J. clin. Path., 1972, 25, 397-400

Xanthogranulomatous pyelonephritisA comparison of the disease in the cat and man with special reference tothe origin of the fat

G. B. D. SCOTT AND P. J. QUIGLEY

From the Department of Morbid Anatomy, The Royal Free Hospital, anid the Blue Cross Hospital forAnimals, Pimlico, London

SYNOPSIS The origin of the intracellular fat in human xanthogranulomatous pyelonephritis has beenthe centre of some discussion in the past. A report of a case in a domestic cat is of interest as normalfeline renal epithelium is rich in stainable fat. A comparison of the human and feline varieties ofxanthogranulomatous pyelonephritis reveals certain fundamental differences between the two andreinforces the view that the fat concerned in theepithelium.

In man the characteristic feature of the xantho-granulomatous variety of chronic pyelonephritis isthe presence of large numbers of macrophages ladenwith fine intracytoplasmic fat. The condition,sometimes called 'foam-cell granuloma', is associatedparticularly with urinary obstruction and suppura-tion (Heptinstall, 1966). The chronic inflammatoryprocess is proliferative, and occasionally cases aremistaken for neoplasm (Avnet, Roberts, andGoldberg, 1963) or tuberculosis (Barrie, 1949; Mackand Mador, 1952).

Its reported incidence varies, Hooper, Kempson,and Schlegel (1962) collecting 15 cases over threeyears and Friedenberg and Spjut (1963) 12 casesover 10 years, while Ghosh (1955) found only threeexamples amongst 222 consecutive kidneys removedsurgically for a variety of inflammatory conditions.On the other hand, Castleman (Leadbetter et al,1962) asserts that fat-laden macrophages occur socommonly in longstanding renal abscesses thatthe specific term 'foam-cell granuloma' is notjustified.

The exact origin of the fat is still undetermined.Visible fat has not been described as occuring in therenal epithelium in cases of chronic pyelonephritis,and therefore a renal origin has tended to be dis-carded in favour of an origin in the polymorphspresent in the inflammatory tissue (Heptinstall,1966).

Since feline renal epithelium is normally laden withvisible fat, the finding in a domestic cat of a chronicrenal disease closely resembling human xantho-Received for publication 9 November 1971.

human disease does not originate in the renal

granulomatous pyelonephritis allowed of a compari-son of the disease in the two species with particularreference to the origin of the fat in the humanvariety.

Case Report

A neutered male cat, whose estimated aged was 8years or more, had developed gingival ulceration.No other abnormal signs could be found andinvestigation showed a haemoglobin of 120 g%(normal 80-14-0 g%) and a total of 7450 whiteblood cells per cmm (normal 8000-25000 per cmm), predominantly polymorphonuclear leucocytes.The urine had a specific gravity of 1056 (normal1020-1045), with heavy albuminuria. Theblood ureawas 42-8 mg% (normal 26 0-80-0 mg%).The gingival ulceration responded to steroids but

recurred once treatment was stopped. Although itresponded again to treatment such relapses becameincreasingly frequent and the animal was destroyed.At necropsy, apart from the gingival ulceration,

the macroscopic changes were confined to thekidneys which were of normal size and showed theextreme cortical pallor characteristic of the species.Irregular shallow cortical scars were present on bothsurfaces of the right kidney (Fig. 1) but the organseemed otherwise normal. Three slightly raised whiteareas, reminiscent of lymphosarcomatous infiltration,were present in the cortex of the left kidney, obliterat-ing the normally readily visible cortico-medullaryjunction. The remainder of the urinary tract waspassed as normal.

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G. B. D. Scott atnd P. J. Qluigley

Fig. I fthlt kidineY with shallows corti(calsc5ar

Fig. Shallow renal scri in right kidnev showing loss of'renal tuibiules and scarring of glom77erul li. HacematoxYlin and

cosin 2O.

Microscopically the tubular cells of the normalareas of cortex were vacuolated due to the presenceof intracellular fat, staining strongly with Oil Red 0but showing very little birefringence. The shallowcortical scars in the right kidney (Fig. I) showedmassive loss of renal tubules and their replacementby fibrous tissue containing small clusters of lymph-oid cells, while the glomeruli. all fibrosed andhyalinized, were crowded together (Fig. 2). A small

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quantity of fine fat, not obviously intracellular,could be demonstrated with Oil Red 0 but no bire-fringence could be seen under polarized light.

In the white expanded areas in the left kidney therenal tissue had been largely replaced by numerousfibroblasts (Fig. 3) and collections of lymphoid andmononuclear cells. many of the latter having foamygranular cytoplasm. Small round or elongated cysts

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Xanthograniulomatous pyelonephritis

containing fat, which stained with Oil Red 0, werescattered throughout these areas, the fat beingsurrounded often by syncytial formations. Whetherthe latter were of epithelial or inflammatory origincould not be determined. Such glomeruli thatremained were either infiltrated with chronicinflammatory cells or showed progressive fibrosis.

These pale areas also contained much finelydivided fat, also staining with Oil Red 0. While aproportion of this material could be identified aslying in the cytoplasm of mononuclear cells, often asquite large discrete droplets (Fig. 3), the exact siteof much of it could not be determined and it mightwell have been lying free amongst the fibroblasts andinflammatory cells. No birefringence could beelicited.

Human Xanthogranulomatous Pyelonephritis

A search of the files of the department of Morbid

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T."Fig. 4 Human case (Royal Free Hospital 176/66) showinglarge numbers of fat-laden cells with clear cytoplasm.Remnants of collecting tubules are present. Haematoxylinand eosin x 120.

