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Background: Clear cell papillary renal cell tumour (CCPRCT) was renamed from previous clear cell papillary renal cell carcinoma (CCPRCC) in the latest WHO Classification of Tumours. It is essential to differentiate RCC from CCPRCT in renal mass biopsies (RMB). Design: RMB cases with subsequent resections were reviewed. The pathology reports and pertinent clinical information were recorded. Results: Fifteen cases displaying either CCPRCT morphology (20% diffuse, 67% focal) or immunohistochemical patterns (cup‐like CA9: 20% diffuse, 47% focal; CK7: 33% diffuse, 40% focal) were identified. One case was positive for TFE3. TSC mutation was identified in one case. Both cases exhibited both CCPRCT morphology and immunohistochemical patterns for CA9 and CK7, with focal high‐grade nuclei. RMB diagnoses were as follows: 6 (40%) as CCRCC, 2 (13%) as CCPRCT, 2 (13%) as CCRCC versus CCPRCT, 2 (13%) as CCRCC versus PRCC, 1 (7%) as RCC with TSC mutation versus CCPRCT, 1 (7%) as TFE3‐rearranged RCC versus PRCC, and 1 (7%) as cyst with low‐grade atypia. 71% of patients underwent nephrectomy, 21% received systemic treatment for stage 4 RCCs, and 7% with ablation for small renal mass (1.6 cm) with low‐grade CCRCC. Conclusions: Our study highlights that morphologic and immunochemical features of CCPRCT may be present in RCCs, including RCC‐TFE3 expression and TSC‐associated RCC, a critical pitfall to misdiagnose aggressive RCC as indolent CCPRCT and result in undertreatment. Careful examination of morphology and immunostains for CA9, CK7, and TFE3, as well as molecular tests, is crucial for distinguishing aggressive RCC from indolent CCPRCT. [ABSTRACT FROM AUTHOR]

Interobserver variability remains a major challenge for cytopathologists despite the development of standardized reporting and classification systems. Indeed, whereas moderate‐to‐good interobserver agreement is generally achievable when the differential diagnosis between benign and malignant entities is straightforward, high levels of variability make the diagnostic interpretation of atypical and suspicious samples not consistent. This review explores the landscape of interobserver agreement in cytopathology across different anatomical sites. [ABSTRACT FROM AUTHOR]

Background: Thyroid fine needle aspiration cytology (FNAC) is an important diagnostic tool for thyroid disorders. The Bethesda technique for Reporting Thyroid Cytopathology (TBSRTC) is an unambiguous, six-category reporting system for thyroid fine needle aspiration (FNA) that is widely acknowledged as a standard reporting guideline for institutes across continents which can minimize needless surgeries. Material and Methods: The study was carried out at the Pathology Department of the Assam Medical College and Hospital, Dibrugarh, Assam, India, from March 2023 to February 2024. The aim is to study the different cytological pattern in thyroid lesion by FNAC The results are interpreted using the features and categories specified in the TBSRTC. A total of 182 cases were studied. The distribution of the various categories from evaluated thyroid FNAs are as follows: nondiagnostic/unsatisfactory-8.2%, benign-75.9%, atypia of undetermined significance-6.0%,follicular neoplasm (FN) or suspicious for a FN-4.3%,suspicious for malignancy - 1%, malignant - 4.3%.Conclusion: The results of a FNA according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) give a standard and systematic approach to managing these nodules. Its standardized nomenclature enhanced thyroid FNAC reporting by facilitating communication and interlaboratory agreement among cytopathologists and clinicians, potentially leading to more standardized patient care management. [ABSTRACT FROM AUTHOR]

The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein (IGFBP) complex, encoded in humans by IGFALS, has a vital role in regulating the endocrine transport and bioavailability of IGF-1 and IGF-2. Accordingly, ALS has a considerable influence on postnatal growth and metabolism. ALS is a leucine-rich glycoprotein that forms high-affinity ternary complexes with IGFBP-3 or IGFBP-5 when they are occupied by either IGF-1 or IGF-2. These complexes constitute a stable reservoir of circulating IGFs, blocking the potentially hypoglycaemic activity of unbound IGFs. ALS is primarily synthesized by hepatocytes and its expression is lower in non-hepatic tissues. ALS synthesis is strongly induced by growth hormone and suppressed by IL-1β, thus potentially serving as a marker of growth hormone secretion and/or activity and of inflammation. IGFALS mutations in humans and Igfals deletion in mice cause modest growth retardation and pubertal delay, accompanied by decreased osteogenesis and enhanced adipogenesis. In hepatocellular carcinoma, IGFALS is described as a tumour suppressor; however, its contribution to other cancers is not well delineated. This Review addresses the endocrine physiology and pathology of ALS, discusses the latest cell and proteomic studies that suggest emerging cellular roles for ALS and outlines its involvement in other disease states. The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein complex regulates the endocrine transport and bioavailability of IGF-1 and IGF-2 and therefore influences postnatal growth and metabolism. This Review addresses the endocrine physiology and pathology of ALS, discusses the emerging cellular roles for ALS and outlines its involvement in disease states. Key points: The insulin-like growth factor (IGF) acid-labile subunit (ALS), encoded by IGFALS, forms a circulating ternary complex with IGF binding protein (IGFBP)-3 or IGFBP-5, and IGF-1 or IGF-2. This ternary complex acts as a reservoir of IGF-1 and IGF-2 in the bloodstream and has a central role in regulating their endocrine transport and tissue bioavailability. Owing to the induction of its expression by growth hormone and suppression by IL-1β, ALS might serve as a marker of growth hormone secretion and/or activity and of inflammation. Mutation, deletion or inactivation of the gene that encodes ALS in humans and mice decreases circulating levels of IGF-1 and IGFBP-3, causing moderate growth deficiency and abnormalities in bone and carbohydrate metabolism. As a marker of inflammation and sepsis, ALS levels are low in critical illness, cardiovascular disease and COVID-19; in some conditions, ALS levels might predict disease progression and mortality. [ABSTRACT FROM AUTHOR]

The transient cellular organelles known as migrasomes, which form during cell migration along retraction fibers, have emerged as a crutial factor in various fundamental cellular processes and pathologies. These membrane vesicles originate from local membrane swellings, encapsulate specific cytoplasmic content, and are eventually released to the extracellular environment or taken up by recipient cells. Migrasome biogenesis entails a sequential membrane remodeling process involving a complex interplay between various molecular factors such as tetraspanin proteins, and mechanical properties like membrane tension and bending rigidity. In this review, we summarize recent studies exploring the mechanism of migrasome formation. We emphasize how physical forces, together with molecular factors, shape migrasome biogenesis, and detail the involvement of migrasomes in various cellular processes and pathologies. A comprehensive understanding of the exact mechanism underlying migrasome formation and the identification of key molecules involved hold promise for advancing their therapeutic and diagnostic applications. [ABSTRACT FROM AUTHOR]

