Pseudoangiomatous stromal hyperplasia (PASH) is commonly present in gynaecomastia, can be seen in some mammary fibroepithelial lesions and in fibrocystic change, and rarely forms a mass. Spindle cell carcinoma of the bre...Pseudoangiomatous stromal hyperplasia (PASH) is commonly present in gynaecomastia, can be seen in some mammary fibroepithelial lesions and in fibrocystic change, and rarely forms a mass. Spindle cell carcinoma of the breast can have a wide range of appearances. This case series describes five spindle cell carcinomas of the breast resembling PASH, a pattern that does not appear to have been reported before. All had bland nuclei like those in fibromatosis-like spindle cell carcinoma. All cases had more close-packed areas, but this was only a very minor component in the index case. Two had associated ductal carcinoma in situ. All were cytokeratin positive with immunohistochemistry. The similarity of the carcinomas in this series to PASH is a diagnostic pitfall particularly in core biopsies as more cellular areas may be only focal.
Kirsten rat sarcoma viral oncogene () is a frequently mutated oncogene in lung cancer, now amenable to targeted therapy with allele-specific G12C inhibitors. Non-small cell lung cancer (NSCLC) driver mutations show geogr...Kirsten rat sarcoma viral oncogene () is a frequently mutated oncogene in lung cancer, now amenable to targeted therapy with allele-specific G12C inhibitors. Non-small cell lung cancer (NSCLC) driver mutations show geographical variability and therefore the mutation breakdown, co-occurring oncogenic mutation rate and associated PD-L1 expression were studied in a large UK cohort. We interrogated archival clinical next-generation sequencing (NGS) data over 5 years. 3283 NSCLC samples were included, referred from 38 centres over 4 years. Somatic mutation hotspots in cancer-associated genes were analysed using ampliseq/ion-torrent based NGS assays. In a subset of the cohort, PD-L1 scores were also collated. 1118 variants were detected. Class I mutations occurred most frequently (86.94%), with G12C, G12V and G12D being most prevalent. Class II (7.96%), III (4.65%) and IV (0.45%) mutations were also detected and mutations in and were the most frequently observed co-mutations. No significant difference in PD-L1 expression was found between wild-type and mutant tumours.
AIMS: Follicular lymphoma (FL) is characterised by significant heterogeneity in both the clinical trajectories and the molecular profiles. This study aimed to investigate clonal dynamics in FL by analysing mutation profi...AIMS: Follicular lymphoma (FL) is characterised by significant heterogeneity in both the clinical trajectories and the molecular profiles. This study aimed to investigate clonal dynamics in FL by analysing mutation profiles at various time points during the disease course including at histological transformation (HT), to gain insight into the mutational changes over time. METHODS: We retrospectively analysed 76 biopsies from 25 patients, including 13 cases with three or more FL biopsies and 12 cases with subsequent HT. Hybrid capture-based Next-Generation Sequencing (NGS) with the EuroClonality-NGS DNA capture (EuroClonality-NDC) assay was used to examine clonal rearrangements and mutations. RESULTS: A total of 204 (potentially) pathogenic mutations were identified. Only 40% of mutations remained stably present during a median follow-up period of 139 months (range 9-198). and were the most frequently mutated genes at diagnosis, exhibiting relative stability in follow-up biopsies. Conversely, displayed a dynamic pattern of mutations gained and lost during the disease course. At HT, pathogenic mutations affecting , and emerged. Changes in mutational burden were observed in both FL-sequential and diagnosis-transformation cohorts, with more pronounced changes in the latter. CONCLUSIONS: This real-world study provides insights into the complex molecular pathogenesis of FL and HT. As targeted therapies emerge as treatment modalities, mutational profiles could influence treatment decisions in the future. Therefore, recognising the significant changes occurring in the mutational landscape of FL throughout the disease course is crucial.
