Diane Wilcock, Deepika Sirohi, Joshua F Coleman, Parisa Adelhardt, Jong Taek Kim, Daniel Albertson, Kajsa Affolter, Cameron Beech, Jolanta Jedrzkiewicz, Ana L Ruano, Allison S Cleary, Jonathan Mahlow, Michael Balatico, H Evin Gulbahce
{"title":"HER2 fluorescence in situ hybridization groups 2-4 breast cancers classified as positive after targeted recounts following equivocal (2+) immunohistochemistry.","authors":"Diane Wilcock, Deepika Sirohi, Joshua F Coleman, Parisa Adelhardt, Jong Taek Kim, Daniel Albertson, Kajsa Affolter, Cameron Beech, Jolanta Jedrzkiewicz, Ana L Ruano, Allison S Cleary, Jonathan Mahlow, Michael Balatico, H Evin Gulbahce","doi":"10.1093/ajcp/aqaf006","DOIUrl":"10.1093/ajcp/aqaf006","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the correlation between the extent of (percentage of tumor cells) immunohistochemistry (IHC) staining and final human epidermal growth factor receptor 2 (HER2)-positive result in fluorescence in situ hybridization (FISH) groups 2 to 4 with equivocal (2+) IHC requiring second, blinded FISH evaluation.</p><p><strong>Methods: </strong>Breast cancer cases submitted for HER2 FISH testing with group 2 to 4 results were included.</p><p><strong>Results: </strong>Of the 2548 cases with HER2 FISH groups 2 to 4 that had HER2 IHC performed, 1104 (43.3%) (76/182 [41.8%] of group 2, 94/161 [58.4%] of group 3, 934/2205 [42.4%] of group 4) had equivocal (2+) IHC. After second blinded, IHC-guided recounts, 217 of 1104 (19.7%) (17/76 [22.4%], 75/94 [79.8%], 125/934 [13.4%] of FISH groups 2, 3, 4 with IHC 2+, respectively) had final HER2-positive status. Only 13 of 217 (6%) of the cases with HER2-positive status had more than 50% circumferential staining of the tumor targeted for rescoring.</p><p><strong>Conclusions: </strong>In over 90% of HER2 FISH group 2 to 4 breast cancers with equivocal (2+) IHC followed by targeted, blinded second FISH evaluation and final HER2-positive result, the amplified population of tumor cells was limited (<50%). Current guidelines recommend cancers having 10% to 50% of the subpopulation with amplified cells classified as having genetic heterogeneity (GH), which have a poor response to targeted therapies. Identifying these tumors as having GH and/or repeat testing may be recommended.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"837-846"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397760","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":"Histopathologic and genetic distinction of well-differentiated grade 3 neuroendocrine tumor versus poorly-differentiated neuroendocrine carcinoma in high-grade neuroendocrine neoplasms.","authors":"Belinda L Sun, Hongxu Ding, Xiaoguang Sun","doi":"10.1093/ajcp/aqaf013","DOIUrl":"10.1093/ajcp/aqaf013","url":null,"abstract":"<p><strong>Objectives: </strong>The classification of neuroendocrine neoplasms has evolved significantly. In the current World Health Organization (WHO) classification, well-differentiated grade 3 neuroendocrine tumors (G3-NETs) are distinguished from poorly-differentiated neuroendocrine carcinomas (NECs) based on morphology despite using the same proliferation indices, which poses diagnostic challenges. This review aims to assist pathologists in making an accurate diagnosis, which is crucial for patient management as G3-NETs and NECs have different prognoses and chemotherapy responses.</p><p><strong>Methods: </strong>A literature review and meta-analyses were conducted to summarize current knowledge of G3-NETs and NECs, focusing on histopathologic and genetic characteristics.</p><p><strong>Results: </strong>Grade 3 neuroendocrine tumors and NECs are distinct entities with differences in histopathology, genetics, and clinical presentations. Grade 3 neuroendocrine tumors have a lower Ki-67 proliferation index and tumor mutational burden compared to NECs. Distinct gene mutations and pathways have been identified in G3-NETs and NECs, offering potential for developing a diagnostic gene panel. The 2022 WHO classification recognizes the use of immunohistochemistry for somatostatin receptors 2/5, TP53, Rb, Menin, P27, ATRX, and DAXX to distinguish G3-NETs and NECs. In particular, TP53 and ATRX immunohistochemistry may be useful in routine diagnostics.</p><p><strong>Conclusions: </strong>Specific immunohistochemistry and genetic tests should be developed and incorporated into the classification to reliably distinguish G3-NETs from NECs.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"804-814"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555530","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}
