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PA27.17 | Kidney Disease & Tumour Morphology — Practical — SDL Guide (Part 2)

Glomerular Diseases: Crescentic GN, Membranous, and MCD

Comparison diagram of crescentic glomerulonephritis, membranous nephropathy, and minimal change disease showing key light microscopy, immunofluorescence, and electron microscopy findings. — **Panel A:** Crescentic rapidly progressive GN: cellular crescent, parietal epithelial cell proliferation, monocytes, fibrin, compressed glomerular tuft, Bowman's space, Bowman's capsule, linear IgG, granular IF, pauci-immune negative IF, large pale flea-bitten kidney.. **Panel B:** Membranous nephropathy: thickened GBM, Jones silver stain, silver-positive GBM spikes, subepithelial electron-dense deposits, spike-and-dome pattern, granular IgG + C3 along GBM.. **Panel C:** Minimal change disease: normal glomerulus on light microscopy, negative IF, podocyte foot process effacement on EM, GBM, podocyte cell body.. **Panel D:** Pattern summary: crescent to rapid renal failure, spike-and-dome silver stain to membranous nephropathy, normal LM plus foot process effacement to MCD..

Crescentic (Rapidly Progressive) GN
• Gross: large, pale, flabby kidneys — so pale they are called 'flea-bitten' in the acute phase if petechiae are present
• Micro: the hallmark is a cellular crescent — a proliferation of parietal epithelial cells + monocytes filling Bowman's space, compressing the tuft. Fibrin is present in early crescents (fibrocellular); fibrosis replaces cells in old crescents (fibrous).
• IF: three patterns — linear IgG (anti-GBM/Goodpasture), granular (immune complex GN), pauci-immune (ANCA vasculitis — negative IF)
• Outcome: rapid progression to renal failure if untreated

Membranous Nephropathy
• Pure nephrotic syndrome in adults; most common cause of adult idiopathic nephrotic syndrome
• Micro: glomeruli appear normal on H&E. Silver (Jones methenamine) stain is essential: reveals spike-and-dome pattern — silver-positive GBM spikes projecting between electron-dense subepithelial deposits
• IF: granular IgG + C3 along GBM
• EM: subepithelial electron-dense deposits

Minimal Change Disease (MCD)
• Most common nephrotic syndrome in children; also called lipoid nephrosis
• Light microscopy (H&E): glomeruli appear completely normal — this is the key diagnostic clue
• IF: negative
• EM: diffuse effacement of podocyte foot processes — the only diagnostic abnormality; LM is normal

Pattern summary: Crescent → rapid renal failure / Spike-and-dome (silver) → membranous / Normal LM + foot process effacement (EM) → MCD

SELF-CHECK

A 6-year-old boy presents with periorbital oedema and heavy proteinuria. His renal biopsy on H&E shows completely normal-looking glomeruli. Which investigation will show the diagnostic abnormality?

A. Immunofluorescence — granular IgG along GBM

B. Silver (Jones) stain — spike-and-dome pattern

C. Electron microscopy — diffuse podocyte foot process effacement

D. PAS stain — Kimmelstiel-Wilson mesangial nodules

Reveal Answer

Answer: C. Electron microscopy — diffuse podocyte foot process effacement

Minimal change disease (MCD) has a normal light microscopy picture. The diagnostic finding is on EM: diffuse effacement (fusion) of podocyte foot processes. IF is negative. Silver stain spike-and-dome (B) = membranous nephropathy. KW nodules (D) = diabetic nephropathy.

Tubulointerstitial Disease: Acute Tubular Necrosis

Four-panel diagram explaining acute tubular necrosis with nephron segment vulnerability, ischaemic versus nephrotoxic patterns, muddy-brown casts, and preserved glomeruli and vessels. — **Panel A:** Pale swollen kidney, widened cortex, nephron, proximal convoluted tubule, pars recta, thick ascending limb, outer medulla watershed zone, normal glomerulus, normal vessels, preserved tubular basement membrane.. **Panel B:** Ischaemic ATN with focal tubular epithelial necrosis and intact basement membrane; nephrotoxic ATN with diffuse proximal convoluted tubule necrosis and severe tubulorhexis.. **Panel C:** Muddy-brown granular casts, tubular lumen, sloughed necrotic epithelial cells, myoglobin or haemoglobin pigment casts.. **Panel D:** Regenerating tubules, flat basophilic epithelial cells, mitotic figures, intact basement membrane, normal glomeruli and vessels, urine sediment with granular casts..

Acute tubular necrosis (ATN) is the most common cause of acute kidney injury in hospitalised patients.

