Journal of Clinical Pathology最新文献

Aims: ELOC (TCEB1)-mutant renal cell carcinoma (RCC) is a recently recognised entity in the 2022 WHO classification. Due to overlapping features, it is frequently misdiagnosed as clear cell RCC (CCRCC). This study characterises the clinicopathological, immunohistochemical and molecular features of six ELOC-mutant RCCs to aid in their diagnostic distinction.

Methods: Twenty-eight RCCs initially diagnosed as CCRCC with cytokeratin 7 (CK7) positivity and/or fibromuscular stroma were re-evaluated. Sanger sequencing was performed to detect ELOC mutations. The histopathological and immunophenotypic features of the six mutation-positive tumours were compared with those of the remaining 22 cases.

Results: The six ELOC-mutant tumours occurred in five men and one woman. All specimens showed a multinodular architecture, separated by a thick fibromuscular stroma. Tumour cells exhibited tubular, papillary, nested and tubulocystic patterns, with small branching papillae often present within cysts. The cytoplasm was predominantly clear, and nuclei were low-grade and basally oriented. CK7 expression was moderate to strong, with diffuse membranous staining in papillary areas. Sanger sequencing confirmed ELOC point mutations in all cases. In contrast, CCRCCs with fibromuscular stroma were rare, more often exhibited eosinophilic cytoplasm, lacked papillary structures and showed negative or only focal expression of CK7. Sanger sequencing showed the wild-type ELOC genotype.

Conclusions: ELOC-mutant RCC exhibits distinctive morphologic and immunohistochemical features; however, a definitive diagnosis requires molecular confirmation. Recognition of its characteristic features, including clustered branching papillae, CK7 positivity in papillary regions and the lack of correlation between cytoplasmic and nuclear grade, can guide appropriate ancillary testing and improve diagnostic accuracy.

Diagnosing and identifying the type of porphyria in a patient requires specialist analysis of porphyrins and/or precursors in blood, urine and faeces. Correct sample storage and handling prior to analysis is essential to minimise preanalytical error.We evaluated the impact of light exposure, time and temperature on erythrocyte and plasma porphyrins in samples from patients with erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) stored as whole blood for up to 96 hours, and in addition, the effect of freeze-thaw on plasma porphyrins in EPP, PCT and hereditary coproporphyria patient samples.Plasma porphyrins in the EPP patient samples decreased on average by 19% after 6 hours despite light protection and fridge storage, 36% by 24 hours stored light protected at room temperature, 67% within 1 hour when light exposed and 33% after one freeze-thaw cycle. In contrast, plasma porphyrin in PCT samples demonstrated greater stability compared to the EPP samples when stored light protected or exposed at room temperature and during freeze-thaw. Erythrocyte porphyrins in EPP samples were stable for 96 hours under all three storage conditions examined.Erythrocyte protoporphyrin analysis should be undertaken as an additional first-line investigation alongside plasma porphyrin analysis whenever protoporphyria needs to be excluded, due to the significant instability of plasma protoporphyrin.

Aims: Annotation of liver biopsies for disease staging is increasingly aided by digital pathology; however, existing systems do not quantify inflammation and steatosis within an anatomical framework. We hypothesise that an artificial intelligence (AI) system that quantifies portal tracts (PT) and the anatomical distribution of steatotic vesicles and inflammatory cells will align with manual pathologist scoring and stratify liver diseases.

Methods: In this observational, cross-sectional study, digitised images of haematoxylin and eosin-stained specimens were pooled from four independent cohorts of metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH) or autoimmune hepatitis (AIH) (n=390: 89 MASLD, 238 MASH, 63 AIH). PT, steatosis, and inflammation were quantified using a proprietary AI system and scored by expert pathologists.

Results: The percentage of steatosis was higher in MASH (7.5%) than in MASLD (3.2%). Lobular regions had larger steatotic vesicles (260 vs 190 μm²). AI-derived steatosis quantification correlated with manual grading (r_s=0.72). The inflammatory cell number (ICN) was twofold higher in AIH than MASLD/MASH in interface (390 vs 140), portal (4600 vs 1500) and lobular (1500 vs 650) regions. Portal inflammation from manual grading correlated with ICN count at PT (r_s=0.71) but not lobular regions (r_s≤0.29). For equivalent grades of portal inflammation, the ICN was up to threefold higher in AIH than in MASLD/MASH (r_s=0.71).

Conclusion: A new AI system for anatomical quantification of liver biopsy features measured variation in fat and inflammation across the lobule. It showed that inflammation burden was higher in AIH than MASLD/MASH, despite equivalent portal grades, providing objective support for histological scoring.

Aim: 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.

Methods: 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.

Results: 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=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).

Conclusions: 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.

Aims: Papillary carcinoma diagnosed in core needle biopsy (CNB) refers to carcinoma with papillary features but no definitive invasion, including papillary ductal carcinoma in situ (DCIS), papilloma with DCIS, encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC). This study assesses the upgrade rate of papillary carcinoma in CNB and supports the use of 'papillary carcinoma' as an umbrella term.

