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Ocular Oncology and Pathology Jun 2024Eugene Wolff (1896-1954) and Jonas S. Friedenwald (1897-1955) were life-long students and educators of anatomic pathology and ophthalmology. Both contributed toward... (Review)
Review
BACKGROUND
Eugene Wolff (1896-1954) and Jonas S. Friedenwald (1897-1955) were life-long students and educators of anatomic pathology and ophthalmology. Both contributed toward narrowing the gap between the two rapidly diverging specialties of pathology and ophthalmology. Friedenwald in 1929 and Wolff in 1934 each published textbooks of ophthalmic pathology that influenced medical education for decades to come.
SUMMARY
Friedenwald's and Wolff's introduced ophthalmologists in training and practice to anatomic pathology, while familiarizing pathologists with the nature of ocular disease. Both books appeared at the time when anatomic pathology was departing from its mostly academic roles in education and research to assume more active participation in clinical care by establishing diagnoses through biopsy.
KEY MESSAGES
Wolff and Friedenwald dedicated their careers to teaching the art and science of anatomic pathology to clinical ophthalmologists. Their efforts helped anchor ophthalmology to the traditions of mainstream medicine.
PubMed: 38882023
DOI: 10.1159/000537784 -
Translational Cancer Research May 2024In lung cancer, molecular testing and next-generation sequencing (NGS) are needed to identify therapeutic targets and are increasingly being used in earlier stages of...
BACKGROUND
In lung cancer, molecular testing and next-generation sequencing (NGS) are needed to identify therapeutic targets and are increasingly being used in earlier stages of the disease. Despite its longstanding use, it remains unclear whether transbronchial needle aspiration (TBNA) of peripheral lung lesions provides as adequate material for genetic testing as transbronchial forceps biopsies (TBFBs). In this study, we aim to analyze the use of TBNA using median viable cell area (MVCA) as a surrogate parameter to analyze sample quality.
METHODS
This prospective single-center study analyzed biopsy specimens or aspirates of patients who underwent bronchoscopy with transbronchial biopsy. Patients underwent bronchoscopy with TBFB and TBNA for suspected lung cancer in peripheral lung lesions. Patients were randomized 1:1 to receive either TBFB or TBNA as the first biopsy technique and then switched to the other. After routine workup, sample slides were digitally scanned, and MVCA was calculated by a pathologist blinded to the biopsy technique used. The primary endpoint was MVCA of TBNA versus TBFB. Secondary endpoints were complications categorized as bleeding, pneumothorax, and other.
RESULTS
Between August 2021 and April 2022, 15 patients were included in the per-protocol analysis. Six patients were included in cohort 1 and nine patients in cohort 2. A malignant diagnosis was confirmed in 11/15 (73.3%) cases, of which nine were primary lung malignancies. Overall, MVCA in samples obtained by TBFB was significantly larger than TBNA samples {TBFB-MVCA 9.80 mm [interquartile range (IQR), 2.70-10.39 mm] . TBNA-MVCA 2.70 mm (IQR, 0.14-8.21 mm), P=0.008}. Despite this difference, molecular testing was feasible in both TBNA and TBFB samples. No major complications were observed.
CONCLUSIONS
Despite a significantly smaller MVCA provided by TBNA, samples were still considered feasible for NGS, indicating that TBNA represents an alternative method to obtain sufficient tumor tissue in peripheral nodules as part of the diagnosis of suspected lung cancer.
PubMed: 38881945
DOI: 10.21037/tcr-23-2320 -
Translational Cancer Research May 2024Cancer is a leading cause of morbidity and mortality worldwide. The emergence of digital pathology and deep learning technologies signifies a transformative era in... (Review)
Review
BACKGROUND AND OBJECTIVE
Cancer is a leading cause of morbidity and mortality worldwide. The emergence of digital pathology and deep learning technologies signifies a transformative era in healthcare. These technologies can enhance cancer detection, streamline operations, and bolster patient care. A substantial gap exists between the development phase of deep learning models in controlled laboratory environments and their translations into clinical practice. This narrative review evaluates the current landscape of deep learning and digital pathology, analyzing the factors influencing model development and implementation into clinical practice.
METHODS
We searched multiple databases, including Web of Science, Arxiv, MedRxiv, BioRxiv, Embase, PubMed, DBLP, Google Scholar, IEEE Xplore, Semantic Scholar, and Cochrane, targeting articles on whole slide imaging and deep learning published from 2014 and 2023. Out of 776 articles identified based on inclusion criteria, we selected 36 papers for the analysis.
