Unleash your potential: Inside interventional pathology.

Interventional pathology has emerged as a pivotal force in modern healthcare, heralding a paradigm shift from traditional diagnostic approaches to patient-centered care. This innovative field bridges the gap between pathology and cytopathology, empowering pathologists to streamline diagnoses and reduce waiting times for patients. Collaborative mentorship and knowledge sharing ensure a lasting legacy of diagnostic excellence for future generations. Interventional pathology stands as a symbol of innovation and patient empowerment, offering a unified approach to diagnostics and improved care in the era of personalized medicine. This narrative chronicles the evolution of interventional pathologists from behind-the-scenes diagnostic specialists to frontline innovators. This is the story of the rise of the interventional pathologist: a testament to innovation, dedication, and an unwavering commitment to patient well-being.

Impact of implementing the first edition of the Paris system for reporting: A systematic review and meta-analysis.

Urine cytology is a noninvasive, widely used diagnostic tool for screening and surveillance of genitourinary tract neoplasms. However, the absence of unified terminology and clear objective morphological criteria limits the clinical benefit of urine cytology. The Paris System for Reporting Urine Cytology (TPS) was developed with the goal of standardizing reporting and improving urine cytology performance in detecting high-grade malignancy (HGM). We aimed to evaluate potential effects of TPS on improving urine cytology diagnostic performance and clinical utility by conducting a systematic review and meta-analysis. We searched six electronic databases to identify cross-sectional and cohort studies written in English assessing the accuracy of urine cytology in detecting genitourinary tract malignancies of patients under surveillance or with clinical suspicion of malignancy from January 2004 to December 2022. We extracted relevant data from eligible studies to calculate relative distribution of cytology diagnostic categories; ratio of atypical to HGM cytology diagnosis; and risk of HGM (ROHGM) and HGM likelihood ratio (HGM-LR) associated with cytology diagnostic categories. We used a generalized linear mixed model with logit transformation to combine proportions and multilevel mixed-effect logistic regression to pool diagnostic accuracy measurements. We performed meta-regression to evaluate any significant difference between TPS and non-TPS cohorts. We included 64 studies for 99,796 combined total cytology samples, across 31 TPS and 49 non-TPS cohorts. Pooled relative distribution [95% confidence interval (CI)] of negative for high-grade urothelial carcinoma (NHGUC)/negative for malignancy (NM); atypical urothelial cells (AUC); suspicious for high-grade urothelial carcinoma (SHGUC)/suspicious for malignancy (SM); low-grade urothelial neoplasm (LGUN); and HGM categories among satisfactory cytology cases were 83.8% (80.3%-86.9%), 8.0% (6.0%-10.6%), 2.2% (1.4%-3.3%), 0.01% (0.0%-0.1%), and 4.2% (3.2%-5.5%) in TPS versus 80.8% (76.8-2.7%), 11.3% (8.6%-14.7%), 1.8% (1.2%-2.7%), 0.01% (0.0%-0.1%), and 3.3% (2.5%-4.3%) in non-TPS cohorts. Adopting TPS classification resulted in a significant increase in the frequency of NHGUC and a reduction in AUC cytology diagnoses, respectively. The AUC/HGM ratio in TPS cohort was 2.0, which showed a statistically significant difference from the atypical/HGM ratio of 4.1 in non-TPS cohort (p-value: 0.01). Moreover, the summary rate (95% CI) of LGUN called AUC on cytology significantly decreased to 20.8% (14.9%-28.3%) in the TPS compared with 34.1% (26.4%-42.8%) in non-TPS cohorts. The pooled ROHGM (95% CI) was 20.4% (6.2%-50.0%) in nondiagnostic (NDX), 15.5% (9.6%-24.2%) in NHGUC, 40.2% (30.9%-50.2%) in AUC, 80.8% (72.9%-86.8%) in SHGUC, 15.1% (5.7%-34.3%) in LGUN, and 91.4% (87.3%-94.3%) in HGM categories in TPS studies. NHGUC, AUC, SHGUC, and HGM categories were associated with HGM-LR (95% CI) of 0.2 (0.1-0.3), 0.9 (0.6-1.3), 6.9 (2.4-19.9), and 16.8 (8.3-33.8). Our results suggest that TPS 1.0 has reduced the relative frequency of AUC diagnosis, AUC/HGM ratio, and the frequency of LGUNs diagnosed as AUC on cytology. Adopting this classification has improved the clinical utility of SHGUC and HGM cytology diagnoses in ruling in high-grade lesions. However, an NHGUC diagnosis does not reliably rule out the presence of a high-grade lesion.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardised reporting systems for non-gynaecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung and more. In February 2018, the first edition of the Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of non-neoplastic, benign and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published, confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarising the use of salivary gland imaging, new advances in ancillary testing and updates in nomenclature.

