‘Information is information’: a public perspective on incidental findings in clinical and research genome‐based testing

The potential for genomic incidental findings is increasing with the use of genome‐based testing. At the same time approaches to clinical decision making are shifting to shared decision‐making models involving both the healthcare community and the public. The public's voice has been nearly absent in discussions on managing incidental findings. We conducted nine focus groups and nine interviews (n = 63) with a broad cross‐section of lay public groups to elucidate public viewpoints on incidental findings that could occur as a result of genome‐based testing in clinical and research situations. Data were analyzed using qualitative content analysis. Participants wanted incidental findings disclosed to them whether or not these were clinical or research findings. Participants used different terms to define and describe incidental findings; they wanted to know that incidental findings are possible and be given a choice to learn about them. Personal utility was an important reason for disclosure, and participants believed that managing information is a shared responsibility between professionals and themselves. Broad public input is needed in order to understand and incorporate the public's perspective on management of incidental findings as disclosure guidelines, and policies are developed in clinical and research settings.     

The FIND Program: Improving Follow-up of Incidental Imaging Findings

Incidental findings are findings identified on imaging which are unrelated to the original reason for examination and require follow-up. The Radiology Finding Incidental Disease (FIND) Program was designed to track and improve follow-up of incidental imaging findings. The purpose of this study was to determine the frequency of incidental findings on cross-sectional imaging and the adherence to suggested follow-up of incidental findings prior to and after implementation of a structured reporting and tracking system. A retrospective analysis of 2000 patients with computed tomographic cross-sectional imaging was performed: 1000 patients prior to implementation of the FIND Program and 1000 patients 1 year after establishment of the program. Data collected included the frequency of incidental findings, inclusion of follow-up recommendations in the radiology report, and adherence to suggested follow-up. There was a higher rate of completion of recommended follow-up imaging in the post-implementation group (34/67, 50.7%) compared to the pre-implementation (16/52, 30.8%) (p = 0.03). Implementation of an incidental findings tracking program resulted in improved follow-up of incidental imaging findings. This has the potential to reduce the burden of clinically significant incidental findings possibly resulting in later presentation of advanced disease.

     

The pathologist's approach to bronchoscopic biopsies

Bronchoscopically retrieved biopsies of lung tissue often provide valuable information for diagnosis and patient management. There value is often relative: the findings are part of the database for a patient and correlated with the other clinical and radiologic data that is available. Less commonly the findings are diagnostic, providing a specific diagnosis that is the major arbiter of management. The pathologist's task with these specimens is to get as much value from them as possible. This cannot be done by tabulating microscopic findings alone; correlation of the pathologic findings with the clinical and radiologic findings is a necessary part of this exercise.     

A history of sport-related concussion on event-related brain potential correlates of cognition

Over the past decade, a growing body of research has detailed persistent changes to neuroelectric indices of cognition in amateur and professional athletes with a concussion history. Here, we review the relevant neuroelectric findings on this relationship while considering the duration from the last concussive event. Collectively, the findings support a negative relation of concussive injury to neuroelectric indices of brain health and cognition in the presence of normal clinical findings. The results suggest that event-related brain potentials are especially well-suited for identifying aspects of cognition that remain dysfunctional for an extended period of time, which are otherwise unidentified using standard neuropsychological tests. Such findings also suggest the need for additional research to fully elucidate the extent to which concussive injuries negatively impact brain health and cognition.     

Pathological findings in homocystinuria

Pathological findings are described in four cases of a new aminoaciduria in which homocystine is excreted in the urine. All the patients were mentally retarded children. Three of them presented diagnostic features of Marfan's syndrome. Necropsy on one case and biopsy findings in the others are described. Fatty change occurs in the liver. The most striking lesions are vascular. Metachromatic medial degeneration of the aorta and of the elastic arteries in the necropsied case are considered in relation to Marfan's syndrome. Other changes, particularly thrombosis which is prevalent in homocystinuria, suggest the possibility of a platelet defect. The findings are discussed in respect of an upset in the metabolism of sulphur-containing amino-acids and with particular reference to Marfan's syndrome.     

Regulatory forum opinion piece: thresholds in toxicologic pathology*

The definition of diagnostic thresholds is an important aspect of identification and recording of histopathologic lesions in toxicology studies. Although the primary goal of the pathology examination is to identify and interpret lesions associated with the administration of the test article, the toxicologic pathologist will encounter many changes in the tissues that are variations in tissue morphology, tissue artifacts, and spontaneous background findings. The pathologist must establish appropriate thresholds to produce a comprehensive record of the findings so that potentially treatment-related lesions may be identified. However, the findings should not be so detailed as to create overly complex data with the appearance of differences when none exist. Care must be taken to be consistent in the identification and recording of background lesions, since they are important for historical control data, which is often used as a reference when interpreting findings in current studies. Insufficient or inconsistent recording of findings may result in a deficiency in the historical control data for the identification and interpretation of a finding in the future.     

