Brain atrophy assessment in multiple sclerosis: technical- and subject-related barriers for translation to real-world application in individual subjects.

INTRODUCTION: Brain atrophy is a well-established MRI outcome for predicting clinical progression and monitoring treatment response in persons with multiple sclerosis (pwMS) at the group level. Despite the important progress made, the translation of brain atrophy assessment into clinical practice faces several challenges. AREAS COVERED: In this review, the authors discuss technical- and subject-related barriers for implementing brain atrophy assessment as part of the clinical routine at the individual level. Substantial progress has been made to understand and mitigate technical barriers behind MRI acquisition. Numerous research and commercial segmentation techniques for volume estimation are available and technically validated, but their clinical value has not been fully established. A systematic assessment of subject-related barriers, which include genetic, environmental, biological, lifestyle, comorbidity, and aging confounders, is critical for the interpretation of brain atrophy measures at the individual subject level. Educating both medical providers and pwMS will help better clarify the benefits and limitations of assessing brain atrophy for disease monitoring and prognosis. EXPERT OPINION: Integrating brain atrophy assessment into clinical practice for pwMS requires overcoming technical and subject-related challenges. Advances in MRI standardization, artificial intelligence, and clinician education will facilitate this process, improving disease management and potentially reducing long-term healthcare costs.

The Alveolar Variant of Lobular Carcinoma and Its Mimickers: A Case Series.

Invasive lobular carcinoma (ILC) is the most common special type of invasive breast cancer (IBC), accounting for 5-15% of IBCs. The distinct histomorphology of ILC reflects a special tumor biology, the hallmark of which is the lack of E-cadherin expression. However, the occasional presence of E-cadherin expression and the presence of IBC of no special type (IBC, NST)-like morphologies in ILC and vice versa make the diagnosis challenging.  We present two cases of the alveolar variant of ILC, a diagnostically challenging entity. The first case is an 81-year-old female with two discrete right breast masses at 1 o'clock and 9 o'clock positions.  The second case is a 61-year-old female with two discrete left breast masses located at 11 o'clock and 12 o'clock positions. Core needle biopsies and subsequent mastectomy were performed in both cases. On histology, three tumor foci were identified in the first case. The 1 o'clock focus showed IBC, NST, grade 3/3, ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). The 9 o'clock focus revealed ILC, classic and alveolar variants, grade 2/3, while a nearby third incidental focus was ILC, alveolar variant, both supported by lack of E-cadherin and ß-catenin immunostaining.  The second case showed ILC, alveolar variant, grade 1 with LCIS component in the 11 o'clock lesion on both biopsy and mastectomy specimens. The lesion at the 12 o'clock position was diagnosed as IBC, NST, grade 2 with high-grade DCIS and LCIS components.  It is challenging to distinguish the alveolar variant of ILC from IBC, NST, and in situ lesions because of the overlapping morphology and occasional E-cadherin expression. Altered adherence of lobular cells may also be due to loss of α-, ß-, and γ-catenins, and cytoplasmic re-localization of p120-catenin. Therefore, in ILC, the lack of ß-catenin can be used as an adjunct along with E-cadherin. Myoepithelial markers such as p63 and smooth muscle myosin heavy chain (SMMHC) can be used to distinguish the alveolar variant of ILC from LCIS.

Sampling data of macro-invertebrates collected in grasslands under restoration succession in a lowland stream-valley system.

