Journal of Clinical Pathology

Journal Information
ISSN / EISSN: 00219746 / 14724146
Published by: BMJ
Total articles ≅ 20,579

Latest articles in this journal

Fumi Okada, , Tomomi Fujii, Tomoko Uchiyama, Shoh Sasaki, Minami Matsuoka, Yuji Nitta, Chiyoko Terada, Katsuya Maebo, Kohei Morita, et al.
Published: 1 December 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208583

Abstract:
Aims: Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of pulmonary adenocarcinoma. Due to its rarity, few pathological and molecular studies have been performed on PEAC. We herein conducted clinicopathological, immunohistochemical and molecular analyses of PEAC with a focus on its differentiation from invasive mucinous adenocarcinoma (IMA).Methods: We examined the clinicopathological features of 16 cases of PEAC and performed a genetic analysis using next-generation sequencing (NGS). The results obtained were compared with those for IMA.Results: The average age of patients with PEAC (seven men and nine women) was 72.9 years. A comparison of clinical data on PEAC and IMA revealed no significant differences in age, sex or smoking history. Fifteen PEAC cases had dirty necrosis. Immunohistochemically, the positive rates for each antibody in PEAC were as follows: CK7, 88% (14/16); CK20, 81% (13/16); CDX2, 88% (14/16); p53, 69% (11/16); MUC1, 100% (16/16); MUC2, 19% (3/16); MUC5AC, 69% (11/16); MUC6, 19% (3/16). The positive rates for these antibodies in IMA were 100%, 87%, 0%, 7%, 93%, 0%, 100% and 80%, respectively.EGFRmutations, theMETexon 14 skipping mutation,BRAFmutations, theALKfusion gene andROS-1fusion gene were not detected in any cases of PEAC or IMA. Among PEAC cases, NGS identifiedKRASmutations in seven (44%, 7/16) andTP53mutations in nine (56%, 9/16). Among IMA cases, the most commonly mutated gene wasKRAS(90%).Conclusions: The rates of dirty necrosis, immunopositivity for CDX2 andTP53mutations were significantly higher, while that ofKRASmutations was significantly lower in PEAC cases than in IMA cases.
Published: 21 November 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208574

Abstract:
Aims: The aim of this study was to investigate the association between oncogenic alterations and programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinomas, as well as the prognostic value ofKRASand/orTP53mutations in patients treated with immunotherapy.Methods: This study is a retrospective cohort study of 519 patients with lung adenocarcinomas analysed for mutations and PD-L1 expression. Data were collected from electronic pathology record system, next-generation sequencing system, and clinical databases. Association between mutations and PD-L1 expression was investigated, as well as survival statistics of the 65 patients treated with immunotherapy.Results: 41% of the samples contained aKRASmutation, predominantly together with mutations inTP53(41%) orSTK11(10%). Higher expression of PD-L1 was seen among patients withKRASmutations (p=0.002) andEGFRwild type (p=0.006). For patients treated with immunotherapy, there was no statistically significant difference for overall survival (OS) and progression-free survival (PFS) according toKRASmutation status,TP53mutation status or PD-L1 expression. The HR for concomitant mutations inTP53andKRASwas 0.78 (95% CI 0.62 to 0.99) for OS and 0.43 (0.21 to 0.88) for PFS. Furthermore, concomitantTP53andKRASmutations predicted a better PFS (p=0.015) and OS (p=0.029) compared with no mutations or a single mutation in eitherTP53orKRAS.Conclusion: Mutations inTP53together withKRASmay serve as a potential biomarker for survival benefits with immunotherapy.
Subit Barua, , Emily Clancy, Christopher Freeman, Mahesh Mansukhani,
Published: 14 November 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208536

