Interobserver agreement and diagnostic challenges of Congo red staining for amyloid detection on fat pad aspiration biopsies.

INTRODUCTION: Congo red staining of fat pad fine needle aspiration specimens is a method utilized for evaluation of amyloid deposition. However, these specimens can pose diagnostic challenges for cytopathologists. As part of ongoing internal quality improvement measures, the objective of this study was to evaluate the intradepartmental interobserver agreement of these specimens and to identify factors that affect the variability of the interpretations. MATERIALS AND METHODS: There were 7 participants, which included 3 trainees, 3 cytopathologists, and 1 cytotechnologist. Each participant reviewed 50 Congo red stained fat pad fine needle aspiration slides. The interpretations were categorized into 3 groups: negative, indeterminate/suspicious, and positive. The participants also noted any interpretation challenges they encountered for each case. RESULTS: There was only slight interobserver agreement among all participants (κ = 0.133). Stratified by participant group, the interobserver agreement among the trainees was slight bordering on poor (κ = 0.028) and among cytopathologists was fair (κ = 0.249). The highest agreement between 2 observers was between 2 cytopathologists and the level of agreement was moderate bordering on fair (κ = 0.426). There were only 3 cases (6.0%) with full agreement among observers, while in 25 cases (50.0%), there were 2 category differences in interpretations. The primary diagnostic challenge reported by participants was when weak or focal birefringence was encountered as well as cases complicated by poor stain quality and overstaining. CONCLUSIONS: We found only slight interobserver agreement among all study participants. A major area of challenge was cases with weak birefringence resulting in high variance of interpretation among participants.

Utility of an anchored multiplex polymerase chain reaction-based fusion assay for diagnosis of soft tissue tumors in cytology.

BACKGROUND: Fine-needle aspiration specimens from soft tissue tumors are complicated by lack of tissue architecture and limited material for ancillary testing. There are little data on the feasibility of next-generation sequencing techniques for fusion detection on soft tissue cytology specimens. This study explored the role of an anchored multiplex polymerase chain reaction (PCR)-based gene fusion assay in aiding the diagnosis of mesenchymal neoplasms on cytology samples. METHODS: The laboratory information system was queried for cytology specimens that had undergone testing by anchored multiplex PCR. After exclusion of epithelial and hematolymphoid neoplasms, clinical and pathologic information was collected on the remaining cases. RESULTS: There were 1609 cytology specimens tested with anchored multiplex PCR. Of these, 48 (3%) were cytology specimens from mesenchymal tumors. Anchored multiplex PCR was positive for a reportable fusion transcript in 14 of 48 cases (29%); there was no fusion detected in 32 cases (67%), and there was insufficient tissue for analysis in two cases (4%). The detectable fusion partners included ALK (n = 4), STAT6 (n = 4), EWSR1 (n = 3), and one each of SS18, YAP1, and PHF1. Of the cases in which a fusion partner was detected, eight of 14 were disease-defining on cytology preparation, and six of 14 provided molecular confirmation of a metastatic focus of a previously diagnosed tumor. CONCLUSIONS: The anchored, multiplex PCR-based gene fusion assay is a powerful orthogonal tool in helping diagnose mesenchymal neoplasms on cytology specimens. The material obtained for cytologic analysis yields sufficient quality/quantity of tissue in the majority of cases tested.

Multi-institutional 10-year retrospective review of amoeba diagnosed on cytologic evaluation of anal pap tests: what is the significance?

INTRODUCTION: Intestinal amoebae are usually transmitted via ingestion of amoebic cysts in fecally contaminated water or food. However, other modes of transmission include sexual contact through anal-oral sex. While the primary role of anal cytology is the detection of anal cancer and precursor lesions, organisms can also be identified. Despite this, assessment of the clinical significance of cytologic identification of amoebae is lacking in the literature. MATERIALS AND METHODS: A 10-year retrospective review of the pathology archives of 2 institutions in Boston, Massachusetts was conducted. Anal Pap tests that identified amoeba were reviewed and correlated with the medical records for investigation into clinical parameters and patient management. RESULTS: A total of 46 cases were identified between the 2 sites. The majority of patients were male (95.7%) and endorsed having sex with men (84.8%). Only a minority endorsed recent travel (6.5%). Most of the patients were also HIV (human immunodeficiency virus)-positive (71.1%) with all of these patients being well-controlled on antiretroviral therapy. Most patients were asymptomatic (87.0%). On review of the anal Pap tests, the average organism number per case was 35.4. In the majority of cases, follow-up microbiology testing for confirmation and/or speciation was not performed (89.1%) and were not treated (93.5%). CONCLUSIONS: While identification of amoeba is possible on anal cytology, the clinical significance remains unclear as most patients were asymptomatic and not treated in this series. Ultimately, the clinical setting likely plays an important role in determination of management.

Factors associated with myocardial SARS-CoV-2 infection, myocarditis, and cardiac inflammation in patients with COVID-19.

