Journal Of Clinical Pathology[JOURNAL]
Sun
200 papers
Defining biochemical, pathological and molecular factors prognostic in terms of disease control and survival in high-grade extremity soft tissue sarcoma: a scoping review.
Peirens K, Creytens D, Cordier F … +3 more , Van Den Berghe T, De Temmerman J, Lapeire L
J Clin Pathol · 2026 Jun · PMID 42373306 · Publisher ↗
AIMS: High-grade extremity soft tissue sarcomas (eSTS) are rare, heterogeneous malignancies with a high metastatic potential. Prognostic assessment remains challenging due to wide variation in outcomes. Current risk stra...
AIMS: High-grade extremity soft tissue sarcomas (eSTS) are rare, heterogeneous malignancies with a high metastatic potential. Prognostic assessment remains challenging due to wide variation in outcomes. Current risk stratification relies on traditional risk factors like age, histology, grade and tumour size, which are embedded in risk classification scores. Recent advances in the fields of biochemistry, pathology and molecular genetics may offer additional prognostic insights, although their clinical utility remains unclear. This scoping review aimed to map the evidence on clinically available biomarkers with potential prognostic value in adults with high-grade eSTS. METHODS: A broad search of MEDLINE and Embase identified 9739 records, of which 74 studies met the eligibility criteria. RESULTS: Overall, available evidence is retrospective and heterogeneous. Potential biomarkers were identified across three domains: biochemical, pathological and molecular. Although several biomarkers showed potential prognostic value, few studies assessed their independence from key confounders. CONCLUSIONS: Standardised validation, with adjustment for established prognostic variables, is needed before these biomarkers can be integrated into risk prediction models for routine clinical practice.
MILGDF: a multi-task, instance-level supervised model for oral squamous cell carcinoma integrating local-global attention and dynamic decision fusion.
Li CX, Chen Y, Xu LH … +4 more , Chen C, Chen C, Lv XY, Gong ZC
J Clin Pathol · 2026 Jun · PMID 42342437 · Publisher ↗
AIMS: This research was designed to establish an innovative diagnostic strategy employing whole-slide imaging (WSI) technology to address the diagnostic difficulties arising from the intricate histological architecture a...
AIMS: This research was designed to establish an innovative diagnostic strategy employing whole-slide imaging (WSI) technology to address the diagnostic difficulties arising from the intricate histological architecture and morphological diversity observed in oral squamous cell carcinoma (OSCC). The developed methodology enables precise early identification and histomorphology-driven prognostic stratification of malignant lesions, thereby improving clinical management and patient prognosis. METHODS: We propose a multi-task learning framework that combines local-global attention mechanisms with adaptive decision fusion (MILGDF). This model utilises instance-level category-specific attention to enhance feature extraction efficacy while overcoming the limitations inherent in traditional bag-level attention methods. An adaptive weighting system was incorporated to dynamically adjust the contribution of local and global features, ensuring optimal performance in dual tasks of OSCC diagnosis and prognostic stratification. RESULTS: Rigorous validation on the HIDOC and TCGA-OSCC datasets revealed the predictive performance of our model. The MILGDF framework attained an area under the curve of 0.952 (accuracy: 0.909) on HIDOC and 0.745 (accuracy: 0.725) on TCGA-OSCC. Statistical comparison using DeLong's test and paired t-tests demonstrated significantly superior performance (p<0.05) over existing comparative models in both diagnostic classification and prognostic stratification. CONCLUSIONS: Our findings demonstrate that the MILGDF model represents an improvement in whole-slide image-based OSCC analysis, delivering enhanced diagnostic accuracy and prognostic reliability relative to current approaches. The framework's consistent performance highlights its computational benchmark value and preliminary translational potential for early OSCC detection and auxiliary treatment planning, serving as a valuable asset for prognostic evaluation and therapeutic strategy formulation.
Paediatric B-lymphoblastic leukaemia with low peripheral blasts: a potential diagnostic pitfall.
Harris EM, Heeney MM, Place AE … +4 more , Harris MH, Fleming MD, Silverman LB, Bledsoe JR
J Clin Pathol · 2026 Jun · PMID 42342436 · Publisher ↗
B cell acute lymphoblastic leukaemia (B-ALL) infrequently presents with undetectable or very low peripheral blood (PB) lymphoblasts, which may cause diagnostic difficulties. We report the clinicopathological features of...