Abstract:
Aims Targeted next-generation sequencing (NGS) panels, which identify genomic alterations, are the stronghold of molecular oncology laboratories. In spite of technological advances, the quantity and quality of DNA from formalin-fixed paraffin-embedded tissue and paucicellular specimens are barriers to successful sequencing. Here, we describe an NGS assay employing single tube stem-loop inhibition mediated amplification technology that delivers highly accurate results with low input DNA. Rigorous quality metrics, regular monitoring and in-depth validation make the test attractive for clinical laboratories. Methods The study used a customised NGS panel, targeting 48 genes across several solid tumour types. Validation, in accordance with guidelines from New York State, sequenced patient samples harbouring 136 known variants, including single-nucleotide variants (SNVs) and indels. Specimen types included formalin-fixed paraffin embedded blocks, core biopsies and cytology material. Neoplastic cellularity of the tumours ranged from 10% to 80%. Results The assay was highly specific and sensitive with excellent accuracy, reproducibility and repeatability/precision. Concordant results for identification of SNVs and indels were obtained from specimens with DNA input of 2–3 ng, tissue with 10% neoplastic cellularity and variant allelic frequencies of 2.5%–3%. Over 99% of the target areas are shown to achieve at least 500X coverage when parsed through two bioinformatics pipelines. With over 2000 clinical specimens analysed, the success of the panel for reporting of results is 95.3% Conclusions The advanced technology enables accurate identification of clinically relevant variants with uniformity of coverage and an impressive turn-around-time. The overall workflow and cost-effectiveness provide added value.
Alexander N Perez, Nooshin K Dashti, Justin M M Cates
Published: 8 November 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208570

Abstract:
Prognostic factors for pleomorphic dermal sarcoma, a rare undifferentiated neoplasm of the skin, are poorly defined, and typical staging systems do not appear to be appropriate for these neoplasms. We; therefore, sought to identify prognostic factors for disease-specific survival and predictors of metastasis.Pleomorphic dermal sarcomas were identified in the Surveillance, Epidemiology and End Results database (N=1911). Multiple imputation was used to overcome inherent limitations in this dataset to assess prognostic factors using multivariable Cox proportional hazard stratified by (neo)adjuvant radiotherapy and logistic regression for presentation with metastasis.Age, tumour size and metastasis were independent prognostic factors for cutaneous sarcoma-specific survival. Only tumour size was associated with increased odds of presentation with metastasis, with tumours >4 cm at highest risk. Metastasis is the most important factor in determining outcomes, with age and size as lesser factors. Only tumour size is predictive of metastasis, with larger tumours at highest risk.
Daisuke Kiyozawa, Kenichi Kohashi, Dai Takamatsu, Shinya Umekita, Masatoshi Eto, Mitsuru Kinjo, Kenichi Nishiyama, Kenichi Taguchi, Yumi Oshiro, Yusuke Kuboyama, et al.
Published: 8 November 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208589

Abstract:
Aims: Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the treatment of RCC. However, tumour-infiltrating neutrophils stimulated by interleukin-8 (IL-8) interfere with PD-L1 inhibitors. Here, we retrospectively analysed PD-L1 and IL-8 expression, and examined its relationship with infiltrating immune cells.Methods: Nine cases of CDC and seven cases of FH-deficient RCC were selected. We defined PD-L1 and IL-8 expression by the Tumour Proportion Score and Combined Positive Score (CPS). We counted the numbers of CD8+, CXCR2+, CD11b+, CD66b+and CD33+immune cells located in the tumour components.Results: A number of CXCR2+(p=0.0058), CD11b+(p=0.0070) and CD66b+(p=0.0067) immune cells infiltrating into CDC were significantly higher than those infiltrating into FH-deficient RCC. In CDC, PD-L1 expression was correlated with a high density of CD8+lymphocytes (p=0.0389), but was not in FH-deficient RCC (p=0.6985). IL-8 CPS was significantly higher in CDC than in FH-deficient RCC (p=0.0069). In addition, among the CDC cases, IL-8 CPS showed significant positive correlations with CXCR2+, CD11b+and CD66b+immune cell densities (p=0.0250, p=0.0104 and p=0.0374, respectively), whereas FH-deficient RCC showed no significant correlations between IL-8 CPS and immune cell densities.Conclusions: Our results suggest the difference of each tumour microenvironment between CDC and FH-deficient RCC, and IL-8 is a potential therapeutic target for treating CDC, but not FH-deficient RCC.
Maike Jm Uijen, Jetty Am Weijers, Gerben Lassche, Stefan G van Ravensteijn, Maartje C van Rijk, Satish Fk Lubeek, Adriana Ch Van Engen-Van Grunsven, Avital Amir, Chantal Ml Driessen, Carla Ml van Herpen
Published: 8 November 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208564

