Wide Age Range Research Articles

Adult norms for the decision-making MindPulse Digital Test

We present adult normalized data for MindPulse (MP), a new tool evaluating attentional and executive functioning (AEF) in decision-making. We recruited 722 neurotypical participants (18–80 years), with 149 retested. The MP test includes three tasks: Simple Reaction Time (SRT), Go/No-go, and complex Go/No-go, involving perceptual components, motor responses, and measurements of reaction time (RT) and correctness. We compare responses, evaluating 14 cognitive indices (including new composite indices to describe AEF: Executive Speed and Reaction to Difficulty). We adjust for age/sex effects, introduce a difficulty scale, and consider standard deviations, aberrant times, and Spearman Correlation for speed-accuracy balance. Wilcoxon unpaired rank test is used to assess sex effects, and linear regression is employed to assess the age linear dependency model on the normalized database. The study demonstrated age and sex effects on RTs, in all three subtests, and the ability to correct it for individual results. The test showed excellent validity (Cronbach Alpha for the three subtasks is 92, 87, 95%) and high internal consistency (p < 0.001 for each subtask significantly faster than the more complex subtask) of the MP across the wide age range. Results showed correlation within the three RT parts of the test (p < .001 for each) and the independence of SRT, RD, and ES indices. The Retest effect was lower than intersubject variance, showing consistency over time. This study highlights the MP test’s strong validity on a homogeneous, large adult sample. It emphasizes assessing AEF and Reaction to Difficulty dynamically with high sensitivity.

Processing adjectives in development: Evidence from eye-tracking.

Combining adjective meaning with the modified noun is particularly challenging for children under three years. Previous research suggests that in processing noun-adjective phrases children may over-rely on noun information, delaying or omitting adjective interpretation. However, the question of whether this difficulty is modulated by semantic differences among (subsective) adjectives is underinvestigated.A visual-world experiment explores how Italian-learning children (N=38, 2;4-5;3) process noun-adjective phrases and whether their processing strategies adapt based on the adjective class. Our investigation substantiates the proficient integration of noun and adjective semantics by children. Nevertheless, alligning with previous research, a notable asymmetry is evident in the interpretation of nouns and adjectives, the latter being integrated more slowly. Remarkably, by testing toddlers across a wide age range, we observe a developmental trajectory in processing, supporting a continuity approach to children's development. Moreover, we reveal that children exhibit sensitivity to the distinct interpretations associated with each subsective adjective.

Age-Related Changes in Blood Volume Pulse Wave at Fingers and Ears.

The decline in vascular elasticity with aging can be manifested in the shape of pulse wave. The study investigated the pulse wave features that are sensitive to age and the pattern of these features change with increasing age were examined. Five features were proposed and extracted from the photoplethysmography (PPG)-based pulse wave or its first derivative wave. The correlation between these PPG features and ages was studied in 100 healthy subjects with a wide range of ages (20-71 years). Piecewise regression coefficients were calculated to examine the rates of change of the PPG features with age at different age stages. The proposed PPG features obtained from the finger showed a strong and significant correlation with age (with r = 0.76 - 0.77, p < 0.01), indicating higher sensitivity to age changes compared to the PPG features reported in previous studies (with r = 0.66 - 0.75). The correlation remained significant even after correcting for other clinical variables. The rate of change of the PPG feature values was found to be significantly faster in subjects aged ≥40 years compared to those aged < 40 years in the healthy population. This rate of change was similar to the age-related progression of arterial stiffness evaluated by pulse wave velocity (PWV), which is considered a gold standard for evaluating vascular stiffness. The proposed PPG features showed a high correlation with chronological age in healthy subjects and exhibited a similar age-related change trend as PWV. With the convenience of PPG measures, the proposed age-related features have the potential to be used as biomarkers for vascular aging and estimating the risk of cardiovascular disease.

Automatic imitation in children: Age-related change and comparison to adults.