Anatomy at the Royal Free Hospital produced twoexamples of the human disease from the last 10 years.Both cases were associated with urinary obstructionand consequent destruction of renal parenchyma.Both human cases contained many more fat-laden'foam cells' than did the feline one and even whenoccurring singly or in small groups they could bemore easily identified amidst the chronic inflam-matory and fibrous tissue as their cytoplasm wasclear compared with that of their feline counterparts(Fig. 4). Giant cells of varying size were present inboth human cases but were absent in the cat.

Unfortunately no unembedded tissue was avail-able and investigation of the fat could not be under-taken.

Discussion

The shallow depressed cortical scars in the rightkidney (Figs. 1 and 2) were more reminiscent of thehuman 'arteriosclerotic' kidney than of classicalchronic pyelonephritis. On the other hand, theprojecting homogeneous white areas in the leftkidney, shown by microscopy to be proliferativechronic inflammatory lesions, rich in fat (Fig. 3),resembled human xanthogranulomatous pyelo-nephritis, the more so since, in the cat, renal scars,whatever their cause, are usually depressed below thecortical surface (Lucke, 1965).Although a search of the literature failed to reveal

any reports of classical xanthogranulomatous or'tumefactive' pyelonephritis, in the cat or indeed inany other animal, the case reported here undoubtedlyresembles those of chronic renal disease described inthe cat by Lucke (1965) in which, following massive'accelerated tubular disruption', intraepithelial fat isreleased into the interstitial tissues exciting anexuberant fibrous tissue reaction.The interest of this single case centres around a

comparative study of the nature of the fat in humanand feline xanthogranulomatous pyelonephritis andconsequently the origin of the fat in the humanvariety.The majority of published descriptions of the

condition in human cases make little or no referenceto the fat present although occasional cholesterolclefts have been reported (Hooper et al, 1962).However, Schlagenhaufer (1916) and Barrie (1948)refer to macrophages containing doubly refractile fatand examination of a recent case of which unembed-ded material was available (Dr R. C. B. Pugh)provided abundant confirmation.

Certain obvious differences between the feline andhuman varieties of the disease emerge. First thefoam cells differ, both in number and in appearance.They are obviously more numerous in the human

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variety and their cytoplasm is clearer, resemblingthat of the cells of a classical hypernephroma.Secondly a high proportion of the fat in the humanvariety is doubly refractile, whilst no birefringencecan be demonstrated in the feline variety even thoughthe fat in both normal renal epithelium and in renalscars has a steroid component (Lobban, 1955;Lucke, 1965).

There can be no doubt that the fat in the granulo-matous lesions in the cat is derived from the renalepithelium. On the other hand, the absence of visibleand stainable intraepithelial fat in human examplesof pyelonephritis has led to the exclusion of an

epithelial origin for the fat in the xanthogranuloma-tous variety (Heptinstall, 1966). Furthermoreexaminations of frozen sections from the apparentlynormal kidneys of six patients dying from diseasesnot affecting the urinary tract, either directly orindirectly, revealed only very sparse droplets ofstainable fat in occasional convoluted tubules and nobirefringence under polarized light.These fundamental differences between feline and

human xanthogranulomatous pyelonephritis rein-force the contention that the fat in the latter varietyis not derived from the renal epithelium.A study of the reported cases of human xantho-

granulomatous pyelonephritis certainly confirms theclose association (Heptinstall, 1966) between thecondition and ureteric obstruction and renalsuppuration. This combination is notorious forproducing changes in the calyces and pelvis togetherwith destruction of renal tissue and involvement of

G. B. D. Scott atnd P. J. Quigleoly

the surrounding adipose tissue, thus raising thepossibility that the latter site is the origin of the fatin human xanthogranulomatous pyelonephritis.

Our thanks are due to Dr R. C. B. Pugh of St Paul'sHospital, London, for allowing us access to thematerial of his case, to Dr V. M. Lucke of theDepartment of Pathology, the University of Bristol,for her opinion on the slides of the feline case, and toProfessor E. Cotchin of the Department of Pathology,The Royal Veterinary College, London, for hisadvice and encouragement.

References

Avnet, N. L., Roberts, T. W., and Goldberg, H. R. (1963). Tumefactivexanthogranulomatous pyelonephritis. .4liner. J. Roenitgeniol., 90,89-96.

Barrie, H. J. (1949). Foam-cell granuloma in chronic pyelonephrosissimulating tuberculosis. Brit. J. Surg., 36, 316-319.

Friedenberg, M. J., and Spjut, H. J. (1963). Xanthogranulomatouspyelonephritis. Attmer. J. Roentgenol., 90, 97-108.

Ghosh, H. (1955). Chronic pyelonephritis with xanthogranulomatoischange. Amer. J. clin. Path., 25, 1043-1049.

Heptinstall, R. H. (1966). Patholog/ o the Kidnei, ch. 15. Little Brow n,Boston, Mass.

Hooper, R. G., Kempson, R. L., and Schlegel, J. U. (1962). Xantho-granulomatous pyelonephritis. J. Urol., 88, 585-593.

Leadbetter, G. W., Jr., et al (1962). Case Records of MassachusettsGeneral Hospital case 9-1962 (Chronic abscess of right kidney).Newt, Engl. J. Med., 266, 255-258.

Lobban, M. C. (1955). Some observations on the intracellular lipid inthe kidney of the cat. J. Anat. (Lond.), 89, 92-99.

Liicke, V. M. (1965). Renal disease in the domestic cat. PhD Thesis.University of Bristol.

Mack, F. G., and Mador, M. L. (1952). Pyogenic (foam-cell) granu-loma in a case of pyelonephritis. J. Urol., 67, 258-261.

Schlagenhaufer, F. (1916). Ober eigentumliche Staphylomykosen derNieren und des pararenalen Bindegewebes. Frankfiurt. Z. Path.,19. 139-148.

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