Stomatal penetration: the cornerstone of plant resistance to the fungal pathogen Zymoseptoria tritici.

BACKGROUND: Septoria tritici blotch (STB), caused by the foliar fungus Zymoseptoria tritici, is one of the most damaging disease of wheat in Europe. Genetic resistance against this fungus relies on different types of resistance from non-host resistance (NHR) and host species specific resistance (HSSR) to host resistance mediated by quantitative trait loci (QTLs) or major resistance genes (Stb). Characterizing the diversity of theses resistances is of great importance for breeding wheat cultivars with efficient and durable resistance. While the functional mechanisms underlying these resistance types are not well understood, increasing piece of evidence suggest that fungus stomatal penetration and early establishment in the apoplast are both crucial for the outcome of some interactions between Z. tritici and plants. To validate and extend these previous observations, we conducted quantitative comparative phenotypical and cytological analyses of the infection process corresponding to 22 different interactions between plant species and Z. tritici isolates. These interactions included four major bread wheat Stb genes, four bread wheat accessions with contrasting quantitative resistance, two species resistant to Z. tritici isolates from bread wheat (HSSR) and four plant species resistant to all Z. tritici isolates (NHR). RESULTS: Infiltration of Z. tritici spores into plant leaves allowed the partial bypass of all bread wheat resistances and durum wheat resistance, but not resistances from other plants species. Quantitative comparative cytological analysis showed that in the non-grass plant Nicotiana benthamiana, Z. tritici was stopped before stomatal penetration. By contrast, in all resistant grass plants, Z. tritici was stopped, at least partly, during stomatal penetration. The intensity of this early plant control process varied depending on resistance types, quantitative resistances being the least effective. These analyses also demonstrated that Stb-mediated resistances, HSSR and NHR, but not quantitative resistances, relied on the strong growth inhibition of the few Z. tritici penetrating hyphae at their entry point in the sub-stomatal cavity. CONCLUSIONS: In addition to furnishing a robust quantitative cytological assessment system, our study uncovered three stopping patterns of Z. tritici by plant resistances. Stomatal resistance was found important for most resistances to Z. tritici, independently of its type (Stb, HSSR, NHR). These results provided a basis for the functional analysis of wheat resistance to Z. tritici and its improvement.

Functional structure of a high resolution thyroid nodule unit. Economic impact and results of its implementation in an Endocrinology department.

BACKGROUND AND OBJECTIVE: The high incidence of nodular thyroid pathology has led to growing concern about the economic impact that this pathology represents on the healthcare system. There are conclusive data about the cost-effectiveness of high-resolution units for nodular thyroid pathology; however, their implementation is not homogeneous in the Endocrinology and Nutrition services of our country. The objective of the present study was to evaluate the economic impact of the implementation of the high-resolution thyroid nodule unit (HRTNU) in our center. PATIENTS AND METHODS: The present work is a prospective, observational and descriptive study carried out in 1314 patients (82% women, mean age 58 years ds = 11) evaluated at the HRTNU during the period of August 2022-August 2023. Demographic data (age and sex) were analyzed, referral center and consultation type, number of total consultations and neck ultrasound performed, number of fine needle aspiration (FNAB) performed, and cytology results were analyzed. RESULTS: In the period from August 2022 to August 2023, a total of 1314 patients were evaluated (neck ultrasound and clinical consultation) and a total of 133 FNAB were performed, of which only 2.26% were non-diagnostic. Compared to the percentage of unsatisfactory FNAB from the previous year August 2021-July 2022 of 25%, a mean saving of 9931.43 euros was estimated. 84.47% of the patients evaluated for the first time by the HRTNU were discharged, estimating a mean saving of 133,200 euros. CONCLUSIONS: The implementation of a HRTNU at the Endocrinology and Nutrition departments, coordinated with primary and specialized care, is a cost-effectiveness alternative, as it reduces the number of medical consultations and is accompanied by a higher rate of diagnostic FNAB.

The Sydney system for lymph node FNA biopsy cytopathology: A detailed analysis of recent publications and meta-analysis and a proposal for the components of an ideal prospective study of a cytopathology reporting system.