AIMS: There are limited data on programmed death ligand 1 (PD-L1) expression in oesophageal cancer (OC) from multicentre studies conducted across China. We aimed to determine the prevalence of high PD-L1 expression in pa...AIMS: There are limited data on programmed death ligand 1 (PD-L1) expression in oesophageal cancer (OC) from multicentre studies conducted across China. We aimed to determine the prevalence of high PD-L1 expression in patients with advanced OC. METHODS: The EXCEED study was a multicentre, retrospective analysis of data from six tertiary hospitals that evaluated PD-L1 expression in adults with advanced OC or advanced head and neck squamous cell carcinoma. PD-L1 expression was evaluated at each site according to a standardised protocol. The primary outcome was the prevalence of high PD-L1 expression (Combined Positive Score (CPS) ≥10) in surgical or tumour biopsy samples. Low PD-L1 expression was defined as CPS <10. Patient demographic and baseline factors associated with high PD-L1 expression were also investigated. This report presents the results for the OC cohort only. RESULTS: Overall, 482 patients were included, the majority were male (87.6%) and the mean age at diagnosis was 63.3 years; 207 had high PD-L1 expression (42.9%; 95% CI 38.5, 47.5) and 275 had low expression (57.1%; 95% CI 52.5, 61.5). There were significant differences in high PD-L1 expression prevalence between subgroups by sex (p=0.044), number of distant metastases (p=0.020), and if chemotherapy (p=0.004) was received prior to the collection of biological samples (ie, biopsy or surgery). CONCLUSIONS: These real-world data provide a robust estimate of the prevalence of high PD-L1 expression in patients with advanced OC and identify clinicopathological and treatment features related to PD-L1 expression that can inform treatment selection.
Santisteban-Espejo A, Benavides-De la Fuente C, Mangas-Rojas A
… +9 more, Montero-Pavon P, Bernal-Florindo I, Aldaco-Puntas E, Prieto-Conde I, Perez-Requena J, Atienza-Cuevas L, Fernández-Valle MDC, Garzón-López S, Garcia-Rojo M
AIMS: The prognostic impact of B lymphocytes surrounding Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) and pathogenic variants in genes associated with apoptosis regulation remains undefined. M...AIMS: The prognostic impact of B lymphocytes surrounding Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) and pathogenic variants in genes associated with apoptosis regulation remains undefined. METHODS: We have quantified the proportion of B lymphocytes in tumour microenvironment (TME) in 220 diagnostic slides from 110 cHL patients applying computational pathology (CP) and sequenced cases using a targeted panel including 47 genes recurrently mutated in mature B-cell neoplasms. Kaplan-Meier estimators and multivariate Cox regression on overall survival (OS) and progression-free survival (PFS) were assessed following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines. RESULTS: The mean percentage of B lymphocytes was 45.1 (SD: 24.8). Genes recurrently affected by nonsynonymous somatic mutations in 25% or more of patients included EP300, NOTCH and ABL1. A lower number of mutations were discovered in Epstein-Barr virus-positive cHL (21.1% vs 78.8%) reinforcing the notion that viral infection could functionally replace the need for genomic aberrations. Classic Hodgkin lymphoma (cHL) patients that jointly presented a reduction in the number of B lymphocytes in TME (<8%) and the absence of mutations in apoptosis-associated genes (ABL1, BIRC3, CASP8 and FAS) presented a lower OS (mean OS: 31.5 months, 95% CI: 0 to 69.7 months) in comparison with patients without this event (mean OS: 84.7 months, 95% CI: 61.9 to 107.5 months) (p=0.01). This high-risk cHL subgroup also presented a significantly lower PFS (mean PFS: 8.5 months, 95% CI: 7.5 to 9.5 months) in comparison with B-cell-enriched or apoptosis-mutated cHL (mean PFS: 55.2 months; 95% CI: 42.4 to 68 months) (p<0.001). CONCLUSIONS: This study expands previous data on the value of CP in cHL, and specifically, the distribution of B cells, identifying patients with an increased risk of treatment failure and progression. Furthermore, immune escape by apoptosis dysregulation during clonal selection occurring in germinal centres constitutes a landmark of cHL. These results could be the basis for further development of targeted therapies directed against apoptosis modulators in cHL.
