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Journal Of Clinical Pathology[JOURNAL]

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Sinonasal alveolar rhabdomyosarcoma with fusion expressing SOX10 and with nodal metastases: a double diagnostic pitfall.

Crane H, Young RJ, Fernando MS … +1 more , Griffin J

J Clin Pathol · 2025 Nov · PMID 39209443 · Publisher ↗

Abstract loading — click title to view on PubMed.

"Find Your Y": histological differences in early stage (pT) and post-treatment (ypT) oesophageal adenocarcinoma with implications for salvage endoscopic resection.

Pacheco RR, Lee G, Yang Z … +7 more , Lin J, Patil DT, Youssef M, Zhang Q, Alkashash AM, Li J, Lee H

J Clin Pathol · 2025 Aug · PMID 39181711 · Publisher ↗

AIMS: Current guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcin... AIMS: Current guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited. We aimed to elucidate histological characteristics influencing salvage ER success in patients with low-stage, pretreated EAC. METHODS: We retrospectively reviewed 272 EAC tumours postoesophagectomy from five US centres and collected clinicopathological data including discontinuous growth (DG), defined as separate tumour foci ≥2 mm from the main tumour. We selected 101 patients with low-stage disease and divided them into treatment-naïve (n=70) and neoadjuvant therapy (n=31) groups. We compared the two groups and differences in clinical, histological and outcome characteristics were identified. RESULTS: In the entire cohort (n=272), DGs were identified in 22% of cases. Multivariate analysis revealed DGs as an independent prognostic factor for recurrence and positive oesophagectomy margins. Lymphovascular invasion (LVI) and background intestinal metaplasia predicted DG presence and absence, respectively. Compared with the treatment-naïve low T-stage subgroup, the pretreated subgroup exhibited higher incidence of poorly differentiated carcinoma (16% vs 46%, p=0.007), larger tumours (14 vs 30 mm, p<0.001), higher tumour, node, metastases stage (7% vs 30%, p=0.004), more nodal disease (7% vs 36%, p<0.001) and frequent DGs (1% vs 13%, p=0.030). CONCLUSIONS: In treated low T-stage EACs, DGs may contribute to suboptimal outcomes following salvage ER. Presence of LVI (as a surrogate for DGs) and poor differentiation in the absence of intestinal metaplasia in biopsy samples may serve as histological poor prognosticators in treated patients with EAC being considered for salvage ER.

Mounting agents with low toxicity and with fast curing time for digital pathology in the intraoperative frozen section laboratory.

Frandsen MW, Bojesen L, Johnsen S … +2 more , Riis LB, Smith J

J Clin Pathol · 2025 Jun · PMID 39181710 · Publisher ↗

AIMS: In intraoperative frozen tissue section laboratories (FS laboratories) conventional practice for mounting coverslips on tissue slides involves the use of xylene-based mounting agents, such as Pertex. However, toxic... AIMS: In intraoperative frozen tissue section laboratories (FS laboratories) conventional practice for mounting coverslips on tissue slides involves the use of xylene-based mounting agents, such as Pertex. However, toxic vapours pose a risk to biomedical laboratory scientists (BLS) and pathologists who handle the wet slides to provide fast and urgent diagnostic results to surgeons during operations. Our study aims to evaluate non-toxic mounting agents to substitute Pertex, preferably with a fast curing time suitable for the demands of the new digital era in pathology. METHODS: Five non-toxic mounting agents were purchased and tested through six different protocols and compared to xylene-based Pertex as our gold standard. With light microscopy, tissue slides were quality assessed by BLS. Mounting agents, which were evaluated comparable to Pertex, were also evaluated by a pathologist, hence scanned digitally and re-evaluated. RESULTS: The protocols for , and had significantly more artefacts (bubbles) compared to gold standard Pertex (p<0.0001, p=0.004 and p<0.0001, respectively) and assessed inadequate as replacements. and were assessed applicable regarding quality, but curing times were long. showed promising results in both quality and fast curing time (protocol was <2 min). CONCLUSIONS: Toxic mounting agents need replacement to health guard professionals, and also digital pathology is revolutionising laboratories. A digitalized FS laboratory requires fast dry/cured slides for digital scanning. Therefore, a substitute for the FS laboratory should have the qualities of being non-toxic to handle and having a fast curing time, and a UV-based mounting agent may solve both requirements.

