Virchows Archiv最新文献

{"title":"Updates on Langerhans cell histiocytosis and other histiocytosis in children: invited review-challenges and novelties in paediatric tumours.","authors":"Laura Galluzzo Mutti, Jennifer Picarsic","doi":"10.1007/s00428-024-04018-w","DOIUrl":"10.1007/s00428-024-04018-w","url":null,"abstract":"<p><p>Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG) family lesions, and Rosai-Dorfman-Destombes disease (RDD) are now classified by the World Health Organization (WHO) under the heading of histiocytic/dendritic cell neoplasms. Each disease may manifest as a focal lesion, as multiple lesions, or as a widespread aggressive systemic disease with visceral organ involvement. Erdheim-Chester disease (ECD) is a rare systemic disease process of adults with limited cases in children. Challenges in diagnosis and novel disease presentations, including ALK-positive histiocytosis (a newly recognized WHO entity), mixed histiocytosis, and secondary histiocytic lesions following a prior leukemia/lymphoma are also discussed. Malignant histiocytic neoplasms (MHN) are distinct high-grade histiocytosis, which while rare in childhood occur both as primary disease and as secondarily after a prior hematologic malignancy. Of note, despite its name, hemophagocytic lymphohistiocytosis (HLH) is not considered a histiocytic neoplasm and does not define one specific disease \"entity.\" HLH is a spectrum of hyperinflammation with various triggers and is not covered for the purposes of this targeted review.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"189-204"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967069","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":"What is new in fibroblastic/myofibroblastic tumors in children.","authors":"Alyaa Al-Ibraheemi, Yan Zhou, Emma Rullo, Rita Alaggio","doi":"10.1007/s00428-024-03964-9","DOIUrl":"10.1007/s00428-024-03964-9","url":null,"abstract":"<p><p>Fibroblastic and myofibroblastic neoplasms represent about 12% of pediatric soft tissue tumors. Most of these neoplasms in children are either benign or locally aggressive with rare metastasis, while malignant cases are uncommon. Diagnosing these tumors is challenging due to overlapping morphologies and the limited utility of immunohistochemistry. Advances in molecular techniques, especially RNA sequencing, have improved our understanding of the molecular drivers of these tumors, leading to better classification. Key molecular alterations, such as RTK and MAPK activation, are central in the development of tumors like infantile fibrosarcoma (IFS) and inflammatory myofibroblastic tumors (IMT). The identification of alternative fusions in IFS and IMT underscores the importance of an integrated diagnostic approach. Furthermore, new RTK-driven lesions, now included in the WHO's \"NTRK-rearranged mesenchymal neoplasms\", have been identified. This review provides an update on recent findings in RTK-driven myofibroblastic tumors and highlights novel entities still in need of classification.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"127-141"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584407","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":"\"Update on pediatric primary liver tumors\".","authors":"Dolores López-Terrada, Jens Stahlschmidt, Antonio R Pérez-Atayde","doi":"10.1007/s00428-024-03985-4","DOIUrl":"10.1007/s00428-024-03985-4","url":null,"abstract":"<p><p>Liver masses are common in children, however primary malignant neoplasms are rare, representing only 1% of all pediatric cancers. Hepatocellular neoplasms are the most common primary liver malignancies and hepatoblastoma (HB) is the most frequently diagnosed. The incidence of HB, which is increasing, is approximately of 2 cases per million in the United States, followed by hepatocellular carcinoma (HCC). Pediatric primary liver tumors of mesenchymal origin are less common, except for benign vascular tumors (hemangiomas). Malignant mesenchymal neoplasms represent approximately 10-15% of all, the most common being embryonal sarcoma and malignant rhabdoid tumor. Malignant vascular tumors are rare, but epithelioid hemangioendothelioma (EHE) and angiosarcoma can be seen in children. The development and adoption of consensus diagnostic, therapeutic and risk-stratifying approaches for pediatric patients with malignant liver tumors has been historically challenged by their rarity and by their diverse clinical and histological appearance. On-going collaborative efforts of international consortia including the Children's Oncology Group (COG) in North America, the German Society of Paediatric Oncology and Haematology (GPOH), the Societe Internationale d' Oncologie Pediatrique Liver Tumor Study Group (SIOPEL) in Europe and the Japanese Liver Tumor group (JPLT), have made significant contributions to understanding the clinical and histopathological features, as well as the underlying biology of