{"title":"The clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma.","authors":"Manami Kajiwara, Hideaki Takahashi, Masato Nakaguro, Daisuke Kawakita, Hideaki Hirai, Yoshitaka Utsumi, Makoto Urano, Yukiko Sato, Kiyoaki Tsukahara, Satoshi Kano, Kenji Okami, Hiroyuki Ozawa, Keisuke Yamazaki, Takuro Okada, Akira Shimizu, Kenji Hanyu, Akihiro Sakai, Mayu Yamauchi, Mariko Sekimizu, Toyoyuki Hanazawa, Yuki Saito, Yushi Ueki, Yoshitaka Honma, Tomoyuki Arai, Sho Iwaki, Koji Yamamura, Yorihisa Imanishi, Yuichiro Sato, Yuichiro Tada, Toshitaka Nagao","doi":"10.1007/s00428-024-03873-x","DOIUrl":"https://doi.org/10.1007/s00428-024-03873-x","url":null,"abstract":"<p><p>Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749167","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}
Virchows ArchivPub Date : 2024-07-22DOI: 10.1007/s00428-024-03876-8
Sandra Sunitsch, Philipp Fischer, Gudrun Pregartner, Peter Regitnig
{"title":"The misunderstanding of the R Classification-a survey amongst medical specialties treating breast cancer.","authors":"Sandra Sunitsch, Philipp Fischer, Gudrun Pregartner, Peter Regitnig","doi":"10.1007/s00428-024-03876-8","DOIUrl":"https://doi.org/10.1007/s00428-024-03876-8","url":null,"abstract":"<p><p>Frequent discussions in the tumour board about the Residual tumour (R) Classification of the UICC's \"TNM Classification of Malignant Tumours\", especially in the case of breast surgery specimens, raised the question about differing interpretations amongst different medical specialties. Thus, we designed a survey about the R Classification with a special focus on breast cancer specimens. An online survey was conducted, where a web link to the survey was distributed via email to various medical professional societies dealing with breast cancer in Austria and Germany with the request to distribute the link to their members. The study population consisted of physicians of all educational levels of different medical professions, who deal with breast carcinomas in their daily routine. Two hundred two participants, of which 160 (79.2%) have more than 10 years' professional experience, took part in the survey; 88 (43.6%) were surgeons/gynaecologists, 80 (39.6%) pathologists, 19 (9.4%) radiation oncologists/ therapists, 8 (4.0%) radiologists, and 7 (3.5%) oncologists. We show that the R Classification is not completely mastered by anyone and that there are significant differences in the interpretation of the R Classification between different medical specialties. For better differentiation between the residual tumour (R Classification) of the TNM and a pure resection margin assessment, we suggest the use of a Resection margin (Rm) Classification to avoid further misunderstandings. To assist better multidisciplinary cooperation and to ensure better patient care all medical disciplines should be educated about the actual meaning and correct application of the R Classification.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735126","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}
Virchows ArchivPub Date : 2024-07-20DOI: 10.1007/s00428-024-03879-5
Bharat Rekhi, Josephine K Dermawan, Karen J Fritchie, Annette Zimpfer, Tareq M Mohammad, Fatima S Ali, Koushik Nandy, Youran Zou, Robert Stoehr, Abbas Agaimy
{"title":"EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms.","authors":"Bharat Rekhi, Josephine K Dermawan, Karen J Fritchie, Annette Zimpfer, Tareq M Mohammad, Fatima S Ali, Koushik Nandy, Youran Zou, Robert Stoehr, Abbas Agaimy","doi":"10.1007/s00428-024-03879-5","DOIUrl":"https://doi.org/10.1007/s00428-024-03879-5","url":null,"abstract":"<p><p>With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56 years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5 cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21 months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731438","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}
Virchows ArchivPub Date : 2024-07-19DOI: 10.1007/s00428-024-03875-9
Fabienne Lange, Carol I Geppert, Veronika Bahlinger, Simone Bertz, Robert Stöhr, Danijel Sikic, Helge Taubert, Sven Wach, Bernd Wullich, Arndt Hartmann, Markus Eckstein
{"title":"Digital volumetric assessment of CIS and tumor mass compliments conventional histopathological assessment in muscle-invasive urothelial bladder cancer.","authors":"Fabienne Lange, Carol I Geppert, Veronika Bahlinger, Simone Bertz, Robert Stöhr, Danijel Sikic, Helge Taubert, Sven Wach, Bernd Wullich, Arndt Hartmann, Markus Eckstein","doi":"10.1007/s00428-024-03875-9","DOIUrl":"https://doi.org/10.1007/s00428-024-03875-9","url":null,"abstract":"<p><p>Carcinoma in situ (CIS) of the bladder is a known parameter regarding the prognosis and recurrence tendency of urothelial carcinomas. Nevertheless, there is little evidence whether the amount of CIS or other precursor lesions, as well as the quantified tumor mass of muscle-invasive urothelial carcinoma, has an influence on the survival or recurrence rate of affected patients. From 80 patients with muscle invasive urothelial bladder cancer and radical cystectomy, 23 samples each were obtained as part of a whole organ mapping in a single institution study, in which the precursor lesions and tumor area were digitally measured and further correlated to pathological standard parameters, patient survival, molecular luminal and basal subtypes, and immune infiltration. Significant correlations