Automatic imitation, in which one person's movement is affected by the observation of another person's movements, has been widely reported. However, it remains unclear how automatic imitation changes over a wide age range, particularly during childhood. In this study, we examined the differences in the tendency for automatic imitation between adults and children and the cross-sectional age-related changes in children aged 5-12 years, using a stimulus-response conflict paradigm. In this task, participants perform a choice-reactive finger movement corresponding to a given response stimulus while observing another participant's compatible or incompatible movement stimuli. The tendency for automatic imitation was assessed based on the reaction time, correct rate, and inverse efficiency score. The results showed that the degree of automatic imitation was weak until the children were 7 years old. Interestingly, our results show that the tendency for automatic imitation during childhood changed to an inverted U-shape, indicating nonlinear changes in automatic imitation during childhood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sialolipoma: a rare case of a hamartoma in the floor of the mouth

Sialolipomas are rare benign mature mesenchymal lipomatous proliferations that present in a wide age range. These tumors are involved in both major and minor salivary glands, and most of them are almost only seen in adults when the minor salivary glands are involved. In this article, it underlines the occurrence of a rare case of sialolipoma that manifests as a swelling in the floor of the mouth of a 53 year old female patient and interferes with speech, mastication, and tongue movement.

Quantifying the stellar ages of dynamically separated bulges and disks of CALIFA spiral galaxies

We employ a recently developed population-orbit superposition technique to simultaneously fit the stellar kinematic and age maps of 82 CALIFA spiral galaxies and obtain the ages of stars in different dynamical structures. We first evaluated the capabilities of this method on CALIFA-like mock data created from the Auriga simulations. The recovered mean ages of dynamically cold, warm, and hot components match the true values well, with an observational error of up to 20% in the mock age maps. For CALIFA spiral galaxies, we find that the stellar ages of the cold, warm, and hot components all increase with the stellar mass of the galaxies, from tcold ~ 2.2 Gyr, twarm ~ 2.3 Gyr, and thot ~ 2.6 Gyr for galaxies with stellar mass M* &lt; 1010 M⊙, to tcold ~ 4.0 Gyr, twarm ~ 5.1 Gyr, and thot ~ 5.9 Gyr for galaxies with M* &gt; 1011 M⊙. About 80% of the galaxies in our sample have thot &gt; tcold, and the mean values of thot − tcold also increase with stellar mass, from 0.7−0.2+0.6 Gyr in low-mass galaxies (108.9 M⊙ &lt; M* ≤ 1010.5 M⊙) to 1.7−0.2+0.7 Gyr in high-mass galaxies (1010.5 M⊙ &lt; M* &lt; 1011.3 M⊙). The stellar age is younger in disks than in bulges, on average. This suggests that either the disks formed later and/or that they experienced a more prolonged and extensive period of star formation. Lower-mass spiral galaxies have younger bulges and younger disks, while higher-mass spiral galaxies generally have older bulges, and their disks span a wide range of ages. This is consistent with the scenario in which the bulges in more massive spirals formed earlier than those in less massive spirals.

The effects of pyrroloquinoline quinone disodium salt on brain function and physiological processes.

Pyrroloquinoline quinone disodium salt (PQQ) is a red trihydrate crystal that was approved as a new food ingredient by FDA in 2008. Now, it is approved as a food in Japan and the EU. PQQ has redox properties and exerts antioxidant, neuroprotective, and mitochondrial biogenesis effects. The baseline intake level of PQQ is considered to be 20 mg/day. PQQ ingestion lowers blood lipid peroxide levels in humans, suggesting antioxidant activity. In the field of cognitive function, double-blind, placebo-controlled trials have been conducted. Various improvements have been reported regarding general memory, verbal memory, working memory, and attention. Furthermore, a stratified analysis of a population with a wide range of ages revealed unique effects in young people (20-40 years old) that were not observed in older adults (41-65 years old). Specifically, cognitive flexibility and executive speed improved more rapidly in young people at 8 weeks. Co-administration of PQQ and coenzyme Q10 further enhanced these effects. In an open-label trial, PQQ was shown to improve sleep and mood. Additionally, PQQ was found to suppress skin moisture loss and increase PGC-1α expression. Overall, PQQ is a food with various functions, including brain health benefits. J. Med. Invest. 71 : 23-28, February, 2024.