Serous effusion cytology is a pivotal diagnostic and staging tool in clinical pathology, valued for its simplicity and cost-effectiveness. Staining techniques such as Giemsa and Papanicolaou are foundational, yet the search for rapid and efficient alternatives continues. Our study assesses the efficacy of an in-house-developed BlueStain, a toluidine blue variant, within the International System for Reporting Serous Fluid Cytopathology (TIS), aiming to optimize diagnostic clarity and resource use. Materials and Methods: This section provides details on the cohort of 237 patients with serous effusions, the ethical approval process, sample collection, and staining procedures with BlueStain, Papanicolaou, and Giemsa. It also describes the microscopic evaluation criteria, scoring system, and statistical methods used to compare the stains. Results: BlueStain demonstrated notable performance, particularly in identifying malignant cells, presenting a competitive alternative to the Papanicolaou stain, which, despite higher quality indices in other categories, requires more resources and time. The study revealed that BlueStain might offer a valuable balance between quality and efficiency, especially in cases where rapid diagnostic turnaround is essential. Conclusions: Our findings suggest that BlueStain is a viable staining method in the context of serous effusions, capable of providing detailed cytomorphological analysis. While traditional stains hold their place for their established diagnostic clarity, BlueStain offers a rapid and resource-optimized alternative. The absence of definitive diagnostic criteria in the atypical category and the inherent sample heterogeneity underscores the necessity for adaptable staining methods like BlueStain. The study highlights the potential trade-offs between detail and practicality in staining techniques, advocating for further research into innovative methods that do not compromise diagnostic precision for cost and time efficiency. [ABSTRACT FROM AUTHOR]

• Aβ42-hIAPP co-oligomers show 2.3–3.5 times higher toxicity than AβO. • Increased apoptosis in glutamatergic neurons exposed to Aβ42-hIAPP. • Aβ42-hIAPP co-oligomers induce more severe AD pathology than AβO. • Novel insights into AD pathogenesis, implicating hIAPP in AD pathology. • Potential for constructing animal models to study Alzheimer's disease. The Aβ hypothesis has long been central to Alzheimer's disease (AD) theory, with a recent surge in attention following drug approvals targeting Aβ plaque clearance. Aβ42 oligomers (AβO) are key neurotoxins. While β-amyloid (Aβ) buildup is a hallmark of AD, postmortem brain analyses have unveiled human islet amyloid polypeptide (hIAPP) deposition in AD patients, suggesting a potential role in Alzheimer's pathology. This study investigates the neurotoxic effects of co-aggregates of Aβ42 and hIAPP, specifically focusing on their impact on cell survival, apoptosis, and AD-like pathology. We analyzed and compared the impact of AβO and Aβ42-hIAPP on cell survival in SH-SY5Y cells, apoptosis and inducing AD-like pathology in glutamatergic neurons. Aβ42-hIAPP co-oligomers exhibited significantly greater toxicity, causing 2.3–3.5 times higher cell death compared to AβO alone. Furthermore, apoptosis rates were significantly exacerbated in glutamatergic neurons when exposed to Aβ42-hIAPP co-oligomers. The study also revealed that Aβ42-hIAPP co-oligomers induced typical AD-like pathology in glutamatergic neurons, including the presence of Aβ deposits (detected by 6E10 and 4G8 immunofluorescence) and alterations in tau protein (changes in total tau HT7, phosphorylated tau AT8, AT180). Notably, Aβ42-hIAPP co-oligomers induced a more severe AD pathology compared to AβO alone. These findings provide compelling evidence for the heightened toxicity of Aβ42-hIAPP co-oligomers on neurons and their role in exacerbating AD pathology. The study contributes novel insights into the pathogenesis of Alzheimer's disease, highlighting the potential involvement of hIAPP in AD pathology. Together, these findings offer novel insights into AD pathogenesis and routes for constructing animal models. [ABSTRACT FROM AUTHOR]

Five types of round cell tumors found in dogs are mast cell tumors (MCT), lymphoma, plasma cell tumors, histiocytoma, and transmissible venereal tumors (TVT). This study focuses on the occurrence and cytopathology of these tumors in dogs of Meerut, Uttar Pradesh (India), spanning the period from 2018 to 2022. A total of 147 samples were gathered from different sites of dogs, notably 95 samples from vaginal specimens, 24 from nodular skin swellings, 7 samples from penile growths, 5 from lymph nodes, and 16 were from various skin lesions. The analysis of these samples revealed 4 cases of lymphoma, 3 cases of MCT, and 28 cases of TVT. In lymphoma, one case was identified as cutaneous lymphoma, while three cases were associated with lymph nodes. Cutaneous lymphoma exhibited numerous small and medium-sized lymphocytes. Lymph node samples exhibited a substantial presence of large-sized and medium-sized lymphocytes. TVT emerged as the most prevalent round cell tumor, observed in both genital and extragenital forms. Extragenital TVT predominantly affected the skin. In mast cell tumors, cells demonstrated round characteristics, with a notable granules in the cytoplasm and infiltration of eosinophils. Minimal anisocytosis and anisokaryosis, coupled with a high nuclear-to-cytoplasmic ratio, were evident in these tumors. [ABSTRACT FROM AUTHOR]

Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood–brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND. [ABSTRACT FROM AUTHOR]

Objective: Thyroid fine‐needle aspiration (FNA) is a principal diagnostic procedure for thyroid nodules. A specific cytomorphological structure, known as the thyroid spherule, is often seen in FNA specimens. The clinical significance of these spherules in terms of diagnosis and prevalence remains largely unexplored. Methods: We performed a retrospective study on 310 thyroid FNA specimens and categorized them according to the Bethesda System for Reporting Thyroid Cytopathology. The presence, size and number of thyroid spherules in each specimen were examined and these data were subsequently correlated with the clinicopathological features. Results: Thyroid spherules were almost exclusively detected in benign cases, comprising 7.6% of all benign diagnoses. The average diameter of spherules in benign cases was 84.9 μm. Benign cases and cases with atypia of undetermined significance cases primarily exhibited low cellularity, while follicular neoplasms and malignant cases typically showed moderate to high cellularity. In the subgroup of FNA cases with moderate to high cellularity, spherules were identified in 12 (20%) of 59 benign FNA cases. Within this group, the sensitivity and specificity of thyroid spherules for detecting benign FNA cases were 20% and 100%, respectively. Conclusions: Our results suggest that the presence of thyroid spherules in FNA specimens can serve as a highly specific marker for benign thyroid conditions. The prevalence of spherule detection is strongly influenced by the cellularity. In cases with moderate to high cellularity, the identification of spherules can assist the cytopathologists in diagnosing thyroid FNA cases as benign. [ABSTRACT FROM AUTHOR]

Objective: There is beauty in cytopathology. That beauty and art can be transmitted and shared through fun images on social media. Methods: As social media becomes more popular, pathologists and related professionals have started to share the images that they capture at work on their profiles, tagging them with the hashtag #Pathart. #Pathart hashtag unites two concepts innately related: Pathology and art. Results: When groups of pathologists share concurring ideas, the result is an explosion of creativity that spreads even to new professionals and students. In addition, it attracts the attention of people, dedicated to other subjects such as journalism, who, with their interactions, give visibility to our field. This helps counteract the stereotypes and gives people a better understanding of what we do and why it is important. Therefore, the more pathologists and related professionals meet and interact with each other, the better. Conclusions: #Pathart images raise great interest among professionals, which contributes to the creation of a united and strong community of pathologists some of whom are dedicated to cytology. Interaction and professional collaboration between these professionals can positively contribute to disseminating scientific content and creating work/research groups. This might have an impact, both direct and indirect, on improving the quality of diagnoses and treatments in our patients. [ABSTRACT FROM AUTHOR]

Cytological specimens play a pivotal role in head and neck nodule/mass work up and diagnoses. The specimens´ importance has grown with the onset of personalized medicine and the routine use of molecular markers in the diagnostic work up. The Updates in Head and Neck Cytopathology Short Course ran during the 35th European Congress of Pathology held in Dublin, Ireland, in 2023 and brought together experts in cytopathology, pathology, and related fields to share their expertise and experience in the field of head and neck cytopathology and its future directions. Topics such as a one‐stop clinic, the Milan System for Reporting Salivary Gland Cytopathology, next generation sequencing, and human papilloma virus detection in the head and neck area were covered during the short course. These topics are briefly summarized in the present review. [ABSTRACT FROM AUTHOR]

