American journal of clinical pathology最新文献

{"title":"Histologic assessment of response to intraocular injection of amphotericin B in advanced rhino-sino-orbital mucormycosis.","authors":"Arshi Tandon, Shilpi Thakur, Rachna Meel, Arulselvi Subramanian, Alok Thakar, Aanchal Kakkar","doi":"10.1093/ajcp/aqag040","DOIUrl":"10.1093/ajcp/aqag040","url":null,"abstract":"<p><strong>Objectives: </strong>Rhino-sino-orbital mucormycosis (RSOM) is a life-threatening, emergent medical and surgical condition with high mortality. Although direct intraorbital delivery methods of amphotericin B have been explored, clear guidelines for its administration and dosing are lacking. We conducted this prospective study to determine the role of intraorbital amphotericin B (IOAB) in the management of advanced RSOM and assessed histologic changes in response to IOAB administration.</p><p><strong>Methods: </strong>Patients with advanced orbital disease were offered treatment with IOAB before exenteration. Individuals who refused IOAB and underwent orbital exenteration made up a control group. Hematoxylin-eosin-stained slides of orbital exenterations were reviewed and representative whole slide images were captured. Areas of necrosis, inflammatory cell infiltrate, and fibrosis were annotated as indicators of tissue inflammatory response, quantified and estimated as a percentage of the total area of the tissue. A semiquantitative assessment of fungal load was conducted.</p><p><strong>Results: </strong>The control group (n = 9) showed statistically significantly greater mean area (P = .004) and percentage area (P = .002) of tissue destruction, angioinvasion (P = .02), and optic nerve invasion (57% vs 33%; P = .31) compared with the intervention group (n = 9). Fungal load was low in test cases but high in most of the control group (P = .15). Inflammation of ocular structures was absent in 5 test cases but present in all control group cases (P = .008).</p><p><strong>Conclusions: </strong>The considerably lower tissue destruction, fungal load, angioinvasion, and invasion of the optic nerve in orbital exenteration specimens following administration of IOAB indicates a promising role in the treatment of patients with RSOM and advanced involvement of the orbit.</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":"148283027","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":"Comprehensive multicriteria life cycle assessment of biopsy processing in a surgical pathology department.","authors":"Alexis Trecourt, Elise André, Charlotte Sierra, Anne Rullier, Cyprien Tilmant, Geneviève Belleannée, Marc Chiffoleau, Nazim Benzerdjeb, Marie Donzel, Benjamin De Sainte Marie, Lucie Gaillot-Durand","doi":"10.1093/ajcp/aqag074","DOIUrl":"10.1093/ajcp/aqag074","url":null,"abstract":"<p><strong>Objectives: </strong>While recent studies have estimated the carbon footprint of surgical pathology, they did not consider the many other impacts this activity has on the environment. We aimed to estimate the environmental impacts of the preparation of hematoxylin-phloxine-saffron (HPS) staining, Congo red (CR) staining, and immunofluorescence (IF) staining for a biopsy analysis.</p><p><strong>Methods: </strong>We used a comprehensive life cycle assessment methodology of 18 environmental indicators. Life cycle assessment is a standardized and robust method for comprehensively assessing the various environmental impacts of a process throughout its entire life cycle. All contributing items (eg, materials, reagents, electricity) within the different technical steps in the surgical pathology department were considered.</p><p><strong>Results: </strong>For the entire procedure (HPS + CR + IF), the electricity consumption of the cryostat for IF staining was the main contributing item for all indicators (from 19.4%-75.8%), except land use. The other most impactful contributing items were (1) single-use materials used during specimen grossing (second or third largest contributing item for 8 indicators), (2) electricity consumption during slide/block storage (second largest contributor for 6 indicators), (3) materials and consumables used during sample receipt (third largest contributor for 6 indicators), (4) materials used during cryostat section (third largest contributor for 6 indicators), and (5) reagents used during IF staining (second or third largest contributor for 5 indicators). Interestingly, for formalin fixation, the main environmental impacts were represented by global warming, fine particle matter formation, and human toxicity.