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Xanthogranulomatous pyelonephritis masquerading as occult malignancy
XANTHOGRANULOMATOUS MASQUERADING WALTER
L. GERBER,
AS OCCULT MALIGNANCY M.D.
WILLIAM
J, CATALONA,
WILLIAM
R. FAIR,
STEPHEN
MICHIGAN,
LEE
MELSON,
PYELONEPHRITIS
M.D.
M.D. M.D.
M.D.
From the Department of Urology, University Iowa Hospitals and Clinics, Iowa City, Iowa
of
ABSTRACT - Xanthogranulomatous pyelonephritis (XGP) can present with weight loss, anemia, leukemoid reaction, and generalized debility; there may be no signs or symptoms referable to the urinary tract. Confusion between XGP and renal adenocarcinoma is well recognized, but other malignancies can also be simulated. Case histories of patients with proved XGP whose clinical presentations suggested occult malignancies are recorded. Proteus urinary tract infection, calculi, and a nonvisualizing kidney on intravenous pyelogram should suggest the correct diagnosis. The pathology, bacteriology, diagnosis, and treatment are reviewed.
Xanthogranulomatous pyelonephritis (XGP) is an unusual form of infection in which renal tissue is replaced by inflammatory cells containing large amounts of lipid.’ Numerous case reports and textbook descriptions indicate that the disease can be mistaken for adenocarcinoma by the surgeon at operation,2-4 by the radiand even by the pathologist.‘ -lo ologis t, 5-7 However, XGP may simulate other types of malignancies. Herein we describe the case histories of 3 patients who illustrate this. Case Reports
Case 1* A sixty-five-year-old black male with maturity onset diabetes and hypertension presented with a three-month history of left flank pain and a 20pound weight loss. He had had recurrent urinary tract infections with Escherichia coli and Proteus mirabilis despite antibiotic therapy. He denied hematuria, colic, or fever, *This case was previously
466
presented.
but did complain of nocturia two to three times with some hesitancy and decreased stream. Physical examination revealed a blood pressure of 120&O mm. Hg and temperature of 99.4” F. There was no flank mass or tenderness; his genitalia were normal, and rectal examination demonstrated a slightly enlarged, clinically benign prostate. Results of laboratory studies 31), were normal except for anemia (hematocrit and the urinalysis revealed pH 8, and 3 to 5 white and 2 to 3 red blood cells. Urine culture grew P. mirabilis. A roentgenogram showed a few small calcifications overlying the kidney and the kidney did not visualize on intravenous pyelogram. Retrograde pyelogram showed a normal distal ureter but multiple filling defects throughout the calyces and pelvis (Fig. 1A). Cytology of urine collected from the left kidney showed only atypia. Sonography revealed a diffusely abnormal kidney with an upper pole mass, and arteriography demonstrated a poorly functioning kidney with neovascularity (Fig. 1B). Selective renal studies showed stretching and
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FIGURE 1. Case 1. (A) Left retrograde pyelogram; multiple filling defects are seen in pelvis. (B) Selective left renal arteriogram showing neovascularity. (C) Selective left renal venogram; amputation of intrarenal branches, encasement of small intrarenal veins, and enlarged capsular veins are demonstration. (Reprinted with permission.7)
attenuation of the intrarenal branches, especially in the upper pole, and an indistinct corticomedullary border. Neovascularity was seen both centrally within the kidney and from the pelviureteric artery on both normal and epinephrine-enhanced studies. Venography revealed amputation of most of the major intrarenal branches, encasement and occlusion of smaller intrarenal veins, and greatly enlarged capsular veins (Fig. 1C). A diagnosis of a diffusely infiltrating transitional cell tumor was made, and the patient underwent nephrectomy. When the grossly swollen kidney was opened, the calyceal system was found to contain thick, yellow-green purulent material and a stone was lodged at the ureteropelvic junction. Pathology demonstrated XGP with renal abscesses and pyonephrosis. One enlarged lymph node was removed which showed reactive hyperplasia. Culture of the kidney also grew P. mirabilis. The postoperative course and follow-up have been uneventful. Case 2 A forty-two-year-old white female was apparently well until five months before admission when anorexia and nausea developed and she began to lose weight (40 pounds total). She denied flank pain, fever, or hematuria. One week before admission she suffered three grand ma1 seizures and was hospitalized. Physical examination was normal except for chronic illness, paleness, and weakness. Laboratory studies showed a hemoglobin of 4 Gm./lOO ml.;
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white blood cell count was 10,400 with 54 polymorphonuclear and 20 band cells. SMA showed sodium 124, potassium 3.1, chloride 72, and carbon dioxide 38. Urinalysis showed red cells, white cells, and bacteria; culture grew P. mirabilis. Workup with chest x-ray film, barium enema, upper gastrointestinal and skull series, electroencephalogram, and scans of liver, lung, and brain was normal. Bone marrow biopsy showed myeloid hyperplasia with an increase of early promyelocytes and occasional blast cells. A diagnosis was made of acute promyelocytic leukemia. She was transferred to our hospital when her temperature began to spike to 103” F. Review of the outside barium enema and upper gastrointestinal series revealed a right staghorn calculus. Intravenous pyelogram showed this stone, but the small left kidney failed to visualize at all (Fig. 2A and B). Findings on cystogram and cystoscopy were normal. A left acorn ureterogram demonstrated a normal distal ureter, but a 2.5-cm. filling defect was noted in the midureter. A no. 5 whistle-tip catheter was easily passed and drained purulent material, and defervescence subsequently occurred. During exploration of her flank a perinephric abscess was encountered; a renal biopsy showed only interstitial nephritis and acute inflammation on frozen section. Because the kidney looked salvageable a nephrostomy was performed and the flank drained. A matrix stone was also removed from the renal pelvis; culture of this stone grew P. mirabilis. The nephrostomy output remained less than 20 cc.
