Xanthogranulomatous pyelonephritis--(a clinicopathological study of 15 cases)BV Mittal, BP Badhe
The clinico-pathological features of 15 patients with xanthogranulomatous pyelonephritis (XGP) are described and the probable histogenesis is discussed. Based on our data and the review of literature, we believe that XGP should be regarded as a destructive and at times tumefactive inflammatory process that may complicate chronic pyelonephritis. The initiation of this process remains obscure, but the features commonly associated with XGP are pelvi-calyceal obstruction, ulceration of the pelvic urothelium with collection of necrotic material and bacterial infection.
Keywords: Adult, Aged, Child, Preschool, Female, Human, Male, Middle Age, Pyelonephritis, Xanthogranulomatous, epidemiology,pathology,
Xanthogranulomatous pyelonephritis (XGP) is an uncommon variant of bacterial infection of the kidney. It is characterised by accumulation of lipid laden macrophages in sufficient numbers to cause yellow nodules in the renal parenchyma, close to the pelvis. There is a destruction of the involved areas of the kidneys. Other characteristics like fibrosis extending into the perinephric fat, hydronephrosis and renal calculi are often observed. The condition is unilateral and results in a non-functioning kidney.
To gain a better understanding into the pathogenesis of the process, we undertook this clinico-pathological study.
Fifteen cases diagnosed as XGP in the last 8 years (1980-1987) were included in the study. Clinical details were obtained from the patients' records. Fourteen patients had undergone a total nephrectomy, while partial nephrectomy was carried out in one case. All the specimens were fixed in 10% buffered formalin and processed for paraffin wax sectioning. The sections were stained with haematoxylin-eosin, elastic Van Gieson (EVG) and Pearl's stain for haemosiderin.
The study comprised 8 males and 7 females. Fourteen cases were between 20 and 70 years of age (mean age 45 years). The youngest patient was 2 years old. Loin pain was the commonest presenting symptom, seen in 13 out of 15 cases (86.6%). Pyrexia and burning micturition were noted in 4 cases; one of these cases had recurrent attacks.
On examination, renal angle tenderness could be elicited in 11 cases (73.3%). In 7 cases (46.6% ), a palpable lump associated with pyonephrosis and hydronephrosis was seen. In one case, perinephric abscess was drained prior to nephrectomy.
On intravenous pyelography, non-functioning kidney was found in 14 cases (93.3%). Unascended kidney lying at L4-5 was seen in one case. Bifid ureter with hydronephrosis was seen in the paediatric patient. Obstructive lesions caused by renal calculi in the pelvis were present in 10 cases (66.6% ). One case had a ureteric calculus as well.
Urine culture reports were available in 12 cases. Gram negative micro-organisms (E. coli in 5 cases, Proteus vulgaris in 2 cases and Klebsiella in one case) were isolated in 8 cases, while urine was sterile in 4 cases.
Ten specimens were from the right kidney, while 5 were from the left kidney. Perinephric abscess was seen in 2 specimens. Increased perinephric fat and adherent capsules were seen in 8 cases, while in 7 cases the capsule could be stripped off easily, indicating no spread of infection to the perinephric tissues. Calculi (staghorn or otherwise) were noted within the renal pelvicalyceal system in 10 cases. Ureteral calculus was seen in one case. A polypoid tumour was seen in the renal pelvis alongwith a calculus in one case. There was diffuse dilatation of the pelvi-calyceal system in all cases. The renal parenchyma was variably scarred and atrophic.
Grossly visible, yellow, nodular areas varying from 2-10 mm in size were seen in 8 cases. These were close to the ulcerated, dilated pelvi-calyceal system. Areas of haemorrhage were noted in 5 cases.
Histological features observed are listed in[Table - 1].
Focal ulceration of the urothelium with acute inflammation was universal. Them was a polymorphous inflammation with presence of lymphocytes, plasma cells admixed with neutrophils. There was a background of chronic pyelonephritis characterised by focal, variable renal tubular atrophy, fibrosis, chronic inflammation and tubular dilatation. Superimposed on this background, were the changes of XGP. These varied from small focal aggregates of foamy histiocytes below the urothelium to large, destructive, nodular lesions. The foci of XGP were composed of macrophages, some with eosinophilic granular cytoplasm. In some cases, the foamy cells had the nucleus pushed to the periphery and resembled fat cells [Figure - 1].
