Journal of Pathology Clinical Research最新文献

{"title":"CD70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma","authors":"Shingo Inaguma,&nbsp;Akane Ueki,&nbsp;Jerzy Lasota,&nbsp;Masayuki Komura,&nbsp;Asraful Nahar Sheema,&nbsp;Piotr Czapiewski,&nbsp;Renata Langfort,&nbsp;Janusz Rys,&nbsp;Joanna Szpor,&nbsp;Piotr Waloszczyk,&nbsp;Krzysztof Okoń,&nbsp;Wojciech Biernat,&nbsp;David S Schrump,&nbsp;Raffit Hassan,&nbsp;Markku Miettinen,&nbsp;Satoru Takahashi","doi":"10.1002/cjp2.310","DOIUrl":"10.1002/cjp2.310","url":null,"abstract":"<p>Diffuse pleural mesothelioma (PM) is a highly aggressive tumour typically associated with short survival. Recently, the effectiveness of first-line immune checkpoint inhibitors in patients with unresectable PM was reported. CD70–CD27 signalling plays a co-stimulatory role in promoting T cell expansion and differentiation through the nuclear factor κB (NF-κB) pathway. Conversely, the PD-L1 (CD274)–PD-1 (PDCD1) pathway is crucial for the modulation of immune responses in normal conditions. Nevertheless, pathological activation of both the CD70–CD27 and PD-L1–PD-1 pathways by aberrantly expressed CD70 and PD-L1 participates in the immune evasion of tumour cells. In this study, 171 well-characterised PMs including epithelioid (<i>n</i> = 144), biphasic (<i>n</i> = 15), and sarcomatoid (<i>n</i> = 12) histotypes were evaluated immunohistochemically for CD70, PD-L1, and immune cell markers such as CD3, CD4, CD8, CD56, PD-1, FOXP3, CD68, and CD163. Eight percent (14/171) of mesotheliomas simultaneously expressed CD70 and PD-L1 on the tumour cell membrane. PMs co-expressing CD70 and PD-L1 contained significantly higher numbers of CD8+ (<i>p</i> = 0.0016), FOXP3+ (<i>p</i> = 0.00075), and CD163+ (<i>p</i> = 0.0011) immune cells within their microenvironments. Overall survival was significantly decreased in the cohort of patients with PM co-expressing CD70 and PD-L1 (<i>p</i> &lt; 0.0001). <i>In vitro</i> experiments revealed that PD-L1 and CD70 additively enhanced the motility and invasiveness of PM cells. In contrast, PM cell proliferation was suppressed by PD-L1. PD-L1 enhanced mesenchymal phenotypes such as N-cadherin up-regulation. Collectively, these findings suggest that CD70 and PD-L1 both enhance the malignant phenotypes of PM and diminish anti-tumour immune responses. Based on our observations, combination therapy targeting these signalling pathways might be useful in patients with PM.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/0d/CJP2-9-195.PMC10073927.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting microsatellite instability and key biomarkers in colorectal cancer from H&E-stained images: achieving state-of-the-art predictive performance with fewer data using Swin Transformer","authors":"Bangwei Guo,&nbsp;Xingyu Li,&nbsp;Miaomiao Yang,&nbsp;Jitendra Jonnagaddala,&nbsp;Hong Zhang,&nbsp;Xu Steven Xu","doi":"10.1002/cjp2.312","DOIUrl":"10.1002/cjp2.312","url":null,"abstract":"Many artificial intelligence models have been developed to predict clinically relevant biomarkers for colorectal cancer (CRC), including microsatellite instability (MSI). However, existing deep learning networks require large training datasets, which are often hard to obtain. In this study, based on the latest Hierarchical Vision Transformer using Shifted Windows (Swin Transformer [Swin‐T]), we developed an efficient workflow to predict biomarkers in CRC (MSI, hypermutation, chromosomal instability, CpG island methylator phenotype, and BRAF and TP53 mutation) that required relatively small datasets. Our Swin‐T workflow substantially achieved the state‐of‐the‐art (SOTA) predictive performance in an intra‐study cross‐validation experiment on the Cancer Genome Atlas colon and rectal cancer dataset (TCGA‐CRC‐DX). It also demonstrated excellent generalizability in cross‐study external validation and delivered a SOTA area under the receiver operating characteristic curve (AUROC) of 0.90 for MSI, using the Molecular and Cellular Oncology dataset for training (N = 1,065) and the TCGA‐CRC‐DX (N = 462) for testing. A similar performance (AUROC = 0.91) was reported in a recent study, using ~8,000 training samples (ResNet18) on the same testing dataset. Swin‐T was extremely efficient when using small training datasets and exhibited robust predictive performance with 200–500 training samples. Our findings indicate that Swin‐T could be 5–10 times more efficient than existing algorithms for MSI prediction based on ResNet18 and ShuffleNet. Furthermore, the Swin‐T models demonstrated their capability in accurately predicting MSI and BRAF mutation status, which could exclude and therefore reduce samples before subsequent standard testing in a cascading diagnostic workflow, in turn reducing turnaround time and costs.","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/91/CJP2-9-223.PMC10073932.