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FIGURE 2. Case 2. (A) KUB with large right staghorn and calci&ation above left ileum. (B) lntravenous pyelogram showing nonfunction of left kidney and stone. (C) Nephrostogram, multiple filling defects are seen in pelvis.
per day although nephrostogram showed the ureter to be patent (Fig. ZC). Multiple small filling defects were noted in the pelvis and ureter on this study. After the surgery the patient’s anemia and leukemoid reaction disappeared and she was discharged. She was readmitted a short time later with purulent drainage through the nephrostomy and the drain site. Renal scan and arteriogram showed essentially no flow to the left kidney and a nephrectomy was performed. Pathologic descriptions of the kidney showed XGP with microabscesses and areas of hemorrhagic infarction. The postoperative course and follow-up have been uneventful except for a superficial wound infection requiring debridement and secondary closure. Case 3 A sixty-nine-year-old white male was admitted with back pain on the right side, decreased appetite, and a three-week history of a 4-pound weight loss. The patient was eleven years postcystectomy and ileal conduit for invasive transitional cell carcinoma of the bladder. He denied chills, fever, or hematuria. Physical examination demonstrated his urinary stoma, mild tenderness in the right flank, and a palpable mass in the right upper quadrant below his liver. Laboratory studies showed a white blood cell count of 22,000 (slight left
shift). Urinalysis showed pH 7, 1 plus protein, 50 white blood cells, and 4 plus bacteria. Urine culture grew Klebsiella pneumoniae, P. mirabilis, and Pseudomonas aeruginosa. Chest x-ray film revealed the diffuse nodular infiltrates of pneumoconiosis and showed no changes from previous studies. Intravenous pyelogram showed an enlarged right kidney with a staghorn calculus and no excretion on that side (Fig. 3A). Computerized axial tomography (EMI) demonstrated a large, inhomogenous right renal mass which extended medially into the retroperitoneum along with enlarged periaortic lymph nodes (Fig. 3B). Angiogram revealed widespread neovascularity (Fig. 3C) and renal vein obstruction. A diagnosis was made of transitional cell carcinoma of the renal pelvis infiltrating the kidney. Further evaluation included a normal bone scan and a liver scan consistent with chronic liver disease. Fevers developed to 103.5” F. which were associated with shaking chills and which did not respond well to antibiotics. His hemoglobin suddenly dropped from 11.4 to 7.9 Cm./100 ml. necessitating a fourunit transfusion. Flank exploration uncovered a large perinephric abscess with pyonephrosis. The removed kidney weighed more than 1,000 Gm. and showed XGP with an obstructing stone. The postoperative course and follow-up were uneventful except for a transient increase in bilirubin.
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FIGURE 3. Case 3. (A) lntravenous pyelogram showing nonfunction of right kidney and staghorn calculus. (B) Computerized axial tomography (EMI) showing large right renal mass extending into retroperitoneum medially. (C) Selective right renal arteriogram showing neovascularity. (Reprinted with permission, Radiology 124: 359 (1977J.j
Comment These patients demonstrate the difficulty in ascertaining the diagnosis of XGP. The first and third cases show how XGP can mimic invasive transitional cell carcinoma of the kidney. Of course, the previous history of bladder cancer made this diagnosis in the kidney even more likely. Excretory urography, retrograde pyelography, sonography, arteriography, venography, and axial tomography all failed to distinguish between the two. All 3 patients demonstrated weight loss, pyuria, bacteriuria, and leukocytosis; these are nonspecific findings. The leukemoid reaction in the bone marrow of Case 2 has been reported in patients with severe chronic infectious processes but not specifically in xanthogranulomatous pyelonephritis. In Case 2 the involved kidney was small; this is unusual for this condition and may be related to an element of interstitial nephritis and chronic pyelonephritis present along with the XGP. Xanthogranulomatous pyelonephritis is an uncommon manifestation of chronic renal infection in which there is segmental or diffuse replacement of the renal parenchyma. Although some have attributed the first description to Schlagenhaufer in 1916,” the first accurate description of the microscopic findings was by Putschar in 1934.” He emphasized the presence of clumps of foam cells which grossly resembled the yellow of renal adenocarcinoma. The disease has been known by many names including staphylomycosis, foam cell granuloma, pyelonephritis xanthomatosis, and tumefactive
