Pathology最新文献

{"title":"Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.","authors":"Jia-Chi Wang, Emma Oo, Elmon Enriquez, Nathan Livingston","doi":"10.1016/j.pathol.2026.06.004","DOIUrl":"10.1016/j.pathol.2026.06.004","url":null,"abstract":"<p><p>Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"697-706"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685356","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":"Retrospective assessment of TCF12 expression in early invasive breast cancer and ovarian cancer: prognostic implications and biological insights.","authors":"Nuanphan Polchai, Denys Ndeke, Khalid Alshammari, Megan R Greener, Tangkam R Marak, Maisie Henman, Suha Deen, Andrew R Green, Ian O Ellis, Emad A Rakha, Stewart G Martin, Sarah J Storr","doi":"10.1016/j.pathol.2026.05.009","DOIUrl":"10.1016/j.pathol.2026.05.009","url":null,"abstract":"<p><p>Transcription factor 12 (TCF12) is a basic helix-loop-helix transcription factor implicated in tissue differentiation and pathogenesis in many types of cancer. Its role in breast and ovarian cancer remains poorly understood. TCF12 protein expression was assessed by immunohistochemistry in 1,514 primary breast tumours and 423 ovarian tumours. TCF12 mRNA expression was analysed in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n=1,980). Associations between protein expression with clinicopathological variables and patient survival were evaluated. In breast cancer, TCF12 was predominantly expressed in the nucleus with low nuclear expression observed in 32% of cases. Both TCF12 protein and mRNA expression were significantly associated with adverse clinicopathological features, including larger tumour size, higher Nottingham Prognostic Index category, and oestrogen receptor-negative tumours. Low nuclear TCF12 expression was associated with adverse breast cancer-specific survival, particularly in oestrogen receptor-positive tumours; it remained an independent adverse prognostic factor in the multivariate analysis. Similar findings were observed when assessing TCF12 mRNA. No association was observed between TCF12 expression and survival of ovarian cancer patients. Low TCF12 expression identified a biologically aggressive subset of breast cancers with poor prognosis. These findings highlight the potential of TCF12 as a prognostic biomarker in breast cancer. No association between TCF12 expression and survival was observed in ovarian cancer patients, suggesting tumour-specific roles.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"679-685"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701853","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":"Clinicopathological characteristics and prognostic factors in renal amyloidosis: a 10-year Australian tertiary centre experience.","authors":"Jonathon W J Loh, Muralikrishna Gangadharan Komala, Gary K K Low, Carol Robinson, Shannon B Fadaee, Adrian Y S Lee, Brian J Nankivell, Seethalakshmi Viswanathan","doi":"10.1016/j.pathol.2026.05.011","DOIUrl":"10.1016/j.pathol.2026.05.011","url":null,"abstract":"<p><p>Renal amyloidosis is an important cause of kidney injury that is often associated with significant morbidity and mortality. In this study, we aim to characterise the clinicopathological patterns and identify potential prognostic factors in renal amyloidosis at an Australian tertiary referral centre over a decade. A total of 63 biopsy-diagnosed cases of renal amyloidosis from 2011 to 2021 were retrospectively reviewed. Cases were initially subtyped by immunofluorescence and immunohistochemistry. Mass spectrometry was performed when rare subtypes were suspected. Histological characteristics were correlated with clinical parameters at the time of biopsy. The primary outcome was severe renal impairment (SRI), defined as an estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m² or commencement of renal replacement therapy. Amyloid light chain (AL) amyloidosis was the most common subtype (79%), followed by amyloid A (AA) (11%), and the rare subtypes included amyloid leukocyte cell-derived chemotactic factor-2 (3.2%); amyloid transthyretin wild-type (1.6%); amyloid apolipoprotein C-II (1.6%); amyloid fibrinogen (1.6%); and amyloid gelsolin amyloidosis (1.6%). Patients with AA amyloidosis were younger than those with other subtypes. The classic histological patterns of common and rare amyloid subtypes, as described in the literature, were replicated in our cohort. Interstitial fibrosis and tubular atrophy had a strong correlation with baseline eGFR and were important prognostic factors for SRI. Nephrotic-range proteinuria showed a trend towards SRI, but amyloid subtype (AL vs AA vs other) did not stratify outcome. Most AL amyloidosis cases (69%) were confirmed to be monoclonal gammopathy of undetermined significance, with a smaller proportion showing an underlying haematological malignancy. All patients with AA subtype had an underlying chronic inflammatory disease condition. We demonstrate classic histopathological features of common and rare subtypes of renal amyloidosis in an Australian cohort. Histological markers at biopsy, indicative of chronic renal damage, have value as prognostic factors.