American journal of clinical pathology最新文献

{"title":"Preanalytical variables in surgical pathology: practical sources of diagnostic error before microscopic interpretation.","authors":"Arthur Vaz Alvares Fernandes","doi":"10.1093/ajcp/aqag098","DOIUrl":"https://doi.org/10.1093/ajcp/aqag098","url":null,"abstract":"<p><strong>Objectives: </strong>To review clinically important preanalytical variables in surgical pathology and their effects on diagnostic accuracy, ancillary testing, and patient safety.</p><p><strong>Methods: </strong>A narrative review was developed from selected literature on surgical pathology preanalytics, fixation, specimen handling, histotechnology, immunohistochemistry, molecular testing, tissue contamination, and quality improvement. Emphasis was placed on practical variables that affect routine anatomic pathology workflows.</p><p><strong>Results: </strong>The diagnostic value of a surgical pathology specimen is shaped before microscopic interpretation. Ischemia time, delayed or inadequate fixation, tissue thickness, container and transport problems, labeling discrepancies, poor orientation, grossing variability, histotechnical artifacts, and tissue contamination can compromise morphology, margin assessment, staging, biomarker interpretation, and molecular testing. These effects are especially consequential in small biopsy specimens and precision oncology specimens, in which the same limited tissue may be required for diagnosis, immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based testing, and next-generation sequencing. Gross examination is a particularly important pathology-controlled preanalytical step because block selection determines what can be assessed microscopically.</p><p><strong>Conclusions: </strong>Preanalytical control should be regarded as a diagnostic quality and patient safety process rather than a technical background activity. Standardized fixation, specimen tracking, communication, grossing protocols, histotechnical quality assurance, and tissue stewardship are essential to reliable surgical pathology practice.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886064","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":"Implementation and early outcomes of an in-house DPYD genotyping program for fluoropyrimidine safety.","authors":"Harpreet Virk, Sneha Challa, Navid Sadri","doi":"10.1093/ajcp/aqag104","DOIUrl":"10.1093/ajcp/aqag104","url":null,"abstract":"<p><strong>Objectives: </strong>Fluoropyrimidines are widely used in the treatment of solid tumors but may cause severe toxicity in patients with reduced dihydropyrimidine dehydrogenase activity caused by specific DPYD variants. Although pretreatment DPYD genotyping is guideline supported, implementation remains inconsistent when testing, interpretation, and result reporting are not integrated into routine care pathways. This study evaluated the implementation of an in-house DPYD genotyping program embedded in prechemotherapy workflows at a multisite cancer center.</p><p><strong>Methods: </strong>A prospective observational cohort study was performed from May 2024 through July 2025 at a multisite community-academic cancer center. Peripheral blood specimens underwent in-house DPYD genotyping for c.1905 + 1G > A, c.1679T > G, c.1236G > A as a proxy for c.1129-5923C > G, c.2846A > T, and c.557A > G using TaqMan allelic discrimination. Raw instrument output was processed through an internally developed automated pipeline that supported genotype calling, quality control review, phenotype and activity assignment, and generation of a note with this information for release into the electronic health record after medical director review. Of 617 genotyped patients, 505 who received systemic fluoropyrimidine-based therapy were included in the primary analysis.</p><p><strong>Results: </strong>Among 505 included patients, pretreatment testing was performed in 439 (86.9%), although only 197 of 439 (44.9%) had results available before cycle 1 chemotherapy. Twenty-two (4.4%) patients were heterozygous for a DPYD variant: c.1236G > A in 11, c.2846A > T in 5, c.1905 + 1G > A in 4, and c.557A > G in 2. In the pretreatment cohort, 10 of 21 (47.6%) patients heterozygous for a DPYD variant underwent dose reduction at cycle 1, and 9 of these reductions were documented as genotype guided. Severe treatment-related adverse events requiring urgent evaluation or hospitalization occurred in 5 of 505 (1.0%) patients, including 1 patient heterozygous for a c.1236G > A variant whose result returned after treatment initiation.</p><p><strong>Conclusions: </strong>In-house DPYD genotyping with integrated clinical reporting was feasible in routine practice and identified actionable variants in a clinically meaningful proportion of patients. The principal implementation limitation was not assay turnaround time itself but rather failure to return results before the first treatment decision in pretreatment-ordered cases. These findings support the value of laboratory-led pharmacogenomic programs that combine rapid testing, structured interpretation, and direct electronic reporting.