IASLC grading system predicts distant metastases for resected lung adenocarcinoma.

Wang Y, Smith MR, Dixon CB … +13 more , D'Agostino R, Liu Y, Ruiz J, Chan MD, Su J, Mileham KF, Lycan T, Green ME, Hassan OA, Jiang Y, Khan Niazi MK, Li W, Xing F

J Clin Pathol · 2025 May · PMID 39168612 · Full text

AIMS: The International Association for the Study of Lung Cancer (IASLC) has proposed a new histological grading system for invasive lung adenocarcinoma (LUAD). However, the efficacy of this grading system in predicting... AIMS: The International Association for the Study of Lung Cancer (IASLC) has proposed a new histological grading system for invasive lung adenocarcinoma (LUAD). However, the efficacy of this grading system in predicting distant metastases in patients with LUAD remains unexplored. This study aims to assess the potential of the IASLC grading system in predicting the occurrence of brain and bone metastases in patients with resectable LUAD, thereby identifying individuals at high risk of post-surgery distant metastasis. METHODS: We retrospectively analysed clinical data and pathological reports of 174 patients with early-stage LUAD who underwent surgical resection between 2008 and 2015 at our cancer center. Patients were monitored for 5 years, and their bone and brain metastasis-free survival rates were determined. RESULTS: 28 out of 174 patients developed distant metastases in 5 years with a median overall survival of 60 months for metastasis-free patients and 38.3 months for patients with distant metastasis. Tumour grading of all samples was evaluated by both IASLC grading and predominant pattern-based grading systems. Receiver operating characteristic (ROC) curves were used to evaluate the predictive capabilities of the IASLC grading system and tumour stage for distant metastasis. Compared with the predominant pattern-based grading system, the IASLC grading system showed a better correlation with the incidence of distant metastasis and lymphovascular invasion. ROC analyses revealed that the IASLC grading system outperformed tumour stage in predicting distant metastasis. CONCLUSIONS: Our study indicates that the IASLC grading system is capable of predicting the incidence of distant metastasis among patients with early-stage invasive LUAD.

Breast phyllodes tumour with epithelioid feature predisposes to malignant transformation.

Shao M, Zhang L, Li X … +7 more , Bi J, Jiang X, Yu X, Liang Y, Xu H, Meng G, Gong X

J Clin Pathol · 2025 May · PMID 39160061 · Full text

AIMS: Phyllodes tumours (PTs) are relatively common fibroepithelial tumours comprising epithelial and stromal component. Usually, PTs show a spindle cell morphology with a fibroblast phenotype, while some tumour cells ex... AIMS: Phyllodes tumours (PTs) are relatively common fibroepithelial tumours comprising epithelial and stromal component. Usually, PTs show a spindle cell morphology with a fibroblast phenotype, while some tumour cells exhibit epithelioid morphological features and sarcomatoid transformation. However, the molecular characteristics of this morphology subset remain unclear. This study aimed to summarise the clinicopathological, morphological and molecular characteristics of seven cases of PT with epithelioid features. METHODS: Morphological and clinicopathological characteristics were observed and retrieved. Immunohistochemistry, immunofluorescence and electron microscope were performed on seven cases of epithelioid PT to explore immunophenotypic and ultrastructural characteristics. Transcriptomic and proteomic analyses were conducted to compare differentially expressed genes and proteins between epithelioid PT and classical PT. RESULTS: Patients with epithelioid PT exhibit a high recurrence rate (42.8%). Morphologically, in addition to having epithelioid cytological features, neoplastic stromal cells exhibit moderate to marked atypia and often exhibit sarcomatoid transformation, similar to the characteristics of borderline PT. Transcriptomic and proteomic analyses demonstrated that epithelioid PTs are distinct from classical PTs in gene expression and protein abundance levels. Immunohistochemical analysis showed that among all differentially expressed proteins, epithelioid PT showed abnormal p16/retinoblastoma expression patterns, similar to those of malignant PT. CONCLUSIONS: Epithelioid PT has unique morphological characteristics, biological behaviour and protein expression profile, which meets the diagnostic criteria of borderline PT and is prone to sarcomatoid transformation. It may be a special morphological subgroup of borderline PT and has partial characteristics of malignant PT, which should be taken seriously in pathological diagnosis and clinical management.