Recently, significant advances in the molecular characterization of salivary gland neoplasms have facilitated the classification and diagnosis of specific diagnostic entities. In the highly challenging diagnostic scenario of salivary malignancies, molecular testing is increasingly being adopted in routine practice to refine the cytological diagnosis of salivary lesions. Here, we reviewed the most recent evidence in the field of salivary glands molecular cytopathology. [ABSTRACT FROM AUTHOR]

Background: Molecular testing (MT) has become standard practice to more accurately rule out malignancy in indeterminate Bethesda III (BIII) thyroid lesions. We sought to assess the adoption of this technology and its impact on cytology reporting, malignancy yield, and rates of surgery across community and academic sites affiliated with a tertiary medical center. Methods: We performed a retrospective cross-sectional study including all fine-needle aspirations (FNAs) analyzed at our institution from 2017 to 2021. We analyzed trends in MT utilization by platform and by community or academic site. We compared BIII call rates, MT utilization rates, rates of subsequent surgery, and malignancy yield on final pathology before and after MT became readily available using chi-square analysis and linear regression. Results: A total of 8960 FNAs were analyzed at our institution from 2017 to 2021. There was broad adoption of MT across both community and academic sites. There was a significant increase in both the BIII rate and the utilization of MT between the pre- and post-MT periods (p < 0.001 and p < 0.001). There was no significant change in the the malignancy yield on final pathology (57.1% vs. 50.0%, p = 0.347), while the positive predictive value of MT decreased from 85% to 50% (p = 0.008 [confidence interval 9.5–52.5% decrease]). Conclusions: The use of MT increased across the institution over the study period, with the largest increase seen after a dedicated pass for MT was routinely collected. This increased availability of MT may have led to an unintended increase in the rates of BIII lesions, MT utilization, and surgery for benign nodules. Physicians who use MT should be aware of potential consequences of its adoption to appropriately counsel patients. [ABSTRACT FROM AUTHOR]

Six previously undescribed prenylated C6-C3 derivatives (1-6) were isolated from the root of Illicium ternstroemioides A. C. Smith. Their structures were elucidated based on extensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of 1-3 were determined using electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD). Compound 3 exhibited weak activity against Coxsackievirus B3 with an IC50 value of 33.3 µM, and compound 5 exhibited more potent activity against Coxsackievirus B3 with an IC50 value of 6.4 µM. [ABSTRACT FROM AUTHOR]

Nondestructive pathology based on three-dimensional (3D) optical microscopy holds promise as a complement to traditional destructive hematoxylin and eosin (H&E) stained slide-based pathology by providing cellular information in high throughput manner. However, conventional techniques provided superficial information only due to shallow imaging depths. Herein, we developed open-top two-photon light sheet microscopy (OT-TP-LSM) for intraoperative 3D pathology. An extended depth of field two-photon excitation light sheet was generated by scanning a nondiffractive Bessel beam, and selective planar imaging was conducted with cameras at 400 frames/s max during the lateral translation of tissue specimens. Intrinsic second harmonic generation was collected for additional extracellular matrix (ECM) visualization. OT-TP-LSM was tested in various human cancer specimens including skin, pancreas, and prostate. High imaging depths were achieved owing to long excitation wavelengths and long wavelength fluorophores. 3D visualization of both cells and ECM enhanced the ability of cancer detection. Furthermore, an unsupervised deep learning network was employed for the style transfer of OT-TP-LSM images to virtual H&E images. The virtual H&E images exhibited comparable histological characteristics to real ones. OT-TP-LSM may have the potential for histopathological examination in surgical and biopsy applications by rapidly providing 3D information. [ABSTRACT FROM AUTHOR]

The withdrawal of the iView detection system (iV) forced many cytopathology laboratories, including ours, to substitute immunocytochemical (ICC) staining protocols for routine practice with other detection systems. Our objective was to optimize, validate, and implement ICC protocols using OptiView (OV) and EnVision FLEX (EnV) detection systems, comparing the results with those obtained using iV. Residual cytologic samples with known diagnoses were used, testing antibodies for the ten most common markers in routine cytopathology diagnostics (calretinin, Ber-EP4, MOC-31, CKAE1/AE3, CK5/6, CD68, LCA, desmin, HBME-1, and WT1). Different staining parameters were tested using OV on BenchMark ULTRA and EnV on Dako Omnis immunostainer, respectively. Optimal staining protocols were then selected and validated on 10 positive and 10 negative cases. The staining results were compared with iV protocols through evaluation of UK NEQAS and internal scores. The optimal staining protocols with OV and EnV demonstrated similar or superior results compared to the existing iV protocols, with slightly stronger intensity regarding positive cells. We have successfully established and validated optimal ICC staining protocols for commonly used markers in routine cytopathology practice. These protocols may benefit other laboratories using similar staining platforms. However, the challenge regarding standardizing ICC protocols across different cytopathology laboratories remains unresolved. [ABSTRACT FROM AUTHOR]

Fine‐needle aspiration cytology (FNAC) is a versatile diagnostic procedure uniquely suited for tissue biopsy of breast carcinomas and axillary metastases and/or recurrences. With the expanding treatment options and accompanying theragnostic tests, it is crucial to recognize the developments on ancillary testing and digital cytopathology techniques related to aspiration cytology of metastatic breast carcinoma. In this review, we aim to summarize and update the evidence of immunocytochemistry, for the detection of carcinoma cells (epithelial markers), confirmation of breast primary (breast‐specific markers), assessment of surrogate immunostains (hormone receptors, ki‐67 proliferative index and HER2) and theragnostic biomarkers, with discussion on potential diagnostic pitfalls, followed by the application of molecular tests, and digital cytopathologic techniques for assessing metastatic breast carcinoma in cytology. [ABSTRACT FROM AUTHOR]

Objective: The three‐tier grading scheme described in "The Papanicolaou Society of Cytopathology (PSC) System for reporting Pancreaticobiliary Cytopathology" (TPSCRPBC) which remained unchanged following the WHO Reporting System for Pancreaticobiliary Cytopathology (WRPBC) was evaluated on pancreatic adenocarcinomas (PACs) reported on endoscopic ultrasound‐guided fine needle aspiration cytology (EUS‐FNAC). Methods: The Papanicolaou and May Grunwald Giemsa‐stained smears from 116 cases of PACs were graded using the three‐tier grading scheme laid down by TPSCRPBC/WRPBC. Cases exhibiting multiple grades were assigned primary, secondary and tertiary grades. Each case was assigned a grade score, either by adding the primary and secondary grades, by adding the primary and tertiary grades when the tertiary grade was 3 or by doubling the grade when only one grade existed. Necrosis was estimated semi‐quantitatively. The inter‐observer reproducibility in grading was evaluated using Kappa and Kendall's tau‐c. Correlations between the various grades, the stage of the tumour and the amount of necrosis were assessed using Spearman rho and Kendall's tau‐b. Results: 31.89% of cases showed one grade, and 68.11% showed at least two grades. 16.38% showed three grades. The two commonest grade scores were 3 and 5. The inter‐observer reproducibility for grading and grade scoring was satisfactory. A positive correlation was noted between the grades and the amount of necrosis. No significant correlation was found between the grades, grade scores and the stage of the tumours. Conclusions: The TPSCRPBC/WRPBC grading scheme can be suitably applied to PACs with good inter‐observer reproducibility. Cases often show multiple grades in the same tumour. [ABSTRACT FROM AUTHOR]

