Xanthogranulomatous inflammation

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The Xanthogranulomatous Process (XP), also known as Xanthogranulomatous Inflammation is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded.[1][2][3] The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.[4]


The xanthogranulomatous type of inflammation is most-commonly seen in pyelonephritis and cholecystitis, although it has more recently been described in an array of other locations including bronchi, lung, endometrium, vagina, fallopian tubes, ovary, testis, epydidymis, stomach, colon, ileum, pancreas, bone, lymph nodes, bladder, adrenal gland, abdomen and muscle.[5] Telling apart clinically a XP from a tumor condition can be challenging as pointed out by several authors. Cozzutto and Carbone suggested that a wide array of entities characterized by a large content of histiocytes and foamy macrophages could be traced back at least in part to a xanthogranulomatous inflammation.[4] These include such varied disturbances as xanthoma disseminatum,[6] ceroid granuloma of the gallbladder, Whipple's disease,[7] inflammatory pseudotumor of the lung,[8][9] plasma cell granuloma of the lung,[10] malakoplakia,[11] verruciform xanthoma, foamy histiocytosis of the spleen in thrombocytopenic purpura,[12][13] isolated xanthoma of the small bowel,[14] xanthofibroma of bone,[15] and gastric xanthelasma.

A pathogenetic model might be suggested as follows:

  1. suppuration, hemorrhage and necrosis,
  2. granulomatous tissue with granular histiocytes and foamy macrophages,
  3. fibrohistiocytoma-like or plasma cell granuloma-like patterns,
  4. possible myofibroblast metaplasia.

A reactive fibrohistiocytic lesion simulating fibrous histiocytoma has been reported by Snover et al.[16] Reactive granular cells in sites of trauma have been regarded of histiocytic nature.[17] Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) might share several aspects of the XP. Likewise there might be some superimpositions between the XP and the plasma cell granuloma/histiocytoma-inflammatory myofibroblastic tumor complex.[18][19] The XP might be an important stage of this complex.


Under microscope, the cellular infiltrate includes neutrophils, lymphocytes, plasma cells, erythrocytes, hemosiderin-laden macrophages and prevalent foamy histiocytes.The latter are interspersed among other cells but often they cluster in a compacted mosaic-like pattern. The large lipid-laden macrophages display an eosinophilic or clear cytoplasm with a granular and vacuolated quality but can also have a spindle shape. Foreign body-type and Touton-type giant cells, calcospherites, cholesterol clefts and hemosiderin deposits are additional findings.

Hemorrhage, suppuration and necrosis are therefore the initial conditions leading to the xanthogranulomatous response. Plasma cells and fibrosis increase in later stages with the former being numerous and prominent. Proteus and Escherichia coli are the most commonly involved bacteria in xanthogranulomatous pyelonephritis. The foam cells of monocyte/macrophage origin are positive for KP1, HAM56, CD11b and CD68 as pointed out by Nakashiro et al. in xanthogranulomatous cholecystitis).[20] Many T lymphocytes were identified by these authors positive to CD4 and CD8. Macrophages and T lymphocytes demonstrated a marked expression of HLA-DR antigen. A delayed type hypersensitivity reaction of cell mediated immunity has been suggested in the pathogenesis of xanthogranulomatous cholecystitis.[20]

Destructive tumor-like masses with variable extension into adjacent fat and connective tissue can occur in cases involving organs such as kidney and gallbladder.[21]

See also[edit]