pediatric liver tumors, in particular HB. A new classification of pediatric liver tumors drafted at the international consensus meeting held in Los Angeles, has been incorporated in the recent WHO classification and is currently used by the PHITT (Paediatric Hepatic Malignancy International Tumour Trial) and other therapeutic protocols. This manuscript provides an overview of salient diagnostic features and updates in classification and molecular characterization for the most common pediatric primary liver neoplasms. It also includes a brief overview of other less common but relevant tumors, which should be considered in the differential diagnosis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"23-47"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012566","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":"Pediatric cancer predisposition syndromes involving non-central nervous system solid pediatric tumors: a review on their manifestations with a focus on histopathology.","authors":"B Schurink, M Reyes-Múgica, R R de Krijger","doi":"10.1007/s00428-025-04029-1","DOIUrl":"10.1007/s00428-025-04029-1","url":null,"abstract":"<p><p>Germline genetic alterations and their associated cancer predisposition syndromes (CPS) are an important cause of pediatric cancer. Early recognition is of great importance for targeted surveillance, early detection, and prompt (personalized) therapeutic interventions. This review provides an overview of non-central nervous system solid pediatric tumor types, in relation to their associated CPS, with an emphasis on their histology. It serves as a guide for (pediatric) pathologists to increase their awareness of histological clues that suggest a CPS and warrant referral to the clinical geneticist.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"3-21"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital melanocytic neoplasms: clinical, histopathological and recent molecular developments.","authors":"Claudia Maria Salgado, Alejandra Tomás-Velázquez, Miguel Reyes-Múgica","doi":"10.1007/s00428-024-04011-3","DOIUrl":"10.1007/s00428-024-04011-3","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"165-176"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germ cell tumors in children.","authors":"Peter Karl Bode, Luis Blasco-Santana, Isabel Colmenero, Miguel Reyes-Múgica","doi":"10.1007/s00428-025-04023-7","DOIUrl":"10.1007/s00428-025-04023-7","url":null,"abstract":"<p><p>Pediatric germ cell tumors represent a rare but biologically diverse group of neoplasms arising from pluripotent primordial germ cells. The 2022 edition of the WHO Classification of Pediatric Tumors introduced the first organ independent classification of germ cell tumors, reflecting advances in molecular biology, histopathology, and clinical practice. This review highlights the key changes, including the refined distinctions between the different subtypes. These updates enhance diagnostic accuracy and provide a framework for understanding age-dependent differences in tumor biology and behavior. Emphasis is placed on integrating the new classification into multidisciplinary care, particularly in addressing diagnostic challenges in pre- and post-pubertal-type germ cell tumors. By bridging the gap between histopathology and oncology, the updated classification represents a pivotal step forward in improving outcomes for children with germ cell tumors.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"65-79"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystic masses of the pediatric lung: update on congenital pulmonary airway malformation and its differential diagnosis.","authors":"Jennifer Pogoriler, Sara O Vargas","doi":"10.1007/s00428-024-04019-9","DOIUrl":"10.1007/s00428-024-04019-9","url":null,"abstract":"<p><p>Localized cystic lung lesions in pediatric patients encompass a spectrum of benign and rare malignant conditions that are quite distinct from cystic lung disease arising in adulthood. The majority have historically fallen under the diagnostic category of \"congenital pulmonary airway malformation,\" a term that has been used to denote a diverse group of diseases ranging in etiology from ectopia to bronchial atresia to mosaic oncogenic mutation or neoplasia. This article reviews the clinical characteristics, gross and histologic features, and pathogenetic underpinnings of congenital pulmonary airway malformation as well as lesions that enter its histologic differential diagnosis. In light of ongoing advances in the field, previously proposed pathology-based classification schemes are critically appraised, and a new diagnostic framework is considered.