Julie M. Jorns

Aims: To investigate the associated histopathology and immunohistochemical (IHC) profile of pseudoangiomatous stromal hyperplasia (PASH) of the breast in a large, contemporary cohort. Methods and results: We reviewed 193 benign breast biopsies with PASH from 185 patients without history of breast atypia or carcinoma. A tissue microarray was created and subjected to a panel of IHC. Ischemic fat necrosis was the most common finding in biopsies with PASH (181/193; 93.8%), while fibrocystic changes (170/193; 88.1%) were frequently present. PASH showed consistent, diffuse, strong staining for CD34 (193/193; 100%) and variable positivity for BCL‐2 (66/193; 34.2%), SMA (47/193; 24.4%), desmin (11/193; 5.7%) and TRPS‐1 (2/193; 1%), while all were negative for ERG and β‐catenin. PR and ER positivity was identified in 33.7% (65/193) and 29% (56/193) of cases, respectively. Hormone receptor positive PASH was significantly associated with a higher rate of non‐proliferative fibrocystic changes as compared to hormone receptor negative PASH (163/193; 84.5% vs 104/193; 53.9%, respectively) ( P = 0.047). Subsequent breast atypia or carcinoma was uncommon (10/185; 5.4%), with median follow‐up of 6.2 years (range 5.3–7.3 years). Conclusions: ER/PR expression in PASH is less frequent than previously reported by some studies. However, the frequency of fat necrosis and associated fibrocystic changes in PASH support a chronic, hormone‐related process. Consistent CD34 positivity and absence of markers seen in histologic mimics aid in the diagnosis of PASH in challenging cases. PASH does not appear to impart increased cancer risk.

Objective: We sought to identify the challenges of paper-based documentation and quantify the benefits of transitioning to a digital platform for resident grossing competency evaluation. Methods: We conducted a retrospective review of resident grossing competency documentation and administered surveys to assess satisfaction with an established paper-based system. Following implementation of a digital laboratory information system (LIS)–based process, we reassessed resident grossing documentation, with a 1-month crossover comparison of the 2 methods and a 6-month follow-up evaluation of the LIS-based method. Results: Overall, resident grossing completion was 37% (745 total completed of 2016 total required) with the paper-based system. Residents forgot documentation “sometimes” (7/17 [41.2%]), “often” (4/17 [23.5%]), or “always” (2/17 [11.8%]); experienced delays in obtaining signatures from attending physicians (14/17 [82.4%]); and reported feeling neutral (6/17 [35.3%]) or dissatisfied (6/17 [35.3%]) with the paper-based system. In the 1-month crossover period, the paper-based system generated 21 competency completions with 3 constructive comments compared with 31 competency completions and 10 ­constructive comments collected through the LIS-based process. Documentation levels further increased in the 6-month period following the switch to LIS alone, with means of 97 competencies and 14 constructive comments documented per month. Conclusions: Transition to a LIS-based system led to greater competency completion capture and constructive feedback. The success of the digital LIS-based system was facilitated by using an easy and familiar system with routine clinical workflows.

Objective: To estimate the prevalence of technical errors in the total testing process of pathology tissue specimens. Design: A systematic review and Meta-analysis of Observational Studies in Epidemiology was performed. Extracted data were pooled using a random-effects model and Grading of Recommendations, Assessment, Development and Evaluation approaches. Data sources: PubMed, CINAHL, Cochrane Library and Science Direct databases were searched on 29 May 2025 for eligible studies. Study selection: Peer-reviewed studies published after 2003 that reported technical error prevalence in any aspect of routine tissue collection and processing. Results: The search returned 30 articles (31 studies), including data from 2 794 987 surgical pathology cases. Pooled effect sizes were calculated for pre-analytic errors at 16.71 per 1000 cases (95% CI 6.42 to 31.67), actively identified errors in the laboratory at 40.17 per 1000 (95% CI 7.04 to 97.61) and reported surgical pathology specimen errors at 4.94 per 1000 (95% CI 1.33 to 10.80). Subgroup analysis showed an occult error prevalence of 2.54 per 1000 cases (95% CI 1.63 to 3.64), and surgical pathology case contamination was 62.23 per 1000 (95% CI 8.22 to 159.33). Conclusion and relevance: The analysis suggests that tissue processing technical errors are more prevalent than reported. A lack of standardised methods for defining and detecting errors contributes to undocumented and unidentified errors, leaving the true error prevalence unknown. The majority of clinical decisions are based on laboratory results; however, without reliable detection and reporting, errors in vulnerable processes risk compromising patient diagnoses. PROSPERO registration number: CRD42024600518.

SignificanceAccurate transfer of annotations from histological images to fluorescence images is essential in developing deep learning (DL)-based optical imaging systems for intraoperative assessment of tumor margins. Manual annotation is time-consuming, prone to interobserver variability, and impractical for large-scale datasets.AimWe present a semi-automated method that can effectively transfer tumor annotations from pathologist-annotated hematoxylin and eosin (H&E) images to fluorescence images captured using microscopy with ultraviolet surface excitation (MUSE). This method is not intended for intraoperative use but rather to facilitate the creation of annotated datasets for DL model development.ApproachOur semi-automated method consists of nonrigid image registration, outline extraction and refinement, and annotation transfer. The method was applied to H&E and MUSE image pairs from 35 breast and lung tissue samples. Manual annotations in MUSE images were used as the ground truth for evaluation.ResultsThe proposed method achieved a Dice score coefficient of 0.87±0.07, convolutional-neural-network-based feature similarity of 0.94±0.04, and a normalized Hausdorff distance of 0.15±0.06 across the dataset.ConclusionThese results demonstrate that the method provides a fast and accurate solution for generating annotated MUSE datasets necessary for training DL algorithms for intraoperative tumor margin detection.