Assessing IgG4-related ophthalmic disease and its mimics: a comparison of ACR/EULAR, organ-specific and revised comprehensive diagnostic criteria.

Bakshi N, Aggarwal A, Dhawan S … +4 more , Grover AK, Duggal L, Badwal S, Rao S

J Clin Pathol · 2025 Jul · PMID 39160060 · Publisher ↗

AIMS: Diagnosis of IgG4-related ophthalmic disease (IgG4-ROD) rests on the correlation of clinical features, serological testing and histopathology, using internationally accepted diagnostic criteria for objective interp... AIMS: Diagnosis of IgG4-related ophthalmic disease (IgG4-ROD) rests on the correlation of clinical features, serological testing and histopathology, using internationally accepted diagnostic criteria for objective interpretation; however, several mimickers of IgG4-RD overlap in clinical presentation and histopathology. We assess histopathological features in a series of presumptive IgG4-ROD cases, with emphasis on histopathological mimics and comparison of three IgG4-ROD diagnostic/classification criteria (organ-specific (OS), revised comprehensive diagnostic (RCD) and American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria). METHODS: The histopathology database was screened for cases with clinical/histopathological suspicion of IgG4-ROD. Slides were reviewed, OS, RCD and ACR/EULAR criteria were applied, and the final clinicopathological diagnosis was recorded. RESULTS: 37 patients (24 females, 13 males; 19-73 years) were diagnosed as either IgG4-ROD (n=18) or non-IgG4-related disease (n=19). Non-IgG4-related disease group showed elevated serum IgG4 (55.5%), fibrosis (100%), dense lymphoplasmacytic inflammation (92.8%), with an increase in tissue IgG4+plasma cells (57.1%) and elevated IgG4:IgG+plasma cell ratio (14.3%). ACR/EULAR missed 50% (9/18, sensitivity-52.8%) of true IgG4-ROD cases, while OS and RCD criteria missed 11.1% (2/18, sensitivity-88.9%) of IgG-ROD cases. ACR/EULAR criteria mislabelled 7.14% (1/14, specificity-90.9%) while OS and RCD criteria wrongly categorised 71.4% (10/14, specificity-47.4%) and 50% (7/14, specificity-63.2%) specific non-IgG4-ROD cases as IgG4-ROD. Storiform fibrosis, obliterative phlebitis, increased IgG4:IgG+plasma cell ratio and elevated serum IgG were statistically significant in distinguishing IgG4-ROD from its mimics. CONCLUSION: ACR/EULAR criteria showed high specificity but were cumbersome and sensitivity was low, while RCD and OS criteria showed low specificity. Stringent clinicopathological correlation to exclude mimics is critical in avoiding diagnostic errors in IgG4-ROD.

Molecular confirmation that fibrocartilaginous dysplasia is a variant of fibrous dysplasia.

