The urinary tract comprises the kidneys, pelvicalyceal systems, ureters, bladder and urethra. The kidney is responsible for excretion of the waste products of metabolism, the waste products being excreted in the form of an aqueous solution called urine . Urine passes from the kidneys into the pelvicalyceal systems and thence via the ureters to the bladder, which acts as a reservoir. Urine is held in the bladder by a series of muscular sphincters until sufficient volume has accumulated. Relaxation of the sphincters and contraction of smooth muscle in the bladder wall allows the urine to be voided to the exterior through the urethra (micturition) at a convenient time.

The kidney

The kidney is divided into two main anatomical divisions, the cortex and medulla ( E-Fig. 15.1 H ). Disorders of the kidney may affect either of these zones, but diseases affecting one part will often have secondary effects on the other component. Disorders may arise from a wide range of pathological causes, many of which are common in other organ systems (e.g. infections, tumours, drug reactions, vascular disorders). However, the kidney is unusual in that it is much more prone to immunological disorders than most other organs. Vascular diseases such as hypertension, diabetes mellitus and vasculitis may also have profound effects on renal function. Disorders of the kidney can be conveniently divided into categories according to which structural component of the kidney is primarily affected:

Glomerulus ( E-Fig. 15.2H )

  • Glomerulonephritis (GN ) of various types, most of which are due to deposition of immunoglobulins and/or complement components (collectively called immune complexes ) within the glomerulus ( Figs 15.2 to 15.7 ).

    Fig. 15.1, End-stage kidney (MP).

    Fig. 15.2, Acute diffuse proliferative (‘endocapillary’) glomerulonephritis (HP).

    Fig. 15.3, Necrotising GN. (A) Segmental necrotising GN (HP); (B) glomerular crescent (HP).

    Fig. 15.4, Mesangial proliferative GN (HP).

    Fig. 15.5, Membranoproliferative (mesangiocapillary) glomerulonephritis. (A) (HP); (B) methenamine silver (HP).

    Fig. 15.6, Membranous nephropathy. (A) H&E (HP); (B) IgG immunofluorescence (HP); (C) EM.

    Fig. 15.7, Focal segmental glomerulosclerosis (HP).

  • Vasculitis: strictly speaking, this is a vascular disorder, but some forms affect the glomerular capillaries giving the clinical and pathological appearances of a GN. ( Fig. 15.3 )

  • Ischaemia: common systemic diseases, including hypertension and diabetes mellitus, as well as a range of thrombotic and embolic conditions may cause glomerular injury.

  • Disorders involving deposition of material in the glomerulus

    • Diabetes mellitus: deposition of abnormal glycosylated proteins causes irreversible structural and functional abnormalities in the glomerulus ( Fig. 15.9 ).

      Fig. 15.8, Minimal change disease (HP).

    • Amyloidosis: deposition of amyloid proteins in the glomerulus alters the structure and therefore the function of the glomerulus ( Fig. 15.10 ).

  • Congenital and structural abnormalities: some inherited conditions result in abnormal glomerular structure and function; an example is the condition thin basement membrane disease.

Tubules and interstitium ( E-Fig. 15.3H )

  • Acute tubular necrosis (ATN) is usually due to profound hypotension causing ischaemic damage to tubular epithelial cells. Some forms of drug toxicity may give rise to similar appearances.

  • Interstitial nephritis (AIN) is an important cause of acute renal failure and is most often due to drug hypersensitivity.

  • Infections including acute and chronic pyelonephritis , renal abscess and TB.

  • Mechanical obstruction of the ureters or bladder may lead to hydronephrosis and recurrent infection.

Blood vessels

  • Hypertension causes marked changes to both large and small renal vessels. The changes of benign/essential hypertension and accelerated/malignant hypertension are discussed in Fig. 15.15 .

  • Thrombotic microangiopathy is a pattern of vascular damage that results in intravascular thrombosis due to endothelial cell injury. It is typically seen in association with haemolytic anaemia, thrombocytopenic purpura and often renal failure. Although many of the pathological changes are due to damage to the microcirculation, especially the glomerular capillaries, thrombosis also occurs in larger vessels.

  • Vasculitis may affect larger vessels as well as glomerular capillaries, but the main manifestations are usually glomerular.

  • Diabetes mellitus is an important metabolic disease that has profound vascular effects, affecting both large vessels and the microvasculature.

