Can hamartoma of the breast be distinguished from fibroadenoma using fine‐needle aspiration cytology?

In an attempt to determine if it is possible to distinguish hamartoma of the breast from fibroadenoma using fine-needle aspiration cytology, we reviewed the cytological slides of 13 histopathologically confirmed cases of hamartoma of the breast and compared them with the cytological features of 13 histologically confirmed fibroadenomas. In each case, we studied the epithelial and stromal features. Cytologic characteristics were retrospectively evaluated in a semiquantitative manner. In conclusion, the finding of intact lobular units and a relative paucity of stroma may suggest the diagnosis of hamartoma.     

Can mucinous lesions of the breast be reliably diagnosed by core needle biopsy?

Lesions of the breast containing extravasated mucin span a continuum from benign mucoceles to invasive mucinous (colloid) carcinoma. It is well known that distinguishing benign from malignant mucinous lesions is difficult infine-needle aspiration material. Whether these lesions also are difficult to distinguish in core needle biopsy material is not known. To address this, I reviewed the results of 4,297 breast core needle biopsies. Mucinous lesions were identified in 22 cases (0.51%), and excisional biopsy material was available for 15 of these. At excision, 0 of 8 benign mucinous lesions showed carcinoma, while 7 of 7 mucinous lesions associated with carcinoma at the time of core needle biopsy showed carcinoma at excision. The vast majority of mucinous lesions of the breast can be diagnosed accurately by core needle biopsy. Whether all such lesions require excision is not known at this time.     

Can the comet assay be used reliably to detect nanoparticle‐induced genotoxicity?

The comet assay is a sensitive method to detect DNA strand breaks as well as oxidatively damaged DNA at the level of single cells. Today the assay is commonly used in nano‐genotoxicology. In this review we critically discuss possible interactions between nanoparticles (NPs) and the comet assay. Concerns for such interactions have arisen from the occasional observation of NPs in the “comet head”, which implies that NPs may be present while the assay is being performed. This could give rise to false positive or false negative results, depending on the type of comet assay endpoint and NP. For most NPs, an interaction that substantially impacts the comet assay results is unlikely. For photocatalytically active NPs such as TiO₂, on the other hand, exposure to light containing UV can lead to increased DNA damage. Samples should therefore not be exposed to such light. By comparing studies in which both the comet assay and the micronucleus assay have been used, a good consistency between the assays was found in general (69%); consistency was even higher when excluding studies on TiO₂ NPs (81%). The strong consistency between the comet and micronucleus assays for a range of different NPs—even though the two tests measure different endpoints—implies that both can be trusted in assessing the genotoxicity of NPs, and that both could be useful in a standard battery of test methods. Environ. Mol. Mutagen. 56:82–96, 2015. © 2014 Wiley Periodicals, Inc.     

Can phyllodes tumours of the breast be distinguished from fibroadenomas using fine needle aspiration cytology?

In an attempt to determine whether it is possible to distinguish phyllodes tumours (PTs) of the breast from fibroadenomas (FAs) using fine needle aspiration cytology (FNAC), we reviewed the cytological slides of eight histopathologically confirmed PTs (six benign and two malignant) and compared them with cytological features of 13 histopathologically confirmed FAs. Each author independently, "blindly" assessed architectural and cytological features of the stromal (six features) and epithelial (seven features) components and the cytological background (three features) and gave a favoured diagnosis for each case. Four of six benign PTs, one of two malignant PTs and 11 of 13 FAs were correctly diagnosed cytopathologically by at least three of the authors. The presence of hypercellular stromal fragments was the most useful feature in distinguishing PTs from FAs, and the presence of cytological atypia of the stromal cells was the most important feature in distinguishing malignant from benign PTs. Sampling error was the most common reason for cytological misdiagnosis of PTs. The two FAs misdiagnosed as PTs were each of cellular type. The results of this study suggest that it is possible to distinguish PTs from FAs using FNAC in most cases. We recommend that if hypercellular stromal fragments are identified in a FNAC specimen of a fibroepithelial lesion, the cytopathologist should raise the possibility of a PT and the surgeon treat the patient accordingly.     