B cell acute lymphoblastic leukaemia (B-ALL) infrequently presents with undetectable or very low peripheral blood (PB) lymphoblasts, which may cause diagnostic difficulties. We report the clinicopathological features of paediatric patients with B-ALL who presented with low (<5%; n=31) PB lymphoblasts by flow cytometry. 15 patients presented with <1% PB lymphoblasts (range: 0.0%-0.9%), a level potentially undetectable by manual smear review and standard 100-cell count. Compared with patients presenting with ≥5% PB lymphoblasts (n=45), those with <5% had more frequent musculoskeletal symptoms, less frequent lymphadenopathy and hepatosplenomegaly, higher platelet counts, lower white blood cell counts and lower lactate dehydrogenase. The presence of low PB lymphoblasts was associated with favourable cytogenetics ( or high hyperdiploidy without deletion) and less frequent central nervous system involvement. Aleukemic/low PB lymphoblast presentation of B-ALL is associated with unique clinicopathological features that overlap with non-malignant disorders. A high degree of clinical suspicion and careful review of PB flow cytometry data are required for timely diagnosis.
MRI-targeted versus systematic needle core biopsies in prostate cancer: a patient-based analysis of potential diagnostic and biologic underestimation.
Saeed F, Osunkoya AO
J Clin Pathol · 2026 Jun · PMID 42336636 · Publisher ↗
AIMS: MRI-targeted needle core biopsy (MRI-NCB) improves detection of clinically significant prostate cancer (csPCa), but whether it can replace systematic ultrasound-guided biopsy (US-NCB) remains debated, as most studi...
AIMS: MRI-targeted needle core biopsy (MRI-NCB) improves detection of clinically significant prostate cancer (csPCa), but whether it can replace systematic ultrasound-guided biopsy (US-NCB) remains debated, as most studies have focused on cancer detection and grade. METHODS: We retrospectively analysed 562 patients with PI-RADS 3-5 lesions who underwent both MRI-NCB and concurrent US-NCB. Outcomes included cancer detection, Grade Group (GG) and adverse features (cribriform morphology and intraductal carcinoma (IDCP)). csPCa was defined as GG ≥2. A composite endpoint of clinically meaningful under-detection or underestimation was defined as missed or under-graded csPCa and/or missed adverse histological features on MRI-NCB relative to US-NCB. RESULTS: MRI-NCB alone would have missed PCa in 13.0% (73/562) of patients, including csPCa in 11.4% (64/562) and would have underestimated GG in 13.3% (75/562). Systematic biopsy identified additional cribriform morphology in 4.3% (24/562) and IDCP in 2.5% (14/562) of patients not detected on MRI-NCB. Overall, MRI-NCB alone would have resulted in clinically meaningful under-detection or underestimation in 16.4% (92/562). Of these, 63.0% had missed or under-graded csPCa only, 30.4% had missed adverse histologic features only and 6.5% had both. Missed cancers were more frequent in lower PI-RADS lesions whereas upgrading was more common in higher PI-RADS lesions. Incremental detection of IDCP was significantly higher in PI-RADS 5 compared with PI-RADS 4 lesions (adjusted p=0.048). CONCLUSIONS: MRI-targeted biopsy alone may incompletely assess cancer detection and tumour biology. Systematic biopsy provides complementary diagnostic value, and omission may result in clinically meaningful under-detection or underestimation, even in high PI-RADS lesions.
Basal plasmacytosis and eosinophilia for distinguishing inflammatory bowel disease from gastrointestinal tuberculosis on mucosal biopsy.
Akhtar S, Mehra L, Mahajan M … +9 more , Hossain S, Bhowmik S, Tiwari A, Dutta R, Kedia S, Yadav R, Makharia G, Ahuja V, Das P
J Clin Pathol · 2026 Jun · PMID 42336635 · Publisher ↗
AIMS: Accurate distinction of inflammatory bowel disease (IBD) and gastrointestinal tuberculosis (GITB) on mucosal biopsies remains challenging, especially in South-East Asia. Our previous meta-analysis highlighted that...