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xanthogranulomatous pyelonephritis. l3 Since Mitchell, Dodson, and Kay3 coined the term xanthogranulomatous pyelonephritis in 1959 several hundred cases have been reported. The disease is most prevalent in women ages forty to sixty with previous histories of urinary there are reports of problems, l4 although infants ages eleven months15 and seventeen monthsI with the disease. Over 90 per cent of reported cases have been in Caucasians,’ and only rare cases have been bilateral.” XGP cannot be diagnosed with certainty by clinical or laboratory means since the clinical presentations vary so widely. Chronic abdominal or flank pain, weight loss, low-grade fever, and repeated episodes or dysuria have been the symptoms most frequently reported.‘* An abdominal or flank mass has been palpable in up to 50 per cent of cases.13 Leukocytosis is common, reported in up to 70 per cent,3*‘0 but this and other abnormalities such as proteinuria, hematuria, and anemia are nonspecific findings. Often the disease is asymptomatic with abnormal radiographs being the only clues; this is especially true in paraplegics.lg The most common findings appear to be the triad of a large, nonfunctioning kidney on intravenous pyelogram (80 per cent of cases13) associated with calculi (70 per cent of case?O), and proteus urinary infection (70 per cent of cases21). It is reported22-24 that arteriography permits exclusion of renal neoplasia, but most of the literature cited and our own experience tend to refute this. Ultrasound cannot differentiate the hydronephrosis of XGP from other causes.25 the kidney is usually On gross inspection, enlarged and contains areas which are different
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shades of yellow and brown due to the replacement of renal tissue by the lipid-laden inflammatory cells. 1 There may also be large nodular masses which appear to invade the perirenal tissues, and this may add to the simulation of renal cell carcinoma. i8 Large cavities may be present and be filled with yellow material similar to the caseous material of tuberculosis. 26 Microscopically, the granulomatous tissue consists primarily of large macrophages with foamy cytoplasm containing large amounts of lipid material. These sheetlike masses of histiocytes are interspersed between bands of fibrous tissue infiltrated with lymphocytes and plasma cells.” This demonstration of irregular sheets of clear mononuclear cells infiltrating and replacing the normal renal architecture may readily be confused with hypernephroma, and may require special stains to make the distinction.* The etiology of XGP is obscure and multiple factors appear to be involved. In most cases there is a chronic renal infective process followed by tissue breakdown and liberation of lipid material; ureteral obstruction and vascular insufficiency appear to modify the subsequent inflammatory responses producing the microscopic picture of XGP.” The fact that most infections are due to proteus may only be related to the infection stone formation produced by alterations in urinary pH, or there may be peculiarities of the organism involved. An association with altered immunologic states has been suggested. l5 Prolonged antibiotic therapy producing a smoldering infection with alterations in both host and bacteria has also been in parathormone proposed, ‘* and alterations with hypercalcemia and hyperactivity, calciuria, have been implicated in the pathogenesis of the disease. 2o Blood lipids have been found to be normal.2s Malek et al. 3o have staged the disease according to the degrees of involvement: Stage 1 nephric; Stage 2 - nephric and perinephric; and Stage 3 - nephric, perinephric, and paranephric. There have been no reported recurrences of XGP after complete surgical removal, despite situations in which there was apparent extracapsular “invasion” of the perirenal tissues.’ Usually the nephrectomy is performed for suspected tumor. It has been suggested that partial nephrectomy may suffice if the process is recognized and limited to a portion of the kidney. 20*31However, it is often mentioned that the disease is usually more
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widespread than may be suspected from radiologic studies or even inspection of the surface of the kidney. Our Case 2 illustrates this, for the kidney appeared relatively healthy when first examined. Children, unlike adults, may have only segmental involvement of the kidney.31 The usual differential diagnosis of this inflammatory condition includes tuberculosis and chronic pyelonephritis as well as renal carcinoma,32*33 and nephroblastoma and Wilms’ tumor in children.34 The radiographic picture may be indistinguishable from renal tuberculosis, and the absence of acid-fast bacilli in the urine may not differentiate an autonephrectomized kidney. However, the limitation of the calculus formation to the renal pelvis should help distinguish XGP from the generalized calcifications seen in the end-stage tuberculous kidney. The palpation of a flank mass and the enlarged renal shadow on radiographs should help distinguish XGP from chronic pyelonephritis in which the kidney is usually shrunken. This was not true in one of our cases. Nonfunction of the kidney is very unusual in childhood tumors. As we have demonstrated by our case reports, the differential diagnosis must also include transitional cell carcinoma invading the kidney and other malignancies which produce generalized constitutional signs