Clinical patterns of renal injury

Damage to one component of the kidney inevitably damages the other parts. Severe reversible damage to any of the above components of the kidney may lead to acute renal failure or acute kidney injury (AKI) . Some conditions are reversible, e.g. some types of AKI and most cases of acute diffuse proliferative GN, but many lead to progressive damage. In cases with progressive damage, there will be some degree of permanent renal impairment and a proportion of these will develop chronic renal failure , a condition that was invariably fatal until the advent of renal dialysis and kidney transplantation.

  • Acute renal failure: Abrupt cessation of activity of the nephrons usually presents initially as a marked fall in urine production (oliguria) , which may even be total (anuria) . This is accompanied by a rapid rise in serum urea and creatinine levels. Disturbances of fluid and electrolyte balance soon follow, particularly a rise in the serum potassium level and metabolic acidosis.

  • Chronic renal failure : Progressive retention of nitrogenous metabolites causes a slow rise in serum creatinine levels due to insufficient glomerular filtration. Concomitant failure of tubular function produces widespread abnormalities in biochemical homeostasis, including salt and water retention, metabolic acidosis and other electrolyte imbalances, particularly hyperkalaemia.

Key to Figures

F fibrosis of glomerulus In interstitial space P protein cast T tubule

Diseases of the glomerulus

Glomerular disorders arise from a variety of causes; the two major causes being immunological (including disorders confined to the kidney and some systemic diseases) and metabolic (the most important being diabetes mellitus). It is confusing to many students that there is not a direct one-to-one relationship between a particular mechanism of damage and a particular histological appearance and/or clinical syndrome. In fact, most causes of glomerular damage will give rise to one of several clinical presentations, summarised in Table 15.1 , along with the diseases with which they are most commonly associated. Acute and chronic renal failure are described above and may supervene in any of the above conditions. For example, an individual with a severe nephritic syndrome may progress quickly to acute renal failure or an individual with undiagnosed diabetes mellitus, who has had undetected proteinuria for some time, may first be diagnosed with chronic renal failure.

Role of Renal Biopsy

The introduction of safe and reliable techniques of percutaneous needle biopsy of the kidney has greatly increased knowledge about the natural history of renal diseases, particularly by elucidating the underlying lesion early in the course of glomerular diseases when treatment might be applied effectively. It is of limited value in chronic renal failure when the kidney is shrunken and histological changes are non-specific, i.e. end-stage kidney ( Fig. 15.1 ). Renal biopsy is also frequently used in the assessment of renal transplants to detect the presence of transplant rejection, drug toxicity and a number of other conditions that may cause reduced function of the graft. Maximum information is obtained from a needle biopsy of renal tissue using a combination of the following methods:

  • Light microscopy , including special stains to define glomerular structures

  • Electron microscopy to show the presence and precise location of immune complexes, which appear as irregular deposits of electron-dense material (dense deposits) , and other deposits such as amyloid, diabetic changes, structural changes to the glomerular basement membrane (GBM) and podocytes.

  • Immunofluorescence microscopy to localise and identify the class of immunoglobulins and complement components.

Table 15.1
Clinical syndromes associated with glomerular disease.
Syndrome Clinical features Histological changes Associated disease
Acute nephritis Haematuria, Hypertension, Uraemia (↑BUN)
Oedema (often periorbital), Oliguria or anuria
Hypercellular glomerulus with obstructed capillary loops Acute post-infective GN
IgA nephropathy/Henoch-Schönlein purpura
Nephrotic syndrome Proteinuria (3.5 g/24 h), Hypoalbuminaemia, Oedema, Hyperlipidaemia Changes to the structure of the glomerular filtration mechanism, including the GBM and/or podocytes Diabetes mellitusAmyloidosis
Minimal change nephropathy
Focal segmental glomerulosclerosis
Membranous nephropathy
Mixed nephritic– nephrotic syndrome Features of both nephritic and nephrotic syndromes Both cellular proliferation and GBM alterations Membranoproliferative GN (mesangiocapillary GN)
Asymptomatic haematuria Periodic dark-coloured urine or microscopic haematuria Proliferation of glomerular cells or structural abnormalities of GBM IgA nephropathy
Thin basement membrane disease
Asymptomatic proteinuria Proteinuria Early stages of the changes in the GBM seen in the nephrotic syndrome Early phases of all of the conditions which cause nephrotic syndrome