Immunotherapy has become a promising cancer treatment in the past decade, and IHC is the most commonly used testing method for PDL‐1/PD1 evaluation. In general, PD‐L1 assays can be performed on both FFPE specimens and cytological samples. However, their use on smears is not yet well‐established or validated. Nowadays, digital images and advanced algorithms can aid in interpreting PD‐L1 in cytological samples. Understanding the immune environment of non‐small cell lung cancer (NSCLC) is critical in developing successful anticancer immunotherapies. The use of a multiplexed immunofluorescence (mIF) assay on cytological samples obtained through minimally invasive methods appears to be a viable option for investigating the immune environment of NSCLC. This review aims to briefly summarize the knowledge of the role of cytopathology in the analysis of PD‐L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting. [ABSTRACT FROM AUTHOR]

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. The second edition of the Milan System for Reporting Salivary Gland Cytopathology, 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, updates in nomenclature and a guide to the practical application of the latest ancillary markers for the diagnosis of selected salivary gland fine‐needle aspiration cases. [ABSTRACT FROM AUTHOR]

Until a few decades ago, most of our knowledge of RNA transcription products was focused on protein-coding sequences, which were later determined to make up the smallest portion of the mammalian genome. Since 2002, we have learnt a great deal about the intriguing world of non-coding RNAs (ncRNAs), mainly due to the rapid development of bioinformatic tools and next-generation sequencing (NGS) platforms. Moreover, interest in non-human ncRNAs and their functions has increased as a result of these technologies and the accessibility of complete genome sequences of species ranging from Archaea to primates. Despite not producing proteins, ncRNAs constitute a vast family of RNA molecules that serve a number of regulatory roles and are essential for cellular physiology and pathology. This review focuses on a subgroup of human ncRNAs, namely mtDNA-encoded long non-coding RNAs (mt-lncRNAs), which are transcribed from the mitochondrial genome and whose disparate localisations and functions are linked as much to mitochondrial metabolism as to cellular physiology and pathology. [ABSTRACT FROM AUTHOR]

Background: The thyroid gland is responsible for various functions, but it is susceptible to pathologies. The gold standard for preliminarily diagnosing thyroid abnormalities is fine-needle aspiration cytology (FNAC), although it has some limitations; thus, postoperative histopathological examination confirms the diagnosis. The aim of the present study was to compare preoperative FNAC results with postoperative histopathological examination. Methods: This study is a retrospective study based on FNAC and postoperative histopathology examination, which were compared and analyzed. Results: This study included 344 patients between 18 and 86 years old (mean age: 53.06 ± 13.89), comprising 274 females and 70 males (mean ages 52.72 ± 13.86 and 54.39 ± 14.05, respectively) with a 3.9:1 female-to-male ratio. Statistical significance between the FNAC and histopathology results was observed (p = 0.0000), and 86 (25.00%) patients were found to have been diagnosed incorrectly based on FNAC. The sensitivity of FNAC was 92.31%, and its specificity was 82.08%, with positive and negative predictive values of 68.57% and 96.08%, respectively. Conclusions: Due to many factors, FNAC may lead to over- or under-diagnosis, increasing the chances of complications associated with the selected treatment. However, we do not have any other more accurate tools; therefore, FNAC should still remain as the gold standard of preliminary examination. [ABSTRACT FROM AUTHOR]

Background: The Bethesda System for Reporting Thyroid Cytopathology is a commonly used classification for fine needle aspiration (FNA) cytology of suspicious thyroid nodules. The risk of malignancy (ROM) for each category has recently been analyzed in three international databases. This paper compares the diagnostic performance of the Bethesda classification in a high‐volume referral center in Belgium. Methods: All consecutive thyroid procedures were registered in a prospective database from January 2010 till August 2022. Patient and surgical characteristics, preoperative Bethesda categories, and postoperative pathology results were analyzed. Results: Out of 2219 consecutive thyroid procedures, 1226 patients underwent preoperative FNA. Papillary thyroid cancer was the most prevalent malignancy (N = 119, 70.4%), followed by follicular (N = 17, 10.1%) and medullary thyroid cancer (N = 15, 8.9%). Micropapillary thyroid cancer was incidentally found in 46 (3.8%) patients. Bethesda categories I, II, III, IV, V, and VI, respectively, represented 250 (20.4%; ROM 4.4%), 546 (44.5%; ROM 3.8%), 96 (7.8%; ROM 20.8%), 231 (18.8%; ROM 15.2%), 62 (5.1%; ROM 72.6%), and 41 (3.3%; ROM 90.2%) patients. Overall ROM was 13.8%. An negative predictive value (NPV) of 96.2% was found. Overall specificity was 64.2% with a positive predictive value (PPV) of 31.9%. Diagnostic accuracy was 67.8%. Compared to international databases (CESQIP, EUROCRINE, and UKRETS), ROM in this study appeared lower for Bethesda category IV (15.2 vs. 26.7% and p = 0.612). Conclusion: Despite being validated in numerous studies, ROM based on preoperative FNA cytology classified according to the Bethesda classification may vary among surgical centers and countries as this study reveals a higher NPV and lower PPV. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has recently published a new lung cytopathology reporting system, which simplifies the diagnostic categories into a five-tier system without subcategorization. The system encourages the use of ancillary diagnostic tests for better categorization of specimens and further management. This correspondence provides a brief outline of the lung reporting system, including standardized nomenclature and the use of terminologies harmonizing with the WHO Blue Book. The system includes categories such as non-diagnostic, benign, atypical, suspicious for malignancy, and malignant, with corresponding risk-based management strategies for clinicians. Ancillary techniques like immunocytochemistry can assist in upgrading the category from suspicious for malignancy to malignancy. The system aims to provide universal simplified criteria for categorizing lung cytology samples and their management options. [Extracted from the article]

Background: Fine-Needle Aspiration Cytology (FNAC) is a valuable, minimally invasive diagnostic tool for discerning benign and malignant thyroid lesions. In the realm of thyroid cytopathology, both the traditional approach and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) are widely utilized for diagnosing and categorizing these lesions. Aims and Objectives: This study aims to classify thyroid cytology smears using both the conventional method and the Bethesda system and to compare their findings with histopathological diagnoses. Method and Materials: A hospital-based cross-sectional study was conducted over one year, spanning from February 1, 2022, to January 31, 2023. We included 191 cases of FNAC thyroid lesions and categorized them following the guidelines of both the conventional system and the Bethesda system for reporting thyroid cytopathology. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for both systems were calculated, with histopathology serving as the gold standard for comparison. Furthermore, we calculated the Risk of Malignancy (ROM) for each category within the Bethesda system. Results: The Bethesda system exhibited a notably high sensitivity of 83.33%, surpassing the conventional method's sensitivity of 50%, while both systems shared the same specificity of 90%. The diagnostic accuracy of the Bethesda system, at 89.13%, outperformed that of the conventional method, which stood at 84.78%. Conclusion: This study demonstrates a strong positive correlation with histopathology, indicating high sensitivity, specificity, and accuracy when employing TBSRTC, in contrast to the conventional method. [ABSTRACT FROM AUTHOR]

Peptidyl-prolyl isomerase NIMA-interacting 1 (PIN1) plays a crucial regulatory role in cells, and it is the only enzyme capable of selectively binding to phosphorylated proline-directed serine/threonine (pSer/Thr-Pro) residues in target proteins and catalyzing their isomerization. The change in the conformational status of the protein, transitioning between cis and trans, affects its three-dimensional structure and, therefore, alters its function and stability. In this manner, PIN1 plays a role in the development of several human pathologies by regulating essential proteins. In cancer, the enzymatic activity of PIN1 induces conformational changes in essential proteins, promoting oncogenic processes and fostering aggressive tumor characteristics and resistance to chemotherapies. Moreover, the effects of PIN1 on viral infections are notable, as it interacts with viral proteins, enhancing their replication and infection mechanisms. In addition, PIN1 participates in autoimmune, cardiovascular, metabolic, neurodegenerative diseases and osteoporosis. These diverse functions render PIN1 as an attractive therapeutic target, leading to the development of PIN1 inhibitors. The critical role of PIN1 in human pathology is further underscored by its relevance to various diseases, rendering it a potential nexus for novel interventions in human pathologies. [ABSTRACT FROM AUTHOR]

