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.

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.

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.

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.

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.

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.

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.

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.

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.

Common pitfalls, and how to avoid them, in child and adolescent psychopharmacology: Part II.

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of autism and intellectual disability, eating disorders, neuropsychiatric correlates of epilepsy, and psychosis. Pitfalls in relation to the treatment of other disorders are addressed in a separate paper (Part I).

Common pitfalls, and how to avoid them, in child and adolescent psychopharmacology: Part I.

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of attention-deficit/hyperactivity disorder, anxiety, bipolar disorder, depression, obsessive-compulsive disorder and related disorders, and tic disorder. Pitfalls in the treatment of other disorders are addressed in a separate paper (part II).

Bone densitometry in Thalassemia major: a closer look at pitfalls and operator-related errors in a 10-year follow-up population.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard for measuring bone mineral density (BMD) with tolerable error rate, high precision, and excellent consistency. Our objective was to investigate the frequency and distribution of errors in a cohort of patients with Thalassemia major (TM). METHODS: We reviewed the DXA examinations of 340 patients with ß-TM followed by our institution, acquired in different imaging centers between 2009 and 2019. We collected sex and age at the time of the first examination and at the last visit, as well as BMD, T-score, and Z-score values. Errors were analyzed by anatomical site (lumbar spine, total hip, femoral neck). RESULTS: Out of 5099 total DXA scans, 11.85% presented one or more errors. Specifically, the incorrect examinations were 315 out of 1707 (18.45%) at the lumbar spine level, 113 out of 1697 (6.66%) at the total hip, 176 out of 1695 (10.38%) at the femoral neck. Errors in vertebral inclusion were the most frequently registered (45.86%). A significant difference resulted from the comparison of the T-score and Z-score median values of all the lumbar spine DXA examinations and the correct ones (p value 0.037 and 0.0003, respectively). CONCLUSION: Although not directly involved in the performance and interpretation of DXA, physicians interested in osteoporosis management should be familiar with the protocols to minimize errors and allow the proper use of bone densitometry. DXA obtained at the spine level is more frequently affected by errors in patients with TM, potentially influencing the diagnostic assessment of bone health status.

[Practical application of immunohistochemistry in pancreatic neuroendocrine neoplasms : Tips and pitfalls]. / Praktische Anwendung von Immunhistochemie in pankreatischen neuroendokrinen Neoplasien : Tipps und Pitfalls.

Pancreatic neuroendocrine neoplasms (PanNEN) are rather rare entities. Morphology, combined with immunohistochemistry, allows typing and grading, thereby leading therapeutic decisions. Depending on tumor stage and differential diagnosis, a broad diagnostic panel may be required. The present work summarizes the minimal diagnostic, prognostic, and predictive markers in PanNEN.Markers of choice for defining a neuroendocrine phenotype are synaptophysin, chromogranin A, and INSM1. The proliferation fraction Ki67 is indispensable for grading, while p53 and Rb1 can help in the differentiation from neuroendocrine carcinoma (NEC). Transcription factors, such as cdx2, TTF­1, and Islet­1, can indicate the site of a primary tumor in the setting of a cancer of unknown primary (CUP). DAXX/ATRX immunohistochemistry has mainly prognostic value. Molecular pathology studies currently have little practical value in the diagnosis of PanNEN.An important pitfall in routine diagnostics is the wide spectrum of differential diagnoses mimicking neuroendocrine neoplasms. An expanded immunohistochemical panel is strongly recommended in case of doubt.

Raising Questions with Lamiell about Future Research Directions of Critical Personalism: A Book Review Essay.

