Modern Pathology最新文献

{"title":"International Expert Consensus Recommendations for HER2 Reporting in Breast Cancer: Focus on HER2-Low and Ultralow Categories","authors":"Emad A. Rakha ,&nbsp;Puay Hoon Tan ,&nbsp;Mieke R. Van Bockstal ,&nbsp;Kimberly H. Allison ,&nbsp;Edi Brogi ,&nbsp;Grace Callagy ,&nbsp;Gábor Cserni ,&nbsp;Shabnam Jaffer ,&nbsp;Maria Pia Foschini ,&nbsp;Helenice Gobbi ,&nbsp;Janina Kulka ,&nbsp;Xiaoxian Li ,&nbsp;Elena Provenzano ,&nbsp;Abeer M. Shaaban ,&nbsp;Gary M. Tse ,&nbsp;Zsuzsanna Varga ,&nbsp;Anne Vincent-Salomon ,&nbsp;Rin Yamaguchi ,&nbsp;Wentao Yang ,&nbsp;Soha ElSheikh ,&nbsp;Cecily Quinn","doi":"10.1016/j.modpat.2025.100925","DOIUrl":"10.1016/j.modpat.2025.100925","url":null,"abstract":"<div><div>The concept of “HER2-negative” breast cancer is evolving, with the recognition of HER2-low and HER2-ultralow subsets. These subsets are clinically relevant regarding treatment with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd), which has shown survival benefit in patients with metastatic carcinoma with minimal HER2 protein expression that lack <em>HER2</em> gene amplification by in situ hybridization. In clinical trials using T-DXd, HER2-low was defined as an immunohistochemistry (IHC) score 1+ or an IHC score 2+ without <em>HER2</em> gene amplification. HER2-ultralow was defined as faint or barely perceptible, incomplete membrane staining in &gt;0% to ≤10% of tumor cells (IHC score 0+/with membrane staining) and HER2-null as the complete absence of staining (IHC score 0/absent membrane staining). These results now necessitate more detailed evaluation and reporting of traditional “HER2-negative” results to identify patients with metastatic breast cancer who may benefit from T-DXd therapy. Both the US Food and Drug Administration and the European Medicines Agency have extended the regulatory approval of T-DXd to patients with metastatic breast cancer showing HER2-low or HER2-ultralow expressions. Updated clinical management guidelines now, therefore, incorporate the spectrum of HER2 results into treatment selection algorithms in the metastatic setting. To align histopathologic practice with these developments, the College of American Pathologists has issued a new biomarker-reporting template that recommends explicit distinction between IHC 0/absent membrane staining and IHC 0+/with membrane staining. Key concerns among pathologists include assay variability, scoring reproducibility, and quality assurance standards for accurately detecting such low levels of HER2 expression. This manuscript provides expert consensus, evidence-based practical recommendations for identifying and reporting tumors with HER2-low and HER2-ultralow expression. We emphasize standardized testing protocols, validated assays, robust internal and external controls, and focused training for pathologists. A universal structured pathology report is proposed to highlight the accurate distinction between IHC 0 (null), IHC 0+ (ultralow), and HER2-low expressions.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100925"},"PeriodicalIF":5.5,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Deposits in Colorectal Cancer: Definitions for Ninth Edition of the Tumor Node Metastasis Staging System","authors":"Iris D. Nagtegaal ,&nbsp;Kay Washington ,&nbsp;James D. Brierley ,&nbsp;George J. Chang ,&nbsp;Richard M. Goldberg ,&nbsp;Qian Shi ,&nbsp;Sanjay Kakar ,&nbsp;Heidi Kaur","doi":"10.1016/j.modpat.2025.100924","DOIUrl":"10.1016/j.modpat.2025.100924","url":null,"abstract":"<div><div>Tumor deposits (TDs) have been a contentious element of the tumor node metastasis staging system for colorectal cancer since their introduction in 1997. Classified within the nodal category, their definition has changed repeatedly due to unclear distinctions from lymph node metastases, extramural vascular invasion, and perineural invasion. Despite updates in the tumor node metastasis system eight edition, ambiguity remains, with current criteria relying heavily on pathologist discretion. The fact that TDs are among the most powerful prognostic indicators warrants