BACKGROUND: The Sydney system for fine-needle aspiration biopsy of lymph nodes has five categories, stressing the role of correlation of cytopathology with clinical, ultrasound, and ancillary findings to achieve diagnosis. The five categories constitute a hierarchical system with increasing risk of malignancy from benign to atypical, suspicious, and malignant categories, which informs recommendations for further workup to achieve a final diagnosis as possible. This article analyzes 10 publications using the Sydney system and a meta-analysis of nine of these studies. The primary goal of the analysis is to ascertain the causes of the large ranges in risk of malignancy for the "atypical" and "inadequate" compared to "benign," "suspicious," and "malignant" categories, which were comparable to well-established reporting systems. Research protocols are proposed to improve future studies. METHODS: PubMed literature search from January 2021 to December 2023 identified studies evaluating performance of the Sydney system. RESULTS: Ten studies showed heterogeneity with clinical setting, study design, ultrasound use and rapid on-site evaluation, operator, cutoff points for "positive" cases, with inherent partial verification biases, resulting in a wide range of risk of malignancy, specificity, and sensitivity values. CONCLUSION: Analysis shows the large range is due to heterogeneity of the studies, which suffer from biases and variable statistical analysis that are ultimately included in any meta-analysis, detracting from the usefulness of the risk of malignancy derived by the meta-analysis. Components for ideal analyses of reporting systems are presented.

The effect of carbomer versus noncarbomer lubricant on the adequacy of cervical cytology specimens.

INTRODUCTION: Cervical cytology remains a critical screening tool for cervical cancer. While various factors can influence cytology quality, the effect of lubricant type used during specimen collection has been previously studied with inconclusive results. This study aimed to evaluate the impact of surgical lubricant on cervical cytology results and elucidate risk factors associated with unsatisfactory results. We hypothesized that switching from a carbomer-containing lubricant to a noncarbomer, water-soluble lubricant would improve specimen adequacy in cervical cytology. MATERIALS AND METHODS: A retrospective chart review was performed examining patient cytologic results from January to December 2017 at a single academic institution. After historical rates of unsatisfactory cytology were higher than acceptable standards, the practice changed lubricant formulation from a carbomer containing lubricant to a noncarbomer, water soluble lubricant. Demographic data and treatment characteristics were collected for eligible patients. Matched analysis was performed to examine factors associated with an unsatisfactory cytology result. RESULTS: After the change in lubricant, there was a significant decline in the rates of unsatisfactory cytology from 9.6% to 5.7%, P = 0.01. This decline was also observed when patients were matched based on menopausal status, personal history of gynecologic malignancy, pregnancy status, and cytology specimen type (10.0% to 4.8%, P = 0.001). CONCLUSIONS: Change in lubricant from a carbomer containing to noncarbomer, water soluble product was associated with a statistically significant decline in the rates of unsatisfactory cytology. Although prior data have had mixed results as to the etiology of unsatisfactory cytology, we feel that this directly contributed to the high rates observed at our institution.

Clinical features and Surgical Outcomes of Thyroid Goitre Presenting to Ear, Nose and Throat Department of Queen Elizabeth Central Hospital, Blantyre, Malawi.

Introduction: In Malawi there is a perception that goitre is common and causes significant public health and economic burdens. The purpose of this study was to assess the demographic distribution, clinical presentation, investigations, management, outcomes and complications of goitre seen at Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. Method: A single hospital-based descriptive retrospective study from January 2017 to December 2018 for all patients presenting with goitre. Results: Out of 9073 patients who presented to ENT department, 105 patients presented with goitre representing 1% of all patients seen during the study period. The Male: Female ratio was 1:25. The mean symptom duration with goitre was 4 years (SD +/- 6.4). Thyroid function test results were available in 54 patients and out of these, 53(98%) patients were euthyroid. Ultrasound scan (USS) reports were available in 44 patients, of these 32(73%) were multinodular goitres. In 70 cases, pathology results were available and showed that 20% were thyroid cancers and that papillary thyroid carcinoma was the commonest cancer (64%). Two recurrent laryngeal nerve injuries were recorded in 79 surgical procedures representing 2.5% of patients (6.3% overall complication rate). Inpatient stay ranged from 2 days to 49 days (median 3 days). Conclusion: Goitre at our centre is more common in women than in men. One in five patients in this cohort had thyroid cancers. This prevalence is higher than other areas in the world highlighting the need for cytology services on every patient before surgery and histology services after surgery. Recurrent laryngeal nerve injury and other complications were infrequent demonstrating local high safety of thyroid surgery, despite late presentation to the ENT department.

The Great Impostor: A challenging case of small-cell melanoma with isolated adrenal metastasis.

