Pathology最新文献

This study explored the relationship between faecal microbiota distribution and local or systemic immune response in patients with colorectal cancer (CRC).

The study population included 114 surgically treated CRC patients. Faeces were analysed using 16S rRNA gene sequencing. The immune score in tumour microenvironment was evaluated using CD3 and CD8 immunohistochemistry. Genetic alterations, microsatellite instability status and five systemic inflammatory markers were also analysed.

Thirty of 114 (26.3%) CRC patients were categorised as the ‘immune type’ with a high density of T-cells. The immune type CRC cases showed lower angiolymphatic invasion and longer overall survival. Of the 123 selected bacterial species, Bacteroides fragilis and Collinsella aerofaciens were prevalent in immune CRC cases, whereas Odoribacter splanchnicus and Phascolarctobacterium succinatutens were prevalent in non-immune CRC patients. Bacteroides fragilis was associated with shorter disease free survival in univariable and multivariable survival analyses. Regarding systemic immunity, a high prevalence of C. aerofaciens was associated with a high modified Glasgow prognostic score.

This study revealed a potential relationship among the gut microbiome, immune microenvironment, and disease progression in patients with CRC. Our findings suggest that abundant B. fragilis in patients with CRC is associated with a ‘cold immune’ tumour microenvironment.

The classification of myeloid neoplasms continues to evolve along with advances in molecular diagnosis, risk stratification and treatment of disease. An approach for disease classification has been grounded in international consensus that has facilitated understanding, identification and management of molecularly heterogeneous entities, as well as enabled consistent patient stratification into clinical trials and clinical registries over time. The new World Health Organization (WHO) and International Consensus Classification (ICC) Clinical Advisory Committee releasing separate classification systems for myeloid neoplasms in 2022 precipitated some concern amongst haematopathology colleagues both locally and internationally. While both classifications emphasise molecular disease classification over the historical use of morphology, flow cytometry and cytogenetic based diagnostic methods, notable differences exist in how morphological, molecular and cytogenetic criteria are applied for defining myelodysplastic neoplasms (MDS) and acute myeloid leukaemias (AML). Here we review the conceptual advances, diagnostic nuances, and molecular platforms required for the diagnosis of MDS and AML using the new WHO and ICC 2022 classifications. We provide consensus recommendations for reporting bone marrow biopsies. Additionally, we address the logistical challenges encountered implementing these changes into routine laboratory practice in alignment with the National Pathology Accreditation Advisory Council reporting requirements for Australia and New Zealand.

The clinical importance of assessing and combining data on TP53 mutations and isoforms is discussed in this article. It gives a succinct overview of the structural makeup and key biological roles of the isoforms. It then provides a comprehensive summary of the roles that p53 isoforms play in cancer development, therapy response and resistance. The review provides a summary of studies demonstrating the role of p53 isoforms as potential prognostic indicators. It further provides evidence on how the presence of TP53 mutations may affect one or more of these activities and the association of p53 isoforms with clinicopathological data in various tumour types. The review gives insight into the present diagnostic hurdles for identifying TP53 isoforms and makes recommendations to improve their evaluation. In conclusion, this review offers suggestions for enhancing the identification and integration of TP53 isoforms in conjunction with mutation data within the clinical context.

Matrix Gla protein (MGP) and trichorhinophalangeal syndrome type 1 (TRPS1) have recently emerged as novel breast-specific immunohistochemical (IHC) markers, particularly for triple-negative breast cancer (TNBC) and metaplastic carcinoma. The present study aimed to validate and compare the expression of MGP, TRPS1 and GATA binding protein 3 (GATA3) in metastatic breast carcinoma (MBC), invasive breast carcinoma (IBC) with special features, including special types of invasive breast carcinoma (IBC-STs) and invasive breast carcinoma of no special type with unique features, and mammary and non-mammary salivary gland-type tumours (SGTs). Among all enrolled cases, MGP, TRPS1 and GATA3 had comparable high positivity for ER/PR-positive (p=0.148) and HER2-positive (p=0.310) breast carcinoma (BC), while GATA3 positivity was significantly lower in TNBC (p<0.001). Similarly, the positive rates of MGP and TRPS1 in MBCs (99.4%), were higher than in GATA3 (90.9%, p<0.001). Among the IBC-STs, 98.4% of invasive lobular carcinomas (ILCs) were positive for all three markers. Among neuroendocrine tumours (NTs), all cases were positive for TRPS1 and GATA3, while MGP positivity was relatively low (81.8%, p=0.313). In the neuroendocrine carcinoma (NC) subgroup, all cases were positive for GATA3 and MGP, while one case was negative for TRPS1. All carcinomas with apocrine differentiation (APOs) were positive for GATA3 and MGP, while only 60% of the cases demonstrated moderate staining for TRPS1. Among mammary SGTs, MGP demonstrated the highest positivity (100%), followed by TRPS1 (96.0%) and GATA3 (72.0%). Positive staining for these markers was also frequently observed in non-mammary SGTs. Our findings further validate the high sensitivity of MGP and TRPS1 in MBCs, IBC-STs, and breast SGTs. However, none of these markers are capable of distinguishing between mammary and non-mammary SGTs.