standardization, based on scientific evidence. A Delphi consensus among expert pathologists confirmed the lack of specificity and reproducibility in the current definition. In response, a new definition was developed, identifying TDs as discrete tumor nodules in pericolic or perirectal fat, distinct from lymph nodes, extramural vascular invasion, or perineural invasion but possibly originating from them. This definition emphasizes the need to report TDs separately when there is unequivocal tumor extension in relation to vessels or nerves. Size and distance from the primary tumor are debated as potential criteria, although they are not part of the proposed definition. The new definition is a first step to incorporate a more robust, biologically relevant definition of TDs into cancer staging.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100924"},"PeriodicalIF":5.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Artificial Intelligence Model to Aid in Measurement of Invasion, Comprehensive Histologic Subtyping, and Grading of Pulmonary Adenocarcinoma","authors":"Jennifer M. Boland ,&nbsp;Lucas Stetzik ,&nbsp;Anja C. Roden ,&nbsp;Joseph J. Maleszewski ,&nbsp;Sarah M. Jenkins ,&nbsp;Trynda N. Kroneman ,&nbsp;Eunhee S. Yi ,&nbsp;Ying-Chun Lo ,&nbsp;Marie Christine Aubry","doi":"10.1016/j.modpat.2025.100923","DOIUrl":"10.1016/j.modpat.2025.100923","url":null,"abstract":"<div><div>The World Health Organization classification of pulmonary adenocarcinoma is complex, posing challenges for pathological reporting. Key difficulties include assessing invasive size in lepidic-predominant tumors and performing comprehensive histologic subtyping. Although these evaluations inform tumor stage, grade, and prognosis, they are time consuming and subjective, leading to interobserver variability. Artificial intelligence (AI) may help streamline these tasks and improve consistency. One representative hematoxylin and eosin slide was selected from each of 100 resected pulmonary adenocarcinomas, which were divided into training (n = 35) and validation (n = 65) sets. Slides were scanned and uploaded to Aiforia for AI model creation. Annotations were completed on the training set by 6 expert pulmonary pathologists and used to train a nested AI model, which was used to evaluate whole slide images of the training and validation sets. Manual assessment of tumor size, invasive size, and comprehensive histologic subtyping was performed by 3 pulmonary pathologists. In both the training and validation sets, the mean and median difference between manual and AI estimations of tumor size was ≤1.3 mm and invasive size was ≤3 mm. The median and mean differences in invasive percentage were ≤15.3% in both the training and validation sets for all patterns except for acinar and lepidic. However, ranges were wide, indicating examples with substantial disagreement. Predominant pattern agreement between AI and each observer ranged from 65.7% to 71.4% in the training set and 45.3% to 54.7% in the validation set. Agreement in grade ranged from 77.1% to 88.6% in the training set and 62.5% to 67.2% in the validation set. There was moderate agreement in grade between the 3 pathologists in the training set and moderate to substantial agreement between AI and each observer. In the validation set, there was substantial agreement in grade between the 3 pathologists and moderate agreement between AI and each observer. Although the AI model shows promise and warrants further refinement, manual pathologist review and potential revision of AI assessments are necessary to ensure the diagnostic accuracy needed for clinical use because disagreement clearly occurs.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100923"},"PeriodicalIF":5.