Lynnette Savaloja Pineault, Nikki Martin, Melissa A Kelly, Robyn L Temple-Smolkin, Alexandra S Brown
{"title":"Standardized protocols for reflexing to a multigene panel for patients with non-small cell lung cancer: prevalence and perceived barriers to comprehensive, pathologist-ordered biomarker reflex testing.","authors":"Lynnette Savaloja Pineault, Nikki Martin, Melissa A Kelly, Robyn L Temple-Smolkin, Alexandra S Brown","doi":"10.1093/ajcp/aqag077","DOIUrl":"10.1093/ajcp/aqag077","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the use of standardized protocols for reflexing to broad, multigene panels in non-small cell lung cancer (NSCLC) and identify barriers that limit timely pathologist‑ordered biomarker reflex testing.</p><p><strong>Methods: </strong>A cross-sectional survey was administered to a national sample of health care professionals involved in NSCLC biomarker testing.</p><p><strong>Results: </strong>Of 111 respondents in the dataset, 77.5% reported using an institutional standardized protocol for comprehensive biomarker testing (CBT), and 88.4% of these protocols included reflexing to a multigene panel. Most respondents with reflex protocols indicated that 80% or more of newly diagnosed patients with NSCLC received CBT; however, fewer respondents reported that results were available before the oncology visit to select first‑line treatment. Pathologists were the primary ordering providers in institutions with standardized protocols. Respondents agreed that pathologist‑ordered reflex biomarker testing improves cancer care and supported Centers for Medicare & Medicaid Services (CMS) recognition of pathologists as ordering physicians for broad biomarker panels. Despite protocol adoption, respondents cited persistent barriers-including reimbursement, insurance authorization delays, and the Medicare 14-day rule.</p><p><strong>Conclusions: </strong>Locally standardized protocols incorporating reflex multigene panel testing have been reported and are associated with high rates of CBT. Institutional and operational barriers delay the availability of results and limit the impact of these protocols on first‑line treatment decisions. Clarifying CMS guidance on pathologists as valid ordering physicians for broad biomarker panels, strengthening coordination with multidisciplinary teams, addressing workflow constraints, and educating the laboratories and payers on pathologists having ordering authority may enhance the effectiveness and adoption of reflex biomarker testing models.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kanika Rastogi, Lavleen Singh, Aparajita Khan, Partha Pratim Roy, Venkateswaran K Iyer
{"title":"Deep learning-based detection of acid-fast bacilli in microscopy images: a systematic review.","authors":"Kanika Rastogi, Lavleen Singh, Aparajita Khan, Partha Pratim Roy, Venkateswaran K Iyer","doi":"10.1093/ajcp/aqag083","DOIUrl":"10.1093/ajcp/aqag083","url":null,"abstract":"<p><strong>Objectives: </strong>Acid-fast bacillus (AFB) detection by microscopy remains a cornerstone of laboratory diagnosis for mycobacterial infections, despite the limitations of variable sensitivity, labor-intensive workflows, and interobserver variability. Recent advances in artificial intelligence, particularly deep learning, offer promising solutions to automate and augment AFB detection on microscopy images.</p><p><strong>Methods: </strong>A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with protocol registration in PROSPERO (registration No. CRD42025633886). PubMed and Embase were searched for studies published in the past decade that applied deep learning-based methods to microscopy-based AFB detection. Eligible studies included original research and review articles using Ziehl-Neelsen-stained or auramine-stained specimens and reporting quantitative diagnostic performance metrics. Data on model architectures, annotation strategies, evaluation metrics, and accuracy were extracted. A forest plot was constructed to summarize pooled accuracy estimates across eligible studies.</p><p><strong>Results: </strong>Forty-nine studies met the inclusion criteria. Deep learning models, including convolutional neural networks, object detectors, and transformer-based architectures, demonstrated high accuracies (80%-98%), despite substantial heterogeneity. Weakly supervised learning, multiview and z-stack imaging, and domain adaptation techniques are being used to address variability in staining, focus, and laboratory conditions. Object detection and segmentation models have enabled improved bacillus localization and quantification, while foundation models and transfer learning approaches are reducing annotation burden and improving generalizability.