Virchows Archiv最新文献

{"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}

{"title":"Prostatic amyloidosis: pathological features of an underdiagnosed condition.","authors":"José A Ortiz-Rey, Jorge Sánchez-Ramos, Samer Abdulkader-Sande, David Muñoz-Raya, José Aguayo-Arjona, Alfonso Fernández-Costas, Carolina Gómez-de María, Lourdes Liste-Tizón, Edgar J Escalona-Canal, Sergio Raposeiras-Roubín, Rafael J Cobas-Paz, Pilar San Miguel-Fraile, Enrique Cespón-Outeda, María Cespón-Fernández","doi":"10.1007/s00428-024-04014-0","DOIUrl":"https://doi.org/10.1007/s00428-024-04014-0","url":null,"abstract":"<p><p>Amyloidosis is a rare disease that can affect genitourinary organs but the involvement of the prostate has been documented in a limited number of cases. We have reviewed morphologic and immunohistochemical features of prostate biopsies or surgical specimens in which an initial diagnosis of amyloidosis was made. Prostatic amyloidosis was diagnosed in 25 patients, 21 of them were needle biopsies (1.16% of these ones). Amyloid was observed inside vessel walls (25 cases) and the stroma (3). No significant differences in the number of affected biopsy samples between patients with and without cardiac amyloidosis were found. In prostatectomies, amyloid was visualized in all the regions of the prostate, being more abundant in the periphery and the posterolateral tissue. Three patients with abundant amyloid in the prostatectomy did not have cardiac amyloidosis. Immunohistochemically prostatic amyloid was positive for transthyretin and P amyloid (24 cases). A amyloid, kappa, and lambda chains were negative. The genetic analysis revealed transthyretin wild-type amyloidosis. Immunohistochemistry was not conclusive in one case of immunoglobulin light chain amyloidosis. In conclusion, prostate amyloidosis is an infrequent finding characterized by the deposition of amyloid inside small vessel walls, and less often in the stroma. It occurs mainly in the periphery of the gland. Amyloid deposits are often subtle and overlooked but relevant as this may be the first sample in which systemic amyloidosis is diagnosed. Immunohistochemistry can be used to subtype amyloid, although there are limitations when confronted with immunoglobulin light chain amyloidosis. Most cases have corresponded to wild-type transthyretin amyloidosis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883100","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":"Interstitial lipoid pneumonia-A complication of intravenous administration of lipid emulsions in critically ill patients.","authors":"E M V de Cuba, W Vreuls, C G Tan, D B Flieder, E Thunnissen","doi":"10.1007/s00428-024-04000-6","DOIUrl":"https://doi.org/10.1007/s00428-024-04000-6","url":null,"abstract":"<p><p>Lipoid pneumonia is a rare entity most often associated with inhalation of foreign material (i.e. \"fire-eater's lung\"), silicone injection, and severe trauma. We present the case of a 61-year old man who developed acute respiratory distress syndrome following endoscopic retrograde cholangiopancreatography (ERCP) for cholelithiasis. Intensive care supportive therapy included mechanical ventilation, dialysis, and total parenteral nutrition. Unresolved pneumothorax necessitated lobectomy. Histology of the lobectomy specimen demonstrated massive intra-alveolar haemorrhage and numerous alveolar septal macrophages with clear cytoplasmic vacuoles. These findings were diagnostic of interstitial lipoid pneumonia due to intravenous administration of lipid emulsions. The differential diagnosis is also discussed. Although rare, interstitial lipoid pneumonia should be considered in critically ill patients presenting with an interstitial pattern of lung disease after intravenous administration of lipid emulsions.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855274","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":"Prognosis and tumor microenvironment in pseudohypoxic pheochromocytoma/paraganglioma.","authors":"Akihiro Ohmoto, Yasuyuki Shigematsu, Rumiko Saito, Akito Dobashi, Yu Fujiwara, Yuki Togashi, Junji Yonese, Kentaro Inamura, Shunji Takahashi","doi":"10.1007/s00428-024-04009-x","DOIUrl":"https://doi.org/10.1007/s00428-024-04009-x","url":null,"abstract":"<p><p>Pheochromocytoma and paraganglioma (PPGL) are rare tumors that occur in the adrenal medulla and extra-adrenal tissues, respectively. The prognosis and tumor microenvironment (TME) of pseudohypoxic PPGL as a major entity have not been fully described. Based on the clinical database of 65 patients with PPGL, we assessed the morphological features as well as the immunohistochemistry of pseudohypoxia-related proteins (SDHB and CAIX) and TME-related immune cell markers. Furthermore, we compared the relapse-free survival (RFS) rates in localized patients between the pathological subgroups. Among 50 available specimens, 84% and 30% of the cases exhibited at least one morphological