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Clinicopathologic Spectrum of EWSR1::SSX-Rearranged Sarcomas: Series of 11 Cases Including Osteosarcomas and a Novel EWSR1::SSX4 Fusion","authors":"John M. Gross ,&nbsp;David I. Suster ,&nbsp;Ying Zou ,&nbsp;Douglas A. Mata ,&nbsp;Fernanda Amary ,&nbsp;Solange De Noon ,&nbsp;Adrienne M. Flanagan ,&nbsp;Kristina M. Wakeman ,&nbsp;Sintawat Wangsiricharoen ,&nbsp;Fei Dong ,&nbsp;Suk Wai Lam ,&nbsp;Judith V.M.G. Bovée ,&nbsp;Aline Baltres ,&nbsp;Daniel Pissaloux ,&nbsp;Eric Pasmant ,&nbsp;Frédérique Larousserie ,&nbsp;Markku Miettinen ,&nbsp;Meera Hameed ,&nbsp;Gregory W. Charville","doi":"10.1016/j.modpat.2025.100922","DOIUrl":"10.1016/j.modpat.2025.100922","url":null,"abstract":"<div><div>Gene rearrangements involving <em>EWSR1</em> or <em>SSX</em> genes are known to play a role in sarcomagenesis; however, sarcomas harboring <em>EWSR1</em>::<em>SSX</em> fusions are rare. To better understand tumors associated with this distinctive genetic event, we studied 11 additional <em>EWSR1::SSX</em> sarcomas, affecting 10 women and 1 man with an average age of 46 years (range, 22-72 years). Eight tumors arose in the bone (rib, femur, pelvis, or vertebra with multifocal bone involvement at presentation in 3 cases); 2 tumors arose in soft tissue (deep thigh or groin); and 1 patient presented with a visceral (lung) mass. The tumors were bulky, averaging 12.1 cm (range, 4-20 cm). Histologically, in keeping with a translocation-driven sarcoma, all tumors were cytologically monotonous. Seven tumors were osteosarcomas, 6 of which were classified as sclerosing osteosarcomas with extensive bone matrix production. Three tumors were composed of uniform fascicles of spindle cells, punctuated in 2 cases by a biphasic glandular or nested epithelioid component, reminiscent of synovial sarcoma. One tumor was an undifferentiated sarcoma with round to spindle cell cytomorphology and focal osteogenic differentiation. By immunohistochemistry, 5 of 5 cases tested were positive for SSX C-terminus; 1 of 5 showed patchy weak staining with SS18::SSX fusion-specific antibody. All tested tumors were positive for CD99 (4/4) and TLE1 (3/3). Next-generation sequencing identified <em>EWSR1</em>::<em>SSX</em> fusions in all cases, involving <em>SSX1</em> (n = 7), <em>SSX2</em> (n = 2), and <em>SSX3</em> (n = 1), along with a novel <em>EWSR1</em>::<em>SSX4</em> fusion. Follow-up was available for 9 patients; 5 patients died of disease 1.5 to 14 years (average, 6 years) after diagnosis, 2 patients were alive with metastatic disease, 1 patient was alive without disease at 25 months, and 1 patient presented recently. Sarcomas with <em>EWSR1::SSX</em> fusions are rare and clinically aggressive; the histologic patterns in this series and in prior reports are heterogeneous, consisting of essentially 3 phenotypes: (1) primitive round or epithelioid cells, (2) osteoblasts that produce bone, or (3) uniform small spindle cells arranged in tight fascicles, sometimes with a biphasic epithelioid component, as seen in synovial sarcoma. By studying 11 additional examples of these rare sarcomas, we provide an expanded view of their clinicopathologic and molecular genetic spectrum.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100922"},"PeriodicalIF":5.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational Signature in Cancers Following Solid Organ or Allogeneic Stem Cell Transplantation","authors":"Igor Odintsov ,&nbsp;Stephanie E. Siegmund ,&nbsp;Navin R. Mahadevan ,&nbsp;Alanna J. Church ,&nbsp;Lynette M. Sholl ,&nbsp;Jonathan A. Nowak","doi":"10.1016/j.modpat.2025.100921","DOIUrl":"10.1016/j.modpat.2025.100921","url":null,"abstract":"<div><div>Transplant recipients are at a heightened risk of cancer, yet the full spectrum of etiologic factors is poorly understood. In this study, we analysed the mutational patterns in a clinically diverse cohort of 41,874 cancers and identified a mutational signature highly associated with a history of solid organ or allogeneic stem cell transplantation. This signature is characterized by a high tumor mutation burden and a striking predominance of C&gt;A single base substitutions, particularly in the 5′-C[C&gt;A]A-3′ trinucleotide context. We identified 13 transplant recipients whose tumors harbored this signature, which is distinct from previously described mutational processes, including those related to tobacco, defective DNA repair, or polymerase mutations. The discovery of this signature points to a mutagenic force in this vulnerable patient group and provides new insights into the pathogenesis of transplant-associated malignancies.