and symptoms. In all cases a high degree of suspicion is indicated in the face of a unilateral nonfunctioning kidney associated with calculi in the pelvis and urinary tract infection with proteus. Summary Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of renal infection. The urologic, radiologic, and pathologic literatures continually emphasize the confusion in differentiating this disease from adenocarcinoma. We have presented 2 cases in which the mistaken diagnosis of invasive transitional cell carcinoma was made and a case in which the associated leukemoid reaction was confused with an acute promyelocytic leukemia. If the diagnosis of XGP is to be made without surgery for suspected tumors, a high index of suspicion is required. XGP is most commonly associated with a large, nonfunctioning kidney by intravenous pyelogram associated with renal calculi and urinary infection with P. mirabilis. Iowa City, Iowa 52242 (DR. GERBER)
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References 1. McKenzie KR: Xanthogranulomatous pyelonephritis: confusion with renal carcinoma, J. Ural. 92: 261 (lQ64). 2. Hooper RC: Kempson RI, and Schlegel JU: Xanthogranulomatous pyelonephritis, ibid. 88: 585 (1962). 3. Mitchell RE, Dodson AI, and Kay S: Xanthogranulomatous pyelonephrttis, Am. Pratt. 10: 2150 (1959). 4. Seizer DW, Dahlin DC, and DeWeeld JH: Tumefactive xanthogramxlomatous pyelonephritis, Surgery 42: 874 (1957). 5. Friedenberg MS, and Spjut HJ: Xanthogranulomatous pyelonephritis, Am. J. Roentgenol. 90: -97 (1963). 6. Avnet NL, Roberts TW, and Goldberg HR: Tumefactive xanthogranulomatous pyelonephritis, ibid. 99: 89 (1863). 7. Barth KH, Lightman NI, Ridoifi RL, and Catalona WJ: Acute pyelonephritis simulating poorly vascularized renal neuplasm. Non-specificity of angiographic criteria, J. UroI. 116:. 650 (lQ76). 8. Saeed SM, and Fine G: Xanthogranulomatous pyelonephritis, Am. J. Clin. Pathol. 39: 616 (1963). 9. Rios-Dalenz JL, and Peacock RC: Xanthogranulomatous pyelonephritis, Cancer 19: 289 (1966). 10. Heptinstall RH: Pathology of the Kidney, 2nd ed., Boston, Little, Brown and Co., 1974, vol. 2, p. 916. 11. Schlagenhaufer R: 0ber eigentumliche Staphylomykosen der Nieren und des pararenalen Birdegewebes, Ztschr. Pathol. 19: 139 (1916). 12. Putschar W: Die entzundlichen Erkrankungen der obleitenden Homwege und der Nierenhullen reiunschliesalich der Pyelonephritis und der Pyonephrose, in Lubarsch D. and Henke, F., Eds.: Handbusch der speziellen -pathologischen Anatomie und Histologie, Berlin, Julius Springer, 1934, vol. 6, pp. 334-564. 13. Anhalt MA, Cawood CD, and Scott R, Jr: Xanthogranulomatous pyelonephritis: a comprehensive review with report of 4 additional cases, J. Urol. 195: 10 (1971). 14. Noyes WE, and Palubinskas AJ: Xanthogranulomatous pyelonephritis, ibid. 101: 132 (1969). 15. Mering JH, Kaplan GW, and McLaughlin AP: Xanthogranulomatous pyelonephritis: unusual clinical presentations, Urology 1: 338 (1973). 16. Ceccarelli FE, Jr, Wurster JC, and Chandor SB: Xanthogranulomatous pyelonephritis in an infant, J. Urol. 104:
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75.5 (1970). 17. Rossi P, Myers DH, Furey R, and Bonfils-Roberts EA: Angiography in bilateral xanthogranulomatous pyelonephritis, Radiology 90: 320 (1968). 18. Hatch CS, and Cockett ATK: Xanthogranulomatous pyelonephritis, J. Urol. 92: 585 (1964). 19. Kawaichi GK, and Reingold IM: Xanthogranulomatous pyelonephritis in the paraplegic, ibid. 97: 58 (1967). 20. Evans AE: Infection of the kidney and bladder in the adult, in Karafin, L, and Kendall, A. R., Eds.: Urology, New York, Harper and Row, 1976, vol. 1, chap. 14, p. 43. 21. Butnick R; Xanthogranulomatous pyelonephritis: an unusual case, J. Urol. 196: 815 (1971). 22. Clark RL, McAllister HA, and Harrell JE: An exercise in radiologic-pathologic correlation, Radiology 92: 597 (1969). 23. Emmett JL, and Witten DM: Clinical Urography, 3rd Ed., Philadelphia: W. B. Saunders, IQ71, vol. 2, p. 753. 24. Bissada NK, Holder JC, and Redman JF: Preoperative diagnosis of xanthogranulomatous pyelonephritis, Urology 7: 228 (1976). 25. Sanders RC: The place of diagnostic ultrasound in the examination of kidneys not seen on excretory urography, J. Urol. 114: 813 (1975). 26. Souto CAV, Monteiro SA, and Andrade LC: Xanthoibid. 102: 393 granulomatous pyelonephritis: 2 case reports, (1969). 27. Parker JM: Xanthogranulomatous pyelonephritis, ibid. 96: 290 (1966). 28. Smout MS, MeAninch LN, and Wyatt JK: Tumefactive xanthogranulomatous pyelonephritis, Br. J. Urol. 35: 129 (1963). 29. Elliott CB, Johnson HW, and Balfour JA: Xanthogranulomatous pyelonephritis and perirenal xanthogranuloma. Br. J. Urol. 40: 548 (1968). 30. Malek RS, Greene LF, DeWeerd JH, and Farrow GM: Xanthogranulomatous pyelonephritis, ibid. 44: 296 (1972). 31. Abbate AD, and Meyers J: Xanthogranulomatous pyelonephritis in childhood, J. Urol. 116: 231 (1976). 32. Becker JA: Xanthogranulomatous pyelonephritis: a case report with angiographic findings, Acta Radiol. 4: 139 (1966). 33. Melicow MM, and Becker JA: Radiographic simulation of certain solid tumors of the renal corpus to renal cyst, J. Urol. 97: 592 (1967).