The immunofluorescence and electron microscopic patterns of immune complex deposition can be vital to differentiate between different types of GN, which have similar patterns of glomerular damage by light microscopy. Examples include:

  • IgA nephropathy: granular deposits of IgA in the mesangium

  • Membranous nephropathy: granular deposits of IgG and complement on the epithelial side of the GBM

  • Goodpasture’s syndrome: linear deposits of IgG along the GBM

  • Systemic lupus erythematosus (SLE): deposits of most classes of immunoglobulin and many complement components at any site in the glomerulus

Interpretation of a renal biopsy also requires information about the clinical history, physical examination and other investigations to arrive at a correct diagnosis. For example, a membranous pattern of GN might be idiopathic, related to use of certain drugs (e.g. gold, penicillamine) or may be part of the spectrum of SLE (Class V lupus nephritis).


Most types of GN are caused by immune complex deposition in the glomerulus. This applies to primary GN , where the condition is confined to the kidney (e.g. membranous nephropathy , membranoproliferative GN ), and to diseases with a systemic component (e.g. Goodpasture’s syndrome , SLE , Henoch-Schönlein purpura ).

The site of immune complex deposition is dependent on the size of the complexes, which is in turn dependent on the type of antigen and on the class of immunoglobulin produced, i.e. the host response. The antigen may be either a normal component of the body (a self antigen as in Goodpasture’s) or an external antigen such as a bacterial product (as in post-streptococcal GN ). Immune complexes may be deposited from the circulating blood or may be formed in situ. In the latter situation, the complexes may involve intrinsic glomerular antigens (basement membrane components in Goodpasture’s) or antigens that have been deposited there from the circulation (e.g. DNA in the case of SLE). An important exception to this rule is minimal change nephropathy where the podocytes are thought to be damaged by a cell-mediated immune response, rather than by immune complex deposition.

Whatever the mechanism of damage to the glomerulus, the various immunological insults alter the structure and therefore the function of the glomerulus and ultimately of the nephron as a whole.

In response to damaging stimuli, the glomerulus appears to react in one or more of the following ways:

  • Swelling and/or proliferation of the normally flat endothelial cells lining the glomerular capillaries

  • Proliferation of the epithelial cells investing the outer surface of the glomerular capillary tuft (the podocytes ( E-Fig. 15.4 H ) and the cells lining Bowman’s capsule (crescent formation)

  • Thickening of glomerular basement membranes ( E-Fig. 15.5 H )

  • Proliferation of the cells of the mesangium and excessive production of acellular mesangial material

These reactions give rise to various histological patterns of GN, which can be identified by light microscopy. This is then put together with the immunofluorescence and electron microscopy findings, clinical history and other investigations to come to a definitive diagnosis. As in many other areas of histopathology, good communication between pathologists and clinicians is vital to arrive at an accurate diagnosis, which is essential for appropriate treatment.

Patterns of GN may be described as:

  • Diffuse: affecting all glomeruli

  • Focal: affecting some glomeruli

  • Global: the entire glomerulus is abnormal

  • Segmental: only part of the glomerulus is abnormal

We shall now consider some specific examples of GN, reviewing the typical histological and immunofluorescence patterns and their associated clinical presentations. As indicated in Table 15.1 , some diseases may present clinically in several different ways, with nephritic or nephritic features or even combinations of these.

For convenience, we shall begin with disorders which typically give rise to acute nephritic features ( acute diffuse proliferative GN ; Fig. 15.2 and necrotising GN ; Fig. 15.3 ) followed by those with mixed patterns of haematuria and proteinuria ( mesangial proliferative GN ; Fig. 15.4 and membranoproliferative GN ; Fig. 15.5 ) and then important causes of nephrotic syndrome ( membranous GN ; Fig. 15.6 , focal segmental glomerulosclerosis ; Fig. 15.7 and minimal change disease ; Fig. 15.8 ).

At the end of this section on glomerular diseases, we shall consider the typical changes of diabetes mellitus in the kidney ( Fig. 15.9 ) and the features of renal amyloidosis ( Fig. 15.10 ). It is worth bearing in mind that primary GN is a relatively rare disease, whilst diabetes and hypertension together account for the bulk of clinically important renal dysfunction in developed counties; in the developing world, toxins and infections are also very important factors in the burden of chronic renal disease.