Small-cell melanoma masquerading as an adrenal non-Hodgkin lymphoma. The index report illustrates the deceptive cytomorphologic features of a small cell type malignant melanoma metastatic to the adrenal gland. The diagnosis was confirmed by performing immunocytochemistry on the cell block sections. The key cytomorphologic mimics and their distinctive features have also been highlighted.

Pulmonary Cytopathology: Current and Future Impact on Patient Care.

Small biopsies of lung are routinely obtained by many methods, including several that result in cytologic specimens. Because lung cancer is often diagnosed at a stage for which primary resection is not an option, it is critical that all diagnostic, predictive, and prognostic information be derived from such small biopsy specimens. As the number of available diagnostic and predictive markers expands, cytopathologists must familiarize themselves with current requirements for specimen acquisition, handling, results reporting, and molecular and other ancillary testing, all of which are reviewed here.

Thyroid Fine-Needle Aspiration: The Current and Future Landscape of Cytopathology.

Thyroid cytology is a rapidly evolving field that has seen significant advances in recent years. Its main goal is to accurately diagnose thyroid nodules, differentiate between benign and malignant lesions, and risk stratify nodules when a definitive diagnosis is not possible. The current landscape of thyroid cytology includes the use of fine-needle aspiration for the diagnosis of thyroid nodules with the use of uniform, tiered reporting systems such as the Bethesda System for Reporting Thyroid Cytopathology. In recent years, molecular testing has emerged as a reliable preoperative diagnostic tool that stratifies patients into different risk categories (low, intermediate, or high) with varying probabilities of malignancy and helps guide patient treatment.

Salivary Gland Fine-Needle Aspiration: The Current and Future Landscape.

Fine-needle aspiration represents a valid tool for the diagnosis/management of salivary gland lesions. The past years assessed the lack of uniform diagnostic reports for salivary cytopathology leading to interpretative issues. In 2015, an international group of cytopathologists developed an evidence-based tiered classification system for reporting salivary gland fine-needle aspiration (FNA) specimens, the "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC). The present landscape of salivary cytology is represented by the growing adoption of the MSRSGC and the assessment of its diagnostic role. The future landscape is characterized by the increasing role of ancillary techniques for diagnostic and prognostic purposes.

Pancreas Fine Needle Aspiration: Current and Future Impact on Patient Care.

Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention.

Minimally Invasive, Maximally Effective: The Power of Precision Cytoanalysis on Effusion Samples-A Comprehensive Exploration from Traditional Methods to Innovative Approaches.

Precision medicine translates through molecular assays and in minimally invasive diagnosis, evident in analyses of effusions that serve therapeutic and diagnostic purposes. This cost-effective and low-risk approach provides advantages, playing a pivotal role in late-stage oncology and frequently standing as the primary resource for cancer diagnosis and treatment pathways. This article outlines the workflow for managing serous fluid and explores how cytology effusion analysis extends beyond immunocytological diagnosis. Combined with current molecular tests it showcases the potential to be a skillful tool in precision cytopathology.

A case report of primary central nervous system lymphoma with immune deficiency/disorder setting diagnosed by cerebrospinal fluid cytology.

Cerebrospinal fluid (CSF) cytology of primary central nervous system lymphoma arising in the immune deficiency/dysregulation setting (IDD-PCNSL) has not been described. This study presented a case of IDD-PCNSL-DLBCL, a GCB phenotype who was successfully diagnosed by CSF cytology in conjunction with ICC, ISH, FCM and clinical information.

Urinary Tract Cytopathology: Current and Future Impact on Patient Care.

Urine cytology is a non-invasive, cost-efficient, and sensitive test to detect high-grade urothelial carcinoma. The Paris System (TPS) for Reporting Urinary Cytology is an evidence-based system that uses the risk of malignancy to guide patient management. Since its inception, TPS has standardized urine cytology reports, facilitating communication among pathologists and between pathologists and clinicians. It is imperative to correlate the urine cytology findings with the concurrent tissue sample to avoid false-negative and false-positive results when possible. Several ancillary tests and artificial intelligence algorithms are being developed to increase the accuracy of urine cytology interpretation.

Pulmonary Cytopathology: Current and Future Impact of Microscopy and Immunohistochemistry.