Zhou J, Su X, Hu D … +5 more , Zhang L, Chen C, Sun K, Zhang H, Liu Z

J Clin Pathol · 2024 Aug · PMID 39153849 · Publisher ↗

AIMS: Fibrocartilaginous dysplasia (FCD) is a subvariant of fibrous dysplasia (FD). This study aims to retrospectively elucidate the clinicopathological and separate genetic features of the cartilaginous and fibro-osseou... AIMS: Fibrocartilaginous dysplasia (FCD) is a subvariant of fibrous dysplasia (FD). This study aims to retrospectively elucidate the clinicopathological and separate genetic features of the cartilaginous and fibro-osseous components of FCD. METHODS: In total, 24 patients (14 men and 10 women) with FCD were included in our cohort. The diagnosis was confirmed morphologically and immunohistochemically, and genetic features were determined via Sanger sequencing. RESULTS: Five patients were polyostotic, and 19 were monostotic, predominantly concerning the femur. Radiography revealed a well-demarcated ground glass appearance with ring-like or scattered calcification. Histologically, the lesions were characterised by proliferative fibroblasts, immature woven bone and highly differentiated hyaline cartilage. The fibro-osseous components exhibited positive immunoreaction with SATB2 and a low Ki-67 proliferation index. The fibro-osseous and cartilaginous components shared mutations at codon 201 in exon 8 of the guanine nucleotide-binding protein/a-subunit ( gene, specifically CGT>CAT (p.R201H) in four patients and the wild-type isocitrate dehydrogenase ( gene. Telomerase reverse transcriptase ( promoter mutations (C288T and C229G) occurred in both fibro-osseous and cartilaginous components in two patients. CONCLUSIONS: FCD encompasses areas of conventional FD with additional cartilage. Importantly, the presence or absence of mutations in the gene and/or the promoter is common between the fibro-osseous and cartilaginous components of the disease. These results further confirmed FCD as a variant of FD.

Prognostic implications, genomic and immune characteristics of lung adenocarcinoma with lepidic growth pattern.

Li Y, Chen D, Xu Y … +5 more , Ding Q, Xu X, Li Y, Mi Y, Chen Y

J Clin Pathol · 2025 Mar · PMID 39097406 · Publisher ↗

AIMS: Conflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A co... AIMS: Conflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A could provide deeper insights into its prognostic implications and treatment determination. METHODS: We conducted a search of articles in PubMed, EMBASE and the Cochrane Library from inception to January 2024. A domestic cohort consisting of 52 LUAD samples was subjected to whole-exome sequencing as internal validation. Data from The Cancer Genomic Atlas and the Gene Expression Omnibus datasets were obtained to characterise the genomic and immune profiles of LP+A. Pooled HRs and rates were calculated. RESULTS: The pooled results indicated that lepidic growth pattern was either predominant (0.35, 95% CI 0.22 to 0.56, p<0.01) or minor (HR 0.50, 95% CI 0.36 to 0.70, p<0.01) histological subtype was associated with favourable disease-free survival. Pooled gene mutation rates suggested higher EGFR mutation (0.55, 95% CI 0.46 to 0.64, p<0.01) and lower KRAS mutation (0.14, 95% CI 0.02 to 0.25, p=0.02) in lepidic-predominant LUAD. Lepidic-predominant LUAD had lower tumour mutation burden and pooled positive rate of PD-L1 expression compared with other subtypes. LP+A was characterised by abundance in resting CD4+memory T cells, monocytes and γδ T cells, as well as scarcity of cancer-associated fibroblasts. CONCLUSIONS: LP+A was a unique histological subtype with a higher EGFR mutation rate, lower tumour mutation burden and immune checkpoint expression levels. Our findings suggested potential benefits from targeted therapy over immunotherapy in LP+A.

Primary desmoplastic small round cell tumour of the prostate.

Qian J, Yang Y, Xie X … +6 more , Kang Y, Zhong J, Chen X, Chen N, Zhou Q, Nie L

J Clin Pathol · 2024 Dec · PMID 39074976 · Full text

Desmoplastic small round cell tumour (DSRCT) is a highly aggressive soft-tissue sarcoma with distinctive morphological features and characteristic gene fusion. DSRCT occurs in a variety of anatomic sites, with abdominal... Desmoplastic small round cell tumour (DSRCT) is a highly aggressive soft-tissue sarcoma with distinctive morphological features and characteristic gene fusion. DSRCT occurs in a variety of anatomic sites, with abdominal cavity being the most common location. Primary DSRCTs arising in the male genital system are exceedingly rare, with no documented definitive cases of primary DSRCT of the prostate to date, although 28 cases of DSRCT in the testicular or paratesticular regions have been reported. We here present two cases of primary DSRCT of the prostate. Both cases demonstrated the distinct morphology and the typical multiphenotypic immunohistochemical profile, and the characteristic fusion verified by fluorescent in situ hybridisation. Our cases expand the anatomic distribution of primary DSRCT and highlight the importance of considering this rare tumour in the differential diagnoses of small cell malignancies of the prostate.

