xanthogranulomatous pyelonephritis (XGP)

[Pseudotumoral xanthogranulomatous pyelonephritis: diagnosis with percutaneous biopsy and success of conservative treatment].


Reul O, Waltregny D, Boverie J, de Leval J, Andrianne R.

Service d'Urologie, Centre Hospitalier Universitaire du Sart-Tilman, Liège, Belgique.
olivierreul  at  hotmail.com

Abstract

Focal xanthogranulomatous pyelonephritis is an unusual form of chronic renal infection that is difficult to diagnose prior to surgery. We report on a 19-year-old woman who presented with a renal mass that mimicked malignancy. The diagnosis of focal xanthogranulomatous pyelonephritis was first suspected by radiological findings and further confirmed by histopathologic examination of percutaneous biopsy specimens of the lesion. Successful treatment of the patient was achieved with antibiotic therapy alone. Maximal efforts, including percutaneous renal biopsy, should be made to establish the diagnosis of focal xanthogranulomatous pyelonephritis before a therapeutic decision is reached. We recommend the use of antibiotics as a first-line treatment for patients with focal xanthogranulomatous pyelonephritis.

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http://www.ncbi.nlm.nih.gov/pubmed/11859664

CASE REPORT
Xanthogranulomatous Pyelonephritis
Successfully Treated with Antibiotics Only
Chang-I Ho1, Yao-Ko Wen1*, Mei-Ling Chen2
1Division of Nephrology, Department of Medicine, and 2Department of Pathology,
Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
A 73-year-old woman with leukemia presented with urinary tract infection, splenic abscess, and a renal mass. Both urine culture and pus culture of the splenic abscess yielded Klebsiella pneumoniae. Percutaneous biopsy of the renal mass confirmed the diagnosis of xanthogranulomatous pyelonephritis. Because of high risk for surgery, the patient received treatment with antibiotic therapy for 2 months. With antibiotic therapy, not only was the splenic abscess cured but follow-up ultrasonography also showed progressive resolution of the renal mass. Xanthogranulomatous pyelonephritis is frequently associated with urinary tract obstruction or nephrolithiasis. In this first report of xanthogranulomatous pyelonephritis in a patient with leukemia and splenic abscess, we provide a short review of xanthogranulomatous pyelonephritis successfully treated with antibiotics only. [J Chin Med Assoc 2008;71(12):643–645]

http://homepage.vghtpe.gov.tw/~jcma/71/12/643.pdf

Xanthogranulomatous pyelonephritis (XPN) is an unusual
variant of chronic pyelonephritis that is frequently
associated with urinary tract obstruction or nephrolithiasis.
The nonspecific presentations may include fever,
chills, flank pain, malaise, weight loss, dysuria, or a palpable
flank mass. The most typical laboratory findings
are anemia and leukocytosis. Azotemia and abnormal
liver function test may be seen. Affected patients usually
have massive destruction of the renal parenchyma, with
granulomatous tissue-replacing infiltrates containing
lipid-laden macrophages that impart a yellowish-tan
appearance to the tissue. It has been believed that removal
of the xanthogranulomatous inflammatory tissue
is required to cure this disease. Therefore, the longstanding
mainstay treatment for XPN has been en bloc
or partial nephrectomy. However, there have been some
reported cases of XPN successfully managed with medical
treatment.1–5 Herein, we describe a case of XPN
concurrent with splenic abscess in a leukemia patient,
which was adequately treated with antibiotics only.