AIMS: Accurate distinction of inflammatory bowel disease (IBD) and gastrointestinal tuberculosis (GITB) on mucosal biopsies remains challenging, especially in South-East Asia. Our previous meta-analysis highlighted that mucosal basal plasmacytosis (BP) can help in identifying IBD although evidence is limited. This study was planned to evaluate the utility of mucosal BP and combined presence of BP and mucosal eosinophilia (ME) (BP+ME) in differentiating ulcerative colitis (UC), Crohn's disease (CD) and GITB using endoscopic mucosal biopsies. METHODS: We retrospectively analysed 500 mucosal biopsies from patients diagnosed with UC, CD and GITB based on clinical, radiological, endoscopic findings and treatment response. Inclusion and exclusion criteria were applied, and histological evaluation was performed independently by two experienced pathologists. Presence of BP and BP+ME was systematically compared across patient groups. RESULTS: Of the 500 biopsies reviewed, 412 met inclusion criteria (UC: 194, CD: 68, GITB: 114, IBD-unclassified: 36). BP was significantly more prevalent in both UC and CD than in GITB. BP+ME was significantly more prevalent in mucosal biopsies from IBD than in GITB. Also, in segmental mucosal biopsies from IBD patients, BP was found significantly more in three or more biopsy fragments than in biopsies from GITB. Both BP and BP+ME demonstrated good diagnostic utility in differentiating IBD from GITB and CD from GITB (positive likelihood ratio 3.24 and 4.35, respectively). CONCLUSIONS: Histological identification of mucosal BP and/or BP+ME provides moderate diagnostic utility in distinguishing IBD from GITB. Identification of BP in three or more biopsy fragments further strengthens histological diagnosis of IBD.
Assay-dependent variability in free thyroxine (FT4): differential interference related to immunoassay design in a patient with subclinical hypothyroidism.
Lum CL, Tay WL, Chiang BS … +2 more , Lim MH, Ho CK
J Clin Pathol · 2026 Jun · PMID 42331602 · Publisher ↗
In clinical practice, thyroid function tests (TFTs) usually comprise thyroid-stimulating hormone (TSH) and free thyroxine (FT4), with free triiodothyronine (FT3) measured less frequently. We report a 76-year-old woman wi...
In clinical practice, thyroid function tests (TFTs) usually comprise thyroid-stimulating hormone (TSH) and free thyroxine (FT4), with free triiodothyronine (FT3) measured less frequently. We report a 76-year-old woman with autoimmune thyroiditis presenting with raised TSH and incongruously elevated FT4. The discordance between biochemical findings and clinical status prompted further investigations for assay interference. TFTs were assessed using four different immunoassay platforms and equilibrium dialysis. Additional studies included heterophilic antibody blocking and polyethylene glycol (PEG) precipitation. PEG precipitation demonstrated a high-molecular-weight interferent, consistent with thyroid hormone autoantibodies. FT4 measured by two-step immunoassays (Abbott Alinity and Beckman DxI) aligned with FT4 reported by equilibrium dialysis, whereas one-step assays (Roche Cobas and Siemens Atellica) reported spuriously elevated FT4. One-step immunoassays are particularly susceptible to interference from thyroid hormone autoantibodies, which may yield misleading results. Recognition of potential TFT assay interference and the use of alternative methodologies are essential for accurate diagnosis and appropriate patient management.
Microbiological characteristics of granulomatous lobular mastitis revealed by metagenomic sequencing.
Diao Y, Li J, Wang L … +8 more , Zhang Q, Xu C, Peng A, Lu C, Lai B, Chen R, Chen J, Pei X
J Clin Pathol · 2026 Jun · PMID 42276765 · Publisher ↗
AIMS: Granulomatous lobular mastitis (GLM) is a rare, chronic, benign inflammatory disease of the breast with an unclear aetiology. This study aimed to characterise the microbial features of GLM using metagenomic next-ge...
AIMS: Granulomatous lobular mastitis (GLM) is a rare, chronic, benign inflammatory disease of the breast with an unclear aetiology. This study aimed to characterise the microbial features of GLM using metagenomic next-generation sequencing (mNGS) and to provide potentially relevant microbial clues for clinical evaluation. METHODS: Twenty fresh lesion tissue samples were collected from 15 female patients with GLM, including one representative sample per patient and five additional deep tissue samples. Clinical data collection, mNGS, bioinformatics analysis and data interpretation were performed to characterise the microbial profiles of GLM lesions. RESULTS: In this study, all patients presented with palpable breast masses, breast pain and abscess formation. More than half showed increased white blood cell counts, neutrophil percentages, C reactive protein levels and erythrocyte sedimentation rates together with decreased lymphocyte percentages. Based on genus-level filtering, mNGS identified 16 bacterial genera, 14 fungal genera and 3 viral genera, revealing a complex but bacteria-dominated microbial profile. The most frequently detected bacterial genera were , , , and , with marked interpatient variation in relative abundance, while fungal profiles were relatively more concentrated. In five patients with both superficial and deep tissue samples, microbial profiles differed across sampling depths, particularly for bacterial composition. CONCLUSIONS: mNGS revealed a complex, bacteria-dominated microbial profile in GLM lesions and indicated that sampling depth may influence the detected microbial profiles. These findings may provide useful clues for clinical evaluation, but the pathogenic significance of these micro-organisms remains to be elucidated.