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"177-188"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910922","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":"Editorial: Challenges and novelties in pediatric pathology.","authors":"Isabel Colmenero, Miguel Reyes-Múgica","doi":"10.1007/s00428-025-04033-5","DOIUrl":"10.1007/s00428-025-04033-5","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1-2"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034180","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":"EGFR status assessment using reflex testing targeted next-generation sequencing for resected non-squamous non-small cell lung cancer.","authors":"Samantha Goffinet, Christophe Bontoux, Simon Heeke, Federica Pezzuto, Marius Ilié, Elodie Long-Mira, Sandra Lassalle, Olivier Bordone, Virginie Lespinet, Maryline Allégra, Virginie Tanga, Christelle Bonnetaud, Georges Garnier, Jonathan Benzaquen, Charlotte Cohen, Victoria Ferrari, Charles Marquette, Jean Philippe Berthet, Fiorella Calabrese, Paul Hofman, Véronique Hofman","doi":"10.1007/s00428-024-04010-4","DOIUrl":"https://doi.org/10.1007/s00428-024-04010-4","url":null,"abstract":"<p><p>EGFR status assessment is mandatory for adjuvant decision-making of resected stage IB-IIIA non-squamous non-small cell lung cancer (NS-NSCLC). It is questionable whether single-gene RT-PCR versus next-generation sequencing (NGS) should be used for this evaluation. Moreover, co-occurring mutations have an impact on tumor behavior and may influence future therapeutic decision-making. We aimed to describe the clinico-pathological and molecular features, as well as the prognostic factors of resected EGFR-mutant NS-NSCLC evaluated with reflex NGS and RT-PCR, so as to compare the results of the two methods. We retrospectively included and collected data from patients with resected EGFR-mutant NS-NSCLC diagnosed in our institution between 2005 and 2024. Additional cases from another center were included. Tumors were analyzed using targeted NGS and RT-PCR. A total of 153 patients were selected. The median follow-up after surgery was 22 months. The positive percent agreement of RT-PCR compared to NGS for the detection of an EGFR mutation was 88%. Common single EGFR mutations (L858R/del19) were observed in 117/153 (77%) cases; 22/153 (14%) and 14/153 (9%) cases had uncommon single and compound EGFR mutations, respectively. 63/153 (41%) patients had a co-occurring mutation, including a TP53 mutation in 43/63 (68%) co-mutated patients. EGFR/TP53-mutant tumors were associated with positive PD-L1 expression compared to EGFR-mutant/TP53-wild-type tumors (62% vs 39%; p = 0.006). Shorter median event-free survival (EFS) in patients with an EGFR exon 18 mutation and those with TP53 exon 7 co-mutation was recorded. The EGFR status should be systematically evaluated using targeted NGS reflex testing for resected NS-NSCLC since future therapeutic decision-making could soon consider integrating the presence of co-occurring mutations.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910923","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":"S100-positive stroma in salivary gland basal cell adenomas: a neoplastic component with CTNNB1 mutations.","authors":"Eiichi Sasaki, Yasuko Fujita, Katsuhiro Masago, Akari Iwakoshi, Nobuhiro Hanai, Hirokazu Matsushita","doi":"10.1007/s00428-024-04021-1","DOIUrl":"https://doi.org/10.1007/s00428-024-04021-1","url":null,"abstract":"<p><p>Basal cell adenomas (BCAs) are benign epithelial tumors of the salivary gland, characterized by the proliferation of basaloid and luminal cells. In addition, a distinctive spindle cell stroma, that is immunohistochemically-positive for S100, is often observed in BCAs. Based on the ultrastructural findings, the S100-positive stroma was presumed to originate from neoplastic myoepithelial cells. However, immunohistochemical studies do not provide strong evidence supporting a myoepithelial origin, and the true nature of this stroma remains elusive. The aim of this study was to determine whether the S100-positive stroma was neoplastic through a molecular analysis. We selected 2 cases involving BCAs with at least one S100-positive stromal area within the tumor, measuring ≥ 0.2 × 0.2 mm. CTNNB1 I35T mutations were detected in both tumors by Sanger sequencing. Two areas of S100-positive stroma from these two tumors were successfully dissected by manual microdissection using a stereomicroscope without contamination from the surrounding neoplastic bilayered epithelial cells. Because of the small number of dissected stromal cells, the mutation status of these two areas was analyzed using digital PCR, and CTNNB1 I35T mutations were detected in both. In conclusion, this study demonstrated that the S100-positive stroma of BCAs exhibits a neoplastic nature from a molecular perspective. While future studies are needed to confirm whether the S100-positive stroma originates from myoepithelial cells, BCAs morphologically display tricellular differentiation, with neoplastic spindle-shaped stromal cells along with a bilayered neoplastic epithelium.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898566","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}