My approach to assessing for colorectal polyp cancer.

Wong NACS

J Clin Pathol · 2024 Nov · PMID 39074975 · Publisher ↗

Assessing a locally excised colorectal adenoma for malignancy is a common but often challenging scenario. This article outlines a simple, stepwise approach to this diagnostic assessment. The first steps are to assess for... Assessing a locally excised colorectal adenoma for malignancy is a common but often challenging scenario. This article outlines a simple, stepwise approach to this diagnostic assessment. The first steps are to assess for high-grade dysplasia and, if present, to determine whether any neoplastic glands lie within the submucosa. If so, a distinction must then be made between epithelial misplacement and adenocarcinoma; this process is aided by certain clinical and endoscopic data together with assessment of six key histological features. If adenocarcinoma is diagnosed, a final step is to report the presence/absence of high-risk features of polyp cancers because this will then determine if further surgical resection is required for that malignancy. Caveats, uncertainties and newly introduced concepts exist at several steps of the assessment pathway presented and are therefore discussed in detail throughout the article.

Combined detection of SHOX2 and PTGER4 methylation with serum marker CYFRA21-1 for improved diagnosis of malignant pleural mesothelioma.

Zhang N, Li Y, Sun Z … +11 more , Dong Y, Zhou L, Zhang C, Liu Z, Zhang Q, Li K, Xu F, Zhang L, She B, Ren X, Che N

J Clin Pathol · 2025 Nov · PMID 39060112 · Publisher ↗

AIMS: To investigate the performance of a combined biomarker approach using the methylation status of the short stature homeobox 2 () and prostaglandin E2 receptor EP4 () genes, along with the serum levels of CYFRA21-1,... AIMS: To investigate the performance of a combined biomarker approach using the methylation status of the short stature homeobox 2 () and prostaglandin E2 receptor EP4 () genes, along with the serum levels of CYFRA21-1, for differential diganosis of malignant pleural mesothelioma (MPM) from benign reactive mesothelial hyperplasia (RMH). METHODS: We analysed 48 MPM tissue or pleural effusion cell block specimens and 42 cases with RMH. Real-time quantitative methylation-specific PCR was used to examine the methylation status of , , ras association domain family 1 isoform A, septin 9 gene and homeobox gene A9 genes. Additionally, we employed electrochemiluminescence immunoassay to measure nine serum tumour markers commonly used in pan-cancer screening tests. RESULTS: The receiver operating curve indicated that , gene methylation and serum biomarker CYFRA21-1 exhibited good diagnostic performance in identifying MPM, with area under curves (AUCs) of 0.761, 0.904 and 0.847, respectively. The combination of , methylation and CYFRA21-1 yielded an AUC value of 0.972. The diagnostic sensitivity and specificity of this panel in differentiating MPM from RMH were 91.3% (42/46) and 97.6% (41/42), respectively. Both tissue and cell block specimens can be used in the diagnostic process. Furthermore, elevated CYFRA21-1 levels were associated with poor prognosis (p<0.05). Hypermethylation level of may indicate an unfavourable prognosis of MPM, but the difference was not statistically significant. CONCLUSIONS: The combined detection of and methylation alongside serum CYFRA21-1 level significantly enhances the diagnosis of MPM. Additionally, CYFRA21-1 can serve as a prognostic indicator for MPM.

Reappraisal and refined diagnosis of ultrasonography and histological findings for hydatidiform moles: a multicentre retrospective study of 821 patients.