Secondary -mutated histiocytic/dendritic cell sarcoma transdifferentiated from follicular lymphoma with prolonged response to BRAF/MEK inhibition and subsequent evolution to high-grade B-cell lymphoma.
Royer-Chardon C, Bisig B, Trimech M … +6 more , Guey B, Missiaglia E, Voruz S, Denys A, Cairoli A, de Leval L
J Clin Pathol · 2026 Jun · PMID 42264920 · Publisher ↗
Transdifferentiation from follicular lymphoma (FL) to histiocytic/dendritic cell sarcoma (HDS) is rare and requires molecular confirmation of shared clonal origin. Targetable mutations such as V600E may offer therapeuti...
Transdifferentiation from follicular lymphoma (FL) to histiocytic/dendritic cell sarcoma (HDS) is rare and requires molecular confirmation of shared clonal origin. Targetable mutations such as V600E may offer therapeutic opportunities in such aggressive neoplasms. We report an exceptional case of untreated localised FL transdifferentiated to an HDS after 18 years. Shared rearrangement and mutation profile confirmed a clonal link, while the HDS acquired an additional V600E mutation. Treatment with BRAF/MEK inhibitors yielded a sustained 18-month clinical response. The disease later relapsed as high-grade B-cell lymphoma with and rearrangements (HGBCL-), still harbouring the mutation. Complete remission was achieved with Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisone, but the double-hit lymphoma relapsed 14 months later.This case illustrates sequential transformation from FL to -mutated HDS with excellent response to BRAF/MEK inhibition, followed by evolution into HGBCL-/ responding transiently to immunochemotherapy, emphasising the value of repeated histological and molecular reassessment in FL evolution.
Triple-negative breast cancer: a threshold-defined diagnostic category within a biological continuum.
Rakha EA
J Clin Pathol · 2026 Jun · PMID 42264919 · Publisher ↗
Triple-negative breast cancer (TNBC) is defined in routine practice by the absence of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression using fixed immunoh...
Triple-negative breast cancer (TNBC) is defined in routine practice by the absence of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression using fixed immunohistochemical and hybridisation cut-offs. Although this framework ensures reproducibility and regulatory consistency, it does not equate to biological uniformity. TNBC is an operational clinicopathological category defined by reproducible biomarker thresholds applied to continuous gradients of receptor expression. This review examines the evolution of hormone receptor assessment from semiquantitative composite scoring systems to the current ≥1% ER positivity threshold, and analyses the diagnostic and clinical implications of ER-low-positive (1%-10%) tumours. We discuss the rarity and interpretative challenges of ER-/PR+ phenotypes, the impact of evolving HER2 testing criteria, including borderline amplification and HER2-low categories, and the consequences of guideline variation on TNBC classification. We also address histological heterogeneity within TNBC and propose a pragmatic three-tier framework that distinguishes definite TNBC, context-dependent/borderline TNBC and non-TNBC categories. Collectively, these considerations highlight that TNBC is a regulatory definition anchored to diagnostic thresholds rather than a discrete molecular entity. Awareness of definitional sensitivity at receptor cut-off margins is essential for accurate reporting, avoidance of misclassification and informed multidisciplinary decision-making. Recognition of TNBC as a biologically heterogeneous spectrum has implications for therapeutic selection, trial eligibility and future refinement of classification systems.
Diagnostic yield and cost of three-level H&E sectioning in prostate biopsies.
Gichinga R, Lepe M, Rainer Q … +2 more , Collins LC, Sun Y
J Clin Pathol · 2026 Jun · PMID 42242896 · Publisher ↗
AIM: The traditional three-level H&E sectioning protocol for prostate biopsies was developed for ultrasound-guided systematic sampling and predates lesion-targeted biopsy approaches. Multiparametrical MRI (mpMRI) has imp...
