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.
This article is the second of two papers relating to the histopathological diagnosis of basaloid skin tumours and the uses of immunohistochemistry. The first paper focused on basal cell carcinoma and variants, and this paper will concentrate on tumours that may be confused with basal cell carcinoma. The basaloid tumours of the skin can be classified according to the general classification of skin tumours, including epidermal, appendageal (hair follicle and sweat gland derived) and others including cutaneous metastases. The areas of discussion concentrate on the distinction of basal cell carcinoma from basaloid squamous cell carcinoma, infiltrative basaloid tumours (desmoplastic trichoepithelioma, infiltrative basal cell carcinoma, microcystic adnexal carcinoma and eccrine epithelioma), follicular induction overlying dermatofibroma, basaloid proliferations in naevus sebaceus, trichoepithelioma, trichoblastoma, trichoepithelioma-like basal cell carcinoma, pilomatrical tumours and selected sweat gland tumours. The immunohistochemical stains that may be of use in differential diagnosis are discussed, including BerEP4, epithelial membrane antigen, CD10, bcl-2, Cam5.2, CK20, carcinoembryonic antigen and p53.
Gliomas are the commonest groups of tumours arising in the central nervous system (CNS) in both children and adults. Their incidence in both age groups appears to be increasing, for reasons that are poorly understood. The biological behaviour of gliomas varies from slow-growing well-demarcated tumours that are curable by excision to malignant invasive tumours that are uniformly fatal. Pathology has a major role to play in the management of patients with gliomas by providing a histological diagnosis and tumour grade, which are of major prognostic significance. Molecular genetic studies have found loss of genetic material in many gliomas, with progressive losses identified with increasing tumour grade. In oligodendrogliomas, loss of heterozygosity on chromosomes 1p and 19q is of therapeutic significance as a predictor of tumour response to chemotherapy. The forthcoming revision of the WHO classification of CNS tumours is expected to provide updated recommendations on glioma diagnosis and grading.
Basal cell carcinoma (BCC) is the prototypical basaloid tumour of the skin, but may show various patterns simulating other cutaneous tumours, particularly squamous cell carcinoma and trichoepithelioma (TE). Other challenges are presented by BCC with marked pleomorphism, glandular differentiation, neuroendocrine differentiation, clear cells and sarcomatoid change. Peripheral palisading and retraction (artefact) of the epithelium from the stroma are the most useful features to support a diagnosis of BCC, but can occasionally be seen in other benign and malignant cutaneous neoplasms and are inconspicuous or lacking in some cases of BCC. Increased ‘stromal’ mucin accompanying retraction and peripheral palisading is extremely suggestive of BCC and is rarely seen in other tumour types. Diffuse and strong BerEP4 staining and absence of epithelial membrane antigen staining is characteristic of BCC, and is an immunophenotype rarely encountered in other tumours except for TE. CD10 staining of the basaloid epithelium, in the absence of significant stromal staining, may support a diagnosis of TE-like BCC rather than TE in more organized variants.
There is a clinico-pathological continuum of infection-driven sepsis syndromes, the most severe being septic shock with multi-organ failure. The organ dysfunctions are due to inflammatory cytokines from remote sources (the site of infection) and constitute the systemic inflammatory response syndrome (SIRS). The common causes are Gram-positive and Gram-negative infections; the common infection sites are (in descending frequency) lung, blood stream, intra-abdominal disease, urological sepsis and surgical wounds; the commonest organ dysfunctions are systemic shock, kidney, lung, and heart. The differential diagnosis of severe sepsis includes disseminated malignancy, atherosclerosis, and haemophagocytic syndrome. New treatments for severe sepsis are being trialled to raise the poor survival rates in intensive care. The role of the autopsy is to describe carefully the organ lesions, provide microbiological evidence of infection, and to correlate these with the clinical features and therapeutic variables.