The present article is a book review essay about James T. Lamiell's Primer in Critical Personalism: A Framework for Reviving Psychological Inquiry and for Grounding a Socio-cultural Ethos published in February 2024. In the beginning of the paper, I am outlining the core tenets of the book that is its separation into two major sections. In the first, Lamiell shows us the origins of psychological research in Germany in the laboratory of Wilhelm Wundt in Leipzig and his peculiar notion of generalizing knowledge. Here, the American psychologist explains that Wundt and his assistants were far away of generalizing knowledge in the way mainstream psychology does today - that is on an aggregate, population-based knowledge. On the contrary, Wundt and his colleagues were generalizing knowledge more in a systemic manner - something which is also in line with the work of William Stern and his critical personalism. Lamiell applies the core tenets of critical personology - that originate in the notion of the adoption of self-purposes (values) which become then linked to foreign purposes/values and produces something higher over the course of that process. Lamiell expands this successfully to the domain of informal focus groups discussing racial issues and how psycho-demographic research comes to fixate individuals into categories that do not apply to the individual level. As such, the American psychologist accomplishes to show that inferential statistics is not only scientifically unsound for many research questions but that it also comes with moral and ethical concerns that should be addressed by scientists. At the end of the book review essay, I point out several pathways of future research - that is the link between critical personalism, phenomenology, existentialism and psychoanalysis as well as how Lamiell would construct and co-construct concrete interventions to facilitate introception to take place in his informal focus groups. I conclude the article by stressing the major highlight of Lamiell's book - that is the interpersonal benefits of adopting a critical personological perspective in science and in life.

Emerging Role of Scintigraphy Using Bone-Seeking Tracers for Diagnosis of Cardiac Amyloidosis: AJR Expert Panel Narrative Review.

Amyloidoses are a complex group of clinical diseases that result from progressive organ dysfunction due to extracellular protein misfolding and deposition. The two most common types of cardiac amyloidosis are transthyretin amyloidosis (ATTR) and light-chain (AL) amyloidosis. Diagnosis of ATTR cardiomyopathy (ATTR-CM) is challenging owing to its phenotypic similarity to other more common cardiac conditions, the perceived rarity of the disease, and unfamiliarity with its diagnostic algorithms; endomyocardial biopsy was historically required for diagnosis. However, myocardial scintigraphy using bone-seeking tracers has shown high accuracy for detection of ATTR-CM and has become a key noninvasive diagnostic test for the condition, receiving support from professional society guidelines and transforming prior diagnostic paradigms. This AJR Expert Panel Narrative Review describes the role of myocardial scintigraphy using bone-seeking tracers in the diagnosis of ATTR-CM. The article summarizes available tracers, acquisition techniques, interpretation and reporting considerations, diagnostic pitfalls, and gaps in the current literature. The critical need for monoclonal testing of patients with positive scintigraphy results to differentiate ATTR-CM from AL cardiac amyloidosis is highlighted. Recent updates in guideline recommendations that emphasize the importance of a qualitative visual assessment are also discussed.

Tumour 63 protein (p63) in breast pathology: biology, immunohistochemistry, diagnostic applications, and pitfalls.

Tumour protein 63 (p63) is a transcription factor of the p53 gene family, encoded by the TP63 gene located at chromosome 3q28, which regulates the activity of genes involved in growth and development of the ectoderm and derived tissues. p63 protein is normally expressed in the nuclei of the basal cell layer of glandular organs, including breast, in squamous epithelium and in urothelium. p63 immunohistochemical (IHC) staining has several applications in diagnostic breast pathology. It is commonly used to demonstrate myoepithelial cells at the epithelial stromal interface to differentiate benign and in situ lesions from invasive carcinoma and to characterize and classify papillary lesions including the distinction of breast intraduct papilloma from skin hidradenoma. p63 IHC is also used to identify and profile lesions showing myoepithelial cell and/or squamous differentiation, e.g. adenomyoepithelioma, salivary gland-like tumours including adenoid cystic carcinoma, and metaplastic breast carcinoma including low-grade adenosquamous carcinoma. This article reviews the applications of p63 IHC in diagnostic breast pathology and outlines a practical approach to the diagnosis and characterization of breast lesions through the identification of normal and abnormal p63 protein expression. The biology of p63, the range of available antibodies with emphasis on staining specificity and sensitivity, and pitfalls in interpretation are also discussed. The TP63 gene in humans, which shows a specific genomic structure, resulting in either TAp63 (p63) isoform or ΔNp63 (p40) isoform. As illustrated in the figure, both isoforms contain a DNA-binding domain (Orange box) and an oligomerization domain (Grey box). TAp63 contains an N-terminal transactivation (TA) domain (Green box), while ΔNp63 has an alternative terminus (Yellow box). Antibodies against conventional pan-p63 (TP63) bind to the DNA binding domain common to both isoforms (TAp63 and p40) and does not distinguish between them. Antibodies against TAp63 bind to the N-terminal TA domain, while antibodies specific to ΔNp63 (p40) bind to the alternative terminus. Each isoform has variant isotypes (α, ß, γ, δ, and ε).