adverse feature including vascular/capsular invasion and a Ki-67 index > 3%, respectively. The SDHB and CAIX positivity rates were 81% and 51%. Concerning the immune cell markers, the CD163-positive cell numbers were higher in hypoxia-associated PPGL composed of SDHB-negative or CAIX-positive cases than in non-hypoxia PPGL (median 66 vs. 23/mm²). Concerning prognosis, RFS rates were significantly lower in cases with Ki-67 indices > 3% and SDHB-negativity than in those with Ki-67 indices ≤ 3% and SDHB-positivity (3-year rate: 64% vs. 100%, P < 0.001; 57% vs. 100%, P = 0.03). In contrast, RFS was comparable between CAIX-positive and CAIX-negative PPGL cases. Our analyses suggested that SDHB-deficient PPGL exhibited a higher incidence of relapse. Furthermore, M2 macrophage infiltration in TME might be crucial in pseudohypoxic PPGL pathogenesis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855278","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":"Primary cutaneous rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion: four new cases with distinctive morphology, immunophenotypic, and genetic profile.","authors":"Isidro Machado, Eva Wardelmann, Ming Zhao, Jing Song, Yanli Wang, Stephan Alexander Braun, Lluís Catasús, Malena Ferré, Irina Leoveanu, Jula Westhoff, Thomas Rüdiger, Sílvia Bagué","doi":"10.1007/s00428-024-04007-z","DOIUrl":"https://doi.org/10.1007/s00428-024-04007-z","url":null,"abstract":"<p><p>EWSR1/FUS::TFCP2-rearranged rhabdomyosarcoma (RMS) is a rare tumor with an aggressive clinical course, a predilection for craniofacial bones, spindled and/or epithelioid histomorphology, and positive immunohistochemistry (IHC) for epithelial and myogenic markers, along with variable ALK expression. Herein, we present four additional cases of primary cutaneous TFCP2-rearranged RMS. Notably, one tumor (case 1) displayed a varied pathological spectrum, initially presenting as a low-grade spindle cell neoplasm, but progressed into a high-grade spindle/epithelioid tumor. Another case (case 2) exhibited a predominant high-grade epithelioid/rhabdoid morphology. The third case (case 3) demonstrated a biphasic appearance of spindle and epithelioid cell proliferation, presenting with a low-grade morphology, and the last case (case 4) showed a predominant epithelioid morphology. All cases showed myogenic differentiation associated with keratins and ALK immunoreactivity. Interestingly, the two cases with high-grade and epithelioid morphology demonstrated CD30 immunoexpression. RNAseq or FISH revealed EWSR1 or FUS::TFCP2 gene fusion, and two cases with aggressive evolution showed ALK cluster-amplification as well, a finding that has not been previously reported. Two cases displayed aggressive behavior, with case 1 experiencing local recurrences and undergoing transformation into a high-grade epithelioid tumor, whereas case 2 initially presented as an epithelioid high-grade neoplasm, subsequently developing lymph node metastases and shortly thereafter distant metastases. In contrast, patients 3 and 4 are alive with no evidence of disease. The distinctive morphology and immunoprofile of this neoplasm may pose challenges in the differential diagnosis with cutaneous neoplasms showing keratins, ALK, and CD30 immunoreactivity. Nonetheless, ALK and CD30 overexpression may offer avenues for targeted therapy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847883","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":"The role of the pathologist in the design and conducting of biomarker-driven clinical trials in cancer: position paper of the European Society of Pathology.","authors":"Xavier Matias-Guiu, Maria Rosaria Raspollini, Janina Kulka, Ales Ryska, Raed Al Dieri, Peter Schirmacher","doi":"10.1007/s00428-024-04005-1","DOIUrl":"https://doi.org/10.1007/s00428-024-04005-1","url":null,"abstract":"<p><p>Clinical trials in oncology are important tools to identify and establish new effective drugs for cancer treatment. Since the development of the concept of precision oncology, a huge number of multi-centric biomarker-driven clinical trials have been performed and promoted by either academic institutions or pharmaceutical companies. In this scenario, the role of pathologists is essential in multiple aspects, with new challenges that should be addressed. In this position paper of the European Society of Pathology, the role of pathologists as contributors to the design of the clinical trial, as local collaborators, or as members of central review laboratories is discussed. Moreover, the paper emphasizes the important role of pathologists in guiding methods and criteria of tissue biomarker testing in the biomarker-driven clinical trials. The paper also addresses issues regarding quality control, training, and the possible role of digital pathology.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847886","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}