Tissue pathology in undergraduate medical education: atrophy or evolution?

Changes are occurring in undergraduate medical curricula and there is limited published information about how contemporary tissue pathology is taught. The aim of this study was to collect information on this topic and to invite expert opinion about best teaching practice. A postal questionnaire survey of medical schools in the UK was performed, with a response rate of 23/28 schools (82%). The two most striking findings were the variation in teaching and learning strategies between schools and the spirit of the respondents, some relishing the challenges associated with reorganization and some thoroughly demoralized. The main concerns about pathology teaching were a feeling of lack of ownership of the content taught, an overall lack of visibility of tissue pathology in teaching and assessment, and staff shortages. Respondents valued the autopsy as an educational tool but were finding it increasingly difficult to provide. On the other hand, key opportunities for pathology teaching were highlighted through the questionnaire. The potential for developments in information technology and the possibility of creating national forums to develop core curricula and generate e-resources was recognized. The findings of this study will provide a milestone against which future change in pathology education can be measured.     

Comorbid Aβ toxicity and stroke: hippocampal atrophy,pathology, and cognitive deficit

Numerous clinical and epidemiological reports indicate that patients with history of vascular illness such as stroke are more likely to develop dementia as the clinical manifestation of Alzheimer's disease. However, there are little data regarding the pathologic mechanisms that link vascular risk factors to the factors associated with dementia onset. We provide evidence that suggests intriguing detrimental interactions between stroke and β-amyloid (Aβ) toxicity in the hippocampus. Stroke was induced by unilateral striatal injection of endothelin-1, the potent vasoconstrictor. Aβ toxicity was modeled by bilateral intracerebroventricular injections of the toxic fragment Aβ. Gross morphologic changes in comorbid Aβ and stroke rats were enlargement of the lateral ventricles with concomitant shrinkage of the hippocampus. The hippocampus displayed a series of synergistic biochemical alterations, including microgliosis, deposition of Aβ precursor protein fragments, and cellular degeneration. In addition, there was bilateral induction of connexin43, reduced neuronal survival, and impaired dendritic development of adult-born immature neurons in the dentate gyrus of these rats compared with either rats alone. Behaviorally, there was impairment in the hippocampal-based discriminative fear-conditioning to context task indicating learning and memory deficit. These results suggest an insight into the relationship between hippocampal atrophy, pathology, and functional impairment. Our work not only highlights the exacerbated pathology that emerges when Aβ toxicity and stroke occur comorbidly but also demonstrates that this comorbid rat model exhibits physiopathology that is highly characteristic of the human condition.     

Is encroachment of the carotid termination into the substantia innominata associated with its atrophy and cognition in Alzheimer's disease?

The internal carotid artery termination (CAT) ends in a T-shaped bifurcation just below the substantia innominata (SI), which contains cognitively strategic cholinergic neurons and undergoes atrophy in Alzheimer's disease (AD). This study investigated whether an elongated CAT with possible resulting encroachment into the SI would correlate with SI atrophy and with cognitive dysfunction in AD. We rated the degree of CAT encroachment upon the SI and measured SI volume on magnetic resonance imaging in 30 AD patients, 30 AD patients with subcortical small vessel disease, and 30 age-matched controls. CAT encroachment significantly correlated with SI volume after adjusting for age within the overall group and the groups with dementia. AD patients with higher CAT encroachment scores had lower SI volumes and lower attention, memory, and executive test scores. These data suggest that CAT encroachment may mechanically injure the SI, exacerbating cholinergic damage and contributing to cognitive impairment. This process may represent a possible previously underappreciated mechanism for interaction between large-vessel cerebrovascular disease and AD.     

A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology

We describe the clinical, neuropathological, and genetic features of a Finnish patient with a novel α-synuclein (SNCA) mutation A53E. The patient was clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at 36 years. In the neuropathological analysis performed at the age of 60 years, highly abundant SNCA pathology was observed throughout the brain and spinal cord showing features of multiple system atrophy and PD. Neuronal and glial (including oligodendroglial) SNCA inclusions and neurites were found to be particularly prominent in the putamen, caudatus, amygdala, temporal and insular cortices, gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the dentate fascia of the hippocampus. The A53E mutation was found in 2 other relatives who had parkinsonism. Our results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy- and PD-type phenotype.     

Integrating pathology and radiology disciplines: an emerging opportunity?