Optimizing schools of cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

[Bethesda 2023: A new terminology for thyroid cytopathology]. / Bethesda 2023: nouvelle terminologie en cytopathologie thyroïdienne.

A third update of The Bethesda System for Reporting Thyroid Cytopathology has been published in 2023 following the first (2010) and second (2017) versions. The main modifications are the following 1) a new co-Editor, 2) 4 associate editors, 3 of them from Europe, 3) the inclusion of 65 co-authors, 19 of them from Europe, 4) 2 new chapters: one dealing with pediatrics thyroid cytopathology and the other one describing molecular cytopathology profiling, 5) updated risks of malignancy (ROM), 6) a terminology in line with the 2022 WHO classification of thyroid tumors, 7) diagnostic categories now defined by a unique name, 8) 2 subtypes in the "Atypia of Undetermined Significance" category with corresponding ROM.

[Serous fluid cytopathology : International system: Ancillary studies for serous fluids and special considerations for peritoneal washings]. / Cytopathologie des séreuses : la classification internationale : À propos des techniques ancillaires prédictives et du cas particulier des lavages péritonéaux.

The International System for serous fluids cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. The exponential discovery of prognostic and theranostic molecular alterations in many cancers, particularly in advanced stages, led the authors to describe the indications and the feasibility of these new markers on cytological samples from serous effusions. The various immunocytochemistry techniques, FISH and those testing DNA and RNA are reported in regard to their ability to identify the main targets currently explored in routine practice. The vast majority of these crucial markers can be reliably tested on effusion fluids. The International System for serous effusion fluids also includes a chapter dedicated to peritoneal washings and the application of the classification to this particular type of sample. The objective is to "wash" the peritoneal cavity with a saline solution to unfix cells from the cavity's wall and collect those that have previously naturally detached. This procedure, performed before surgery of tumors and before any manipulation, allows a cytological analysis that specifies the staging of gynecological and non-gynecological tumors and excludes occult malignant cells in the presence of tumors appearing benign.

[Serous fluid cytopathology: International system]. / Cytopathologie des séreuses : la classification internationale.

The International System for Serous Fluid Cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. Five diagnostic categories are proposed associated to an increased rate of malignancy and specific cytological criteria. The categories are reported as: (I) Non-diagnostic (ND), the cells are insufficient for interpretation; (II) Negative for malignancy (NFM), only benign cells are present; (III) Atypia of undetermined significance (AUS), the cells present mild atypia more likely to be benign, but a malignant process cannot be definitively excluded; (IV) Suspicious for malignancy (SFM), the cells are present with atypia or in a number suspect of malignancy but with insufficient ancillary studies to give a positive malignant diagnosis; (V) Malignant (MAL), the cytological criteria are absolutely and definitively malignant. Malignant neoplasia can be primitive, it involves mesothelioma and serous lymphoma but most are secondary and correspond mainly to adenocarcinomas in adults and leukemia/lymphoma in children. The diagnostic should always be provided in the appropriate clinical context and be as definitive as possible. The ND, AUS and SFM are temporary or last intention categories. Immunocytochemistry in association with FISH or flow cytometry allow in most cases a conclusive diagnosis. These ancillary studies as well as ADN and ARN tests on effusion's fluids are particularly suited to give reliable theranostic results for personalized therapies.

Statistical methods for evaluating the fine needle aspiration cytology procedure in breast cancer diagnosis.