Aims Adequate lymph node examination is key to accurate cancer staging. This study investigates the effectiveness of shortwave infrared imaging in increasing the overall and positive lymph node numbers. Methods Specimens from various anatomic sites, including colorectal, pancreatic, breast, gastric, skin and small bowel resections, were evaluated. 104 specimens were first grossed with manual palpation and then grossed with the assistance of shortwave infrared imaging. The overall and positive lymph node numbers were documented. Results In 90 of the 104 cases (86.5%), shortwave infrared imaging helped identify additional lymph nodes. On average, 4.81 additional lymph nodes were found. In 11 of the 104 cases (10.6%), additional positive lymph nodes were found. In 4 of the 104 cases (3.8%), cancer stages were changed. Conclusions Shortwave infrared imaging may increase the number of lymph nodes identified and has the potential to improve cancer staging accuracy. Further validation in larger, randomised or prospective studies is warranted.

Background: Standard treatment for patients with early-stage estrogen receptor-positive (ER+) breast cancer often includes sequential adjuvant radiation and endocrine therapies. Unfortunately, ~1/3 of patients eventually experience disease recurrence, partly due to residual disease in the form of drug-tolerant persister cancer cells. The anti-cancer efficacy of radiation therapy is partly attributable to the production of oxyradicals that damage biomolecules. We previously showed that endocrine therapy increases mitochondrial content in ER+ breast cancer cells; we postulated that this may also increase oxidative stress. Methods: Herein, we tested the efficacy of concurrent endocrine and radiation therapies, including both conventional (CDR) and ultra-high dose rate (UHDR) radiation. Results: We found that estrogen deprivation and radiation inhibit cell growth, induce apoptosis, and force cells into an oxidatively stressed state. DNA damage was almost exclusive to cells treated with the combination of endocrine and radiation therapy. Radiation slowed tumor growth in two xenograft models, and combination with estrogen deprivation prolonged the time to regrowth in ZR75-1 tumors. Conclusions: These findings indicate that simultaneous treatment with endocrine and radiation therapies can be advantageous, warranting further evaluation to identify tumor features predictive of response to individual and combination treatments.

Aims: Adequate lymph node examination is key to accurate cancer staging. Lymph node search in surgical resection specimens is a challenging task because it can be labor intensive and inconsistent. This study investigates the effectiveness of shortwave infrared imaging technology in increasing the overall and positive lymph node numbers. Methods: 104 surgical resection specimens from two hospitals were first grossed with traditional manual palpation. The residual tissues were then grossed with the assistance of shortwave infrared imaging. The numbers of lymph nodes and positive lymph nodes within these two steps were documented and compared. Results: In 90 of the 104 cases (86.5%), shortwave infrared imaging assisted gross examination identified additional lymph nodes. In 11 of 104 cases (10.6%), shortwave infrared imaging assisted gross examination identified additional positive lymph nodes. Conclusions: Shortwave infrared imaging increases the number of lymph nodes and the number of positive lymph nodes in surgical pathology specimens compared to traditional visual and manual dissection.

Distinction of metastasis to the breast from a breast primary, particularly high-grade triple-negative breast cancer (TNBC), can be challenging due to nonspecific morphology and immunohistochemical (IHC) profiles. Among metastases to the breast, high-grade serous carcinoma (HGSC) of müllerian origin is most likely to be misdiagnosed as TNBC. We assessed breast and müllerian markers on TNBC and HGSC, including keratin 7, keratin 20, GATA3, GCDFP15, mammaglobin, p53, PAX8 (MRQ50 and BC12 clones), TRPS1, SOX10, and WT1. Of 151 TNBC cases, TRPS1 had the highest sensitivity, showing expression in 149 (98.7%) cases, followed by SOX10 (110/151; 72.8%), GATA3 (102/151; 67.5%), GCDFP15 (29/151; 19.2%), and mammaglobin (27/151; 17.9%). PAX8 positivity was seen in 40.4% (61/151) of TNBC via the MRQ50 clone but was negative in all via the BC12 clone. Of 185 HGSC cases, PAX8 via the MRQ50 clone was the most sensitive (179/185; 96.8%), followed by WT1 (171/185; 92.4%) and PAX8 via the BC12 clone (164/185; 88.6%). In addition, TRPS1 positivity was seen in 75 HGSC cases (40.5%). Aberrant p53 patterns were seen in 64.9% (98/151) of TNBC and 94.1% (174/185) of HGSC. TRPS1 positivity in HGSC and PAX8 positivity via the MRQ50 clone in TNBC represent potential pitfalls in assessing high-grade carcinoma for which the differential diagnosis includes TNBC and HGSC. However, with this knowledge, utilization of a panel of breast and müllerian markers, including preferential use of the PAX8 BC12 clone, can facilitate accurate diagnosis.