A 73-year-old woman was admitted with a 1-week
history of fever and chills. The patient had a history of
left breast cancer and had received operation and adjuvant
hormone therapy when she was 50 years old.
Positron emission tomography 3 years before this present
admission showed no abnormal findings except for
thyroid nodular goiter. Chronic myeloid leukemia was
diagnosed 1 year previously, and the patient had been
maintained on hydroxyurea therapy. Other comorbidities
included congestive heart failure and chronic
hepatitis B. About 1 month prior to admission, the
patient experienced an episode of urinary tract infection
and was treated with 1 week of oral ciprofloxacin.
Over the ensuing days, she continued to note frequent
urination. One week prior to admission, she developed
fever with chills and left flank pain, and did not respond
to another 1 week of oral ciprofloxacin.
Physical examination on admission found abdominal
tenderness in the left upper quadrant area. Complete
blood count showed a white blood cell count of
32,100/μL with 19.5% segmented neutrophils, 8%
lymphocytes, 20% bands and 25.5% blast cells, hemoglobin
of 7.6 g/dL, hematocrit of 22.2%, and platelet
count of 46,000/μL. Blood chemistry showed aspartate
aminotransferase of 20 U/L (normal, 8–40 U/L), alanine
aminotransferase of 11 U/L (normal, 4–44U/L),
blood urea nitrogen of 16.9 mg/dL (normal,
5–25 mg/dL), and creatinine of 1.0mg/dL (normal,
0.7–1.4 mg/dL). Urinalysis revealed occult blood (++),
protein (+), and nitrite (+), with 20–25 red blood cells,
numerous white blood cells, and many bacteria per
high-power field in the urinary sediments. Urine culture
grew Klebsiella pneumoniae with the presence of
ciprofloxacin resistance.
Ultrasonography of the abdomen revealed a hypoechogenic
area in the spleen, with the features of splenic
abscess, and a heterogeneously dense mass in the left
kidney. Enhanced computed tomography of the abdomen
demonstrated a hypodense area in the spleen and
a hypoattenuating mass in the left kidney (Figure 1).
The differential diagnosis of the renal mass included
unliquefied renal abscess, XPN, and renal cell carcinoma.
Ultrasound-guided aspiration from the splenic
lesion showed thick yellowish pus; however, aspiration
from the left renal mass was negative. Pus culture of
the splenic abscess also yielded K. pneumoniae.
The patient was treated with the intravenous
antibiotic cefmetazole after admission. After 2 weeks of
antibiotic therapy, follow-up ultrasonography showed
resolution of the splenic abscess with no change in the
renal lesion. At this time, percutaneous biopsy of the
renal mass was performed. The specimen showed many
characteristic foamy lipid-laden macrophages of XPN.
On periodic acid–Schiff (PAS) stain, no obvious intracytoplasmic
PAS-positive Michaelis-Gutmann bodies
could be found within the macrophages (Figure 2)

http://homepage.vghtpe.gov.tw/~jcma/71/12/643.pdf

MRI IMAGING

RCC?
magnetic resonance imaging is useful in the differentiation.

Surgical intervention for XPN was indicated. Because
of the patient's underlying comorbidity, the risk for
surgery was relatively high. Therefore, the patient was
continued on medical treatment. With antibiotic therapy,
follow-up ultrasonography 4 weeks later showed
that the renal mass had decreased in size. The patient
was maintained on the oral antibiotic cefixime for another
1 month, and follow-up ultrasonography showed
complete resolution of the renal mass.