AIMS: Concerns over population-level immunity have been heightened with each successive wave of COVID-19, prompting questions about whether it is primarily derived from vaccination efforts or from previous natural infect...AIMS: Concerns over population-level immunity have been heightened with each successive wave of COVID-19, prompting questions about whether it is primarily derived from vaccination efforts or from previous natural infections with the virus. We wished to determine the seroprevalence of SARS-CoV-2 antibodies among healthcare workers (HCWs) in Pretoria (Tshwane), South Africa, and to establish whether they were derived from vaccination or natural infection. METHODS: Serum samples were collected from HCWs during the fourth wave of COVID-19 between 1 December 2021 and 13 March 2022. The samples were tested using the Abbott SARS-CoV-2 Spike IgG (S-IgG), IgM (S-IgM) and the SARS-CoV-2 Nucleocapsid IgG (NC-IgG) kits. RESULTS: Of the 221 participants, 76% (n=168) were women and 24% (n=53) were men. A total of 96.4% (n=213) of the participants were vaccinated. Natural infection-derived antibodies were detected in 23% (n=51) of participants, and vaccine-derived antibodies in 74% (n=164) of the HCWs. CONCLUSIONS: Even after three waves of COVID-19, HCWs derived most of their detectable antibodies from vaccination. Vaccination remains an essential tool to protect HCWs and patients from SARS-CoV-2 infection.
AIMS: Progesterone receptor (PR) is a crucial prognostic marker in breast cancer. However, achieving consistent results in PR immunohistochemistry (IHC) remains challenging due to the lack of well-defined low-positive co...AIMS: Progesterone receptor (PR) is a crucial prognostic marker in breast cancer. However, achieving consistent results in PR immunohistochemistry (IHC) remains challenging due to the lack of well-defined low-positive controls. This study aimed to identify benign tissues with consistent low-level PR expression to serve as ideal controls for IHC. METHODS: We evaluated PR expression in the squamous epithelium of the uterine cervix, nipple smooth muscle and pancreatic islets. QuPath digital image analysis was employed to compare the intensity and quantity of PR staining in target cells within a 2×2 mm area. RESULTS: The squamous epithelium of the secretory phase cervix, nipple smooth muscle and pancreatic islets displayed appreciable weak PR expression, with mean values of 73, 55 and 60 cells, respectively. Notably, 62% (8/13) of the 2×2 mm areas in the atrophic cervix were completely negative for PR expression. The coefficients of variation for weak PR-expressing cells in pancreatic islets (57.4%) and nipple smooth muscle (65.0%) were lower than those observed in the cervix (96.2%-222.0%). The squamous epithelium of the cervix, especially during the secretory phase, exhibited weak positivity confined to the basal layers, providing another viable control option. However, variations in PR expression may be influenced by physiological factors, such as hormonal fluctuations. CONCLUSIONS: Pancreatic islets and nipple smooth muscle, with their consistent low-level PR expression, offer a promising solution to the challenges associated with PR IHC. This approach may help minimise variations resulting from differing staining methods across laboratories.
AIMS: To reveal clinicopathological characteristics of alcoholic foamy degeneration (AFD)-an uncommon form of alcoholic liver injury. METHODS: Clinicopathological features of AFD (n=9) were examined in comparison to thos...AIMS: To reveal clinicopathological characteristics of alcoholic foamy degeneration (AFD)-an uncommon form of alcoholic liver injury. METHODS: Clinicopathological features of AFD (n=9) were examined in comparison to those of severe alcoholic hepatitis (SAH; n=12). RESULTS: Patients with AFD presented with either biochemical liver dysfunction (n=1) or clinical jaundice (n=8). One case had undergone liver transplantation for alcohol-related cirrhosis and hepatocellular carcinoma 2 years and 3 months before presentation. AFD cases were histologically classified into three groups. The non-jaundiced case had mixed macro- and microvesicular bland steatosis. Seven jaundiced cases showed more complex microscopic features with lobular inflammation, acidophilic bodies, cholestasis and lobular distortion. Hepatocytes were pleomorphic, some extensively enlarged with clear cytoplasm, somewhat resembling ballooning degeneration; however, it was mainly due to accumulated lipid droplets ('pseudoballooning'). The remaining case also had predominant changes of AFD, but a few foci showed classical ballooning hepatocytes and Mallory-Denk bodies, in keeping with mixed AFD and steatohepatitis. When compared with patients with SAH, those with AFD had lower white blood cell and neutrophil counts and higher cholesterol levels (all p<0.001). On imaging, ascites and varices were less common in AFD than in SAH (11% vs 75%, p=0.014; 0% vs 67%, p=0.008, respectively). All seven patients with AFD who successfully abstained from alcohol experienced rapid improvement in liver function. CONCLUSIONS: Microscopic findings of AFD are more complex than currently thought, and some cases may be mistaken for steatohepatitis. AFD may also develop in conjunction with steatohepatitis or following liver transplantation.
