American Journal of Surgical Pathology最新文献

{"title":"Mark R. Wick, MD.","authors":"Stacey E Mills, Mark H Stoler","doi":"10.1097/PAS.0000000000002524","DOIUrl":"10.1097/PAS.0000000000002524","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"467-468"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580280","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":"Clinicopathologic and Molecular Characteristics of Merkel Cell Polyomavirus Positive T-Cell Lymphoproliferative Disorders.","authors":"Philip Bulterys, Christine W Zhou, Shunyou Gong, Eric Gars, Jingjing Zhang, Sheren Younes, Andrew Stone, Christian Hirt, Lianna Marks, Christina Su, Henning Stehr, Lauren Lawrence, Brent Tan, Kenneth Weinberg, Jonathan Tan, Petr Starostik, Michael Khodadoust, Shachar Naor, Dita Gratzinger, Yasodha Natkunam, Jason Kurzer, Sebastian Fernandez-Pol","doi":"10.1097/PAS.0000000000002521","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002521","url":null,"abstract":"<p><p>Previous work described 3 cases of CD4+ T-cell lymphomas harboring Merkel cell polyomavirus (MCPyV), as demonstrated by in situ hybridization (ISH), next generation sequencing, and polymerase chain reaction. Two of these cases were cutaneous T-cell lymphomas compatible with mycosis fungoides in postcardiac transplant patients, while the third was a peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), in a patient without known immunosuppression. In this study, we assess an expanded cohort of T-cell neoplasms from 4 institutions for expression of MCPyV by ISH. This cohort includes 9 T-cell lymphomas occurring in the post solid organ transplant setting, of which 5 (60%) were positive for MCPyV by ISH. Four of these cases were classified as PTCL-NOS and the remaining case as nodal T follicular helper cell lymphoma, angioimmunoblastic type. In addition, we performed MCPyV ISH on a variety of neoplastic and non-neoplastic lymphoid tissues from both transplant and nontransplant patients. No evidence of MCPyV infection was found in lymphoid tissues in the absence of T-cell lymphoma, suggesting that the presence of MCPyV is specific to this rare subset of T cell lymphomas. Furthermore, all MCPyV-positive T-cell lymphomas (8 of 8) were CD4+ and the large majority were observed in the post-transplant setting (7 of 8). Multiplex single-molecule fluorescence ISH confirmed the presence of MCPyV in CD4+ T-cells. These findings support the hypothesis that MCPyV infection is specifically associated with rare CD4+ T-cell lymphomas, particularly in transplant recipients.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":"50 5","pages":"481-500"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687754","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":"Extrapancreatic Gastrointestinal Tract Grade 3 Well-Differentiated Neuroendocrine Tumors Behave Aggressively Compared With Lower-Grade Tumors Despite Similar Morphology.","authors":"Monika Vyas, Andrew M Bellizzi, Kelsey McHugh, Daniela Allende, Chanjuan Shi, Changqing Ma, Stuti Shroff, Brian K Cox, Aatur Singhi, Nandan Padmanabha, Raul S Gonzalez","doi":"10.1097/PAS.0000000000002514","DOIUrl":"10.1097/PAS.0000000000002514","url":null,"abstract":"<p><p>The WHO 2019 classification of digestive tract tumors introduced a high-grade (G3) category for well-differentiated neuroendocrine tumors (NETs). These neoplasms appear to have a better prognosis than poorly differentiated neuroendocrine carcinomas (NECs) and may not respond to platinum-based chemotherapy, which is the treatment of choice for NECs, justifying the creation of this new category. Most existing data on G3 NETs are derived from pancreatic neuroendocrine neoplasms, as the majority of G3 neuroendocrine neoplasms (NENs) arise there. G3 NETs are rare at extrapancreatic sites, and their prognosis and behavior are not well studied. We collected and analyzed a multi-institutional cohort of 24 extrapancreatic primary gastrointestinal G3 NETs based on mitotic rate and/or Ki67 index (5 gastric, 13 small bowel, 6 colorectal/anal). Mean Ki67 index was 29.3% (range: 10.5% to 50.2%). Cases generally showed typical well-differentiated NET morphology. Nodal metastases were present in 17/17 (100%) patients; 13/24 (45%) had distant metastases at initial presentation, and 7 patients developed them on follow-up. With a median of 29 months of follow-up, only 2 patients (8%) were alive without disease. Outcomes of G3 NETs were compared with a separate cohort of 125 extrapancreatic G1/G2 gastrointestinal NETs. G3 tumors presented at a higher pT-category stage ( P <0.001) and overall stage ( P =0.002), and patients with G3 disease were more likely to die than those with G1/G2 disease ( P <0.001). Our data show that, like pancreatic G3 NETs, rare extrapancreatic gastrointestinal G3 NETs exhibit aggressive behavior compared with their G1/G2 counterparts (although small bowel NETs tend to recur irrespective of grade). In most cases, the G3 designation is driven by Ki67 index, though exceptions exist, emphasizing the need for reviewing mitotic count in every case.