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068887","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":"Saline whole-blood impedance aggregometry for detection of heparin-independent platelet-activating anti-platelet factor 4 antibodies.","authors":"Jing Jin, Lu M Yang, Juan Zhang, Krinaben Patel, James L Zehnder","doi":"10.1093/ajcp/aqag100","DOIUrl":"https://doi.org/10.1093/ajcp/aqag100","url":null,"abstract":"<p><strong>Objectives: </strong>This study evaluates the practice of incorporating a saline testing condition into the heparin-induced thrombocytopenia (HIT) functional assay using whole-blood impedance aggregometry (WBIA) to identify a subgroup of highly pathogenic anti-platelet factor 4 (PF4) antibodies with heparin-independent platelet-activating properties.</p><p><strong>Methods: </strong>From 2023 to 2025, we analyzed 150 evaluable patients (65 WBIA Negative, 85 WBIA Positive). Positive cases were subdivided into Classic-Positive (low-dose heparin positive only; n = 46) and Saline-Positive (positive under both low-dose heparin and saline; n = 35). The diagnosis of clinical HIT by hematologists was used as reference. PF4/IgG was measured by chemiluminescent immunoassay; WBIA was performed with low-dose heparin, high-dose heparin, and saline; and available serotonin release assay (SRA) results were analyzed.</p><p><strong>Results: </strong>Saline-Positive patients exhibited significantly higher incidences of HIT-associated thrombosis (89% vs 54%, P = .005), delayed-onset HIT (23% vs 0%, P = .001), refractory HIT (40% vs 7%, P < .001), spontaneous HIT (14% vs 0%, P = .013), and more venous thromboembolism (pulmonary embolism and deep vein thrombosis, P < .05) compared with Classic-Positive patients. All 35 Saline-Positive cases were classified as autoimmune HIT (aHIT). The spontaneous HIT subset (n = 5) displayed a distinct pattern of low-titer anti-PF4 antibodies discordant with strong saline-WBIA reactivity and a high SRA false-negative rate (57.1%). High-dose intravenous immunoglobulin neutralized saline positivity in real time.</p><p><strong>Conclusions: </strong>Saline-positivity in WBIA identifies a heparin-independent aHIT phenotype with higher pathogenicity and thrombotic risk. This rapid saline protocol addresses diagnostic gaps where standard 2-condition SRA protocols may fail, offering a practical tool to identify high-pathogenic anti-PF4 antibodies and guide clinical management.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928721","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":"LGALS3::POU5F1 gene fusion identified in a low-grade myxoid spindle cell tumor.","authors":"Shuanzeng Wei, Rajeswari Nagarathinam, Jianming Pei, Douglas B Flieder, Arthur S Patchefsky, Praveen Chatani, Leonardo Weber Graeff, Margaret von Mehren, Jeffrey M Farma","doi":"10.1093/ajcp/aqag102","DOIUrl":"https://doi.org/10.1093/ajcp/aqag102","url":null,"abstract":"<p><strong>Objectives: </strong>Myoepithelial tumor (MET) of soft tissue can harbor POU5F1-associated fusions, including EWSR1/FUS::POU5F1 and SS18::POU5F1. We present a low-grade myxoid spindle cell tumor with a novel LGALS3::POU5F1 mimicking MET.</p><p><strong>Methods: </strong>Immunohistochemistry, DNA/RNA next-generation sequencing (NGS), and chromosomal microarray were performed.</p><p><strong>Results: </strong>A 54-year-old man presented with a firm 4.5-cm left upper extremity mass superficial to the fascia. Microscopically, the tumor was partially encapsulated with extracapsular invasion and involvement of surrounding fat. The predominantly hypocellular tumor featured a reticular growth pattern with a myxoid stroma, mimicking extraskeletal myxoid chondrosarcoma. The hypercellular areas demonstrated epithelioid tumor cells embedded in sclerotic stroma, mimicking sclerosing epithelioid fibrosarcoma. Tumor necrosis was absent, and mitotic figures were rare. The tumor cells were only focally and weakly positive for S100 and CAM5.2, but negative for MUC4, AE1/3, CD34, EMA, desmin, GFAP, SMA, p63, SOX10, and calponin. Chromosomal microarray showed gains of whole chromosomes or segment of 5, 6, 7, 8, 12, 14q, and 16. DNA NGS did not show pathogenic mutations.</p><p><strong>Conclusions: </strong>More similar cases are needed to determine whether this LGALS3::POU5F1-positive low-grade myxoid spindle cell tumor represents a new tumor entity or a variant of a MET.