Journal of Clinical Pathology最新文献

{"title":"Cholangiocarcinoma classification: current approach, relevance and challenges.","authors":"Benjamin Goeppert, Yoh Zen, Juan Valle, David Klimstra, Vikram Deshpande","doi":"10.1136/jcp-2024-209708","DOIUrl":"10.1136/jcp-2024-209708","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological characteristics of light chain proximal tubulopathy: a multicentre case series.","authors":"Yao Lin, Guolan Xing, Ruimin Hu, Shaojun Liu, Guisen Li, Ping Zhang, Feng Xu, Dandan Liang, Xiaodong Zhu, Mingchao Zhang, Fan Yang, Xinchen Yao, Feng Liu, Yujie Wang, Shihui Dong, Shaoshan Liang, Caihong Zeng","doi":"10.1136/jcp-2024-209620","DOIUrl":"10.1136/jcp-2024-209620","url":null,"abstract":"<p><strong>Aims: </strong>Light chain proximal tubulopathy (LCPT) is a rare complication of paraprotein-related diseases. We report a case series to present the clinicopathological characteristics and outcomes of LCPT.</p><p><strong>Methods: </strong>A multicentre retrospective case series of 47 patients with LCPT, consisting of 36 crystalline, three non-crystalline, and eight mixed LCPTs, was studied between January 2007 and December 2023.</p><p><strong>Results: </strong>The median age at diagnosis was 57 years. Presentations included proteinuria (100%), renal insufficiency (62%) and Fanconi syndrome (68%). The underlying haematological diagnoses were monoclonal gammopathy of renal significance in 81% and multiple myeloma in 19%. Monoclonal light chain (LC) was detected in all cases using serum/urine-free LC assays or immunofixation electrophoresis. Among 36 crystalline LCPTs, 34 were κ-restricted and 2 λ-restricted. Three non-crystalline LCPTs were all λ-restricted. In mixed LCPTs, seven were κ-restricted and one was λ-restricted. Notably, 66% frozen-section immunofluorescence failed to reveal restricted LC, requiring paraffin-immunofluorescence or immunoelectron microscopy. The appearance of inclusions displayed intraindividual homogeneity but interindividual heterogeneity in 42 patients and notable intraindividual heterogeneity in the remaining 5 patients. Haematological complete response, very good partial response and partial response occurred in 61%. Kidney function improved or remained stable in 84%, worsened in 8% and progressed to end-stage renal disease in 8%.</p><p><strong>Conclusions: </strong>Proteinuria and kidney dysfunction are the most common but less-specific renal manifestations of LCPTs, with most featuring Fanconi syndrome. Crystalline LCPT, primarily associated with κ-LC, is the predominant form. Most inclusions displayed intraindividual homogeneity and interindividual heterogeneity by electron microscopy. Most achieved haematological responses and favourable renal outcomes.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphoid enhancer-binding factor 1 (LEF1) immunostaining as a surrogate for β-catenin (<i>CTNNB1</i>) mutations.","authors":"Ekkehard Hewer, Pascal David Fischer, Erik Vassella, Laura Knabben, Sara Imboden, Michael D Mueller, Tilman T Rau, Matthias S Dettmer","doi":"10.1136/jcp-2024-209695","DOIUrl":"10.1136/jcp-2024-209695","url":null,"abstract":"<p><strong>Aims: </strong>Mutations affecting exon 3 of the β-catenin (<i>CTNNB1</i>) gene result in constitutive activation of WNT signalling and are a diagnostic hallmark of several tumour entities including desmoid-type fibromatosis. They also define clinically relevant tumour subtypes within certain entities, such as endometrioid carcinoma. In diagnostics, β-catenin immunohistochemistry is widely used as a surrogate for <i>CTNNB1</i> mutations. Yet, it is often difficult to assess in practice, given that the characteristic nuclear translocation may be focal or hard to distinguish from the spillover of the normal membranous staining.</p><p><strong>Methods: </strong>We therefore examined lymphoid enhancer-binding factor 1 (LEF1) immunostaining, a nuclear marker of WNT activation that serves as a potential surrogate for <i>CTNNB1</i> mutations.