</p><p><strong>Conclusions: </strong>These data allow us to better understand the environmental impacts of our activities and to propose more pertinent eco-design solutions.</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":"148343792","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":"Flow cytometric quantitation of CD34+ progenitors in peripheral blood: an adjunct tool for diagnostic evaluation of pancytopenia.","authors":"Lauren Reiman, My H Vu, Michael Cortez-Bacolot, Brent L Wood, Alexandra E Kovach","doi":"10.1093/ajcp/aqag058","DOIUrl":"10.1093/ajcp/aqag058","url":null,"abstract":"<p><strong>Objectives: </strong>In healthy individuals, CD34+ stem cells are detectable in peripheral blood in relatively low and stable numbers. The clinical utility of peripheral blood CD34+ stem cell quantitation in the evaluation of pancytopenia has not been systematically studied.</p><p><strong>Methods: </strong>We used a large archival clinical cohort (n = 154) of pediatric patients from our pediatric-only institution without a history of hematologic disorder or circulating blasts on morphology who underwent peripheral blood flow cytometric screening for any reason. Circulating CD34+ stem cells and total progenitors were quantified and correlated with clinical characteristics and outcomes.</p><p><strong>Results: </strong>Patients ultimately diagnosed with aplastic anemia (n = 15) showed significantly decreased circulating progenitors compared with those with cytopenias of alternative causes, whereas patients with infectious, inflammatory, or other presumed reactive conditions often demonstrated larger CD34+ progenitor populations, consistent with preserved or responsive marrow function. Using receiver operating characteristic analysis, the optimal cutoff for %CD34+ progenitors was 0.0124%, which was rounded to 0.01% for clinical interpretability.</p><p><strong>Conclusions: </strong>These findings support the potential clinical utility of peripheral blood CD34+ quantitation in the diagnostic workup of pediatric pancytopenia.</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":"148269922","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":"MYC gene amplification drives protein overexpression and its clinical prognostic value in prostate cancer: a study of 152 Chinese cases.","authors":"Mei Tang, Chunyan Xie, Rongfei Huang, Chuanfen Lei, Xianjing Yu, Ping Zhou","doi":"10.1093/ajcp/aqag059","DOIUrl":"10.1093/ajcp/aqag059","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the expression patterns of ERG, PTEN, and c-Myc proteins in prostate adenocarcinoma; analyze the status of the MYC gene; and evaluate their correlations with clinicopathologic parameters and patient prognosis.</p><p><strong>Methods: </strong>In this retrospective study, 152 prostate adenocarcinoma cases were analyzed. Immunohistochemistry was performed for ERG, PTEN, and c-Myc protein expression. Fluorescence in situ hybridization was used to assess ERG rearrangement, MYC gene breakage, and amplification. Statistical analyses were conducted to evaluate associations between molecular markers and clinicopathologic variables, as well as their impact on survival outcomes.</p><p><strong>Results: </strong>The positive expression rates for ERG, PTEN, and c-Myc high expression (immunoreactive score ≥5) were 9.9%, 86.8%, and 50%, respectively. The detection rate of MYC gene amplification was 27.6%. Both c-Myc high expression and MYC gene amplification were significantly associated with the high-grade group (defined as Grade Group ≥3 and/or with cribriform pattern), lymphovascular invasion, advanced T stage, metastasis, and poor prognosis, with gene amplification demonstrating higher prognostic specificity. ERG protein expression was significantly correlated with PTEN positivity, whereas no significant association was found between MYC gene amplification and ERG protein expression; only a nonsignificant mutually exclusive trend was observed.