Classification of fibreoptic bronchoscopic findings: analysis of 2,698 cases

Fibreoptic and rigid bronchoscopy are widely used diagnostic and therapeutic tools in pulmonary medicine, but there is little available knowledge regarding the classification of bronchoscopy findings. We aimed to propose a practical classification, to reveal interrelationship among endoscopic findings and to demonstrate demographic characteristics in our region. We analysed 2,698 consecutive bronchoscopy reports, retrospectively. Bronchoscopic findings were divided into four classes: direct tumour findings (malignant or benign), indirect tumour findings, chronic bronchitic changes and findings of mucosal injury. Bronchial secretions were classified into four categories: serous, seromucous/mucous, purulent/mucopurulent, and haemorrhagic/haemorrhage/coagulum. There was no endobronchial pathology in 18.3% of the patients. The frequency of the findings of direct tumour, indirect tumour, mucosal injury, and chronic bronchitic changes were 19.1%, 20.2%, 14.8%, and 27.6%, respectively. The frequencies of seromucous/mucous and purulent/mucopurulent secretions were lowest in the patients who had direct tumour findings. Mucosal injury findings were most common concomitant observation in the group of indirect tumour findings. All types of secretions except haemorrhagic were strongly associated with mucosal injury findings. We think that it is necessary for a classification of endoscopic findings to be developed to optimise clinical practice.     

Diagnostic yield of the autopsy in a university hospital and a community hospital

To determine the extent to which autopsies yield unexpected findings that are relevant to the patient's death and whether cases with a high yield of such findings can be identified selectively, we studied a total of 233 autopsies at a university hospital and at a community hospital. The rates at which autopsies detected major unexpected findings whose premortem diagnosis would probably have improved survival were 11 percent at the university hospital and 12 percent at the community hospital. Major unexpected findings whose premortem diagnosis would not have prolonged survival were found in another 12 and 21 percent of cases, respectively. Pulmonary embolism and fungal infections in immuno-compromised hosts were the most common major unexpected findings. Neither we nor the patients' physicians were able to identify from the clinical data the autopsies likely to have high yields. Furthermore, the physicians' estimates of an autopsy's expected yield were similar for patients evaluated by autopsy and for matched patients who were not. We conclude that the autopsy continues to yield clinically relevant findings at a high level and that it is not currently possible to predict which cases will have high yields. Autopsies are vital to ensure the quality of medical care, and autopsy rates must be increased substantially if this role is to be fully realized.     

Etiological factors in the development of PTSD in clinical samples of Vietnam combat veterans

This paper presents a review of empirical literature that deals with etiological factors in combat-related post-traumatic stress disorder (PTSD). Variables implicated in PTSD from three time frames, premilitary, military, and postmilitary, are identified, and findings from relevant research are discussed. There is consistency across studies in showing significant correlations between PTSD and combat exposure and post-military psychosocial adjustment. Less consistent are the findings with regard to relationships between premilitary psychosocial factors and PTSD. Recent findings from studies that have explored possible physiological correlates of PTSD also are discussed. Based on current literature, implications for future research on etiological factors in combat-related PTSD are presented.     

Perspective on the interpretation of research and translation to clinical care with therapy-associated metastatic breast cancer progression as an example

This commentary was written as a collaboration between the Board of the Metastasis Research Society and two patients with metastatic breast cancer. It was conceived in response to how preclinical scientific research is sometimes presented to non-scientists in a way that can cause stress and confusion. Translation of preclinical findings to the clinic requires overcoming multiple barriers. This is irrespective of whether the findings relate to exciting responses to new therapies or problematic effects of currently used therapies. It is important that these barriers are understood and acknowledged when research findings are summarized for mainstream reporting. To minimize confusion, patients should continue to rely on their oncology care team to help them interpret whether research findings presented in mainstream media have relevance for their individual care. Researchers, both bench and clinical, should work together where possible to increase options for patients with metastatic disease, which is still in desperate need of effective therapeutic approaches.     

Prenatal diagnosis of the megacystis-microcolon-intestinal hypoperistalsis syndrome.

The ultrasonographic and necropsy findings in a male fetus with the megacystis-microcolon-intestinal hypoperistalsis syndrome are reported. The presence of vacuolation and degeneration in smooth muscle of bowel and bladder wall supports a previous suggestion that the macroscopic findings in this syndrome are the consequence of an underlying visceral myopathy. The unusual degree of severity of the findings in this fetus may explain the marked skewing of the sex ratio observed in affected liveborn infants.     

Chromosome rearrangements in a metastatic adenocarcinoma of the prostate

Cytogenetic analysis of a metastatic tumor derived from an adenocarcinoma of the prostate revealed a hypodiploid karyotype with the presence of six marker chromosomes. The findings are discussed in relation to cytogenetic findings in other cancers, including those in prostatic cancer.     

