Anatomical Pathology Interesting Case Conference

Microscopic Description:

Hallmark - Foamy histiocytes with abundant clear cytoplasm, or rarely with focal eosinophilic cytoplasm, present as small clusters under urothelium to large destructive nodular lesions with secondary renal parenchymal involvement.

  • Admixed polymorphous inflammation with lymphocytes, plasma cells, neutrophils, variable number of multinucleated giant cells, and microabscesses.

Extension of process to ureter &/or perirenal fat commonly present.

Zonal distribution of inflammation may be seen:

  • Inner zone: bacteria, inflammatory cells (neutrophils, lymphocytes, plasma cells), foreign body giant cells, foreign body granulomas, Liesegang rings, calcifications.
  • Middle zone (hallmark for the diagnosis): granulation tissues surrounded by lipid laden foamy CD68+ macrophages (xanthoma cells), Touton giant cells, cholesterol crystal clefts.
  • Outer zone:  giant cells, cholesterol clefts and fibrous tissues with lymphoid follicles.

Positive stain – CD68

Negative stains - Pankeratin, PAX8, Melanocytic markers, Acid fast bacteria

Discussion:

Rare subtype of pyelonephritis.

Often occurs as a chronic consequence of nephrolithiasis or infections.

Pathophysiology - Urinary obstruction occurs because of calculus, most commonly staghorn calculus (in almost 80% of patients), which serves as a nidus for infection, resulting in the destruction of the renal parenchyma.

Flank pain (92.5%), fever (62.5%), dysuria (47.5%), renal angle tenderness (40%) and a palpable lump on per abdomen examination (30%).

All ages, more often in women and elderly patients.

Usually unilateral, left kidney more commonly affected (60%).

May extend to perirenal / perinephric fat, perirenal and pararenal spaces or diffusely into the retroperitoneum.

Imaging- Bear paw sign (i.e., dark dilated calyces surrounded by brighter renal parenchyma on CT imaging). Staghorn calculus on radiography in case of nephrolithiasis.

Excellent overall prognosis (Prognosis is better in unilateral cases).

Treatment of choice in diffuse cases is nephrectomy without any incidence of recurrence.

Differential Diagnosis:

Malakoplakia: 

  • Michaelis-Gutmann bodies  1–10 μm laminated or targetoid basophilic focal inclusions of iron and calcium salts seen on light microscopy. They are also periodic acid–Schiff, and diastase-resistant 1.
  • They usually occur in the cytoplasm of histiocytes (von Hansemann cells) as well as in the surrounding stroma.

Renal clear cell carcinoma: 

  • Cells with clear cytoplasm may resemble histiocytes but are keratin+, PAX8+, CD68-
  • Arranged in compact, tubulocystic, alveolar or rarely papillary patterns
  • Often glassy hyaline globules
  • Usually, nuclear grade 2 or higher
  • Chicken wire / delicate vasculature is common (sinusoids near each packet of cells)

Renal replacement lipomatosis: 

  • Atrophic renal parenchyma is replaced by adipose tissue, not xanthoma cells

Renal tuberculosis: 

  • Granulomas with caseating necrosis surrounded by histiocytes and Langhans type giant cells
  • Acid fast bacteria stain (Ziehl-Neelsen) demonstrates red, rod shaped bacilli at periphery of necrosis
References:

Jesrani G, Gupta S, Raju T, Bhardwaj N, Gupta M. Bilateral Renal Replacement Lipomatosis: A Case Report on Rare Complication of Obstructive Uropathy. Cureus. 2021 Jul 23;13(7):e16596. doi: 10.7759/cureus.16596. PMID: 34447641; PMCID: PMC8380856.

Renshaw AA, Gould EW. Ancillary studies in fine needle aspiration of the kidney. Cancer Cytopathol. 2018 Aug;126 Suppl 8:711-723. doi: 10.1002/cncy.22029. PMID: 30156770.

Jha SK, Leslie SW, Aeddula NR. Xanthogranulomatous Pyelonephritis. 2024 May 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 32491331.

Hortling N, Layer G, Albers P, Schild HH. Xanthogranulomatöse Pyelonephritis mit septischen Lungenmetastasen und Infiltration des Kolons. Schwierige präoperative Differentialdiagnose zum pulmonal metastasierten Hypernephrom [Xanthogranulomatous pyelonephritis with septic lung metastases and infiltration of the colon. Difficult preoperative differential pulmonary hypernephroma metastasis diagnosis]. Aktuelle Radiol. 1997 Nov;7(6):317-20. German. PMID: 9467024.

Akyol Onder EN, Ozkol M, Nese N, Taneli C, Cankorur OO, Ozunan I. Focal Xanthogranulomatous Pyelonephritis in Brachydactyly Mental Retardation Syndrome (2q37 Deletion Syndrome). J Pediatr Genet. 2020 Jun;9(2):114-116. doi: 10.1055/s-0039-1697624. Epub 2019 Sep 23. PMID: 32341815; PMCID: PMC7183408.

Harley F, Wei G, O'Callaghan M, Wong LM, Hennessey D, Kinnear N. Xanthogranulomatous pyelonephritis: a systematic review of treatment and mortality in more than 1000 cases. BJU Int. 2023 Apr;131(4):395-407. doi: 10.1111/bju.15878. Epub 2022 Sep 26. PMID: 35993745.

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