Key to Figures

N neutrophils U urinary space

Key to Figures

B normal glomerular basement membrane C crescent D double contour basement membrane F fibrin M increased mesangial matrix and cellularity N normal glomerular segment R glomerular remnant

The Spectrum of C3 Nephropathy: Dense Deposit Disease and C3 Glomerulonephritis

This new classification affecting MPGN is based upon immunofluorescence findings. If immunoglobulins are identified as well as C3, the disease is viewed as immunoglobulin-mediated and is still defined as MPGN type I or type III, depending upon the location of the immune complexes. In contrast, those cases with isolated C3 in the glomerulus fall within the category of C3 nephropathy . Morphological and EM patterns vary and almost any pattern of glomerular damage can occur in C3GN, although MPGN is most common. All cases formerly called MPGN type II or dense deposit disease are now known to fall within this spectrum, as do a proportion of those previously classified as types I or III (now called C3 glomerulonephritis or C3GN ).

We now know that these patients have various congenital or acquired abnormalities affecting the alternative pathway of complement activation, some of which can be detected by serological tests or by genetic screening. Testing should be offered whenever the renal biopsy findings are of glomerulonephritis with dominant C3. Traditionally, renal outcomes in patients with MPGN were quite varied and some groups, including those with dense deposit disease, had a high chance of recurrence in transplanted kidneys. As well as conventional immunosuppressant drugs, there are now emerging targeted therapies such as anti-C5 antibodies, which may modify the underlying disease process in some patients.

Key to Figures

B glomerular basement membrane DD dense deposit M mesangial matrix S spike Sc sclerosis

Outcomes of Glomerular Disorders

The renal disorders in which the major abnormality involves the glomerulus may subside spontaneously or with treatment. However, if they progress, glomerular blood flow is obstructed, glomerular filtration ceases and the tubules associated with affected glomeruli become involved; thus many nephrons may cease to function. When sufficient nephrons have been affected, the clinical features of the disease gradually progress to chronic renal failure.

By way of illustration, a patient with the nephrotic syndrome caused by diabetic glomerular disease may slowly develop the features of chronic renal failure as individual nephrons are destroyed. In contrast, a patient who initially presents with the acute nephritic syndrome caused by a rapidly progressive GN with extensive crescents ( Fig. 15.3 ) may quickly progress to acute renal failure. As the glomeruli are rapidly destroyed by the disease process this becomes irreversible.

Key to Figures

BM glomerular basement membrane C capsular drop En endothelial cell cytoplasm FC fibrin cap H hyalinised arteriole K Kimmelsteil-Wilson nodule P podocyte foot process

Fig. 15.9, Diabetic glomerulosclerosis. (A) Nodular glomerulosclerosis (HP); (B) diffuse glomerulosclerosis (HP); (C) capsular drop (PAS) (HP); (D) normal glomerular basement membrane (EM); (E) diabetic basement membrane (EM).

Fig. 15.10, Renal amyloidosis. (A) H&E (HP); (B) sirius red (HP); (C) EM.

Fig. 15.11, Acute pyelonephritis (MP).

Disorders of the renal tubules and interstitium

The tubules and interstitium may be primarily damaged as a result of hypovolaemic shock, by inorganic and organic toxins or as the result of infection. In hypovolaemic states and intoxication, tubular epithelial cells may exhibit marked cytoplasmic degenerative changes or frank necrosis leading to the pathological term acute tubular necrosis ( Fig. 15.12 ) and producing the clinical syndrome of acute renal failure. Tubular epithelial cells have considerable powers of recovery and regeneration and acute renal failure may be reversible under such circumstances if the patient can be sustained in the interim by dialysis and other supportive measures.

Fig. 15.12, Acute tubular necrosis (MP).

Another increasingly important cause of tubulo-interstitial disease is drug toxicity giving rise to interstitial nephritis ( Fig. 15.13 ). In this condition, a large number of drugs have been implicated including certain antibiotics, non-steroidal anti-inflammatory drugs, thiazide diuretics and proton pump inhibitors. Onset may be acute or chronic. There is a mixed inflammatory infiltrate in the interstitium in which eosinophils may be prominent. Tubular damage occurs and the condition may proceed to chronic renal failure.

Fig. 15.13, Acute tubulo-interstitial nephritis (MP).

