BACKGROUND: Approximately, 55% of breast carcinomas are reported to be HER-2 low breast carcinomas. Trastuzumab-Deruxtecan is a new FDA-approved targeted therapy for HER-2 low metastatic breast carcinomas, making it essential that all efforts are made to identify these tumors in specimens submitted for pathologic examination. Cytology specimens are often the first and only modality of this assessment due to the ease of specimen procurement. This study aimed to determine the variability in HER-2 immunostaining interpretation among observers using cytologic specimens from metastatic sites.
METHODS: A pathology database search was made to identify metastatic breast carcinoma reported in cytology specimens. A manual search was then done to identify cases of HER-2 low category, H&E cell block and HER-2 neu immunostain slides were retrieved for a total of 50 cases. Reviewer #1 and #2 independently interpreted HER-2 immunostain of all 50 cases. Only discordant cases were sent for reviewer-3 interpretation. All three were blinded by the metastatic site, and original HER-2 interpretation.
RESULTS: Of 50 cases, 11 cases (22%) were reported as concordant scores between reviewer #1 and reviewer #2 but had a discordant original IHC report. Additionally, 4 cases (8%) had discordant reporting of HER2 IHC stain between reviewer #1 and reviewer #2 making a total of 15 cases (30%) with overall discordant results.
CONCLUSIONS: This study highlights the interobserver variability of HER-2 immunostain interpretation for HER-2 low category of breast carcinomas. We recommend the need for more robust laboratory techniques including molecular for uniform identification of these unique targetable metastatic breast carcinoma groups.

OBJECTIVE: This study aimed to understand reasons for interobserver variability in the grading of oral epithelial dysplasia (OED) through a survey of pathologists to provide insight for improvements in the reliability and reproducibility of OED diagnoses.
METHODS: The study design included quantitative and qualitative methodology. A pre-validated 31-item questionnaire was distributed to general, head and neck, and oral and maxillofacial histopathology specialists worldwide.
RESULTS: A total of 132 pathologists participated and completed the questionnaire. Over two-thirds used the three-tier grading system for OED, while about a third used both binary and three-tier systems. Regular reporters of OED preferred the three-tier system and grading architectural features. Continuing education significantly aided recognition of architectural and cytological changes. Irregular epithelial stratification and drop-shaped rete ridges had the lowest prognostic value and recognition scores, while loss of epithelial cell cohesion had the highest. Most participants used clinical information and often sought a second opinion when grading OED.
CONCLUSIONS: Our study has found that frequency of OED reporting and attendance of CME/CPD can play an important role in grading OED. Variations in the prognostic value of individual histological features and the use of clinical information may further contribute to interobserver variability.

Grading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphological feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability. A retrospective cohort of 249 consecutive patients primarily resected with LUSC in Bern (2000-2013, N=136) and Lausanne (2005-2020 N=113) with available preoperative biopsies was analyzed for TB and additional histomorphological parameters such as spread through airspaces (STAS) and desmoplasia by two expert pathologists. Results were correlated with clinicopathological parameters and survival. In resection specimens, peritumoral budding (PTB) score was low (0-4 buds/0.785 mm2) in 47.6%, intermediate (5-9 buds/0.785 mm2) in 27.4 %, and high (≥10 buds/0.785 mm2) in 25 % of cases (median bud count = 5, IQR = 0 - 26). Both the absolute number of buds and TB score were similar when comparing tumor edge and intratumoral zone (p=0.192) but significantly different from the score obtained in the biopsy (p<0.001). Interobserver variability was moderate, regardless of score location (Cohen\'s kappa 0.59). The discrepant cases were reassessed, and consensus was reached in all cases with identification of causes of discordance. TB score was significantly associated with stage (p=0.002), presence of lymph node (p=0.033) and distant metastases (p=0.020), without significant correlation with overall survival, tumor size or pleural invasion. Desmoplasia was significantly associated with higher PTB (p<0.001). STAS was present in 34% and associated with lower PTB (p<0.001). To conclude, despite confirming TB as a reproductible factor in LUSC we disclose areas of scoring ambiguity. Preoperative biopsy evaluation was insufficient in establishing the final tumor budding score of the resected tumor.