Ultrasonography Features of Adenocarcinoma Mimicking Cystadenoma of Rete Testis

Background: Adenocarcinoma of rete testis is an extremely rare intra-scrotal extra-testicular neoplasm, this tumor usually occurs in men over 60 years of age but there are a few cases of younger patients described as well, has a wide age range of 8-91 years. Case Presentation: In this case, we report A 23-year-old Asian male patient with right scrotal swelling for the last 3 months. Scrotal ultrasound revealed an anechoic multiloculated cystic lesion mass in the right scrotum with the size of 11.89 cm x 7.73 cm lesion that fills almost the entire testicle. There are no solid parts, visible thickening of the scrotum, and visible fluid echo intensity outside the mass. Color Doppler showed a normal flow of blood signals within the mass. Pathological examination is also needed as a gold standard diagnosis, the results concluded that it was adenocarcinoma-type testicular carcinoma. Conclusion: This case highlights the utility of radiological findings, supported by other examinations to determine the diagnosis of Adenocarcinoma of rete testis.

Comprehensive evaluation of body composition in a wide age range of Iranian adults using bioelectrical impedance analysis: Tehran Lipid and Glucose Study.

To evaluate sex- and age-stratified body composition (BC) parameters in subjects with wide age range of 20-79 years. Cross-sectional. Participants of Tehran Lipid and Glucose Study (TLGS). Two thousand nine hundred seventy participants met our inclusion criteria. They were divided into five age groups, and BC parameters were analysed based on sex and age using a bioelectrical impedance analyser (BIA). The mean age of the participants was 42·1 ± 12·5 years, and 54 % of them were males. The mean BMI was 26·7 ± 3·7 kg/m2. Obesity indices were significantly higher in females (P < 0·001); however, skeletal muscle mass (SMM) and fat-free mass (FFM) were significantly higher in males (P < 0·001). Both SMM and FFM decreased significantly after the age of 50 years. Obesity indices significantly increased from the age group of 20-29 to 30-39 years in males and the age groups of 30-39 to 40-49 years and 40-49 to 50-59 years in females. The fat mass ratio (fat mass/SMM) showed two peaks in both sexes (after the ages of 30 and 50 years in males and 40 and 50 years in females). A strong correlation was found between BMI and percentage of body fat (r = 0·823 in females v. r = 0·768 in males). This is the first community-based study in the MENA region identifying sex- and age-stratified BC values using BIA. Our findings can be used as a reference for comparison in appropriate settings.

Attenuation of the hemodynamic response to laryngoscopy and tracheal intubation: A randomized controlled trial

Background: Fentanyl and lidocaine are two drugs that are often suggested to lower the reaction of the blood flow to laryngoscopy and endotracheal intubation. Aims and Objectives: The main goal of our study is to find out how the heart and blood vessels react when laryngoscopy and intubation are used. A comparison was made between fentanyl 2 mcg/kg and fentanyl 2 mcg/kg plus 15 mg of paracetamol per kg of body weight. The goal was to find the best and safest ways for these options to reduce stress during laryngoscopy and intubation. Materials and Methods: The anesthesiology department and the general surgery department at the medical college and hospital that is connected to it worked together on the study. The study included a total of 120 patients, covering a wide age range from 20 to 70 years, and including both males and females. The patients had physical statuses I and II, indicating their overall health. In Group A, patients were given a pre-medication of 0.02 mg/kg of glycopyrrolate and then 2 mg/kg of fentanyl through an intravenous (IV) 90 s before they were intubated. Fentanyl at a dose of 2 mcg/kg was given to patients in Group B 90 s before they were intubated. A dose of 15 mg/kg of paracetamol was also given 10 min before the operation. As a starting point, the medical team wrote down the patient’s heart rate (HR), systolic and diastolic blood pressures, and mean artery pressure before they started intubation. Results: Large rise in HR was seen in Group A, while Group B’s HR stayed close to the baseline. There was a clear rise in mean blood pressure in both groups after intubation. Group A, on the other hand, saw a rise that was clear and lasted for 6 min, while Group B did not. When compared to IV fentanyl alone, IV fentanyl and paracetamol work better at lowering the changes in blood flow that happen during laryngoscopy and airway intubation. Conclusion: This finding highlights the potential benefits of combining these two medications for improved patient outcomes. Endotracheal intubation, fentanyl, paracetamol, and laryngoscopy are all important medical terms that are commonly used in health-care settings. These procedures and medications play a crucial role in various medical interventions and treatments. Understanding the significance and proper usage of these terms is essential for health-care professionals to provide effective care to their patients.