Infections of the kidney include acute and chronic pyelonephritis and tuberculosis (see Ch. 5 ). Acute suppurative bacterial infections of the kidney ( pyelonephritis ) usually follow ascending infection from the lower urinary tract, particularly when there is obstruction to urinary outflow such as in benign prostatic hyperplasia or pressure from the fetus in pregnancy; in such cases, coliform organisms (such as Escherichia coli and Proteus species) are the most frequent infecting agents. Infection may also spread to the kidney by the haematogenous route during episodes of bacteraemia. Acute pyelonephritis may be complicated by the development of papillary necrosis ( Fig. 15.14 ) or pus accumulation in a dilated, obstructed pelvicalyceal system ( pyonephrosis ) . Acute pyelonephritis is illustrated in Fig. 15.11 . Tuberculous infection of the kidneys and lower urinary tract may also arise by similar routes of spread.

Fig. 15.14, Renal papillary necrosis (LP).

Patients with urinary reflux or obstruction are prone to develop recurrent pyelonephritis Repeated attacks lead to scarring and after many episodes the kidney becomes coarsely scarred, a phenomenon termed chronic pyelonephritis .

Key to Figures

AA afferent arteriole G glomerulus N neutrophil polymorphs T dilated tubule

Vascular disorders

The kidney is especially vulnerable to the effects of arterial hypertension as illustrated in Figs 11.1 and 11.2 , and irreversible damage to nephrons may result either acutely from accelerated (malignant) hypertension or progressively over a period of years in benign (essential) hypertension.

Hypertensive nephrosclerosis resulting from benign (essential) hypertension is illustrated in Fig. 15.15 . Malignant or accelerated hypertension causes a different pattern of renal damage, similar to the changes seen in acute scleroderma , and may result in acute renal failure. In reality, hypertension cannot be neatly divided into essential and accelerated types; individuals who have had mild hypertension for many years may progress quite suddenly to very high blood pressures that put eyesight, kidneys and other organs at severe risk. This is especially the case where the individual has underlying renal disease that progresses. Other individuals may develop accelerated hypertension out of the blue.

Fig. 15.15, Hypertensive nephrosclerosis. (A) Benign hypertensive nephrosclerosis (HP); (B) malignant hypertensive nephrosclerosis (HP).

Fig. 15.16, Renal transplant rejection. (A) T cell mediated rejection, Type I (MP); (B) T cell mediated rejection Type II (HP).

Various forms of vasculitis may also affect the kidney, including polyarteritis nodosa (see Fig. 11.6 ) and those associated with antineutrophil cytoplasmic antibody (ANCA) such as granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis) and microscopic polyarteritis (see Fig.11.7 ).

Small infarcts of the renal cortex are common in patients with the above vascular disorders. They are usually seen as incidental findings in kidneys removed for other reasons (e.g. tumours). The infarcts are usually seen as wedge-shaped pale scars with the base abutting the renal capsule, although they may be seen in any stage of infarction (see Fig. 10.1 ). In kidneys with extensive infarcts, the cortical surface is pitted and the kidney is shrunken. In rare cases, abrupt interruption to the blood supply, such as renal artery thrombosis, may lead to renal cortical infarction where the entire renal cortex undergoes coagulative necrosis. The renal medulla is much more resistant to ischaemia.

Key to Figures

D dilated tubules E eosinophil I mononuclear inflammatory cells J junction between normal and necrotic tissue O interstitial oedema P renal papilla T tubulitis

Key to Figures

AA afferent arteriole H hyalinised sclerosed glomerulus S segment of glomerulus

Pathology of renal transplantation

Renal transplantation has become a routine treatment for chronic renal failure in many countries. The transplant recipient is freed from a life of regular dialysis with a consequent improvement in quality of life. The function of the transplanted kidney may however be affected by a number of factors in the days, weeks and months following transplantation. The most important of these include:

  • Acute tubular necrosis : this is identical to acute tubular necrosis from other causes ( Fig. 15.12 ). The major factor here is the ‘cold ischaemic time’, i.e. the length of time between harvesting of the kidney and re-establishment of vascular perfusion in the donor. Supportive measures may be needed in the immediate post-transplantation phase but usually this will resolve.

  • Rejection (see Fig. 15.16 )

  • Drug toxicity : routinely used immunosuppressive agents, such as ciclosporin A and related compounds (the calcineurin inhibitors), may have a range of effects on the kidney. Histologically, there may be changes in the tubules and/or the blood vessels. Exquisite control of dosage and sometimes transfer to a different agent will usually control this problem.