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"524-534"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257062","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":"Surgical Pathology of Diffuse Parenchymal Lung Disease in Adults With IgA Vasculitis or IgA Nephropathy.","authors":"Samantha A Moore, Yasmeen M Butt, Maxwell L Smith, Henry D Tazelaar, Brandon T Larsen","doi":"10.1097/PAS.0000000000002522","DOIUrl":"10.1097/PAS.0000000000002522","url":null,"abstract":"<p><p>IgA vasculitis (IgAV) and IgA nephropathy (IgAN) are closely related disorders that usually present in childhood. Pulmonary involvement is rare and histopathologic features thereof in adults are poorly understood. Institutional archives were searched for adults with IgAV or IgAN and diffuse parenchymal lung disease. Ten patients (6 men, median age 59 years) with lung tissue sampling were enrolled. Clinical history and pathology slides were reviewed. All patients were diagnosed with IgAV or IgAN before or concurrently with lung disease. Symptoms were nonspecific but hemoptysis was common. Radiologically, bilateral ground-glass opacities, consolidation, and reticulonodular densities were typical. Histologically, 6 cases (60%) featured acute or subacute diffuse alveolar hemorrhage (DAH) accompanied by definite (40%) or probable (20%) capillaritis. Two cases (20%) featured resolved DAH only, manifesting as alveolar hemosiderosis without other changes. And 2 cases featured organizing pneumonia without DAH. Five patients had a chronic interstitial pneumonia in the background, including 3 with nonspecific interstitial pneumonia (NSIP) and 2 with unclassifiable fibrosis. Findings were similar in IgAV versus IgAN. Of 4 patients with follow-up information, 2 died during hospitalization, one died 9 weeks later of secondary complications, and one was treated with rituximab and nintedanib and is alive 2 years later. To our knowledge, this is the largest series detailing pulmonary histopathologic findings in adults with IgAV or IgAN. Most cases show acute DAH with capillaritis; less commonly, old DAH, organizing pneumonia, NSIP, or unclassifiable fibrosis may be observed. Some patients do well with treatment but fatal cases also occur.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"579-588"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324443","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":"DICER1 -Related Primitive Polyphenotypic Neoplasm : A Report of 15 Cases of an Underrecognized Tumor of the Gynecologic Tract and Peritoneum.","authors":"Kyle M Devins, Lawrence Hsu Lin, Adam S Fisch, Dora Dias-Santagata, Andre Pinto, Robert H Young, Esther Oliva, Gulisa Turashvili","doi":"10.1097/PAS.0000000000002517","DOIUrl":"10.1097/PAS.0000000000002517","url":null,"abstract":"<p><p>Somatic or germline pathogenic/likely pathogenic variants in DICER1 have known associations with certain neoplasms in the gynecologic tract, including Sertoli-Leydig cell tumors, embryonal rhabdomyosarcoma, and adenosarcoma. However, recent studies have highlighted DICER1- related malignant neoplasms with complex admixtures of sarcomatous, primitive glandular, and/or neuroectodermal elements, which are underrecognized and lack consistent nomenclature. We report the largest series of these primitive polyphenotypic DICER1 -related neoplasms arising in the gynecologic tract or peritoneum. The 15 patients were aged 10 to 77 (median: 37) years. Tumors involved the endometrium (n=6), cervix (n=3), endometrium and cervix (n=2), ovary (n=2), or pelvic peritoneum (n=2). Twelve were organ-confined and 3 were at an advanced stage at presentation. All contained sarcomatous elements composed of sheets and aggregates of ovoid/spindled cells with rhabdomyoblastic differentiation in 13. Periglandular condensation (n=13), cambium layer (n=12), fetal-type cartilage (n=11), and anaplasia (n=4) were also identified. Primitive