Methods: A retrospective review identified 41 CNB cases of non-invasive papillary carcinoma with subsequent excision (2011-2018). H&E and immunohistochemistry slides from CNBs were reviewed, and excisional diagnoses were retrieved.

Results: All 41 CNB cases were either DCIS or upgraded to invasive carcinoma upon excision, with an overall upgrade rate to invasive carcinoma of 39% (16/41). Subtypes showed varying upgrade rates: 16.7% (1/6) for papillary DCIS, 25% (1/4) for papilloma with DCIS, 83.3% (5/6) for SPC, 100% (1/1) for EPC and 33.3% (8/24) for unclassifiable papillary carcinoma. No lymph node metastases, recurrences or breast cancer-related mortality were observed during the follow-up period.

Conclusions: Given the high upgrade rate, subclassification of papillary carcinoma in CNB lacks clinical significance. The term 'papillary carcinoma' should be used in CNB, and lymph node removal warrants further investigation.

Aims: A synthetic lifting agent, ORISE, used for endoscopic mucosal resections, has been recalled from the market since November 2022 due to clinical complications. Despite this, the impact of ORISE-associated complications is expected to persist in the foreseeable future. We present a large single institutional series of therapeutic resections from patients for whom ORISE was used for initial endoscopic procedures, highlighting the pitfalls and complications associated with its use.

Methods: All specimens showing lifting agent granulomata (LAGs) associated with the use of ORISE were identified. The H&E slides were reviewed to define the morphological characteristics and extent of LAG in the intestinal wall and other organs. The clinical impression and gross findings were compared with the final pathological diagnosis.

Results: 34 cases (28 resections and 6 repeat endoscopic mucosal resection specimens) showed LAG. On microscopy, 20.5% showed no residual disease, 64.7% also showed residual precursor lesion and 14.7% also showed malignancy. In 64.2% of cases, a mass lesion was seen grossly but no malignancy was identified microscopically. ORISE was present in vascular spaces (n=9), lymph nodes (n=2), other organs such as appendix (n=1) and omentum/peritoneum (n=1). The major discordance between clinical impression (mass/neoplasm) and final pathology (no residual malignancy) was seen in 4/34 (11.8%) cases. LAGs were seen up to 10 months after the use of ORISE in the prior endoscopic procedure.

Conclusion: ORISE deposits may mimic residual/disseminated neoplasm and prompt inadvertent changes in surgical decisions. Awareness of this pitfall is essential to prevent unwarranted surgical resections in patients undergoing follow-up for endoscopically resected lesions.

p53 immunohistochemistry (IHC) is widely used as a rapid surrogate for detecting TP53 mutations, with TP53 mutations being a key biomarker for poor outcomes in lymphomas. We developed two algorithms using digital quantification tools to assess p53 expression from whole slide images of 77 lymphoma samples. An experienced pathologist visually evaluated the p53 slides, classifying cases as likely wild-type or mutated TP53 genotype. We correlated the results of the algorithms and visual inspection with the actual TP53 genotype. For cases with p53 overexpression (likely missense mutations), the algorithms achieved 86.7% sensitivity and 98.2% specificity (visual inspection: 80% and 95.2%). For cases with reduced p53 expression (likely 'other' mutations), the algorithms showed 92.7% sensitivity and 100% specificity (visual inspection: 40% and 95.8%). This study demonstrates that combining digital pathology with digital quantification tools-based algorithms can reliably predict TP53 genotype from p53 IHC patterns, with comparable or slightly superior performance to an experienced pathologist.

We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into 'essential' and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma classification, providing guidance on how to apply the WHO classification in resource-limited settings.

Aims: To investigate immunohistochemical expression of the E26 transformation-specific factors (ETS)-related gene (ERG) in a large number of soft tissue neoplasms using a tissue microarray technique.

Methods: 489 cases of soft tissue neoplasms, including benign and malignant entities, were collected from the files of the respective institutions and constructed into tissue microarrays. Tissue microarrays were stained for ERG immunohistochemistry using two antibodies, EP111 and EPR3864.

Results: A total of 25 cases (5.1%) were identified that were positive for ERG using the monoclonal antibody EP111 and 15 cases (3%) using the monoclonal antibody EPR3864, including rhabdomyosarcoma, peripheral nerve sheath tumours, synovial sarcoma, myxofibrosarcoma, epithelioid sarcoma, dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, nodular fasciitis and dedifferentiated liposarcoma. The most consistently stained tumours included synovial sarcoma, rhabdomyosarcoma and benign and malignant peripheral nerve sheath tumours. Various other fibroblastic proliferations, including dermatofibrosarcoma protuberans, myxofibrosarcoma, low-grade fibromyxoid sarcoma and nodular fasciitis, also showed positive staining in a small fraction of cases. One case of dedifferentiated liposarcoma showed nuclear positivity for ERG, and one case of epithelioid sarcoma was also positive.

Conclusions: This study supports the value of ERG as a highly sensitive and specific marker for the diagnosis of vascular neoplasms but also demonstrates rare cases of aberrant staining and underscores the need to assess soft tissue tumours using a panel of stains and interpret the results of immunohistochemistry in the appropriate histological and clinical context.