Virchows Archiv最新文献

{"title":"Neovascular prostate specific membrane antigen (PSMA) expression in bone and soft tissue sarcoma: a systematic analysis.","authors":"Irene A Spiridon, Sheena L M Ong, Jiri Soukup, Oana-Maria Topirceanu-Andreoiu, Lioe-Fee de Geus-Oei, Hans Gelderblom, Suk Wai Lam, Inge H Briaire de Bruijn, Brendy E W M van den Akker, Linda Hijmen, Karoly Szuhai, Judith V M G Bovée","doi":"10.1007/s00428-025-04086-6","DOIUrl":"https://doi.org/10.1007/s00428-025-04086-6","url":null,"abstract":"<p><p>Bone and soft tissue sarcomas are a highly heterogeneous group of rare cancers of mesenchymal origin. Treatment options other than surgery have limited efficacy due to low response rates with some exceptions. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may provide a novel treatment option, as it was recently suggested that soft tissue sarcomas express PSMA in the neovasculature, and on PET/CT imaging, multiple sarcomas have shown intense PSMA-tracer accumulation. Moreover, in prostate cancer patients, incidental PSMA uptake was seen in hemangiomas. In addition to confirming previous results in soft tissue sarcoma, the current study aims to systematically explore the expression of PSMA in bone tumors and in vascular tumors. Immunohistochemistry for PSMA was performed on a total of 706 tumors. High PSMA expression in the neovasculature was seen in 29% of the soft tissue sarcomas and 33% of the bone sarcomas. Malignant tumors showed a higher frequency of PSMA expression (score 2) as compared to benign tumors, with a high frequency in rhabdomyosarcoma (2 of 2, 100%), mesenchymal chondrosarcoma (14 of 20, 70%), undifferentiated sarcoma of bone (4 of 6, 67%) and of soft tissue (13 of 20, 65%), and osteosarcoma (46 of 81, 57%). In addition, giant cell tumor of bone displayed a high PSMA labelling in 67% of the cases. In contrast, high PSMA expression was seen in only 0-40% of the non-neoplastic vessels in vascular tumors, while 8% of them expressed PSMA in the tumor cells. Thus, with variable frequency among the different subtypes, a subset of bone and soft tissue tumors, both malignant and intermediate behavior, express PSMA and these patients may benefit from PSMA-targeting PET/CT scans or PSMA targeted radioligand therapy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR2 fusion/rearrangement analysis in intrahepatic cholangiocarcinoma using DNA/RNA-based NGS and FISH.","authors":"Xin Zhang, Qianming Bai, Yulin Wang, Zhengzeng Jiang, Jing Han, Cheng Xue, Kai Huang, Lijuan Luan, Xiaoyong Huang, Xiaowu Huang, Guoming Shi, Yingyong Hou, Yuan Ji","doi":"10.1007/s00428-025-04067-9","DOIUrl":"https://doi.org/10.1007/s00428-025-04067-9","url":null,"abstract":"<p><p>Patients with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusion/rearrangement benefit from targeted therapies, highlighting the need for reliable testing strategies to identify FGFR2 alterations. We assessed 226 iCCA cases using RNA-based NGS, DNA-based NGS, and break-apart FISH to evaluate the effectiveness of these methods in detecting FGFR2 fusion/rearrangement. The detection rates for FGFR2 fusion/rearrangement were 9.7% (22/226) for RNA-based NGS, 7.1% (16/226) for DNA-based NGS, and 10.2% (23/226) for FISH. Among the 26 FGFR2 fusion/rearrangement-positive cases identified by any method, only 15 (57.7%) were positive by all three techniques, yielding a concordance rate of 95.1% (215/226). RNA-based NGS confirmed oncogenic FGFR2 fusion in 81% (21/26) of positive cases and identified five novel oncogenic fusions. Thirty-five percent (6/17) of the partner genes were located on chromosome 10, with BICC1 being the most common fusion partner, while the rest were distributed across the other 9 chromosomes. FISH demonstrated a sensitivity of 95.2% and specificity of 98.5%, compared to oncogenic FGFR2 fusions confirmed by RNA-based NGS, while DNA-based NGS exhibited a sensitivity of 71.4% and specificity of 99.5%, identifying FGFR2 mutations in 4 cases. FGFR2-FISH positive cases displayed no significant heterogeneity in positive cell distribution. Oncogenic FGFR2 fusion/rearrangement was associated with small duct type iCCA, especially in cases with positive serum HBsAg and absent cholangiolocarcinoma components and peripheral liver steatosis. This study provides a comprehensive comparison of three assays for detecting FGFR2 fusion/rearrangement, along with clinicopathologic characterization of oncogenic FGFR2 fusion in iCCA.