Background: Publication of data from past field studies on invertebrate populations is of high importance, as there is much added value for them to be used as baselines to study spatiotemporal population and community dynamics in these groups. Therefore, a dataset consisting of occurrence data on epigaeic invertebrates collected in 1996 was standardised into the Darwin core format and cross-checked in order to make it publicly available following FAIR data principles. With publication, it can contribute to the biodiversity assessment of terrestrial invertebrates, thereby improving the availability and accessibility of much-needed historical datasets on macro-invertebrates.Here, we present sampling event data on invertebrates from four grasslands taken out of agricultural production over the span of several decades, effectively displaying a chronosequence on the effects of agricultural extensification. The data were collected by means of a standardised sampling design using pyramid traps, pitfall traps and soil samples. New information: The raw data presented in this data paper have not been published before. They consist of 20,000+ records of nearly 70,000 specimens from 121 taxonomic groups. The data were collected using a standardised field study set-up and specimens were identified by taxonomic specialists. Most groups were identified up to family level, with eight groups identified up to species level. The occurrence data are complemented by information on plant composition, meteorological data and soil physical characteristics. The dataset has been registered in the Global Biodiversity Information Facility (GBIF): http://doi.org/10.15468/7n499e.

Zone-specific pitfalls in flexor tendon rehabilitation: management and prevention.

Despite significant advancements in flexor tendon repair techniques and rehabilitation strategies, achieving complete restoration of digital motion remains a formidable challenge. The most prevalent complications associated with tendon repair are the development of tendon adhesions and joint contractures. Left unaddressed, these complications can further lead to secondary pathomechanical changes, resulting in fixed deformities significantly affecting hand function. This review of zone-specific considerations in flexor tendon rehabilitation provides an in-depth analysis of the dynamics of tendon motion after repair and strategies to minimize common secondary complications.

Intraoperative frozen section evaluation of ovarian sex cord-stromal tumours and their mimics: a study of 121 cases with emphasis on potential diagnostic pitfalls.

Ovarian sex cord-stromal tumours (SCSTs) present diagnostic difficulties during frozen section (FS) consultations due to their diverse morphology. This study aimed to evaluate the accuracy of FS evaluation of SCSTs in our institution, as well as to examine the reasons leading to incorrect FS diagnosis. Cases mimicking SCSTs and diagnosed as such during FS were also highlighted. We analysed 121 ovarian SCST cases and their mimics which underwent FS consultations over a 10-year period, to evaluate FS accuracy, reasons for deferrals and discrepancies. FS diagnoses were concordant, deferred and discrepant compared to the final diagnosis in 50 (41.3%), 39 (32.2%) and 32 (26.5%) cases, respectively. Major discrepancies (9/121, 7.4%) were mostly related to the diagnosis of adult granulosa cell tumour (AGCT). A fibromatous AGCT was misinterpreted as fibroma on FS, while a cystic AGCT was called a benign cyst. Conversely, a mesonephric-like adenocarcinoma, a sertoliform endometrioid carcinoma and a thecoma were misinterpreted as AGCT on FS. Another discrepant case was a Krukenberg tumour with prominent fibromatous stroma in which malignant signet ring cells were overlooked and misinterpreted as fibroma. Minor discrepancies were primarily associated with fibroma (21/23, 91.3%), wherein minor but potentially impactful details such as cellular fibroma and mitotically active cellular fibroma were missed due to sampling issues and misinterpretation as leiomyoma. FS evaluation for ovarian SCSTs demonstrated an overall accuracy of 78.5%, 81.0% and 81.8% for benign, uncertain/low malignant potential and malignant categories, respectively. There was no FS-related adverse clinical impact in all cases with available follow-up information (120/121 cases). Intraoperative FS evaluation of ovarian SCSTs is challenging. A small number of cases were misinterpreted, with AGCTs being the primary group where errors occur. Awareness of common diagnostic pitfalls and difficulties, alongside application of a stepwise approach, including (1) obtaining comprehensive clinical information, (2) thorough macroscopic examination and directed sampling, (3) meticulous microscopic examination with consideration of pitfalls and mimics, (4) effective communication with surgeons in difficult cases, and (5) consultation of subspecialty colleagues in challenging cases, will enhance pathologists' reporting accuracy and management of such cases in the future.

Observational studies: practical tips for avoiding common statistical pitfalls.

This Personal View is intended for early-career researchers who are not yet experts in statistics. The Personal View focuses on common but usually avoidable flaws in the context of observational studies. I point out how study design, data collection, and statistical methods impact statistical results and research conclusions. With particular attention to study planning, sample selection, biases, lack of transparency and results misinterpretations.