</p><p><strong>Conclusions: </strong>c-Myc activation, particularly MYC gene amplification, is a key driver and specific biomarker for an aggressive phenotype and poor prognosis in prostate adenocarcinoma. Combined detection of ERG, PTEN, and c-Myc status contributes to refining risk stratification systems. The lack of significant association between MYC amplification and ERG expression suggests they may represent distinct oncogenic pathways, warranting further validation in large prospective studies.</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":"148269992","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":"Impact of tumor budding on recurrence risk prediction in stage I-III colorectal cancer: a Swedish cohort study.","authors":"Shabane Barot, Mikael Andersson-Franko, Sam Ghazi, Ulrik Lindforss, Petri Rantanen, Johannes Blom, Annika Lindblom, Annelie Liljegren","doi":"10.1093/ajcp/aqag057","DOIUrl":"10.1093/ajcp/aqag057","url":null,"abstract":"<p><strong>Objectives: </strong>Tumor budding is an emerging micromorphologic predictor of recurrence in localized colorectal cancer (CRC). Whether its addition to established CRC recurrence risk factors routinely assessed in clinical practice improves prediction accuracy remains unclear.</p><p><strong>Methods: </strong>This study included patients with stage I through III CRC. A detailed micromorphologic assessment was performed for each case according to protocol, using hematoxylin-eosin-stained slides. Clinical characteristics, including treatment and follow-up data, were extracted from patient records. Two logistic regression models were devised to assess recurrence risk, both including established recurrence risk factors chosen a priori. One model also included tumor budding as a dichotomous variable. Receiver operating characteristic curves were used to evaluate and compare the prognostic performance of each model.</p><p><strong>Results: </strong>Of the 1083 cases of CRC included in the study, 441 (41%) displayed tumor budding. Tumor budding was more common in right-sided colon cancer, following a right-to-left gradient in the bowel. It occurred more frequently in patients with adverse prognostic factors and in patients presenting with surgical emergencies necessitating emergency resection. Median follow-up time was 4.3 years. Tumor budding was strongly associated with disease recurrence in univariate analysis, but the association was not maintained in multivariate analysis. There was no statistically significant difference between the areas under the curve of the 2 models.</p><p><strong>Conclusions: </strong>Tumor budding did not substantially contribute to recurrence risk prediction in this study. Further research exploring the association between tumor budding, established recurrence risk factors, and CRC prognosis is warranted.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215948","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":"Diagnostic challenges in pathologic staging of renal cell carcinoma following systemic immunotherapy.","authors":"Christina A Hansen, Tracy L Rose, Sara E Wobker","doi":"10.1093/ajcp/aqag047","DOIUrl":"10.1093/ajcp/aqag047","url":null,"abstract":"<p><strong>Objectives: </strong>Immune checkpoint inhibitors (ICIs) are increasingly used prior to surgical resection of clear cell renal cell carcinoma (RCC) and can produce varied histologic response patterns, including complete tumor regression. Response to treatment can mimic or obscure residual tumor, leading to diagnostic pitfalls that are not well characterized in the RCC literature.</p><p><strong>Methods: </strong>A retrospective search was performed to identify cases of clear cell RCC treated with preoperative ICIs at our institution. Pathology reports and slides were reviewed by a fellowship-trained genitourinary pathologist. Clinicopathologic, radiographic, gross, and microscopic features were assessed, including treatment-related histologic changes.</p><p><strong>Results: </strong>A total of 13 clear cell RCC cases treated with ICI before nephrectomy were identified. Three cases demonstrated no residual carcinoma (ypT0). Histologic features after ICI therapy included fibrosis, myxoid change, and histiocytes, often hemosiderin laden. Foamy histiocytes often mimicked clear cell RCC tumor cells, including 9 cases classified as \"moderate\" or \"difficult\" to distinguish and necessitating immunohistochemistry in 5 cases. Resected lymph nodes (n = 8) showed similar features of treatment effect. One lymph node resection demonstrated extensive well-formed granulomas mimicking sarcoidosis.