Two morphological patterns correspond to two aetiologies:

1. Ischaemic ATN (shock, hypotension, sepsis)
• Gross: kidneys pale, swollen, cortex widened
• Micro: focal necrosis of tubular epithelium with preserved basement membrane (tubular BM intact = potential for regeneration). Necrosis predominates at the straight segment of the proximal tubule (pars recta) and the thick ascending limb in the outer medulla (watershed zone)
• Regenerating tubules show flat, basophilic cells with mitoses

2. Nephrotoxic ATN (aminoglycosides, heavy metals, myoglobin/haemoglobin)
• Micro: diffuse necrosis of the entire proximal convoluted tubule (most active reabsorbers, most drug-concentrated)
• Muddy-brown granular casts in tubular lumens (myoglobin/haemoglobin pigment) — pathognomonic of myoglobinuric/haemoglobinuric ATN
• Basement membrane may be disrupted (tubulorhexis) in severe nephrotoxic ATN

Key shared feature: the glomeruli and vessels are NORMAL — distinguishing ATN from glomerulonephritis.

Urine sediment correlation: granular casts (muddy brown) are the urinalysis correlate of ATN on biopsy.

Tubulointerstitial Disease: Acute and Chronic Pyelonephritis

Diagram of acute pyelonephritis showing renal cortical histology with WBC casts, neutrophilic microabscesses, oedematous interstitium, spared glomerulus, and gross cortical abscesses with medullary streaks. — **Panel A:** Main H&E renal cortex field showing WBC cast, intratubular neutrophils, microabscess, disrupted tubular basement membrane, oedematous interstitium, and normal glomerulus spared.. **Panel B:** Magnified schematic of two adjacent tubules highlighting intratubular neutrophilic infiltrate, WBC cast, tubular wall disruption, and microabscess formation.. **Panel C:** Gross kidney cut surface showing enlarged congested kidney, yellow-white cortical abscesses, and linear yellow medullary streaks extending toward the cortex..

Acute Pyelonephritis (APN)

Gross:
• Kidneys enlarged, congested
• Cortical surface shows small yellow-white cortical abscesses (suppurative foci)
• Cut surface: linear yellowish streaks in medulla extending to the cortex

Micro (the diagnostic triad):
1. Intratubular neutrophilic infiltrate (tubular lumens stuffed with PMNs)
2. WBC casts (casts composed of neutrophils) — pathognomonic on urine microscopy AND on biopsy sections of tubular lumens
3. Microabscesses — clusters of neutrophils destroying tubular BM, creating sharply demarcated foci of suppurative necrosis
• Interstitium is oedematous and neutrophil-infiltrated
• Glomeruli typically SPARED (unlike GN)

H&E-style renal cortex illustration of acute pyelonephritis showing a WBC cast, tubular microabscess, oedematous neutrophil-rich interstitium, and a normal glomerulus. — **Panel A:** Main H&E 20x renal cortex field showing WBC cast, microabscess disrupting tubular wall, interstitial oedema with scattered neutrophils, and normal glomerulus.. **Panel B:** Magnified schematic detail of two adjacent tubules highlighting neutrophil-filled tubular lumen, disrupted tubular wall, microabscess, and oedematous interstitium..

Chronic Pyelonephritis (CPN)

Gross (distinctive and examinable):
• Coarse, irregular scars that overlie a dilated, blunted calyx — the calyceal blunting + cortical scar combination is unique to CPN (not seen in other scarring diseases)
• The cortex between scars can appear almost normal or slightly thinned
• The kidney is asymmetrically scarred, shrunken, and distorted

Micro:
• Thyroidisation of tubules: dilated tubules packed with homogeneous, eosinophilic, colloid-like casts — resembles thyroid follicles; a distinctive and frequently asked feature
• Periglomerular fibrosis (concentric collagen rings around glomeruli) — distinguishes CPN from glomerulonephritis-related scarring
• Chronic inflammatory infiltrate (lymphocytes, plasma cells) in interstitium
• Fibrosis and tubular atrophy
• Arterial wall thickening in advanced disease

SELF-CHECK

A museum specimen shows a kidney with coarse, irregular scars overlying blunted, dilated calyces. Microscopy reveals dilated tubules packed with homogeneous eosinophilic casts resembling thyroid follicles, and concentric periglomerular fibrosis. What is the diagnosis?

A. Benign nephrosclerosis

B. Chronic pyelonephritis

C. Focal segmental glomerulosclerosis

D. Membranoproliferative GN

Reveal Answer

Answer: B. Chronic pyelonephritis

The combination of coarse scars + calyceal blunting (gross) + thyroidisation of tubules + periglomerular fibrosis (micro) is pathognomonic of chronic pyelonephritis. Benign nephrosclerosis (A) causes fine granular scarring without calyceal change. FSGS (C) and MPGN (D) are primarily glomerular diseases without the tubular or calyceal pattern.