471
L. GERBER,
AS OCCULT MALIGNANCY M.D.
WILLIAM
J, CATALONA,
WILLIAM
R. FAIR,
STEPHEN
MICHIGAN,
LEE
MELSON,
PYELONEPHRITIS
M.D.
M.D. M.D.
M.D.
From the Department of Urology, University Iowa Hospitals and Clinics, Iowa City, Iowa
of
ABSTRACT - Xanthogranulomatous pyelonephritis (XGP) can present with weight loss, anemia, leukemoid reaction, and generalized debility; there may be no signs or symptoms referable to the urinary tract. Confusion between XGP and renal adenocarcinoma is well recognized, but other malignancies can also be simulated. Case histories of patients with proved XGP whose clinical presentations suggested occult malignancies are recorded. Proteus urinary tract infection, calculi, and a nonvisualizing kidney on intravenous pyelogram should suggest the correct diagnosis. The pathology, bacteriology, diagnosis, and treatment are reviewed.
Xanthogranulomatous pyelonephritis (XGP) is an unusual form of infection in which renal tissue is replaced by inflammatory cells containing large amounts of lipid.’ Numerous case reports and textbook descriptions indicate that the disease can be mistaken for adenocarcinoma by the surgeon at operation,2-4 by the radiand even by the pathologist.‘ -lo ologis t, 5-7 However, XGP may simulate other types of malignancies. Herein we describe the case histories of 3 patients who illustrate this. Case Reports
Case 1* A sixty-five-year-old black male with maturity onset diabetes and hypertension presented with a three-month history of left flank pain and a 20pound weight loss. He had had recurrent urinary tract infections with Escherichia coli and Proteus mirabilis despite antibiotic therapy. He denied hematuria, colic, or fever, *This case was previously
466
presented.
but did complain of nocturia two to three times with some hesitancy and decreased stream. Physical examination revealed a blood pressure of 120&O mm. Hg and temperature of 99.4” F. There was no flank mass or tenderness; his genitalia were normal, and rectal examination demonstrated a slightly enlarged, clinically benign prostate. Results of laboratory studies 31), were normal except for anemia (hematocrit and the urinalysis revealed pH 8, and 3 to 5 white and 2 to 3 red blood cells. Urine culture grew P. mirabilis. A roentgenogram showed a few small calcifications overlying the kidney and the kidney did not visualize on intravenous pyelogram. Retrograde pyelogram showed a normal distal ureter but multiple filling defects throughout the calyces and pelvis (Fig. 1A). Cytology of urine collected from the left kidney showed only atypia. Sonography revealed a diffusely abnormal kidney with an upper pole mass, and arteriography demonstrated a poorly functioning kidney with neovascularity (Fig. 1B). Selective renal studies showed stretching and
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FIGURE 1. Case 1. (A) Left retrograde pyelogram; multiple filling defects are seen in pelvis. (B) Selective left renal arteriogram showing neovascularity. (C) Selective left renal venogram; amputation of intrarenal branches, encasement of small intrarenal veins, and enlarged capsular veins are demonstration. (Reprinted with permission.7)
attenuation of the intrarenal branches, especially in the upper pole, and an indistinct corticomedullary border. Neovascularity was seen both centrally within the kidney and from the pelviureteric artery on both normal and epinephrine-enhanced studies. Venography revealed amputation of most of the major intrarenal branches, encasement and occlusion of smaller intrarenal veins, and greatly enlarged capsular veins (Fig. 1C). A diagnosis of a diffusely infiltrating transitional cell tumor was made, and the patient underwent nephrectomy. When the grossly swollen kidney was opened, the calyceal system was found to contain thick, yellow-green purulent material and a stone was lodged at the ureteropelvic junction. Pathology demonstrated XGP with renal abscesses and pyonephrosis. One enlarged lymph node was removed which showed reactive hyperplasia. Culture of the kidney also grew P. mirabilis. The postoperative course and follow-up have been uneventful. Case 2 A forty-two-year-old white female was apparently well until five months before admission when anorexia and nausea developed and she began to lose weight (40 pounds total). She denied flank pain, fever, or hematuria. One week before admission she suffered three grand ma1 seizures and was hospitalized. Physical examination was normal except for chronic illness, paleness, and weakness. Laboratory studies showed a hemoglobin of 4 Gm./lOO ml.;
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white blood cell count was 10,400 with 54 polymorphonuclear and 20 band cells. SMA showed sodium 124, potassium 3.1, chloride 72, and carbon dioxide 38. Urinalysis showed red cells, white cells, and bacteria; culture grew P. mirabilis. Workup with chest x-ray film, barium enema, upper gastrointestinal and skull series, electroencephalogram, and scans of liver, lung, and brain was normal. Bone marrow biopsy showed myeloid hyperplasia with an increase of early promyelocytes and occasional blast cells. A diagnosis was made of acute promyelocytic leukemia. She was transferred to our hospital when her temperature began to spike to 103” F. Review of the outside barium enema and upper gastrointestinal series revealed a right staghorn calculus. Intravenous pyelogram showed this stone, but the small left kidney failed to visualize at all (Fig. 2A and B). Findings on cystogram and cystoscopy were normal. A left acorn ureterogram demonstrated a normal distal ureter, but a 2.5-cm. filling defect was noted in the midureter. A no. 5 whistle-tip catheter was easily passed and drained purulent material, and defervescence subsequently occurred. During exploration of her flank a perinephric abscess was encountered; a renal biopsy showed only interstitial nephritis and acute inflammation on frozen section. Because the kidney looked salvageable a nephrostomy was performed and the flank drained. A matrix stone was also removed from the renal pelvis; culture of this stone grew P. mirabilis. The nephrostomy output remained less than 20 cc.