KEY CONTENT AND FINDINGS
Most articles in this review focus on the in-laboratory phase of deep learning model development, a critical stage in the deep learning lifecycle. Challenges arise during model development and their integration into clinical practice. Notably, lab performance metrics may not always match real-world clinical outcomes. As technology advances and regulations evolve, we expect more clinical trials to bridge this performance gap and validate deep learning models' effectiveness in clinical care. High clinical accuracy is vital for informed decision-making throughout a patient's cancer care.
CONCLUSIONS
Deep learning technology can enhance cancer detection, clinical workflows, and patient care. Challenges may arise during model development. The deep learning lifecycle involves data preprocessing, model development, and clinical implementation. Achieving health equity requires including diverse patient groups and eliminating bias during implementation. While model development is integral, most articles focus on the pre-deployment phase. Future longitudinal studies are crucial for validating models in real-world settings post-deployment. A collaborative approach among computational pathologists, technologists, industry, and healthcare providers is essential for driving adoption in clinical settings.
PubMed: 38881914
DOI: 10.21037/tcr-23-964 -
Transplantation Direct Jul 2024Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff score is not reproducible and may miss important ME features. The...
BACKGROUND
Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss.
METHODS
We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME (%glomeruli with ME in ≥2 lobules, like Banff ); (2) %ME (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss.
RESULTS
From 1- to 5-y biopsies, the mean Banff score increased from 0.18 to 0.34, whereas %ME increased from 2.5% to 13.3%. Banff score had modest correlations with morphometric ME measures. Moderate-severe %ME was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %ME had the highest c-statistic (0.872).
CONCLUSIONS
Banff score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.
PubMed: 38881746
DOI: 10.1097/TXD.0000000000001652 -
Urologic Oncology Jun 2024Pathologic re-review of transurethral resection of bladder tumor (TURBT) specimen is a common practice at our tertiary care center, but its impact on disease risk...
OBJECTIVES
Pathologic re-review of transurethral resection of bladder tumor (TURBT) specimen is a common practice at our tertiary care center, but its impact on disease risk stratification remains unknown. We sought to determine how pathologic re-review of specimen initially read at an outside institution changed grade, clinical T (cT) stage, and AUA non-muscle-invasive bladder cancer (NMIBC) risk stratification.
METHODS AND MATERIALS
The laboratory information system was searched for patients who underwent TURBT from 2021 to 2022, yielding 561 records. 173 patients met inclusion criteria: 113 with
RESULTS
For
CONCLUSIONS
Re-review of TURBT pathology by a dedicated GU pathologist led to change in AUA NMIBC risk stratification in over one-fifth of patients, with potential for changing management.
PubMed: 38880703
DOI: 10.1016/j.urolonc.2024.05.020 -
Cardiovascular Pathology : the Official... Jun 2024Electron microscopy (EM) was a popular diagnostic tool in the 1970s and early 80s. With the adoption of newer, less expensive techniques, such as immunohistochemistry,... (Review)
Review
Electron microscopy (EM) was a popular diagnostic tool in the 1970s and early 80s. With the adoption of newer, less expensive techniques, such as immunohistochemistry, the role of EM in diagnostic surgical pathology has dwindled substantially. Nowadays, even in academic centers, EM interpretation is relegated to renal pathologists and the handful of (aging) pathologists with experience using the technique. As such, EM interpretation is truly arcane-understood by few and mysterious to many. Nevertheless, there remain situations in which EM is the best or only ancillary test to ascertain a specific diagnosis. Thus, there remains a critical need for the younger generation of surgical pathologists to learn EM interpretation. Recognizing this need, cardiac EM was made the theme of the Cardiovascular Evening Specialty Conference at the 2023 United States and Canadian Academy of Pathology (USCAP) annual meeting in New Orleans, Louisiana. Each of the speakers contributed their part to this article, the purpose of which is to review EM as it pertains to myocardial tissue and provide illustrative examples of the spectrum of ultrastructural cardiac pathology seen in storage/metabolic diseases, cardiomyopathies, infiltrative disorders, and cardiotoxicities.
PubMed: 38880163
DOI: 10.1016/j.carpath.2024.107670 -
Health Expectations : An International... Jun 2024Stroke survivors with aphasia (impaired language/communication) have poor outcomes and gaps in the clinical implementation of best practice contribute to this. Little is...
Qualitative Exploration of Speech Pathologists' Experiences and Priorities for Aphasia Service Design: Initial Stage of an Experience-Based Co-Design Project to Improve Aphasia Services.