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"686-696"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679575","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":"Placental pathology in stillbirth.","authors":"Adrian Charles, Disna Abeysuriya, Mitali N Fadia, Gretchen Pomare, Jane E Dahlstrom","doi":"10.1016/j.pathol.2026.07.002","DOIUrl":"10.1016/j.pathol.2026.07.002","url":null,"abstract":"<p><p>Placental assessment following a stillbirth is a crucial investigation. It helps identify possible causes or contributing factors to stillbirth. It can help evaluate the risk of recurrence in future pregnancies and may indicate whether further tests are needed. It also provides guidance for managing subsequent pregnancies. In this review, we discuss practical considerations in placental assessment following stillbirth, including how both pre-analytical and analytical factors can influence the assessment. We outline the changes that occur in the placenta after stillbirth and explain how to distinguish these changes from antemortem placental pathology known to cause stillbirth. In addition, we highlight incidental findings and artefacts in the placenta that can be confused with true pathology. Finally, we address current controversies, identify areas for future research, and propose a practical approach to assessing the placenta in cases of stillbirth.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"664-678"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796508","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":"Unmasking aggressive NK-cell leukaemia with secondary haemophagocytic lymphohistiocytosis in a non-endemic region.","authors":"Enrique Blanco-Peláez, Fernando Martín-Moro, Miguel Piris-Villaespesa, Beatriz Astibia-Mahillo, Ana Lario-Arribas, Ernesto Roldán-Santiago, Mónica García-Cosío, Javier López-Jiménez","doi":"10.1016/j.pathol.2026.04.004","DOIUrl":"10.1016/j.pathol.2026.04.004","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"742-745"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437544","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":"Kava and consequence: a toxicological cautionary tale of hepatic harm.","authors":"An Thien An Hong, Talal Valliani, Purnima Bhat, Joo-Shik Shin, David G Bowen, Ken Liu, Simone I Strasser, Catriona McKenzie","doi":"10.1016/j.pathol.2026.05.003","DOIUrl":"10.1016/j.pathol.2026.05.003","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"749-751"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562649","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":"On the difference between functional reference limit and clinical decision limit: a response from the authors of Loh et al. (2026).","authors":"Cherie Chiang, Tze Ping Loh","doi":"10.1016/j.pathol.2026.07.001","DOIUrl":"10.1016/j.pathol.2026.07.001","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"764-765"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685409","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":"Cutaneous spindle cell lesion with PRKAR1A::ALK fusion.","authors":"Mark James Wilsher, Charles Yuen Yung Loh, Nicholas Francis","doi":"10.1016/j.pathol.2026.06.003","DOIUrl":"10.1016/j.pathol.2026.06.003","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"761-763"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679547","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":"Post-infantile 'giant cell hepatitis' (giant cell transformation): a morphological pattern of drug-induced liver injury in adults.","authors":"Badr AbdullGaffar, Huda Quarishi","doi":"10.1016/j.pathol.2026.05.002","DOIUrl":"10.1016/j.pathol.2026.05.002","url":null,"abstract":"","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"745-748"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579308","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":"Investigation of non-immune hydrops fetalis in singleton pregnancy: a practical guide for the perinatal pathologist.","authors":"Nicole S Graf, Ali Moghimi, Victoria Yachmenikova, Maria-Elisabeth Smet","doi":"10.1016/j.pathol.2026.06.002","DOIUrl":"10.1016/j.pathol.2026.06.002","url":null,"abstract":"<p><p>Hydrops fetalis is defined by abnormal fluid accumulation in at least two fetal compartments, resulting from a range of underlying pathological processes, and with a high mortality at the severe end of the spectrum. Identifying the specific cause is crucial for managing both current and future pregnancies. Despite comprehensive antenatal investigations, including obstetric imaging, serology and genetic testing, many cases of non-immune hydrops fetalis (NIHF) remain unexplained at delivery. Some diagnostic features may not be apparent on ultrasound, with perinatal autopsy providing additional valuable information, particularly when structural fetal anomalies are absent. In this review, a structured, phenotype-based approach to autopsy has been developed for cases of indeterminate aetiology, with categories including NIHF with bilateral cystic hygromas, the pale hydropic baby, NIHF associated with cardiovascular system abnormalities, NIHF with no obvious structural abnormality, and NIHF with prominent ascites. Both genetic and non-genetic causes are considered across all groups, with a particular focus on recently described entities and newly identified underlying aetiologies. Placental examination is also vital and may offer key diagnostic clues; though certain pitfalls must be avoided. Comprehensive evaluation by specialist perinatal pathologists can provide crucial diagnostic information in investigation of NIHF.</p>","PeriodicalId":19915,"journal":{"name":"Pathology","volume":" ","pages":"653-663"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723636","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}