  • Infection : transplant recipients require immunosuppression to prevent rejection of the graft and this makes them susceptible to a range of infections.

  • Recurrent GN : this is more likely to be a problem months to years after transplantation than in the early stages.

Key to Figures

A adipose tissue I intimal arteritis M smooth muscle cells N tumour cell nest S oedematous stroma SM smooth muscle of artery wall T tubulitis V blood vessels

Tumours of the kidney

A range of benign and malignant tumours occurs in the kidney and many are unique to the kidney. Benign tumours include papillary adenoma , a fairly common incidental finding in nephrectomy specimens, oncocytoma , illustrated in Fig. 15.17 , and angiomyolipoma , shown in Fig. 15.18 .

Fig. 15.17, Oncocytoma (HP).

Fig. 15.18, Angiomyolipoma (LP).

The most common and important malignant renal tumour in adults is renal cell carcinoma. Several subtypes are recognised and some of the more common variants are illustrated in Fig. 15.19 . One of its important methods of spread is by venous invasion, typically giving rise to ‘cannon ball’ lung metastases and often bone metastases.

Fig. 15.19, Renal cell carcinoma. (A) Clear cell carcinoma (MP); (B) clear cell carcinoma (HP); (C) papillary carcinoma (MP); (D) chromophobe carcinoma (MP); (E) collecting duct carcinoma (LP); (F) collecting duct carcinoma (HP).

Our understanding of renal tumour pathology has been transformed in recent years by the use of new molecular techniques. Classification is now based upon a combination of histological appearances, immunohistochemical findings and the presence of typical genetic changes in certain tumour types. For example, papillary renal cell carcinomas typically show gains of chromosomes 7 and/or 17, as well as loss of the Y chromosome. These new investigative techniques have also revealed a range of rare but important hereditary renal cell carcinomas.

The kidney is the site of an important malignant tumour of children, nephroblastoma or Wilms’ tumour ( Fig. 15.20 ); this is an example of a ‘small round blue cell tumour’ and is of embryological origin.

Key to Figures

C undifferentiated cells G normal glomeruli I inflammation M foamy macrophages P papillary structures T malignant tubules Tu primitive tubular structures V blood vessel

Fig. 15.20, Nephroblastoma (MP).

Diseases of the lower urinary tract

The most important disorders of the lower urinary tract are infection and neoplasia. Infections are common, but usually remain confined to the bladder (cystitis) ; ascending spread into the ureters and pelvicalyceal systems may result in renal parenchymal involvement (acute pyelonephritis) as shown in Fig. 15.11 . Persistent or repeated infection in the urinary tract predisposes to the development of urinary stones (calculi) , particularly in the bladder and pelvicalyceal systems. Infections of the urethra (urethritis) are commonly sexually transmitted, often involving the organisms N. gonorrhoeae and Chlamydia .

The pelvicalyceal system, ureters and bladder are lined by a specialised epithelium known as transitional epithelium (urothelium) ( E-Fig. 15.11 H ). Malignant tumours of the urothelium, known as transitional cell or urothelial carcinomas ( Fig. 15.22 ), are common and are of particular interest because of the possible role of chemical carcinogens such as aniline dyes in their pathogenesis. Urothelial carcinomas may be either invasive or non-invasive. Most of the deeply invasive tumours are high-grade carcinomas. Malignant tumours are probably preceded by the development of urothelial dysplasia and carcinoma in situ ( Fig. 15.21 ). Benign tumours include transitional cell papillomas and inverted papillomas .

Fig. 15.21, Bladder carcinoma in situ (HP).

Fig. 15.22, Urothelial (transitional cell) carcinoma. (A) Low grade (LP); (B) high grade (LP); (C) high grade (HP).

Classification and grading of transitional cell neoplasms is complex and continues to evolve. The traditional WHO 1973 system recognised benign papillomas as well as transitional cell carcinomas of grades 1, 2 and 3. This system has some limitations as the criteria for these categories are not very well defined and a large proportion of tumours tend to be classified as grade 2. Also, some tumours that are now known to behave in a benign fashion are classified as grade 1 carcinomas. The newer WHO/ISUP 2004 system uses the term papillary urothelial neoplasm of low malignant potential (PUNLMP) for these very low grade tumours with likely benign behaviour and it splits the remaining malignant tumours into low grade and high grade groups. The two systems do not directly correspond. Despite the limitations described above, the old 1973 WHO classification remains in widespread use as a validated and reproducible system, but now it is used alongside the newer WHO/ISUP 2004 system as these are thought to provide the best prognostic information when applied in conjunction. This is illustrated in Table 15.2 .