Accurate measurement of testicular volume (TV) in boys is an important tool in clinical practice, e.g., in varicocele treatment. This study aims to assess the degree of intra- and interobserver variability of testicular volume measurements. In a prospective study, boys between 11 and 17 years of age without testicular pathology were enrolled. Testicular ultrasound was performed by three investigators (A: pediatric radiologist; B: pediatric surgery/urology resident; C: pediatric urologist). Intraobserver variability was calculated in investigators B and C and interobserver variability between all three investigators. A total of 30 boys were enrolled. Mean intraobserver variability in both observers was +0.3% with a range of -39.6 to 51.5%. The proportion of measurements with a difference >20% was 18.6%. The mean interobserver variability was -1.0% (range: -74.1% to 62.8%). The overall proportion of measurements with a difference >20% was 35%. A lower testicular size of < 4 mL showed a significantly higher rate of >20% difference in both the intraobserver group (31.1% vs. 14.4%; p = 0.035) and the interobserver group (63.2% vs. 26.2%; p = 0.000031). Furthermore, the rate of >20% difference was significantly lower in obese compared to non-obese patients in both the intraobserver (2.8% vs. 22.4%; p = 0.0084) and the interobserver group (24% vs. 40.8%, p = 0.0427). Both intraobserver and interobserver variability in ultrasound-based TV measurements in pubertal boys contain a relevant degree of uncertainty that renders them unsuitable for individualized follow-up care. At the cohort level, however, mean differences in ultrasound-based TV measurements are low enough to make ultrasound comparisons reasonable.

OBJECTIVE: To explore the topic of Prostate Imaging-Reporting and Data System (PI-RADS) interobserver variability, including a discussion of major sources, mitigation approaches, and future directions.
METHODS: A narrative review of PI-RADS interobserver variability.
RESULTS: PI-RADS was developed in 2012 to set technical standards for prostate magnetic resonance imaging (MRI), reduce interobserver variability at interpretation, and improve diagnostic accuracy in the MRI-directed diagnostic pathway for detection of clinically significant prostate cancer. While PI-RADS has been validated in selected research cohorts with prostate cancer imaging experts, subsequent prospective studies in routine clinical practice demonstrate wide variability in diagnostic performance. Radiologist and biopsy operator experience are the most important contributing drivers of high-quality care among multiple interrelated factors including variability in MRI hardware and technique, image quality, and population and patient-specific factors such as prostate cancer disease prevalence. Iterative improvements in PI-RADS have helped flatten the curve for novice readers and reduce variability. Innovations in image quality reporting, administrative and organisational workflows, and artificial intelligence hold promise in improving variability even further.
CONCLUSIONS: Continued research into PI-RADS is needed to facilitate benchmark creation, reader certification, and independent accreditation, which are systems-level interventions needed to uphold and maintain high-quality prostate MRI across entire populations.

BACKGROUND: Early Barrett cancer can be curatively treated by endoscopic resection. The choice of the resection technique, however-endoscopic mucosal resection (EMR) or submucosal dissection (ESD)-largely depends on the assumed infiltration depth as judged by the endoscopist. However, the accuracy of endoscopic diagnosis of the degree of cancer infiltration is not known.
METHODS: Three to four high-quality images (both in overview and close-up) from 202 of early Barrett esophagus cancer cases (82% men, mean age 66.9 years) were selected from our endoscopy database (73.3% stage T1a and 26.7% in stage T1b). Images were shown to 9 Barrett esophagus experts, with patients\' clinical data (age, sex, Barrett esophagus length) and biopsy results. The experts were asked to predict infiltration depth (T1b vs. T1a), and to suggest the appropriate endoscopic resection technique (EMR or ESD, or surgery). Interobserver variability (kappa values) was also determined for these parameters.
RESULTS: Overall positive (PPV) and negative predictive values (NPV) to diagnose T1b versus T1a infiltration were 40.7% (95% CI: 36.7, 44.8) and 79.8% (95% CI: 77.5, 81.9), respectively; kappa value was 0.41. Paris classification (kappa 0.51) and suggested treatment also varied between experts. In a post hoc analysis, only the correlation between lesions classified as invisible or flat according to the Paris classification (IIB; 25% of all cases) and the suggested resection technique was better: In this subgroup, EMR was recommended in >80% of cases, with a high complete (basal R0) resection rate (mean of 88.1%).
CONCLUSIONS: Precise endoscopic distinction between mucosal and submucosal involvement of Barrett esophagus cancer by experts as a basis for choosing the resection technique has limited predictive values and high interobserver variability. It seems that mainly invisible/flat lesions may result in good resection outcomes when treated by EMR, but this stratification strategy has to be assessed in further studies.