Overcoming Pitfalls in Breast Fine-Needle Aspiration Cytology: A Practical Review.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a cornerstone technique for the initial assessment of breast lesions, offering a rapid and minimally invasive option for cytological evaluation. While FNACs can forego the need for core needle biopsies (CNBs), variations in technique, subjective interpretation, and intrinsic limitations present diagnostic challenges. The International Academy of Cytology (IAC) established the Yokohama system and is developing the WHO Reporting System for Breast Cytopathology jointly with IARC, to standardize diagnostic criteria, aiming to enhance diagnostic precision and consistency. Due to the preference for CNBs, expertise in breast FNAC is low in the developed world. SUMMARY: This review assesses common pitfalls in breast cytopathology. These common and uncommon entities may easily lead to false-negative or false-positive diagnoses, due to morphological overlap or misleading clinical and radiological contexts. For instance, pauci-cellular lesions, such as lobular carcinomas, often lead to false-negative diagnoses, whereas complex sclerosing lesions, fibroadenomas, and papillary lesions may show concerning features, resulting in a false positive. The same is true for some benign inflammatory pathologies, such as steatonecrosis, and uncommon lesions, such as collagenous spherulosis. Ductal carcinoma in situ can lead to both false-negative and false-positive diagnoses, and high-grade lesions are impossible to tell apart from invasive carcinomas. These are discussed in detail. Procedural and preanalytical conditions, and the role of ancillary testing, are also briefly addressed. KEY MESSAGES: Breast FNAB is a powerful diagnostic technique, fast and minimally invasive. Even in contexts which lack expertise, this technique can be successfully adopted with a cautious approach and as long as pitfalls are kept in mind, benefiting patients and healthcare systems.

Pitfalls in Gynecological Cytology: Review of the Common and Less Frequent Entities in Pap Test.

BACKGROUND: Pitfalls in Pap test could be defined as false positive, false negative, or underdiagnosed results which can lead to unnecessary diagnostic procedures or delayed and inadequate treatment. It can be a consequence of misinterpretation of certain morphological entities which are described in this paper. SUMMARY: The paper presents an overview of the morphological features and look-alikes of the common sources of pitfalls such as atrophy, repair, intrauterine device change, tubal metaplasia, hyperchromatic crowded groups, and radiation changes. Rare causes of pitfalls such as Arias-Stella changes, pemphigus, tumor diathesis per se, rare types of cervical cancer, including verrucous and papillary squamous cell cancer, gastric type, and endometrioid adenocarcinoma are also described. KEY MESSAGES: The awareness of pitfalls in cervical cytology is important for cytopathologists and clinicians to avoid future errors. Review of Pap tests with erroneous diagnosis is important for quality control in cytology laboratory, and it must be considered an educational- and experience-building procedure. Cytopathologist should not pull back in significant diagnoses, especially in human papillomavirus-negative cases.

Effect of limb and cuff positioning on measurement of arterial blood pressure with an oscillometry device (PetMAP) in anaesthetized cats.

Arterial blood pressure (ABP) is often measured with oscillometry during anaesthesia. Changing the height of the measuring cuff with respect to the level of the heart is known to affect oscillometry accuracy in some species; however, this effect has not been investigated in cats. The objective of this study was to determine the effects of raising and lowering the measuring cuff from standard position (level of the heart) on ABP, measured with PetMAP, in anaesthetised cats. ABP readings were obtained from 29 cats with the cuff at standard position (baseline), and 5 cm above and below the heart. The end-tidal isoflurane concentrations were maintained constant during data acquisition. There were no differences between baseline values and those measured below the heart, while ABP measured above the heart was consistently lower than baseline for both the thoracic and pelvic limbs (P < 0.001), with absolute differences of 8.2 (2.5 - 14) mmHg and 6.5 (3.0 - 15.0) mmHg, respectively. Systolic ABP readings at the pelvic limb were consistently higher than those at the thoracic limb at standard position (112 ± 26 versus 103 ± 21 mmHg, p = 0.010), above (106 ± 22 versus 95 ± 20 mmHg, p = 0.003), and below the heart (116 ± 26 versus 107 ± 22 mmHg, p = 0.011). This study shows that raising the cuff by 5 cm above the heart, which may become necessary during procedural positioning, results in clinically significant underestimation of ABP measured with PetMAP.

