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PA27.17 | Kidney Disease & Tumour Morphology — Practical — SDL Guide (Part 3)

Vascular Disease: Benign and Malignant Nephrosclerosis

A side-by-side pathology diagram compares gross and microscopic features of benign and malignant nephrosclerosis. — **Panel A:** Gross benign nephrosclerosis: symmetrically reduced kidney size, finely granular cortical surface, 1-2 mm pits and bumps, thickened prominent vessels on cut surface.. **Panel B:** Microscopic benign nephrosclerosis: hyaline arteriolosclerosis, narrowed arteriole lumen, intimal fibrosis of interlobular artery, ischemic glomerular obsolescence, tubular atrophy, interstitial fibrosis.. **Panel C:** Gross malignant nephrosclerosis: normal or enlarged kidneys with petechial cortical hemorrhages producing a flea-bitten appearance.. **Panel D:** Microscopic malignant nephrosclerosis: hyperplastic arteriolosclerosis with onion-skin concentric smooth muscle and collagen layers, plus fibrinoid necrosis with eosinophilic fibrin, necrotic debris, and neutrophils..

Benign Nephrosclerosis (Hypertensive nephrosclerosis, chronic)

Gross:
• Both kidneys symmetrically reduced in size
• Surface is finely granular — tiny (1-2 mm) pits and bumps corresponding to ischaemic nephron loss alternating with hypertrophied surviving nephrons
• Vessels on cut surface appear thickened and prominent

Micro:
• Hyaline arteriolosclerosis: homogeneous, eosinophilic (pink) material replacing the vessel wall of small arteries and arterioles — the morphological signature of chronic hypertension
• Intimal fibrosis of interlobular arteries (concentric, cellular proliferation)
• Downstream: ischaemic glomerular changes — wrinkling/retraction of capillary tuft, periglomerular fibrosis, eventual obsolescence (ischaemic obsolescence)
• Tubular atrophy + interstitial fibrosis in areas of nephron loss

Malignant Nephrosclerosis (Accelerated/malignant hypertension)

Gross: kidneys may be normal or enlarged; petechial haemorrhages on cortical surface ("flea-bitten" kidney)

Micro — two key patterns:
• Hyperplastic arteriolosclerosis (onion-skin lesion): concentric layers of proliferating smooth muscle cells and collagen in the arteriolar wall, giving an onion-skin appearance — this is the hallmark of malignant hypertension
• Fibrinoid necrosis of arterioles: eosinophilic smudgy material (fibrin + necrotic debris) replacing the vessel wall, often with neutrophilic infiltration

Key distinction: benign → hyaline (homogeneous) / malignant → onion-skin + fibrinoid (cellular, with necrosis)

SELF-CHECK

A 35-year-old woman presents with sudden BP of 230/140 mmHg, acute kidney injury, and retinal haemorrhages. Her renal biopsy arterioles show concentric layers of proliferating smooth muscle cells and collagen within the vessel wall, and one arteriole shows replacement of the wall by smudgy eosinophilic material. What are these two findings respectively?

A. Hyaline arteriolosclerosis and fibrinoid necrosis

B. Onion-skin hyperplastic arteriolosclerosis and fibrinoid necrosis

C. Amyloid angiopathy and thrombotic microangiopathy

D. Hyaline arteriolosclerosis and onion-skin arteriolosclerosis

Reveal Answer

Answer: B. Onion-skin hyperplastic arteriolosclerosis and fibrinoid necrosis

Malignant hypertension produces two arteriolar lesions: (1) onion-skin hyperplastic arteriolosclerosis — concentric smooth muscle + collagen lamellae; and (2) fibrinoid necrosis — smudgy eosinophilic fibrin replaces/destroys the wall. Hyaline arteriolosclerosis (A/D) is the benign form. Amyloid (C) would show Congo red positivity.

Gross Kidneys at a Glance: End-Stage, PKD, Hydronephrosis, RCC

A four-panel gross pathology comparison diagram shows end-stage contracted kidney, ADPKD, hydronephrosis, and clear-cell renal cell carcinoma with labeled distinguishing features. — **Panel A:** End-stage contracted granular kidney; small kidney, finely granular surface, severely thinned cortex, distorted medulla, prominent cut-surface vessels.. **Panel B:** Autosomal dominant polycystic kidney disease; massively enlarged kidney, multiple cysts of varying size, grape-cluster appearance, compressed residual parenchyma, clear yellow or haemorrhagic cyst fluid.. **Panel C:** Hydronephrosis; dilated renal pelvis, dilated calyces, urine-filled collecting system, thin compressed cortical-medullary rim, obstructing calculus at pelvi-ureteric junction.. **Panel D:** Clear-cell renal cell carcinoma; solitary cortical mass, well-circumscribed border, pseudocapsule, golden-yellow tumour, haemorrhage, necrosis, cystic areas, renal vein tumour thrombus..