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9623034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First proficiency testing for NGS-based and combined NGS- and FISH-based detection of FGFR2 fusions in intrahepatic cholangiocarcinoma","authors":"Olaf Neumann,&nbsp;Ulrich Lehmann,&nbsp;Stephan Bartels,&nbsp;Nicole Pfarr,&nbsp;Thomas Albrecht,&nbsp;Katharina Ilm,&nbsp;Jens Christmann,&nbsp;Anna-Lena Volckmar,&nbsp;Hannah Goldschmid,&nbsp;Martina Kirchner,&nbsp;Michael Allgäuer,&nbsp;Maria Walker,&nbsp;Hans Kreipe,&nbsp;Andrea Tannapfel,&nbsp;Wilko Weichert,&nbsp;Peter Schirmacher,&nbsp;Daniel Kazdal,&nbsp;Albrecht Stenzinger","doi":"10.1002/cjp2.308","DOIUrl":"10.1002/cjp2.308","url":null,"abstract":"<p>Intrahepatic cholangiocarcinoma harbours druggable genetic lesions including <i>FGFR2</i> gene fusions. Reliable and accurate detection of these fusions is becoming a critical component of the molecular work-up, but real-world data on the performance of fluorescence <i>in situ</i> hybridisation (FISH) and targeted RNA-based next-generation sequencing (NGS) are very limited. Bridging this gap, we report results of the first round robin test for <i>FGFR2</i> fusions in cholangiocarcinoma and contextualise test data with genomic architecture. A cohort of 10 cholangiocarcinoma (4 fusion positive and 6 fusion negative) was tested by the Institute of Pathology, University Hospital Heidelberg, Germany. Data were validated by four academic pathology departments in Germany. Fusion-positive cases comprised <i>FGFR2</i>::<i>BICC1</i>, <i>FGFR2</i>::<i>DBP</i>, <i>FGFR2</i>::<i>TRIM8</i>, and <i>FGFR2</i>::<i>ATE1</i> fusions. In a second step, a round robin test involving 21 academic and non-academic centres testing with RNA-based NGS approaches was carried out; five participants performed FISH testing in addition. Thirteen of 16 (81%) centres successfully passed the NGS only and 3 of 5 (60%) centres passed the combined NGS + FISH round robin test. Identified obstacles were bioinformatic pipelines not optimised for the detection of <i>FGFR2</i> fusions and assays not capable of detecting unknown fusion partners. This study shows the benefit of targeted RNA-NGS for the detection of <i>FGFR2</i> gene fusions. Due to the marked heterogeneity of the genomic architecture of these fusions, fusion partner agnostic (i.e. open) methodological approaches that are capable of identifying yet unknown fusion partners are superior. Furthermore, we highlight pitfalls in subsequent bioinformatic analysis and limitations of FISH-based tests.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD47 and CD68 expression in breast cancer is associated with tumor-infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis","authors":"Ying Chen,&nbsp;Tor Audun Klingen,&nbsp;Hans Aas,&nbsp;Elisabeth Wik,&nbsp;Lars A Akslen","doi":"10.1002/cjp2.309","DOIUrl":"10.1002/cjp2.309","url":null,"abstract":"<p>CD47 expressed on tumor cells binds to signal regulatory protein alpha on macrophages, initiating inhibition of phagocytosis. We investigated the relationships between tumor expression of CD47 and CD68 macrophage content, subsets of tumor-infiltrating lymphocytes (TILs), and vascular invasion in breast cancer. A population-based series of 282 cases (200 screen detected and 82 interval patients) from the Norwegian Breast Cancer Screening Program was examined. Immunohistochemical staining for CD47 and CD68 was evaluated on tissue microarray (TMA) slides. For CD47 evaluation, a staining index was used. CD68 tumor-associated macrophages were counted and dichotomized. TIL subsets (CD45, CD3, CD4, CD8, and FOXP3) were counted and dichotomized using immunohistochemistry on TMA slides. Vascular invasion (both lymphatic and blood vessel) was determined on whole tissue slides. High CD47 tumor cell expression or high counts of CD68 macrophages were significantly associated with elevated levels of all TIL subsets (<i>p</i> &lt; 0.02), CD163 macrophages (<i>p</i> &lt; 0.001), blood vessel invasion (CD31 positive) (<i>p</i> &lt; 0.01), and high tumor cell Ki67 (<i>p</i> &lt; 0.004). High CD47 expression was associated