Federica Miglietta, Valentina Carraro, Ottavia Amato, Gaia Griguolo, Michele Bottosso, Giada Munari, Giovanni Zarrilli, Marcello Lo Mele, Caterina Barbieri, Angelo Paolo Dei Tos, Valentina Guarneri, Maria Vittoria Dieci, Matteo Fassan
{"title":"PI3K/PTEN/mTOR pathway dynamic tracking and prognostic value in HR+/HER2- BC patients with residual disease after neoadjuvant chemotherapy: a cohort study.","authors":"Federica Miglietta, Valentina Carraro, Ottavia Amato, Gaia Griguolo, Michele Bottosso, Giada Munari, Giovanni Zarrilli, Marcello Lo Mele, Caterina Barbieri, Angelo Paolo Dei Tos, Valentina Guarneri, Maria Vittoria Dieci, Matteo Fassan","doi":"10.1136/jcp-2023-208856","DOIUrl":"10.1136/jcp-2023-208856","url":null,"abstract":"<p><strong>Aims: </strong>Hormone receptor-positive (HR)+/HER2- breast cancer (BC) is highly heterogeneous, with PI3K/PTEN/mTOR pathway alterations emerging as possible players within this complexity. We longitudinally tracked PI3K/PTEN/mTOR pathway dynamics from baseline biopsy to residual disease (RD)-and to metastases in case of relapse-in HR+/HER2- BC patients receiving neoadjuvant chemotherapy (NACT).</p><p><strong>Methods: </strong>HR+/HER2- BC patients with RD after NACT were identified. We assessed <i>PIK3CA</i> mutational, Pten-loss and phosphorylation levels of mTOR and its substrates (p70S6K and 4EBP1) on baseline biopsies and matched RD samples; in case of disease relapse, we also assessed <i>PIK3CA</i> mutational status on metastatic samples. Recurrence-free survival (RFS) was adopted as endpoint.</p><p><strong>Results: </strong>92 patient were included. The conversion rate of <i>PIK3CA</i> mutational status was 12.8%; 1 patient acquired <i>PIK3CA</i> mutation at relapse; the rate of Pten conversion was 33.3%; mTOR phosphorylation levels significantly increased from baseline biopsy to RD, while its substrates significantly decreased. Baseline phosphorylated-mTOR significantly predicted poorer RFS in patients with <i>PIK3CA</i> wild-type status; baseline phosphorylated-70S6K was positively associated with RFS.</p><p><strong>Conclusions: </strong>We observed that PI3K/PTEN/mTOR pathway is highly dynamic under NACT exposure and the assessment of <i>PIK3CA</i> mutations may capture only a small fraction of such complexity. In this context, mTOR activation trough alternative pathways with respect to <i>PIK3CA</i> signalling may have a crucial role in shaping the molecular landscape of HR+/HER2- BC with RD after NACT. It is imperative to further elucidate the role of <i>PIK3CA</i> and mTOR-dependent pathways in shaping chemoresistance and endocrine resistance in high-risk HR+/HER2- early/locally advanced BC patients.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"690-696"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9835326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hiroshi Silva, Camila Gabriela Xavier de Brito, Andrew Hall, Nadia Eden, Henry Somers, Niall Burke, Siobhan O Burns, David Lowe, Douglas Thorburn, Neil Halliday, Alberto Quaglia
{"title":"Common variable immunodeficiency disorder (CVID)-related liver disease: assessment of the main histological aspects using novel semiquantitative scoring systems, image analysis and correlation with clinical parameters of liver stiffness and portal hypertension.","authors":"Hiroshi Silva, Camila Gabriela Xavier de Brito, Andrew Hall, Nadia Eden, Henry Somers, Niall Burke, Siobhan O Burns, David Lowe, Douglas Thorburn, Neil Halliday, Alberto Quaglia","doi":"10.1136/jcp-2023-208977","DOIUrl":"10.1136/jcp-2023-208977","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to investigate the relationship between T-cell-mediated sinusoidal injury, nodular regenerative hyperplasia like changes (NRH-LC) and fibrosis, clinical measures of fibrosis and portal hypertension, and progression rate in common variable immunodeficiency disorder (CVID)-related liver disease.</p><p><strong>Methods: </strong>This is a retrospective single-centre study. Liver biopsies from CVID patients with liver disease were reviewed to assess for NRH-LC, fibrosis and elastosis, including collagen and elastin proportionate areas. CD3 positive T-cells infiltration and sinusoidal endothelial changes by CD34 expression were quantified by image analysis and a semiquantitative method, respectively. These findings were correlated with liver stiffness measurements (LSM) and hepatic venous pressure gradient (HVPG).