Natasha Hunter, Lisa Han, Haley Corbin, Eric Q Konnick, William R Gwin, Shaveta Vinayak, Hannah Linden, William Audeh, Lavanya Samraj, Andrea R Menicucci, T Rinda Soong
{"title":"Clinicopathologic and molecular characterization of low-grade, early-stage, and HER2-positive invasive breast carcinoma.","authors":"Natasha Hunter, Lisa Han, Haley Corbin, Eric Q Konnick, William R Gwin, Shaveta Vinayak, Hannah Linden, William Audeh, Lavanya Samraj, Andrea R Menicucci, T Rinda Soong","doi":"10.1093/ajcp/aqaf010","DOIUrl":"10.1093/ajcp/aqaf010","url":null,"abstract":"<p><strong>Objectives: </strong>Breast carcinomas overexpressing human epidermal growth factor receptor 2 (HER2) are typically associated with higher tumor grade and faster progression. HER2 positivity is rare in low-grade breast carcinomas with unclear biological implications. We aimed to characterize their clinicopathologic and molecular profiles in this study.</p><p><strong>Methods: </strong>There were 2 cohorts of Nottingham grade 1, HER2-positive invasive breast carcinomas examined: (1) an institutional series (n = 14) and (2) tumors from patients (n = 59) enrolled in the FLEX multicenter clinical registry with MammaPrint and BluePrint profiling.</p><p><strong>Results: </strong>Most (79%) in the case series were both estrogen receptor (ER) and progesterone receptor (PR)-positive. Over half were pathologic or clinical T1N0 tumors. In the 9 cases with adequate material for next-generation sequencing, the majority (66%) demonstrated ERBB2 copy number variations. Most (66%) received HER2-targeted therapy. No recurrences were observed, with a median follow-up time of 43 months. In the FLEX cohort, most tumors were ER-positive (86%) and PR-positive (68%), and over half were clinical T1. Most (70%) were of the luminal phenotype, and over half (54%) were low-risk on MammaPrint.</p><p><strong>Conclusions: </strong>Low-grade HER2-positive breast carcinomas constitute mostly low-stage, luminal-type, and apparently low-risk tumors, warranting investigation into whether therapy de-escalation could achieve favorable outcomes with less toxicity in this population.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"854-865"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565766","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}
Hamilton C Tsang, Ryan J Morse, Jing Zhang, Tho Bui, Brooke Emrich, Rida A Hasan, Joshua A Lieberman
{"title":"The clinical pathology laboratory in 360° virtual reality.","authors":"Hamilton C Tsang, Ryan J Morse, Jing Zhang, Tho Bui, Brooke Emrich, Rida A Hasan, Joshua A Lieberman","doi":"10.1093/ajcp/aqaf031","DOIUrl":"10.1093/ajcp/aqaf031","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to enhance medical education by integrating virtual reality (VR) tours into the clinical pathology curriculum, comparing VR with traditional didactic methods.</p><p><strong>Methods: </strong>Seven 360° VR tours were developed for the Microbiology and Transfusion Services laboratories. A controlled crossover study involved 171 medical students (83% MS4) from April 2021 to April 2023. Students were randomly assigned to either the VR or PowerPoint (PP) presentation groups. Surveys and assessments measured understanding, interactivity, relevance, and engagement.</p><p><strong>Results: </strong>With more than a 90% response rate, VR participants rated the interactivity significantly higher than PP participants (mean, 4.48 vs 3.48; P < .001). The VR format also showed higher scores for understanding the laboratory environment (mean, 4.38; P = .6) and engagement (mean, 4.21; P = .004). Although assessment scores were slightly lower for VR participants (6.2 vs 6.5; P = .1), the VR tours increased engagement and provided a more interactive learning experience.</p><p><strong>Conclusions: </strong>Integrating 360° VR tours into the clinical pathology curriculum enhances interactivity and learner engagement, offering a scalable solution for remote learning. This method addresses the limitations of traditional remote learning, promoting a more immersive educational experience.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"936-946"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957816","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}
Ming-Tseh Lin, Eric S Christenson, Aparna Pallavajjala, James R Eshleman