with ER negativity (<i>p</i> &lt; 0.001), HER2 positive status (<i>p</i> = 0.03), and interval-detected tumors (<i>p</i> = 0.03). Combined high expression of CD47–CD68 was associated with a shorter recurrence-free survival (RFS) by multivariate analysis (hazard ratio [HR]: 2.37, <i>p</i> = 0.018), adjusting for tumor diameter, histologic grade, lymph node status, and molecular subtype. Patients with luminal A tumors showed a shorter RFS for CD47–CD68 high cases by multivariate assessment (HR: 5.73, <i>p</i> = 0.004). This study demonstrates an association of concurrent high CD47 tumor cell expression and high CD68 macrophage counts with various TIL subsets, blood vessel invasion (CD31 positive), other aggressive tumor features, and interval-presenting breast cancer. Our findings suggest a link between CD47, tumor immune response, and blood vessel invasion (CD31 positive). Combined high expression of CD47–CD68 was an independent prognostic factor associated with poor prognosis in all cases, as well as in the luminal A category.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ripened and Revamped-Adult T Cell Leukaemia/ Lymphoma","authors":"Anubha Bajaj","doi":"10.23880/cprj-16000151","DOIUrl":"https://doi.org/10.23880/cprj-16000151","url":null,"abstract":"Adult T cell leukaemia/ lymphoma is an aggressive T cell malignant disorder comprised of significantly pleomorphic, miniature to intermediate, mature CD4+ T cells. Factors such as demographic distribution within HTLV1 endemic zones, hypercalcemia, cutaneous lesions and a leukemic phase contribute to disease emergence. Adult T cell leukaemia/ lymphoma incriminates peripheral blood, lymph nodes, spleen, cutaneous surfaces, pulmonary or hepatic parenchyma, gastrointestinal tract and central nervous system. Bone marrow may demonstrate diffuse, interstitial or sinusoidal pattern of neoplastic occurrence. Generally, tumour cells are permeated with basophilic cytoplasm, absent intracytoplasmic granules, irregular or poly-lobulated nuclei with homogeneous, condensed nuclear chromatin and miniature nucleoli.","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135550315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral &amp; Maxillofacial Space Infections-A 10-Year Retrospective Study","authors":"Ashok Kumar","doi":"10.23880/cprj-16000153","DOIUrl":"https://doi.org/10.23880/cprj-16000153","url":null,"abstract":"Oral &amp; Maxillofacial space infections have been recognized since the time of Galen in the second century. In spite of great advances in health care, these infections remain a major problem. Oral &amp; Maxillofacial space infection ranges from periapical abscess to superficial and deep neck infections. The infections generally follow the path of least resistance through connective tissue and along fascial planes [1]. The infections spread to distant sites from the site of origin. Oral &amp; Maxillofacial infections can be potentially lethal infections, at times. Various life-threatening complications associated with oral &amp; maxillofacial infections are respiratory obstruction, necrotizing fasciitis, descending mediastinitis, pericarditis, brain abscess, and sepsis. The successful management of orofacial infection depends on the early recognition of orofacial infection. Appropriate and prompt therapy is mandatory for successful management. Thorough knowledge of anatomy is necessary to predict pathways of spread and to drain these spaces adequately. We present our experience in treating oral &amp; maxillofacial space infection at our centre","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135550575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compartment Syndrome of the Hand after Multiple Fractures of the Metacarpals: A Rare Localization with a Poor Prognosis: Two Case Reports and a Literature Review","authors":"Bouziane W","doi":"10.23880/cprj-16000156","DOIUrl":"https://doi.org/10.23880/cprj-16000156","url":null,"abstract":"Compartment syndrome is a surgical emergency. In fact, it is a “race against the clock” we will discuss our experience with two cases who presented with hand compartment syndrome after suffering numerous metacarpal fractures The treatment included a discharge incisions, metacarpal pinning, and close hand surveillance.","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135550746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Polymyositis Treated with the Homoeopathic Medicine Lathyrus Satyvus","authors":"Yasmin Firdaus