glands were present in 14 (abundant in 8) and comprised single or clustered simple (n=14) or variably dilated/elongated glands resembling those seen in adenosarcoma (n=9). The epithelium had a primitive appearance with frequent subnuclear vacuoles (n=14), intracytoplasmic granules (n=7), or minimal amphophilic cytoplasm (n=3), and frequently stained for SALL4, glypican-3, and AFP. Neuroectodermal elements were seen in 12, composed of compact small round blue cells punctuated by neuroepithelial tubules. DICER1 alterations were present in all tumors. DICER1 -related primitive polyphenotypic neoplasms present significant diagnostic difficulty due to their varied appearances and lack of consistent nomenclature in the rare reports to date. Recognition of the morphologic features of these unusual neoplasms should prompt confirmatory DICER1 testing and consideration of germline evaluation, particularly in young patients.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"469-480"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376053","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":"ALK -Rearranged Renal Cell Carcinoma : Morphologic Spectrum and Genomic Landscape From a Multi-Institutional Cohort of 16 Cases.","authors":"Anandi Lobo, Mahmut Akgul, Ankur R Sangoi, Khaleel I Al-Obaidy, Andres M Acosta, Shivani R Kandukuri, Rahul Kapoor, Sourav K Mishra, Shilpy Jha, Seema Kaushal, Swati Satturwar, Adeboye O Osunkoya, Anil V Parwani, Jasreman Dhillon, Ekta Jain, Sean R Williamson, Rajal B Shah, Sambit K Mohanty, Liang Cheng","doi":"10.1097/PAS.0000000000002525","DOIUrl":"10.1097/PAS.0000000000002525","url":null,"abstract":"<p><p>Due to its heterogeneous morphology and its rarity, anaplastic lymphoma kinase gene-rearranged renal cell carcinoma ( ALK RCC) is a diagnostically challenging entity, often leading to labelling these tumors as RCC, not otherwise classified. This may have clinical and managerial implications, given that patients with ALK oncogene rearrangement may benefit from ALK -inhibitors. Therefore, we attempted to elucidate the clinicopathologic and immunophenotypical characteristics of ALK RCC in a large international cohort. Sixteen multi-institutional tumors were included in the study. Clinical, macroscopic, microscopic, immunohistochemical (IHC), molecular (DNA and RNA sequencing, FISH) and follow-up data were evaluated. There were 9 male and 7 female patients with tumor size ranging from 2 to 12.2 cm (mean=7.1 cm). All tumors had solid, tan-white with focal cystic changes and gelatinous appearance. Cystic changes and necrosis were seen in 7 and 6 tumors, respectively. Microscopically, a heterogeneous growth pattern was observed including solid (12), tubular (7), papillary (5), tubulocystic (2), pleomorphic epithelioid cells (6), sarcomatoid (2), rhabdoid (4), and intranuclear pseudoinclusions. All tumors were ALK-positive, coexpressing PAX8, KRT7, SDH, FH, and variably CD10, Vimentin, and AMACR. Molecular analysis through next-generation sequencing (NGS) was performed on 14/16 tumors. EML4::ALK (n=5) was the most common gene fusion observed; others included TPM1::ALK (n=4) , TPM3::ALK (n=2), SLIT1::ALK (n=2)and VCL::ALK (n=1). Despite focal TFE3 immunoreactivity in 4/13 cases, the absence of TFE3 gene rearrangement by molecular analysis excludes TFE3 - rearranged RCC as a differential diagnosis. Our study further expands the clinicopathologic, morphologic, and molecular genetic spectrum of ALK -RCC. ALK -RCC can be morphologically heterogeneous and mimic other well-established entities posing a misdiagnosis if appropriate IHC and/or molecular studies are not performed. Accurate diagnosis is of clinical significance as patients with this neoplasm may potentially benefit from ALK- inhibitors, particularly in a metastatic setting. As TFE3 immunoreactivity is not uncommon in ALK -RCC, documentation of ALK gene rearrangement is critical, either by surrogate IHC staining or cytogenetic/molecular analysis is essential.