immunostaining. According to 2013 ASCO/CAP guideline, 124 were in IHC score 2+ and 56 in 1+ category. The percentage of Her2 immunostained invasive tumor cells were determined by visual estimation at the time of diagnosis and categorized into three groups; <10%, 10–50%, and >50% for this review. FISH was performed by dual DNA probe and data of Her2/cep17 ratio, Her2/cell and Cep17/cell were recorded applying 2013 ASCO/CAP criteria. There were 22 cases (12.2%) in >50% group, 102 (56.7%) in 10–50% group, and 56 (31.1%) in <10% group. Overall Her2 amplification was 25.5%. Her2 was amplified in 12 (54.5%) cases in >50% group; 26 (25.4%) in 10–50% and 8 (14.3%) in <10%. Her2 amplification was more frequent in cancers with >50% moderately immunostained cells in IHC equivocal group. However, most of Her2 IHC equivocal breast cancers contain moderate amount (10–50%) of immunostained cells. Relatively small but non-neglectable number (14%) of cases in <10% group was Her2 amplified by FISH which approaches to overall incidence of Her2 overexpression (15–20%) in all breast cancer. Breast cancers with moderate complete/incomplete membrane Her2 IHC staining in <10% of invasive tumor cells should be regarded as equivocal and reflex FISH should be performed in these cases. [ABSTRACT FROM AUTHOR]

Objective: We have encountered occasional equivocal findings when assessing cerebral cortical amyloid retention with C-Pittsburgh compound B (PiB) PET. We investigated the diagnostic significance of equivocal PiB PET findings. Methods: This retrospective study included 101 consecutive patients complaining of cognitive disorders (30 Alzheimer's disease, 25 mild cognitive impairment, 8 Lewy body disease, 7 frontotemporal lobar degeneration, 31 others) who underwent both C-PiB PET and F-fluorodeoxy- d-glucose (FDG) PET. We visually classified PiB-positive, PiB-equivocal or PiB-negative ratings according to cortical uptake. For quantitative assessments of PiB PET, standard uptake values referred to cerebellar cortex (SUVR) were calculated in regional template volume of interests (frontal, temporoparietal, precuneus/posterior cingulate cortex, cerebral white matter and cerebellar cortex). The results of visual assessment were compared with the regional and mean cortical SUVRs and cortical-to-white matter ratio of PiB uptake, as well as clinical and FDG PET findings. Results: Among the 101 scans, 41 were PiB negative, 11 were PiB equivocal, and 49 were rated PiB positive in the visual assessments. The mean cortical SUVR and cortical-to-white matter ratio were 0.97 ± 0.07 and 0.57 ± 0.21 in PiB-negative, 1.51 ± 0.17 and 0.75 ± 0.06 in PiB equivocal and 2.10 ± 0.33 and 0.97 ± 0.11 in PiB-positive group, respectively. Nine of 11 subjects with PiB-equivocal findings had cognitive impairments and FDG distribution compatible with Alzheimer's disease or dementia with Lewy bodies. Conclusions: We considered equivocal visual findings on PiB PET equivalent to PiB-positive with slight cortical uptake. In addition, slight cortical amyloid deposits were considered to cause cerebral metabolic abnormality and cognitive impairment. Although mean cortical SUVR was more sensitive than visual assessment because of low cortical-to-white matter contrast due to non-specific accumulation in white matter, it is important not to overlook small amounts of cortical uptake of PiB in visual inspection for exact diagnosis. [ABSTRACT FROM AUTHOR]

Current guidelines recommend HER2 testing on all primary invasive breast cancers and re-biopsy at disease relapse. The discordance rate between HER2-negative primaries and HER2 IHC2+ metastases that are ISH-amplified is unknown. We hypothesize that the majority of such cases are non-amplified. ISH testing is time-consuming and resource-intensive, and there may be situations where it is unnecessary. A retrospective review of IHC2+ metastatic lesions assessed with ISH at our center from 2013 to 2021 was undertaken. 105 cases were identified after exclusion of cases missing HER2 results, with primaries of unconfirmed origin, and cases of synchronous primary and metastatic disease. IHC and ISH results were recorded with detailed slide review of discordant cases. 91/105 metastases had HER2-negative primaries (87%). A metastasis was significantly more likely to be HER2-negative when the primary was HER2-negative (93%) versus positive (43%) (p < 0.0001). 54/91 primaries were IHC2+/ISH-non-amplified, and 50/54 (93%) corresponding metastases had identical results. Of the 37 HER2-negative primaries that were IHC0/1+, 35 (95%) corresponding metastases were ISH-non-amplified. Six metastases in cases with HER2-negative primaries were discordant. Characteristics of metastases suggesting ISH testing was warranted to assess for discordance included IHC heterogeneity, morphological discordance, increased staining of moderate intensity, and ER/PR discordance. One or more of these factors were present in all discordant metastases. Our results suggest selective ISH testing on HER2 IHC2+ breast cancer metastases in the context of HER2-negative primary disease may be appropriate when there is careful review of the IHC. Validation of our findings awaits further studies with larger sample sizes. • HER2 is negative in most metastases that have a HER2 negative primary tumor. • A selective approach to HER2 ISH testing in metastases may be appropriate. • HER2 discordance in metastases may be predicted by morphologic or IHC differences. [ABSTRACT FROM AUTHOR]