467
FIGURE 2. Case 2. (A) KUB with large right staghorn and calci&ation above left ileum. (B) lntravenous pyelogram showing nonfunction of left kidney and stone. (C) Nephrostogram, multiple filling defects are seen in pelvis.
per day although nephrostogram showed the ureter to be patent (Fig. ZC). Multiple small filling defects were noted in the pelvis and ureter on this study. After the surgery the patient’s anemia and leukemoid reaction disappeared and she was discharged. She was readmitted a short time later with purulent drainage through the nephrostomy and the drain site. Renal scan and arteriogram showed essentially no flow to the left kidney and a nephrectomy was performed. Pathologic descriptions of the kidney showed XGP with microabscesses and areas of hemorrhagic infarction. The postoperative course and follow-up have been uneventful except for a superficial wound infection requiring debridement and secondary closure. Case 3 A sixty-nine-year-old white male was admitted with back pain on the right side, decreased appetite, and a three-week history of a 4-pound weight loss. The patient was eleven years postcystectomy and ileal conduit for invasive transitional cell carcinoma of the bladder. He denied chills, fever, or hematuria. Physical examination demonstrated his urinary stoma, mild tenderness in the right flank, and a palpable mass in the right upper quadrant below his liver. Laboratory studies showed a white blood cell count of 22,000 (slight left
shift). Urinalysis showed pH 7, 1 plus protein, 50 white blood cells, and 4 plus bacteria. Urine culture grew Klebsiella pneumoniae, P. mirabilis, and Pseudomonas aeruginosa. Chest x-ray film revealed the diffuse nodular infiltrates of pneumoconiosis and showed no changes from previous studies. Intravenous pyelogram showed an enlarged right kidney with a staghorn calculus and no excretion on that side (Fig. 3A). Computerized axial tomography (EMI) demonstrated a large, inhomogenous right renal mass which extended medially into the retroperitoneum along with enlarged periaortic lymph nodes (Fig. 3B). Angiogram revealed widespread neovascularity (Fig. 3C) and renal vein obstruction. A diagnosis was made of transitional cell carcinoma of the renal pelvis infiltrating the kidney. Further evaluation included a normal bone scan and a liver scan consistent with chronic liver disease. Fevers developed to 103.5” F. which were associated with shaking chills and which did not respond well to antibiotics. His hemoglobin suddenly dropped from 11.4 to 7.9 Cm./100 ml. necessitating a fourunit transfusion. Flank exploration uncovered a large perinephric abscess with pyonephrosis. The removed kidney weighed more than 1,000 Gm. and showed XGP with an obstructing stone. The postoperative course and follow-up were uneventful except for a transient increase in bilirubin.
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FIGURE 3. Case 3. (A) lntravenous pyelogram showing nonfunction of right kidney and staghorn calculus. (B) Computerized axial tomography (EMI) showing large right renal mass extending into retroperitoneum medially. (C) Selective right renal arteriogram showing neovascularity. (Reprinted with permission, Radiology 124: 359 (1977J.j
Comment These patients demonstrate the difficulty in ascertaining the diagnosis of XGP. The first and third cases show how XGP can mimic invasive transitional cell carcinoma of the kidney. Of course, the previous history of bladder cancer made this diagnosis in the kidney even more likely. Excretory urography, retrograde pyelography, sonography, arteriography, venography, and axial tomography all failed to distinguish between the two. All 3 patients demonstrated weight loss, pyuria, bacteriuria, and leukocytosis; these are nonspecific findings. The leukemoid reaction in the bone marrow of Case 2 has been reported in patients with severe chronic infectious processes but not specifically in xanthogranulomatous pyelonephritis. In Case 2 the involved kidney was small; this is unusual for this condition and may be related to an element of interstitial nephritis and chronic pyelonephritis present along with the XGP. Xanthogranulomatous pyelonephritis is an uncommon manifestation of chronic renal infection in which there is segmental or diffuse replacement of the renal parenchyma. Although some have attributed the first description to Schlagenhaufer in 1916,” the first accurate description of the microscopic findings was by Putschar in 1934.” He emphasized the presence of clumps of foam cells which grossly resembled the yellow of renal adenocarcinoma. The disease has been known by many names including staphylomycosis, foam cell granuloma, pyelonephritis xanthomatosis, and tumefactive