Discussion
XPN is a particular type of chronic renal infection with
an unusual inflammatory response. Pyuria and bacteriuria
are frequent but not uniformly present. One third
of patients have sterile urine, and the infectious organism
will be found only by tissue culture. The most common
offending organisms are Proteus mirabilis, Escherichia
coli, K. pneumoniae and Streptococcus faecalis. Computed
tomography provides the most useful information,
especially by defining the extent of renal involvement
and spread to adjacent organs. Computed tomography
features that have been considered to be characteristic,
though not pathognomonic, for XPN include
renal enlargement, strands in the perinephric fat,
thickening of Gerota's fascia, and thick enhancing
septa separating hypodense areas in the renal parenchyma.
6 However, focal XPN may be erroneously
interpreted as renal cell carcinoma. The heterogeneous
and solid aspect on computed tomography is indeed
often indistinguishable from hypovascular renal cell
carcinoma. Especially when, as in our case, there is no
sign of urinary tract obstruction or nephrolithiasis, the
diagnosis may be equivocal. It is reported that magnetic
resonance imaging may be useful in the differentiation.
The diagnosis of focal XPN is suggested in
the absence of hyperintensity on fast T2-weighted
sequences.5 The histologic hallmark xanthoma cells are
lipid-laden macrophages or foamy macrophages, which
on electron microscopy are initially found to contain
bacteria and subsequently contain numerous phagolysosomes.
It is hypothesized that XPN may be caused by
a lysozymal defect of macrophages that prevents complete
digestion of ingested bacteria. The cause of lipid
accumulation in the lesion is not well understood.
Although the pathogenesis of XPN remains unknown,
the most common factors predisposing to the
development of XPN are urinary tract obstruction
and nephrolithiasis. The occurrence of XPN has rarely
been reported in the absence of clear predisposing
uropathy.7 To the best of our knowledge, this is the
first report of XPN occurring in leukemia patients and
concurrent with splenic abscess. Whether the underlying
immunocompromised state due to leukemia further
predisposes to an abnormal inflammatory response,
as seen in XPN, is speculative.
Surgical nephrectomy has been the treatment of
choice for diffuse XPN. For focal XPN, most patients
undergo surgical exploration because of the difficulty
of preoperatively differentiating it from renal malignancy.
8 Furthermore, the association of malignancy
with XPN has prompted several authors to dispute the
wisdom of medical therapy for XPN. As a result, the
response to medical therapy has rarely been reported.
Focal XPN has been successfully treated with antibiotics
only for 3–10 weeks without surgical intervention.
1,2,4,5 XPN has also been seen in the transplanted
kidney. A trial of antibiotic therapy prior to surgery
was attempted to salvage the renal allograft and was
successful in 2 cases.3
In conclusion, since focal XPN commonly presents
with a renal mass and is frequently difficult to differentiate
from renal cell carcinoma, maximal efforts, including
renal biopsy, should be made to establish the diagnosis
before a therapeutic decision is reached. This case and
review of the literature suggest that successful treatment
of focal XPN can be achieved with antibiotic therapy
alone. Therefore, a trial of antibiotic therapy is warranted
and unnecessary nephrectomy may be avoided.


====  previous accespted wisdom ====

Xanthogranulomatous pyelonephritis (XGP) is a rare, serious, debilitating illness characterized by an infectious renal phlegmon. This disease process ultimately results in focal or diffuse renal destruction and is characterized pathologically by lipid-laden foamy macrophages. XGP shares many characteristics with true renal neoplasms in terms of its radiographic appearance and ability to involve adjacent structures or organs. Most cases of XGP are unilateral and are often associated with urinary tract obstruction, infection, nephrolithiasis, diabetes, and/or immunocompromise. The treatment of XGP is almost universally extirpative and can pose a formidable challenge to the surgeon.


History of the Procedure

Schlagenhaufer first described XGP in 1916. The first pediatric case was not described until 1963. Historically, open extirpative therapy has been the hallmark of management, although an increasing number of reports have recently described successful laparoscopic intervention. 

Problem

XGP is defined as a chronic inflammatory disorder of the kidney characterized by a destructive mass that invades the renal parenchyma. The condition is most commonly associated with Proteus or Escherichia coli infection. Pseudomonas species have also been implicated. The kidney is usually nonfunctional. Most cases of XGP involve a diffuse process; however, up to 20% are focal. 

Although most cases of XGP are unilateral, bilateral disease has been reported. Bilateral nephrectomy and long-term dialysis is a treatment option. Although Perez et al described successful treatment with partial nephrectomies in one patient,1 bilateral XGP is usually fatal.