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100921"},"PeriodicalIF":5.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Molecular Characterization of Adenoid Ameloblastoma by Assessing a Panel of Oncogenes and Tumor Suppressor Genes","authors":"Ygor G. Fonseca ,&nbsp;Victor C. Bastos ,&nbsp;Rennan G. Moreira ,&nbsp;Felipe P. Fonseca ,&nbsp;Pablo A. Vargas ,&nbsp;John M. Wright ,&nbsp;Renato S. Aguiar ,&nbsp;Edward W. Odell ,&nbsp;Ricardo S. Gomez ,&nbsp;Letícia M. Guimarães ,&nbsp;Carolina C. Gomes","doi":"10.1016/j.modpat.2025.100920","DOIUrl":"10.1016/j.modpat.2025.100920","url":null,"abstract":"<div><div>Adenoid ameloblastoma (AA) is a rare epithelial odontogenic tumor microscopically characterized by ameloblastoma-like epithelium, duct-like structures, epithelial whorls, cribriform architecture, and dentinoid matrix. Wnt/β-catenin activation, usually by <em>CTNNB1</em> mutations, is thought to characterize AA, which are <em>BRAF</em> and <em>KRAS</em> wild type. The present study aimed to expand the genetic characterization of AA by interrogating variants at several sites known to be linked to solid tumor pathogenesis. Six AA samples were sequenced at an unprecedented sequencing depth using a 22-gene panel including oncogenes and tumor suppressor genes commonly mutated in solid human tumors, namely <em>AKT1, ALK, BRAF, CTNNB1, EGFR, ERBB2, ERBB3, ESR1, FOXL2, GNA11, GNAQ, IDH1, IDH2, KRAS, KIT, MET, NRAS, PDGFRA, PIK3CA, RAF1, RET</em>, and <em>TP53.</em> Reinforcing the distinct molecular identity of AA, absence of <em>BRAF</em> p.Val600Glu and <em>KRAS</em> p.Gly12Val/Arg mutations was observed. <em>CTNNB1</em> mutations were identified in 4 of 6 cases (67%), including previously reported variants (p.Ser33Cys and p.Gly34Arg) as well as novel ones (p.Leu31Leu and p.Gln68∗), supporting the involvement of the Wnt/β-catenin signaling pathway in AA pathogenesis. In 2 cases, <em>CTNNB1</em> variants co-occurred with either <em>TP53</em> or <em>ERBB2</em> and <em>PIK3CA</em> variants, suggesting potential secondary oncogenic events. Notably, in 2 cases, no variants were detected. Our findings provide further evidence for AA classification as a separate tumor entity. The identification of previously reported <em>CTNNB1</em> and novel genetic variants contributes to better characterization of the molecular profile of AA. Future studies are required to interrogate variants in other genes in wild-type cases.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100920"},"PeriodicalIF":5.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Programmed Death-Ligand 1 and Programmed Cell Death-1 Across the Anal Neoplasia Disease Continuum and Association With Survival in Anal Cancer","authors":"Sona Chowdhury ,&nbsp;Cynthia Gasper ,&nbsp;Ann A. Lazar ,&nbsp;Kathryn Allaire ,&nbsp;Teresa M. Darragh ,&nbsp;Lawrence Fong ,&nbsp;Joel M. Palefsky","doi":"10.1016/j.modpat.2025.100918","DOIUrl":"10.1016/j.modpat.2025.100918","url":null,"abstract":"<div><div>High-risk human papillomavirus (HPV) is associated with anal high-grade intraepithelial lesion (aHSIL) and anal squamous cell carcinoma (aSCC). The prognostic significance of programmed death-ligand 1 (PD-L1)- expression in aSCC and its impact on overall survival is controversial. ASCC can evade immune surveillance by coopting the PD-L1/programmed cell death-1 (PD-1) immune checkpoint pathway, enhancing tumorigenesis. To assess the potential role of the PD-L1/PD-1 axis on tumor progression, we assessed PD-L1 and PD-1 expression on epithelial cells and immune cells by immunohistochemistry in nonlesional anal tissue (n = 22), aHSIL (n = 22), and aSCC (n = 52) from HIV-negative participants and people living with HIV. PD-L1 expression on epithelial cells was restricted to tumor cells with no expression in nonlesional and HSIL tissues, whereas PD-L1-positive immune cells were present across all 3 diagnostic stages. PD-1 expression was absent on