We present the sequence of events leading to the permanent human kidney. Nephrogenesis begins around 22 days after fertilisation and completes around the 34–36th week of gestation. There are three pairs of kidneys in human development: the pronephros, mesonephros and metanephros, arising sequentially from intermediate mesoderm on the dorsal body wall. The first two pairs involute and are resorbed during fetal life, but they are essential precursors to the metanephros and normal adult kidneys do not develop if they are disrupted. Human metanephric kidney development begins around day 28 post conception when the ureteric bud arises as an outpouching of the distal mesonephric duct/Wolffian duct. Glomeruli form from 8–9 weeks and nephrogenesis continues in the outer rim of the cortex until 34 weeks. Perturbation of early pathways can lead to a range of phenotypes including renal agenesis, dysplasia and duplex kidneys, as well as malpositioning defects such as pelvic or horseshoe kidneys if they fail to ascend to their normal 12th thoracic to 3rd lumbar vertebral site during development.

The use of imaging in epilepsy care is a powerful tool to show a patient why they have epilepsy. You can use it to correlate your semiology history with an imaging finding. Magnetic resonance imaging (MRI) is the most widely used modality for epilepsy care. Ordering an epilepsy protocol MRI on a 3 Tesla (3T) machine increases the likelihood of finding an epilepsy’s etiology. Common findings include stroke, tumor (i.e., ganglioglioma), hippocampal sclerosis, encephalocele, cortical dysplasia, heterotopia, polymicrogyria, or cavernoma. For MRI-negative epilepsy, additional tests to identify the epileptogenic region include PET (positron emission tomography) and SPECT (single photon emission computed tomography). Functional MRI (fMRI) can delineate brain areas critical for specific functions.Lastly, the use of CT (computed tomography) is limited to identification of acute findings like hemorrhage and tumors in new onset seizures.

Aplasia is a pathologic term that is broadly defined as the absence or near-absence of one or more haematopoietic lineages in the bone marrow (BM). Clinically, BM aplasia affecting more than one lineage is referred to as aplastic anaemia (AA), despite the fact that this group of disorders often results in pancytopaenia rather than anaemia alone. Cytopaenias can be seen in a number of different conditions, and new-onset pancytopaenia in children and adults requires an extensive work-up, including a BM core biopsy (BMB) for confirmation of haematopoietic aplasia/hypoplasia and exclusion of an infiltrative marrow process or fibrosis. Bone marrow aplasia develops as a result of injury to multipotent haematopoietic stem cells, which can occur in the context of constitutional (primary aplasia) or acquired (secondary aplasia) disorders (Table 4.1). This chapter will discuss the diagnostic criteria and pathophysiology of specific disorders presenting with aplasia and demonstrate an algorithmic approach to the diagnostic evaluation of patients presenting with this common and non-specific finding (Table 4.2).

The term ‘dysplasia’ refers to ‘an unequivocal neoplastic epithelial alteration without invasive growth’. The term ‘intraepithelial neoplasia’ often replaces ‘dysplasia’ in World Health Organization (WHO) guidance. Dysplasia is a precursor lesion of cancer and a marker for high cancer risk, offering a window of opportunity for early detection and cure of neoplasia. Most pathologists now classify columnar dysplasia as low grade (LGD) and high grade (HGD). The criteria for grading dysplasia include both cytological and architectural abnormalities. The diagnosis of dysplasia can be challenging in some clinical settings, especially when there is a background of active or resolving inflammation [e.g., in Barrett’s oesophagus (BO) or inflammatory bowel disease (IBD)] that may cause reactive epithelial atypia. In addition, there is significant inter- and intra-observer variability for the diagnosis and grading of dysplasia. The variability may reflect the limitations of morphology-based criteria and has led to the development of adjunctive diagnostic methods such as immunohistochemistry. These methods, although promising, are controversial and require evaluation in further studies. This chapter describes the classification, microscopic features, and grading of dysplasia at different sites in the gastrointestinal (GI) tract.

Gastro-oesophageal reflux disease (GORD) is a condition that develops as a result of retrograde flow (reflux) of gastro-duodenal contents into the oesophagus, with or without mucosal tissue damage. The main symptoms include heartburn without a specific frequency or duration. Histological mucosal changes include mild basal cell hyperplasia, scattered intraepithelial eosinophils, dilated intracellular spaces, and lamina propria papillae reaching the upper one-third of the squamous epithelium. Other histological findings that can be present in the setting of GORD are balloon cells, keratinocyte vacuolization, intraepithelial lymphocytosis, vascular lakes, and parakeratosis. Ulceration can also occur if GORD is severe. Barrett’s oesophagus (BO) is an acquired condition defined by endoscopically visible metaplastic columnar epithelium more than 1 cm above the gastro-oesophageal junction (GOJ) with biopsy confirmation of columnar metaplasia. Presence or absence of intestinal metaplasia (IM) should be documented as it harbours an increased risk of progression to oesophageal adenocarcinoma (OAC). The risk of progression of BO to OAC increases if there is dysplasia in addition to columnar metaplasia. Endoscopic examination in conjunction with histopathological evaluation and documentation of presence or absence of dysplasia is the current recommended method of surveillance.

Various intestinal and extraintestinal conditions may complicate inflammatory bowel disease (IBD). Intestinal complications include infections, strictures, obstruction, fistulas, dysplasia, and malignancy. Extraintestinal complications or associations include cutaneous disease, arthropathy, ocular problems, primary sclerosing cholangitis, and other forms of liver disease. The intestinal complications whose diagnosis and assessment relies most heavily on histopathology are cytomegalovirus (CMV) infection, dysplasia, and malignancy. Reactivation of latent CMV is more likely in ulcerative colitis than Crohn’s disease, is more common in those with immunosuppression and/or severe disease, and is associated with a worse clinical outcome. CMV inclusions are often detectable on H&E examination. Immunohistochemistry for CMV is specific and sensitive. Histopathology may also play a role in recognising other infections such as amoebiasis and TB and may contribute to the assessment of fissures and fistulas. Confident recognition of dysplasia depends on histology, although endoscopic methods of detection are becoming more reliable. Colorectal carcinoma (CRC) is the most common malignancy to complicate IBD and is more likely than non-IBD CRC to present at a younger age and to be right-sided and is more likely to show signet ring cell differentiation, a peritumoral lymphocytic reaction, and a mucinous phenotype. Small bowel cancer may complicate Crohn’s disease but is rare overall. A lymphoproliferative disorder may complicate IBD, especially in the setting of thiopurine therapy.