Day case orthopaedic trauma surgery effectiveness: a systematic review

Day case surgery facilitates effective orthopaedic care for ambulatory trauma cases and can act as an effective pathway in times of reduced resource availability within acute hospitals. A systematic review of the available literature was performed using a narrative synthesis to look for themes underpinning day case trauma practice. A 25 papers were selected from a total of 9956 papers screened to identify those papers that considered day case trauma surgery and its impact on clinical outcome, patient satisfaction and feasibility of delivery within the UK. 9014 patients had day case trauma operations within the 25 papers identified, 86% had general anaesthesia and 14% either regional or local anaesthesia. The mean reported age was 37.5 years with a wide age range (2-83) years treating roughly similar proportions of men and women with a high satisfaction rate when recorded. All areas of the upper limb were operated on apart from the scapula the commonest being the wrist. In the lower limb surgery was undertaken in the knee, ankle or foot with removal of foreign body or ankle fixation being the commonest procedures undertaken. Prevalence of complications at 0.0156% of cases undergoing day case surgery was seen to be lower than in a similar group of inpatient cases. resources are stretched. Day case surgery for trauma procedures within orthopaedics is safe, cost effective and well tolerated by patients. It frees up resources to facilitate treatment and should be utilised within each hospital to enable timely care.

Improved test-retest reliability of and susceptibility quantification using multishot multi-echo 3D EPI.

This study aimed to evaluate the potential of 3D EPI for improving the reliability of -weighted data and quantification of decay rate and susceptibility (χ) compared with conventional gradient-echo (GRE)-based acquisition. Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of and χ were quantified, and their interscan differences were used to evaluate the test-retest reliability. Interprotocol differences of and χ between GRE and EPI were also measured voxel by voxel and in selected regions of interest to test the consistency between the two acquisition methods. The quantifications of and χ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. The result suggests that multishot multi-echo 3D EPI can be a useful alternative acquisition method for -weighted MRI and quantification of and χ with reduced scan time, improved test-retest reliability, and similar accuracy compared with commonly used 3D GRE.

Advancement In Neuroplasticity Trainings in Multiple Fields Since 2018

Neuroplasticity training is a rapidly growing practice that has great potential in the treatment of neurological diseases and disorders. This review aims to discuss the advancements in neuroplastic training in the form of motor, auditory, and other training methods. Neuroplastic training has seen promising results in patients encompassing a wide range of ages and conditions. Improvements in parameters such as executive function, gray &amp; white matter, neuronal connectivity, neuron excitation, mini mental state examination (MMSE) score, activities of daily living (ADL) score, and others were observed. The training methods and results are summarized and organized into a table in the review.

Exploring the Prospects and Development of Transforming Petrol Stations into Community Green Spaces

Against the backdrop of global climate change, environmental pollution, and the spread of new energy sources, petrol stations as a potential source of pollution are becoming an important issue in the energy transition. The aim of this paper is to explore the prospects and potential of transforming urban petrol stations into community green spaces. It also explores the possible positive impacts of petrol station transformation in terms of improving the environment and enhancing the quality of life of community residents. The research methodology covered questionnaires and in-depth interviews. The questionnaire drew on the views of community residents from a wide range of ages, occupations, and backgrounds. In-depth face-to-face interviews provide a fuller understanding of residents' expectations and needs. The results of the study show that community residents expect petrol stations to transform into community green spaces and integrate into community life. In addition, it is hoped that the transformed space sites will actively build green infrastructure and promote sustainable community development. A comprehensive analysis of the questionnaire and interview data led to the conclusion that there are challenges and opportunities for the transformation of petrol stations into community green spaces. In the future, it should continue to promote energy transformation and facilitate the transformation of petrol filling stations into community green spaces, so as to jointly enhance the urban environment and the quality of life of community residents. This research provides a useful reference for urban planning and sustainable development, expanding the perspectives and methods of urban green transformation.