</p><p><strong>Results: </strong>In a cohort of endometrial carcinomas with known mutation status (n=130) LEF1 was 85% accurate in predicting <i>CTNNB1</i> mutation status (64% sensitivity, 90% specificity) while β-catenin was 76% accurate (72% sensitivity; 77% specificity). Across a variety of entities characterised by <i>CTNNB1</i> mutations as putative drivers, we found diffuse and strong expression of LEF1 in 77% of cases. LEF1 immunostaining proved easier to interpret than β-catenin immunostaining in 54% of cases, more difficult in 1% of cases and comparable in the remaining cases.</p><p><strong>Conclusion: </strong>We conclude that LEF1 immunostaining is a useful surrogate marker for <i>CTNNB1</i> mutations. It favourably complements β-catenin immunohistochemistry and outperforms the latter as a single marker.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of metastases in parotid gland lesions: clinical and cytological insights.","authors":"Federica Policardo, Angela Feraco, Pietro Tralongo, Federica Vegni, Antonino Mule', Liron Pantanowitz, Esther Diana Rossi","doi":"10.1136/jcp-2024-209663","DOIUrl":"https://doi.org/10.1136/jcp-2024-209663","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>NKX2-1</i> gene variants in solid tumours: the spectrum of gene variants and potential impact in surgical pathology diagnosis.","authors":"Ju-Yoon Yoon, Farah El-Sharkawy Navarro, Qiang Ding, Jason Rosenbaum, Salvatore Priore","doi":"10.1136/jcp-2024-209860","DOIUrl":"https://doi.org/10.1136/jcp-2024-209860","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking digital displays (monitors) for histological diagnoses: the nephropathology use case.","authors":"Giorgio Cazzaniga, Francesco Mascadri, Stefano Marletta, Alessandro Caputo, Gabriele Guidi, Giovanni Gambaro, Albino Eccher, Angelo Paolo Dei Tos, Fabio Pagni, Vincenzo L'Imperio","doi":"10.1136/jcp-2024-209418","DOIUrl":"10.1136/jcp-2024-209418","url":null,"abstract":"<p><strong>Aim: </strong>The digital transformation of the pathology laboratory is being continuously sustained by the introduction of innovative technologies promoting whole slide image (WSI)-based primary diagnosis. Here, we proposed a real-life benchmark of a pathology-dedicated medical monitor for the primary diagnosis of renal biopsies, evaluating the concordance between the 'traditional' microscope and commercial monitors using WSI from different scanners.</p><p><strong>Methods: </strong>The College of American Pathologists WSI validation guidelines were used on 60 consecutive renal biopsies from three scanners (Aperio, 3DHISTECH and Hamamatsu) using pathology-dedicated medical grade (MG), professional grade (PG) and consumer-off-the-shelf (COTS) monitors, comparing results with the microscope diagnosis after a 2-week washout period.</p><p><strong>Results: </strong>MG monitor was faster (1090 vs 1159 vs 1181 min, delta of 6-8%, p<0.01), with slightly better performances on the detection of concurrent diseases compared with COTS (κ=1 vs 0.96, 95% CI=0.87 to 1), but equal concordance to the commercial monitors on main diagnosis (κ<i>=</i>1). Minor discrepancies were noted on specific scores/classifications, with MG and PG monitors closer to the reference report (r=0.98, 95% CI=0.83 to 1 vs 0.98, 95% CI=0.83 to 1 vs 0.91, 95% CI=0.76 to 1, κ=0.93, 95% CI=077 to 1 vs 0.93, 95% CI=0.77 to 1 vs 0.86, 95% CI=0.64 to 1, κ=1 vs 0.50, 95% CI=0 to 1 vs 0.50, 95% CI=0 to 1, for IgA, antineutrophilic cytoplasmic antibody and lupus nephritis, respectively). Streamlined Pipeline for Amyloid detection through congo red fluorescence Digital Analysis detected amyloidosis on both monitors (4 of 30, 13% cases), allowing detection of minimal interstitial deposits with slight overestimation of the Amyloid Score (average 6 vs 7).</p><p><strong>Conclusions: </strong>The digital transformation needs careful assessment of the hardware component to support a smart and safe diagnostic process. Choosing the display for WSI is critical in the process and requires adequate planning.