</p><p><strong>Conclusions: </strong>Recognition of the varied histologic features seen after ICI treatment is critical for accurate pathologic staging. Consensus guidelines for gross and microscopic examination in this setting have not yet been determined but should consider the specific pathologic changes associated with ICI therapy.</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":"148196581","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":"Utility of ultrasensitive, US Food and Drug Administration-approved κ and λ dual in situ hybridization assay in the diagnosis of Hodgkin lymphomas.","authors":"Mohamed Eltahir, Kelly Young, Sheren Younes, Shuchun Zhao, Oscar Silva, Yasodha Natkunam","doi":"10.1093/ajcp/aqag043","DOIUrl":"10.1093/ajcp/aqag043","url":null,"abstract":"<p><strong>Objectives: </strong>Determination of B-cell clonality in formalin-fixed, paraffin-embedded tissues is challenging, especially in cases where tumor B cells are sparse. Flow cytometry is of limited utility in Hodgkin lymphomas, at least in part due to the rarity and fragility of the malignant cells.</p><p><strong>Methods: </strong>We used a recently US Food and Drug Administration-approved, ultrasensitive κ and λ dual in situ hybridization assay (K/L dual ISH; Roche/Ventana Medical Systems) to evaluate B-cell clonality in 184 classic Hodgkin lymphomas (CHLs) and 113 nodular lymphocyte-predominant Hodgkin lymphomas (NLPHLs).</p><p><strong>Results: </strong>Five CHLs and 11 NLPHLs were not scorable due to preanalytical variables. Of the 179 scorable CHL cases, none showed light chain messenger RNA expression in the Hodgkin/Reed-Sternberg cells, whereas 89% of NLPHLs (91/102) exhibited light chain expression in lymphocyte-predominant (LP) cells. Among NLPHLs, 66% (68/102) showed κ restriction, 20% (21/102) showed λ restriction, and 1.9% (2/102) showed dual κ and λ expression in the LP cells. There was no appreciable light chain expression in 10% (11/102) of cases.</p><p><strong>Conclusions: </strong>Although morphology and immunohistochemistry are usually sufficient to separate CHL from NLPHL, determining light chain restriction by K/L dual ISH could provide a valuable adjunct in challenging cases, potentially improving diagnostic accuracy and patient outcomes.</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":"148196863","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":"Dissecting the direct antiglobulin test in warm autoimmune hemolytic anemia: clinical and laboratory correlations.","authors":"Douglas P Blackall, Stacy K Lewis","doi":"10.1093/ajcp/aqag071","DOIUrl":"10.1093/ajcp/aqag071","url":null,"abstract":"<p><strong>Objectives: </strong>The direct antiglobulin test (DAT) is critical in determining whether a patient has an immune-mediated hemolytic process, but the appropriate interpretation of this test requires a nuanced understanding of what it measures, how it is performed, and how it is reported by the clinical laboratory.</p><p><strong>Methods: </strong>To avoid diagnostic errors, the DAT must not be viewed in isolation. Instead, it should be assessed in combination with other blood bank testing, hemolytic laboratory testing, and patients' clinical condition. In this way, accurate diagnosis of an immune-mediated hemolytic process can ensue, including the diagnosis of warm autoimmune hemolytic anemia.</p><p><strong>Results: </strong>This review sheds light on 2 scenarios that require an enhanced understanding of the DAT: (1) the DAT as a marker for warm autoimmune hemolytic anemia and (2) the DAT in cases of so-called \"Coombs'-negative\" or DAT-negative hemolytic anemia.</p><p><strong>Conclusions: </strong>A more comprehensive view of the DAT, including its diagnostic strengths and weaknesses, will reduce the risk of overcalling autoimmune hemolysis in patients with positive DATs and undercalling autoimmune hemolysis in patients with negative testing.