BACKGROUND: Statistical issues present while evaluating a diagnostic procedure for breast cancer are non rare but often ignored, leading to biased results. We aimed to evaluate the diagnostic accuracy of the fine needle aspiration cytology(FNAC), a minimally invasive and rapid technique potentially used as a rule-in or rule-out test, handling its statistical issues: suspect test results and verification bias. METHODS: We applied different statistical methods to handle suspect results by defining conditional estimates. When considering a partial verification bias, Begg and Greenes method and multivariate imputation by chained equations were applied, however, and a Bayesian approach with respect to each gold standard was used when considering a differential verification bias. At last, we extended the Begg and Greenes method to be applied conditionally on the suspect results. RESULTS: The specificity of the FNAC test above 94%, was always higher than its sensitivity regardless of the proposed method. All positive likelihood ratios were higher than 10, with variations among methods. The positive and negative yields were high, defining precise discriminating properties of the test. CONCLUSION: The FNAC test is more likely to be used as a rule-in test for diagnosing breast cancer. Our results contributed in advancing our knowledge regarding the performance of FNAC test and the methods to be applied for its evaluation.

False positive cases in thyroid cytopathology - the experience of a single laboratory and a systematic review.

INTRODUCTION: Fine needle aspiration (FNA) is fundamental in the pre-operative assessment of thyroid nodules. However, the shining success of thyroid FNA is occasionally eclipsed by false positive (FP) cytological diagnoses. We describe our experience regarding FP cytological diagnoses and present a literature review concerning FP rates. MATERIALS AND METHODS: We retrospectively analyzed 2031 consecutive cytology reports. FP was defined as a case with "suspicious for malignancy" or "malignant" cytology, whose surgical follow-up failed to confirm the initial diagnosis of malignancy. We used the PubMed database for the literature review using specific search terms ("thyroid", "cytology", "false positive"). RESULTS: Out of 2031 FNA reports, 93 cases with "suspicious for malignancy" or "malignant" cytology underwent surgical excision. Histopathology did not confirm malignancy in 10 cases (0.6% FP rate). Nodules with FP cytology were significantly larger (P = 0.0024) than those with with TP (true positive) cytology. A review of 25 publications shows comparable results to ours with some slight differences. The majority of studies achieve a FP rate below 3%. Most FP cytological diagnoses turn out to be non-neoplastic lesions (nodular hyperplasia, adenomatous nodule, lymphocytic thyroiditis), which combined account for 80.5% of all histological diagnoses. CONCLUSIONS: Thyroid nodules with FP cytology were larger than nodules with TP cytology. Most studies manage to adhere to the recommended FP rates, or values close to them, with some outliers. Nevertheless, the mean FP rate values are very close to the value recommended by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The FP rate value depends on how one defines true negative cases, which can be either histologically proven benign cases, via a benign clinical course, or by assuming that cytologically benign cases remain as such.

Juggling the COVID-19 pandemic: A cytopathology point of view.

Since its first identification in China at the end of 2019, severe acute respiratory syndrome coronavirus 2 has rapidly spread all over the world, becoming an international healthcare emergency. In the era of coronavirus disease-2019 (COVID-19), several aspects of normal life, including those related to the medical activities, have been radically changed. Extraordinary measures have been adopted by different nations to cope with the rapid diffusion of COVID-19 all over the world. In hospitals, careful attention has been paid to manage infected patients with a possible detrimental effect for patients affected by other diseases. As with other medical fields, cytopathology laboratories have also drastically modified their activities to cope with the COVID-19 healthcare emergency. Here, the main effects of COVID-19 pandemic on the routine practice of cytopathology are summarised, focusing on the prioritisation policy adopted by cytopathologists worldwide.

Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner.

While blocking tumor growth by targeting autophagy is well established, its role on the infiltration of natural killer (NK) cells into tumors remains unknown. Here, we investigate the impact of targeting autophagy gene Beclin1 (BECN1) on the infiltration of NK cells into melanomas. We show that, in addition to inhibiting tumor growth, targeting BECN1 increased the infiltration of functional NK cells into melanoma tumors. We provide evidence that driving NK cells to the tumor bed relied on the ability of autophagy-defective tumors to transcriptionally overexpress the chemokine gene CCL5 Such infiltration and tumor regression were abrogated by silencing CCL5 in BECN1-defective tumors. Mechanistically, we show that the up-regulated expression of CCL5 occurred through the activation of its transcription factor c-Jun by a mechanism involving the impairment of phosphatase PP2A catalytic activity and the subsequent activation of JNK. Similar to BECN1, targeting other autophagy genes, such as ATG5, p62/SQSTM1, or inhibiting autophagy pharmacologically by chloroquine, also induced the expression of CCL5 in melanoma cells. Clinically, a positive correlation between CCL5 and NK cell marker NKp46 expression was found in melanoma patients, and a high expression level of CCL5 was correlated with a significant improvement of melanoma patients' survival. We believe that this study highlights the impact of targeting autophagy on the tumor infiltration by NK cells and its benefit as a novel therapeutic approach to improve NK-based immunotherapy.