Blind people can actively manipulate virtual objects with a novel tactile device

Frequently in rehabilitation, visually impaired persons are passive agents of exercises with fixed environmental constraints. In fact, a printed tactile map, i.e. a particular picture with a specific spatial arrangement, can usually not be edited. Interaction with map content, instead, facilitates the learning of spatial skills because it exploits mental imagery, manipulation and strategic planning simultaneously. However, it has rarely been applied to maps, mainly because of technological limitations. This study aims to understand if visually impaired people can autonomously build objects that are completely virtual. Specifically, we investigated if a group of twelve blind persons, with a wide age range, could exploit mental imagery to interact with virtual content and actively manipulate it by means of a haptic device. The device is mouse-shaped and designed to jointly perceive, with one finger only, local tactile height and inclination cues of arbitrary scalar fields. Spatial information can be mentally constructed by integrating local tactile cues, given by the device, with global proprioceptive cues, given by hand and arm motion. The experiment consisted of a bi-manual task, in which one hand explored some basic virtual objects and the other hand acted on a keyboard to change the position of one object in real-time. The goal was to merge basic objects into more complex objects, like a puzzle. The experiment spanned different resolutions of the tactile information. We measured task accuracy, efficiency, usability and execution time. The average accuracy in solving the puzzle was 90.5%. Importantly, accuracy was linearly predicted by efficiency, measured as the number of moves needed to solve the task. Subjective parameters linked to usability and spatial resolutions did not predict accuracy; gender modulated the execution time, with men being faster than women. Overall, we show that building purely virtual tactile objects is possible in absence of vision and that the process is measurable and achievable in partial autonomy. Introducing virtual tactile graphics in rehabilitation protocols could facilitate the stimulation of mental imagery, a basic element for the ability to orient in space. The behavioural variable introduced in the current study can be calculated after each trial and therefore could be used to automatically measure and tailor protocols to specific user needs. In perspective, our experimental setup can inspire remote rehabilitation scenarios for visually impaired people.

Data-driven Parsing Evaluation for Child-Parent Interactions

Abstract We present a syntactic dependency treebank for naturalistic child and child-directed spoken English. Our annotations largely follow the guidelines of the Universal Dependencies project (UD [Zeman et al., 2022]), with detailed extensions to lexical and syntactic structures unique to spontaneous spoken language, as opposed to written texts or prepared speech. Compared to existing UD-style spoken treebanks and other dependency corpora of child-parent interactions specifically, our dataset is much larger (44,744 utterances; 233,907 words) and contains data from 10 children covering a wide age range (18–66 months). We conduct thorough dependency parser evaluations using both graph-based and transition-based parsers, trained on three different types of out-of-domain written texts: news, tweets, and learner data. Out-of-domain parsers demonstrate reasonable performance for both child and parent data. In addition, parser performance for child data increases along children’s developmental paths, especially between 18 and 48 months, and gradually approaches the performance for parent data. These results are further validated with in-domain training.

Comparative Evaluation of Broth Microdilution With Disc Diffusion and VITEK 2 for Susceptibility Testing of Colistin on Multidrug-Resistant Gram-Negative Bacteria.