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary melanoma of the urinary tract: a clinicopathological study of cases and literature review.","authors":"Lisha Wang, Mohammed Wali, Yue Sun","doi":"10.1136/jcp-2024-209684","DOIUrl":"https://doi.org/10.1136/jcp-2024-209684","url":null,"abstract":"<p><strong>Aim: </strong>Primary malignant melanomas in the bladder or urethra are exceedingly rare. Diagnosing these tumours presents substantial challenges due to their close resemblance in gross appearance and histology to urothelial carcinomas.</p><p><strong>Methods: </strong>A retrospective review of our department archives from 2000 to 2023 identified four cases of primary malignant melanoma in the urinary tract. Demographic and clinical data were extracted from electronic medical records.</p><p><strong>Results: </strong>This retrospective case series investigates the clinical presentations, histopathological characteristics, immunohistochemical profiles and molecular features of four unique cases of primary malignant melanoma in the bladder or urethra.</p><p><strong>Conclusion: </strong>Our analysis aims to deepen the understanding of the diagnostic and management strategies for this extremely rare disease.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idiopathic granulomatous mastitis: a 5-year retrospective review of cases in a tertiary centre in Dublin, Ireland.","authors":"Elaine Houlihan, Katherine Ryan, Jennifer Mannion, Grace Hennessy, Barbara Dunne, Elizabeth Connolly, Brian O'Connell","doi":"10.1136/jcp-2023-209028","DOIUrl":"10.1136/jcp-2023-209028","url":null,"abstract":"<p><strong>Aims: </strong>Idiopathic granulomatous mastitis (IGM) is a rare, benign, inflammatory breast disorder of unknown aetiology usually affecting women of reproductive age. It classically presents as a unilateral painful breast mass. It is frequently mistaken for carcinoma or other inflammatory breast diseases. Diagnostic investigations include clinical examination, appropriate imaging and tissue sampling. A link between IGM and infection with the <i>Corynebacterium</i> species in particular <i>Corynebacterium kroppenstedtii</i> has been described.</p><p><strong>Methods: </strong>A retrospective single-centre cohort study was conducted over a 5-year period (2017-2022); all cases of IGM were identified.</p><p><strong>Results: </strong>Forty-one patients were diagnosed with IGM. Breast lump was the most common presenting complaint (n=29). The average age was 45 years. Eighteen patients had samples sent for culture and sensitivity, 11 of which had positive microbiology results indicative of <i>Corynebacterium</i> spp infection.An 82% resolution rate (27 of 33) was recorded in those who received either a short-antibiotic course or none at all. Eight patients reported persistent disease at 3 months, five of which had evidence of <i>Corynebacterium</i> spp.</p><p><strong>Discussion: </strong>This 5-year review highlights the impact of IGM in a tertiary centre in Dublin, Ireland. Although no treatment guidelines exist, options include antibiotics, immunomodulators and surgery. Due to risk of fistulae and unfavourable cosmetic outcomes, surgery should be reserved for refractory IGM. We suspect that there may be a subset of patients where prolonged antibiotic therapy should be considered. Defining this subgroup requires further study, but likely includes those with cystic neutrophilic granulomatous mastitis, relapsing disease and in whom <i>Corynebacterium</i> spp is recovered.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"835-841"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance evaluation of a CRISPR Cas9-based selective exponential amplification assay for the detection of KRAS mutations in plasma of patients with advanced pancreatic cancer.","authors":"Yue Shen, Xiaoling Zhang, Liyi Zhang, Zuoying Zhang, Bao Lyu, Qian Lai, Qinglin Li, Yuhua Zhang, Jieer Ying, Jinzhao Song","doi":"10.1136/jcp-2023-208974","DOIUrl":"10.1136/jcp-2023-208974","url":null,"abstract":"<p><strong>Aims: </strong>Pancreatic ductal adenocarcinoma (PDAC) is highly malignant, with shockingly mortality rates. KRAS oncoprotein is the main molecular target for PDAC. Liquid biopsies, such as the detection of circulating tumour DNA (ctDNA), offer a promising approach for less invasive diagnosis. In this study, we aim to evaluate the precision and utility of programmable enzyme-based selective exponential amplification (PASEA) assay for rare mutant alleles identification.