Focal squamous metaplasia of the urothelium, lining the pelvis was noted in 2 cases. Grade III transitional cell carcinoma with focal areas of squamous metaplasia was noted in yet another case [Figure - 2]. This tumour had spread to the ureter and to the hilar lymph nodes. All the three cases were associated with calculi in the pelvis.
EVG stained slides revealed a variable degree of intimal thickening and medial hypertrophy of the medium-sized vessels. There was no other arterial or venous abnormality seen. There was no evidence of thrombosis or phlebitis. Areas of haemorrhage, adjacent to the ulcerated pelvis and to the xanthomatous areas were seen in 5 cases. Cholesterol granulomas were seen in 3 of these [Figure - 3].
Extension of the XGP process to the ureter with presence of foamy cells and calcification were noted in one case. Inflammatory infiltrate extended to the perirenal fat in 8 cases.
Since the first description of XGP by Schlagenhaufer in 1916 (quoted by Parsons et al), more than 400 cases have been reported in the world literature; the largest series being of 87 cases. This is a rare, so called `inflammatory tumour' of the kidney, involving the calyces, renal parenchyma and renal sinus areas. Unlike chronic pyelonephritis, it may spread into the perinephric tissue with formation of abscesses and even fistula.
Two other lesions, megalocytic interstitial nephritis (MIN) and malakoplakia have a common denominator with XGP, in the sense that they all represent varied histologic expressions of chronic renal disease. The hallmark of these lesions is the PAS positive, diastase resistant material in their cytoplasm. In addition to the histiocytes, one can identify a mixed cellular infiltrate composed of polymorphonuclear cells, plasma cells, lymphocytes and fibroblasts. Zollinger (quoted by Heptinstall) described MIN as an extremely rare form of interstitial nephritis affecting mainly the renal cortex. XGP involves the cortex and medulla and is frequently associated with severe renal disease and calculi. Malakoplakia of the kidney is primarily a disease of the renal pelvis with involvement of renal parenchyma and Michaelis-Gutmann bodies are the characteristics of the lesion. The lesions seen in all our cases involved the renal pelvis and the adjacent parenchyma but Michaelis-Gutmann bodies were not seen, hence they were labelled as XGP. Grossly visible, nodular, tumefactive lesions were noted in 53% of the cases while in the remaining cases, foamy cell collections were seen only on microscopic examination.
The demographic and clinical features in cases of XGP as reported by various workers are presented in [Table - 2]
XGP is more common in females., It may occur at any age, in the paediatric population as well as in elderly persons In our series, the sex distribution was nearly equal (8 males and 7 females). The youngest patient seen by us was 2 years old.
The lesion is generally unilateral and more often involves the right kidney. In 10 of our 15 cases, the right kidney was involved. None of the cases had bilateral lesions. A non-functioning kidney, with stone and infection or a `tumourous' lesion. in the kidney, indistinguishable from a malignant tumour, are the usual presenting features. Fourteen of the 15 cases that we studied, had a non-functioning kidney.
Etiology of XGP remains obscure, though a number of factors have been incriminated as causative factors, viz. urinary tract obstruction,, specific inflammatory agent, previous ineffective antibiotic treatment, a block in lipid transport, altered immunologic response, lymphatic obstruction, arterial insufficiency, venous occlusion and haemorrhage and necrosis of peri-calyceal fat.
We have analysed our data to find out the pathogenic features which are commonly encountered.
Urinary tract obstruction was observed in 13 of 15 cases. Calculi were noted in 11 cases, while abnormal ureteric openings in the, bladder were noted in 2 cases. Ulceration of the pelvi-calyceal urothelium with inflammatory infiltrate in the subepithelial area, extending into the parenchyma was noted in all cases. Thus, obstruction and infection seemed to be the commonest features.