</p><p><strong>Results: </strong>NRH-LC and pericellular elastosis were present in most biopsies (32/40 and 38/40, respectively). All biopsies showed fibrosis, which was limited to pericellular in 21/40 (52.5%) and included bridging fibrous septa in 19/40 (47.5%). 28/40 liver biopsies showed enhanced sinusoidal expression of CD34. There were more CD3 positive cells in biopsies with NRH-LC compared with those without. There was no significant correlation between LSM, HVPG and fibrosis/elastosis scores. Five of seven patients with at least two biopsies showed progression in fibrosis stage.</p><p><strong>Conclusions: </strong>NRH-LC and fibrosis in CVID patients often coexist along with the presence of sinusoidal endothelial changes and sinusoidal lymphocytic infiltration. Fibrosis progresses over time, and significant fibrosis can be observed in young patients (<30 years old), potentially reflecting a more aggressive form of CVID-related liver disease. Further studies are necessary to investigate the relationship between histological findings, clinical measures of fibrosis and portal hypertension and outcome.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"709-716"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Larissa V Furtado, Teresa Santiago, Zachary R Abramson, Marija Kacar, Zonggao Shi, Selene C Koo, Robert E Ruiz, Roya Mostafavi, Matthew J Krasin, Barry Shulkin, Lindsay J Talbot, Alberto S Pappo, Jessica Gartrell
{"title":"High-grade osteosarcoma arising from a clinically aggressive infantile fibrosarcoma.","authors":"Larissa V Furtado, Teresa Santiago, Zachary R Abramson, Marija Kacar, Zonggao Shi, Selene C Koo, Robert E Ruiz, Roya Mostafavi, Matthew J Krasin, Barry Shulkin, Lindsay J Talbot, Alberto S Pappo, Jessica Gartrell","doi":"10.1136/jcp-2024-209384","DOIUrl":"10.1136/jcp-2024-209384","url":null,"abstract":"","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"717-720"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rasiah Thayakaran, Richard Hotham, Krishna M Gokhale, Nicola J Adderley, Joht Singh Chandan, Krishnarajah Nirantharakumar
{"title":"Seasonal variation of serum potassium and related prescription pattern: an ecological time series.","authors":"Rasiah Thayakaran, Richard Hotham, Krishna M Gokhale, Nicola J Adderley, Joht Singh Chandan, Krishnarajah Nirantharakumar","doi":"10.1136/jcp-2023-208759","DOIUrl":"10.1136/jcp-2023-208759","url":null,"abstract":"<p><p><b>Aims</b> To assess if ambient temperature-related effects on serum potassium levels impact clinical decision-making. <b>Methods</b> This study is an ecological time series consisiting of 1 218 453 adult patients with at least one ACE inhibitor (ACEI) prescription who participate in a large UK primary care dataset.Descriptive statistics and a quasi-Poisson regression model using time series data at regular time intervals (monthly) were undertaken to examine the association between potassium measurements and ACEI/potassium supplement prescriptions. RESULTS: It is noted that correlating with lower ambient temperature, serum potassium values follow a seasonal pattern; peaks in winter months and troughs in summer. During summer months, there are clear annual spikes in the number of potassium prescriptions suggesting a change in prescribing practice during periods of potentially spurious hyperkalaemia. The converse pattern is seen in the ACEI prescription proportion which spikes annually during the winter period with lower average ambient temperatures. Our time series modelling demonstrated that each one unit increase in potassium is associated with a 33% increased rate of ACEI prescriptions (risk ratio, RR 1.33; 95% CI 1.12 to 1.59) and 63% decreased rate of potassium supplements (RR 0.37; 95% CI 0.32 to 0.43). CONCLUSIONS: Our findings highlight the seasonal pattern in serum potassium and we observe a corresponding alteration in prescribing practice for potassium sensitive medications. These findings demonstrate the importance of educating clinicians on the presence of seasonal potassium variability in addition to standard measurement error, and its potential impact on their prescribing activity.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"663-668"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9588463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rima Koka, Laura M Wake, Nam K Ku, Kathryn Rice, Autumn LaRocque, Elba G Vidal, Serge Alexanian, Raymond Kozikowski, Yair Rivenson, Michael Edward Kallen