epithelial cells, whereas PD-1-positive immune cells increased along the disease continuum from nonlesional to aSCC. The overall PD-L1 expression on epithelial cells and immune cells measured by the combined positive score (CPS) in aSCC and the aggregate PD-L1 score in nonlesional and HSIL showed a substantial increase from nonlesional to aHSIL to aSCC. In aSCC, PD-L1 expression on immune cells was more prominent than in tumor cells and correlated with increased immune cell infiltration and interferon gamma secretion. Ninety-two percent of aSCC exhibited an adaptive PD-L1 expression pattern characterized by PD-L1 expression on tumor cells, immune cells, or both. HIV status did not affect PD-L1/PD-1 expression in nonlesional, aHSIL, or aSCC. PD-L1 expression in treatment-naive aSCC was associated with improved overall survival. Those with CPS of 0 had a higher risk of death (hazard ratio, 15.2 [95% CI, 3.3-69; <em>P</em> = .0004; log-rank <em>P</em> &lt; .0001]) compared with those with CPS &gt;0. CPS may indicate the presence of immune activation and serve as a potential prognostic marker.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100918"},"PeriodicalIF":5.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perianal Intestinal-Type Paget Disease With and Without Invasion, Unassociated With Internal Malignancy: A Distinct Form of Primary Perianal Adenocarcinoma","authors":"Dorukhan Bahceci ,&nbsp;Carla Saoud ,&nbsp;Raymond A. Isidro ,&nbsp;Diogo Caires ,&nbsp;Conrad James Moher ,&nbsp;Nil Urganci ,&nbsp;Melissa Pulitzer ,&nbsp;Julio Garcia-Aguilar ,&nbsp;Martin R. Weiser ,&nbsp;Efsevia Vakiani ,&nbsp;Amitabh Srivastava ,&nbsp;Jinru Shia","doi":"10.1016/j.modpat.2025.100917","DOIUrl":"10.1016/j.modpat.2025.100917","url":null,"abstract":"<div><div>Primary perianal adenocarcinoma of intestinal type (PPAI) has been described in recent literature and proposed as a subtype of extramucosal anal adenocarcinoma. Whether this represents a unique entity remains to be elucidated. Herein, we analyzed the clinicopathologic and genomic features of 14 cases of PPAI. Fourteen patients, predominantly older adults with a median age of 73 years (range, 50-85), with a slight woman predilection (5 men and 9 women) were identified. All cases presented with pagetoid intraepithelial growth, and 9 were eventually found to have underlying invasive carcinoma at the site of the Paget disease. Clinical and radiographic evaluation failed to detect another primary site, either in the anorectal region or elsewhere, in all patients. By immunohistochemistry, all but 1 case showed an intestinal phenotype with cytokeratin 20 and caudal-related homeobox transcription factor 2 (CDX2) positivity and variable cytokeratin 7. Metastasis developed in 4 of 14 patients, including regional lymph node and distant bone metastasis. Patient survival for localized disease ranged from 29 to 176 months (median, 62 months), whereas for metastatic disease, it ranged from 13 to 75 months (mean, 31 months). Genomic profiling revealed a high frequency of <em>TP53</em> mutations (86%, 12/14), <em>ERBB2</em> alterations (57%, 8/14), and <em>MYC</em> amplification (36%, 5/14), with absence of genetic alterations typically seen in rectal adenocarcinomas, such as <em>APC, KRAS,</em> and <em>BRAF</em>. In contrast, a control group of primary extramammary Paget disease cases displayed distinct genomic features, including recurrent <em>PIKC3A</em> and <em>KMT2C</em> mutations. Treatment included surgical excision, radiation therapy, and systemic chemotherapy in metastatic cases, with radiation proving effective in preventing local recurrence among those with localized disease. In metastatic cases, chemotherapeutic regimens including capecitabine/oxaliplatin and folinic acid, fluorouracil, and oxaliplatin were employed. The absence of anorectal or other visceral adenocarcinomas along with distinct genomic findings supports the classification of PPAI as a distinct clinicopathologic entity.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100917"},"PeriodicalIF":5.