Brockmoeller SF, Slaney H, Curd A
… +6 more, Bono A, Felce JH, Arora D, Lewington A, Miklosi AG, Quirke P
J Clin Pathol
· 2025 Apr · PMID 39805676
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AIMS: Establishment of a protocol for routine single-molecule localisation microscopy (SMLM) imaging on formalin fixed paraffin embedded (FFPE) tissue using medical renal disease including minimal change disease (MCD) an...AIMS: Establishment of a protocol for routine single-molecule localisation microscopy (SMLM) imaging on formalin fixed paraffin embedded (FFPE) tissue using medical renal disease including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). METHODS: Protocol for normal and diseased renal FFPE tissue was developed to investigate the clinical diagnostic potential of SMLM. Antibody concentrations were determined for confocal microscopy and transferred to SMLM. Different fixatives and lengths of fixation were studied. To reduce autofluorescence, additional quenching and UV bleaching steps were compared. Optimal SMLM acquisition settings were established. SMLM data were imaged, digitally captured, stored, visually inspected and analysed quantitatively. RESULTS: Protocol was established on normal renal FFPE tissue and then applied to clinical diseased tissue with single and multiple markers. Antibodies against key diagnostic proteins including podocin, nephrin, collagen, laminin, synaptopodin, CD31, IgG, IgM and IgA antibodies were established for MCD, FSGS and immune-mediated renal disease. We found important characteristic differences in the renal diseases listed above. CONCLUSIONS: We established a routine super-resolution microscopy protocol for clinical FFPE material on medical renal biopsies, which could visualise fluorescently labelled proteins in all glomeruli present with a precision of approximately 10-20 nm, with a turnaround under 48 hours. We visualised and quantitated specific protein distributions in different conditions. SMLM opens subcellular microscopy in FFPE to histopathologists on routine FFPE tissue, which can in the future be an adjunct and, in some aspects, a rapid superior alternative to electron microscopy.
AIMS: Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and gene fusions. Its rarity and similarities to ot...AIMS: Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and gene fusions. Its rarity and similarities to other soft tissue tumours pose diagnostic challenges. This study aims to deepen understanding of CCMN, highlighting molecular pathology's role in diagnosis to reduce misdiagnosis, overdiagnosis and overtreatment. METHODS: We conducted a clinicopathological analysis of five newly identified CCMN cases and reviewed 87 cases documented in PubMed. Next-generation sequencing was used to detect molecular alterations, while clinical, radiological and histopathological features were extensively reviewed. RESULTS: CCMN typically affects adults, presenting as a slow-growing, painless mass in soft tissue. Histologically, CCMN exhibits a chondroid matrix with variable calcification. Molecular analyses in our cases identified , and fusions. Review of the 87 cases revealed consistent clinical, imaging and molecular profiles, underscoring CCMN's distinct characteristics. CONCLUSIONS: CCMN should be considered in the differential diagnosis of soft tissue tumours with chondroid and calcified components. Detecting gene fusions aids in distinguishing CCMN from morphologically similar tumours.
AIMS: esophagitis is usually readily identified on routine H&E-stained sections as the infection typically presents with prominent acute inflammation as a clue to search for organisms. However, in some cases, inflammati...AIMS: esophagitis is usually readily identified on routine H&E-stained sections as the infection typically presents with prominent acute inflammation as a clue to search for organisms. However, in some cases, inflammation is absent, and detection of organisms relies on the observation of zones exhibiting parakeratosis with a delicate 'flaky' appearance. Our study aimed to establish a correlation between the histomorphology of oesophageal candidiasis and an associated clinical profile. METHODS: We reviewed 53 sequential biopsy specimens from patients with esophagitis collected over 1 year. Biopsies were assessed for acute inflammation, intraepithelial lymphocytosis and lymphoid aggregates. Patients' medical records were reviewed for data on age, gender, race, immune status, smoking, corticosteroid use, HIV status and organ transplantation history. Correlations between these factors and histomorphological patterns were assessed using test. RESULTS: Of the 53 biopsies, 20 lacked acute inflammation and 33 had it. 15 biopsies showed both acute and lymphoid inflammation and 5 showed lymphocytosis only. Among 16 smokers, 6 (37%) had acute inflammation and 10 (63%) had parakeratosis. In non-smokers, 24 (71%) had acute inflammation and 10 (29%) had parakeratosis. A significant correlation was found between smoking and absence of acute neutrophilic infiltration (p=0.025), but no other clinical factor was associated with inflammatory patterns. CONCLUSIONS: esophagitis can be uninflamed with 'flaky' parakeratosis or associated with acute inflammation or lymphocytosis with or without neutrophilic infiltration. Inflammation was often absent in smokers, suggesting synergistic local immunosuppressive effect is this overall immunosuppressed population.
