Current diagnostic pathology最新文献

A positive blood culture or culture of cerebrospinal fluid (CSF) obtained postmortem could be due to a genuine positive, to agonal spread, to postmortem translocation or to contamination. A review of published evidence indicates that, if specimens are taken with care, the majority is sterile. Mixed growth occurs in less than 10% and is mainly due to contamination. Postmortem translocation is rarely a problem if the body is refrigerated promptly after death. Agonal change is less common than often assumed. A single isolate of a potential pathogen in perinatal cases and in adult practice is likely to be a genuine positive (PPV>50%); in sudden unexpected death in infancy (SUDI), however, a single isolate should be regarded as only a possible cause of death (PPV<50%) in the absence of corroboration. If bacterial invasion causes or contributes to rapid death, there might not be time for the histological changes of inflammation to develop and more subtle signs should be sought; including cell counts and protein estimations of CSF. Sampling upper-airways secretions shortly after death and before refrigeration provides useful information if infection is suspected. The results can be compared with community controls in epidemiological studies. In the future, genomic and proteomic techniques need to be added to standard methods to determine the role of bacteria in sudden death. The key message is that if specimens are taken with care, and interpreted with care, then useful information can be obtained.

Advances in our understanding of glomerulonephritis (GN) have come from both clinical and research studies. New animal models of human GN, human and mouse genetic studies, and molecular and immunological tools have helped to identify new inflammatory mediators and regulatory molecules, resulting in a better understanding of the pathogenesis of human GN and novel therapeutic strategies. In this article, we review recent advances in Goodpasture's disease, antineutrophil cytoplasmic antibody-associated GN, membranous glomerulopathy, membranoproliferative GN and a new classification of lupus nephritis.

The UK National External Quality Assessment Schemes in renal pathology and renal transplant pathology have accumulated evidence on the problems encountered by diagnostic histopathologists in routine practice. These can be subdivided into qualitative (getting the diagnosis right) and quantitative (achieving consistency in assessing the severity of a process). Some cases simply present difficult diagnostic problems. But in the qualitative group, problems often arise because descriptive terms (such as focal segmental glomerulosclerosis (FSGS) or interstitial nephritis) are accepted as a ‘diagnosis’ without further thought to explaining the underlying cause of the pattern. This often demands clinical, biochemical and serological information; the renal pathologist should be capable of discussing such evidence with nephrologists. There is sometimes a tendency to overdiagnose recently described or ‘fashionable’ diseases. In transplant pathology, early (and potentially catastrophic) antibody-mediated rejection is particularly easily missed, as is polyoma virus infection. In transplant pathology, the main quantitative problem is the evaluation of acute rejection and chronic allograft nephropathy, in which, despite the development of the Banff classification, interobserver variation remains high. Quantitation is an obvious problem in native renal biopsies in evaluating lupus nephritis, but an assessment of disease ‘grade and stage’ is likely to be important when reporting most biopsies.

Although the principles the pathologist uses to assess renal biopsies are similar when reporting adult and paediatric biopsies, the interpretation of the findings may differ owing to relative differences in the frequencies of particular diagnoses in childhood versus adulthood, as well as age-related changes in normal histological appearances. In addition, there are a range of conditions that are either unique to or much more frequent in childhood compared with adult practice, for example congenital nephrotic syndrome subtypes, whereas other conditions, such as hypertensive renal disease or diabetic nephropathy, remain a significant component of adult renal pathology practise but are almost never encountered in childhood. The renal biopsy plays a central role in the management of many paediatric conditions presenting to the nephrologist, and percutaneous ultrasound-guided renal biopsy in children appears safe, with a low frequency (<1%) of serious complications. The most common indication for renal biopsy in childhood is nephrotic syndrome, either in the first year of life, in which the differential diagnoses are usually relatively specific to this age group, or in later childhood, when the major differential diagnoses are minimal-change nephropathy (minimal-change disease) and focal segmental glomerulosclerosis. Other entities that may be encountered commonly in paediatric renal biopsy practise include congenital disorders of the glomerular capillary basement membrane, such as Alport nephropathy, and a range of cystic diseases of the kidney. This review will provide an overview of these issues, focusing predominantly on those issues and entities specific to paediatric practise.

Drug-induced renal disease is common and responsible for a variety of pathological effects on the kidney, many of which are potentially recoverable. The main types of renal injury predominantly involve the tubules and interstitium, leading to acute tubular injury and necrosis, or interstitial nephritis with inflammatory tubular injury. Aminoglycoside antibiotics, β-lactam antibiotics and non-steroidal anti-inflammatory agents are common offenders. Other types of renal injury are related to vascular damage and more rarely glomerular injury. Thrombotic microangiopathy is one of the most common types of acute vascular injury, whereas more chronic vascular changes leading to ischaemic fibrosis occur with long-term therapy with calcineurin inhibitors and analgesics. A knowledge of the drug history and possible nephrotoxic effects is crucial in renal biopsy interpretation for identifying drug-related renal disease.

The spectrum of histopathological lesions of pulmonary hypertensive vascular disease is extraordinarily varied. A number of distinct patterns can be recognized, and these correlate with aetiological factors and clinical data. Recent research has yielded important new insights on the pathogenesis of pulmonary hypertension at the molecular and cellular level, and various key mechanisms are emerging. These include induction and maintenance of vasoconstriction, endothelial activation and proliferation, and thrombosis. In the light of these developments, a re-evaluation of lesions at the histopathological level is receiving a new level of significance, as histological data complement those from research based on non-morphological techniques. We review the main histopathological features of hypertensive pulmonary vascular disease in this perspective.

Lung cancer is the leading cause of cancer death in the world. The vast majority are of the non-small-cell lung carcinoma (NSCLC) histological type, for which the only effective treatment remains surgical resection. However, most of NSCLC are non-resectable at the time of diagnosis and some patients would benefit from adjuvant chemotherapy. Predicting the prognosis and the response to therapy requires identifying prognostic factors and therapeutic targets specific to each histological subtype of NSCLC and—ideally—of each patient. With the aim of compiling the most important prognostic biomarkers reported in the literature, this review focuses on those that can be investigated by in-situ approaches. These biomarkers are implicated in regulation of the cell cycle, resistance to apoptosis, immortality and—as recent discoveries on tyrosine kinase (TK) receptor mutations have led to promising clinical applications—in the TK signalling pathway.

Pulmonary and thoracic sarcomas are rare tumours arising from any of the tissues of the chest, including soft tissue and bone of chest wall, lung, pleura and thymus and heart. They show a wide range of histological appearances and are classified on histological grounds by the presence of specific and characteristic differentiation features and, increasingly, the presence of specific chromosomal translocations. The relative frequency of individual tumour types varies with the anatomical site and age of the patient. Most pulmonary and thoracic sarcomas present as large, heterogeneous masses, although presentation as solitary pulmonary nodules, central endobronchial tumours, and intraluminal masses within the pulmonary arteries has also been described. Metastatic sarcomas are much more likely to be encountered than primary lesions and, as such, the diagnosis of primary sarcoma of the thorax should be made only after sarcoma-like primary lung and pleural malignancies and metastatic disease have been excluded.

Assessment of inflammatory processes in the lung can be difficult and interpreting the clinical significance can be daunting. An important part of the diagnostic process is the assessment of the pattern and distribution of the disease process in the lungs. Inflammatory conditions by and large show a limited number of distributions—airway, parenchymal or both, with the last being split into those that show an airway distribution in the parenchyma and those that largely spare the airways. This article aims to review patterns of inflammation involving the airways and their clinical associations.