[Salivary gland cytopathology: Milan system 2018]. / Cytopathologie des glandes salivaires : le système de Milan 2018.

The salivary glands cytology is one of the most challenging area in cytopathology because of the wide diversity of benign and malignant tumors also because of their heterogeneity. However, fine needle aspiration cytology, with magnetic resonance imaging, represents a first-line examination to guide a possible surgical procedure and its extent. An accurate diagnosis of a specific tumor is sometimes difficult to assess in cytology. Also, as for gynecological, thyroid or urinary cytologies, a panel of experts met to develop a cytological classification of salivary gland lesions associated with a risk of malignancy and management proposals. The Milan System for Reporting Salivary Gland Cytopathology was published in 2018. The French Society of Clinical Cytology (SFCC) offers here an official summarized French version oh this terminology and recommends its use.

Combinatorial expression of microtubule-associated EB1 and ATIP3 biomarkers improves breast cancer prognosis.

PURPOSE: The identification of molecular biomarkers for classification of breast cancer is needed to better stratify the patients and guide therapeutic decisions. The aim of this study was to investigate the value of MAPRE1 gene encoding microtubule-end binding proteins EB1 as a biomarker in breast cancer and evaluate whether combinatorial expression of MAPRE1 and MTUS1 gene encoding EB1-negative regulator ATIP3 may improve breast cancer diagnosis and prognosis. METHODS: Probeset intensities for MAPRE1 and MTUS1 genes were retrieved from Exonhit splice array analyses of 45 benign and 120 malignant breast tumors for diagnostic purposes. Transcriptomic analyses (U133 Affymetrix array) of one exploratory cohort of 150 invasive breast cancer patients and two independent series of 130 and 155 samples were compared with clinical data of the patients for prognostic studies. A tissue microarray from an independent cohort of 212 invasive breast tumors was immunostained with anti-EB1 and anti-ATIP3 antibodies. RESULTS: We show that MAPRE1 gene is a diagnostic and prognostic biomarker in breast cancer. High MAPRE1 levels correlate with tumor malignancy, high histological grade and poor clinical outcome. Combination of high-MAPRE1 and low-MTUS1 levels in tumors is significantly associated with tumor aggressiveness and reduced patient survival. IHC studies of combined EB1/ATIP3 protein expression confirmed these results. CONCLUSIONS: These studies emphasize the importance of studying combinatorial expression of EB1 and ATIP3 genes and proteins rather than each biomarker alone. A population of highly aggressive breast tumors expressing high-EB1/low-ATIP3 may be considered for the development of new molecular therapies.

[A new terminology for urinary cytopathology: The Paris System for Reporting Urinary Cytology (2015)]. / Une nouvelle terminologie pour la cytopathologie urinaire : le Système de Paris (2015).

As for the Bethesda system for cervical and thyroid cytopathology, a terminology for reporting urinary cytology has been published in 2015. The new "Paris System" provides a consensus terminology for urinary cytology which underlines the criteria for the recognition of high-grade urothelial carcinoma (HGUC) and of those excluding HGUC, or suspicious for HGUC. It also focuses on new rules to recognize and report the subgroup of "atypical urothelial cells". Here we describe and illustrate the various categories as in the reference book. We analyse the main diagnostic criteria, including microscopic features as well as the risk of malignancy associated to every diagnostic category.

Preclinical ex vivo evaluation of the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses.