The International System for Reporting Serous Fluid Cytology (TIS) has been proposed by an expert working team composed of the International Academy of Cytology and the American Society of Cytopathology, following an international survey. Since its introduction, the TIS has gained worldwide acceptance, and this review aims to assess its global impact. A literature search revealed 25 studies which have presented data on the impact of the TIS. Most of them provide data, including risk of malignancy (ROM) for each diagnostic category, separately for pleural, peritoneal and pericardial effusions, while a few do not separate them. A few studies focus on specific diagnoses like mesothelioma on specific types of fluids or more specific issues like the optimal fluid volume for cytology or interobserver variability. A synopsis of the data from the literature search is presented in four tables. The ROM assessment is discussed, as well as interobserver variability and the use of ancillary diagnostic immunochemistry. In conclusion, our review of the published data suggests that the TIS is a valid classification scheme that has been widely accepted by pathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management. [ABSTRACT FROM AUTHOR]

The guidelines for the workup of thyroid nodules have been established in adult populations and secondarily applied to paediatric populations. In particular, The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is commonly applied to both adult and paediatric thyroid nodules. However, as paediatric nodules have distinct molecular drivers and behavioural trajectories, there is renewed interest in diagnostic and management strategies that are paediatric specific. Here, we review key differences between paediatric and adult thyroid cancer and recent literature evaluating the use of TBSRTC in paediatric populations. [ABSTRACT FROM AUTHOR]

Fine needle aspiration biopsy (FNAB) is a diagnostic modality for the evaluation of suspicious soft tissue masses. Despite its reasonable sensitivity, specificity and positive predictive value in differentiating benign from malignant neoplasms, the exact subtyping of the primary soft tissue tumours can be challenging. Certain tumours constitute "pitfalls" and add to the diagnostic challenge. This review provides a detailed account of the diagnostic challenges in soft tissue cytopathology, including pitfalls and, more importantly, the ways to overcome these challenges by integrating clinical details, key cytomorphological features and judicious application of ancillary techniques. [ABSTRACT FROM AUTHOR]

Introduction: Imaging techniques in evaluating palpable breast masses is an initial point in multidisciplinary approach. Ultrasound is a cost-effective technique and is useful in the detection of breast masses as well as in the differentiation of masses seen on mammography as solid or cystic. This study was done to evaluate palpable breast masses using Breast Imaging-Reporting and Data System (BI-RADS) and compare it with cytopathology which is gold standard categorized based on The International Academy of Cytology Yokohama System (IAC) for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology. Material and methods: A longitudinal study was done in 100 adult female patients with palpable breast mass attending a tertiary care center during May 2022 to May 2023. After obtaining ethical committee clearance and patient's informed consent, study was done. Convenient sampling method was executed to enroll the patients in to study. Palpable breast masses were examined for benign and malignant features using ultrasound (BIRADS) and cytopathology (IAC Yokohama system). Statistical analysis done with chi-square test with P<0.05. Sensitivity, specificity, positive and negative predictive value as well as accuracy of ultrasound were calculated compared with cytopathology. Results: Mean ± SD of age was 32.5± 23.3 with a range of 18-65 years. The IAC Cytopathology showed 16% patients have malignant lesions (which is C5) and 84% patients have benign lesions (which is C2,C3,C4). Ultrasound diagnosed 97.7% of malignant lesions and 94% of benign lesions with a significant association between BI-RADS and IAC Yokohama system (X²-58.1, p ≤ 0.001). Diagnostic accuracy of ultrasound was 93.1% at 95% CI (83.4% to 95.76%). Conclusions: Breast neoplasms were 16% and benign were 84%, Sensitivity and specificity of ultrasound in diagnosing palpable breast mass at 95% CI was 87.5% (61.65% to 98.45%) and 94.05% (86.65% to 98.04%) with accuracy of 93.1% at 95% CI (83.4% to 95.76%). [ABSTRACT FROM AUTHOR]

Background: The diverse morphology and varying reporting terminology of salivary gland lesions present several challenges to pathologists and clinicians when making a cytological diagnosis. The Milan system for reporting salivary gland cytopathology was introduced as a solution to address these shortcomings. The objective of this study was to classify cases of salivary gland pathology that were diagnosed through histopathological examination using the Milan system, and to establish a correlation between the Milan system and the histopathological diagnosis. The objective of the study is to evaluate the effectiveness of the Milan system and the likelihood of malignancy in each category. Materials and Methods: This study is a retrospective analysis that spanned a period of eighteen months. The study encompassed all instances of salivary gland pathology with fine-needle aspiration cytology findings recorded between March 2021 and September 2022. These cases were subsequently categorized based on the Milan system. Histopathologyfollow-up was conducted in 58 cases, and the risk of malignancy was assessed. The metrics of sensitivity, specificity, positive predictive value, and negative predictive value were computed by employing histopathological diagnosis as the reference standard. Results: A total of 77 cytology slides were examined, and the Milan system was utilized for evaluation. Follow-up histopathology was obtained in 58 cases. The distribution of cases across different categories was as follows: nondiagnostic (9.27%), nonneoplastic (4.64%), atypia of undetermined significance (3.97%), benign neoplasm (23.84%), neoplasm of uncertain malignant potential (8.61%), suspicious for malignancy (11.92%), and malignant (37.75%). The Milan system demonstrated a sensitivity of 94.20%, specificity of 96.00%, positive predictive value of 98.48%, and negative predictive value of 85.71%. Conclusion: The Milan system demonstrates superior sensitivity and specificity when compared to histopathology. This system is beneficial for both pathologists and clinicians as it ensures consistency in reporting terminology by categorizing salivary gland lesions into subcategories that have prognostic significance. [ABSTRACT FROM AUTHOR]

Objectives: To correlate the screening ability of ultrasound-based TIRADS with the FNAC-based Bethesda system when the latter is kept as a gold standard. Material and methods: A cross-sectional study was conducted in the Histopathology department, Rehman Medical Institute, Peshawar 15th June 2022-14th June 2023. A total of 363 patients from any age group of either gender diagnosed with thyroid nodules were included in the trial. All the participants underwent ultrasound followed by ultrasound-guided fine needle aspiration of thyroid nodules. TIRADS and Bethesda grading was done for each participant. Demographics and grading scores were recorded. Keeping Bethesda scoring as gold standard diagnostic performance of TIRADS grading was calculated. Results: Mean age of the patients was 46.68 ± 12.28 years with a female-to-male ratio of 2.3:1. TIRADS grading revealed 210 (69.8%) from TIRADS 2 while 70(82.4%), 12(50%), and 09(23.7%) patients were from TIRADS 3, 4 and 5 categories respectively. Bethesda grades were 301(82.9%), 21(5.8%), 09(2.5%), 28(7.7%), and 04(1.1%) from Bethesda 2, 3, 4, 5, and 6 categories respectively. The sensitivity of the TIRADS was 93.8%, specificity 89.1%, positive predictive value 45%, negative predictive value 99.3%, and a diagnostic accuracy of 89.5%. Conclusion: TIRADS grading has a high diagnostic ability when Bethesda scoring is kept as the gold standard. It can be used effectively in segregating benign from malignant nodules and is recommended for screening patients presenting with thyroid nodules. [ABSTRACT FROM AUTHOR]

