PathologyPub Date : 2026-09-10DOI: 10.1016/j.pathol.2026.07.011
Paul Sun Woo Kim, Stephen Adelstein, Alex Stoyanov
{"title":"The clinical utility and healthcare cost of antinuclear antibody testing in inpatients at a major tertiary hospital.","authors":"Paul Sun Woo Kim, Stephen Adelstein, Alex Stoyanov","doi":"10.1016/j.pathol.2026.07.011","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.07.011","url":null,"abstract":"<p><p>Antinuclear antibody (ANA) tests lack specificity and are often ordered in low pretest probability settings, leading to a low positive predictive value (PPV). Limited data exist on the clinical utility and cost of ANAs and ANA-related tests, such as extractable nuclear antigens for hospital inpatients, which this retrospective cohort study aimed to investigate. Among 183 adult inpatients who underwent ANA testing from January to February 2023 at Royal Prince Alfred Hospital, Sydney, 105 patients with a positive ANA were examined in greater detail. The primary outcomes were the PPV of ANAs in detecting autoimmune ANA-related diseases (ARDs) such as systemic lupus erythematosus, the indication for ordering the ANA, and the Medicare Benefits Schedule fees of ANAs and related tests ordered up to 6 months after the initial ANA. A total of 117 positive ANAs (including repeats) were recorded, but only two ARDs were newly diagnosed (PPV=1.7%), demonstrating a high rate of false positives. Most positive tests were ordered for workup of organ-specific dysfunction, the top three categories being hepatic (n=38), neurological (n=16), and haematological (n=13) abnormalities. The most common specific indication was undifferentiated abnormal liver function tests (LFTs) (n=27). The total fees of ANAs and related tests were AUD$11,415, equating to AUD$5,707.50 per diagnosis given a positive ANA. This study is among the first to show the low PPV of ANAs in inpatients and to quantify the high costs of ANAs and ANA-related testing in this population. This low PPV may be due to ANAs being requested contrary to the 'Choosing Wisely' guidelines which encourages more judicious ordering in low pretest probability settings such as screening in LFT abnormalities. Since the most common reason for ANA requests was for investigation of hepatic dysfunction, development of scoring tools to evaluate pretest probability before ordering ANAs should be considered.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166852","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}
PathologyPub Date : 2026-09-09DOI: 10.1016/j.pathol.2026.08.004
Mark James Wilsher, Talvinger Singh
{"title":"Myopericytoma with a glomangiomatous component associated with a CARMN::NOTCH3 rearrangement.","authors":"Mark James Wilsher, Talvinger Singh","doi":"10.1016/j.pathol.2026.08.004","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.08.004","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113511","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}
PathologyPub Date : 2026-09-09DOI: 10.1016/j.pathol.2026.07.009
Laura Ling Ying Tan, Daryl Chen Lung Tan, Andy Sing Ong Tang, Kian Meng Chang, Siong Leng Hon, Kim Wah Ho, Chee Leong Cheng
{"title":"SMARCB1-deficient peripheral T-cell lymphoma in a 17-year-old male: an emerging entity which expands the spectrum of SMARCB1-deficient tumours.","authors":"Laura Ling Ying Tan, Daryl Chen Lung Tan, Andy Sing Ong Tang, Kian Meng Chang, Siong Leng Hon, Kim Wah Ho, Chee Leong Cheng","doi":"10.1016/j.pathol.2026.07.009","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.07.009","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165953","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}
PathologyPub Date : 2026-09-09DOI: 10.1016/j.pathol.2026.08.003
Amelia Cecchin, Claire Reynolds, Phillippa A Pucar, Jovanka King, Tatjana Banovic, Syed B Ali
{"title":"Immunoglobulin products and neuronal antibody assays: implications in clinical interpretation.","authors":"Amelia Cecchin, Claire Reynolds, Phillippa A Pucar, Jovanka King, Tatjana Banovic, Syed B Ali","doi":"10.1016/j.pathol.2026.08.003","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.08.003","url":null,"abstract":"<p><p>Immunoglobulin (Ig) products are prescribed for the treatment of a range of immune-mediated disorders, including autoimmune neurological disease. Both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) formulations are available. While Ig products can interfere with immunoassay result interpretation, their influence on neuronal antibody screening methods specifically is unknown. Twenty-five Ig products were sourced and processed at 10 g/L to reflect physiological IgG levels, with these preparations then subjected to the manufacturer-recommended dilution protocols for neuronal line immunoassay (LIA), neuronal tissue indirect immunofluorescence (IIF) and glutamic acid decarboxylase (GAD) 65 enzyme-linked immunosorbent assay (ELISA). To provide clinical context, three cases are illustrated, specifically for GAD65 ELISA and Ig interference. Both IVIg and SCIg demonstrated variable positivity across neuronal LIA, tissue IIF and GAD65 ELISA. At 10 g/L, 16 of 25 (64%) products were positive by neuronal LIA, with a median signal intensity of 19 (1+), whereas no products were positive at the manufacturer-recommended dilution. In six individual batches, a reproducible antibody profile was observed (GAD65, CV2/CRMP5, Titin, Zic4). Positive neuronal tissue IIF staining was observed for all Ig products at the manufacturer-recommended dilution and for 22 of 25 (88%) of products at 10 g/L; however, the patterns were non-specific and showed no correlation with LIA or GAD65 ELISA results. On average, GAD65 ELISA titres were elevated for all Ig products: 200.5 IU/mL at 10 g/L and 441.4 IU/mL for neat preparations. Three patients developed positive GAD65 ELISA results after IVIg, having previously shown no detectable titres. Immunoglobulin-related assay interference was observed under experimental conditions, with variations likely attributable to pooled donor Ig, product matrices and the working dilution. Under routine concentrations, the diagnostic applicability of these findings varied by assay. Collectively, these findings highlight the need for cautious interpretation of results if performed after the administration of Ig products.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168453","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}
PathologyPub Date : 2026-09-09DOI: 10.1016/j.pathol.2026.08.002
Simon F Roy, Riza Milante, Karina Butani, Klaus J Busam, Boris C Bastian, Arnaud de la Fouchardière, Iwei Yeh
{"title":"Spitz tumours with MET gene fusions: 17 cases with identifiable histomorphological and genetic features.","authors":"Simon F Roy, Riza Milante, Karina Butani, Klaus J Busam, Boris C Bastian, Arnaud de la Fouchardière, Iwei Yeh","doi":"10.1016/j.pathol.2026.08.002","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.08.002","url":null,"abstract":"<p><p>The present study reports a series of 17 melanocytic tumours harbouring activating fusions of MET, which encodes a key receptor tyrosine kinase (RTK) implicated in mitogen-activated protein kinase (MAPK) signalling. Tumours were diagnosed as Spitz naevus (n=12, 71%) or melanocytoma (n=5, 29%). No cases of melanoma were identified. Three histopathological patterns emerged. The first, 'plexiform maturing fascicles' (n=7), was characterised by spindle-shaped melanocytes arranged in superficial fascicles maturing into smaller rounded nests embedded in desmoplasia. The second, 'Reed-like' (n=6), featured spindled or epithelioid melanocytes at the dermoepidermal junction with epidermal hyperplasia and scattered melanophages. The third, 'BAP1-inactivated melanocytoma-like' (n=2), showed predominantly intradermal epithelioid melanocytes with pleomorphism and a brisk inflammatory infiltrate. Two cases could not be classified in these pattern categories. Cases classified as melanocytomas more frequently exhibited cellular atypia; for example, prominent nucleoli or giant atypical melanocytes. Moreover, TRIM4::MET fusion genes were identified as a recurring initiating genomic alteration, and tumours with this fusion gene (n=5) showed distinctive features: predominantly intradermal nodular growth, fibromyxoid stroma, intercellular clefting, and nested melanocytes. MET fusion kinases represent targetable genetic alterations, with potential therapeutic implications in melanomas. Recognising these three histopathological patterns provides critical insights for diagnosis and targeted ancillary testing.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183768","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":"Laboratory performance of two commercially available Aspergillus antigen lateral flow assays compared to Platelia Aspergillus galactomannan antigen assay.","authors":"Eileen Hor, Francesca Azzato, Monica Slavin, Chuan Kok Lim, Maryza Graham","doi":"10.1016/j.pathol.2026.07.008","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.07.008","url":null,"abstract":"<p><p>Invasive aspergillosis (IA) infections remain a significant threat to immunosuppressed patients, resulting in considerable morbidity and mortality. While newer non-culture-based methods, such as the galactomannan antigen enzyme immunoassay (EIA) and molecular techniques, provide improved sensitivity and faster results, these methods have notable limitations. These include high costs, long turnaround times, and requirement for specialised instrumentation and