ABSTRACT: Pathology and radiology form the core of cancer diagnosis, yet the workflows of both specialties remain ad hoc and occur in separate "silos," with no direct linkage between their case accessioning and/or reporting systems, even when both departments belong to the same host institution. Because both radiologists' and pathologists' data are essential to making correct diagnoses and appropriate patient management and treatment decisions, this isolation of radiology and pathology workflows can be detrimental to the quality and outcomes of patient care. These detrimental effects underscore the need for pathology and radiology workflow integration and for systems that facilitate the synthesis of all data produced by both specialties. With the enormous technological advances currently occurring in both fields, the opportunity has emerged to develop an integrated diagnostic reporting system that supports both specialties and therefore improves the overall quality of patient care.     

Ear and temporal bone pathology: is anything new?

The ear and temporal bone are a challenging areas for the diagnostic pathologist. The anatomy is complex and lesions may be small and relatively inaccessible. Many tumours occurring at this site are rarely encountered. Biopsy tissue samples may be crushed, small and often associated with bone, which complicates processing. Correlation with imaging is essential and interpretation often requires specialist expertise. In this article selected lesions are discussed in order to illustrate diagnostic difficulty the surgical pathologist encounters with small biopsies and on approaching the cut up of complex resection specimens from this site. The aim is to raise awareness of the recently introduced ICCR minimum data set for the reporting of tumours from ear and temporal bone and to alert readers to the discovery of new entities in middle ear investigated by novel molecular diagnostic techniques.     

Cholinergic systems and schizophrenia: primary pathology or epiphenomena?

Post mortem schizophrenia research has been driven first by the dopamine and then the glutamate hypotheses. These hypotheses posit primary pathology in pathways dependent upon dopamine or glutamate neurotransmission. Although the dopamine and glutamate hypotheses retain considerable theoretical strength, neurobiological findings of altered dopamine or glutamate activity in schizophrenia do not explain all features of this disorder. A more synthetic approach would suggest that focal pathological change in either the prefrontal cortex or mesial temporal lobe leads to neurochemical changes in multiple neurotransmitter systems. Despite the limited experimental evidence for abnormal cholinergic neurotransmission in psychiatric disorders, increased understanding of the role of acetylcholine in the human brain and its relationship to other neurotransmitter systems has led to a rapidly growing interest in the cholinergic system in schizophrenia. This review focuses on the basic anatomy of the mammalian cholinergic system, and its possible involvement in the neurobiology of schizophrenia. Summaries of cholinergic cell groups, projection pathways, and receptor systems, in the primate and human brain, are followed by a brief discussion of the functional correlations between aberrant cholinergic neurotransmission and the signs and symptoms of schizophrenia.     

Fine-needle aspiration and intraoperative consultation in thyroid pathology: when and how?

Fine-needle aspiration (FNA) and frozen section evaluation are traditional components of the management of thyroid lesions. Their role and usefulness are dictated by some basic facts about thyroid pathology: (a) nodules are very common; (b ) they are benign in the majority of cases; and (c) the diagnosis of malignancy is primarily based on cytologic features in the case of papillary carcinoma, and on the presence of invasion of the tumor capsule or of blood vessels in the case of follicular carcinoma. The common occurrence of benign thyroid nodules mandates a cost-effective effective method for preoperative screening. Since, as already stated, the diagnosis of papillary thyroid carcinoma (by far the most common thyroid malignancy) is based on the identification of characteristic cytologic features, FNA has easily emerged in the past 30 years as the most accurate and cost-effective tool-indeed a true cornerstone-for the preoperative management of thyroid nodules. Standardized terminology to report cytologic diagnoses is highly recommended and is being implemented worldwide. Conversely, the importance of intraoperative frozen section diagnosis has been constantly decreasing over the past years, as a direct consequence of the widespread application of FNA. It may, however, be very useful in cases that are suspicious for papillary carcinoma on FNA and in selected cases with an indeterminate cytologic diagnosis.     

'One medicine---one pathology': are veterinary and human pathology prepared?

The American Medical Association and the American Veterinary Medical Association have recently approved resolutions supporting 'One Medicine' or 'One Health' that bridge the two professions. The concept is far from novel. Rudolf Virchow, the Father of Modern Pathology, and Sir William Osler, the Father of Modern Medicine, were outspoken advocates of the concept. The concept in its modern iteration was re-articulated in the 1984 edition of Calvin Schwabe's 'Veterinary Medicine and Human Health.' The veterinary and medical pathology professions are steeped in a rich history of 'One Medicine,' but they have paradoxically parted ways, leaving the discipline of pathology poorly positioned to contribute to contemporary science. The time has come for not only scientists but also all pathologists to recognize the value in comparative pathology, the consequences of ignoring the opportunity and, most importantly, the necessity of preparing future generations to meet the challenge inherent in the renewed momentum for 'One Medicine.' The impending glut of new genetically engineered mice creates an urgent need for prepared investigators and pathologists.     