AIM: The traditional three-level H&E sectioning protocol for prostate biopsies was developed for ultrasound-guided systematic sampling and predates lesion-targeted biopsy approaches. Multiparametrical MRI (mpMRI) has improved detection of clinically significant prostate carcinoma but has also increased biopsy volume, workload, costs and digital pathology requirements, including whole-slide imaging and artificial intelligence (AI) integration. METHODS AND RESULTS: A retrospective institutional cost-yield analysis was performed on prostate biopsy cases at Beth Israel Deaconess Medical Center (2015-2022), comparing systematic 12-core biopsies with combined systematic and mpMRI-targeted biopsies. Case volume, tissue blocks and H&E slides were analysed. Per-slide costs were calculated, and additional digital pathology and AI workflow costs were estimated using published data and vendor pricing. Case volume increased by 27% over 7 years, while combined systematic and mpMRI-targeted protocols increased tissue blocks and H&E slides by 39%. The cost per H&E slide was $7.18, with digital pathology and AI workflows adding an estimated $4.30-5.00 per slide. In systematic 12-core biopsies, third-level sectioning identified four additional low-volume carcinomas at a cost of $2283 per diagnosis. In combined biopsies, two additional carcinomas were detected exclusively on the third level, both Grade Group 1, with a cost of $27 657 per diagnosis. CONCLUSION: Routine three-level H&E sectioning in combined systematic and mpMRI-targeted prostate biopsies demonstrated low incremental diagnostic yield and substantial additional processing cost. A two-level protocol with selective third-level sectioning may preserve detection of clinically significant carcinomas in this institutional cohort, while reducing workload and cost in the digital pathology era.
Mesenchymal neoplasms with RAF/BRAF alterations: eight cases revealing novel fusions, V600E mutation and clonal evolution.
Feng X, Huang X, Hao W … +6 more , Wei J, Liu X, Wen Y, Cao Q, Jiang Y, Gong L
J Clin Pathol · 2026 Jun · PMID 42236131 · Publisher ↗
OBJECTIVE: While kinase-altered spindle cell tumours were classically recognised in paediatric superficial soft tissues, recent literature indicates an expanding clinicopathologic spectrum. This study investigates a coho...
OBJECTIVE: While kinase-altered spindle cell tumours were classically recognised in paediatric superficial soft tissues, recent literature indicates an expanding clinicopathologic spectrum. This study investigates a cohort of -altered mesenchymal tumours to further characterise their presentations in adults, deep-seated/visceral locations, variable immunophenotypes and complex molecular evolution. METHODS: Eight molecularly confirmed -altered mesenchymal tumours were retrospectively evaluated. Clinical characteristics, histomorphology, immunohistochemistry, targeted next-generation sequencing profiles and follow-up data were comprehensively analysed. RESULTS: The cohort comprised seven females and one male (median age, 34.5 years). Tumours arose in soft tissues (n=5, including the deep pelvis) and visceral organs (n=3; two breast, one lung). Histologically, the neoplasms exhibited a broad morphologic spectrum: three demonstrated low-grade spindle cell morphology, whereas five displayed high-grade pleomorphic or fibrosarcoma-like features, including one pelvic tumour mimicking myxoid leiomyosarcoma. Immunophenotypes diverged significantly with histologic grade: low-grade tumours retained CD34 and S100 coexpression, whereas high-grade lesions consistently lost both markers, with one case exhibiting focal Desmin positivity. Molecular profiling revealed ubiquitous mitogen-activated protein kinase pathway activation, identifying six kinase gene fusions (including novel and variants) and two V600E mutations. High-grade tumours frequently harboured concurrent tumour suppressor gene alterations (eg, , ). Notably, one pelvic tumour exhibited a trunk mutation alongside a subclonal V600E mutation. Notably, despite the alarming high-grade histomorphology in several cases, clinical behaviour remained relatively indolent, with no disease-related deaths to date. CONCLUSIONS: -driven mesenchymal tumours possess a broader clinicopathologic spectrum than traditionally recognised, frequently affecting adults and deep/visceral sites. Their inherently variable immunophenotypes and the presence of high-grade morphologic features do not strictly predict an aggressive clinical trajectory. Comprehensive molecular profiling is essential to refine diagnostic criteria, accurately identify these neoplasms, and elucidate the genomic events associated with tumour progression.