Epidermoid cyst of the spleen: diagnosis suggested by fine-needle aspiration biopsy.

The authors report a case of epidermoid cyst of the spleen, in which cytologic findings were characteristic and suggested this diagnosis. Histologic and immunohistochemical findings are described in the attempt to clarify the histogenesis of this cystic lesion.     

The impact of reporting incidental findings from exome and whole-genome sequencing: predicted frequencies based on modeling

PurposeThe American College of Medical Genetics and Genomics released practice guidelines recommending reporting of incidental findings from exome and whole-genome sequencing by massively parallel (next-generation) sequencing for multiple conditions. Policy statements from other agencies are still being developed, and many attempt to take into consideration the predicted increase in workload caused by reporting incidental findings. We describe the effects of changing the sensitivity and the specificity, as well as the implications of varying diagnostic criteria and a priori prevalence, and those of increasing the number of included conditions, on rates of incidental findings.MethodsWe developed a simple mathematical model based on binomial probability for predicting rates of incidental findings. We primed and validated the model using published variant frequencies.ResultsThe model correctly calculates observed rates of incidental findings. Changing the model’s parameters shows that even minor changes in diagnostic criteria or sequencing accuracy cause large variation in rates of incidental findings.ConclusionOur model correctly explains observed rates of incidental findings. Key drivers of rates include diagnostic criteria, variant frequency, disease penetrance, and sequencing and bioinformatics accuracy. Rates of incidental findings are relatively insensitive to even large increases in the number of conditions included.     

Adverse tissue reactions after total hip arthroplasty

Hip arthroplasty is commonly performed on patients with debilitating hip disease to relieve symptoms and improve quality of life. Generally, long-term success rates are excellent. However, a subset of patients requires revision due to prosthesis failure. A wide array of microscopic findings can be seen in surrounding tissues and many of the findings are etiologically nonspecific. The aim of this review is to discuss the etiologies and accompanying adverse tissue reactions seen with prosthesis failure, including the findings seen in aseptic lymphocyte–dominated vasculitis-associated lesion. Aseptic lymphocyte–dominated vasculitis-associated lesion is an important diagnostic consideration as its proposed pathogenesis is a type VI hypersensitivity response to metal ions. In addition, we also propose a diagnostic algorithm that incorporates clinical and histopathologic findings to suggest an etiologic cause. This proposed algorithm may be clinically useful as, to date, there is no consensus on nomenclature.     

CT interpretation of gastrointestinal tract diseases

Most inflammatory, neoplastic and vascular disorders manifest bowel wall thickening on computed tomography (CT). Therefore, it is very important to understand the patterns of bowel wall involvement (degree, length, symmetry and contrast enhancement patterns) in each category to make a correct diagnosis. Observing extraluminal changes also help to classify the primary causes of pathological conditions involving the gastrointestinal tract. Adequate CT examinations with optimal opacification of the gastrointestinal tract are essential not only to avoid false positive findings but also to detect subtle or minimal lesions. If findings for establishing a diagnosis are equivocal, the use of combined findings increases the diagnostic accuracy of CT.     

Neurogenic tissue syndrome. Review and specific results

A review is given of the skeletal muscle and specific methods required for its examination, before major findings from the neurogenic tissue syndrome are discussed in some detail. These findings, not specific of the diseases involved, may be grouped as follows along three lines: alterations resulting from (repetitive) denervation; re-innervation; secondary myopathic alterations (also called concomitant myopathy). Evaluation and rating of all findings and data relative to percentual incidence are followed by postulation of a guideline for diagnosis.     

Juxtacortical osteosarcoma. A distinct malignant bone neoplasm

The purpose of this report is the study of a malignant bone tumor of similar histological picture with conventional (intramedullary) osteosarcoma. Contributing factors in the study of juxtacortical osteosarcoma are the clinical, X-ray and histologic pictures. A case of parosteal osteosarcoma in a 28-year-old male is reported. In conjuction with X-ray findings we review the histological characteristics of the tumor through serial sections of the peripheral, central and parosteal parts and the findings are described in detail. In addition to the histological findings, differential diagnosis and prognosis are also discussed. From the general study of the tumor it has been shown that juxtacortical osteogenic sarcoma behaves differently in contrast to classic osteosarcoma, depending on the degree of differentiation of the tumor.     

Cutaneous meningioma

Cutaneous meningioma is a rare tumor that most commonly occurs on the scalp and occurs in both congenital and acquired forms. It invokes a wide clinical differential diagnosis, but diagnosis is based on characteristic histologic and cytologic findings. Congenital lesions can often present years after birth and even in adult patients. Acquired lesions occur in adulthood. We review histologic, cytologic, and electron microscopic findings and explore how these are used to separate this entity from other entities in the differential diagnosis. While ultrastructural and cytologic findings are similar to those of more common intracranial meningiomas, these tumors exhibit a range of histologic differences. A lack of awareness of this entity precludes correct diagnosis.