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD180 as a Robust Immunophenotypic Marker for Differentiating Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia From Marginal Zone Lymphoma","authors":"Zhen Guo ,&nbsp;Jing Su ,&nbsp;Lu Liu ,&nbsp;Ninghan Zhang ,&nbsp;Xiao Chen ,&nbsp;Qing Zhong ,&nbsp;Chun Qiao ,&nbsp;Huimin Jin ,&nbsp;Jianyong Li ,&nbsp;Lei Fan ,&nbsp;Yujie Wu","doi":"10.1016/j.modpat.2025.100919","DOIUrl":"10.1016/j.modpat.2025.100919","url":null,"abstract":"<div><div>Precise differential diagnosis between lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and marginal zone lymphoma (MZL) remains a challenging issue because of overlapping clinicopathological and immunophenotypic features. In the present study, the differential diagnostic potential of CD180 was assessed by determining its expression patterns in patients with MZL and LPL/WM through flow cytometry. The results indicated that LPL/WM cases exhibited a complete absence of CD180 expression on malignant B cells, whereas MZL cases showed robust CD180 expression (<em>P</em> &lt; .001). Receiver operating characteristic analysis demonstrated that CD180 expression percentage showed optimal diagnostic accuracy in LPL/WM and MZL cases (area under the curve = 0.998, sensitivity = 100%, and specificity = 98.0%), with a further improvement in differentiation potential by the CD180 mean fluorescence intensity ratio (lymphocytes/monocytes) of ≤ 0.47 (area under the curve = 0.937). Moreover, although the <em>MYD88</em>^{<em>L265P</em>}/<em>CXCR4</em> mutation was not detected by next-generation sequencing in 2 LPL/WM cases, these cases still showed the absence of CD180 expression. Subsequently, droplet digital PCR revealed low-frequency <em>MYD88</em>^{<em>L265P</em>} mutations (0.95% and 1.6% variant allele frequency) in these CD180-negative cases, which confirmed the superior sensitivity of CD180 in identifying LPL/WM with low tumor burden. Overall, our findings establish CD180 as a novel, rapid, and precise flow cytometry-based biomarker with robust ability for the differential diagnosis of LPL/WM and MZL, particularly relevant in resolving diagnostically challenging cases and providing prompt tumor diagnosis in time-constrained situations.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 12","pages":"Article 100919"},"PeriodicalIF":5.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cribriform Tumor of the Skin: Identification of 6q and 9q Loss as a Recurrent Cytogenomic Alteration","authors":"Shira Ronen ,&nbsp;David G. Grand ,&nbsp;Wahab A. Khan ,&nbsp;Michael Michal ,&nbsp;Donald C. Green ,&nbsp;Jennifer S. Ko ,&nbsp;Robert E. LeBlanc ,&nbsp;Jeffrey M. Cloutier","doi":"10.1016/j.modpat.2025.100916","DOIUrl":"10.1016/j.modpat.2025.100916","url":null,"abstract":"<div><div>Cribriform tumor is a rare sweat-gland neoplasm of uncertain malignant potential. Although its histopathologic features are well described, the molecular underpinnings of cribriform tumor remain incompletely characterized. We performed comprehensive molecular profiling of 6 cribriform tumors from 3 institutions using whole-exome sequencing, transcriptome sequencing, and single-nucletide polymorphism array copy number analysis. The cohort included 3 women and 3 men (median age, 54 years; range, 40-66 years), with tumors measuring 0.3 to 2.0 cm. Most arose on the extremities, with one located on the back. The most consistent genomic alteration was arm-level losses of chromosomes 6q and 9q, detected in 5 out of 6 cases. These alterations were validated across independent sequencing and single-nucletide polymorphism array platforms. Whole-exome sequencing identified likely pathogenic variants in 2 tumors (<em>CHEK2</em> p.R145W and <em>NF1</em> p.R1830H). No gene fusions were detected. Taken together, these findings provide independent confirmation that 6q/9q loss represents a consistent cytogenomic alteration in cribriform tumor, supporting its use as a molecular hallmark of this tumor.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"39 1","pages":"Article 100916"},"PeriodicalIF":5.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}