Challenges and pitfalls in the perioperative management of mediastinal mass syndrome: an up-to-date review.

The perioperative management of patients undergoing mediastinal mass operations presents a persistent challenge across multiple clinical specialties. General anesthesia administration further increases the risk of perioperative cardiorespiratory decompensation. The interdisciplinary team plays a crucial role in ensuring a safe perioperative period. However, due to the rarity and variability of mediastinal mass syndromes, specific management protocols are lacking. This review aims to outline the multitude of challenges and pitfalls encountered during perioperative management in patients with the mediastinal mass syndrome. We describe diagnostic evaluation, preoperative optimization, intraoperative considerations, and postoperative care strategies, emphasizing the paramount significance of a multidisciplinary approach and personalized treatment plans. Preoperative multidisciplinary discussions, meticulous anesthetic management, and well-established protocols for emergency situations are pivotal to ensuring patient safety. Healthcare providers involved in the care of patients with mediastinal mass syndrome must grasp these challenges and pitfalls, enabling them to deliver safe and effective perioperative management.

Pitfalls in the Diagnostic Evaluation of Pheochromocytomas.

Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical rarity and polymorphic symptomatology. The clinical cases demonstrate the importance of an integrated approach that combines clinical assessment, biochemical testing, and imaging to distinguish PPGLs from mimicking conditions, such as obstructive sleep apnea and interfering medication effects, which can lead to false-positive biochemical results. Although a rare condition, false-negative metanephrine levels can occur in pheochromocytomas, but imaging findings can give some clues and increase suspicion for a pheochromocytoma diagnosis. This expert endocrine consult underscores the critical role of evaluating preanalytical conditions and pretest probability in the biochemical diagnosis of PPGLs. Moreover, a careful differentiation of PPGLs from similar conditions and careful selection and interpretation of diagnostic tests, with focus on understanding and reducing false positives to enhance diagnostic accuracy and patient outcomes, is crucial.

Solid pseudopapillary tumor of the pancreas mistaken for gastrointestinal stromal tumor: A case report.

Solid pseudopapillary epithelial neoplasms of the pancreas are rare entities, first described in 1959 by Frantz. These tumors represent less than 2% of pancreatic cancers and mainly affect young women. They can reach a significant size and its radiological features can lead to diagnostic pitfalls, such as gastrointestinal stromal tumors, which are rare soft-tissue sarcomas that can appear anywhere along the gastrointestinal tract. Clinicians and radiologists need to be aware of the existing diagnostic pitfalls between these two entities, because of their possible similarities. We report here the case of a 33-year-old woman with a solid pseudopapillary epithelial neoplasms of the pancreas initially misdiagnosed as an exophytic gastric stromal tumor.

Recombinant monoclonal antibody production in yeasts: Challenges and considerations.

Monoclonal antibodies (mAbs) are laboratory-based engineered protein molecules with a monovalent affinity or multivalent avidity towards a specific target or antigen, which can mimic natural antibodies that are produced in the human immune systems to fight against detrimental pathogens. The recombinant mAb is one of the most effective classes of biopharmaceuticals produced in vitro by cloning and expressing synthetic antibody genes in a suitable host. Yeast is one of the potential hosts among others for the successful production of recombinant mAbs. However, there are very few yeast-derived mAbs that got the approval of the regulatory agencies for direct use for treatment purposes. Certain challenges encountered by yeasts for recombinant antibody productions need to be overcome and a few considerations related to antibody structure, host engineering, and culturing strategies should be followed for the improved production of mAbs in yeasts. In this review, the drawbacks related to the metabolic burden of the host, culturing conditions including induction mechanism and secretion efficiency, solubility and stability, downstream processing, and the pharmacokinetic behavior of the antibody are discussed, which will help in developing the yeast hosts for the efficient production of recombinant mAbs.