A case of Adams-Oliver syndrome with associated brain and pulmonary involvement: further evidence of vascular pathology?

We report on a case of Adams-Oliver syndrome (AOS) with typical skin and limb defects along with the unique findings of pulmonary hypertension and central nervous system (CNS) involvement. Adams-Oliver syndrome has a wide spectrum of physical anomalies ranging from characteristic aplasia cutis congenita (ACC), transverse limb defects, and cutis marmorata telangiectica to extensive lethal anomalies. While pulmonary hypertension is usually not associated with AOS, the abnormal endothelial regulation of vascular tone seen in the pulmonary vasculature may enhance current pathophysiologic concepts of vascular abnormalities in AOS. There is accumulating evidence of significant CNS defects in AOS. This infant had hypoplastic corpus callosum and focal findings in the periventricular white matter. Evaluation for pulmonary hypertension and CNS anomalies in patients suspected to have AOS, can help identify those who are at risk for acute morbidities and associated developmental delays.     

Autosomal dominant optic atrophy with unilateral facial palsy: a new hereditary condition?

A mother and daughter are reported with bilateral optic atrophy with onset in infancy and unilateral facial palsy. This appears to be a novel autosomal dominant disorder.     

Dysplasia classification: pathology in disgrace?

Grading of dysplasia is demanded almost daily from most diagnostically active pathologists. It is also notoriously subjective and lacks intra- and inter-observer reproducibility. This is partly due to the lack of validated morphological criteria, upon which pathologists have reached consensus. It is largely due to the biological nature of the evolution of dysplasia, not in discrete steps but as a continuum. Better morphological definition, but also fundamental research into the nature of the process, is necessary to resolve this issue.     

Eosinophilic angiocentric fibrosis and granuloma facial with extra facial presentation, the same pathology?

Eosinophilic angiocentric fibrosis is a rare fibro inflammatory lesion of unknown etiology which occurs usually in the upper respiratory tract mucosa of middle-aged adults. The histologic features show an eosinophilic vasculitis and an angiocentric fibrosis with onion-skin pattern. Firstly described as a mucosal variant of the granuloma facial, which is a rare cutaneous vasculitis with eosinophils, it is considerated by some authors as separated entities. Four cases have been described in the orbit and three of them were in fact an extension of a sinusal lesion. We report the first case affecting a 69-years-old male patient who showed an isolated orbital involvement in association with granuloma facial, extra facial. This observation illustrates the relationship between these two pathologies and consolidates the first hypothesis of a single disease with cutaneous or mucosal involvement.     

Tissue microarrays: what will they bring to molecular and anatomic pathology?

The analysis of a large number of tumor tissues with conventional techniques of molecular pathology is tedious and slow. The authors recently developed the tissue microarray technology that makes it possible to sample up to 1,000 tumors on one glass slide, which then can be analyzed by fluorescence in situ hybridization, RNA in situ hybridization, or immunohistochemistry. The tissue microarray technology has the potential to significantly accelerate molecular studies that seek associations between molecular changes and clinicopathologic features of the cancer. Examples of potential applications for tissue microarrays include testing and optimization of probes and antibodies, the organization of large tissue repositories, and the facilitation of multicenter studies. Further, tissue microarrays can be used for educational purposes as well as to improve quality control and standardization of staining methods and interpretation. Tissue microarrays have become one of the most promising tools for the molecular and anatomic pathologist and will have many applications in cancer research, as well as in other fields of pathology. This review article gives an overview of current applications of tissue microarrays as well as possible future development of the technology.     

Immunity and cognition: what do age-related dementia, HIV-dementia and 'chemo-brain' have in common?

Until recently, dogma dictated that the immune system and the central nervous system (CNS) live mostly separate, parallel lives, and any interactions between the two were assumed to be limited to extreme cases of pathological insult. It was only a decade ago that T cells in the injured brain were shown to play a protective rather than a destructive role. In this article, we explore the role of the immune system in the healthy brain, focusing on the key function that T lymphocytes have in the regulation of cognition. We discuss candidate mechanisms underlying T cell-mediated control of cognitive function in human cognitive diseases associated with immune decline, such as age- and HIV-related dementias, 'chemo-brain' and others.