</p><p><strong>Conclusions: </strong>Deep learning-based AFB detection systems demonstrate high accuracy and strong potential to enhance tuberculosis microscopy. Heterogeneity in study design and limited external validation, however, highlight the need for standardized evaluation and multicenter clinical studies before widespread implementation.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The essentials-measurable residual disease in hematopoietic neoplasms: current testing landscape and future directions.","authors":"Savanah D Gisriel, Alexa Siddon","doi":"10.1093/ajcp/aqag079","DOIUrl":"10.1093/ajcp/aqag079","url":null,"abstract":"<p><strong>Objectives: </strong>Measurable residual disease (MRD) analysis, also known as minimal residual disease analysis, has become an essential component of routine clinical management in many hematopoietic neoplasms. Measurable residual disease status in the absence of morphologic disease holds prognostic value and can acutely affect treatment decisions.</p><p><strong>Methods: </strong>Measurable residual disease monitoring is described in acute leukemia, multiple myeloma, and chronic lymphocytic leukemia. We discuss the approach to MRD assessment of these hematologic neoplasms using flow cytometry and molecular techniques.</p><p><strong>Results: </strong>The appropriate use of available ancillary techniques is crucial to assess patients for MRD. Interpreting these results in the appropriate clinical context is challenging and often requires expertise. Incorporating the results into disease management is critical for improved outcomes.</p><p><strong>Conclusions: </strong>Consensus guidelines on MRD assessment in hematopoietic neoplasms continue to evolve. Further, emerging technologies and laboratory availability are important practical considerations for pathologists who are implementing MRD analysis. From this review, pathologists can gain an anecdotal perspective on the application and interpretation of advanced studies to assess the MRD status of patients with hematopoietic malignancies.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Busra N Delikkaya, Jaime Eberle-Singh, Joanna Chan, Allison Goldberg
{"title":"Communication patterns among surgical pathologists: a retrospective review of ideal strategies in a tertiary care setting.","authors":"Busra N Delikkaya, Jaime Eberle-Singh, Joanna Chan, Allison Goldberg","doi":"10.1093/ajcp/aqag075","DOIUrl":"10.1093/ajcp/aqag075","url":null,"abstract":"<p><strong>Objectives: </strong>Timely communication of significant surgical pathology results is essential for patient safety, yet quantitative data on how pathologists select result recipients, especially in urgent settings, are limited. We examined real-world communication patterns, focusing on STAT vs routine orders.</p><p><strong>Methods: </strong>We retrospectively reviewed pathologist-initiated notifications of significant surgical pathology results at a tertiary academic medical center (January to July 2024). In 324 events, we recorded recipient/provider characteristics, care team involvement, urgency status, procedural setting, and turnaround time (TAT). Events were compared by ordering provider (OP) vs alternate provider (AP) contact and by STAT vs routine designation using χ2 tests.</p><p><strong>Results: </strong>Most notifications were sent to OPs (67%), with 33% sent to APs. Alternate provider contact was more frequent for STAT cases, biopsies, and shorter TATs (all P < .05). Contacted OPs were more often subspecialty trained (P < .001) and on the care team (P = .001). Ordering providers were more likely to be contacted directly when they were attending physicians and subspecialty trained; radiology was the predominant AP specialty (62%), while obstetrics and gynecology and gastroenterology were most common among OPs. STAT cases showed faster TATs, outpatient settings, and more frequent notification of nonordering but subspecialty-trained clinicians (all P < .05). Recipient role did not differ by urgency.</p><p><strong>Conclusions: </strong>Pathologists adjust communication based on urgency, prioritizing rapid notification to qualified clinicians when needed. Flexible recipient selection may support timely clinical action and inform institutional communication policies.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nandan Padmanabha, Adam S Sperling, Elizabeth A Morgan, Phillip D Michaels, Sam Sadigh