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"513-523"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147363799","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":"Clinicopathologic Analyses of 34 Cases of High-Grade Serous-Like Carcinoma (HG-SL-Ca) of the Breast.","authors":"Yulin Haw, Gregor Krings, Wen-Yu Hsiao, Haiying Zhan, Yanjun Hou, Gloria Zhang, Huina Zhang, Shi Wei, Wei Yang, Marick Laé, Miriam D Post, Yi Liu, Eliah R Shamir, Marilin Rosa, Kalliopi Siziopikou, Stuart Schnitt, Yunn-Yi Chen, Xiaoxian Li","doi":"10.1097/PAS.0000000000002516","DOIUrl":"10.1097/PAS.0000000000002516","url":null,"abstract":"<p><p>High-grade serous-like carcinoma (HG-SL-Ca) of the breast is a newly recognized entity. We present the largest series with 34 cases. Inclusion criteria were breast carcinoma with ≥70% areas showing discordant well-formed tubules and high nuclear grade. Twenty-four (70.6%) were triple negative; 5 (14.7%) were ER+/HER2-; 2 (5.9%) were ER+/HER2+; and 3 (8.8%) were ER-/HER2+. Axillary lymph node metastasis was seen in 10 (31.3%) of 32 cases. Nine patients had neoadjuvant chemotherapy and 2 (22.2%) achieved pathologic complete response (pCR). Of the 32 patients with available follow-up data, 2 (6.3%) had local recurrence; 6 (18.8%) had distant metastasis; and 1 (3.1%) had both local recurrence and metastasis; 6 (18.8%) died of disease. Univariate analysis showed that only larger tumor size ( P =0.04) was associated with shorter metastasis-free survival; and larger tumor size ( P =0.003) and higher percentage of serous-like pattern ( P =0.03) were associated with worse overall survival. 27 (81.8%) of 33 cases had aberrant p53 expression; 16 (64.0%) of 25 showed p16 block positivity; 26 (86.7%) of 30 showed at least focal GATA-3 staining; 25 (89.3%) of 28 were negative for nuclear WT1 (3 had focal staining); and 28 (96.6%) of 29 were negative for PAX-8 (1 had focal staining). HG-SL-Ca of the breast has distinct morphology and the majority show aberrant p53 expression. Patients showed a low pCR rate and poor outcomes. The distinct morphology, immunohistochemistry (IHC) profile and clinical presentations warrant classifying these tumors as a new entity. The morphologic features and IHC studies can help differentiate breast HG-SL-Ca from other carcinomas.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"543-549"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282092","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":"Comprehensive Assessment of CD19 Immunohistochemical Staining in Classic Hodgkin Lymphoma.","authors":"Sarah R Helman, Fikru Merechi, Hanan Alharthy, Rima Koka, Seung Tae Lee, Aaron P Rapoport, Jennie Y Law, Michael E Kallen","doi":"10.1097/PAS.0000000000002519","DOIUrl":"10.1097/PAS.0000000000002519","url":null,"abstract":"<p><p>Classic Hodgkin Lymphoma (CHL) remains difficult to treat in patients with relapsed and refractory disease. The utility of immunotherapies, many of which target B-cell markers, is still under investigation. Although the neoplastic Hodgkin and Reed-Sternberg (HRS) cells are thought to lose most B-cell markers, studies have shown retention of these markers, mainly CD20, in some cases. However, the CD19 staining profile of HRS cells has not been thoroughly assessed and warrants exploration in the era of CD19-directed immunotherapies. We assessed CD19 immunohistochemical staining in 41 cases of CHL and correlated with histologic subtype, other markers, and clinical parameters. 13/41 cases (31.7%) demonstrated CD19 staining in HRS cells, with variation in staining pattern and intensity. When compared with CD19-negative cases, CD19 positivity correlated significantly with mixed-cellularity subtype (53.8% vs. 7.1%, P =0.002), CD20 (46.2% vs. 14.3%, P =0.0485), CD79a (53.8% vs. 9.1%, P =0.006), Epstein-Barr Virus (EBV) positivity (53.8% vs. 7.1%, P =0.002), and older age (median age 52 vs. 28.5 y, P =0.0006). 7/9 (77.8%) EBV+ cases demonstrated CD19 expression on HRS cells. By Kaplan-Meier analysis, CD19+ cases demonstrated worse overall survival compared with CD19- cases ( P =0.011), with EBV-, CD19- cases demonstrating the best overall survival. On the basis of these findings, CD19 expression on HRS cells should not preclude the pathologic diagnosis of CHL, particularly in the context of mixed-cellularity or EBV+ disease. In addition, older patients with mixed-cellularity and/or EBV+ disease may represent a subgroup of patients with CHL who could benefit from CD19-directed therapies.