skilled personnel. Lateral flow assays (LFA) offer a promising alternative for screening of IA, delivering rapid results with enhanced cost-effectiveness. In this study, we compared the clinical performance, precision, and accuracy of two LFAs for detecting Aspergillus antigen: the IMMY sōna Aspergillus Galactomannan Lateral Flow Assay (sōna-LFA) and the OLM Diagnostics Aspergillus-specific lateral flow device (OLM-LFD). These assays were evaluated in serum and bronchoscopy fluid samples against the Bio-Rad Laboratories Platelia Aspergillus Antigen EIA as the reference method. For the 70 clinical samples analysed (38 of which were positive by Platelia assay), the sōna-LFA demonstrated 95% sensitivity and 100% specificity. In comparison, the OLM-LFD showed 100% sensitivity and 81% specificity. Additionally, the quantitative components of the Platelia assay and the sōna-LFA were evaluated using linear regression analysis. The positive index values revealed a strong linear correlation, with a p value ≤0.05 and an r<sup>2</sup> value of 0.83. The sōna-LFA demonstrated high sensitivity and specificity for detecting Aspergillus antigen with high correlation of the quantitative component of testing when compared to the Platelia assay.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128307","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}
PathologyPub Date : 2026-09-04DOI: 10.1016/j.pathol.2026.07.007
Michael Chang, David Bowen, Ken Liu, Simone Strasser, Catriona McKenzie
{"title":"When weight loss hurts the liver: three cases of aggressive steatohepatitis following bariatric surgery.","authors":"Michael Chang, David Bowen, Ken Liu, Simone Strasser, Catriona McKenzie","doi":"10.1016/j.pathol.2026.07.007","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.07.007","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113450","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}
PathologyPub Date : 2026-08-29DOI: 10.1016/j.pathol.2026.07.006
Cheuk Lam Shannon Zhuang, Kamal Sud, Stephen Fuller, Seethalakshmi Viswanathan
{"title":"Acute kidney injury caused by leukaemic infiltrate: a diagnostic challenge on kidney biopsy.","authors":"Cheuk Lam Shannon Zhuang, Kamal Sud, Stephen Fuller, Seethalakshmi Viswanathan","doi":"10.1016/j.pathol.2026.07.006","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.07.006","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113498","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":"PNH clone distribution in aplastic anaemia: heterozygous germline carriers exhibit immune-mediated clone patterns rather than inherited bone marrow failure phenotype.","authors":"Sudhanshi Raina, Arihant Jain, Nabhajit Mallik, Praveen Sharma, Man Updesh Singh Sachdeva, Venus Thakur, Anand Balakrishnan, Parveen Bose, Prateek Bhatia, Deepak Bansal, Pankaj Malhotra, Reena Das, Sreejesh Sreedharanunni","doi":"10.1016/j.pathol.2026.07.005","DOIUrl":"https://doi.org/10.1016/j.pathol.2026.07.005","url":null,"abstract":"<p><p>Distinguishing immune-mediated aplastic anaemia (AA) from inherited bone marrow failure syndromes (IBMFS) is critical but challenging. The diagnostic value of paroxysmal nocturnal haemoglobinuria (PNH) clones in this context remains uncertain. We prospectively studied 222 AA patients (median age 21.5 years, range 0.8-67) who underwent high-sensitivity PNH flow cytometry (≥0.01%) and next-generation sequencing. Patients were classified as category 1 (pathogenic/likely pathogenic variants fully explaining phenotype; confirmed IBMFS), category 2 (single heterozygous variants), and categories 3/4 (variants of uncertain significance or no variants). Of 222 cases, PNH clones ≥0.01% were detected in 124 (55.9%), ≥1% in 73 (32.9%), and ≥10% in 27 (12.2%). Category 1 IBMFS was identified in 17 of 222 cases (7.7%). Among category 1 patients, only one of 17 (5.9%) had clones ≥1%, and, critically, none had clones ≥10%. At the ≥1% threshold, PNH detection showed 94.1% specificity and 98.3% positive predictive value (PPV) against IBMFS (odds ratio 9.2, p=0.013). Category 2 patients (15/222, 6.8%) demonstrated PNH frequencies (40.0% at ≥1%) indistinguishable from those of acquired AA (36.4%; p=0.785), supporting an immune-mediated disease mechanism on a genetically permissive background. In this comprehensive single-centre cohort, PNH clones ≥1% demonstrated high specificity (94.1%) and PPV (98.3%) for immune-mediated disease. Notably, heterozygous germline carriers exhibited PNH clone distributions indistinguishable from those in acquired AA. These findings warrant validation in larger multicentre cohorts to establish generalisable diagnostic thresholds.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128295","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}