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adnexal carcinoma with ACTB: ZMIZ2 fusion: a third case.","authors":"Thibault Kervarrec, Amélie Osio, Baptiste Louveau, Maxence Mancini, Maxime Battistella","doi":"10.1007/s00428-025-04097-3","DOIUrl":"https://doi.org/10.1007/s00428-025-04097-3","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant chondroblastoma of the rib with scalp metastases in an adult patient: case report with molecular characterization.","authors":"Eva Manuela Pena-Burgos, Carolina Agra-Pujol, Francisco Alijo-Serrano, Luis Lombardía Ferreira, Lydia Mediavilla Santos, Miguel Cuervo-Dehesa, Ángel Santos-Briz, Pilar Escalonilla García-Patos, Álfonso Tejerizo García, Mar Tapia-Viñe, Julia Suárez-González, Jose Juan Pozo-Kreilinger","doi":"10.1007/s00428-025-04092-8","DOIUrl":"https://doi.org/10.1007/s00428-025-04092-8","url":null,"abstract":"<p><p>Chondroblastomas represent less than 1% of all bone tumors. They are currently classified as benign neoplasms and \"benign lung implants\" have been described. Exceedingly rare case of malignant chondroblastomas have been published, and only three of them have scalp metastases. We present the case of a 57-year-old healthy man who noticed a rapidly growing mass on his left chest. Radiological imaging revealed an 8 cm expansile and lytic lesion located in the anterior segment of the sixth costal arch with a thinned cortex without periosteal reaction. The tumor was removed with wide margins. Seven years later, he presented with multiple superficial movable lesions on the scalp that were surgically removed. The costal mass was histologically composed of fused nests of discohesive polygonal cells with grooved nuclei, and scattered osteoclast-like giant cells embedded in an eosinophilic chondroid matrix. It presented a permeative growth pattern with entrapped pre-existing bone trabeculae and focal soft tissue extension. Scanty \"chicken-wire\" calcifications were detected. Moderate atypia and necrotic foci were observed. Occasional non-atypical mitotic figures were also observed. The cutaneous lesions demonstrated the same histopathological findings. Both the metastases and the primary tumor showed diffuse immunoreactivity for anti-histone H3K36M. Molecular study of the H3 histone family member 3B gene demonstrated a p.K37M mutation in exon 2 in the original mass and in the metastasis. Next-generation sequencing did not detect any other molecular alterations in the metastases. Malignant chondroblastomas are extremely rare tumors that most commonly arise in unusual locations, such as the rib or scapula, and in older adults. Permeative growth pattern, soft tissue extension, greater atypia, and higher mitotic rates are histopathological features of malignancy. H3K36M immunoreactivity and H3F3B gene mutations are key to achieving correct diagnosis. Wide resection and close follow-up of patients should be recommended. There is currently no consensus regarding the administration of adjuvant chemotherapy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenal mixed corticomedullary tumors: report of a case with molecular characterization and systematic review.","authors":"Edurne Pérez-Béliz, Benjamín Alfonso Thorpe-Plaza, Everardo Josué Díaz-López, Lourdes Loidi, Carmen Villalba-Martín, Ihab Abdulkader-Nallib, José Manuel Cameselle-Teijeiro","doi":"10.1007/s00428-025-04091-9","DOIUrl":"https://doi.org/10.1007/s00428-025-04091-9","url":null,"abstract":"<p><p>Adrenal mixed corticomedullary tumors (MCMTs) are rare lesions showing a mixture of two cell populations of cortical and medullary lineage. We describe an MCMT case presented in a 56-year-old woman with a history of arterial hypertension and high levels of aldosterone, accompanied by a review of the literature. The adrenalectomy specimen showed a well-circumscribed nodule of 30 mm in size, containing 60% of cells with a cortical phenotype (positive for α-inhibin and melan-A) and 40% of cells with a medullary phenotype (positive for chromogranin-A, GATA-3 and somatostatin receptor 2). There was no significant mitotic activity, necrosis, nor lymphovascular invasion. The GNAS p.(Arg844Cys) mutation, as well as variants of uncertain significance AKAP13 p.(His641Pro) and EPAS1 p.