Validation of polymerase chain reaction-indexed next-generation sequencing assay on the Illumina iSeq 100 platform for MPL exon 10 mutation detection: a robust alternative to Sanger sequencing.
Lau D, Loo JYQ, Ng SY … +7 more , Van DT, Kuek WCD, Chai CN, Tan JKM, Lee CK, Yan BJ, Chan THM
J Clin Pathol · 2026 Jun · PMID 42225400 · Publisher ↗
Abstract loading — click title to view on PubMed.
Liver disease diagnostics and access barriers in African settings: a narrative review.
Jagunmolu HA, Oyetola EO, Lawal YA … +8 more , Akinsanya SO, Ibrahim MA, Idowu TO, Oyelude SO, Jubreel MA, Ajibade DO, Olaniyi TO, Sheriff AA
J Clin Pathol · 2026 May · PMID 42215293 · Publisher ↗
In Africa, chronic liver conditions are discordantly higher due to infectious and parasitic aetiologies, especially viral hepatitis. Early diagnosis is a linchpin for successful management and improved outcomes; however,...
In Africa, chronic liver conditions are discordantly higher due to infectious and parasitic aetiologies, especially viral hepatitis. Early diagnosis is a linchpin for successful management and improved outcomes; however, diagnostic power is extremely limited. Yet, profound gaps compromise every step of the diagnostic continuum. Histopathological evaluation through liver biopsy remains the gold standard for establishing aetiology, grading inflammation and staging fibrosis. Biopsy services in Africa are limited by limited infrastructure, a deficit of qualified professionals, substantial costs, unreliable tissue samples and limited access to advanced pathology techniques such as immunohistochemistry and molecular testing. Non-invasive diagnostic tools such as serum markers, transient elastography and imaging techniques are unequally accessible, poorly updated for African-specific aetiologies and largely inaccessible outside tertiary centres. This review explores the aetiological spectrum of chronic liver disease in Africa and evaluates the availability and performance of both histological and non-invasive diagnostic techniques. This review illustrates gaps affecting screening, staging, initiation of management and hepatocellular carcinoma surveillance. Addressing these diagnostic limitations through improved infrastructure, expanded professional training and local validation of non-invasive tools is essential to reducing the burden of liver disease across Africa. In addition, it offers tiered and feasible recommendations while considering the current reality of healthcare in sub-Saharan Africa.
Digital diagnostic pathology between promise and professional erosion: artificial intelligence and the future of diagnostic sovereignty.
Kristiansen G
J Clin Pathol · 2026 May · PMID 42215292 · Publisher ↗
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Contextual interpretation of luminal phenotype in low-grade breast epithelial proliferations.
Rakha EA
J Clin Pathol · 2026 May · PMID 42215291 · Publisher ↗
Diagnosing low-grade intraductal epithelial proliferations and distinguishing hyperplasia from neoplasia has traditionally relied on well-established morphological and immunophenotypic criteria. However, in routine pract...
Diagnosing low-grade intraductal epithelial proliferations and distinguishing hyperplasia from neoplasia has traditionally relied on well-established morphological and immunophenotypic criteria. However, in routine practice, differentiating luminal epithelial proliferations that are not necessarily clonal from bona fide neoplastic precursor lesions remains challenging. In specific clinical scenarios, such as gynaecomastia, adolescent breast tissue and fibroepithelial lesions, epithelial proliferations may appear morphologically and immunophenotypically worrisome for neoplasia, yet the clinical context supports a non-neoplastic process. Rather than representing conventional clonal neoplasia, these changes may reflect hormonally driven or stromal-induced luminal differentiation and often lack the sharp demarcation typical of conventional neoplasia. This narrative review delineates these context-dependent diagnostic pitfalls and proposes an integrated framework that emphasises architectural features, clonal demarcation and the clinical setting. By positioning these borderline lesions within a biological continuum and refining diagnostic thresholds in context, this approach aims to improve diagnostic reproducibility, mitigate the risk of overdiagnosis and support appropriate, risk-adapted patient management.
Myeloid-derived suppressor cells in anaplastic thyroid carcinoma: insights from prospective immune profiling and implications for targeted immunotherapy.
