Xanthogranulomatous pyelonephritis (XGP) is a rare and aggressive variant of chronic pyelonephritis resulting in a non-functioning kidney. It is most often associated with chronic obstruction and stones with ongoing infection. It is also referred to as a pseudotumor due to an enlarged kidney resembling a tumor and the ability of local invasion and destruction. The disease is characterized by the destruction and replacement of renal or peri-renal tissue with granulomatous tissue containing lipid-laden macrophages. The term "xantho" (Greek meaning yellow) is used in its name due to the infiltration of lipid-laden macrophages that appear yellow in the pathological section. XGP was first described by Schlagenhaufer in 1916 and was named as xanthogranuloma by Osterlin in 1944.
Xanthogranulomatous pyelonephritis is often confused with a true neoplasm, most commonly renal cell carcinoma due to its similarity in clinical and radiographic features, as well as the ability to involve the adjacent structures or organs. Therefore, early identification and treatment are required to decrease the morbidity and mortality associated with this condition. Although antibiotics can be given in acute infection, the treatment of choice for XGP is nephrectomy.
(a) Diffuse: Kidney involvement is diffuse.
(b) Segmental: Kidney involvement is segmental.
(c) Focal: Involvement within the cortex of the kidney.
The etiology of XGP remains unknown. However, most of the cases result from chronic urinary obstruction and infection. The organisms most commonly associated with XGP are Escherichia coli, Proteus mirabilis, Pseudomonas, Enterococcus faecalis, and Klebsiella, etc. Urinary obstruction occurs as a result of calculus, most commonly, staghorn calculus (in almost 80% of patients), which serves as a nidus for infection resulting in the destruction of the renal parenchyma. However, in children, congenital ureteropelvic abnormalities may result in chronic urinary obstruction.
Risk factors for XGP:
The incidence of XGP varies from 0.6% to 1% of all cases of renal infections. The disease can occur in all age groups but is more common in women than in men, usually in their fifth and sixth decade of life. There is no specific race predilection. Although in most patients, the unilateral kidney is involved, bilateral involvement can rarely occur in a few cases. Both the kidney are affected with equal frequency.
XGP is extremely rare in children, but when it occurs, there are two different presentations. The most common form involves the entire kidney and equally affects males and females. The less common form includes a localized area of the kidney and mostly affects females.
The exact pathophysiology of XGP is unclear. The mechanism involved in the pathogenesis of XGP is nephrolithiasis leading to chronic obstruction and infection. It is an inflammatory disorder that may occur due to a defect in the degradation of bacteria by a macrophage. The disease is characterized by the destruction and replacement of renal or peri-renal tissue with granulomatous tissue containing lipid-laden macrophages. However, the accumulation of lipids and cholesterol in the lesion is not well understood. It starts from the renal pelvis and calyces spreading to the renal parenchyma and finally to the adjacent organs if left untreated. Adjacent organs such as liver, spleen, duodenum, pancreas, and great vessels can be involved in a severe form of XGP.
The microscopic examination of xanthogranulomatous pyelonephritis lesion shows three distinct zones centered by a calyx with the following findings in each zone:
The gross pathology of the mass may show yellow tissue with necrosis and hemorrhage.
The typical history of a patient with XGP is a middle-aged female presenting with recurrent urinary tract infections most commonly due to Escherichia coli and Proteus mirabilis. In children, the presenting complaint may be fever, flank or abdominal pain, and growth retardation.
The presentation is similar to renal tuberculosis. Hence, the history of travel to the endemic region should be evaluated.
The adult patient with XGP may present with the following symptoms:
Evaluation of a patient with XGP requires appropriate history, physical examination, and comprehensive lab work. The detailed laboratory and radiographic findings are explained below:
The preoperative diagnosis of XGP can be difficult due to the similar findings associated with renal cell carcinoma. CT scan helps differentiate these two conditions as well as knowing the extension of the disease. However, confirmatory diagnosis of XGP is made by pathological examination.
Individuals with a clinical presentation and pre-operative diagnosis of focal or segmental XGP can be treated with antibiotics and percutaneous drainage. With no improvement, partial nephrectomy or nephrectomy can be done.
In patients with a diagnosis of diffuse or advanced stage XGP, the treatment of choice is nephrectomy. The use of antibiotics before and after surgery controls the local infection and avoids septic complications. The aim of surgery is to remove all granulomatous tissue so that there is no fistula formation in the future. Sinuses or fistulas should be repaired if found.
Rare cases of bilateral XGP should be treated with bilateral nephrectomy and long-term dialysis.
There has been debate regarding open versus laparoscopic nephrectomy. Because of the inflammatory nature of the disease, laparoscopic nephrectomy is often challenging, and the conversion rate from laparoscopic to open nephrectomy is 50%. Laparoscopic nephrectomy can be done in selected patients by a surgeon with advanced laparoscopic experience and skills. Laparoscopic nephrectomy is associated with less blood loss and reduced hospital stay in patients with XGP.
The differential diagnosis for xanthogranulomatous pyelonephritis includes:
The clinical presentation and radiographic appearance of XPG and renal cell carcinoma are similar, however, fever and raised inflammatory markers (CRP and ESR) are most commonly associated with XPG. If present, the "bear paw" sign is a pathognomonic feature of XPG. However, histology gives the confirmatory diagnosis for XGP.
Xanthogranulomatous pyelonephritis is classified as focal, segmental, and diffuse. The diffuse form is more common, which is further staged by Malek and Elder into three different stages according to the extent of involvement in the nearby tissues.
The overall prognosis of XGP is excellent. Unilateral cases have a better prognosis, while bilateral cases are usually fatal. Nephrectomy is the treatment of choice without any incidence of recurrence.
Xanthogranulomatous pyelonephritis is a rare and aggressive form of chronic pyelonephritis. It is often confused with renal cell carcinoma and renal tuberculosis due to similar signs and symptoms. The diagnosis of XGP is based on the CT scan finding of the "bear paw" sign and histology showing lipid-laden foamy macrophage. It has the ability to involve the adjacent structures or organs if left untreated. Hence, early diagnosis and treatment can prevent the complications of this disease. Treatment with nephrectomy has an excellent prognosis.
As the disease can involve multiple organs when left untreated, a team consisting of an infectious disease specialist, oncologist, radiologist, urologist, and a urological surgeon should carefully evaluate the disease and look for any complication.
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