Background The rise of antibiotic resistance, particularly in Gram-negative bacteria, poses a significant global health threat. Colistin, a last-resort antibiotic, has witnessed renewed use. However, accurate susceptibility testing for colistin is challenging, with various methods available, leading to potential discrepancies. Ensuring reliable testing is crucial for effective patient treatment and antimicrobial stewardship. This study addresses the need to compare different colistin susceptibility testing methods, providing insights into their accuracy and relevance in clinical settings. Methods In this one-year prospective observational cross-sectional study conducted atIndira Gandhi Institute of Medical Sciences (IGIMS), Bihar, India, atertiary care hospital from July 2021 to June 2022, we aimed to evaluate the concordance between two widely used methods, VITEK 2 and Disc Diffusion, for antibiotic susceptibility testing in clinical multidrug-resistant Gram-negative bacterial isolates. These isolates, including species like Klebsiella pneumoniae, Acinetobacter baumannii, Klebsiella oxytoca, Pseudomonas aeruginosa, Citrobacter freundii, and Escherichia coli, were isolated from various clinical specimens. After rigorous species-level identification and quality control measures, antibiotic susceptibility testing was performed using both methods, and their agreement was assessed through Percentage Agreement analysis. Results In our study, we isolated and identified bacterial isolates from 105 patients, with a mean age of 47.30 years, demonstrating a wide age range. Pus samples were the most common type (25.7%), and K. pneumoniae was the most prevalent organism (45.7%). Antibiotic resistance patterns revealed significant challenges in treating infections caused by K. pneumoniae and A. baumannii, with resistance rates exceeding 70% for certain antibiotics. Among the 48 isolates of K. pneumoniae, the agreement was 93.8%, with 89.6% being sensitive and 6.3% being resistant by Disc Diffusion, while VITEK 2 indicated 0% resistance. E. coli isolates (n=21) had an agreement of 90.5%, with 90.5% sensitivity and 9.5% resistance by Disc Diffusion, and no resistance by VITEK 2. Conclusion The comparative analysis of antibiotic susceptibility testing methods reveals the superior performance of the VITEK 2 system, particularly in sensitivity and negative predictive value, emphasizing its potential as a reliable tool for guiding antibiotic therapy decisions.

Non-interventional epidemiological program for investigating the real-life practice of using quetiapine (Seroquel®) in patients with schizophrenia and bipolar affective disorder (EPIDEMICUS)

The polymorphism of the clinical manifestations of schizophrenia and bipolar affective disorder (BD), late referral to the doctor, comorbidity with somatic diseases and the use of somatotropic medications by psychiatric patients, as well as the frequent development of adverse events (AEs), require constant analysis and improvement of the methods and means of psychopharmacotherapy.Objective: to study the characteristics of the use of quetiapine (Seroquel®) in real outpatient clinical practice.Material and methods. A patient was enrolled in the program if there was a need to prescribe quetiapine (Seroquel®) or to switch from the current therapy to quetiapine. During the program visit, the doctor filled in an individual registration card with information about patient and therapy. The data were statistically analyzed.Results. Quetiapine is prescribed by practicing psychiatrists in Russia not only according to the official indications, but also for psychopathological disorders of other nosology with similar clinical manifestations, such as dementia, organic and affective (depressive episode, recurrent depressive disorder), as well as psychogenic disorders. Up to 27.3% of physicians consider the effect of quetiapine to be quite sufficient in a mixed affective state within the framework of BD dynamics. Quetiapine is used by physicians to treat patients with varying duration of mental disorder (mean 5.1–13.5 years), severity of current mental state (mean CGI-S score 4.3–4.97) and a wide age range (mean age 34.5–60.8 years). When prescribing quetiapine, physicians note that the drug has antidepressant, anxiolytic, sedative and hypnotic effects, regardless of the type of mental disorder. Quetiapine is mainly prescribed as a monotherapy, either primary or resumed after a break – 815 (64.5%) observations. At the same time, quetiapine is used significantly more frequently as monotherapy for BD (69.4%) and mental illnesses of other origin (64.7%) than for schizophrenia (53.8%; p &lt;0.005).Conclusion. In real clinical practice, quetiapine is perceived by psychiatrists as a highly effective and well-tolerated antipsychotic with a broad spectrum of activity that goes beyond the official indications. The practical experience of physicians in Russia shows that in addition to sedative, antipsychotic, antimanic and antidepressant effects, the drug also has antinegative, procognitive, anxiolytic, antiresistant and mood-stabilizing properties.