(Ser478del) were detected in the tumor. MCMT is more common in women (75%) with a mean age of 46.6 years (range 16-78). Most patients present with hypertension (79%), frequently associated with Cushing's syndrome, (39%), diabetes (21%), aldosteronism (15%), and/or hyperandrogenism (6%). Laboratory data showed elevated levels of both cortisol and cathecholamines and/or their metabolites in more than 50% of cases, supporting the dual nature of the tumor. Most MCMTs are benign, but aggressive behavior was detected in four (12%) cases, all of them showing large size (80-220 mm), poor delimitation, venous invasion, necrosis, and/or high proliferation rates. The pathogenesis is unknown, but our findings suggest a tumor histogenesis from the cortical cellular component through the regulation of the protein kinase A pathway and secondary proliferation of the medullary component.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of a thymic neuroblastoma in an adult associated with inappropriate antidiuretic hormone secretion syndrome.","authors":"Sofia Lérias, Rafael Cabrera, Leonor Branquinho-Ruivo, Ana Saramago, Robert Stoehr, Abbas Agaimy, Carmo Martins","doi":"10.1007/s00428-025-04085-7","DOIUrl":"https://doi.org/10.1007/s00428-025-04085-7","url":null,"abstract":"<p><p>Neuroblastoma (NB) is extremely rare in adults, and anterior mediastinal location is even more unusual. We report a primary thymic NB in a 72-year-old male, who presented with the inappropriate antidiuretic hormone secretion (SIADH) syndrome. Molecular testing revealed copy number alterations of chromosome 3, i.e., loss of whole 3p and partial gain of distal 3q, including gain of copies of the PIK3CA gene. To the best of our knowledge, only five mediastinal NB cases in adults have been reported with genetic evaluation. One case showed loss of 3p material with SETD2 gene mutation and gain of PIK3CA gene, similar to our case. As thymic NB is extremely rare, report of more genetically characterized cases should help to delineate their pathobiology and shed light on possible mechanisms involved in the associated SIADH syndrome.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dermatofibrosarcoma protuberans with PDGFD rearrangements: a case series featuring a novel EMILIN1::PDGFD fusion and comprehensive literature review.","authors":"Sotiris Sotiriou, Kyriakos Chatzopoulos, Gregory W Charville, Gregory R Bean, Michael Michal, John M Gross, Julia A Bridge, Jerad M Gardner, Abbas Agaimy, Tony L Ng, Jeffrey M Cloutier, Carla Saoud, Konstantinos Linos","doi":"10.1007/s00428-025-04088-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04088-4","url":null,"abstract":"<p><p>Dermatofibrosarcoma protuberans (DFSP) is a locally infiltrative mesenchymal neoplasm usually characterized by a COL1A1::PDGFB fusion. A minority of DFSPs have recently been shown to harbor alternative fusions, involving the PDGFD gene. The aim of this case series and literature review is to highlight the clinicopathologic and molecular features of PDGFD-rearranged DFSPs. Eighteen patients (twelve females and six males) with PDGFD-rearranged DFSPs were collected from the authors' institutional archives. Eight (44%) cases harbored a COL6A3::PDGFD fusion, five (28%) an EMILIN2::PDGFD fusion, and two (11%) an EMILIN1::PDGFD fusion. In three (17%) cases, the fusion partner was unknown. A literature review revealed 29 additional cases. Cumulatively, four alternative fusion genes have been detected: COL6A3::PDGFD (24/47, 51%), EMILIN2::PDGFD (12/47, 26%), EMILIN1::PDGFD (2/47, 4%), and TNC::PDGFD (1/47, 2%). In eight (17%) cases, the fusion partner was unknown. Most (20/24, 83%) COL6A3::PDGFD-fused DFSPs occurred in females with only four (17%) cases described in males. Additionally, half of them (12/24, 50%) developed in the breast/chest wall. EMILIN2::PDGFD-fused DFSPs often occurred in males, were located in the extremities (9/12, 75%), exhibited fibrosarcomatous transformation (9/12, 75%), were confined exclusively or primarily to the subcutis (10/12, 83%), and had a well-circumscribed contour (10/12, 83%). Specific molecular alterations in DFSPs correlate with certain clinicopathologic features. Notably, EMILIN2::PDGFD-fused DFSPs have a slight predilection for males, develop almost exclusively in the subcutis, tend to be well-circumscribed, and often exhibit fibrosarcomatous transformation, while COL6A3::PDGFD-fused DFSPs might have a predilection for the breast/chest wall of female patients. To the best of our knowledge, this is the first report of EMILIN1::PDGFD-fused DFSP.