Objective Evaluating an artificial intelligence (AI) tool (AIATELLA, version 1.0; AIATELLA Oy, Helsinki, Finland) in interpreting cardiac magnetic resonance (CMR) imaging to produce measurements of the aortic root and valve by comparison of accuracy and efficiency with that of three National Health Service (NHS) cardiologists. Methods AI-derived aortic root and valve measurements were recorded alongside manual measurements from three experienced NHS consultant cardiologists (CCs) over three separate sites in the northeast part of the United Kingdom. The study utilised a comprehensive dataset of CMR images, with the intraclass correlation coefficient (ICC) being the primary measure of concordance between the AI and the cardiologist assessments. Patient imaging was anonymised and blinded at the point of transfer to a secure data server.  Results The study demonstrates a high level of concordance between AI assessment of the aortic root and valve with NHS cardiologists (ICC of 0.98). Notably, the AI delivered results in 2.6 seconds (+/- 0.532) compared to a mean of 334.5 seconds (+/- 61.9) by the cardiologists, a statistically significant improvement in efficiency without compromising accuracy. Conclusion AI\'s accuracy and speed of analysis suggest that it could be a valuable tool in cardiac diagnostics, addressing the challenges of time-consuming and variable clinician-based assessments. This research reinforces AI\'s role in optimising the patient journey and improving the efficiency of the diagnostic pathway.

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UNASSIGNED: Differences in the contours created during magnetic resonance imaging-guided online adaptive radiotherapy (MRgOART) affect dose distribution. This study evaluated the interobserver error in delineating the organs at risk (OARs) in patients with pancreatic cancer treated with MRgOART. Moreover, we explored the effectiveness of drugs that could suppress peristalsis in restraining intra-fractional motion by evaluating OAR visualization in multiple patients.
UNASSIGNED: This study enrolled three patients who underwent MRgOART for pancreatic cancer. The study cohort was classified into three conditions based on the MRI sequence and butylscopolamine administration (Buscopan): 1, T2 imaging without butylscopolamine administration; 2, T2 imaging with butylscopolamine administration; and 3, multi-contrast imaging with butylscopolamine administration. Four blinded observers visualized the OARs (stomach, duodenum, small intestine, and large intestine) on MR images acquired during the initial and final MRgOART sessions. The contour was delineated on a slice area of ±2 cm surrounding the planning target volume. The dice similarity coefficient (DSC) was used to evaluate the contour. Moreover, the OARs were visualized on both MR images acquired before and after the contour delineation process during MRgOART to evaluate whether peristalsis could be suppressed. The DSC was calculated for each OAR.
UNASSIGNED: Interobserver errors in the OARs (stomach, duodenum, small intestine, large intestine) for the three conditions were 0.636, 0.418, 0.676, and 0.806; 0.725, 0.635, 0.762, and 0.821; and 0.841, 0.677, 0.762, and 0.807, respectively. The DSC was higher in all conditions with butylscopolamine administration compared with those without it, except for the stomach in condition 2, as observed in the last session of MR image. The DSCs for OARs (stomach, duodenum, small intestine, large intestine) extracted before and after contouring were 0.86, 0.78, 0.88, and 0.87; 0.97, 0.94, 0.90, and 0.94; and 0.94, 0.86, 0.89, and 0.91 for conditions 1, 2, and 3, respectively.
UNASSIGNED: Butylscopolamine effectively reduced interobserver error and intra-fractional motion during the MRgOART treatment.

The overexpression of somatostatin receptor type 2 (SSTR2) is a property of various tumor types. Hybrid imaging utilizing [68Ga]1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA) may improve the differentiation between tumor and healthy tissue. We conducted an experimental study on 47 anonymized patient cases including 30 meningiomas, 12 PitNET and 5 SBPGL. Four independent observers were instructed to contour the macroscopic tumor volume on planning MRI and then reassess their volumes with the additional information from DOTA-PET/CT. The conformity between observers and reference volumes was assessed. In total, 46 cases (97.9%) were DOTA-avid and included in the final analysis. In eight cases, PET/CT additional tumor volume was identified that was not detected by MRI; these PET/CT findings were potentially critical for the treatment plan in four cases. For meningiomas, the interobserver and observer to reference volume conformity indices were higher with PET/CT. For PitNET, the volumes had higher conformity between observers with MRI. With regard to SBGDL, no significant trend towards conformity with the addition of PET/CT information was observed. DOTA PET/CT supports accurate tumor recognition in meningioma and PitNET and is recommended in SSTR2-expressing tumors planned for treatment with highly conformal radiation.