More is more: toddlers do not show choice overload

Psychological theory and research demonstrate the positive effects of personal choice on human motivation. However, there is evidence in adults that an overabundance of options can lead to choice overload, when choices become demotivating. Little is known about the early development of behaviors involving choice. Across two studies, we investigated whether toddlers (M age = 2.5 years) preferred choice over non-choice and tested for the presence of choice overload using a novel sticker-book task. Moreover, we explored associations between children's executive function (EF) skills and choice preference behavior. In Study 1 (N = 106), children preferred choice on 70% of trials, and this preference increased as a function of the number of options from 2-26. There was no evidence of choice overload. Study 2 (N = 52) replicated findings from Study 1 with up to 53 options, but there was no linear effect. Age (inversely) and sex (female) predicted choice preference in Study 2. Some aspects of parent-reported EF were inversely related to children's preference for choice, whereas a direct assessment of EF was positively correlated, independent of age. Future research should test for choice overload using alternative measures with a wider age range and clarify associations between EF and choice preference.

Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.

Keratocystoma is a rare salivary gland lesion that has been reported primarily in children and young adults. Because of a scarcity of reported cases, very little is known about it, including its molecular underpinnings, biological potential, and histologic spectrum. Purported to be a benign neoplasm, keratocystoma bears a striking histologic resemblance to benign lesions like metaplastic Warthin tumor on one end of the spectrum and squamous cell carcinoma on the other end. This overlap can cause diagnostic confusion, and it raises questions about the boundaries and definition of keratocystoma as an entity. This study seeks to utilize molecular tools to evaluate the pathogenesis of keratocystoma as well as its relationship with its histologic mimics. On the basis of targeted RNA sequencing (RNA-seq) results on a sentinel case, RUNX2 break-apart fluorescence in situ hybridization (FISH) was successfully performed on 4 cases diagnosed as keratocystoma, as well as 13 cases originally diagnosed as tumors that morphologically resemble keratocystoma: 6 primary squamous cell carcinomas, 3 metaplastic/dysplastic Warthin tumors, 2 atypical squamous cysts, 1 proliferating trichilemmal tumor, and 1 cystadenoma. RNA-seq and/or reverse transcriptase-PCR were attempted on all FISH-positive cases. Seven cases were positive for RUNX2 rearrangement, including 3 of 4 tumors originally called keratocystoma, 2 of 2 called atypical squamous cyst, 1 of 1 called proliferating trichilemmal tumor, and 1 of 6 called squamous cell carcinoma. RNA-seq and/or reverse transcriptase-PCR identified IRF2BP2::RUNX2 in 6 of 7 cases; for the remaining case, the partner remains unknown. The cases positive for RUNX2 rearrangement arose in the parotid glands of 4 females and 3 males, ranging from 8 to 63 years old (mean, 25.4 years; median, 15 years). The RUNX2 -rearranged cases had a consistent histologic appearance: variably sized cysts lined by keratinizing squamous epithelium, plus scattered irregular squamous nests, with essentially no cellular atypia or mitotic activity. The background was fibrotic, often with patchy chronic inflammation and/or giant cell reaction. One case originally called squamous cell carcinoma was virtually identical to the other cases, except for a single focus of small nerve invasion. The FISH-negative case that was originally called keratocystoma had focal cuboidal and mucinous epithelium, which was not found in any FISH-positive cases. The tumors with RUNX2 rearrangement were all treated with surgery only, and for the 5 patients with follow-up, there were no recurrences or metastases (1 to 120 months), even for the case with perineural invasion. Our findings solidify that keratocystoma is a cystic neoplastic entity, one which appears to consistently harbor RUNX2 rearrangements, particularly IRF2BP2::RUNX2 . Having a diagnostic genetic marker now allows for a complete understanding of this rare tumor. They arise in the parotid gland and affect a wide age range. Keratocystoma has a consistent morphologic appearance, which includes large squamous-lined cysts that mimic benign processes like metaplastic Warthin tumor and also small, irregular nests that mimic squamous cell carcinoma. Indeed, RUNX2 analysis has considerable promise for resolving these differential diagnoses. Given that one RUNX2 -rearranged tumor had focal perineural invasion, it is unclear whether that finding is within the spectrum of keratocystoma or whether it could represent malignant transformation. Most important, all RUNX2 -rearranged cases behaved in a benign manner.