  1. ^ Goodman M, Curry T, Russell T (March 1979). "Xanthogranulomatous pyelonephritis (XGP): a local disease with systemic manifestations. Report of 23 patients and review of the literature". Medicine (Baltimore). 58 (2): 171–81. doi:10.1097/00005792-197903000-00005. PMID 431402.
  2. ^ Goodman ZD, Ishak KG (October 1981). "Xanthogranulomatous cholecystitis". Am. J. Surg. Pathol. 5 (7): 653–9. doi:10.1097/00000478-198110000-00007. PMID 7337158.
  3. ^ Franco V, Aragona F, Genova G, Florena AM, Stella M, Campesi G (June 1990). "Xanthogranulomatous cholecystitis. Histopathological study and classification". Pathol. Res. Pract. 186 (3): 383–90. doi:10.1016/S0344-0338(11)80297-9. PMID 2377572.
  4. ^ a b Cozzutto C, Carbone A (August 1988). "The xanthogranulomatous process. Xanthogranulomatous inflammation". Pathol. Res. Pract. 183 (4): 395–402. doi:10.1016/S0344-0338(88)80085-2. PMID 3054826.
  5. ^ Snoj, Z; Savic, N; Regvat, J. "Late complication of a renal calculus: fistulisation to the psoas muscle, skin and bronchi" (PDF). International Braz J Urol. International Braz J Urol. Retrieved 31 August 2015.
  6. ^ Altman J, Winkelman RK (1962). "Xanthoma disseminatum". Arch. Dermatol. 86 (5): 582–596. doi:10.1001/archderm.1962.01590110018003.
  7. ^ Haubrich WS, Watson JH, Sieracki JC (October 1960). "Unique morphologic features of Whipple's disease. A study by light and electron microscopy". Gastroenterology. 39: 454–68. PMID 13712267.
  8. ^ Bahadori M, Liebow AA (January 1973). "Plasma cell granulomas of the lung". Cancer. 31 (1): 191–208. doi:10.1002/1097-0142(197301)31:1<191::AID-CNCR2820310127>3.0.CO;2-D. PMID 4683037.
  9. ^ Titus JL, Harrison EG, Clagett OT, Anderson MW, Knaff LJ (1962). "Xanthomatous and inflammatory pseudotumors of the lung". Cancer. 15 (3): 522–38. doi:10.1002/1097-0142(196205/06)15:3<522::AID-CNCR2820150312>3.0.CO;2-7. PMID 13921408.
  10. ^ Buell R, Wang NS, Seemayer TA, Ahmed MN (July 1976). "Endobronchial plasma cell granuloma (xanthomatous pseudotumor); a light and electron microscopic study". Hum. Pathol. 7 (4): 411–26. doi:10.1016/S0046-8177(76)80055-X. PMID 939538.
  11. ^ Bleisch VR, Konikov NF (October 1952). "Malakoplakia of urinary bladder; report of four cases and discussion of etiology". AMA Arch Pathol. 54 (4): 388–97. PMID 12984945.
  12. ^ Dollberg L, Casper J, Djaldetti M, Klibansky C, De Vries A (January 1965). "Lipid-laden histiocytes in the spleen in thrombocytopenic purpura". Am. J. Clin. Pathol. 43: 16–25. PMID 14259121.
  13. ^ Cohn J, Tygstrup I (January 1976). "Foamy histiocytosis of the spleen in patients with chronic thrombocytopenia". Scand J Haematol. 16 (1): 33–7. doi:10.1111/j.1600-0609.1976.tb01113.x. PMID 1251138.
  14. ^ Coletta U, Sturgill BC (April 1985). "Isolated xanthomatosis of the small bowel". Hum. Pathol. 16 (4): 422–4. doi:10.1016/S0046-8177(85)80237-9. PMID 3980010.
  15. ^ Ide F, Kusuhara S, Onuma H, Miyake T, Umemura S (January 1982). "Xanthic variant of non-ossifying fibroma (so-called xanthofibroma) of the mandible. An ultrastructural study". Acta Pathol. Jpn. 32 (1): 135–42. doi:10.1111/j.1440-1827.1982.tb02034.x. PMID 6176096.
  16. ^ Snover DC, Phillips G, Dehner LP (August 1981). "Reactive fibrohistiocytic proliferation simulating fibrous histiocytoma". Am. J. Clin. Pathol. 76 (2): 232–5. PMID 6267932.
  17. ^ Sobel HJ, Avrin E, Marquet E, Schwarz R (February 1974). "Reactive granular cells in sites of trauma. A cytochemical and ultrastructural study". Am. J. Clin. Pathol. 61 (2): 223–34. PMID 4359728.
  18. ^ Spencer H (November 1984). "The pulmonary plasma cell/histiocytoma complex". Histopathology. 8 (6): 903–16. doi:10.1111/j.1365-2559.1984.tb02409.x. PMID 6098549.
  19. ^ Coffin CM, Watterson J, Priest JR, Dehner LP (August 1995). "Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases". Am. J. Surg. Pathol. 19 (8): 859–72. doi:10.1097/00000478-199508000-00001. PMID 7611533.
  20. ^ a b Nakashiro H, Haraoka S, Fujiwara K, Harada S, Hisatsugu T, Watanabe T (November 1995). "Xanthogranulomatous cholecystis. Cell composition and a possible pathogenetic role of cell-mediated immunity". Pathol. Res. Pract. 191 (11): 1078–86. doi:10.1016/S0344-0338(11)80651-5. PMID 8822108.
  21. ^ Snoj, Z; Savic, N; Regvat, J. "Late complication of a renal calculus: fistulisation to the psoas muscle, skin and bronchi" (PDF). International Braz J Urol. Retrieved 31 August 2015.