Frequency

XGP occurs in approximately 1% of all renal infections. Although XGP is rare in the pediatric population, it is found in approximately 16% of pediatric nephrectomy specimens. XGP is 4 times more common in women than in men and is usually noted in the fifth and sixth decades of life. XGP affects both kidneys with equal frequency.

Etiology

The exact etiology of XGP is unknown, but it is generally accepted that the disease process requires long-term renal obstruction and infection. Stones (frequently of staghorn proportions) develop in 80% of patients with XGP but are not required to make the diagnosis. XGP is often observed in patients with diabetes and/or immunocompromise. Abnormal lipid metabolism has also been hypothesized as an etiologic factor in individuals with XGP.

Pathophysiology

XGP displays neoplasmlike properties capable of local tissue invasion and destruction and has been referred to as a pseudotumor. Adjacent organs, including the spleen, pancreas, or duodenum, may be involved. 

The gross appearance of XGP is a mass of yellow tissue with regional necrosis and hemorrhage, superficially resembling renal cell carcinoma. The pathognomonic microscopic feature is the lipid-laden foamy macrophage accompanied by both chronic- and acute-phase inflammatory cells. Focal abscesses may be observed.

Presentation

Patients with XGP often appear chronically ill. Symptoms include anorexia, fever, chills, weight loss, and flank pain. The pain of XGP is not colicky in nature; it is usually dull and persistent. Urine typically contains both leukocytes and bacteria. The pH is often basic because Proteus mirabilis is a urease-producing organism. The erythrocyte sedimentation rate is frequently elevated.

XGP is notorious for fistulization. Pyelocutaneous and ureterocutaneous fistulae have been well-described. Other organs are occasionally involved in this process, including surrounding viscera with resulting pyeloenteric fistulae.

In children, XGP is more common in boys and usually affects those younger than 8 years. Obstruction associated with XGP in the pediatric population is more due to congenital factors than obstructive calculi.

Renal cell carcinoma may be indistinguishable from XGP radiographically and clinically. A case of XGP involving thrombus of the renal vein has been reported.2 XGP and renal cell carcinoma have even been observed in the same specimen. Shah et al have reported a mistaken diagnosis of renal XGP that was subsequently proven to be renal tuberculosis.3 XGP must be diagnosed based on histology rather than based solely on radiographic imaging studies.

Illustrating the varied presentation of XGP, a recent case report by Hitti et al describes XGP located in a renal allograft.4 Another recent report describes a case of XGP associated with psoas abscess in a young pregnant woman in her third trimester.5


http://emedicine.medscape.com/article/439747-media  << PICTURES


Indications

Xanthogranulomatous pyelonephritis (XGP) is a surgically managed disease requiring either nephrectomy or, in rare circumstances, partial nephrectomy. Extirpation is necessary because the disease occurs or results in an infected, nonfunctioning kidney.

Relevant Anatomy

The kidneys are paired organs in the retroperitoneum. They are covered in a thin, fibrous capsule that is in turn covered by Gerota fascia. On the right, the liver and adrenal gland abut the superior pole of the kidney. The second part of the duodenum is medial to the right kidney and may be reflected medially to gain exposure to the inferior vena cava (Kocher maneuver). On the left, the superior pole of the kidney is attached to the spleen superolaterally (splenorenal ligament) and is very near to or in direct contact with the tail of the pancreas medially.

The colon is anterior to the kidneys and is easily reflected anteriorly and medially when transabdominal exposure is required. The renal hilar structure from anterior to posterior includes the vein, artery, and collecting system. The left renal vein has 3 draining tributaries, ie, the adrenal, gonadal, and posterior lumbar veins.