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xanthogranulomatous pyelonephritis. l3 Since Mitchell, Dodson, and Kay3 coined the term xanthogranulomatous pyelonephritis in 1959 several hundred cases have been reported. The disease is most prevalent in women ages forty to sixty with previous histories of urinary there are reports of problems, l4 although infants ages eleven months15 and seventeen monthsI with the disease. Over 90 per cent of reported cases have been in Caucasians,’ and only rare cases have been bilateral.” XGP cannot be diagnosed with certainty by clinical or laboratory means since the clinical presentations vary so widely. Chronic abdominal or flank pain, weight loss, low-grade fever, and repeated episodes or dysuria have been the symptoms most frequently reported.‘* An abdominal or flank mass has been palpable in up to 50 per cent of cases.13 Leukocytosis is common, reported in up to 70 per cent,3*‘0 but this and other abnormalities such as proteinuria, hematuria, and anemia are nonspecific findings. Often the disease is asymptomatic with abnormal radiographs being the only clues; this is especially true in paraplegics.lg The most common findings appear to be the triad of a large, nonfunctioning kidney on intravenous pyelogram (80 per cent of cases13) associated with calculi (70 per cent of case?O), and proteus urinary infection (70 per cent of cases21). It is reported22-24 that arteriography permits exclusion of renal neoplasia, but most of the literature cited and our own experience tend to refute this. Ultrasound cannot differentiate the hydronephrosis of XGP from other causes.25 the kidney is usually On gross inspection, enlarged and contains areas which are different
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shades of yellow and brown due to the replacement of renal tissue by the lipid-laden inflammatory cells. 1 There may also be large nodular masses which appear to invade the perirenal tissues, and this may add to the simulation of renal cell carcinoma. i8 Large cavities may be present and be filled with yellow material similar to the caseous material of tuberculosis. 26 Microscopically, the granulomatous tissue consists primarily of large macrophages with foamy cytoplasm containing large amounts of lipid material. These sheetlike masses of histiocytes are interspersed between bands of fibrous tissue infiltrated with lymphocytes and plasma cells.” This demonstration of irregular sheets of clear mononuclear cells infiltrating and replacing the normal renal architecture may readily be confused with hypernephroma, and may require special stains to make the distinction.* The etiology of XGP is obscure and multiple factors appear to be involved. In most cases there is a chronic renal infective process followed by tissue breakdown and liberation of lipid material; ureteral obstruction and vascular insufficiency appear to modify the subsequent inflammatory responses producing the microscopic picture of XGP.” The fact that most infections are due to proteus may only be related to the infection stone formation produced by alterations in urinary pH, or there may be peculiarities of the organism involved. An association with altered immunologic states has been suggested. l5 Prolonged antibiotic therapy producing a smoldering infection with alterations in both host and bacteria has also been in parathormone proposed, ‘* and alterations with hypercalcemia and hyperactivity, calciuria, have been implicated in the pathogenesis of the disease. 2o Blood lipids have been found to be normal.2s Malek et al. 3o have staged the disease according to the degrees of involvement: Stage 1 nephric; Stage 2 - nephric and perinephric; and Stage 3 - nephric, perinephric, and paranephric. There have been no reported recurrences of XGP after complete surgical removal, despite situations in which there was apparent extracapsular “invasion” of the perirenal tissues.’ Usually the nephrectomy is performed for suspected tumor. It has been suggested that partial nephrectomy may suffice if the process is recognized and limited to a portion of the kidney. 20*31However, it is often mentioned that the disease is usually more
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widespread than may be suspected from radiologic studies or even inspection of the surface of the kidney. Our Case 2 illustrates this, for the kidney appeared relatively healthy when first examined. Children, unlike adults, may have only segmental involvement of the kidney.31 The usual differential diagnosis of this inflammatory condition includes tuberculosis and chronic pyelonephritis as well as renal carcinoma,32*33 and nephroblastoma and Wilms’ tumor in children.34 The radiographic picture may be indistinguishable from renal tuberculosis, and the absence of acid-fast bacilli in the urine may not differentiate an autonephrectomized kidney. However, the limitation of the calculus formation to the renal pelvis should help distinguish XGP from the generalized calcifications seen in the end-stage tuberculous kidney. The palpation of a flank mass and the enlarged renal shadow on radiographs should help distinguish XGP from chronic pyelonephritis in which the kidney is usually shrunken. This was not true in one of our cases. Nonfunction of the kidney is very unusual in childhood tumors. As we have demonstrated by our case reports, the differential diagnosis must also include transitional cell carcinoma invading the kidney and other malignancies which produce generalized constitutional signs and symptoms. In all cases a high degree of suspicion