{"title":"Clinicopathologic characterization of plasma cell neoplasms with IGH::CCND3.","authors":"Nandan Padmanabha, Adam S Sperling, Elizabeth A Morgan, Phillip D Michaels, Sam Sadigh","doi":"10.1093/ajcp/aqag080","DOIUrl":"10.1093/ajcp/aqag080","url":null,"abstract":"<p><strong>Objectives: </strong>Plasma cell neoplasms (PCNs) harboring IGH::CCND3 (t(6;14)) are rare (<1% of PCNs). We sought to study these cases, as they have not been studied as a distinct entity, and their clinicopathologic features are not well characterized.</p><p><strong>Methods: </strong>Cytogenetics databases were searched for positive IGH::CCND3 interphase fluorescence in situ hybridization (FISH) results in plasma cell neoplasms. We analyzed the clinical, morphologic, immunophenotypic, and cytogenetic features of these cases and evaluated the utility of cyclin D3 immunohistochemistry (IHC) for identifying these neoplasms.</p><p><strong>Results: </strong>Sixteen patients were identified, presenting with multiple myeloma (n = 9), monoclonal gammopathy of undetermined significance (n = 3), smoldering myeloma (n = 2), plasma cell leukemia (n = 1), and amyloid light chain amyloidosis (n = 1). Median age at diagnosis was 68.9 years. Most cases showed lymphoplasmacytoid morphology (63%, 10/16), with frequent CD20 expression (53%, 8/15) and aberrant expression of CD56 (71%, 10/14) and CD117 (69%, 9/13). Monosomy 13 was the most frequent concurrent cytogenetic abnormality (50%, 7/14). Cyclin D3 IHC showed nuclear expression in plasma cells in all tested patients (11/11). Background erythroid precursors and megakaryocytes also showed variable positivity. When performed as a dual immunostain with CD138, cyclin D3 served as a highly sensitive and specific method for detecting these neoplastic plasma cells.</p><p><strong>Conclusions: </strong>IGH::CCND3 PCNs frequently exhibit lymphoplasmacytoid features and CD20 expression, resembling the more common t(11;14) PCNs. Cyclin D3 IHC is an effective surrogate for the t(6;14) translocation in PCNs. We recommend using cyclin D3 IHC in the workup of PCNs with lymphoplasmacytoid morphology but negative cyclin D1 to appropriately trigger reflex FISH testing in positive cases and rescue them from the \"partner-negative\" category.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Yu, Sophia Bellegarde, Jacqueline Chen, Kristin Kupczewski, Ryan Fogaren
{"title":"Structured workflow for send-out test review: operational performance and utilization patterns.","authors":"Min Yu, Sophia Bellegarde, Jacqueline Chen, Kristin Kupczewski, Ryan Fogaren","doi":"10.1093/ajcp/aqag086","DOIUrl":"10.1093/ajcp/aqag086","url":null,"abstract":"<p><strong>Objectives: </strong>Send-out laboratory testing has increased substantially with the expansion of specialized assays, introducing operational complexity and risk of inefficiencies in test ordering and review. While laboratory stewardship programs emphasize appropriate test utilization, practical approaches to standardizing send-out test review at the individual request level remain limited.</p><p><strong>Methods: </strong>We implemented a structured, informatics-enabled workflow for send-out test review at an academic medical center. The workflow standardized request submission, reviewer notification, decision documentation, and communication without modifying existing clinical review criteria. This quality improvement initiative was evaluated over 8 months (August 2025 to March 2026).</p><p><strong>Results: </strong>A total of 3055 requests were reviewed. Median monthly volume was 381 (range, 306-446). Documentation completeness was 98%. Median review turnaround time was 1 day (IQR, 0-1), with 83.9% completed within 1 day. Overall, 81.2% were approved, 11.8% were declined or canceled, and 6.9% were replaced. Review outcomes varied across clinical services, and a limited number of tests accounted for a disproportionate share of declined and modified requests.</p><p><strong>Conclusions: </strong>Implementation of a structured workflow for send-out test review enabled standardized documentation, rapid turnaround, and improved visibility into utilization patterns. This approach provides a scalable framework for enhancing laboratory oversight and supporting targeted test utilization interventions.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiannan Li, Andrew E O Hughes, Tianjiao Wang, Kathleen Byrnes, Eric J Duncavage, Xiuli Liu