Contraindications

Contraindications to surgical therapy of xanthogranulomatous pyelonephritis (XGP) are those consistent with all major operations and intolerance to anesthesia, uncorrected coagulopathy, and severe connective-tissue disorders. ]



Workup
Laboratory Studies

   * CBC count with differential may reveal leukocytosis and anemia. Expect these conditions to gradually resolve after nephrectomy.
   * Liver function findings are abnormal in up to 50% of patients with xanthogranulomatous pyelonephritis (XGP).
   * Serum chemistries are used to determine the presence of any baseline electrolyte abnormalities, although none is pathognomonic of XGP. Creatinine levels prior to nephrectomy may be abnormal, but removal of the nonfunctioning xanthogranulomatous kidney should not be expected to alter baseline renal function.
   * Urinalysis often demonstrates pyuria and proteinuria.
   * Urine cultures are important in determining the offending organism involved in the XGP process and in assisting the appropriate selection of antibiotics.

Imaging Studies

XGP cannot be diagnosed solely based on radiographic findings.

   * CT scanning
         o CT scanning is the most useful radiographic technique in evaluating XGP.
               +

                     Xanthogranulomatous pyelonephritis (XGP) appearin...
                     Xanthogranulomatous pyelonephritis (XGP) appearing as enhancing loculated mass

                 [ CLOSE WINDOW ]

                     Xanthogranulomatous pyelonephritis (XGP) appearin...

                 Xanthogranulomatous pyelonephritis (XGP) appearing as enhancing loculated mass
         o A CT scan demonstrates a heterogenous nonenhancing mass on a hydronephrotic nonfunctioning kidney with a central stone. In higher-stage disease, the mass may appear to involve adjacent organs.
         o A large staghorn calculus may be found within the collecting system.
               +

                     Xanthogranulomatous pyelonephritis (XGP) with obs...
                     Xanthogranulomatous pyelonephritis (XGP) with obstruction and staghorn calculus

                 [ CLOSE WINDOW ]

                     Xanthogranulomatous pyelonephritis (XGP) with obs...

                 Xanthogranulomatous pyelonephritis (XGP) with obstruction and staghorn calculus
   * Renal ultrasonography usually reveals an enlarged kidney with multiple hypoechoic masses, irregular thinned parenchyma, and a dilated collecting system.
   * Mercaptotriglycine (MAG-3) or technetium-99m dimercaptosuccinic acid (Tc-DMSA) renal scanning may be used to evaluate or confirm differential renal function.
   * MRI is being studied selectively, but recent reports show little diagnostic benefit of MRI over traditional CT scanning.

Histologic Findings

The pathognomonic microscopic feature is the lipid-laden foamy macrophage. These cells can be difficult to distinguish from clear cell carcinoma on frozen section.
Staging

Malek and Elder have proposed the following stages of XGP involvement:6

   * Kidney
   * Perinephric fat
   * Adjacent retroperitoneal structures





Medical Therapy

Medical therapy has proven sufficient for treatment of xanthogranulomatous pyelonephritis (XGP) in only a handful of cases. Antibiotics may be appropriate as a temporizing measure in patients who require a medical workup prior to nephrectomy. Similarly, appropriate antibiotics should be administered prior to operative intervention.

The choice of antibiotic should be geared toward the identity and sensitivity of the organism. Proteus organisms and E coli are usually sensitive to various antibiotics, including first-generation cephalosporins and trimethoprim-sulfamethoxazole. Pseudomonas species have a narrower spectrum to which they are sensitive, however, and may require the use of aminoglycosides, third-generation cephalosporins, or fluoroquinolones. In patients who are not septic and who have been evaluated on an outpatient basis, the author's preference is to use an oral antibiotic until surgery, when intravenous antibiotics may be administered. Guidelines have not been established regarding the duration of antibiotic therapy after nephrectomy, but the author usually continues an active oral agent for 1 week.
Surgical Therapy

Nephrectomy is the criterion standard of treatment for XGP. These are often challenging cases, particularly in patients with local organ involvement. The goal is to remove all involved granulomatous tissue. If this is not accomplished, the remaining infected tissue may lead to cutaneous fistulae.