AIMS: WNT signalling pathway dysregulation is often a critical early component in colorectal neoplasia, particularly the chromosomal instability pathway. Using two WNT reporters, and , we sought to assess whether these...AIMS: WNT signalling pathway dysregulation is often a critical early component in colorectal neoplasia, particularly the chromosomal instability pathway. Using two WNT reporters, and , we sought to assess whether these polyps demonstrate predictable expression patterns and if these patterns show diagnostic value. METHODS: We evaluated 23 adenomas (TA), 23 sessile serrated lesions (SSLs), 14 SSL with dysplasia and 38 traditional serrated adenomas (TSA). Chromogenic in situ hybridisation stains (ISH) for and were performed. Reactivity was defined as strong, intermediate or weak. Upper third crypt reactivity was defined as full-thickness staining. Accentuation within ectopic crypts (ECF) was recorded. RESULTS: TAs (91%) showed strong reactivity and full-thickness staining with . TSAs showed full-thickness and weak to intermediate reactivity (79%) and ECF with accentuation was exclusively seen in TSA. SSL showed weak reactivity confined to the basal crypt region (100%). SSL with dysplasia also showed weak or intermediate (100%) reactivity, but the reactivity pattern was full thickness (88%). expression parallels expression (Pearson coefficient=0.63) regarding signal intensity for the examined polyp groups. CONCLUSIONS: Qualitative and quantitative differences in and expression assist in the diagnosis of SSL with dysplasia.
Patel T, Bemiss B, Panah E
… +4 more, Chaiprasit T, McHenry A, Venkataraman G, Ananthanarayanan V
J Clin Pathol
· 2025 Mar · PMID 39779317
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AIMS: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway in...AIMS: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD. METHODS: A retrospective, single-centre observational study of cystic fibrosis LTRs between 2002 and 2021 was performed. Data from biopsy slides, pulmonary function testing and bronchoalveolar lavage fluid microbiology tests were collected. The primary outcome was bronchiolitis obliterans syndrome (BOS) or death after transplant, with an 8-year follow-up period. RESULTS: 40 patients were identified with an average age of 35.3 at first transplantation, including 5 redo lung transplants. Fungal infections were correlated with higher rejection scores (p<0.01) and survival status (p=0.027). Fungal and bacterial infection rates were reduced in later transplants (2014-2021) compared with earlier (2002-2014). Fungal infections were associated with significantly worsened outcomes (p≤0.001). Eosinophils in large airways was associated with worse BOS-free survival (p=0.03). CONCLUSIONS: Subcategorisation of the inflammatory milieu (particularly noting eosinophils) in surveillance biopsies may help detect CLAD earlier and improve long-term outcomes in cystic fibrosis LTRs.
