Journal of Clinical Pathology最新文献

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.

Aims: Analysis of the F8 gene helps predict the risk of developing factor VIII (FVIII) inhibitors and the depth of phenotype in haemophilia A (HA) patients. Since data in Southeast Asian countries remain scarce, we aim to study F8 variation correlated with HA phenotypes in Thailand.

Methods: Thai patients with HA were enrolled from seven haemophilia treatment centres during 2022-2023. Using peripheral blood DNA, inverse shifting-polymerase chain reaction (IS-PCR) for F8-intron 22 inversion (Inv22) and F8-intron 1 inversion (Inv1) was performed. Whole exome sequencing (WES) was explored in cases without Inv22/Inv1.

Results: Of 124 patients with HA, 91.9% were detected with a causative F8 variant, including Inv22 (30.6%), Inv1 (1.6%), missense (23.4%), nonsense (16.9%) and small insertion/deletion (16.1%) mutations. Inv22, small insertion/deletion and nonsense were associated with severe HA, compared with missense variants, by the ORs of 13.9 (95% CI, 4.2 to 56.7), 14.7 (95% CI, 3.4 to 104.7) and 15.6 (95% CI, 3.6 to 110.2), respectively. While nonsense variants affecting the light chain increased the risk of developing FVIII inhibitors (OR, 6.8; 95% CI, 1.5 to 32.6) compared with the low-risk (small insertion/deletion, missense and splice-site) variants. Twelve patients (9.7%) harboured novel F8 variants, comprising five missense (p.Pro540Leu, p.Ser564Pro, p.Leu668Pro, p.Ala1721Glu, p.His2024Pro), five small insertion/deletion (p.Val502SerfsTer13, p.Ile522PhefsTer13, p.Phe992LysfsTer11, p.Leu1223PhefsTer18, c.6427_6429+3delATGGTA) and one nonsense mutations (p.Glu1292Ter).

Conclusions: IS-PCR followed by WES successfully assesses F8 alterations in most HA cases. With several unique variants, severe HA in Thailand is considerably caused by Inv22, small insertion/deletion and nonsense, whereas missense variants are more responsible for nonsevere HA phenotypes.

Aims: Cancer diagnostics have been evolving rapidly. In England, the new National Health Service Genomic Medicine Service (GMS) provides centralised access to genomic testing via seven regional Genomic Laboratory Hubs. The PATHways survey aimed to capture pathologists' experience with current diagnostic pathways and opportunities for optimisation to ensure equitable and timely access to biomarker testing.

Methods: A nationwide survey was conducted with consultant pathologists from regional laboratories, via direct interviews based on a structured questionnaire. Descriptive analysis of responses was undertaken using quantitative and qualitative methods.

Results: Fifteen regional centres completed the survey covering a median population size of 2.5 (1.9-3.6) million (each for n=12). The median estimated turnaround time (calendar days) for standard molecular markers in melanoma, breast and lung cancers ranged from 2 to 3 days by immunohistochemistry (excluding NTRKfus in breast and lung cancers, and PD-L1 in melanoma) and 6-15 days by real-time-PCR (excluding KIT for melanoma), to 17.5-24.5 days by next-generation sequencing (excluding PIK3CA for breast cancer). Tests were mainly initiated by pathologists and oncologists. All respondents discussed the results at multidisciplinary team (MDT) meetings. The GMS roll-out was perceived to have high impact on services by 53% of respondents, citing logistical and technical issues. Enhanced education on new pathways, tissue requirements, report interpretation, providing patient information and best practice sharing was suggested for pathologists and other MDT members.

Conclusion: Our survey highlighted the role of regional pathology within the evolving diagnostic landscape in England. Notable recommendations included improved communication and education, active stakeholder engagement, and tackling informatics barriers.

Aims: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays.

Methods: A total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen's (dual) and Fleiss (triple) κ coefficients.

Results: In-house BRCA1/2 molecular testing yielded a concordance rate >90.0% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0% to 90.0% with a positive percentage agreement ranging from 75.0% to 80.0% and a negative percentage agreement ranging from 80.0% to 100%.

Conclusions: In-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays.

While the overwhelming majority of colorectal carcinomas (CRC) are diagnosed as adenocarcinoma not otherwise specified, there are numerous under-recognised morphologic patterns of CRC. These patterns are recognised by the WHO, appear in reporting manuals for the American Joint Committee of Cancer, and/or are listed on synoptic reports, while many other variants have either fallen out of favour or are emerging as future bona fide patterns. Herein, we discuss 13 variants: serrated adenocarcinoma, micropapillary adenocarcinoma, medullary carcinoma, neuroendocrine carcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, adenosquamous carcinoma, adenoma-like adenocarcinoma, lymphoglandular complex-like CRC, carcinoma with sarcomatoid components, cribriform-comedo-type adenocarcinoma, undifferentiated carcinoma and low-grade tubuloglandular adenocarcinoma. The purpose of this review is to scrutinise these variants by assessing their clinical characteristics, morphologic cues, as well as pitfalls, and address their prognostic significance. Our analysis aims to bring clarity and updated understanding to these variants, offering valuable insights for pathologists. This contributes to more nuanced CRC diagnosis and treatment strategies, highlighting the importance of recognising a broad spectrum of morphologic patterns in CRC.

Background: Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity.

Methods: We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared.

Results: A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively).

Conclusions: Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.

RB1 stands as the pioneering discovery in tumour-suppressor genes, marking a pivotal breakthrough in comprehending cancer development. This overview delves into the role of RB1 in both health and disease, exploring its association with the tumourigenesis of various cancers and a distinct subset of soft-tissue neoplasms. Additionally, we discuss the application of immunohistochemistry and fluorescence in situ hybridisation to detect RB1 alterations.

Aim: Colorectal cancer (CRC) is the fourth most common cancer in the UK. Following National Institute for Health and Care Excellence guidance for faecal immunochemical testing (FIT), we introduced a service for the measurement of faecal haemoglobin (f-Hb) in symptomatic patients. Previously, we evaluated the first 6 months of the service in three local boroughs, here we re-examine the use of FIT, over a similar 6 months in the two successive years.

Methods: Patients who had FIT requested in April-September 2020 and 2021 were studied. Results were obtained from the laboratory information systems and matched with the clinical outcomes of those referred via the urgent lower gastrointestinal cancer pathway. Patient demographics, reason for referral, clinical outcome and diagnostic test performance are reported.

Results: In 2020, 4042 samples were analysed and 57 CRC detected. In 2021, 10 508 samples were analysed and 65 CRC detected. Six (4.9%) patients with CRC had f-Hb <10 µg/g, of whom three were anaemic. In 2020, 27.7% of samples were from patients under 50 years; and in 2021, 32.8%. Sensitivity, specificity, positive predictive value and negative predictive value of f-Hb at ≥10 µg/g for CRC were 92.9%, 46.6%, 6.4% and 99.4% in 2020 and 96.9%, 29.9%, 3.2% and 99.8% in 2021.

Conclusions: As currently used in primary care in North East London, specificity of FIT at a cut-off of 10 µg/g is much lower than in published studies and the impact of this on colorectal services needs to be considered.