A","doi":"10.23880/cprj-16000158","DOIUrl":"https://doi.org/10.23880/cprj-16000158","url":null,"abstract":"Polymyositis is one of the idiopathic inflammatory myopathies, a rare connective tissue disorders defined by the presence of weakness of muscles and inflammation. The estimated prevalence of polymyositis and dermatomyositis is 5 to 22 per 100,000 persons, and the incidence is approximately 1.2 to 19 per million persons at risk per year. Polymyositis rarely occurs in the paediatric age group, and the mean age is between 50 to 60 years. This article is on a case of polymyositis which was completely bed ridden before reaching our hospital. With thorough case taking and finding out the Totality Lathyrus Sativus 200 was prescribed. Muscle strength grading was done to evaluate the improvement before and after treatment. The case started improving within a period of 1 week. The muscle strength grading which was Grade 1 during the beginning of treatment improved to Grade 3 within a period of 1 month. The improvement was gradual and also within a period of 1 month the patient started walking with support. This shows the management of polymyositis with the Homeopathic medicine Lathyrus Sativus.","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135550760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenteric Mesothelial Cyst Presented as Acute Abdominal Pain","authors":"Jagtap SV","doi":"10.23880/cprj-16000154","DOIUrl":"https://doi.org/10.23880/cprj-16000154","url":null,"abstract":"Mesenteric cysts are rare intra-abdominal tumors. The preoperative diagnosis of mesenteric cysts is challenging due to its rarity. We present a case of 65 -years-old female with history of progressive increasing abdominal discomfort and swelling she presented with sudden acute abdominal pain of 5 days. Physical examination revealed a mildly tender, palpable abdominal swelling occupying right iliac fossa measuring 10x8x3 cm. Plain and contrast computed tomography scan abdomen and pelvis showed an intra-abdominal well defined, thin walled cystic lesion in right iliac fossa and extending upto right hypochondriac region. It showed multiple thin internal septae and low level mobile internal echoes. On radio imaging suggestive of a mesenteric cyst was given and histopathological correlation was advised. The exploratory laprotomy with complete surgical excisions of cystic mass was done. The histopathological diagnosis of benign mesothelial cyst of mesentry was given. We are presenting rare case of simple mesenteric cyst for its clinical, radio imaging and histomorphological features.","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135551008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic Characterization of Double PIK3CA Mutated Advanced Breast Cancer: A Retrospective Cohort Study from a Single Institution","authors":"Zhan H","doi":"10.23880/cprj-16000155","DOIUrl":"https://doi.org/10.23880/cprj-16000155","url":null,"abstract":"Objectives: We aimed to characterize the clinicopathologic and molecular features of double PIK3CA mutated advanced breast cancer in a retrospective cohort study. Methods: This retrospective study included 196 advanced breast cancer patients who had the Oncomine next generation sequencing analysis. The clinicopathologic parameters were recorded for each individuals including age, tumor type, grade, ER, PR, HER2, and recurrence free survival. Results: PIK3CA mutations were detected in 77.5% (152/196) of advanced breast cancer patients, 129 (84.8%) of which contained single mutations, 20 (13.1%) of which contained double mutations, and 3 (2%) of which contained triple mutations. Double PIK3CA mutated tumors were mostly seen in postmenopausal women, had lower combined histologic grade, and were enriched in hormone receptor positive human epidermal growth factor receptor negative (HR+/HER2-) disease. Double PIK3CA mutations were more frequently associated with concurrent mutations of ESR1 (p=0.017) and ARID1A (p=0.054) compared to single PIK3CA mutations. No significant progression free survival differences were observed between PIK3CA mutated and wild-type groups and between double and single PIK3CA mutated groups when applied to all patients or HR+/ HER2- patients. Conclusion: Double PIK3CA mutated advanced breast cancer have similar clinicopathologic features as single mutated ones but demonstrate unique molecular features.","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135550765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}