Four gross patterns you must instantly recognise:

End-Stage (contracted granular) Kidney
• Small (often < 100 g), finely granular surface
• Cortex severely thinned, medulla distorted
• Vessels prominent on cut surface
• Arises from: benign nephrosclerosis, diabetic nephropathy, chronic GN (any)
• The gross cannot tell you the aetiology — micro (or history) does

Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Dramatically enlarged kidneys (can reach 40 cm, 4 kg each)
• Replaced by multiple bilateral cysts of varying sizes (grape-cluster appearance)
• Normal parenchyma is compressed and almost absent
• Cyst fluid: clear, yellow, or haemorrhagic
• Associated: berry aneurysms, hepatic cysts, mitral valve prolapse

Hydronephrosis
• Kidney enlarged; cut surface reveals massively dilated pelvis and calyces filled with urine
• Parenchyma is compressed to a thin rim — cortex + medulla flattened
• Cause: any obstruction (calculus, BPH, tumour, stricture) must be sought at the ureter/pelvis junction

Clear-Cell Renal Cell Carcinoma (RCC)
• Solitary cortical mass, well circumscribed, may have a pseudocapsule
• Cut surface: golden yellow (lipid + glycogen in tumour cells) with zones of haemorrhage and necrosis
• Cystic areas common
• Occasionally invades renal vein as a tumour thrombus

Renal Tumours: RCC, Wilms, and Urothelial Carcinoma

A four-panel renal tumour teaching diagram comparing Wilms tumour triphasic histology, clear cell RCC microscopic and gross features, tumour sites, and key diagnostic clues. — **Panel A:** Wilms tumour triphasic pattern with blastemal small round blue cells, primitive epithelial tubules, glomeruloid structures, and loose stromal mesenchyme; mnemonic Wilms = BSE.. **Panel B:** Clear cell renal cell carcinoma showing nests of clear cells, small round nuclei, delicate chicken-wire vascular sinusoids, and golden-yellow gross cut surface.. **Panel C:** Gross kidney site comparison showing RCC in adult renal cortex, Wilms tumour as a large child cortical mass with pseudocapsule and necrosis, and urothelial carcinoma arising from renal pelvis urothelium.. **Panel D:** Diagnostic comparison thumbnails for RCC clear cell, Wilms tumour triphasic BSE pattern, and urothelial carcinoma papillary transitional epithelial tumour..

Renal Cell Carcinoma (RCC) — Clear Cell Type

Micro:
• Sheets and nests of cells with abundant clear cytoplasm (dissolved lipid + glycogen on routine processing) and small, round nuclei
• Delicate thin-walled vascular sinusoids between nests (chicken-wire vascular pattern)
• Fuhrman nuclear grade reflects prognosis (Grade 1 = small uniform nuclei; Grade 4 = pleomorphic, prominent nucleoli)

Gross correlate: golden-yellow on cut surface = cleared cytoplasm

Wilms Tumour (Nephroblastoma)

Gross: large, well-circumscribed cortical mass in a child; soft grey-white with haemorrhage/necrosis; pseudocapsule present

Micro: the classic triphasic pattern:
1. Blastemal component: sheets of small, round, primitive blue cells (high N:C ratio, hyperchromatic — looks like small blue cell tumour)
2. Stromal component: loose, undifferentiated mesenchyme, may show heterologous differentiation (skeletal muscle, cartilage)
3. Epithelial component: primitive tubules and glomeruloid structures (abortive attempt at nephrogenesis)

Mnemonic: Wilms = Blue Stroma Epithelium (BSE — all three components)

Split H&E histology diagram of Wilms tumour showing dense blue blastema on the left and primitive epithelial tubules with loose stromal mesenchyme on the right. — **Panel A:** Dense blue blastema: sheets of small round blue cells with hyperchromatic nuclei and scant cytoplasm. **Panel B:** Primitive epithelial tubule formation: small gland-like structures with tiny lumina; loose stromal mesenchyme: pale pink spindle-cell background. **Bottom legend:** Triphasic Wilms tumour components: Blastema, Primitive epithelial tubules, Loose stromal mesenchyme.

Urothelial (Transitional Cell) Carcinoma

Site: renal pelvis (urothelium-lined), not renal parenchyma

Gross: papillary, frond-like mass projecting into the pelvic lumen; may obstruct and cause hydronephrosis

Micro: multilayered transitional epithelium on fibrovascular cores (papillary architecture); cytological atypia graded low vs. high grade; invasion of lamina propria = invasive carcinoma

Key distinction from RCC: location (pelvis not cortex), papillary not solid sheets, transitional not clear-cell cytology

SELF-CHECK

A 4-year-old child is found to have a large abdominal mass. Biopsy shows three components: (1) sheets of small, round, hyperchromatic blue cells with scant cytoplasm; (2) loose spindle-cell stroma with heterologous muscle differentiation; (3) primitive tubular and glomeruloid structures. Which is the most likely diagnosis?

A. Clear-cell renal cell carcinoma

B. Neuroblastoma

C. Wilms tumour (Nephroblastoma)

D. Ewing sarcoma

Reveal Answer

Answer: C. Wilms tumour (Nephroblastoma)

The triphasic pattern — blastemal (small round blue cells) + stromal + epithelial (tubular/glomeruloid) components — is pathognomonic of Wilms tumour (nephroblastoma). Clear-cell RCC (A) occurs in adults and shows clear cytoplasm without triphasic pattern. Neuroblastoma (B) lacks epithelial/stromal components and arises from adrenal/retroperitoneum. Ewing sarcoma (D) is monophasic (all blastemal) and shows CD99 positivity.