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital transformation of pathology - the European Society of Pathology expert opinion paper.","authors":"Catarina Eloy, Filippo Fraggetta, Paul J van Diest, António Polónia, Mónica Curado, Jordi Temprana-Salvador, Inti Zlobec, Elvira Purqueras, Cleo-Aron Weis, Xavier Matias-Guiu, Peter Schirmacher, Aleš Ryška","doi":"10.1007/s00428-025-04090-w","DOIUrl":"https://doi.org/10.1007/s00428-025-04090-w","url":null,"abstract":"<p><p>An expert group mandated by the European Society of Pathology (ESP) outlines its recommendations on the digital transformation of pathology departments, aiming to facilitate the acquisition of resources for better patient care. This statement is directed at pathology professionals, offering guidance for the safe implementation of digital pathology while emphasizing the necessity of standardization, quality control, and sustainability. Digital pathology involves automating and standardizing laboratory workflows to produce high-quality whole slide images (WSIs), which are crucial for diagnosis, research, and education. A successful digital transformation requires a multidisciplinary approach, significant investment in human, structural, and informatic resources, and progressive adaptation of laboratory workflows. Key components include robust infrastructure; continuous training; and clear policies for hardware renewal, data storage, and interoperability. The transition demands attention to quality and production control, ensuring efficient WSI generation and timely diagnostic reporting. ESP strongly recommends that pathology departments, supported by funding organizations, start to prioritize digital transformation as a step toward improved patient care and in alignment with global healthcare initiatives. Collaboration, investment, and adherence to quality standards are critical to benefiting the most the full potential of digital pathology.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid granular cell tumor/perineurioma: a report of two rare cases with PIK3CA mutations.","authors":"Ani Toklu, Gauri Panse, George Jour, Konstantinos Linos, Jeffrey M Cloutier, Carina A Dehner","doi":"10.1007/s00428-025-04089-3","DOIUrl":"https://doi.org/10.1007/s00428-025-04089-3","url":null,"abstract":"<p><p>Hybrid peripheral nerve sheath tumors (PNSTs) are rare mesenchymal neoplasms with dual differentiation, most often combining two of the three main PNST types: schwannoma, neurofibroma, and perineurioma. Recognized by the WHO since 2013, these tumors can also exhibit fewer common combinations, such as hybrid granular cell tumor/perineurioma. We herein report two rare cases of hybrid granular cell tumor perineurioma with molecular analysis. Both tumors presented as dermal to subcutaneous, well-circumscribed lesions composed of a combination of spindled and granular cell components. By immunohistochemistry, the granular cells were positive for S100, SOX10, and CD68, while the perineurial cells were highlighted by EMA and GLUT1 stains. Subsequent molecular testing revealed pathogenic mutations involving PIK3CA in both cases. Our study expands on the clinical and pathologic spectrum and provides the first molecular data on these unusual neoplasms. Further, we provide a comprehensive review of the literature of all previously reported cases and briefly discuss relevant differential diagnoses and their molecular features.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral neuroblastic tumors behaving badly: an update on high-risk morphologic and molecular groupings.","authors":"Jason A Jarzembowski, Samuel Navarro, Hiroyuki Shimada","doi":"10.1007/s00428-025-04083-9","DOIUrl":"https://doi.org/10.1007/s00428-025-04083-9","url":null,"abstract":"<p><p>Peripheral neuroblastic tumors occur on a histologic spectrum from benign ganglioneuromas to malignant neuroblastomas, but even within the latter category, there is extensive heterogeneity in morphologic appearance and genetic composition. The International Neuroblastoma Pathology Committee classification has traditionally been used to successfully categorize tumors with favorable or unfavorable histology, but morphology must be supplemented with the results of additional testing. While MYCN amplification, diploid DNA content, and 11q loss have long been known to be negative prognostic factors, a new group of molecular biomarkers has emerged that define discrete high-risk categories. These include MYCN/MYC overexpression, dysregulated telomere maintenance mechanisms (both increased expression of telomere reverse transcriptase and alternate lengthening of telomeres), and ALK aberrations. Testing for these biomarkers and an integrated classification scheme may lead to improved risk stratification and selection of emerging targeted therapies.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}