Zhao Y, Cai L, Huang B … +13 more , Yin X, Pan D, Dong J, Zheng L, Chen H, Lin J, Shou H, Zhao Z, Jin L, Zhu X, Cai L, Zhang X, Qian J

J Clin Pathol · 2025 Jun · PMID 39048306 · Full text

AIMS: Specific identification of a hydatidiform mole (HM) and subclassification of a complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) are critical. This study aimed to reappraise the diagnostic perform... AIMS: Specific identification of a hydatidiform mole (HM) and subclassification of a complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) are critical. This study aimed to reappraise the diagnostic performance of ultrasonography and histology with a refined diagnosis. METHODS: This was a retrospective, multicentre cohort study of 821 patients with histologically suspected HM specimens. Refined diagnostic algorithms with p57 immunohistochemistry and short tandem repeat (STR) genotyping were performed and used as the true standard for assessing the diagnostic performance of the original ultrasonography and morphology methods. The diagnostic performance was calculated using accuracy, agreement rate, sensitivity and the positive predictive value (PPV) compared with refined diagnostic results. RESULTS: Of the 821 histologically suspected HM cases included, 788 (95.98%) were successfully reclassified into 448 CHMs, 213 PHMs and 127 non-molar (NM) abortuses. Ultrasonography showed an overall accuracy of 44.38%, with a sensitivity of 44.33% for CHM and 37.5% for PHM. The overall classification accuracy of the original morphological diagnosis was 65.97%. After exclusion of the initially untyped HMs, the overall agreement rate was 59.11% (κ=0.364, p<0.0001) between the original and refined diagnoses, with a sensitivity of 40.09% and PPV of 96.05% for diagnosing CHMs and a sensitivity of 84.98% and a PPV of 45.59% for diagnosing PHMs. The interinstitutional variability of morphology in diagnosing HMs was significant among the 15 centres (range, 8.33%-100.00%, p<0.0001). CONCLUSION: The current diagnosis of HM based solely on ultrasound or morphology remains problematic, and ancillary techniques, particularly p57 immunohistochemistry and DNA genotyping, should be integrated into routine practice as much as possible.

Frequency and clinicopathologic features of renal low-grade oncocytic tumour and eosinophilic vacuolated tumour: reclassification of 605 eosinophilic tumours including patients managed with active surveillance.

Choiniere R, Al Qa'qa' S, Cheung CC … +2 more , Finelli A, Prendeville S

J Clin Pathol · 2025 Jun · PMID 39033022 · Publisher ↗

AIMS: Low-grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT) are recently described emerging entities, which demonstrate distinct features but are not yet recognised as separate neoplasms in the fifth... AIMS: Low-grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT) are recently described emerging entities, which demonstrate distinct features but are not yet recognised as separate neoplasms in the fifth WHO classification. Published series to date have been largely multi-institutional and based on surgically resected tumours. This study aims to determine the frequency, clinicopathologic features and outcome of LOT and EVT in a single institutional series of oncocytic/eosinophilic renal neoplasms, including patients managed with active surveillance and non-surgical intervention. METHODS AND RESULTS: Cases were identified from a consecutive institutional series of in-house renal tumours diagnosed on biopsy and/or nephrectomy (2003-2023). Tumours with a diagnosis or differential diagnosis of oncocytoma, chromophobe renal cell carcinoma or oncocytic neoplasm not otherwise specified (including LOT, EVT and tumours with overlapping hybrid features) were retrospectively reviewed and classified/reclassified.In total, 605 oncocytic/eosinophilic renal neoplasms were reviewed, among which 33 LOT (5.5%) and 5 EVT (0.8%) were identified. LOT were CK7+, CD117- and GATA3+ (94%). EVT were CD117+, CK7 focal+ (80%) and cathepsin K+ (80%). At the median follow-up of 34 months (range 2-253) and 56 months (range 8-90) for LOT and EVT, respectively, there was no evidence of recurrence following ablation/surgical resection, metastasis or death from disease for all patients, including the 22 managed with active surveillance (20 LOT and 2 EVT). CONCLUSIONS: LOT and EVT comprised a minority of oncocytic renal neoplasms in this series. We report a large institutional series including patients managed non-surgically, with no adverse outcome, adding to the existing literature indicating a benign outcome.

Paediatric Crohn's disease: histologic findings at initial presentation.