{"title":"Unique characteristics of Lynch syndrome-associated mismatch repair-deficient colorectal intramucosal carcinoma.","authors":"Jiannan Li, Andrew E O Hughes, Tianjiao Wang, Kathleen Byrnes, Eric J Duncavage, Xiuli Liu","doi":"10.1093/ajcp/aqag090","DOIUrl":"10.1093/ajcp/aqag090","url":null,"abstract":"<p><strong>Objectives: </strong>Intramucosal carcinoma (IMC) of the colorectum is a rare and diagnostically challenging neoplasm frequently recognized in patients with Lynch syndrome (LS) recently. This study aimed to compare the clinicopathologic features and immunophenotypes of LS-associated mismatch repair-deficient (MMR-D) colorectal IMCs with mismatch repair-proficient (MMR-P) IMCs and sporadic MMR-D IMCs, as well as to examine APC pathway alterations in LS-associated MMR-D IMCs.</p><p><strong>Methods: </strong>Pathology archives from 2004 to 2024 were reviewed for colorectal IMC cases. Clinical, endoscopic, morphologic, immunohistochemical, and next-generation sequencing data were analyzed.</p><p><strong>Results: </strong>A total of 31 IMC cases were identified, including 9 LS-associated MMR-D, 5 sporadic MMR-D, and 17 MMR-P. Patients with LS who had MMR-D IMCs were significantly younger (P = .013), had more prior malignancies (P = .003), and had shorter colonoscopy intervals (P = .011) compared with patients with MMR-P and sporadic MMR-D. The LS-associated MMR-D IMCs were larger, more often infiltrated normal mucosa, and exhibited medullary and mucinous features more frequently than other IMCs. While expressing CDX2 and SATB2, LS-related MMR-D tumors showed less CK20 positivity than sporadic MMR-D and MMR-P IMCs (P = .003). Among LS-associated MMR-D IMCs, 37.5% exhibited nuclear β-catenin immunoreactivity, regardless of the specific MMR gene affected.</p><p><strong>Conclusions: </strong>These findings suggest that LS-associated MMR-D IMCs have distinct clinicopathologic and immunophenotypic profiles compared with MMR-P and sporadic MMR-D IMCs, emphasizing the need for unique diagnostic and management strategies for these patients.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana María Colino-Gallardo, María Jesús Fernández-Aceñero, Jesús Vega-González, Montserrat De La Torre-Serrano, María Pilar Díaz-Suárez, Luis Ortega-Medina, Luis Ignacio Diez-Valladares, Javier Martínez-Useros
{"title":"Lymph node ratio as an independent predictor of survival in pancreatic adenocarcinoma: Insights from a retrospective cohort study.","authors":"Ana María Colino-Gallardo, María Jesús Fernández-Aceñero, Jesús Vega-González, Montserrat De La Torre-Serrano, María Pilar Díaz-Suárez, Luis Ortega-Medina, Luis Ignacio Diez-Valladares, Javier Martínez-Useros","doi":"10.1093/ajcp/aqag037","DOIUrl":"10.1093/ajcp/aqag037","url":null,"abstract":"<p><strong>Objectives: </strong>We evaluated the prognostic impact of lymph node yield (LNY) and lymph node ratio (LNR) on disease-free survival (DFS) and overall survival (OS) after resection for pancreatic adenocarcinoma.</p><p><strong>Methods: </strong>Using a retrospective cohort of 214 patients who had undergone surgical resection between 2000 and 2022), LNY was dichotomized at the median (≤13 vs >13 nodes). The LNR was categorized as 0, 0.01 to 0.20, and greater than 0.20. Survival was analyzed using Kaplan-Meier/log rank and multivariable Cox regression; node-negative category (N0) sensitivity analyses were performed.</p><p><strong>Results: </strong>The LNY was not significantly associated with differences in DFS (14 vs 15 months; P = .72) or OS (18 vs 26 months; P = .27), although N0 patients showed a trend toward longer OS with higher LNY (22 vs 36 months; P = .087). The LNR statistically significantly separated DFS (19 vs 10 vs 12 months; P = .003) and OS (28 vs 20 vs 18 months; P = .045). In Cox models, an LNY below 13 was protective for DFS (hazard ratio [HR], 0.633; P = .03) and borderline for OS (HR, 0.705; P = .07). Compared with an LNR of 0, an LNR of 0.01 to 0.20 or greater than 0.20 independently predicted recurrence (HR, 1.921; P = .006 and HR, 1.745; P = .02); for OS, only an LNR greater than 0.20 remained significant (HR, 1.752; P = .01). A higher LNR was associated with lymphovascular/perineural invasion and progression.</p><p><strong>Conclusions: </strong>Lymph node ratio is an independent prognostic marker after resection that predicts recurrence and-when above 0.20-mortality, whereas LNY mainly reflects staging adequacy.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shahzan Anjum, Seema Sen, Mehar C Sharma, Sameer Bakhshi, Kunzang Chosdol, Seema Kashyap, Neelam Pushker, Mandeep S Bajaj, Rachna Meel