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"570-578"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389191","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":"Genome-Wide Copy-Number Landscape of Germ Cell Tumors With Synchronous Conventional and \"Somatic-Type\" Malignancy Components.","authors":"Kvetoslava Michalova, Melissa Hruby, Nicholas Baniak, Jennifer B Gordetsky, Muhammad T Idrees, William J Anderson, Petr Martinek, Marian Grendar, Michal Michal, Thomas M Ulbright, Andres M Acosta","doi":"10.1097/PAS.0000000000002515","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002515","url":null,"abstract":"<p><p>So-called \"somatic-type\" malignancies (SMs) of germ cell tumor (GCT) origin resemble malignant neoplasms that arise from true somatic tissue. Except for enrichment in TP53 pathway alterations, the mutational profile of GCTs with SMs does not significantly differ from that of typical GCTs. Prior studies have suggested that copy number alterations (CNAs) of SMs may differ from those of conventional GCTs, but comparative genome-wide CNA analyses of paired components of GCTs with SMs have not been previously performed. The objective of this study was to compare CNAs in paired SMs and conventional components of individual GCTs. Twenty-two paired samples from 11 tumors were included in the study (6 metastases, 4 testicular primaries, and 1 mediastinal primary). Each paired sample represented synchronous conventional GCT and SM components from the same tumor, without pretreatment and post-treatment or primary-metastatic comparisons. The molecularly studied conventional GCT components included: teratoma (n=7), teratoma and yolk sac tumor (n=1), teratoma and seminoma (n=1), and seminoma (n=2). The SM components included: embryonic-type neuroectodermal tumor (ENT; n=3), rhabdomyosarcoma (RMS; n=2), ENT and RMS (n=1), unclassified sarcoma (n=2), nephroblastoma (n=1), carcinoma, NOS (n=1), and acinar cell carcinoma (n=1). In most tumors (8/11; 73%), CNA profiles of the paired samples were similar. In the remaining 3 tumors (3/11; 27%), the CNA profiles showed noticeable differences, with a higher number of CNAs in SM. Two of these were metastatic and the remaining was a mediastinal primary. No highly recurrent CNAs were identified in the SM components. The similar CNA profiles of paired SMs and conventional GCTs reinforces their common clonal origin. The differences observed in a subset likely reflect earlier divergent evolution of the SM subclones, with CNAs possibly underlying tumor progression.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":"50 5","pages":"535-542"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687764","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":"Novel EPS15 :: KLF17 and EPS15L1 :: KLF17 Fusions Define a Distinctive Group of MUC4-Positive Spindled to Epithelioid Sarcomas.","authors":"Faizan Malik, Maia Vong, Carina A Dehner, Zonggao Shi, Marie Karanian, Daniel Pissaloux, Soniya N Pinto, Patrick R Blackburn, Quynh T Tran, Brent A Orr, Selene C Koo","doi":"10.1097/PAS.0000000000002520","DOIUrl":"10.1097/PAS.0000000000002520","url":null,"abstract":"<p><p>A subset of epithelioid-to-spindle cell sarcomas remains difficult to classify due to lack of defining molecular alterations or pathologic features that do not fit neatly into a single tumor class. After identification of a primary mesenchymal neoplasm with EPS15L1::KLF17 gene fusion, we retrospectively collected 4 additional soft tissue tumors with EPS15L1 :: KLF17 or EPS15 :: KLF17 fusions. The cohort comprised 4 males and one female with age range of 5 to 64 years. The tumors arose in soft tissue of the extremities, head/neck, paraspinal region, and intra-abdominal mesentery. Two patients developed metastatic disease with one death from disease at 62 months; one showed late metastases at 5 and 11 years. Histologically, these were cellular neoplasms composed of epithelioid and spindled tumor cells with prominent cystic spaces and focal stromal sclerosis. All tumors demonstrated diffuse, strong MUC4 positivity (5/5) with cytokeratin (3/3), EMA (4/4), and S100 (3/4) expression. Whole transcriptome RNA sequencing identified EPS15L1 :: KLF17 fusions in 2 cases and EPS15 :: KLF17 fusions in 3 cases. RNA expression profiles, available in 2 cases, showed high expression of MUC4 and CD24. DNA methylation profiling revealed distinct epigenetic clustering, separate from EWSR1 :: KLF15 -rearranged soft tissue myoepithelial tumor, sclerosing epithelioid fibrosarcoma, low-grade fibromyxoid sarcoma, and other mesenchymal neoplasms. EPS15/EPS15L1 :: KLF17 -rearranged sarcoma has distinctive histologic findings, including diffuse MUC4 expression. Recognition is clinically important given its potential for late recurrence and metastasis.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"501-512"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347043","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}