{"title":"Highly sensitive and specific markers for detection of mismatch repair deficiency by next-generation sequencing.","authors":"Ming-Tseh Lin, Eric S Christenson, Aparna Pallavajjala, James R Eshleman","doi":"10.1093/ajcp/aqaf026","DOIUrl":"10.1093/ajcp/aqaf026","url":null,"abstract":"<p><strong>Objective: </strong>To identify exonic markers that could improve analytic performance characteristics of next-generation sequencing (NGS) in detecting mismatch repair deficiency (dMMR) using colorectal cancer (CRC) as a model.</p><p><strong>Methods: </strong>Coding sequences of a target NGS panel (~1.13 megabase) were compared between dMMR CRC and mismatch repair-proficient (pMMR) CRC in a training cohort (41 dMMR CRCs and 213 pMMR CRCs) and a validation cohort (33 dMMR CRCs and 307 pMMR CRCs) with documented mismatch repair status by immunohistochemical and/or microsatellite instability assays.</p><p><strong>Results: </strong>The dMMR CRC cases showed significantly higher insertion/deletion (indel) mutations within exonic homopolymers (homo-indels), occurring predominantly within longer repeats of 5 to 10 nucleotides (92%, P < .0001), rather than shorter repeats of 2 to 4 nucleotides seen in pMMR CRC (62%). Homo-indels in dMMR CRC were not random. Hotspot loci were consistent between the training and validation cohorts. The dMMR defined by indels within homopolymers of 5 or more nucleotides, homopolymers of 7 or more nucleotides, or a panel of hotspots all showed 100% sensitivity and specificity with a range of cutoffs.</p><p><strong>Conclusions: </strong>We propose that this approach allows one to identify highly sensitive and specific markers for detecting dMMR CRC by NGS alone. Further studies are warranted to test whether these markers are applicable to non-CRC neoplasms.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"909-919"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965266","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}
Jae Won Lee, Suk Won Seo, Yousun Chung, Hyungsuk Kim, Sang-Hyun Hwang, Heung-Beom Oh, Han Joo Kim, Dae-Hyun Ko
{"title":"Quality control and maintenance of intraoperative cell salvage instruments.","authors":"Jae Won Lee, Suk Won Seo, Yousun Chung, Hyungsuk Kim, Sang-Hyun Hwang, Heung-Beom Oh, Han Joo Kim, Dae-Hyun Ko","doi":"10.1093/ajcp/aqaf027","DOIUrl":"10.1093/ajcp/aqaf027","url":null,"abstract":"<p><strong>Objectives: </strong>Intraoperative cell salvage (ICS) is broadly used in high-risk surgical procedures to facilitate rapid autologous red blood cell transfusion, minimizing the need for allogeneic blood and its associated risks. However, standardized guidelines are lacking for the quality control of ICS devices.</p><p><strong>Methods: </strong>We retrospectively assessed biannual quality control tests performed on 8 ICS devices at our institution between 2017 and 2023. The quality control assessments included visual inspection for hemolysis, albumin levels, potassium (K+) levels, and free hemoglobin levels, as well as microbial cultures.</p><p><strong>Results: </strong>Among 90 quality control tests, albumin and K+ levels were consistently within acceptable ranges. However, visual inspections revealed 14 and 20 instances of unacceptable hemolysis and free hemoglobin levels, respectively. Two devices exhibited higher frequencies of these unacceptable outcomes. Most microbial cultures identified contaminants, with Klebsiella pneumoniae being the only notable pathogen. Follow-up simulations demonstrated acceptable performance, indicating equipment reliability.</p><p><strong>Conclusions: </strong>Our findings highlight the need for standardized quality control protocols for ICS devices. Although current guidelines are limited, our biannual quality control standard is both practical and effective. We hope our findings provide a framework for other institutions aiming to optimize ICS device performance.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"920-925"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959952","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}
Diyna Altrmanini, Ibrahim Hassan, Andrés Pérez-López, Mohammed Suleiman
{"title":"Implementing AI in clinical microbiology: Key challenges ahead.","authors":"Diyna Altrmanini, Ibrahim Hassan, Andrés Pérez-López, Mohammed Suleiman","doi":"10.1093/ajcp/aqaf003","DOIUrl":"10.1093/ajcp/aqaf003","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"947"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472095","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}
Yembur Ahmad, Kwabena A N Sarpong, Lois Y Bansah, Ruth Adafia, Felix Asare, Timothy K Amukele