OBJECTIVES: To assess the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses in freshly removed surgical specimens, in preparation for its clinical development. METHODS: Sixty-four breast masses from consenting patients who had undergone either a lumpectomy or a mastectomy were included. Label-free fluorescence spectral acquisitions were obtained with a 25G fibre-containing needle inserted into the mass. Data from benign and malignant masses were compared to establish the most discriminating thresholds and measurement algorithms. Accuracy was verified using the bootstrap method. RESULTS: The final histological examination revealed 44 invasive carcinomas and 20 benign lesions. The maximum intensity of fluorescence signal was discriminant between benign and malignant masses (p < .0001) whatever their sizes. Statistical analysis indicated that choosing five random measurements per mass was the best compromise to obtain high sensitivity and high negative predictive value with the fewest measurements. Thus, malignant tumours were identified with a mean sensitivity, specificity, negative and positive predictive value of 98.8%, 85.4%, 97.2% and 93.5%, respectively. CONCLUSION: This new in situ tissue autofluorescence evaluation device allows accurate discrimination between benign and malignant breast masses and deserves clinical development. KEY POINTS: • A new device allows in situ label-free fluorescence analysis of ex vivo breast masses • Maximum fluorescence intensity discriminates benign from malignant masses (p < .0001) • Five random measurements allow a high negative predictive value (97.2%).

Patient satisfaction with a rapid diagnosis of suspicious breast lesions: Association with distress and anxiety.

Few studies have explored with standard measures patient satisfaction with care at the time of the diagnosis through rapid diagnostic pathways. This study aimed to assess satisfaction levels at the time of the diagnosis in a One-Stop Breast Unit and to examine associations with psychological states. An anonymous cross-sectional survey was conducted at a single center's One-Stop Breast Unit, to assess patient satisfaction regarding several aspects of the Unit. Two days after the diagnosis, 113 participants completed self-reported questionnaires evaluating satisfaction (Out-Patsat35), anxiety (State Anxiety Inventory), and psychological distress (Distress Thermometer). Overall, patients were very satisfied (80.7±20.7) with the One-Stop Breast Unit. The highest mean satisfaction scores concerned nurses' technical skills, interpersonal skills and availability. The lowest mean scores concerned physicians' availability, waiting time, and the provision of information. The results revealed a significant association between high state anxiety levels, lower levels of satisfaction with doctors' interpersonal skills (r=-.41, P<.001) and lower levels for information provided by nurses (r=-.38, P<.001). Moreover, greater psychological distress was associated with less satisfaction with the different aspects of care (doctors' interpersonal skills, doctors' availability and waiting-time). The results of regression models showed that doctor-related satisfaction scales explained 20% of the variance in anxiety (P<.01). Facing cancer diagnosis remains a stressful situation. However, our study suggested that a substantial part of this anxiety is sensitive to the quality of the patient-doctor relationship. Consequently, further efforts should be expended on adapting patient-doctor communication to improve patient reassurance.

First-in-human phase 1 of YS110, a monoclonal antibody directed against CD26 in advanced CD26-expressing cancers.

BACKGROUND: YS110 is a humanised IgG1 monoclonal antibody with high affinity to the CD26 antigen. YS110 demonstrated preclinical anti-tumour effects without significant side effects. METHODS: This FIH study was designed to determine the maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) to assess the tolerance, pharmacokinetics (PK) and pharmacodynamics profiles of YS110 and preliminary efficacy. YS110 were initially administered intravenously once every 2 weeks (Q2W) for three doses and then, based on PK data, once every week (Q1W) for five doses in patients with CD26-expressing solid tumours. RESULTS: Thirty-three patients (22 mesothelioma) received a median of 3 (range 1-30) YS110 infusions across six dose levels (0.1-6 mg kg-1). MTD was not reached and two dose-limiting toxicities (infusion hypersensitivity reactions) led to the institution of a systemic premedication. Low-grade asthenia (30.3%), hypersensitivity (27.3%), nausea (15.2%), flushing (15.2%), chills (12.1%) and pyrexia (12.1%) were reported as ADRs. Pharmacokinetic parameters (AUC and Cmax) increased in proportion with the dose. sCD26/DPPIV assays indicated CD26 modulation. Prolonged stable diseases were observed in 13 out of 26 evaluable patients. CONCLUSIONS: YS110 is well tolerated up to 6 mg kg-1 Q1W, which has been defined as the RP2D, with encouraging prolonged disease stabilisations observed in a number of patients with advanced/refractory mesothelioma.