Pitfalls in Respiratory Tract Cytopathology.

BACKGROUND: Cytopathology is integral to the investigation and diagnosis of respiratory disease, and, in the last decade or so, transbronchial needle aspiration by endobronchial ultrasound has made possible diagnosis and staging of malignant thoracic tumours at a single procedure. In addition, interventional teams increasingly include cytopathologists and cytotechnologists who, by providing rapid onsite evaluation, ensure efficient sampling of intrathoracic targets with the ultimate goal of accurate diagnosis as well as sufficient material for comprehensive predictive testing. Nonetheless, "traditional" cytological investigations such as bronchial washings, brushings, and lavages are still carried out for investigation of both suspected neoplastic and non-neoplastic conditions, and all these procedures still produce specimens in which florid benign cells mimic malignancy, while truly neoplastic cells lurk quietly in the background. Furthermore, even when neoplasia is not suspected, issues in preparation and interpretation may render a final assessment inaccurate and, therefore, clinically unhelpful or misleading. In this overview, we have tried to adopt a format partly modelled on the passage of a specimen from clinical acquisition to laboratory endpoint, thus taking in potential pitfalls in communication, clinical interaction, transport, and clinic-based preparation, as well as in morphology, immunocytochemistry, and suitability for predictive testing. It is not exhaustive but highlights areas that may frequently be encountered or are part of our personal experience. SUMMARY: The account highlights potential pitfalls in respiratory cytopathology at key stages of the process from acquisition to reporting and presents these in both flow diagram and tabular form. We hope this is useful for the increasingly collaborative roles of cytotechnologist and cytopathologist and their wider involvement in the clinical investigative teams. KEY MESSAGES: Correct clinical and radiological information is crucially important and promotes the correct acquisition and processing of cytopathological specimens. Cross-discipline collaborative working ensures the most efficient use of the specimen such that diagnoses and predictive tests are performed on optimal material, reducing the potential for misinterpretation. Nonetheless, even with optimal material, morphological mimics and atypical antigen expression may mislead and render accurate diagnosis challenging.

Intense prostate-specific membrane antigen receptor expression in coronary artery pypass graft scar tissue: A potential molecular imaging pitfall.

68Gallium-PSMA positron emission tomography/computer tomography has been utilized recently for the diagnosis and staging of prostate cancer. PSMA is a transmembrane protein that is expressed not only in the prostate gland but also in other tissues. While some pitfalls have been addressed, there are still uncertainties. Herein, we report a 79-year-old male with prostate cancer who underwent a PSMA scan after coronary artery bypass graft surgery, revealing disease progression and PSMA-avid foci at the surgical stitch sites. This report discusses the immunohistochemical and molecular imaging mechanisms underlying PSMA expression in surgical scar tissues, providing critical insights for optimizing radiologic reporting in such situations.

SMARCA4-Deficient Undifferentiated Tumor of the Esophagus: Diagnostic Pitfalls in Immunohistochemical Profiles.

SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are a newly described entity and are typically seen in the thoracic cavity. However, these tumors have been described in other body sites, including the esophagus. These tumors are rare, aggressive neoplasms, characterized by the loss of protein product of SMARCA4 (Brahma-related gene-1) and the preservation of INI1 (SMARCB1) expression. Here, we present two tumors of SMARCA4-UT of the esophagus with its microscopic appearance and immunohistochemical profile. We also include a literature review of SMARCA4-deficient tumors of the tubular gastrointestinal tract with their immunohistochemical and mismatch repair profiles for each specimen. Due to its non-specific histologic appearance and variable staining in expanded immunohistochemical panels, this tumor frequently overlaps with other tumor types, making the diagnosis of SMARCA4-UT challenging. These tumors are often associated with intestinal metaplasia of the esophagus and are thought to represent a high-grade undifferentiated transformation of a conventional esophageal adenocarcinoma. These tumors are typically associated with poor clinical outcomes and have poor response to conventional therapies. Currently, there are no standard guidelines for treatment of these tumors; however, palliative radiotherapy and systemic chemotherapy may provide benefit. More recently, immunotherapy and novel therapeutic targets have shown some promise for these patients.