, Lars Egevad, Martin Eklund, , , , , Peter-Paul M Willemse, Richard P Meijer,
Published: 3 November 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208506

Abstract:
Aims Prostate cancer (PCa) grading is an important prognostic parameter, but is subject to considerable observer variation. Previous studies have shown that interobserver variability decreases after participants were trained using an e-learning module. However, since the publication of these studies, grading of PCa has been enhanced by adopting the International Society of Urological Pathology (ISUP) 2014 grading classification. This study investigates the effect of training on interobserver variability of PCa grading, using the ISUP Education web e-learning on Gleason grading. Methods The ISUP Education Prostate Test B Module was distributed among Dutch pathologists. The module uses images graded by the ISUP consensus panel consisting of 24 expert uropathologists. Participants graded the same 10 images before and after e-learning. We included those who completed the tests before and after training. We evaluated variation in PCa grading in a fully crossed study design, using linearly weighted kappa values for each pathologist, comparing them to other pathologists and to the ISUP consensus panel. We analysed the improvement in median weighted kappas before and after training, using Wilcoxon’s signed rank-test. Results We included 42 pathologists. Inter-rater reliability between pathologists improved from 0.70 before training to 0.74 after training (p=0.01). When compared with the ISUP consensus panel, five pathologists improved significantly, whereas the kappa of one pathologist was significantly lower after training. All pathologists who improved significantly, graded with less than substantial agreement before training. Conclusions ISUP Prostate Test B e-learning reduces variability in PCa grading. E-learning is a cost-effective method for standardisation of pathology.
Mahsa Vahdatinia, Fatemeh Derakhshan, Arnaud Da Cruz Paula, Higinio Dopeso, Antonio Marra, Andrea M Gazzo, David Brown, Pier Selenica, Dara S Ross, Pedram Razavi, et al.
Published: 2 November 2022
by BMJ
Journal of Clinical Pathology; https://doi.org/10.1136/jcp-2022-208611

Abstract:
Aims: Activating somatic mutations or gene amplification ofKITresult in constitutive activation of its receptor tyrosine kinase, which is targetable in various solid tumours. Here, we sought to investigate the presence ofKITgenetic alterations in breast cancer (BC) and characterise the histological and genomic features of these tumours.Methods: A retrospective analysis of 5,575 BCs previously subjected to targeted sequencing using the FDA-authorised Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay was performed to identify BCs withKITalterations. A histological assessment ofKIT-altered BCs was conducted, and their repertoire of genetic alterations was compared with that of BCs lackingKITgenetic alterations, matched for age, histological type, oestrogen receptor/HER2 status and sample type.Results: We identified 18 BCs (0.32%), including 9 primary and 9 metastatic BCs, with oncogenic/likely oncogenic genetic alterations affectingKIT, including activating somatic mutations (n=4) or gene amplification (n=14). AllKIT-altered BCs were of high histological grade, although no distinctive histological features were observed. When compared with BCs lackingKITgenetic alterations, no distinctive genetic features were identified. In two metastaticKIT-altered BCs in which the matched primary BC had also been analysed by MSK-IMPACT, theKITmutations were found to be restricted to the metastatic samples, suggesting that they were late events in the evolution of these cancers.Conclusions: KITgenetic alterations are vanishingly rare in BC.KIT-altered BCs are of high grade but lack distinctive histological features. Genetic alterations inKITmight be late events in the evolution and/or progression of BC.
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