Key to Figures

BV blood vessels M mitotic figures S stroma SM smooth muscle T tumour

Table 15.2
Classification of urothelial tumours.
WHO 1973 classification WHO/ISUP 2004 classification
Papilloma Papilloma
Transitional cell carcinoma Grade 1 Papillary urothelial neoplasm of low malignant potential (PUNLMP)
Transitional cell carcinoma Grade 2 Low-grade urothelial carcinoma
Transitional cell carcinoma Grade 3 High-grade urothelial carcinoma

Table 15.3
Chapter review.
Site Disorder Main pathological features Figure
Kidney: glomerular disorders End-stage kidney Sclerosed glomeruli, atrophic tubules, interstitial fibrosis 15.1
Acute diffuse proliferative GN Enlarged hypercellular glomeruli, infiltration by neutrophils, obstructed capillary loops 15.2
Necrotising GN Necrosis of glomerular tuft, may be segmental, may be associated with crescent formation 15.3
Mesangial proliferative GN Expanded mesangium with increased mesangial cells 15.4
Membranoproliferative (mesangiocapillary) GN Hypercellular, hyperlobular glomeruli with double contour GBM 15.5
Membranous nephropathy Thickened GBM, ‘spikes’ (silver stain) 15.6
Focal segmental glomerulosclerosis Idiopathic or secondary to segmental necrosis or nephron loss. Segment of tuft replaced by fibrosis 15.7
Minimal change disease Normal light microscopy and immunofluorescence, ‘fused’ podocyte foot processes on electron microscopy 15.8
Diabetic nephropathy Diffuse and nodular glomerulosclerosis, hyalinised arterioles, capsular drops, fibrin caps, thickened GBM 15.9
Renal amyloidosis Deposition of insoluble fibrillar protein in glomerulus and vessel walls, stains with Congo and Sirius red 15.10
Kidney: interstitial disorders Acute pyelonephritis Infiltration of interstitium and tubules by neutrophil polymorphs. May form abscesses and pyonephrosis 15.11
Acute tubular necrosis Dilated renal tubules with flattened ‘simplified’ epithelium, vacuolation and fragmentation of tubular cell cytoplasm 15.12
Acute tubulo-interstitial nephritis Often due to drug hypersensitivity. Interstitial oedema with eosinophils and mononuclear cells. Focal tubulitis 15.13
Renal papillary necrosis Infarction of renal papilla with inflammation at edge of infarcted area 15.14
Kidney: vascular disorders Essential hypertension Hypertrophied arteries with fibroelastic intimal thickening, sclerosed glomeruli 15.15A
Accelerated hypertension Fibrinoid necrosis of arterioles, ‘onion-skin’ intimal thickening of medium and large sized arteries, vascular thrombosis, acute ischaemia of glomeruli 15.15B
Kidney: transplant rejection Acute T-cell mediated rejection Inflammation of tubules (tubulitis) and interstitium (type I)
Inflammation of arteries (intimal arteritis, transmural arteritis, fibrinoid necrosis of artery wall (types II and III))
Kidney: tumours Oncocytoma Brown tumour macroscopically, often with central scar. Nests of bland epithelial cells with round nuclei and eosinophilic granular cytoplasm 15.17
Angiomyolipoma Mixture of abnormal blood vessels, smooth muscle cells and adipose tissue. Most are benign 15.18
Renal cell carcinoma Clear cell: cells have clear cytoplasm
Papillary: papillary epithelial structures with foamy macrophages in papillary cores
Chromophobe: cells with pale-stained cytoplasm and prominent cell borders
Collecting duct: infiltrating tumour with desmoplasia
Nephroblastoma Primitive undifferentiated cells, tubular structures 15.20
Bladder Carcinoma in situ Flat lesion consisting of highly atypical epithelial cells with mitotic figures and no maturation of cells towards the surface 15.21
Urothelial carcinoma (transitional cell carcinoma Papillary structures covered by abnormal urothelial cells. High grade lesions may form solid ulcerated plaque. Graded as high or low (and/or 1, 2, 3) 15.22

E-Fig. 15.1 H, Kidney H&E (LP).