Eyewitness evidence is amongst the most important types of evidence in investigative and juridical proceedings. Yet, eyewitness evidence frequently derives from observations made under situationally equivocal conditions, including such factors as darkness and physical obstruction of view. The effect of the violence of a given crime on potential jurors' evaluation of such equivocal evidence was addressed. A witness's identification of a suspect in a violent crime was generated in three versions, varying only in the level of violence of the crime. Respondents were more likely to accept this identification as accurate under more violent conditions and were also less likely to report noticing or considering equivocal aspects (darkness and physical obstruction) in situations of greater violence. Predisposing factors to judgement of guilt lay significantly in the acceptance of punishment as a viable deterrent to crime and of societal guilt for the criminal's behaviour, although political or religious orientations were not shown to influence these results, and none of these factors interacted with the violence of the crime to influence judgement of guilt or innocence. These findings indicate the importance of affective factors in judgements of guilt or innocence, especially when these judgements are based on situationally equivocal eyewitness evidence. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Derecho UNED is the property of Editorial UNED and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Biren Parikh Introduction  Hormonal status and HER2 expression are valuable biomarkers and dictate the management of the patients diagnosed with invasive breast cancer (IBC). It is crucial to identify the patients who truly respond to anti-HER2 targeted therapy. Updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines has recommended certain modifications in HER2 interpretation by fluorescence in situ hybridization (FISH) with concomitant immunohistochemistry (IHC). Objectives  We aimed to evaluate HER2 FISH interpretation in IBC with equivocal IHC results as per 2018 ASCO/CAP recommendations and compare FISH results with hormonal receptor status. Materials and Methods  FISH results of 502 cases of IBC with equivocal IHC report between January 2016 to January 2022 were reviewed retrospectively. FISH results were categorized according to ASCO/CAP guidelines 2018 into five respective groups. Results  FISH testing in IHC equivocal cases showed 219 (43.6%) cases were classic amplified (positive) belonged to group 1, 217(43.2%) cases were classic nonamplified (negative) fell into group 5, 39 (7.8%) and 02 (0.4%) patients were in group 2 (negative) and group 3 (positive), and 25 (5.0%) cases were in group 4 (negative). About 52.1 and 49.3% of cases with estrogen receptor and progesterone receptor positivity were reported as HER2 positive. Among 502 cases, 25 equivocal cases according to the 2013 guidelines were redefined as HER2 negative and 02 (0.4%) cases reported positive were classified negative as per updated 2018 guidelines. Conclusion  Revised 2018 guidelines is helpful in accurate identification of HER2 status and in avoiding targeted therapy in unwarranted cases. Updated 2018 guidelines has removed equivocal HER2-FISH category that has eliminated management dilemma in these cases. Only long-term clinical follow-up will establish the validity of the updated guidelines., Competing Interests: Conflict of Interest None declared., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Abstract: One presumed drawback of performing fluorescence in situ hybridization on routine tissue sections for HER-2 status evaluation in breast carcinomas is nuclear truncation. Therefore, HER-2/CEP 17 ratios were compared in routine (4 μm) vs. thicker (15 μm) tissue sections. Additionally, the distances of both signals from the nuclear center were measured by three-dimensional image analysis. HER-2 and CEP 17 signals’ number increased in thick sections; however, HER-2/CEP 17 ratios were decreased. This could be attributed to a preferential increase in CEP17 signals explained by their more peripheral localization and apparent "loss" in truncated nuclei. The aforementioned decrease of HER-2 ratios did not alter HER-2 status except in cases in the equivocal category where it changed from equivocal to non-amplified. Thus, at least a subset of the equivocal cases could represent an artifactual increase of HER-2 ratio related to nuclear truncation and loss of peripheral CEP 17 signals in routine sections. [Copyright &y& Elsevier]

Breast magnetic resonance imaging (MRI) is routinely used as a problem-solving tool, but its benefit for this indication remains unclear. The records of 3001 consecutive breast MR examinations between January 1, 2003 and June 6, 2007 were reviewed to identify all those performed for the clinical indication of problem solving. Details of clinical presentation, mammography and ultrasound (US) findings, follow-up recommendations, and pathology outcomes were recorded. Benign versus malignant outcomes were determined by biopsy or 12 months of follow-up imaging and linkage with the regional tumor registry. Problem solving was the clinical indication for 204 of 3001 (7%) of all examinations. Forty-two of 204 examinations (21%) had suspicious or highly suspicious MRI assessments with recommendation for biopsy and 62 of 204 (79%) examinations were assessed as negative, benign, or probably benign. Thirty-six biopsies were performed based on MRI findings and 14 cancers were diagnosed. Biopsy was indicated for 11 of 14 (79%) cancers based on suspicious mammographic or US findings identified prior to MRI. One incidental cancer was detected by MRI alone in a patient at high risk for breast cancer, and two cancers were detected in patients with suspicious nipple discharge and negative mammogram and US. A single false-negative MRI occurred in a patient whose evaluation for a palpable lump prompted biopsy. Problem-solving breast MRI rarely identifies otherwise occult cancer and can be falsely negative in patients with suspicious findings on mammogram and US. Until the benefits and risks of problem-solving MRI are clarified, it should be used judiciously. [ABSTRACT FROM AUTHOR]

The article examines the ability of multitarget fluorescence in situ hybridization for dissecting equivocal respiratory cytology into reactive and malignant categories. For the elucidation of equivocal lung cytology, multitarget FISH in conjunction with automated relocation is a powerful approach.

Copyright of Revista Ibero-Latinoamericana de Seguros is the property of Pontificia Universidad Javeriana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)