AIMS: Light chain proximal tubulopathy (LCPT) is a rare complication of paraprotein-related diseases. We report a case series to present the clinicopathological characteristics and outcomes of LCPT. METHODS: A multicentr...AIMS: Light chain proximal tubulopathy (LCPT) is a rare complication of paraprotein-related diseases. We report a case series to present the clinicopathological characteristics and outcomes of LCPT. METHODS: A multicentre retrospective case series of 47 patients with LCPT, consisting of 36 crystalline, three non-crystalline, and eight mixed LCPTs, was studied between January 2007 and December 2023. RESULTS: The median age at diagnosis was 57 years. Presentations included proteinuria (100%), renal insufficiency (62%) and Fanconi syndrome (68%). The underlying haematological diagnoses were monoclonal gammopathy of renal significance in 81% and multiple myeloma in 19%. Monoclonal light chain (LC) was detected in all cases using serum/urine-free LC assays or immunofixation electrophoresis. Among 36 crystalline LCPTs, 34 were κ-restricted and 2 λ-restricted. Three non-crystalline LCPTs were all λ-restricted. In mixed LCPTs, seven were κ-restricted and one was λ-restricted. Notably, 66% frozen-section immunofluorescence failed to reveal restricted LC, requiring paraffin-immunofluorescence or immunoelectron microscopy. The appearance of inclusions displayed intraindividual homogeneity but interindividual heterogeneity in 42 patients and notable intraindividual heterogeneity in the remaining 5 patients. Haematological complete response, very good partial response and partial response occurred in 61%. Kidney function improved or remained stable in 84%, worsened in 8% and progressed to end-stage renal disease in 8%. CONCLUSIONS: Proteinuria and kidney dysfunction are the most common but less-specific renal manifestations of LCPTs, with most featuring Fanconi syndrome. Crystalline LCPT, primarily associated with κ-LC, is the predominant form. Most inclusions displayed intraindividual homogeneity and interindividual heterogeneity by electron microscopy. Most achieved haematological responses and favourable renal outcomes.
Hewer E, Fischer PD, Vassella E
… +5 more, Knabben L, Imboden S, Mueller MD, Rau TT, Dettmer MS
J Clin Pathol
· 2025 Dec · PMID 39653501
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AIMS: Mutations affecting exon 3 of the β-catenin () gene result in constitutive activation of WNT signalling and are a diagnostic hallmark of several tumour entities including desmoid-type fibromatosis. They also define...AIMS: Mutations affecting exon 3 of the β-catenin () gene result in constitutive activation of WNT signalling and are a diagnostic hallmark of several tumour entities including desmoid-type fibromatosis. They also define clinically relevant tumour subtypes within certain entities, such as endometrioid carcinoma. In diagnostics, β-catenin immunohistochemistry is widely used as a surrogate for mutations. Yet, it is often difficult to assess in practice, given that the characteristic nuclear translocation may be focal or hard to distinguish from the spillover of the normal membranous staining. METHODS: We therefore examined lymphoid enhancer-binding factor 1 (LEF1) immunostaining, a nuclear marker of WNT activation that serves as a potential surrogate for mutations. RESULTS: In a cohort of endometrial carcinomas with known mutation status (n=130) LEF1 was 85% accurate in predicting mutation status (64% sensitivity, 90% specificity) while β-catenin was 76% accurate (72% sensitivity; 77% specificity). Across a variety of entities characterised by mutations as putative drivers, we found diffuse and strong expression of LEF1 in 77% of cases. LEF1 immunostaining proved easier to interpret than β-catenin immunostaining in 54% of cases, more difficult in 1% of cases and comparable in the remaining cases. CONCLUSION: We conclude that LEF1 immunostaining is a useful surrogate marker for mutations. It favourably complements β-catenin immunohistochemistry and outperforms the latter as a single marker.
The healthcare sector significantly contributes to global greenhouse gas emissions, with surgical pathology (SP) playing a notable role. This review explores the ecological transformation of SP, offering a global overvie...The healthcare sector significantly contributes to global greenhouse gas emissions, with surgical pathology (SP) playing a notable role. This review explores the ecological transformation of SP, offering a global overview of existing challenges and sustainable initiatives worldwide.While some countries, such as the UK and France, have developed national strategies to reduce the carbon footprint of healthcare, including SP, many regions remain at an early stage of implementing green practices. Several studies have assessed the carbon footprint of SP, focusing on key aspects such as laboratory operations, pathology procedures and functional units, highlighting materials and transportation as major contributors to emissions. The integration of digital pathology and artificial intelligence (AI) presents opportunities to enhance efficiency and address medical deserts but also poses challenges due to the associated energy consumption.Local initiatives such as the 'Transformation Ecologique en Anatomie et Cytologie Pathologiques' (Ecological transformation in SP) or TEAP collective in France, Belgium's 'Green Team' and sustainable practices in Tunisia and New Zealand demonstrate the global effort to reduce the environmental impact of SP. Key strategies discussed include ecodesign of care, circular economy practices, green AI and partnerships with industry. However, achieving meaningful reductions in SP's environmental impact requires international cooperation and support from national health policies. This review emphasises the importance of collaborative efforts to implement sustainable solutions without compromising the quality and safety of healthcare services.