E-Fig. 15.2 H, Renal corpuscle. (A) Schematic diagram; (B) PAS (HP).

E-Fig. 15.3 H, (A) Renal cortex H&E (MP), proximal and distal convoluted tubules. (B) PCT, Azan (HP); (C) PCT, PAS (HP); (D) DCT, H&E (HP); (E) DCT, PAS (HP).

E-Fig. 15.4 H, Glomerulus. (A) SEM ×1500; (B) SEM ×6000.

E-Fig. 15.5 H, Glomerulus. (A) EM ×4800; (B) EM ×14 000; (C) EM ×30 000. When examining both light and electron microscope specimens of glomeruli, the podocytes, endothelial cells and mesangium are identified most easily by tracing out the glomerular basement membrane. Micrograph (A) shows several capillary loops C lined by a thin layer of fenestrated endothelial cytoplasm. The endothelial cell nuclei E can be seen bulging into the capillary lumina. The capillary endothelial fenestrations F are better seen at higher magnification in micrographs (B) and (C) . The nuclei of several podocytes P can be seen, their primary processes P 1 giving rise to numerous secondary foot processes P 2 that rest on the glomerular basement membrane BM . At right midfield a branched mesangial stalk comprising mesangial cells M and mesangial matrix MM provides support for the capillary loops. The mesangium is separated from the capillary lumen only by the cytoplasm of the endothelial cells, while the podocytes and their basement membrane continue around the mesangial stalk, separating it from Bowman’s space. Part of Bowman’s capsule BC is seen at the periphery, consisting of a squamous epithelial cell and underlying basement membrane. The subpodocyte space SPS and interpodocyte space IPS are easily identified, although the subpodocyte space exit pore is not seen. At the periphery of the glomerulus, Bowman’s space BS is delineated by the podocyte cell bodies on one side and the parietal epithelial cells on the other. Micrograph (B) shows three glomerular capillaries C lined by attenuated endothelial cytoplasm E with wide fenestrations F . A podocyte P extends several primary processes P 1 onto the capillaries, these in turn giving rise to multiple secondary foot processes P 2 separated by filtration slits FS . The subpodocyte space SPS can again be identified. The glomerular basement membrane BM separates the podocytes and capillary endothelium. The thickness of the basement membrane appears variable, but this is due to the slightly oblique plane of section; the basement membranes are in fact of uniform width. At even higher magnification in micrograph (C) , three of the components of the glomerular filter are seen. The fenestrated capillary endothelium E is closely applied to the luminal surface of the glomerular basement membrane BM ; on the opposite side are podocyte secondary foot processes P 2 , separated by filtration slits of uniform width and bridged by the slit diaphragms. Part of the subpodocyte SPS space is seen, but the podocyte cell body which delimits the subpodocyte space is not apparent. The wide central lamina densa of the glomerular basement membrane can be seen bordered on each side by a narrow lamina rara. The glycocalyces of the endothelial cells and podocytes are not apparent in these micrographs; special fixation and processing techniques are required to demonstrate them.

E-Fig. 15.6, Amyloidosis .

E-Fig. 15.7, ∗ Diabetic kidneys with pyelonephritis and papillary necrosis. M/47. Infection is an important complication of diabetes and renal infection may sometimes cause death, as in this case.

E-Fig. 15.8 G, Oncocytoma. M/65. Vertical slice through the middle of the right kidney. In the anterior portion of the right upper pole there is a well circumscribed spherical tumour 30 mm in diameter. It has a dark reddish-brown, homogeneous cut surface. These tumours are benign, but this kidney was removed because of a radiological diagnosis of renal carcinoma.

E-Fig. 15.9 G, Renal cell carcinoma. There is a well circumscribed, spherical tumour 30 mm in diameter bulging through the cortical surface of the kidney. Its cut surface is bright yellow. It shows solid areas, cystic areas and areas of haemorrhage.

E-Fig. 15.10 G, Wilms’ tumour. F/5. The tumour occupies the whole upper pole of the kidney. Its cut surface shows some firm, homogeneous areas and other areas of necrosis.

E-Fig. 15.11 H, Transitional epithelium H&E (HP).

E-Fig. 15.12 G, Carcinoma of the bladder. M/88. The entire mucosal surface is replaced by a transitional cell carcinoma. It has caused obstruction with bilateral hydroureter and hydronephrosis.

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