Early induction response assessment with day-21 bone marrow (D21-BM) is commonly performed in patients with FLT3-mutated acute myeloid leukaemia (AML), where detection of residual leukaemia (RL; blasts ≥5%) typically results in the administration of a second induction course. However, whether D21-BM results predict for RL at the end of first induction has not been systematically assessed.

This study evaluates the predictive role of D21-BM morphology in detecting RL following first induction.

Between August 2018 and March 2022, all patients with FLT3-AML receiving 7+3 plus midostaurin, with D21-BM performed, were identified. Correlation between D21-BM morphology vs D21-BM ancillary flow/molecular results, as well as vs D28-BM end of first induction response, were retrospectively reviewed. Subsequently, D21-BMs were subjected to anonymised morphological re-assessments by independent haematopathologists (total in triplicate per patient).

Of nine patients included in this study, three (33%) were designated to have RL at D21-BM, all of whom entered complete remission at D28-BM. Furthermore, only low-level measurable residual disease was detected in all three cases by flow or molecular methods at D21-BM, hence none proceeded to a second induction. Independent re-evaluations of these cases failed to correctly reassign D21-BM responses, yielding a final false positive rate of 33%.

In summary, based on morphology alone, D21-BM assessment following 7+3 intensive induction plus midostaurin for FLT3-AML incorrectly designates RL in some patients; thus correlating with associated flow and molecular results is essential before concluding RL following first induction. Where remission status is unclear, repeat D28-BMs should be performed.

Oesophagogastric adenocarcinoma (EGA) includes oesophageal (EA), gastro-oesophageal junctional (GEJA), and gastric (GA) adenocarcinomas. The prognostic values of clinicopathological factors in these tumours remain obscure, especially for GEJA that has been inconsistently classified and staged. We studied the prognosis of EGA patients among the three geographic groups in 347 consecutive patients with a median age of 70 years (range 47–94). All patients were male, and 97.1% were white. Based on tumour epicentre location, EGAs were sub-grouped into EA (over 2 cm above the GEJ; n=3, 18.1%), GEJA (within 2 cm above and 3 cm below the GEJ; n=231, 66.6%), and GA (over 3 cm below the GEJ; n=53, 15.3%). We found that the median overall survival (OS) was the longest in EA (62.9 months), compared to GEJA (33.4), and GA (38.1) (p<0.001). Significant risk factors for OS included tumour location (p=0.018), size (p<0.001), differentiation (p<0.001), adenocarcinoma subtype (p<0.001), and TNM stage (p<0.001). Independent risk factors for OS comprised low-grade papillary adenocarcinoma [odds ratio (OR) 0.449, 95% confidence interval (CI) 0.214–0.944, p<0.05), mixed adenocarcinoma (OR 1.531, 95% CI 1.056–2.218, p<0.05), adenosquamous carcinoma (OR 2.206, 95% CI 1.087–4.475, p<0.05), N stage (OR 1.505, 95% CI 1.043–2.171, p<0.05), and M stage (OR 10.036, 95% CI 2.519–39.993, p=0.001)]. EGA was further divided into low-risk (common well-moderately differentiated tubular and low-grade papillary adenocarcinomas) and high-risk (uncommon adenocarcinoma subtypes, adenosquamous carcinoma) subgroups. In this grouping, the median OS was significantly longer in the low-risk (83 months) than in the high-risk (10 months) subgroups (p<0.001). In conclusion, the prognosis of EGA patients was significantly better in EA than in GEJA or GA and could be stratified into low and high-risk subgroups with significantly different outcomes.