{"title":"Feasibility and potential impact of a local proficiency testing program in Accra, Ghana.","authors":"Yembur Ahmad, Kwabena A N Sarpong, Lois Y Bansah, Ruth Adafia, Felix Asare, Timothy K Amukele","doi":"10.1093/ajcp/aqaf007","DOIUrl":"10.1093/ajcp/aqaf007","url":null,"abstract":"<p><strong>Objectives: </strong>To implement a pilot proficiency testing (PT) program in Accra, Ghana, using locally produced PT materials and to explore the relationship between laboratory test costs and laboratory quality in Accra, Ghana.</p><p><strong>Methods: </strong>Remnant serum samples from a local laboratory were pooled, aliquoted, and distributed to a convenience sample of 23 laboratories in Accra, Ghana, 2 of which had International Organization for Standardization (ISO) accreditation. One of the ISO-accredited laboratories was designated as the reference/target, and the range for passing was based on international criteria. Test cost, test results, and testing instruments used were compiled.</p><p><strong>Results: </strong>Of the 23 laboratories, 18 submitted results. Total testing costs ranged from 80 to 312 Ghanaian cedi (GH₵) (7-26 USD). Overall accuracy (pass rate) was calculated per laboratory and per analyte. The mean laboratory accuracy was 61% (15%-92%). The pass rate for individual analytes ranged from 18% to 94% (mean, 72%). There was no correlation between test cost and pass rate.</p><p><strong>Conclusions: </strong>The pass rates of clinical laboratories in Accra, Ghana, varied from 15% to 92%, and there was no relationship to test cost. A PT program to objectively evaluate each laboratory's performance is needed. Making the PT material locally, as in this study, is a financially sustainable approach.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"847-853"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389878","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}
Erin Graf, Amr Soliman, Mohamed Marouf, Anil V Parwani, Preeti Pancholi
{"title":"Reply to \"Implementing AI in clinical microbiology\": Key challenges ahead.","authors":"Erin Graf, Amr Soliman, Mohamed Marouf, Anil V Parwani, Preeti Pancholi","doi":"10.1093/ajcp/aqaf005","DOIUrl":"10.1093/ajcp/aqaf005","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"950"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472103","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}
Burak Tekin, John C Cheville, Fabrice Lucien, Michael McCarthy, Haidong Dong, Karla J Kopp, Nate R Torell, Roxane R Lavoie, Ava Farrell, Brandy L Jaszewski, Carin Y Smith, Sarah M Jenkins, Surendra Dasari, Santosh Menon, Rumeal D Whaley, Stephen A Boorjian, Lance C Pagliaro, Lori A Erickson, Ruifeng Guo, Sounak Gupta
{"title":"Biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and the immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma.","authors":"Burak Tekin, John C Cheville, Fabrice Lucien, Michael McCarthy, Haidong Dong, Karla J Kopp, Nate R Torell, Roxane R Lavoie, Ava Farrell, Brandy L Jaszewski, Carin Y Smith, Sarah M Jenkins, Surendra Dasari, Santosh Menon, Rumeal D Whaley, Stephen A Boorjian, Lance C Pagliaro, Lori A Erickson, Ruifeng Guo, Sounak Gupta","doi":"10.1093/ajcp/aqaf022","DOIUrl":"10.1093/ajcp/aqaf022","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to assess the expression of biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma (pSCC).</p><p><strong>Methods: </strong>Our archive was queried for patients who had a penectomy for pSCC between 2000 and 2022. Primary tumors were immunostained for B7-H3 and NKG7, while metastatic specimens were immunostained for TROP2 and nectin-4. Expression of PD-L1, TROP2, and nectin-4 in primary tumors was previously characterized. H-scores (0-300) were used to quantify expression. Associations between biomarkers, tumor-infiltrating lymphocytes (TILs), and clinicopathologic and outcome parameters were evaluated.</p><p><strong>Results: </strong>For both TROP2 and nectin-4, H-scores within the lymph node metastases were higher compared to those within the primary tumors (mean, 264.5 vs 244.8, P = .0003; mean, 170.6 vs 146.7, P = .05, respectively; 33 paired specimens). For B7-H3 (n = 107), 32.7% of the primary tumors had an H-score of more than 0. In 34.8% of the cases, NKG7 expression was observed in 25% to 50% of the TILs. A significant association was noted between TIL density, B7-H3, NKG7, and PD-L1 expression.</p><p><strong>Conclusions: </strong>Therapeutic strategies targeting TROP2 and nectin-4 hold promise for patients with advanced pSCC. The potential of PD-L1, B7-H3, and NKG7 for predicting response to immunomodulatory treatment warrants further research.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"898-908"},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958528","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}