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001019","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":"Risk factors for lymph node metastasis in a contemporary radical prostatectomy cohort.","authors":"Oleksii A Iakymenko, Sheida Khosravaniardakani, Angelica Menendez, Sasha R Sioni, Merce Jorda, Sanoj Punnen, Dipen J Parekh, Mark L Gonzalgo, Oleksandr N Kryvenko","doi":"10.1093/ajcp/aqag095","DOIUrl":"https://doi.org/10.1093/ajcp/aqag095","url":null,"abstract":"<p><strong>Objective: </strong>We sought to assess how centrally reviewed radical prostatectomy (RP) Grade Group (GG), tumor volume (TV), prostate-specific antigen density (PSAD), pathologic stage, tumor topography, patient age, and race and ethnicity relate to regional lymph node metastasis (LN+).</p><p><strong>Methods: </strong>We reviewed patient cases with treatment-naive RPs performed from 2013 through 2026. All specimens underwent centralized histologic review by 1 urologic pathologist. Grade Group was assigned from the highest-grade tumor, and its TV was measured. Tumor volume and PSAD were modeled on the log2 scale (odds ratios per doubling), and multivariable Firth penalized logistic regression assessed factors associated with LN+.</p><p><strong>Results: </strong>No metastasis was seen in GG1 cases (n = 368). The final cohort comprised 3142 node-staged GG2 to GG5 RP specimens. Positive regional LNs were identified in 135 (4.3%) patients, with a median of 1 positive node (IRQ, 1-2 LNs; range, 1-17 LNs). Cases with LN+ disease had a median of 9 LNs (range, 1-31 LNs) examined compared with 5 LNs (range, 1-45 LNs) in cases without metastasis (P < .001). Grade Group 5 cancer was associated with a clinically significantly lower value for PSAD divided by TV (PSAD/TV) than for GG2 to GG4 cancers. In the augmented multivariable Firth model, PSAD, TV, GG, posterior or extensive bilateral topography, and pT3a/pT3b stage were independently associated with LN+. Age, race, and ethnicity were not independently associated. Anterior topography inversely correlated with LN+.</p><p><strong>Conclusions: </strong>In this centrally reviewed RP cohort, no LN+ was observed in GG1 cancer. Among GG2 to GG5 cancers, LN+ was associated with increasing GG, larger TV, higher PSAD, pT3a/pT3b stage, and posterior or extensive bilateral topography after adjustment for age, race, and ethnicity. Grade Group 5 cancers showed lower PSA production than did GG2 to GG4 cancers, indicating a different PSAD-TV relationship.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757324","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":"Pathology goes viral: a qualitative review of #pathology content on TikTok.","authors":"Riley Jepkema, Meredith Herman, Sanjay Gadasalli, Sean Hacking, Julia Kochanowski, Casey Schukow, Kamran Mirza","doi":"10.1093/ajcp/aqag065","DOIUrl":"10.1093/ajcp/aqag065","url":null,"abstract":"<p><strong>Objectives: </strong>The use of #pathology and #pathologist is increasing on TikTok, a short-form video platform with over 1 billion users. As of July 2024, #pathology had over 21 000 posts and 468 million views, while #pathologist had over 3000 posts. It could be a useful tool for education and recruitment if the content is accurate and engaging.</p><p><strong>Methods: </strong>To assess the accuracy, engagement, and educational value of this growing content, we conducted a cross-sectional study analyzing 105 English-language TikTok videos identified using these keywords over a 72-hour period. Videos were evaluated using the Patient Education Assessment Tool for audiovisual material (PEMAT-AV) for audiovisual quality, the Global Quality Scale (GQS) for overall content quality, and a modified JAMA benchmark score for information accountability. Additionally, a harm-benefit score categorized educational impact.</p><p><strong>Results: </strong>Statistical analysis revealed that educational content demonstrated significantly higher quality scores on GQS (P = .0001) and PEMAT-AV (P = .0007) than other content types. In contrast, medical profile type was associated with higher PEMAT-AV (P = .0147), JAMA (P = .0332), and harm-benefit (P = .0004) scores.</p><p><strong>Conclusions: </strong>While the volume of pathology-specific content is currently limited, the high average engagement metrics-298 100 followers, 1.5 million views, and 67 884 likes per video-indicate substantial user interest. The higher-quality scores for educational and medical content suggest that pathology content creators are generally knowledgeable and accurately represent the field on TikTok, highlighting TikTok's potential as a valuable platform for disseminating reliable pathology-related information.