Spasic S, Pankaj A, Kaplan JL … +3 more , Patil D, Moran CJ, Deshpande V

J Clin Pathol · 2025 Sep · PMID 39025491 · Publisher ↗

BACKGROUND: Diagnosing paediatric Crohn's disease (CD) based on histology can present challenges. We evaluate the histological spectrum of treatment-naïve biopsies from children with CD and assess these findings' diagnos... BACKGROUND: Diagnosing paediatric Crohn's disease (CD) based on histology can present challenges. We evaluate the histological spectrum of treatment-naïve biopsies from children with CD and assess these findings' diagnostic and predictive value. METHODS: Three cohorts were identified: (1) 137 patients with CD, (2) 116 patients with ulcerative colitis (UC) and (3) 50 patients without inflammatory bowel disease. Biopsies from the gastrointestinal (GI) tract were re-examined for signs of active and chronic inflammation, including lymphocyte-pattern oesophagitis, focal enhancing gastritis and indicators of chronicity. Additionally, granulomas and microgranulomas (defined as clusters of 4-9 epithelioid histiocytes) were evaluated. RESULTS: Lymphocyte-pattern oesophagitis was observed in 15% of patients (n=20). Moderate-to-severe diffuse gastritis was noted in 50.4% of patients (n=68), while focal enhancing gastritis was identified in 11.1% (n=15). In terminal ileal biopsies, 46.1% exhibited activity and 5.3% showed features of chronicity. Active colitis was present in 73% of patients (n=100), with chronic colitis seen in 11.7% (n=16). Granulomas and microgranulomas were observed in 31.4% (43/137) and 48.9% (67/137) of patients, respectively. Notably, 30.7% (42/137) of patients with microgranulomas were without granulomas. Previously undetected microgranulomas were found in 20 of 27 cases. 2.5% of patients with UC and none of the control cohort showed microgranulomas. Lymphocyte-pattern oesophagitis was associated with an increased need for anti-tumor necrosis factor (TNF) therapy (p=0.007). CONCLUSIONS: GI microgranulomas, often overlooked, are specific to CD in the proper clinical context. Oesophageal lymphocytosis may predict a need for more aggressive treatment. The study brings to light under-recognised aspects of CD's histological diagnosis, including the oversight of microgranulomas, the high prevalence of diffuse gastritis and low prevalence of focal enhancing gastritis, the frequent absence of terminal ileitis and the infrequent occurrence of chronic colitis.

Pitfalls in the diagnosis and management of acid-base disorders in humans: a laboratory medicine perspective.

Carlton H, Shipman KE

J Clin Pathol · 2024 Oct · PMID 39025490 · Publisher ↗

Diagnostic errors affect patient management, and as blood gas analysis is mainly performed without the laboratory, users must be aware of the potential pitfalls. The aim was to provide a summary of common issues users sh... Diagnostic errors affect patient management, and as blood gas analysis is mainly performed without the laboratory, users must be aware of the potential pitfalls. The aim was to provide a summary of common issues users should be aware of.A narrative review was performed using online databases such as PubMed, Google Scholar and reference lists of identified papers. Language was limited to English.Errors can be pre-analytical, analytical or post-analytical. Samples should be analysed within 15 min and kept at room temperature and taken at least 15-30 min after changes to inspired oxygen and ventilator settings, for accurate oxygen measurement. Plastic syringes are more oxygen permeable if chilled. Currently, analysers run arterial, venous, capillary and intraosseous samples, but variations in reference intervals may not be appreciated or reported. Analytical issues can arise from interference secondary to drugs, such as spurious hyperchloraemia with salicylate and hyperlactataemia with ethylene glycol, or pathology, such as spurious hypoxaemia with leucocytosis and alkalosis in hypoalbuminaemia. Interpretation is complicated by result adjustment, for example, temperature (alpha-stat adjustment may overestimate partial pressure of carbon dioxide (pCO) in hypothermia, for example), and inappropriate reference intervals, for example, in pregnancy bicarbonate, and pCO ranges should be lowered.Lack of appreciation for patient-specific and circumstance-specific reference intervals, including extremes of age and altitude, and transformation of measurements to standard conditions can lead to inappropriate assumptions. It is vitally important for users to optimise specimen collection, appreciate the analytical methods and understand when reference intervals are applicable to their specimen type, clinical question or patient.

Rosai-Dorfman Disease of pancreas: rare aetiology mimicking malignancy.