With the advancement of tissue procurement techniques, in-depth knowledge of morphology is crucial for cytopathologists to diagnose neoplastic and nonneoplastic lung diseases optimally. Cytopathologists must also be well versed in immunohistochemistry/immunocytochemistry markers and their interpretation for an accurate diagnosis.

Occult Thyroid Carcinoma with Cervical Lymph Node Metastasis: A Rare Case Report.

Cervical lymph node metastasis is one of the most common clinical presentations of papillary thyroid carcinoma (PTC). Occult thyroid carcinoma is described as absence of primary tumour or with presence of microcarcinoma in thyroid with cervical lymph node metastasis. Frequency of occult thyroid cancer has decreased due to developments in imaging and improved accuracy of histological examinations. 38 year old male presented to us with complaints of swelling over the left side of neck for the past 2 months. Ultrasonography was suggestive of multiple suspicious enlarged nodes in left level II, III, IV and V and fine needle aspiration cytology showed features of metastatic PTC. He was planned for total thyroidectomy with central compartment clearance and bilateral functional neck dissection. Final histopathology staging was pT0N1b. Radioactive iodine (RAI) screening showed residual functioning thyroid and later therapeutic RAI was administered. He has been on regular follow up and disease free for 1 year post treatment. Occult thyroid carcinoma is a rare diagnosis with multiple treatment plans. Few hypothesis for this entity includes tumor regression, ectopic thyroid carcinoma or missed pathological findings.

Diagnostic Utility of Cytomorphometric Evaluation of Exfoliated Oral Mucosal Cells in Type II Diabetes Mellitus: A Systematic Review and Meta-analysis.

Diabetes Mellitus (DM) is the sixth leading cause of mortality and morbidity in the world. Early diagnosis and periodic monitoring are mandatory to prevent complications. The custom of noninvasive exfoliative cytology diagnostic technique is the need of the hour in diabetes, where the invasive methods lose viability. The purpose of this meta-analysis is to analyze the cytomorphometric changes in the exfoliated cells of the oral mucosa, as an adjunct to the diagnosis of type II diabetes. A thorough search was made by using PubMed, Google Scholar, and Cochrane Library databases. Original research articles, that evaluated cytomorphometric parameters (nuclear area, cytoplasmic area, cytoplasmic nuclear ratio) in type II diabetes patients were included in this review. Risk of bias was analysed for each study using Joanna Briggs Institute and Review Manager was used for meta-analysis. All nine subgroups included for qualitative and quantitative data synthesis revealed that there was a significant increase in nuclear area and a decrease in cytoplasmic nuclear ratio in diabetic patients as compared to non-diabetics. Random-effects model also confirmed cytologically altered (nuclear area and cytoplasmic nuclear ratio) parameters to have a significantly increased risk of association with diabetes. Furthermore, these morphometry parameters were also associated with glycemic control and there was no gender disparity among them. Mounting evidence authenticate that cytomorphometric analysis of oral mucosal cells using exfoliative cytology might be aid as an adjunct non-invasive diagnostic tool for type II diabetes.

First case of feline cryptococcosis in Bosnia and Herzegovina.

Case summary: A 2-year-old domestic longhair crossbred female cat was referred for a second opinion on a non-healing surgical wound after left eye enucleation. In addition to the left orbital lesion, ulcerative granular masses protruding from the left nostril and on the base of the left ear were noted. A diagnosis of cryptococcosis was established using histopathological examination and a latex cryptococcal antigen agglutination test. The cat was successfully treated with itraconazole. Relevance and novel information: Cryptococcosis, commonly reported in Australia, western Canada and the western USA, is rarely reported in companion animals in Europe. This marks the first report of cryptococcosis in cats in Bosnia and Herzegovina, emphasising the need to raise awareness within the veterinary community, both local and regional, about this disease.

Comparison of Claudin-4, BerEP4, Carcinoembryonic Antigen and MOC31 in Serous Fluids Metastases Demonstrate High Sensitivity of Claudin-4 at Low Cellularity.