Boruah M, Agarwal S, Mir RA … +4 more , Singh CA, Kumar R, Sikka K, Kataria K
J Clin Pathol · 2026 May · PMID 42191358 · Publisher ↗
PURPOSE: Anaplastic thyroid carcinoma (ATC) exhibits limited responsiveness to immunotherapy. The current study characterises the immune cell repertoire in ATC compared with differentiated thyroid carcinoma (DTC) and thy...
PURPOSE: Anaplastic thyroid carcinoma (ATC) exhibits limited responsiveness to immunotherapy. The current study characterises the immune cell repertoire in ATC compared with differentiated thyroid carcinoma (DTC) and thyroid follicular nodular disease (TFND) and evaluates and mRNA expression. METHODS: Cytotoxic T lymphocytes (CTLs), regulatory T cells (TREGs), natural killer cells (NK), B lymphocytes and myeloid-derived suppressor cells (MDSCs) were analysed by multicolour flow cytometry in prospectively collected ATC, DTC and TFND tissues. and mRNA expression was quantified using RT-PCR. RESULTS: ATC demonstrated significantly higher MDSC infiltration than DTC or TFND. CTLs were elevated in ATC relative to DTC, while TREGs, NK and B-cells were lower. and expression did not differ significantly although expression was higher in DTC and ATC than in TFND. CONCLUSION: ATC microenvironment is rich in immunosuppressive MDSCs. These findings support MDSC-focused immunomodulation as a promising adjunct therapy in ATC.
Concordance of conventional two-tier HER2 classification versus three-tier classification (including HER2-low status) in invasive breast carcinoma: a retrospective real-world analysis.
Juneja A, Sahay A, Padwale P … +9 more , Patil A, Pai T, Panjwani P, Joshi S, Wadasadawala T, Popat P, Shet TM, Gupta S, Desai SB
J Clin Pathol · 2026 May · PMID 42191357 · Publisher ↗
AIM: To compare changes in HER2 expression status on reassessment across multiple clinical groups using new three-tier versus traditional binary HER2 reporting schemas. METHODS: Retrospective study of 1107 paired IBC sam...
AIM: To compare changes in HER2 expression status on reassessment across multiple clinical groups using new three-tier versus traditional binary HER2 reporting schemas. METHODS: Retrospective study of 1107 paired IBC samples wherein HER2 immunohistochemistry (IHC) and, where needed, in-situ hybridisation (ISH) were performed at least twice in four clinical groups: core needle biopsy (CNB)-upfront resection (n=277); CNB-post-chemotherapy resection (n=104); primary (CNB/resection)-recurrence (local/metastatic, n=702); initial and subsequent distant metastasis (n=24). Concordance was noted for HER2-positive (HER2-IHC 3+ or 2+ ISH-amplified), negative (HER2-IHC 0) and low (HER2-IHC 1+ and 2+ ISH-non-amplified) status, and compared with the concordance of binary HER2 status (positive/negative). RESULTS: HER2 concordance dropped sharply to 69.7% (k=0.53, 95% CI 0.48 to 0.57) on reassessment after applying the three-tier schema, driven primarily by bidirectional shifts between HER2-negative (IHC 0) and HER2-low. Referral specimens showed poorer concordance than in-house tissue in both binary (p value <0.001, OR: 2.40, 95% CI 1.40 to 4.10) and ternary classification (p value <0.001, OR: 1.72, 95% CI 1.31 to 2.2), emphasising the effects of pre-analytical factors like fixation on HER2 interpretation. CONCLUSIONS: The three-tier HER2-low classification schema demonstrates poor reproducibility on re-evaluation, with nearly one-third of cases discordant. This fluidity has significant therapeutic implications. We recommend HER2 re-evaluation with careful attention to the 0 versus 1+ distinction, especially in metastatic and post-treatment settings and when pre-analytical factors are suboptimal.
Digital Ki-67 quantification in neuroendocrine tumours: comparing performance of camera-captured images and open-source platforms across imaging modalities.
Padmanabha N, Oganesyan R, O'brien L … +8 more , Li D, Widener S, Hakamy B, Yilmaz O, Collins LC, Deshpande V, Gonzalez RS, Vyas M
J Clin Pathol · 2026 May · PMID 42185043 · Publisher ↗
AIMS: Accurate assessment of the Ki-67 proliferation index (PI) is essential for grading and prognostication of gastrointestinal well-differentiated neuroendocrine tumours (NETs). While manual counting (MC) of 500-2000 t...