Qama E, Rodriguez CC, Sekhri R … +3 more , Lu C, McAuliffe J, Bhalla A

J Clin Pathol · 2024 Nov · PMID 39025489 · Publisher ↗

Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis which usually presents as painless lymphadenopathy. Extranodal involvement is known to occur in various organs, and less than ten cases with primary panc... Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis which usually presents as painless lymphadenopathy. Extranodal involvement is known to occur in various organs, and less than ten cases with primary pancreatic involvement have been reported previously. This case report details the clinical course of an elderly female, presenting with upper abdominal discomfort and imaging suggestive of malignancy. Multiple non-diagnostic fine-needle aspirations were followed by surgical intervention. Histopathological evaluation revealed a pancreatic mass with characteristic features of RDD. The large hallmark RDD histiocytes showed pale, watery-clear cytoplasm, central round nucleus, and prominent nucleolus, with and without lymphocyte emperipolesis. The RDD histiocytes showed positive immunostaining for CD68, CD163, S100 (nuclear and cytoplasmic), OCT-2, Cyclin D1 and are negative for CD1a, Factor XIIIa, fascin and langerin. This case underscores the importance of considering RDD in the differential diagnosis of pancreatic masses alongwith comprehensive evaluation, multidisciplinary approach and pancreatic core needle biopsy evaluation.

Gone but not forgotten: expanding the spectrum of ORISE (submucosal lifting agent) associated diagnostic pitfalls and complications.

Dhorajiya P, Mahmood S, Fabrizio A … +2 more , Deshpande V, Vyas M

J Clin Pathol · 2025 Oct · PMID 39025488 · Publisher ↗

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 complicati... 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.

Some issues to consider with the use of serum indices.

Reeve JLV, Housley D, Twomey PJ

J Clin Pathol · 2024 Sep · PMID 38991706 · Publisher ↗

Abstract loading — click title to view on PubMed.

Haemolysis index conundrum in a COVID-19 patient.

Zhao CQM, Steinberg J, Otero Espinal D … +1 more , Vele O

J Clin Pathol · 2024 Sep · PMID 38991705 · Publisher ↗

In this study, we report a preanalytical challenge noted in our laboratory on plasma samples from a critically ill COVID-19 patient treated with hydroxychloroquine. This is significant because, in critically ill COVID-19... In this study, we report a preanalytical challenge noted in our laboratory on plasma samples from a critically ill COVID-19 patient treated with hydroxychloroquine. This is significant because, in critically ill COVID-19 patients on hydroxychloroquine, plasma samples can have a high measured haemolysis index in the absence of haemolysis, with the impact on reporting the results for potassium and other analytes.

The road ahead: a brief guide to navigating the 2022 WHO classification of endocrine and neuroendocrine tumours.

Juhlin CC

J Clin Pathol · 2024 Dec · PMID 38981664 · Full text

The most recent WHO classification of endocrine and neuroendocrine tumours has brought about significant changes in the diagnosis and grading of these lesions. For instance, pathologists now have the ability to stratify... The most recent WHO classification of endocrine and neuroendocrine tumours has brought about significant changes in the diagnosis and grading of these lesions. For instance, pathologists now have the ability to stratify subsets of thyroid and adrenal neoplasms using various histological features and composite risk assessment models. Moreover, novel recommendations on how to approach endocrine neoplasia involve additional immunohistochemical analyses, and the recognition and implementation of these key markers is essential for modernising diagnostic capabilities. Additionally, an improved understanding of tumour origin has led to the renaming of several entities, resulting in the emergence of terminology not yet universally recognised. The adjustments in nomenclature and prognostication may pose a challenge for the clinical team, and care providers might be eager to engage in a dialogue with the diagnosing pathologist, as treatment guidelines have not fully caught up with these recent changes. Therefore, it is crucial for a surgical pathologist to be aware of the knowledge behind the implementation of changes in the WHO classification scheme. This review article will delve into the most significant diagnostic and prognostic changes related to lesions in the parathyroid, thyroid, adrenal glands and the gastroenteropancreatic neuroendocrine system. Additionally, the author will briefly share his personal reflections on the clinical implementation, drawing from a couple of years of experience with these new algorithms.
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