</p><p><strong>Methods: </strong>PASEA uses CRISPR-Cas9 to continuously shear wild-type alleles during recombinase polymerase amplification, while mutant alleles are exponentially amplified, ultimately reaching a level detectable by Sanger sequencing. We applied PASEA to detect KRAS mutations in plasma ctDNA. A total of 153 patients with stage IV PDAC were enrolled. We investigated the relationship between ctDNA detection rates with various clinical factors.</p><p><strong>Results: </strong>Our results showed 91.43% vs 44.83% detection rate in patients of prechemotherapy and undergoing chemotherapy. KRAS ctDNA was more prevalent in patients with liver metastases and patients did not undergo surgical resection. Patients with liver metastases prior to chemotherapy showed a sensitivity of 95.24% (20/21) with PASEA. Through longitudinal monitoring, we found ctDNA may be a more accurate biomarker for monitoring chemotherapy efficacy in PDAC than CA19-9.</p><p><strong>Conclusions: </strong>Our study sheds light on the potential of ctDNA as a valuable complementary biomarker for precision targeted therapy, emphasising the importance of considering chemotherapy status, metastatic sites and surgical history when evaluating its diagnostic potential in PDAC. PASEA technology provides a reliable, cost-effective and minimally invasive method for detecting ctDNA of PDAC.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"853-860"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal carcinoembryonic antigen (CEA) cutoff values in the diagnosis of neoplastic mucinous pancreatic cysts differ among assays.","authors":"David Kim, Elizabeth Margolskee, Abha Goyal, Momin T Siddiqui, Jonas J Heymann, Rema Rao, Joshua Hayden","doi":"10.1136/jcp-2023-209136","DOIUrl":"10.1136/jcp-2023-209136","url":null,"abstract":"<p><strong>Aim: </strong>Pancreatic cyst fluid carcinoembryonic antigen (CEA) is a pivotal test in the diagnosis and management of neoplastic mucinous cysts (NMC) of the pancreas. Cyst fluid CEA levels of 192 ng/mL have been widely used to identify NMC. However, CEA values are unique to and significantly differ between individual assays with various optimal cutoffs reported in the literature for NMC. Here, we investigate the optimal CEA cut-off value of pancreatic cysts from two different assays to identify differences in thresholds.</p><p><strong>Methods: </strong>Pancreatic cyst fluid CEA levels, CEA assay platform (Beckman Dxl (BD) or Siemens Centaur XP (SC)), and clinical/pathological information were retrospectively collected. Cases were categorised into either NMC or non-NMC. Optimal CEA cut-off values were calculated via a receiver operator characteristic curve. Cut-off values were then identified separately by assay platform.</p><p><strong>Results: </strong>In total, 149 pancreatic cystic lesions with concurrent CEA values (SC: n=47; BD: n=102) were included. Histological correlation was available for 26 (17%) samples. The optimal CEA cut-off value for all samples at the study institution was 45.9 ng/mL (area under the curve (AUC)=86, Sn=85.7%, Sp=73.8%). When analysed separately by CEA assay, the cut-off values were 45.9 ng/mL (AUC=84.27, Sn=89.7%, Sp=71.4%) for BD and 24.4 ng/mL (AUC=77, Sn=81.8%, Sp=75%) for SC (p=0.48).</p><p><strong>Conclusions: </strong>This study showed an optimal pancreas cyst CEA cut-off threshold of 45.9 ng/mL, which is lower than commonly cited literature with different cutoffs on the two separate platforms (BD: 45.9 ng/mL, SC: 24.4 ng/mL).</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"848-852"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}