Can clinical features of bipolar-I disorder be assessed reliably on the telephone?

BACKGROUND: The reliability of telephone interviews for rating 25 selected individual items of the Diagnostic Interview for Genetic Studies (DIGS) was assessed among persons with remitted bipolar disorder I (BPD I, n = 20). METHODS: The Diagnostic Interview for Genetic Studies (DIGS) was administered directly (with two raters present) and by telephone in random order to 20 adults with bipolar disorder I. RESULTS: Telephone interviews achieved reliability comparable to direct interviews for 16 items (64%), but were considered unsatisfactory for seven others (28%). Two other items, which evaluated the overlap between substance abuse and mood disorder, were considered unreliable for both methods of interview. LIMITATIONS: The presence of two interviewers for the in-person interview may have led to over-estimation of in-person reliability. Investigator bias in favor of phone interviews and a relatively small sample may have confounded the results. CONCLUSIONS: Telephone interviews may be used to evaluate individuals with BPD I in remission, provided the limitations of this method are recognized. They have limited reliability for dissecting overlap between mood abnormalities and psychotic phenomena or substance abuse.     

Can synaptophysin be used as a marker of breast cancer diagnosed by core‐needle biopsy in epithelial proliferative diseases of the breast?

The differential diagnosis of epithelial proliferative disease using core needle biopsy (CNB) is problematic because it is difficult to differentiate between intraductal papilloma, ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Many studies have reported that breast cancer lesions are positive for neuroendocrine (NE) markers, whereas only a small number of studies have reported immunopositivity for NE markers in normal mammary tissues or benign lesions. We asked whether NE factors could be used as markers of breast cancer. We determined the immunopositivity rate of synaptophysin, an NE marker, in 204 lesions excised from the breast using CNB in patients who visited a university‐affiliated comprehensive medical facility and examined whether synaptophysin is a marker of breast cancer. The specimens were classified as synaptophysin‐negative cases (56 benign, 99 malignant); equivocal cases (<1 %: 2 benign, 15 malignant); and synaptophysin‐positive cases (1 benign, 31 malignant). The sensitivity, specificity, positive predictive value, and negative predictive value for malignancy of the lesions classified as synaptophysin positive were 23.3 %, 98.2 %, 96.9 %, and 36.1 %, respectively. The respective values for lesions classified as equivocal were 11.6 %, 96.6 %, 88.2 %, and 36.1 %. Synaptophysin may provide a marker of breast cancer diagnosed by CNB.     

Can carcinogenic potency be predicted from in vivo genotoxicity data? a meta‐analysis of historical data

Genotoxicity is generally a parameter used for hazard identification, however, the applicability of using in vivo genotoxicity tests for hazard characterization has never been thoroughly investigated in a quantitative manner. Genotoxicity assays could be useful for the determination of cancer potency parameters given that genotoxicty tests measure mutations and/or chromosomal aberrations which are strongly associated with carcinogenesis. A detailed literature survey was performed in search for dose-response data in various in vivo genotoxicity and carcinogenicity studies. The benchmark dose (BMD) approach was applied using the dose-response modeling program PROAST. Dose-response data were available from 18 compounds in the micronucleus assay (MN), the in vivo transgenic rodent mutation assay (TG) and the comet assay, and their BMD(10) values were compared to the BMD(10) from carcinogenicity studies in mice. Of the 18 compounds, 15 had acceptable dose-response data from the MN and the TG, but only 4 from the comet assay. A major limitation in our analysis was the lack of proper dose-response studies using the recommended protocols. Nevertheless, our findings are promising because even with these suboptimal studies, a positive correlation was observed when the lowest BMD(10) from the genotoxicity tests (MN and TG) was compared to the tissue-matched carcinogenicity BMD(10) . It is evident that more compounds need to be analyzed with proper dose-response schemes to further validate our initial findings. Experimental designs of genotoxicity assays need to shift from focusing only on hazard identification where positive and negative results are reported, to a more quantitative, dose-response assessment.     

Is core needle biopsy superior to fine‐needle aspiration biopsy in the diagnosis of papillary breast lesions?