Background Fine needle aspiration cytology of salivary glands (FNAC) has become a most accepted method of evaluating salivary gland tumors preoperatively. It has many pitfalls, to overcome this the Milan System for reporting Salivary gland Cytopathology (MSRGC) was introduced. The Milan System for reporting Salivary gland Cytopathology (MSRGC) represents a standardized, evidence based reporting system for salivary gland lesions. The present study was undertaken to study and categorize various salivary gland lesion according to MSRSGC and do histological correlation. Methods Present study is a retrospective study done over a period of four year duration. Cytological slides were retrieved and reviewed and categorised into six categories according to MSRGC. Histopathological correlation was done wherever possible. Results A total of 273 cases were studied, males were commonly affected compared to females. Percentage of cases in each category as follows: nondiagnostic-2.93%, Nonneoplastic-58.6%, AUS-0%, benign 34.4%, suspicious of uncertain malignant potential-0.73%, suspicious of malignancy-1.46% and malignant in 1.83% cases. Surgical follow up was available in 85 cases, out of which 96.5% (82 cases) showed concordance and 3 cases showed discordance. Sensitivity, specificity, positive predictive value and negative predictive value of salivary gland lesions with the application of Milan system was 66.7%,100%, 100% and 96.25%. ROM was calculated for each category which is category I-0, category II-56%, category III-0, category Iva-2.63%, category IVb-50%, category V & VI-100%. Conclusion MSRSGC on FNA of salivary gland lesion has standardized the reporting method to classify the lesions, facilitating risk stratification and deciding the treatment protocol. [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation is a major mechanism for organizing macromolecules, particularly proteins with intrinsically disordered regions, in compartments not limited by a membrane or a scaffold. The cell can therefore be perceived as a complex emulsion containing many of these membraneless organelles, also referred to as biomolecular condensates, together with numerous membranebound organelles. It is currently unclear how such a complex concoction operates to allow for intracellular trafficking, signaling and metabolic processes to occur with high spatiotemporal precision. Based on experimental observations of synaptic vesicle condensates - a membraneless organelle that is in fact packed with membranes - we present here the framework of dipping contacts: a novel type of contact site between membraneless organelles and membranes. In this Hypothesis, we propose that our framework of dipping contacts can serve as a foundation to investigate the interface that couples the diffusion and material properties of condensates to biochemical processes occurring in membranes. The identity and regulation of this interface is especially critical in the case of neurodegenerative diseases, where aberrant inclusions of misfolded proteins and damaged organelles underlie cellular pathology. [ABSTRACT FROM AUTHOR]

Background: This prospective study assesses the use of rapid remote online cytological evaluation for diagnosing endoscopical achieved biopsies. It focuses on its effectiveness in identifying benign and malignant conditions using digital image processing. Methods: The study was conducted between April 2021 and September 2022 and involved analyses of 314 Rapid Remote Online Cytological Evaluations in total (154 imprint cytologies, 143 fine needle aspirations and 17 brush cytologies) performed on 239 patients at the LungenClinic Grosshansdorf. During on-site evaluation via telecytology, the time requirement was recorded and the findings were compared with the cyto-/histological and final diagnoses. Results: By means of rapid remote online evaluation, findings of 86 cytological benign, 190 malignant and 38 unclear diagnoses were recorded (Ø assessment time, 100 s; range, 11–370 s). In 27 of the 37 specimens with unclear diagnoses, the final findings were malignant tumours and only 6 were benign changes. The diagnosis of another 4 of these 37 findings remained unclear. Excluding these 37 specimens, rapid remote online evaluation achieved a sensitivity of 90.5% with a specificity of 98.5% and a correct classification rate of 92.4% with regard to the final diagnosis of all cases. As expected, an increase in the sensitivity rate for the cytological detection of malignant tumours (76.1% vs. 92.5%) was found especially in fine-needle aspirations. Conclusions: Rapid remote online analysis allows the fast quantitative and qualitative evaluation of clinically obtained cytological specimens. With a correct classification rate of more than 93%, sampling deficiencies can be corrected promptly and diagnostic and therapeutic approaches can be derived. [ABSTRACT FROM AUTHOR]

Objective: Despite an increase in thyroid fine needle aspiration (FNA) and advances in whole slide imaging (WSI) adoption, digital pathology is still considered inadequate for primary diagnosis of these cases. Herein, we aim to validate the utility of WSI in thyroid FNAs employing the Delphi method strategy. Methods: A panel of experts from seven reference cytology centres was recruited. The study consisted of two consecutive rounds: (1) an open‐ended, free‐response questionnaire generating a list of survey items; and (2) a consensus analysis of 80 selected shared WSIs from 80 cases by six investigators answering six morphological questions utilising a 1 to 5 Likert scale. Results: High consensus was achieved for all parameters, with an overall average score of 4.27. The broad majority of items (84%) were ranked either 4 or 5 by each physician. Two badly scanned cases were responsible for more than half of the low‐ranked (≤2) values (57%). Good to excellent (≥3) diagnostic confidence was reached in more than 95.2% of cases. For most cases (78%) WSI assessment was not limited by technical issues linked to the image acquisition process. Conclusion: This systematic Delphi study indicates broad consensus among participating physicians on the application of DP to thyroid cytopathology, supporting expert opinion that WSI is reliable and safe for primary diagnostic purposes. [ABSTRACT FROM AUTHOR]

Background: Bone fine needle aspiration (FNA) presents several diagnostic challenges including limited sample material, reduced ability to assess the architecture, and lack of a standardised reporting system. The aim of our study is to present our experience regarding bone FNA. Methods: We performed a 6‐year retrospective search of our archives to identify all FNA cases of bone lesions. Available data regarding patients' demographics, cytopathology, and surgical pathology were recorded. The FNA cases were then grouped into five categories (atypical, neoplasm‐benign, neoplasm of unknown malignant potential, suspicious for malignancy, and malignant) and the risk of malignancy (ROM) was calculated. Results: A total of 341 FNA cases performed in 337 patients (M = 173, F = 164; mean age = 57.2 years) were identified. The iliac crest was the most commonly biopsied site (n = 134). The adequacy of bone FNA was 77.4%. The sensitivity and specificity regarding the nature of the lesion were 96.5% and 100%, respectively. The overall diagnostic accuracy of bone FNA was 77%. The accuracy of bone FNA for non‐metastatic bone lesions including non‐neoplastic lesions was 74%, while the diagnostic accuracy of bone FNA for a metastatic disease was 83.5%. The diagnostic accuracy for primary neoplastic lesions was 70%. The frequency (n,%) of cytomorphological categories were as follows: atypical (30, 8.8%); neoplasm‐benign (6, 1.8%); neoplasm of unknown malignant potential (18, 5.3%); suspicious for malignancy (4, 1.2%); and malignant (145, 42.5%). The ROM in these categories was respectively as follows: 51.7%, 0%, 46.7%, 100%, and 99.1%. Conclusion: FNA is a sensitive and specific technique for the diagnosis of bone lesions. In most instances, an accurate diagnosis can be achieved if adequate material, ancillary studies, and radiological correlation are available. [ABSTRACT FROM AUTHOR]