{"title":"Prognostic significance of Myb protein and its downstream target genes in lacrimal gland adenoid cystic carcinoma.","authors":"Shahzan Anjum, Seema Sen, Mehar C Sharma, Sameer Bakhshi, Kunzang Chosdol, Seema Kashyap, Neelam Pushker, Mandeep S Bajaj, Rachna Meel","doi":"10.1093/ajcp/aqag073","DOIUrl":"10.1093/ajcp/aqag073","url":null,"abstract":"<p><strong>Objectives: </strong>Lacrimal gland adenoid cystic carcinoma (ACC) is a rare and lethal malignancy associated with a poor prognosis, with no known therapeutic targets. The clinical relevance of Myb, Sox4, c-Kit protein expression, and the MYB::NFIB fusion gene in lacrimal gland ACC is not well known. The current study aims to investigate the prognostic significance of Myb, Sox-4, c-Kit protein, and the MYB::NFIB fusion gene in lacrimal gland ACC.</p><p><strong>Methods: </strong>A total of 30 histopathologically diagnosed lacrimal gland ACC cases were included in this study. Myb, Sox4, c-Kit expression, and MYB::NFIB gene fusion were evaluated by immunohistochemistry and fluorescence in situ hybridization, respectively. The results were correlated with clinicopathologic features and patient survival.</p><p><strong>Results: </strong>Immunoexpression of Myb, Sox4, and c-Kit was observed in 70%, 63%, and 63% of ACC cases, respectively. Myb expression showed a significant association with the solid and cribriform histologic patterns, Sox-4 expression, and disease-free survival. On univariate analysis, Myb expression, solid histologic pattern, bone erosion, intracranial extension, and advanced tumor stage were indicators of poor prognosis. c-Kit expression showed a significant association with advanced tumor stage. MYB::NFIB fusion, detected in 47% of cases, was significantly associated with intracranial extension.</p><p><strong>Conclusions: </strong>Myb protein emerged as a prognostic indicator in the pathogenesis and clinical outcomes of patients with lacrimal gland ACC.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic characterization of papillary thyroid carcinoma: Insights into the role of PD-L1 and mutational landscape in disease aggressiveness and outcome.","authors":"Chanchal Rana, Prabhakar Mishra, Isha Makkar, Kulranjan Singh, Pooja Ramakant, Anand Mishra, Gagan Chhabra","doi":"10.1093/ajcp/aqag049","DOIUrl":"10.1093/ajcp/aqag049","url":null,"abstract":"<p><strong>Objectives: </strong>Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer, generally associated with an excellent prognosis. However, a subset of tumors behaves aggressively, highlighting the need for reliable prognostic biomarkers to improve risk stratification beyond traditional clinicopathologic parameters. This study evaluates the prognostic value of PD-L1 expression and its association with key molecular alterations in PTC.</p><p><strong>Methods: </strong>This retrospective study included 84 patients with PTC treated at King George's Medical University between 2016 and 2024. PD-L1 expression was assessed using the tumor proportion score. Correlations with clinicopathologic features, BRAF and TERT promoter mutations, recurrence, and survival outcomes were analyzed. Multivariable analysis was performed to identify independent prognostic factors.</p><p><strong>Results: </strong>PD-L1 expression was positive in 60.7% of cases, with 38.1% classified as high expressors. High PD-L1 expression was significantly associated with advanced tumor stage, lymph node metastasis, aggressive histologic variants, and absence of thyroiditis. PD-L1 upregulation correlated strongly with BRAF and TERT promoter mutations. Coexisting BRAF and TERT mutations emerged as independent predictors of recurrence and poor survival. Clinically, recurrence occurred in 20.2% of patients and metastasis in 8.3%, both significantly associated with high PD-L1 expression. Multivariable analysis confirmed multiple mutations and PD-L1 overexpression as key prognostic factors.</p><p><strong>Conclusions: </strong>PD-L1 is a robust biomarker of aggressiveness in PTC. Integrating PD-L1 testing with molecular profiling can enhance postoperative risk stratification and guide personalized management.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}