Considerations for the use of biochemical laboratory registry data in clinical and public health research.

OBJECTIVES: To inform researchers of central considerations and limitations when applying biochemical laboratory-generated registry data in clinical and public health research. STUDY DESIGN AND SETTING: After review of literature on registry-based studies and the utilization of clinical laboratory registry data, relevant paragraphs and their applicability toward the creation of considerations for the use of biochemical registry data in research were evaluated. This led to the creation of an initial ten considerations. These were elaborated, edited, and merged after several read-throughs by all authors and discussed thoroughly under influence by the authors' personal experiences with laboratory databases and research registries in Denmark, leading to the formulation of five central considerations with corresponding items and illustrative examples. RESULTS: We recommend that the following considerations should be addressed in studies relying on biochemical laboratory-generated registry data: why are biochemical laboratory data relevant to examine the hypothesis, and how were the variable(s) utilized in the study? What were the primary indications for specimen collection in the study population of interest? Were there any pre-analytical circumstances that could influence the test results? Are data comparable between producing laboratories and within the single laboratory over time? Is the database representative in terms of completeness of study populations and key variables? CONCLUSION: It is crucial to address key errors in laboratory registry data and acknowledge potential limitations.

Radioiodine whole body scan pitfalls in differentiated thyroid cancer.

PURPOSE: whole body scan (WBS) performed following diagnostic or therapeutic administration of I-131 is useful in patients with differentiated thyroid carcinoma. However, it can be falsely positive in various circumstances. We aimed to report a series of pitfalls in a clinical perspective. METHODS: A search in the database PubMed utilizing the following terms: "false radioiodine uptake" and "false positive iodine 131 scan" has been made in January 2023. Among the 346 studies screened, 230 were included in this review, with a total of 370 cases collected. Physiological uptakes were excluded. For each patient, sex, age, dose of I-131 administered, region and specific organ of uptake and cause of false uptake were evaluated. RESULTS: 370 cases of false radioiodine uptake were reported, 19.1% in the head-neck region, 34.2% in the chest, 14.8% in the abdomen, 20.8% in the pelvis, and 11.1% in the soft tissues and skeletal system. The origin of false radioiodine uptake was referred to non-tumoral diseases in 205/370 cases (55.1%), benign tumors in 108/370 cases (29.5%), malignant tumors in 25/370 cases (6.7%), and other causes in 32/370 cases (8.7%). CONCLUSIONS: WBS is useful in the follow-up of patients with differentiated thyroid carcinoma, however it can be falsely positive in various circumstances. For this reason, it is critically important to correlate the scintigraphic result with patient's medical history, serum thyroglobulin levels, additional imaging studies and cytologic and/or histologic result.

Musculoskeletal Pitfalls on Molecular Imaging Studies of Oncologic Patients: How to Stay Out of Trouble.

An increasing amount of molecular imaging studies are ordered each year for an oncologic population that continues to expand and increase in age. The importance of these studies in dictating further care for oncologic patients underscores the necessity of differentiating benign from malignant findings, particularly for a population in whom incidental findings are common. The aim of this review is to provide pictorial examples of benign musculoskeletal pathologies which may be found on molecular imaging and which may be mistaken for malignant processes. Imaging examples are provided in the form of radiographs, bone scintigraphy, computed tomography, and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans. Special attention is paid to specific features that help narrow the differential diagnosis and distinguish benign from malignant processes, with the goal of avoiding unnecessary invasive procedures.