</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":"148248786","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":"Mutation-specific NPM1 immunohistochemistry is a sensitive method for detecting residual disease in mid- and postinduction bone marrows: comparison of NPM1 immunohistochemistry, NPM1 real-time polymerase chain reaction, and flow cytometric studies.","authors":"Ellie Hong, Nathanael G Bailey, Katelynn E Davis, Nana P Matsumoto, Erika M Moore, Bryan Rea, Nidhi Aggarwal, Sara A Monaghan, Majd Jawad","doi":"10.1093/ajcp/aqag062","DOIUrl":"10.1093/ajcp/aqag062","url":null,"abstract":"<p><strong>Objectives: </strong>Per National Comprehensive Cancer Network guidelines for acute myeloid leukemia (AML), bone marrow (BM) evaluation is recommended after starting induction chemotherapy at 14 to 21 days (mid-induction) and 30 to 35 days (postinduction). Timely assessment of residual morphologic and molecular disease is challenging at these time points, given the low cellularity, the lack of CD34 or CD117 expression by blasts in most NPM1-mutated (NPM1mut) AML, and the longer turnaround time for molecular testing.</p><p><strong>Methods: </strong>NPM1 mut AML undergoing BM evaluation at mid- and postinduction with concurrent flow cytometry and NPM1 real-time polymerase chain reaction or next-generation sequencing was evaluated. Different cell types positive by NPM1 immunohistochemistry (IHC) were enumerated, and the results were compared with flow cytometry and molecular findings.</p><p><strong>Results: </strong>NPM1 IHC demonstrated a sensitivity of 78% and 41% for detecting residual mutation at mid- and postinduction, respectively, with a positive predictive value ranging from 88% to 100%. Of 16 IHC-negative cases, 3 had no residual NPM1 mutation, 12 had very low-level mutation at a variant allele frequency of less than or equal to 21 transcripts, and only 1 had a high-level mutation in a markedly hypocellular BM. Of 24 IHC-positive cases, 22 had residual NPM1 mutation, and 2 showed false-positive staining in only a single cell with no residual NPM1 mutation. The level of IHC staining was mostly proportional to the level of residual mutation.</p><p><strong>Conclusions: </strong>Mutation-specific NPM1 IHC is a valuable tool for a rapid assessment of residual morphologic and molecular disease in mid- and postinduction NPM1mut AML.</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":"148269933","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":"Mismatch repair protein \"nonclassic expression loss\" pattern in colorectal cancer: an important staining pattern that is not well understood.","authors":"Jinchuan Yu, Xuexue Xiao, Weiying He, Yanan Yang, Junqiu Yue","doi":"10.1093/ajcp/aqag070","DOIUrl":"10.1093/ajcp/aqag070","url":null,"abstract":"<p><strong>Objectives: </strong>The expression of mismatch repair (MMR) proteins does not follow a simple \"intact\" or \"loss\" pattern. Rather, \"nonclassic loss\" patterns can be presented.</p><p><strong>Methods: </strong>We retrospectively collected data on 569 patients with colorectal cancer. According to the MMR protein expression patterns of intact expression (pattern A), complete absence (pattern B), regional/patchy loss of 10% or more tumor cells (pattern C), and positive signals of 10% or more tumor cells weaker than control cells (pattern D), the patients were divided into 3 groups: MMR proficiency (all 3 MMR proteins were pattern A), classic MMR deficiency (proteins exhibiting pattern B), and nonclassic possible MMR deficiency (regardless of the presence or absence of pattern B, with at least 1 protein exhibiting pattern C or D).</p><p><strong>Results: </strong>Patients with both complete and nonclassic loss patterns had microsatellite instability high status (17/17 [100.00%]); 64.71% (11/17) had MLH1/PMS2 co-complete loss combined with MSH6 regional loss. Microdissection of the MSH6 loss region and next-generation sequencing detection were performed, and pathogenic mutations were found in 6 patients (6/7 [85.71%]), 83.33% of whom had somatic mutations in the MSH6 gene. Among the 26 patients with only a nonclassic loss pattern, 8 (30.77%) had microsatellite instability high status, of whom 7 (26.92%) had MMR gene mutations and 3.85% probably had pathogenic germline heterozygous mutations.</p><p><strong>Conclusions: </strong>Microsatellite instability high status (30.77%) and Lynch syndrome (3.85%) can occur in patients with only nonclassic loss of MMR proteins (without the B pattern). It is necessary to deepen our understanding of nonclassical MMR expression patterns to avoid missing patients with microsatellite instability high status and Lynch syndrome.</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":"148293016","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}