is indicated in the face of a unilateral nonfunctioning kidney associated with calculi in the pelvis and urinary tract infection with proteus. Summary Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of renal infection. The urologic, radiologic, and pathologic literatures continually emphasize the confusion in differentiating this disease from adenocarcinoma. We have presented 2 cases in which the mistaken diagnosis of invasive transitional cell carcinoma was made and a case in which the associated leukemoid reaction was confused with an acute promyelocytic leukemia. If the diagnosis of XGP is to be made without surgery for suspected tumors, a high index of suspicion is required. XGP is most commonly associated with a large, nonfunctioning kidney by intravenous pyelogram associated with renal calculi and urinary infection with P. mirabilis. Iowa City, Iowa 52242 (DR. GERBER)
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References 1. McKenzie KR: Xanthogranulomatous pyelonephritis: confusion with renal carcinoma, J. Ural. 92: 261 (lQ64). 2. Hooper RC: Kempson RI, and Schlegel JU: Xanthogranulomatous pyelonephritis, ibid. 88: 585 (1962). 3. Mitchell RE, Dodson AI, and Kay S: Xanthogranulomatous pyelonephrttis, Am. Pratt. 10: 2150 (1959). 4. Seizer DW, Dahlin DC, and DeWeeld JH: Tumefactive xanthogramxlomatous pyelonephritis, Surgery 42: 874 (1957). 5. Friedenberg MS, and Spjut HJ: Xanthogranulomatous pyelonephritis, Am. J. Roentgenol. 90: -97 (1963). 6. Avnet NL, Roberts TW, and Goldberg HR: Tumefactive xanthogranulomatous pyelonephritis, ibid. 99: 89 (1863). 7. Barth KH, Lightman NI, Ridoifi RL, and Catalona WJ: Acute pyelonephritis simulating poorly vascularized renal neuplasm. Non-specificity of angiographic criteria, J. UroI. 116:. 650 (lQ76). 8. Saeed SM, and Fine G: Xanthogranulomatous pyelonephritis, Am. J. Clin. Pathol. 39: 616 (1963). 9. Rios-Dalenz JL, and Peacock RC: Xanthogranulomatous pyelonephritis, Cancer 19: 289 (1966). 10. Heptinstall RH: Pathology of the Kidney, 2nd ed., Boston, Little, Brown and Co., 1974, vol. 2, p. 916. 11. Schlagenhaufer R: 0ber eigentumliche Staphylomykosen der Nieren und des pararenalen Birdegewebes, Ztschr. Pathol. 19: 139 (1916). 12. Putschar W: Die entzundlichen Erkrankungen der obleitenden Homwege und der Nierenhullen reiunschliesalich der Pyelonephritis und der Pyonephrose, in Lubarsch D. and Henke, F., Eds.: Handbusch der speziellen -pathologischen Anatomie und Histologie, Berlin, Julius Springer, 1934, vol. 6, pp. 334-564. 13. Anhalt MA, Cawood CD, and Scott R, Jr: Xanthogranulomatous pyelonephritis: a comprehensive review with report of 4 additional cases, J. Urol. 195: 10 (1971). 14. Noyes WE, and Palubinskas AJ: Xanthogranulomatous pyelonephritis, ibid. 101: 132 (1969). 15. Mering JH, Kaplan GW, and McLaughlin AP: Xanthogranulomatous pyelonephritis: unusual clinical presentations, Urology 1: 338 (1973). 16. Ceccarelli FE, Jr, Wurster JC, and Chandor SB: Xanthogranulomatous pyelonephritis in an infant, J. Urol. 104:
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75.5 (1970). 17. Rossi P, Myers DH, Furey R, and Bonfils-Roberts EA: Angiography in bilateral xanthogranulomatous pyelonephritis, Radiology 90: 320 (1968). 18. Hatch CS, and Cockett ATK: Xanthogranulomatous pyelonephritis, J. Urol. 92: 585 (1964). 19. Kawaichi GK, and Reingold IM: Xanthogranulomatous pyelonephritis in the paraplegic, ibid. 97: 58 (1967). 20. Evans AE: Infection of the kidney and bladder in the adult, in Karafin, L, and Kendall, A. R., Eds.: Urology, New York, Harper and Row, 1976, vol. 1, chap. 14, p. 43. 21. Butnick R; Xanthogranulomatous pyelonephritis: an unusual case, J. Urol. 196: 815 (1971). 22. Clark RL, McAllister HA, and Harrell JE: An exercise in radiologic-pathologic correlation, Radiology 92: 597 (1969). 23. Emmett JL, and Witten DM: Clinical Urography, 3rd Ed., Philadelphia: W. B. Saunders, IQ71, vol. 2, p. 753. 24. Bissada NK, Holder JC, and Redman JF: Preoperative diagnosis of xanthogranulomatous pyelonephritis, Urology 7: 228 (1976). 25. Sanders RC: The place of diagnostic ultrasound in the examination of kidneys not seen on excretory urography, J. Urol. 114: 813 (1975). 26. Souto CAV, Monteiro SA, and Andrade LC: Xanthoibid. 102: 393 granulomatous pyelonephritis: 2 case reports, (1969). 27. Parker JM: Xanthogranulomatous pyelonephritis, ibid. 96: 290 (1966). 28. Smout MS, MeAninch LN, and Wyatt JK: Tumefactive xanthogranulomatous pyelonephritis, Br. J. Urol. 35: 129 (1963). 29. Elliott CB, Johnson HW, and Balfour JA: Xanthogranulomatous pyelonephritis and perirenal xanthogranuloma. Br. J. Urol. 40: 548 (1968). 30. Malek RS, Greene LF, DeWeerd JH, and Farrow GM: Xanthogranulomatous pyelonephritis, ibid. 44: 296 (1972). 31. Abbate AD, and Meyers J: Xanthogranulomatous pyelonephritis in childhood, J. Urol. 116: 231 (1976). 32. Becker JA: Xanthogranulomatous pyelonephritis: a case report with angiographic findings, Acta Radiol. 4: 139 (1966). 33. Melicow MM, and Becker JA: Radiographic simulation of certain solid tumors of the renal corpus to renal cyst, J. Urol. 97: 592 (1967).
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