COVID-19 has been associated with cardiac injury and dysfunction. While both myocardial inflammatory cell infiltration and myocarditis with myocyte injury have been reported in patients with fatal COVID-19, clinical-pathologic correlations remain limited. The objective was to determine the relationships between cardiac pathological changes in patients dying from COVID-19 and cardiac infection by SARS-CoV-2, laboratory measurements, clinical features, and treatments. In a retrospective study, 41 consecutive autopsies of patients with fatal COVID-19 were analyzed for the associations between cardiac inflammation, myocarditis, cardiac infection by SARS-CoV-2, clinical features, laboratory measurements, and treatments. Cardiac infection was assessed by in situ hybridization and NanoString transcriptomic profiling. Cardiac infection by SARS-CoV-2 was present in 30/41 cases: virus+ with myocarditis (n = 4), virus+ without myocarditis (n = 26), and virus- without myocarditis (n = 11). In the cases with cardiac infection, SARS-CoV-2+ cells in the myocardium were rare, with a median density of 1 cell/cm2. Virus+ cases showed higher densities of myocardial CD68+ macrophages and CD3+ lymphocytes, as well as more electrocardiographic changes (23/27 vs 4/10; P = 0.01). Myocarditis was more prevalent with IL-6 blockade than with nonbiologic immunosuppression, primarily glucocorticoids (2/3 vs 0/14; P = 0.02). Overall, SARS-CoV-2 cardiac infection was less prevalent in patients treated with nonbiologic immunosuppression (7/14 vs 21/24; P = 0.02). Myocardial macrophage and lymphocyte densities overall were positively correlated with the duration of symptoms but not with underlying comorbidities. In summary, cardiac infection with SARS-CoV-2 is common among patients dying from COVID-19 but often with only rare infected cells. Cardiac infection by SARS-CoV-2 is associated with more cardiac inflammation and electrocardiographic changes. Nonbiologic immunosuppression is associated with lower incidences of myocarditis and cardiac infection by SARS-CoV-2.

Predictors of vitamin D status in subjects that consume a vitamin D supplement.

BACKGROUND/OBJECTIVE: Although dietary supplement use has increased significantly among the general population, the interplay between vitamin D supplementation and other factors that influence vitamin D status remains unclear. The objective of this study was to identify predictor variables of vitamin D status in free-living subjects to determine the extent to which vitamin D supplements and other factors influence vitamin D status. SUBJECTS/METHODS: This was a retrospective, cross-sectional study involving 743 volunteers. Serum 25-hydroxy-vitamin D (25(OH)D) level and the variables diet, supplement usage, latitude of residence, ethnicity, age and body mass index (BMI) were used to predict vitamin D status in a summer and winter cohort. RESULTS: Supplemental vitamin D3 consumption was the most significant positive predictor, whereas BMI was the most significant negative predictor, of vitamin D status in each cohort. Other positive predictors were fortified beverage and dairy consumption in the summer and winter cohort, respectively. Negative predictors were: African American, Asian and Hispanic race in the summer; latitude of residence >36°N, Asian and Hispanic ethnicity in the winter. Mean(± s.d.) 25(OH)D levels were 101.1 (± 42.1) and 92.6 (± 39.0) nmol/l in summer and winter, respectively. Comparing non-supplement vs supplement users, approximately 38 vs 2.5% in the winter and 18 vs 1.4% in the summer had vitamin D levels <50 nmol/l. CONCLUSIONS: Vitamin D supplementation was the most significant positive predictor of vitamin D status. Collectively, these data point to the practicality of utilizing vitamin D supplements to reduce hypovitaminosis D in adults throughout the United States.

Brain asymmetry for language in dyslexic children.

Studies of brain asymmetry in dyslexia have yielded mixed results both with respect to patterns of asymmetry and their cognitive correlates. This paper assessed language lateralisation inferred from dichotic listening with forced attention in a clinical group of young dyslexic subjects. As a whole the dyslexic group showed a deviant asymmetry pattern compared to a control group. Subdivision into two subgroups by receptive language abilities yielded differential patterns within the dyslexia group. Both subgroups exhibited a weaker response pattern to right ear stimuli than the control group. In addition, the subgroup with no language impairment showed bilateral language representation, whereas the subgroup with impaired receptive language abilities showed reversed dominance patterns.

Executive functions in dyslexia.

This study focused on executive functions in dyslexia. A group of 43 heavily-affected young dyslexics, divided into two groups based on the results of a receptive language test, and 20 non-dyslexic controls, were tested with a Dichotic Listening Test, the Stroop Color Word Test and the Wisconsin Card Sorting Test. The dyslexic subjects demonstrated significant impairment on all tasks, but with different patterns of impairment according to the subgrouping. The subgroups were equally impaired on the Dichotic Listening Test, but differed on the Stroop and the Wisconsin Tests. The data support a hypothesis suggesting executive problems in dyslexia, depending on receptive language skills.

Absence of ear advantage on the consonant-vowel dichotic listening test in adolescent and adult dyslexics: specific auditory-phonetic dysfunction.

The present study investigated auditory-phonetic processing in a group of adolescent and adult reading disabled subjects. Right- and left-handed dyslexic subjects were compared with an age, sex, and handedness matched control group. All subjects were studied with a consonant-vowel version of the dichotic listening task with repeated presentations of dichotically presented pairs of CV-syllables. Left and right ear correct scores were compared for ear advantage in each of the different subgroups of subjects. The main finding was the absence of an expected right-ear advantage (REA) in the right-handed dyslexic group as compared to the right-handed normal readers. Both the dyslexic and normal left-handed groups did not show a REA. The findings are discussed within a theoretical framework that focuses on a basic auditory-phonetic processing dysfunction in developmental dyslexia that persists into adulthood.