{"title":"Assessment of AI-based computational H&E staining versus chemical H&E staining for primary diagnosis in lymphomas: a brief interim report.","authors":"Rima Koka, Laura M Wake, Nam K Ku, Kathryn Rice, Autumn LaRocque, Elba G Vidal, Serge Alexanian, Raymond Kozikowski, Yair Rivenson, Michael Edward Kallen","doi":"10.1136/jcp-2024-209643","DOIUrl":"https://doi.org/10.1136/jcp-2024-209643","url":null,"abstract":"<p><p>Microscopic review of tissue sections is of foundational importance in pathology, yet the traditional chemistry-based histology laboratory methods are labour intensive, tissue destructive, poorly scalable to the evolving needs of precision medicine and cause delays in patient diagnosis and treatment. Recent AI-based techniques offer promise in upending histology workflow; one such method developed by PictorLabs can generate near-instantaneous diagnostic images via a machine learning algorithm. Here, we demonstrate the utility of virtual staining in a blinded, wash-out controlled study of 16 cases of lymph node excisional biopsies, including a spectrum of diagnoses from reactive to lymphoma and compare the diagnostic performance of virtual and chemical H&Es across a range of stain quality, image quality, morphometric assessment and diagnostic interpretation parameters as well as proposed follow-up immunostains. Our results show non-inferior performance of virtual H&E stains across all parameters, including an improved stain quality pass rate (92% vs 79% for virtual vs chemical stains, respectively) and an equivalent rate of binary diagnostic concordance (90% vs 92%). More detailed adjudicated reviews of differential diagnoses and proposed IHC panels showed no major discordances. Virtual H&Es appear fit for purpose and non-inferior to chemical H&Es in diagnostic assessment of clinical lymph node samples, in a limited pilot study.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Head-to-head comparative study: evaluating three panels for MSI-PCR testing in patients with colorectal and gastric cancer.","authors":"Xinhui Fu, Jinglin Huang, Xinjuan Fan, Chao Wang, Weihao Deng, Xiaoli Tan, Zhiting Chen, Yacheng Cai, Lin Hanjie, Liang Xu, Jiaxin Zou, Huanmiao Zhan, Shuhui Huang, Yongzhen Fang, Yan Huang","doi":"10.1136/jcp-2023-209089","DOIUrl":"10.1136/jcp-2023-209089","url":null,"abstract":"<p><strong>Aims: </strong>Due to the lack of large clinical cohorts in the Chinese populations with colorectal cancer (CRC) and gastric cancer (GC), there is no consensus among the preferred panel for microsatellite instability (MSI)-PCR testing. This study aims to evaluate a more appropriate panel.</p><p><strong>Methods: </strong>We tested the MSI status of 2572 patients with CRC and GC using the NCI panel and 2 mononucleotide panels (5 and 6 mononucleotide panels). Immunohistochemistry (IHC) was employed to perform mismatch repair protein testing in 1976 samples.</p><p><strong>Results: </strong>We collected 2572 patients with CRC and GC. The National Cancer Institute (NCI) panel failed to detect 13 cases. Of the 2559 cases that received results from all three panels, 2544 showed consistent results. In the remaining 15 cases, 9 showed discrepancies between MSI-H and MSI-L, and 6 showed discrepancies between MSI-L and microsatellite stability (MSS). The misdiagnosis rate of MSI-L was significantly lower in two mononucleotide panels than in the NCI panel (12.5% vs 87.5%, p=0.010) in CRC. In patients with GC, only the NCI panel detected three MSI-L cases, while the results of the two mononucleotide panels were one MSI-H and two MSS. Based on their IHC results, the MSI-L misdiagnosis rate of the NCI panel was 33.3%. Furthermore, compared with two mononucleotide panels, the NCI panel had a much lower rate of all loci instability in CRC (90.8% and 90.3% vs 25.2%) and GC (89.5% and 89.5% vs 12.0%).</p><p><strong>Conclusion: </strong>In Chinese patients with CRC and GC, the five and six mononucleotide panels have advantages for detecting MSI over the NCI panel.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"683-689"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pooja Navale, Jonathan Glickman, Imad Nasser, Jinru Shia, Monika Vyas