INTRODUCTION AND AIMS
Stroke survivors with aphasia (impaired language/communication) have poor outcomes and gaps in the clinical implementation of best practice contribute to this. Little is known, however, about speech pathologist perspectives on the touchpoints (key moments shaping experiences) in the clinical care pathway that have the greatest impact on service delivery nor how this varies by geographical location. We explored the experiences of speech pathologists who provide aphasia services to establish priorities for improvement and design.
METHODS AND ANALYSIS
This is the initial experience gathering and priority identification stage of an experience-based co-design (EBCD) project. Speech pathologists were recruited from 21 geographically diverse Hospital and Health Services in Queensland, Australia. Speech pathologists working in acute, rehabilitation and community services shared positive and negative experiences of delivering aphasia care in interviews and focus groups. Experiential data were analysed using qualitative thematic analysis to determine touchpoints. Priorities for service design were identified using an adapted nominal group technique.
RESULTS
Speech pathologists (n = 62) participated in 16 focus groups and nine interviews and shared 132 experiences of delivering aphasia care. Providing care in teams with poor awareness of the impacts of aphasia was identified as a key challenge, as poor patient-provider communication was perceived to increase risk of adverse outcomes for patients. Speech pathologists identified areas for improvement related to their own professional needs (e.g., greater access to clinical supervision); collaborative health care (e.g., better coordination and interdisciplinary care to increase therapy time); and the service context and environment (e.g., psychological services able to support diverse communication needs).
CONCLUSIONS
Speech pathologist delivery of aphasia services could be improved through increased access to clinical supervision, opportunities for peer debriefing and interdisciplinary care. Priorities for service design varied by geographical location and included: education to support care transitions (remote areas), improved referral pathways and service linkage (regional areas) and dedicated aphasia staffing (metropolitan areas).
PATIENT OR PUBLIC CONTRIBUTION
A consumer advisory committee comprising people with aphasia (n = 3, authors K.M., K.D. and B.A.), their significant others (n = 2, authors J.D. and P.M.), and a Cultural Capability Officer (author G.B.) guided this research. The team: (1) reviewed participant information; (2) co-designed surveys and workshop resources; (3) copresented research outcomes and contributed to publications. Research questions and study design (e.g., analysis methods and assessment measures) were developed by the research team (authors L.A., V.J.P., D.A.C. and S.J.W.).
Topics: Humans; Aphasia; Speech-Language Pathology; Queensland; Qualitative Research; Focus Groups; Interviews as Topic; Female; Male; Stroke
PubMed: 38879788
DOI: 10.1111/hex.14105 -
Diagnostic Pathology Jun 2024Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti-PD-1/PD-L1...
BACKGROUND
Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti-PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC.
METHODS AND RESULTS
The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p < 0.001 and p = 0.003, separately). PD-L1 was expressed equally or more in the recurrent lesion compared with its matched primary lesion.
CONCLUSIONS
In conclusion, anti-PD-1/PD-L1 inhibitors are a promising therapeutic choice for OCCC. For evaluation of PD-L1 expression, CPS is more recommended than TPS. Evaluation of recurrent lesion was still suitable and predictive when the primary tumor tissue was not available. Distant metastatic lesions can serve as alternative samples for PD-L1 evaluation, while usage of lymphatic metastatic lesions is not recommended.
Topics: Humans; Female; B7-H1 Antigen; Retrospective Studies; Middle Aged; Ovarian Neoplasms; Adult; Aged; Biomarkers, Tumor; Adenocarcinoma, Clear Cell; Immunohistochemistry; Drug Resistance, Neoplasm; Neoplasm Recurrence, Local; Aged, 80 and over
PubMed: 38879528
DOI: 10.1186/s13000-024-01510-4 -
ESMO Open Jun 2024Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort...
BACKGROUND
Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers.
PATIENTS AND METHODS
Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value.
RESULTS
The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value.
CONCLUSIONS
This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.
Topics: Humans; Lung Neoplasms; Neuroendocrine Tumors; Female; Ki-67 Antigen; Male; Biomarkers, Tumor; Middle Aged; World Health Organization; Histones; Aged; Prognosis; Deep Learning
PubMed: 38878324
DOI: 10.1016/j.esmoop.2024.103591 -
NPJ Precision Oncology Jun 2024There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an...
There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an artificial intelligence-driven real-time evaluation model for gastric cancer tissue using confocal laser endomicroscopic system. The remarkable performance of the model suggests its potential utilization as a standalone modality for instantaneous histologic assessment and as a complementary tool for pathologists' interpretation.
PubMed: 38877301
DOI: 10.1038/s41698-024-00621-x