Since the 1980s core needle biopsy (CNB) has gained remarkable popularity and in many institutions it has replaced fine-needle aspiration biopsy (FNAB). However, similar to FNAB, limitation remains in the ability of this procedure to reliably diagnose a small, but prognostically significant, number of breast lesions. These include entities such as atypical ductal hyperplasia, fibro-epithelial tumors, radial scar, papillary lesions, and lobular neoplasia. To assess the diagnostic accuracy of CNB vs. FNAB in the same breast lesions, we reviewed our cases of papillary lesions of the breast. In a retrospective study, we identified 36 cases of FNAB and 11 cases of CNB diagnosed as papillary lesions and compared the results with their corresponding surgical specimen. Interpretation ranged from papillary vs. atypical papillary lesions favoring benign vs. malignant tumors, respectively. Occasionally, definitive diagnosis of papillary carcinoma was entertained. Immunohistochemical staining with smooth muscle actin was used to evaluate the presence or absence of a myoepithelial cell layer. FNAB had benign findings in 21 lesions, atypical in 10, and malignant in five. Of the five lesions yielding malignant features, four had invasive carcinoma and one had micropapillary ductal carcinoma in situ (DCIS). Surgery revealed invasive carcinoma in three of the cases interpreted as atypical papillary lesions and invasive cancer and micropapillary DCIS in three of the cases diagnosed as benign lesions. Similar results were obtained with CNB. DCIS was found in one out of six of the cases diagnosed as papilloma. Out of the four cases that were interpreted as atypical papillary lesion, surgery revealed invasive carcinoma in one case and one case had micropapillary DCIS. Diagnosis of malignancy was confirmed by histology in one case interpreted as papillary carcinoma by CNB. This study suggested that both FNAB and CNB share similar diagnostic challenges and a follow-up surgical excision is indicated when diagnosis of a papillary lesion is entertained by both procedures.     

Can the electromyographic fatigue threshold be determined from superficial elbow flexor muscles during an isometric single-joint task?

The purpose of this study was to compare the electromyographic fatigue threshold (EMG_FT) values determined simultaneously from superficial elbow flexor muscles during an isometric single-joint task. Eight subjects performed isometric elbow flexions at randomly ordered percentages of maximal voluntary contraction (20, 30, 40, 50 and 60%). During these bouts, electromyographic (EMG) activity was measured in the anterior head of Deltoïd, lateral head of Triceps brachii, Brachioradialis and both short and long head of Biceps brachii. For each subject and each muscle, the EMG amplitude data were plotted as function of time for the five submaximal bouts. The slope coefficient of the EMG amplitude versus time linear relationships were plotted against force level. EMG_FT was determined as the y-intercept of this relationship and considered as valid only if the following criteria were met: (1) significant positive linear regression (P < 0.05) between force and slope coefficient, (2) an adjusted coefficient of determination for force versus slope coefficient relationship greater than 0.85, and (3) a standard error for the EMG_FT below 5% of maximal voluntary contraction. The EMG_FT could only be determined for one muscle (the long head of Biceps brachii) and only in three out of the eight subjects (mean value = 24.9 ± 1.1% of maximal voluntary contraction). The lack of EMG_FT in most of the subjects (5/8) could be explained by putative compensations between elbow muscles which were indirectly observed in some subjects. In this way, EMG_FT should be studied from a more simple movement i.e., ideally a movement implying mainly one muscle.     

Variations in the processing of prostatic needle cores in the UK; what is safe?

AIMS: To determine the variation in the processing of prostatic needle cores in the UK and to compare the results with suggested guidelines. METHODS: A standard questionnaire was sent to 210 pathology departments enquiring about current practices. RESULTS: One hundred and thirty replies were received, which showed considerable variation in current methods. The number of cores received for each case ranged from three to 21, with the number of cores processed for each cassette varying from one to 10. Sixty per cent of centres used no special embedding techniques, and the number of sections cut for each case varied from two to 128, with a median of 12 sections for each case. Forty two per cent of laboratories did not take spare slides for immunochemistry. CONCLUSIONS: There is great variation in the processing of prostatic cores in the UK. In particular, some laboratories process a large number of cores in each cassette and do not use special embedding techniques. At present there are no established guidelines for the processing of these specimens. Enhanced techniques may well increase the sensitivity of the test but would increase the workload and costs to the pathology department. In view of the increasing workload from these specimens, a consensus for their optimum processing is required.     