were found between tumor mass and surface lining CIS amount for pT-stage, lymphovascular invasion, and perineural infiltration. Furthermore, an increased tumor mass as well as an increased amount of CIS combined with an increased tumor mass showed a significantly reduced survival rate in multivariable analysis (HR = 2.75; P = 0.019 vs. HR = 3.54; P = 0.002) as well as a significantly increased recurrence. No correlations could be found with molecular subtypes and immune infiltration. The exact measurement of the tumor mass with and without the CIS surface area, whether manually or, more specifically, digitally, could be incorporated into routine diagnostics and implemented as an independent predictor for patient post-surgical outcomes. It can therefore serve as an additional predictor for risk stratification and, if necessary, intensified follow-up care or therapy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724605","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}
Virchows ArchivPub Date : 2024-07-18DOI: 10.1007/s00428-024-03877-7
Diana Bell, Michelle Afkhami
{"title":"Conundrum of 3N: nasopharyngeal nonkeratinizing non-viral carcinoma-reappraisal of fusions and report of two consecutive cases with unusual molecular findings.","authors":"Diana Bell, Michelle Afkhami","doi":"10.1007/s00428-024-03877-7","DOIUrl":"https://doi.org/10.1007/s00428-024-03877-7","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634590","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}
Virchows ArchivPub Date : 2024-07-18DOI: 10.1007/s00428-024-03858-w
Frederico Portugal-Gaspar, Antonio Lopez-Beltran, Gladell P Paner, Ana Blanca, Enrique Gómez Gómez, Rodolfo Montironi, Alessia Cimadamore, Andreia Bilé, Metka Volavšek, Liang Cheng
{"title":"Giant cell carcinoma of the urinary bladder : Clinicopathologic analysis and oncological outcomes.","authors":"Frederico Portugal-Gaspar, Antonio Lopez-Beltran, Gladell P Paner, Ana Blanca, Enrique Gómez Gómez, Rodolfo Montironi, Alessia Cimadamore, Andreia Bilé, Metka Volavšek, Liang Cheng","doi":"10.1007/s00428-024-03858-w","DOIUrl":"https://doi.org/10.1007/s00428-024-03858-w","url":null,"abstract":"<p><p>We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60-90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50-90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634591","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}
Virchows ArchivPub Date : 2024-07-12DOI: 10.1007/s00428-024-03865-x
Vincent Francis Castillo, Kiril Trpkov, Rola Saleeb
{"title":"Contemporary review of papillary renal cell carcinoma-current state and future directions.","authors":"Vincent Francis Castillo, Kiril Trpkov, Rola Saleeb","doi":"10.1007/s00428-024-03865-x","DOIUrl":"https://doi.org/10.1007/s00428-024-03865-x","url":null,"abstract":"<p><p>Historically, papillary renal cell carcinoma (PRCC) was divided into two types, type 1 and type 2, based solely on morphology. However, it is apparent that PRCC is far more complex and represents a histological, clinical, and molecular spectrum. There has been a significant evolution in our understanding of PRCC, highlighted by the recognition of new and molecularly defined entities that were previously included in PRCC type 2. This contemporary review addresses the evolving concepts regarding the PRCC, including why it is no longer needed to subtype PRCC, the current molecular landscape, prognostic parameters, and PRCC variants, including biphasic PRCC, papillary renal neoplasm with reverse polarity, and Warthin-like PRCC. Pathologists should also be aware of the potential mimickers of both low-grade and high-grade PRCCs as well as some new and emerging entities that may show papillary growth that should be excluded in the diagnostic workup. The evolving knowledge of PRCC biomarkers, morphologic patterns, and PRCC variants could also have important implications for clinical management. Lastly, the heterogeneity within the PRCC spectrum needs to be further studied, aiming to better stratify PRCC for appropriate clinical management and systemic therapy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591522","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}
Virchows ArchivPub Date : 2024-07-12DOI: 10.1007/s00428-024-03869-7
Michaela Kendall Bártů, Miroslava Flídrová, Kristýna Němejcová, Jan Hojný, Jiří Dvořák, Květoslava Michalová, Pavel Dundr
{"title":"Endometrial stromal tumor with whorling and GREB1::CTNNB1 fusion-a case report on a rare entity.","authors":"Michaela Kendall Bártů, Miroslava Flídrová, Kristýna Němejcová, Jan Hojný, Jiří Dvořák, Květoslava Michalová, Pavel Dundr","doi":"10.1007/s00428-024-03869-7","DOIUrl":"https://doi.org/10.1007/s00428-024-03869-7","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591523","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}
Virchows ArchivPub Date : 2024-07-12DOI: 10.1007/s00428-024-03868-8
Satoshi Tanikawa, Danielle M Andrade, Ekaterina Rogaeva, Maria Carmela Tartaglia, Gabor G Kovacs
{"title":"Novel neuropathological findings in a long-term survivor of D-2-hydroxyglutaric aciduria type 1.","authors":"Satoshi Tanikawa, Danielle M Andrade, Ekaterina Rogaeva, Maria Carmela Tartaglia, Gabor G Kovacs","doi":"10.1007/s00428-024-03868-8","DOIUrl":"https://doi.org/10.1007/s00428-024-03868-8","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591524","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}