Experimentally, XGP has been successfully produced by permanent ligation of the ureter and a single intravenous injection of a suspension of E. coli 04: H5 strain. Tan and Heptinstall have also shown similar results with injections of P. mirabilis and Staphylococci. Obstruction and infection thus have been shown to be important factors.
In majority of the reported cases, Gram negative bacterial infections, especially E. coli and Proteus species have been noted. In some patients more than one organism even Gram positive cocci (e.g. coagulase negative Staphylococcus aureus) have been incriminated. Occasionally, negative urine cultures are found. These may be due to previous antibiotic treatment. In our study, urine culture reports were available in 12 of the 15 cases; 4 cases revealed sterile urine, while Gram negative microorganisms (E. coli in 5 cases, Proteus vulgaris in two and Klebsiella in one) were isolated from the rest. These findings are in confirmity with the reported literature.
Lipid laden cells are seen in these lesions. These foam cells may be PAS positive macrophages related in some way to the infective background. They appear to concentrate in the areas of destruction. The necrotic, purulent material is considered to be the main source of the lipid droplets, though a partial endogenous origin cannot be ruled out. Electron microscopic studies have revealed cytosomes containing myelin figures. Bacterial antigens may also be seen. No intrinsic abnormality of monocytes has been described in association with XGP, but Abdou and associates described a patient with malakoplakia who had monocyte lysosomal abnormalities with decrease in cyclic guanyl monophosphate, corresponding to decrease in bactericidal activities. Since XGP and malakoplakia are related lesions, one cannot rule out the possibility of such an abnormality existing in XGP too. XGP has also been reported in native kidneys of patients with renal transplants receiving immunosuppressants. Thus, abnormality in cellular immune response may be one of the causative factors.
Foam cells, the hallmark of this disease process, have also been described in the ureter. One of our cases, too, showed presence of foam cells and foci of calcification in the ureter. The origin of lipid in these cells is not from the lining epithelium, as unlike feline urothelium, normal human urothelial lining does not show presence of stainable fat.
The role of venous obstruction which can lead to haemorrhage has been emphasized by McDonald. He has proposed that the released lipids from cellular elements undergo phagocytosis by histiocytes. We scanned the elastic Van Gieson stained sections for presence of venous, or arterial abnormalities, thrombi or phlebitis. Pearl stain for haemosiderin deposits was carried out, when fresh haemorrhage was not observed. No abnormal neovascularisation, lymphatic or vascular obstruction were noted in any of the cases. Evidence of haemorrhage, fresh or old, was seen in 5 cases. This was adjacent to the ulcerated pelvi-calyceal epithelium and was thought to be a part of acute on chronic inflammatory process rather than due to venous obstruction. Presence of cholesterol granulomas was observed in 3 cases. Though haemorrhage was present in one third of our cases, inflammatory component was predominant and present in all cases. As polymorphonuclear cells and red blood cells are commonly present in `pus' as well as in haemorrhage, the breakdown product of these cells seems to be a probable factor in the development of foam cells
Three cases showed foci of squamous metaplasia of the pelvic urothelium. As metaplasias are known to occur in association with calculi, their presence alongwith XGP is not surprising. One of our cases with XGP had calculus obstruction, as well as transitional cell carcinoma (TCC) arising in the pelvis, with spread into the ureter and to the hilar lymph nodes. It is uncertain whether stones and chronic non-specific inflammatory conditions are important in the pathogenesis of cancer of the urothelium however, vesical calculi are common among patients with TCC. Similarly, association between TCC and XGP is known.
Reversible hepatic dysfunction has been noted in 50% of the cases by Malek et al. No such abnormalities were noted in our cases.
Before XGP was recognised, the foamy cells were mistaken for renal tubular adenocarcinoma; but even today one can encounter this difficulty in differentiating it from carcinoma while interpreting fine needle aspiration material. Thus, taking into account the difficulties in a clinical, and even at times, histological diagnosis, nephrectomy rather than segmental resection seems advisable.
We sincerely thank the Dean and the Head of the Dept. of Pathology, Seth G.S. Medical College, Parel, Bombay-400 012, for allowing us to use the medical records and the pathology material of K.E.M. Hospital.
[Figure - 1], [Figure - 2], [Figure - 3][Table - 1], [Table - 2]