Some authors have advocated a role for partial nephrectomy if the disease is limited and therefore amenable to this operation.7

Laparoscopic nephrectomy is feasible for certain cases of XGP. Small pediatric series of XGP have reported success with the laparoscopic technique. However, Bercowsky et al reported that the technical difficulty and associated complications of the procedure negated any benefits over open nephrectomy.8 The increased use of hand-assisted laparoscopic nephrectomy may allow for an acceptable compromise between technical feasibility and acceptable patient morbidity. The laparoscopic approach may be entertained in all cases, but the patient and the patient's family can expect a conversion rate of nearly 50%.
Preoperative Details

   * Appropriate preoperative imaging studies are essential. This is best accomplished with CT scanning.
   * Administer a bowel preparation and preoperative antibiotics.
   * Surgical consent should include provisions for the possibility of operation on adjacent organs.
   * If the patient is diabetic, establish control of hyperglycemia prior to surgery.
   * Correct any preexisting coagulopathy.

Intraoperative Details

A flank approach through the appropriate intercostal/subcostal subcostal space (often the 11th rib) is desirable to avoid contamination of the peritoneum. Transabdominal subcostal exposure may be unavoidable if adjacent organs are involved with the mass.

The basic principles of nephrectomy apply to the extirpation of renal XGP. If possible, a radical nephrectomy (including Gerota fascia) should be performed, since the mass may still represent a neoplasm. All involved tissue must be removed. Liberal irrigation with antibiotic fluid is performed, and a suction drain is left in place.
Postoperative Details

The immediate postoperative care for patients with XGP is consistent with care that follows standard nephrectomy.

   * Watch for signs of sepsis.
   * Institute aggressive pulmonary toilet.
   * Encourage early ambulation.

Follow-up

Annual imaging of the contralateral urinary tract is important. Aggressively treat all urinary tract infections. If possible, eliminate or control the agent or illness that is predisposing the patient to XGP. Evaluation of lower urinary tract pathology and voiding dysfunction may be important in these patients.


Complications

The urological surgeon should maintain a low threshold to involve a general surgeon in patients with xanthogranulomatous pyelonephritis (XGP). Bleeding should be aggressively controlled. On the left, splenic injury may result; if possible, preservation of the spleen should be attempted. Any pancreatic injuries must be identified, repaired, and appropriately drained.

Similarly, right-sided injuries may occur to the duodenum and liver. Liver lacerations during nephrectomy are frequently limited to capsular tears, which may be easily controlled with argon-beam coagulation and pressure. Duodenal injuries require repair and nasogastric and cutaneous drainage. The colon is vulnerable to injury on either side. A patient who has received adequate bowel preparation may typically have these colonic injuries primarily repaired.

Vascular injury, especially on the right side, that involves the inferior vena cava can be humbling. The right-sided processes are often very inflamed and stuck, involving the adrenal and gonadal veins, lending them to avulsion and injury. Great care must be taken when dissecting out the right renal hilum. An alternative is to cross-clamp the hilum, transect it, and oversew the entire bundle. This can be planned or used in an emergency.

Postoperative abscess and cutaneous fistulization may occur, often after the drain has been removed and the patient has been discharged from the hospital. Patients typically present with drainage from the wound and fevers. CT scanning and percutaneous drainage should be performed, along with administration of intravenous antibiotics.

http://emedicine.medscape.com/article/439747-media  


Outcome and Prognosis

The overall prognosis for xanthogranulomatous pyelonephritis (XGP) is good. Death from this entity is exceedingly rare, although morbidity is substantial.
Future and Controversies

   * Nephron-sparing surgery will continue to be explored, provided that viable renal parenchyma is demonstrated.

   * Now that laparoscopic nephrectomy is the criterion standard in many regions, this approach can be entertained depending on the individual surgeon's skill level.

   * Further investigation is necessary to determine the underlying pathophysiologic mechanism responsible for the formation of xanthogranulomatous pyelonephritis (XGP).