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676779","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":"Measurement of hemolysis in packed red blood cell segments and units using H index.","authors":"Erik Fong, Noah Mehr, Timothy Carll","doi":"10.1093/ajcp/aqag091","DOIUrl":"https://doi.org/10.1093/ajcp/aqag091","url":null,"abstract":"<p><strong>Objectives: </strong>Packed red blood cell (pRBC) units are tested before transfusion to confirm compatibility, safety, and quality. Segments are lengths of heat-sealed tubing from the pRBC unit that enable compatibility testing without compromising sterility. If the degree of hemolysis differs between the segment and the parent unit, hematologic or metabolic testing of segments may lead to inaccurate assessment of the corresponding unit. We directly compared hemolysis indices between paired pRBC units and their corresponding segments to assess the degree of hemolysis and possible association with pRBC unit characteristics.</p><p><strong>Methods: </strong>Discarded pRBC units bearing at least 1 attached segment were obtained from a university hospital blood bank. Recorded characteristics included product expiration date, ABO/Rh type, and anticoagulant/additive solutions. Supernatant plasma was analyzed for hemolysis using the Roche cobas 8000 automated chemistry system H index. Associations between the H index and pRBC unit characteristics were also evaluated.</p><p><strong>Results: </strong>A total of 42 paired pRBC units and corresponding segments were analyzed. The segment H index was statistically significantly higher than that of parent units (median [IQR], 309 [189-512] vs 98 [72-177]; Wilcoxon signed rank P < .001), with 39 of 42 (93%) paired samples demonstrating a higher H index in segments. The H index increased with the number of days past expiration both for segments (Spearman ρ = 0.69) and parent units (ρ = 0.61; both P < .001). No statistically significant association between H index and ABO blood group, Rh type, or additive solution type was identified.</p><p><strong>Conclusions: </strong>Our investigation revealed that pRBC segments had statistically significantly increased hemolysis compared with corresponding parent units. As a result, caution should be taken when using segments to assess hemolysis and other hematologic or metabolic testing.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696882","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":"Optical genome mapping refines diagnosis of high-grade myeloid neoplasms through detection of MECOM rearrangements cryptic to conventional karyotype.","authors":"Nicolas Salcedo-Porras, Fatma AlBulushi, Julia N C Parlow, Eric McGinnis, Tara Spence","doi":"10.1093/ajcp/aqag087","DOIUrl":"10.1093/ajcp/aqag087","url":null,"abstract":"<p><strong>Objectives: </strong>MECOM rearrangements (MECOM-r) are high-risk events in myeloid neoplasms often cryptic or incompletely characterized by conventional karyotype analysis. We used optical genome mapping (OGM) to define the frequency and spectrum of MECOM-r in an unselected, consecutively collected cohort of individuals with high-grade myeloid neoplasms (HGMNs) and compared these findings with standard cytogenetic approaches.</p><p><strong>Methods: </strong>A total of 252 HGMN specimens, including 224 with definitive diagnoses of acute myeloid leukemia, were processed over a 2-year period using OGM, G-banded karyotyping and, in some cases, reflex fluorescence in situ hybridization (FISH) for the MECOM locus. Cases were retrospectively reviewed to determine whether the identification of MECOM-r by OGM refined diagnosis and/or prognosis.</p><p><strong>Results: </strong>Our diagnostic workflow identified MECOM-r in 12 cases (4.7%), only 6 of which were identified by combined karyotype and FISH analyses, the latter for suspected chromosome 3 abnormalities. The remaining 6 cases were cryptic due to normal karyotypes, highly complex karyotypes lacking apparent chromosome 3 involvement, or culture failure and thus were identified by OGM and reflex FISH. Furthermore, OGM clarified complex architectures, resolved genetic alterations, and identified diverse partner loci, including GATA2, THADA, MYC, PHACTR1, MB21D2, XR_001744423.2, IL12A-AS1, TRIM59, CDK6, and MSI2. Detection of these structural alterations prompted diagnostic and/or risk reclassification in 5 cases.</p><p><strong>Conclusions: </strong>Optical genome mapping doubled the detection rate and improved the structural resolution of MECOM-r by identifying rearrangements incompletely resolved or missed by conventional cytogenetics. Implementation of OGM showed that MECOM-r can be cryptic and frequently overlooked, highlighting the value of high-resolution testing in HGMNs.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682986","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}