Introduction: Benign sebaceous salivary gland (SG) neoplasms represent approximately 0.2% of all salivary gland neoplasms. Not only are fine needle aspiration (FNA) biopsy findings of sebaceous adenoma (SA) and sebaceous lymphadenoma (SLA) limited, but their findings are also rarely compared with one another. Materials and Methods: Our cytopathology files were searched for examples of benign sebaceous SG neoplasms with concomitant histopathological verification. FNA biopsy and cell collection were performed using standard technique. Results: One case each of parotid SA and parotid SLA showed markedly dissimilar cytomorphology. The SA case was composed of a repetitive population of profusely multivacuolated polygonal cells with single and multiple nuclei, and was specifically recognised cytologically as a sebaceous neoplasm due to its characteristic cytoplasmic vacuolisation. The SLA case, however, was characterised by smears filled primarily with lymphocytes and only scant widely scattered basaloid cell clusters. A non‐specific diagnosis of basaloid neoplasm was rendered. In retrospect, recognition of sebaceous differentiation was limited to rare cell groups. Conclusion: Though nominally, epidemiologically, and to a degree histopathologically analogous, the cytopathology of SA and SLA are markedly dissimilar, reflecting the dominant cell component in each. With FNA biopsy, a specific interpretation is more likely for SA than SLA due to the overwhelming obscuring lymphoid population in the latter. [ABSTRACT FROM AUTHOR]

Background: The age‐standardised incidence rate of thyroid cancer in India is 1 in 416 in the general population. This increased incidence has mainly been attributed to improved detection methods for small thyroid lesions. Two such methods are the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Aims and Objectives: To study the correlation between ACR TIRADS and TBSRTC, and between each system and the final histopathological report. Materials and Methods: Thyroid cytopathology cases were retrieved for the period January 2019 to July 2022. For each case, the TIRADS score and Bethesda category were noted. Histopathology specimens were also traced. Results: The study comprised 1100 cases, with 955 female and 145 male patients (M:F = 1:6.59), and ages ranging between 7 and 85 years. The TIRADS scoring was available for 1036 cases. Histopathology was available for 231 cases. There was a significant correlation between TIRADS and TBSRTC, with a p‐value of 0.000 and a substantial Kappa agreement of 0.688. Both TIRADS and TBSRTC also had significant correlations with the histopathology data, with a p‐value of 0.000 for each. The sensitivity values for TBSRTC and TIRADS were 69.4% and 65.8%; specificity, 99.3% and 96.5%; positive predictive value (PPV), 98.3% and 91.8%; and negative predictive value (NPV) 84.7% and 84.4%, respectively. The risk of malignancy (ROM) was also calculated and was found to be high, especially for TBSRTC II, III, IV and V (11.3%, 20%, 61.5%, 97.4% respectively) and TIRADS 2 and 3 (10.3% and 29.6% respectively). Conclusion: The TIRADS and TBSRTC systems of categorisation of thyroid lesions are concordant and could help improve the overall survival rate of patients with thyroid malignancies. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quickly spread worldwide and led to over 581 million confirmed cases and over 6 million deaths as 1 August 2022. The binding of the viral surface spike protein to the human angiotensinconverting enzyme 2 (ACE2) receptor is the primary mechanism of SARS-CoV-2 infection. Not only highly expressed in the lung, ACE2 is also widely distributed in the heart, mainly in cardiomyocytes and pericytes. The strong association between COVID-19 and cardiovascular disease (CVD) has been demonstrated by increased clinical evidence. Preexisting CVD risk factors, including obesity, hypertension, and diabetes etc., increase susceptibility to COVID-19. In turn, COVID-19 exacerbates the progression of CVD, including myocardial damage, arrhythmia, acute myocarditis, heart failure, and thromboembolism. Moreover, cardiovascular risks post recovery and the vaccination-associated cardiovascular problems have become increasingly evident. To demonstrate the association between COVID-19 and CVD, this review detailly illustrated the impact of COVID-19 on different cells (cardiomyocytes, pericytes, endothelial cells, and fibroblasts) in myocardial tissue and provides an overview of the clinical manifestations of cardiovascular involvements in the pandemic. Finally, the issues related to myocardial injury post recovery, as well as vaccination-induced CVD, has also been emphasized. [ABSTRACT FROM AUTHOR]

This article discusses the development of a new reporting system for lymph node cytopathology by the World Health Organization (WHO). The system aims to use standardized nomenclature and terminology that aligns with the WHO Blue Book on hematolymphoid tumors. The article explains the process of collaboration between the International Academy of Cytology (IAC), the International Agency for Research on Cancer (IARC), and the WHO to create this system. It also provides an outline of the possible interpretation categories within the reporting system, including insufficient/inadequate/nondiagnostic, benign, atypical, suspicious for malignancy, and malignant. The authors believe that implementing this standardized reporting system will improve the quality of diagnostic assessment and communication between cytopathologists and clinicians. [Extracted from the article]

The high prevalence of oral potentially-malignant disorders exhibits diverse severity and risk of malignant transformation, which mandates a Point-of-Care diagnostic tool. Low patient compliance for biopsies underscores the need for minimally-invasive diagnosis. Oral cytology, an apt method, is not clinically applicable due to a lack of definitive diagnostic criteria and subjective interpretation. The primary objective of this study was to identify and evaluate the efficacy of biomarkers for cytology-based delineation of high-risk oral lesions. A comprehensive systematic review and meta-analysis of biomarkers recognized a panel of markers (n: 10) delineating dysplastic oral lesions. In this observational cross sectional study, immunohistochemical validation (n: 131) identified a four-marker panel, CD44, Cyclin D1, SNA-1, and MAA, with the best sensitivity (>75%; AUC>0.75) in delineating benign, hyperplasia, and mild-dysplasia (Low Risk Lesions; LRL) from moderate-severe dysplasia (High Grade Dysplasia: HGD) along with cancer. Independent validation by cytology (n: 133) showed that expression of SNA-1 and CD44 significantly delineate HGD and cancer with high sensitivity (>83%). Multiplex validation in another cohort (n: 138), integrated with a machine learning model incorporating clinical parameters, further improved the sensitivity and specificity (>88%). Additionally, image automation with SNA-1 profiled data set also provided a high sensitivity (sensitivity: 86%). In the present study, cytology with a two-marker panel, detecting aberrant glycosylation and a glycoprotein, provided efficient risk stratification of oral lesions. Our study indicated that use of a two-biomarker panel (CD44/SNA-1) integrated with clinical parameters or SNA-1 with automated image analysis (Sensitivity >85%) or multiplexed two-marker panel analysis (Sensitivity: >90%) provided efficient risk stratification of oral lesions, indicating the significance of biomarker-integrated cytopathology in the development of a Point-of-care assay. [ABSTRACT FROM AUTHOR]