Can patients’ preferences for involvement in decision-making regarding the use of medicines be predicted?

OBJECTIVE: The current study aimed to develop a model of patients' preferences for involvement in decision-making concerning the use of medicines for chronic conditions in the UK and test it in a large representative sample of patients with one of two clinical conditions. METHODS: Following a structured literature review, an instrument was developed which measured the variables that had been identified as predictors of patients' preferences for involvement in decision making in previous research. Five hundred and sixteen patients with rheumatoid arthritis or type 2 diabetes were recruited from outpatient and primary care clinics and asked to complete the instrument. RESULTS: Multivariate analysis revealed that age, social class and clinical condition were associated with preferences for involvement in decision-making concerning the use of medicines for chronic illness but gender, ethnic group, concerns about medicines, beliefs about necessity of medicines, health status, quality of life and time since diagnosis were not. In total, the fitted model explained only 14% of the variance. CONCLUSION: This study has demonstrated that current research does not provide a basis for predicting patients' preferences for involvement in decision-making. PRACTICE IMPLICATIONS: Building concordant relationships may depend on practitioners developing strategies to establish individuals' preferences for involvement in decision-making as part of the ongoing prescriber-patient relationship.     

Can an index of smokers’ emotional status predict the chances of success in attempts to quit smoking?

Smoking cessation still is a great challenge for smokers and health care professionals. Most subjects try cigarettes in adolescence under predominant environmental influences, and some psychological features are clearly associated with the establishment of continuous cigarette use. As a result, it is acceptable to assume that the risk of becoming regular smokers should be higher for subjects exhibiting imperfect psychological well-being. Since nicotine exhibits recognized psychopharmacological actions, an important reason for smoking would be the comfort of smokers’ emotional afflictions. In this scenario, cigarettes might be seen as effective coping instruments for smokers. We hypothesize that a simple measure covering major emotional features of smokers might become a useful instrument for predicting the chances of success in attempts to quit smoking. The development of this new test aimed to measure the degree of smokers’ emotional imbalance has the potential to predict the chances of success in response to standard therapy, as well as the need for introduction of intensive individualized psychological or psychiatric interventions. Preliminary analyses of a new test called Smokers’ Emotional Index (SEI) support such a hypothesis. The SEI scores showed significant correlations with the values of the Fagerström test of nicotine dependence (FTND) for adult smokers. More numerous and better correlation coefficients were also observed between aspects of smoking history with SEI punctuations than with FTND scores. A clinical trial is proposed to test this hypothesis that could help to improve the results of current approaches to smoking cessation.     

Atrophic vaginitis versus invasive squamous cell carcinoma on ThinPrep® cytology: Can the background be reliably distinguished?

The presence of pronounced squamous epithelial atrophy/atrophic vaginitis on cervicovaginal preparations can present diagnostic difficulties, particularly in the presence of a granular background. The purpose of this study was to compare and contrast the background material present on ThinPrep cytology in cases of atrophic vaginitis and invasive squamous cell carcinoma (SCC). Thirty-three cases of atrophic vaginitis showed a heavy background of granular material containing acute inflammatory cells, apoptotic bodies, and fresh/crenated red blood cells. These findings were indistinguishable from those present in five cases of invasive SCC. The only significant finding was the presence of malignant squamous epithelial cells in the latter. Since the background material in pronounced squamous epithelial atrophy/atrophic vaginitis mimics that present in invasive SCC on ThinPrep cytology, close attention must be paid to the cells present on the slide in order to render an accurate diagnosis.     

Can the passive elasticity of muscle be explained directly from the mechanics of individual titin molecules?

Recent progress in understanding the role of titin/connectin in muscle elasticity has been heavily based on results from single molecule mechanical experiments. The shape of force–extension curves from such data is similar to curves from muscle fibres and it has been tempting to assume that muscle elasticity can be extrapolated directly from the single molecule data. In this paper we discuss some of the factors that act on titin in the sarcomere that are likely to preclude such a direct extrapolation.     