AIMS: Accurate assessment of the Ki-67 proliferation index (PI) is essential for grading and prognostication of gastrointestinal well-differentiated neuroendocrine tumours (NETs). While manual counting (MC) of 500-2000 tumour cells remains the standard, digital image analysis (DIA) offers potential advantages in efficiency and reproducibility. We evaluated the comparability of open-source DIA platforms on camera-captured (CC) images and whole-slide images (WSI) for Ki-67 quantification. METHODS: Ki-67 hotspot areas of 70 NETs were photographed using a microscope-mounted camera. PI was determined by MC (gold standard) and compared with automated counts in 68 cases (two excluded owing to high background staining) using QuPath (V.0.4.4). In a randomly selected subset of 20 cases, the same hotspot areas were analysed using ImageJ, ChatGPT V.4.0 (colour-based segmentation) and the IHCexpert.com platform. Additionally, WSI files of these 20 cases were imported into QuPath for DIA; PI of identical areas were compared against static images. RESULTS: DIA using QuPath (on CC images) demonstrated excellent agreement with MC (intraclass correlation coefficient). Only one case showed grade reclassification (manual G1, 2.92%; DIA G2, 3.38%). In the subset analysis (n=20), comparable Ki-67 indices were observed across all digital platforms and between CC images and WSI. Grade switches from changes in Ki-67 PI were observed in two additional cases (G2 to G1 in IHCexpert.com group and G1 to G2 in ChatGPT group). CONCLUSIONS: Our findings offer the prospect of eliminating variability in the analysis of PI estimation. Of note, CC images yield results similar to WSI, supporting broader applicability in resource-limited practice settings.
Reporting of both positive and negative concordance is necessary to recognise and investigate bias in digital algorithms.
Troxell ML, Karakas C, Lam MM … +3 more , Dussaq AM, Bean G, Allison KH
J Clin Pathol · 2026 May · PMID 42167914 · Publisher ↗
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UK participation in the UK National External Quality Assessment Scheme for mismatch repair immunohistochemistry: insights from the last decade.
Farmkiss LA, Dodson A, Parry S … +3 more , James MC, Frayling IM, Arends MJ
J Clin Pathol · 2026 Jun · PMID 42156160 · Full text
AIM: Comparison of immunohistochemical detection of mismatch repair (MMR) proteins within tumours, as deficient MMR is important for (1) the detection of Lynch Syndrome, caused by inherited variants affecting the DNA MMR...
AIM: Comparison of immunohistochemical detection of mismatch repair (MMR) proteins within tumours, as deficient MMR is important for (1) the detection of Lynch Syndrome, caused by inherited variants affecting the DNA MMR genes and , (2) aiding MMR gene variant interpretation and (3) deciding on use of immune checkpoint blockade therapy. METHODS: This retrospective analysis compares the performance of different MMR immunohistochemistry (IHC) antibody clones, detection systems and automation IHC platforms using a decade of technical data submitted to the UK National External Quality Assessment Scheme (NEQAS) as part of its MMR EQA programme, with calculation of participants' final aggregated scores (FAS) for performance comparison. RESULTS: Between 2011 and 2022, there were 38 MMR assessment runs, with an average of 44.8 submissions per antigen per assessment run. MMR module participation greatly increased over this decade. Average FAS showed a small non-significant upward trend with the lowest scores (14.6) observed in the first half of the decade, with greater concordance between FAS scores (15.1) in the second half of the decade. For MMR IHC, the antibody clones most frequently used were M1 and ES05 (FAS 15.7 and 15.1) for MLH1, G219-1129 and FE11 (FAS 14.8 and 14.1) for MSH2, EP51 and A16-4 (FAS 15.2 and 15.2) for PMS2 and SP93 and EP49 (FAS 16.1 and 15.6) for MSH6. The most common detection systems were Ventana Optiview, Leica BondMax, Leica Bond Refine, Dako FLEX+ and Ventana UltraView. CONCLUSIONS: The quality of submitted MMR IHC sections has risen, with recent assessment scores showing lower variability, indicating better antibody clone performance, improved detection systems and IHC automation platform technology, allied to increasing technical competence among participants. UK NEQAS provides insight and feedback relating to MMR IHC protocols that most reliably produce high-quality MMR IHC staining to facilitate accurate reporting of the increasingly important tumour MMR status.
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