{"title":"Single-cohort next-generation sequencing analysis of 713 anaplastic thyroid carcinomas: unreported gene alterations and actionable targets.","authors":"Xiaoming Zhang, Naiwei Chen, Sarah Claxton, Mikhail Kovalenko, Dean C Pavlick, Matthew C Hiemenz, Laura M Dooley, Richard D Hammer","doi":"10.1093/ajcp/aqag092","DOIUrl":"https://doi.org/10.1093/ajcp/aqag092","url":null,"abstract":"<p><strong>Objectives: </strong>Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal thyroid malignancies, with limited effective treatment options. We aimed to identify previously unreported gene alterations and evaluate the potential for clinically actionable targeted therapies in ATC using the largest single next-generation sequencing (NGS) cohort to date.</p><p><strong>Methods: </strong>This retrospective genomic analysis included deidentified NGS data from 713 patients with ATC obtained from the FoundationCORE database. Pathogenic gene alterations were analyzed for frequency. A comprehensive review of the literature and genomic databases was performed to identify alterations not previously reported in ATC and to assess associated targeted therapies.</p><p><strong>Results: </strong>Targeted sequencing of 713 ATC tumor specimens identified 250 genes with pathogenic or likely pathogenic alterations, including 108 not previously reported in ATC. Among these novel genes, 24 were altered in 5 or more cases, with MTAP (methylthioadenosine phosphorylase) showing the highest frequency (15.26%). MTAP was also co-deleted with CDKN2A/B at significantly higher rates than previously reported. Notably, 99.58% of cases harbored at least 1 gene alteration associated with a potentially actionable therapy. Among the 250 altered genes, 150 (60.0%) had at least 1 available corresponding targeted therapy, and 75.0% of drug categories demonstrated multiple-gene targeting capabilities.</p><p><strong>Conclusions: </strong>This largest single-cohort NGS data analysis identified 108 previously unreported genomic alterations in ATC, significantly expanding the understanding of the genomic landscape of this aggressive cancer. Moreover, these findings highlight a broad range of potentially actionable alterations and underscore the importance of identifying driver mutations and combination therapeutic strategies.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696887","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":"Acute myeloid leukemia with 4q12 rearrangements involving CHIC2: \"pitfalls\" in fluorescence in situ hybridization diagnosis of PDGFRA rearrangements.","authors":"Long Chen, Hong Zhang, Sasa Chai, Shaobin Yang, Jingya Yao, Xiaoju Hou, Xin Tian, Enbin Liu, Yani Lin, Kun Ru","doi":"10.1093/ajcp/aqag084","DOIUrl":"https://doi.org/10.1093/ajcp/aqag084","url":null,"abstract":"<p><strong>Objectives: </strong>Chromosome 4q12 rearrangements are recurrent in hematologic malignancies, most frequently involving PDGFRA. Fluorescence in situ hybridization (FISH) is routinely used for detecting 4q12 rearrangements. This study aimed to clarify 4q12 rearrangements misdiagnosed by FISH and explore the transcriptomic profile of acute myeloid leukemia (AML) with CHIC2 rearrangements.</p><p><strong>Methods: </strong>Fluorescence in situ hybridization with a PDGFRA/CHIC2/FIP1L1 probe set detected 4q12 rearrangements. RNA sequencing (RNA-seq) characterized fusion transcripts and compared transcriptomic profiles between CHIC2-rearranged AML and NPM1-mutated controls, identifying differentially expressed genes and enriched pathways. Previously reported PDGFRA-independent 4q12 cases were reviewed.</p><p><strong>Results: </strong>RNA sequencing of 2 AML cases with FISH signals suggestive of PDGFRA rearrangement identified CHIC2 fusions instead: a novel CDK6::CHIC2 and a known ETV6::CHIC2. Integrating our cases with a systematic literature review, we identified 41 hematologic neoplasms with PDGFRA-independent 4q12 rearrangements, of which 38 (92.7%) were AML. The 4q12 breakpoints most frequently involved CHIC2 (27 cases, 65.9%), followed by GSX2, SCFD2, and intergenic regions. Among 15 cases assessed by both FISH and molecular methods, FISH misclassified 9 (60.0%; 9/15) as PDGFRA rearranged; subsequent molecular testing revealed rearrangements of genes adjacent to PDGFRA (eg, CHIC2, GSX2) or intergenic regions. Transcriptomic profiling of CHIC2-rearranged AML revealed a distinct expression signature with 492 differentially expressed genes, including PDGFRA upregulation. Pathway analysis showed significant enrichment for cytokine-cytokine receptor interaction and JAK-STAT signaling (false discovery rate <0.05).</p><p><strong>Conclusions: </strong>Molecular methods such as RNA-seq are effective for resolving cryptic 4q12 rearrangements in cases where FISH falsely suggests PDGFRA involvement. The distinct transcriptional profile of CHIC2-rearranged AML suggests dysregulated cytokine signaling and JAK-STAT activity in its pathogenesis.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"166 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676781","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}