Which cranial regions reflect molecular distances reliably in humans? Evidence from three‐dimensional morphology

Knowledge of the degree to which various subsets of morphological data reflect molecular relationships is crucial for studies attempting to estimate genetic relationships from patterns of morphological variation. This study assessed the phylogenetic utility of six different human cranial regions, plus the entire cranium. Three‐dimensional landmark data were collected for 83 landmarks from samples of skulls from 14 modern human populations. The data were subsequently divided into anatomical regions: basicranium, upper face, mandible, temporal bone, upper jaw, cranial vault, and a subset of points from around the entire cranium. Depictions of population molecular distances were calculated using published data on microsatellites for the same or closely related populations. Distances based on morphological variation of each of the anatomical regions were compared with molecular distances, and the correlations assessed. The morphology of the basicranium, temporal bone, upper face, and entire cranium demonstrated the highest correlations with molecular distances. The morphology of the mandible, upper jaw, and cranial vault, as measured here, were not significantly correlated with molecular distances. As the three‐dimensional morphology of the temporal bone, upper face, basicranium, and entire cranium appear to consistently reflect genetic relationships in humans, especially with more reliability than the cranial vault, it would be preferable to focus on these regions when attempting to determine the genetic relationships of human specimens with no molecular data. Am. J.Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.     

Evaluation of thyroid fine‐needle aspirations: Can ThinPrep be used exclusively to appropriately triage patients having a thyroid nodule?

Thyroid fine-needle aspiration (FNA) represents an ideal management tool for thyroid nodules. ThinPrep is routinely used in preparation of a variety of nongynecologic cytology specimens, including FNA. The authors investigated ThinPrep to determine if its diagnostic accuracy is sufficient to triage patients presenting with a thyroid nodule. ThinPrep (TP) slides from four separate study categories were reviewed in a blind fashion. Twenty-five cases of papillary carcinoma, follicular lesion, Hashimoto's thyroiditis and multinodular goiter were examined retrospectively. Diagnostic accuracy of TP for each diagnostic category was determined relative to the final FNA diagnosis. Of 100 total study cases, 46 (46%) had noncorrelation. Twenty five (25%) of the study cases had noncorrelation as a result of insufficient cellularity. The diagnostic accuracy of TP for papillary carcinoma was 64%, for follicular lesion 24%, for Hashimoto's thyroiditis 72% and for multinodular goiter 56%. Cytologic features of papillary carcinoma, Hashimoto's thryoiditis, and multinodular goiter are preserved in TP slides. Cytologic features of follicular lesion are less predictable in TP slides. When all cases of noncorrelation were examined, we concluded that insufficient or marginal cellularity most often accounts for the discrepancy between TP and CS diagnoses in each study category. If techniques can be established to improve cellularity of TP slides, particularly in follicular lesions, we believe that sufficient diagnostic accuracy can be achieved to result in appropriate patient triage. Additional studies exploring methods to improve TP cellularity are needed before TP can be used as the sole diagnostic test for thyroid FNA.     

The extracellular matrix – the under‐recognized element in lung disease?

The lung is composed of airways and lung parenchyma, and the extracellular matrix (ECM) contains the main building blocks of both components. The ECM provides physical support and stability to the lung, and as such it has in the past been regarded as an inert structure. More recent research has provided novel insights revealing that the ECM is also a bioactive environment that orchestrates the cellular responses in its environs. Changes in the ECM in the airway or parenchymal tissues are now recognized in the pathological profiles of many respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Only recently have we begun to investigate whether these ECM changes result from the disease process, or whether they constitute a driving factor that orchestrates the pathological outcomes. This review summarizes our current knowledge of the alterations in the ECM in asthma, COPD, and IPF, and the contributions of these alterations to the pathologies. Emerging data suggest that alterations in the composition, folding or rigidity of ECM proteins may alter the functional responses of cells within their environs, and in so doing change the pathological outcomes. These characteristics highlight potential avenues for targeting lung pathologies in the future. This may ultimately contribute to a better understanding of chronic lung diseases, and novel approaches for finding therapeutic solutions. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.