{"title":"Ciliated foregut cysts involving the hepatopancreaticobiliary system: a clinicopathological evaluation with focus on atypical features.","authors":"Pooja Navale, Jonathan Glickman, Imad Nasser, Jinru Shia, Monika Vyas","doi":"10.1136/jcp-2023-208947","DOIUrl":"10.1136/jcp-2023-208947","url":null,"abstract":"<p><strong>Aims: </strong>Foregut cystic malformations are rare developmental abnormalities, which may involve the hepatopancreaticobiliary tract (HPBT). These cysts are composed of inner ciliated epithelium; subepithelial connective tissue layer; smooth muscle layer; and an outer fibrous layer. While radiopathologic findings are often diagnostic, atypical location and histologic features can pose a diagnostic challenge. We aimed to study ciliated foregut cysts (CFCs) in the HPBT, assess their clinicopathological features with a focus on atypical features.</p><p><strong>Methods: </strong>We collected cases of CFCs involving the HPBT from three large academic medical centres. H&E-stained slides and immunohistochemical stains (where available) were reviewed for each case. Relevant demographic, clinical and pathological information was collected from the medical records.</p><p><strong>Results: </strong>21 cases were identified. The median age was 53 years (range, 3-78 years). 17 cysts were identified within the liver (segment 4 was the most common location, n=10) and 4 in the pancreas. Cysts were mostly identified incidentally (n=13), abdominal pain was a common symptom (n=5). Cyst size ranged from 0.7 to 17.0 cm (median, 2.5 cm). Radiological findings were available in 17 cases. Cilia were identified in all cases. 19 of 21 cases demonstrated the presence of a smooth muscle layer (thickness, <0.1 mm to 3.0 mm). Three cases showed gastric metaplasia, while one case revealed additional low-grade dysplasia, with features similar to intraductal papillary neoplasm of the bile duct.</p><p><strong>Conclusions: </strong>We highlight clinicopathological features of CFCs in the HPBT. The histomorphology is usually straightforward; however, unusual location and atypical features can pose a diagnostic challenge.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"697-701"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Pejcic, Zlatibor Andjelkovic, Dragan Marjanovic, Ivan Minic, Vladimir Matvijenko, Zoran Arsic, Radovan Jovanovic, Ljiljana Subaric
{"title":"Comparative analysis of antigen-presenting cells in gingival tissues in healthy and periodontitis patients.","authors":"Ana Pejcic, Zlatibor Andjelkovic, Dragan Marjanovic, Ivan Minic, Vladimir Matvijenko, Zoran Arsic, Radovan Jovanovic, Ljiljana Subaric","doi":"10.1136/jcp-2021-207975","DOIUrl":"10.1136/jcp-2021-207975","url":null,"abstract":"<p><strong>Aims: </strong>Microbial flora of dental plaque trigger innate and adaptive immune responses. The function of antigen-presenting cells (APCs) is to bridge the innate and adaptive immune systems. The human immune system contains three main types of APCs: dendritic cells (DC) (Langerhans cells (LCs) and interstitial DCs, IDCs), macrophages and B lymphocytes. In this study, the distribution and density of all APCs in healthy and inflamed human gingival tissue were comparatively analysed.</p><p><strong>Methods: </strong>Research was conducted on gingival biopsy specimens obtained from 55 patients and classified in three groups: healthy gingiva (control group, n=10), moderate periodontal disease (PD) (n=21) and severe PD (n=24). For APCs' identification antibodies raised against CD<sub>1a</sub> (for LCs), S<sub>100</sub> protein (for iDCs), CD<sub>68</sub> (for macrophages) and CD<sub>20</sub> (for B lymphocytes) were used.</p><p><strong>Results: </strong>Increased density of IDCs, macrophages and B lymphocytes in lamina propria and reduced density of LCs in the gingival epithelium were found in patients with periodontitis. Simultaneously, it was noticed an increased concentration of macrophages and B cells in the gingival epithelium in patients with PD. No statistically significant difference in the distribution and density of APC was found among patients with moderate and advanced periodontitis.</p><p><strong>Conclusions: </strong>It was hypothesised that in the periodontitis the role of antigen presentation was largely taken from LCs by the DCs, macrophages and B cells. These APCs are thought to have less protective and tolerogenic potential than LCs and this is a significant reason for alveolar bone destruction in periodontitis.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":"702-708"},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9826474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Murali Varma, Daniel M Berney, Glen Kristiansen, Theodorus H van der Kwast
