Overview
- Rare chronic subtype of pyelonephritis, often secondary to nephrolithiasis and infection.
- Hallmark: lipid-laden foamy CD68+ macrophages (xanthoma cells) producing yellow-orange tissue.
- Usually unilateral; left kidney affected in ~60% of cases.
- Can mimic renal cell carcinoma clinically, macroscopically, and microscopically.
Essential Features
- Pathognomonic cells: foam (xanthoma) cells, CD68 positive.
- Zonal gross and microscopic architecture often present (inner, middle, outer zones).
- Extrarenal extension suggests malignancy but may occur with severe infection.
- Bear paw sign on CT can be pathognomonic if present.
Epidemiology & Risk Factors
- All ages, more common in women and elderly.
- Frequently associated with staghorn calculi (≈80%) and chronic obstruction.
- Risk factors: diabetes, hypertension, immunocompromise, abnormal lipid metabolism, renal transplant, certain pediatric syndromes.
Pathophysiology
- Urinary obstruction (commonly staghorn calculus) → nidus for infection → parenchymal destruction.
- In children, congenital ureteropelvic abnormalities may cause chronic obstruction.
Clinical Presentation
- Nonfunctional kidney common.
- Symptoms: flank pain (≈92.5%), fever (≈62.5%), dysuria (≈47.5%), renal angle tenderness (≈40%), palpable abdominal lump (≈30%).
- Possible complications: septic metastases, nephrobronchial/intraabdominal fistulae, secondary amyloid A leading to nephrotic syndrome in prolonged disease.
Diagnostics
- Labs: anemia, leukocytosis, elevated ESR and CRP, elevated BUN/creatinine.
- Urinalysis: pyuria, bacteriuria, hematuria; urine cultures positive in many cases (E. coli, Proteus mirabilis, Klebsiella, Enterococcus), sterile in ~25%.
- Imaging: CT bear paw sign (dilated dark calyces surrounded by brighter parenchyma); radiography may show staghorn calculus.
- Frozen section: dense sheets of round cells with clear/vacuolated cytoplasm, inflammatory cells, multinucleated giant cells, no significant atypia.
Gross Pathology
- Zonal structure:
- Inner zone: dilated pelvis/calyces with necrotic debris.
- Middle zone: granulation tissue with lipid-laden macrophages (yellow-orange).
- Outer zone: fibrosis that may extend into perirenal fat; decapsulation may be difficult.
Microscopic Findings
- Zonal distribution (may be admixed):
- Inner: bacteria, neutrophils, lymphocytes, plasma cells, foreign-body giant cells, calcifications (Liesegang rings).
- Middle (diagnostic): granulation tissue surrounded by foamy CD68+ macrophages, Touton giant cells, cholesterol clefts.
- Outer: giant cells, cholesterol clefts, fibrosis, lymphoid follicles.
- CD68 positive, cytokeratin and PAX8 negative in xanthoma cells (helps differentiate from carcinoma).
Differential Diagnosis
- Malakoplakia: Michaelis-Gutmann bodies (distinguishing feature).
- Renal clear cell carcinoma: keratin+, PAX8+, CD68−; compact/alveolar architecture, glassy hyaline globules, higher nuclear grade.
- Renal replacement lipomatosis: adipose tissue replaces atrophic parenchyma, not xanthoma cells.
- Renal tuberculosis: caseating granulomas with Langhans giant cells; acid-fast bacilli on Ziehl-Neelsen stain.
Prognosis
- Generally excellent for unilateral disease.
- Bilateral disease often fatal.
- Diffuse cases: nephrectomy is treatment of choice with low recurrence.
Treatment
- Focal/segmental disease: antibiotics and percutaneous drainage; partial or total nephrectomy if unsuccessful.
- Diffuse/advanced disease: nephrectomy.
Case Examples (selected)
- Reports include tumor-like lesions, palpable lumbar masses, ureteral granulomatous inflammation involving IVC, and cases with concomitant squamous cell carcinoma or renal cell carcinoma.
Practice Questions (Key Points)
- Typical histologic finding: foam cells (xanthoma cells).
- Immunophenotype of pathognomonic cells: CD68 positive.
Action Items
- Consider CT imaging looking for bear paw sign and staghorn calculi when xanthogranulomatous pyelonephritis suspected.
- Use CD68 immunostain to confirm xanthoma cells and exclude epithelial renal neoplasms with PAX8/keratin stains.
Decisions
- Diffuse disease: proceed to nephrectomy.
- Focal disease: attempt conservative management (antibiotics, drainage) before partial/total nephrectomy if needed.
Reference Summary Table
| Feature | Key Points |
| Etiology/Risk Factors | Nephrolithiasis (staghorn calculus), chronic pyelonephritis, diabetes, immunosuppression |
| Epidemiology | Unilateral (left > right ~60%), more common in women and elderly |
| Pathognomonic Cell | Lipid-laden foamy macrophages (xanthoma cells), CD68+ |
| Imaging | CT bear paw sign; radiograph may show staghorn calculus |
| Gross Zones | Inner: necrotic debris; Middle: xanthoma-rich granulation; Outer: fibrosis |
| Microscopy | Foam cells, Touton giant cells, cholesterol clefts, mixed inflammation |
| Differential Diagnoses | Malakoplakia, renal clear cell carcinoma, renal replacement lipomatosis, TB |
| Treatment | Focal: antibiotics ± drainage; Diffuse: nephrectomy |
| Prognosis | Good for unilateral disease; bilateral disease often fatal |