INTRODUCTION: Claudin-4 has been described as a highly sensitive immunocytochemical marker for detection of metastatic carcinoma cells in effusion cytology specimens. This study aims to challenge the performance of claudin-4 in different types of malignancies and low cellularity specimens, by comparison with other markers in a large cohort of carcinomatous effusion specimens. METHODOLOGY: Cell block preparations from peritoneal and pleural fluid specimens were retrieved, with malignant (carcinoma) diagnoses confirmed by review of hospital diagnosis code and pathology reports. Claudin-4, BerEP4, CEA, and MOC31 immunocytochemistry were performed and scored by expression proportion and intensity. Tumor cellularity was assessed for subgroup analysis of low cellularity specimens. RESULTS: Totally 147 specimens (70 pleural, 77 peritoneal) of 68 lung, 62 breast, 9 gynecological, and 7 gastrointestinal carcinomas were retrieved. The average proportion expression of claudin-4 was highest (89.6%, vs. CEA 40.5%, BerEp4 18.6%, MOC31 16.8%) and the percentage of strong expression was highest for claudin-4 (72.1%). Expression levels of claudin-4 were consistently higher than other markers in subgroups of all primary sites. The difference was more significant for low cellularity specimens. High (≥50%) proportion expression was seen for 96.61% of cases for claudin-4 (vs. BerEp4 8.77%, CEA 46.55%, MOC31 8.77%, p < 0.001). These factors contributed to a low concordance between claudin-4 and BerEp4, CEA and MOC31 (K = 0.010-0.043). CONCLUSION: Claudin-4 is more sensitive than CEA, BerEp4 and MOC31, suitable for low cellularity specimens of most types of metastatic carcinoma and is a robust immunocytochemical marker for carcinoma that can be used solitarily.

Self-collected versus clinician-collected anal swabs for anal cancer screening: A systematic review and meta-analysis.

Anal squamous cell carcinoma (ASCC) incidence is increasing globally. International consensus guidelines published in 2024 include HPV and/or cytology testing of anal swabs in those at greatest risk of ASCC. Self-collected anal swabs may be important for increasing screening uptake, but evidence is needed as to their equivalence to clinician-collected swabs. We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to 13 June 2023. Studies were included if reporting data on HPV testing, cytology testing, or acceptability, for both self- and clinician-collected anal swabs. Risk of bias was assessed using the QUADAS-2 assessment tool. The primary outcome was HPV and cytology sampling adequacy. Secondary outcomes were HPV and cytology results, and acceptability of collection methods. Thirteen papers describing 10 studies were eligible. Sample adequacy was comparable between self- and clinician-collected swabs for HPV testing (meta-adequacy ratio: 1.01 [95% CI 0.97-1.05]) but slightly lower for cytology by self-collection (meta-adequacy ratio: 0.91 [95% CI 0.88-0.95]). There was no significant difference in prevalence (meta-prevalence ratio: 0.83 (95% CI 0.65-1.07) for any HR-HPV, 0.98 (95% CI 0.84-1.14) for any HPV, and 0.68 (95% CI 0.33-1.37) for HPV16), or any cytological abnormality (meta-prevalence ratio 1.01 [95% CI 0.86-1.18]). Only three papers reported acceptability results. Findings indicate self-collection gives equivalent sample adequacy for HPV testing and ~ 10% inferior adequacy for cytological testing. Meta-prevalence was similar for HPV and cytology, but confidence intervals were wide. Larger studies are required to definitively assess use of self-collected swabs in anal cancer screening programs, including acceptability.

Impact of endoscopic ultrasound-guided fine needle aspiration on positive peritoneal lavage cytology in patients with resectable pancreatic body and tail cancer.

BACKGROUND/PURPOSE: A recent study has demonstrated that the timing of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) significantly influences the peritoneal lavage cytology (CY) outcomes in pancreatic body-tail cancer. The aim of this study was to clarify the impact of EUS-FNA on CY positivity in patients with resectable pancreatic body-tail cancer. METHODS: Patients with anatomically resectable pancreatic body-tail cancer surgically resected at Hiroshima University Hospital were enrolled, and elated clinicopathological factors, including EUS-FNA variables and CY positivity rate, were analyzed. RESULTS: Of the 129 eligible patients, 16 (12%) had positive CY. The EUS-FNA rates of the CY-positive and CY-negative groups were not significantly different (63% vs. 52%, p = .440). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for CY positivity (odds ratio: 5.734, p = .031). A total of 10 (14%) of the 69 patients who underwent EUS-FNA had positive CY; however, needle specifications and the interval between EUS-FNA and CY examination did not differ between the CY-positive and CY-negative groups. CY positivity rates were comparable for intervals ≤14 days and ≥15 days (17% vs. 14%, p = 1.000). CONCLUSIONS: EUS-FNA may not affect CY positivity in patients with resectable pancreatic body-tail cancer, regardless of the timing.