Since the publication of the first edition in 2010, The Bethesda System for Reporting Thyroid Cytopathology has allowed cytopathologists to use a standardized, category-based reporting system for thyroid fine needle aspirations. The third edition builds on the success of the 2 earlier editions and offers several key updates. The most important is the assignment of a single name for each of the 6 diagnostic categories: (i) nondiagnostic; (ii) benign; (iii) atypia of undetermined significance; (iv) follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. Each of the categories has an implied risk of malignancy (ROM), which has been updated and refined based on data reported after the second edition. The third edition offers an average ROM for each category, in addition to the expected range of cancer risk. The atypia of undetermined significance subcategorization is simplified into 2 subgroups based on the implied ROM and molecular profiling. A discussion of pediatric thyroid disease has been added, and pediatric ROMs and management algorithms are discussed in the relevant sections. Nomenclature has been updated to align with the 2022 World Health Organization Classification of Thyroid Neoplasms. Two new chapters have been added: one that addresses the significant and expanded use of molecular and ancillary testing in thyroid cytopathology, and another that summarizes clinical perspectives and imaging findings in thyroid disease. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the impact of the COVID‐19 pandemic on cytopathology training at an international level. An anonymous online questionnaire was distributed by members of the international cytopathological community to medical practitioners in cytopathology. The survey explored perceived changes in cytology workload and workflow during the pandemic, and its effect on both non‐cervical and cervical cytology reporting and teaching. A total of 82 responses were received from seven countries. Approximately half of the respondents reported a decrease in the number and range of cytology cases during the pandemic. Nearly half (47%) saw a reduction in the opportunity to co‐report with consultants/attendings, and 72% of the respondents reported that their consultants/attendings were working remotely during the pandemic. Another 34% of the respondents were redeployed for 3 weeks to 1 year, with 96% stating that this period was only partially compensated for during their training, if at all. The pandemic negatively affected the opportunity to report cervical cytology, perform fine needle aspirations, and participate in multidisciplinary team meetings. Most respondents (69%) saw a decrease in the amount and quality (52%) of face‐to‐face departmental cytology teaching, whereas remote departmental teaching improved in amount (54%) and quality (49%). Almost half (49%) reported that cytology teaching in the regional, national, and international settings increased in both amount and quality. The pandemic catalysed many changes in cytopathology training, affecting the trainees' exposure to cases, the use of remote reporting, consultant/attending working practices, redeployment, and local as well as external teaching. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has had a global impact on the environment and economy and has affected hospital administration and patient behaviour. Since human‐to‐human coronavirus transmission occurs via droplets and physical contact, health care professionals are particularly vulnerable to contracting COVID‐19. Many cytopathology laboratories updated their workflow, established new standard biosafety protocols, and built digital pathology or telescope platforms to mitigate these risks and deal with the shortage of health care personnel. The COVID‐19 pandemic also disrupted medical education—all indoor training events, including conferences, multidisciplinary tumour boards, seminars, and microscope inspections were postponed. As a result, many laboratories now use new web‐based applications and platforms to maintain educational programs and multidisciplinary tumour boards. To comply with government directives, health care facilities postponed non‐emergency surgeries, reduced the number of routine medical examinations, restricted visitor numbers, and scaled back cancer screening activities, resulting in a sharp decline in cytopathology diagnoses, cancer screening specimens, and molecular testing for cancer. Subsequent misses or delays in the diagnosis and treatment of cancer were not uncommon. This review aims to provide comprehensive summaries of the consequences of the COVID‐19 pandemic for cytopathology, particularly in terms of cancer diagnosis, workload, human resources, and molecular testing. [ABSTRACT FROM AUTHOR]

Introduction: Pleomorphic dermal sarcoma (PDS) is an uncommon cutaneous mesenchymal neoplasm. It is cytomorphologically identical to atypical fibroxanthoma (AFX), but differs due to its invasion beyond the dermis. We undertook an examination of our experience with fine needle aspiration (FNA) biopsy cytology of PDS. Materials and Methods: Our cytopathology files were searched for examples of PDS with concomitant histopathological verification. FNA biopsy smears and cell collection were performed using standard techniques. Results: Seven cases of PDS were retrieved from four different patients (M:F, 1:1; age range: 63–88 years; mean age = 78 years). All patients (57%) presented with a primary tumour with one having an FNA biopsy of two local recurrences and a single distant metastasis. Five aspirates were from the extremities and two from the head/neck. Tumours ranged from 1.0 to 3.5 cm (mean, 2.2 cm). Specific cytological diagnoses were pleomorphic spindle/epithelioid sarcoma (3 cases), PDS (2), AFX (1), and atypical myofibroblastic lesion, query nodular fasciitis (1). Immunohistochemical (IHC) staining from FNA‐generated cell blocks in two cases showed non‐specific staining with vimentin in both cases; positive CD10, CD68, and INI‐1 staining in one case; and smooth muscle actin expression in the other. Multiple negative stains were performed in both of these cases to exclude malignant melanoma, carcinoma, and specific forms of sarcoma. Cytopathology consisted of a mixture of spindle, epithelioid, and bizarre pleomorphic cells. Conclusion: Coupled with ancillary IHC stains, FNA biopsy can help recognise PDS as a sarcomatous cutaneous neoplasm, but is unable to distinguish PDS from AFX. [ABSTRACT FROM AUTHOR]

The Covid‐19 pandemic and ongoing war in Ukraine caused unprecedented disruption in healthcare, including cytopathology activities. This paper elucidates the effect of two consecutive disasters—the COVID‐19 pandemic followed by the war—on cytopathology practice in Ukraine through a single‐centre retrospective study. Total testing volumes, geographic distribution, and indicators of laboratory operations were assessed during three periods of 3 months each: the first 3 months of the acute phase of the war (March‐May 2022, period 1); summer (June‐August 2022, period 2); and the fall (September‐November 2022, period 3, associated with massive attacks on the energy infrastructure in Ukraine). These data were compared with the corresponding periods in 2020, during the COVID‐19 pandemic, and in 2021, the post‐lockdown period. The ongoing war in Ukraine has caused a dramatic disruption in routine health maintenance and cytological practice. A net decline in both PAP testing and non‐gynaecological pathology was associated with a geographic redistribution of cytopathological testing, and an increase in the rate of abnormal sample reporting. Despite these challenges, cytopathology practice in Ukraine demonstrates resilience, allowing for maintaining the healthcare system and addressing the needs of the civil population during the war. The ongoing war in Ukraine heavily affected cytological practice. The decline in PAP testing during the early period of the war was associated with an increase in the abnormal sample rate. Further study of the war's impact on the cervical pathology rate and the health of the population in the next decades is needed. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has acted as a powerful change driver in the field of pathology and has had relevant consequences on the practice of cytopathology, in terms of changes in workload, rates of malignancy, and the performance of cytology. At the same time, regulatory authorities have relaxed their requirements for the deployment of digital pathology for remote diagnostic reporting. However, most of these improvements have concerned digital histopathology. Data from a literature search show that experiences in digital cytopathology during the pandemic have concerned mainly educational and academic activities. From a broader point of view, when searching for all published literature on digital pathology, only a minority of papers deal with cytopathology, but a noticeable increase in publications has been seen in the last 10 years, with an upward trend toward a maximum of papers in 2021. Indeed, the pandemic has led to greater awareness of the possibility of digital for cytopathology as well. [ABSTRACT FROM AUTHOR]

Introduction: Salivary gland tumors (SGT) represent 6 to 8 percent of head and neck tumors. The cytologic diagnosis of SGT is performed by fine-needle aspiration cytology (FNAC) with variable sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) categorizes the cytological results and provides the risk of malignancy (ROM). The aim of our study was to evaluate the cytological findings with the definitive pathological findings to assess the sensitivity, specificity, and diagnostic accuracy of FNAC in SGT according to MSRSGC classification. Method: An observational, retrospective, single-center study was carried out at a tertiary referral hospital over a period of 10 years. Patients that underwent FNAC for major SGT and that have undergone surgery to remove the tumor were included. A histopathological follow-up was performed on the surgically excised lesions. Results from the FNAC were categorized into one of the six MSRSGC categories. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of FNAC for determining benign and malignant cases were calculated. Results: A total of 417 cases were analyzed. The cytological prediction of ROM was 10% in nondiagnostic, 12.12% in non-neoplastic, 3.58% in neoplasm benign group, 60% in AUS and SUMP groups, and 100% in suspicious and malignant group. The statistical analysis of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for determining benign cases was 99%, 55%, 94%, 93%, and 94%, respectively, and for determining malignant neoplasm was 54%, 99%, 93%, 94%, and 94%, respectively. Conclusion: In our hands, MSRSGC is highly sensitive for benign tumors and highly specific for malignant tumors. The low sensitivity to differentiate malignant from benign cases makes it necessary to apply an adequate anamnesis, physical examination, and imaging tests to consider surgical treatment in most cases. [ABSTRACT FROM AUTHOR]