{"title":"Intraductal carcinoma of the prostate: conflicting recommendations confuse clinicians","authors":"Murali Varma, Daniel M Berney, Glen Kristiansen, Theodorus H van der Kwast","doi":"10.1136/jcp-2024-209690","DOIUrl":"https://doi.org/10.1136/jcp-2024-209690","url":null,"abstract":"Intraductal carcinoma of the prostate (IDCP) generally represents a growth pattern of invasive aggressive acinar prostate cancer but may rarely represent a non-invasive putative precursor of prostate cancer.1 IDCP in needle biopsies may be encountered in isolation or in association with invasive prostate cancer. While there is consensus that pure IDCP in needle biopsies should not be graded, it is controversial whether IDCP associated with invasive cancer should be included in the Gleason score (GS). The International Society of Urological Pathology (ISUP) recommended incorporating the IDCP component into the GS, but the Genitourinary Pathology Society (GUPS) proposed grading only the invasive component with comments on the presence of associated IDCP and its adverse prognostic significance.2 3 The impact of these conflicting recommendations is greatest in needle biopsies with invasive GS 3+3 and extensive IDCP because such cases would be graded as at least GS 4+3 (grade group 3) based on the ISUP guidelines but GS 3+3 (grade group 1) as per the GUPS recommendation. In this issue, McDonald et al describe such a case where the …","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":"41 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monica Falleni, Matteo Dal Lago, Delfina Tosi, Giorgio Ghilardi, Loredana De Pasquale, Alberto M Saibene, Giovanni Felisati, Mario Cozzolino, Umberto Gianelli
{"title":"Vascular mimicry and mosaic vessels in parathyroid tumours: a new diagnostic approach?","authors":"Monica Falleni, Matteo Dal Lago, Delfina Tosi, Giorgio Ghilardi, Loredana De Pasquale, Alberto M Saibene, Giovanni Felisati, Mario Cozzolino, Umberto Gianelli","doi":"10.1136/jcp-2024-209703","DOIUrl":"https://doi.org/10.1136/jcp-2024-209703","url":null,"abstract":"Aims Evaluation of ‘alternative’ vascularisation in human cancer is considered an important prognostic parameter; the 2022 WHO classification of parathyroid tumours despite progresses in clinical triaging of patients strongly emphasises new histopathological parameters to properly stratify these lesions. ‘Alternative’ and ‘classic’ vessels were here investigated for the first time in parathyroid tumours for their possible histopathological and clinical relevance during progression. Methods Using a double CD31/PAS staining, microvessel density (MVD, ‘classic’ CD31+ vessels), mosaic vessel density (MoVD, ‘alternative’ CD31+/−vessels) and vessel mimicry density (VMD, ‘alternative’ CD31−/PAS+ vessels) were evaluated in 4 normal parathyroid glands (N), 50 Adenomas (A), 35 Atypical Tumours (AT) and 10 Carcinomas (K). Results Compared with N, MVD significantly increased in A (p=0.012) and decreased in K (p=0.013) with vessel counts lower than in AT and A (p<0.001). MoVs and VMs, absent in normal tissue, were documented in non-benign parathyroid lesions (AT, K) (p<0.001), with MoVs and VMs most represented in AT and K, respectively (p<0.001), in peripheral growing areas. Vessel distribution was correlated to neoplastic progression (r=−0.541 MVD; r=+0.760 MoVD, r=+0.733 VMD), with MVD decrease in AT and K inversely related to MoVD and VMD increase (r=−0.503 and r=−0.456). Conclusions ‘Alternative’ vessel identification in parathyroid tumours is crucial because it: (1) explains the paradox of non-angiogenic tumours, consisting in a new bloody non-endothelial vessel network and (2) helps pathologists to unmask worrisome lesions. Furthermore, detection of alternative vascular systems in human tumours might explain the limited success of antiangiogenic therapies and encourage new oncological studies. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":"55 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}