Discussion

 “Xanthogranulomatous” is a descriptive term referring to the presence of chronic inflammatory cells, including lymphocytes, plasma cells, and foamy, lipid-laden macrophages. This variety of reactive lesion occurs in various sites throughout the body, most notably the gallbladder (xanthogranulomatous cholecystitis, or XGC), lung, and kidney (xanthogranulomatous pyelonephritis, or XGP.) The latter is associated with chronic infection by Proteus Mirabilis or E. coli, obstruction of urinary outflow.⁴ Cutaneous xanthogranulomas occur frequently in children, and less commonly in adults. The ocular adnexae are occasionally involved.⁶

 XGP is known to be a chronic process predominantly affecting adults over 40 years of age resulting in diffuse renal parenchymal destruction. A  secondary chronic infection leads to tissue destruction and granulomatous formation replacing the renal parenchyma. Women are affected three times more often than men, and incidence peaks in the fifth to seventh decades.^1,4 The reported age range of the disease is 21 days to 90 years. Curiously, the disease affects the left kidney (57%) more often than the right (43%) in children, while in some reports of adult disease, the right kidney has been noted to be involved more often than the left. In both children and adults, the disease is usually a unilateral condition.¹

The precise etiology of XGP remains a mystery. There are many well-documented cases of genitourinary obstruction that have been associated with XGP. Obstruction due to calculi has been reported in as many as 83% of cases of XGP, and chemical analysis of these stones reveals calcium oxalate, either alone or combined with calcium phosphate or calcium carbonate. Thirty-one to 50% of the stones are of the staghorn variety. In one series of children with XGP, 75% had urolithiasis.¹

Positive urine cultures have been reported in 50-75% of cases of XGP, with E. coli and Proteus being found in up to 95% of positive cultures. However, other bacteria have also been occasionally implicated in XGP, including Klebsiella, Pseudomonas, and S. Aureus. Other factors, including diabetes mellitus, lymphatic obstruction, malignancy, renal arterial insufficiency, hyperparathyroidism, and alcoholism have also been suggested to play a role.

Symptoms are often nonspecific and include fever, flank pain, dysuria, and hematuria. A palpable flank mass is occasionally noted. Laboratory findings include an elevated sedimentation rate, normochromic or hypochromic anemia, and elevated white cell count. BUN and creatinine levels generally do not increase. IV pyelography and ultrasonography are helpful to assess the kidney’s level of functioning and to determine the size and site of a mass lesion. Definitive diagnosis requires biopsy, either through percutaneous fine-needle aspiration or surgery.¹

By comparison, Xanthogranulomatous Cholecystitis, or XGC, is a recognized variant of chronic cholecystitis, and is also characterized by the accumulation of lipid-laden macrophages. The incidence of this lesion, first described in 1970, ranges from 0.7% in parts of the US, to 1.8% in Sheffield, UK, with an intermediate incidence of 1.2% in Japan. In 1982, Fligiel and Lewin suggested a role for gallstones in the pathogenesis of this disorder, likening XGC to xanthogranulomatous pyelonephritis, where obstruction with stasis was known to be an important etiologic factor. A 1995 study of 460 cholecystectomy specimens in Wales failed to establish any firm correlation between XGC and carcinoma of the gallbladder (2).

 Xanthogranulomas are also frequent occurrences in the skin, albeit much more commonly in children than adults. The older term nevoxanthoendothelioma has gradually been replaced by juvenile xanthogranuloma. These lesions generally appear as several red to yellow nodules on the face, scalp, trunk, and limbs. The adult form of this disorder was first described in 1963, and contains more prominent giant cells (both foreign body and “ground-glass” variants) than in the juvenile form.⁷

Malakoplakia is thought to represent an incomplete phagocytic response to infection, i.e. bacteria. The renal variety of this condition is characterized by large collections of PAS-positive, plump macrophages known as Hansemann cells, with characteristic Michaelis-Gutmann bodies (iron and calcium-laden intracytoplasmic inclusions). Both renal malakoplakia and XGP are likely related to bacterial infections with improper intracytoplasmic processing of the microorganisms. In this case, the conspicuous absence of Michaelis-Gutmann bodies casts doubt on this diagnosis.⁵

Nephrectomy has been the treatment of choice for XGP and is considered curative, although segmental resection of affected areas has been successfully performed. There are rare reports of successful treatment of focal XGP with antibiotics only, although the rare association of the disease with malignancy has prompted several authors to dispute the wisdom of medical therapy alone for XGP.

References

1. Brown, Perry S. Mia Dodson. Peggy S. Weintrub. “Xanthogranulomatous Pyelonephritis: Report of Nonsurgical Management of a Case and Review of the Literature” Clinical Infectious Diseases 1996;22:308-14.
2. Dixit, Vinod K. et. al., “Xanthogranulomatous Cholecystitis” Digestive Diseases and Sciences Vol. 43 No. 5 (May 1998), 940-2.
3. Nadasdy, Tibor. Fred G. Silva. “Adult Renal Diseases” Diagnostic Surgical Pathology Third Edition. Lippincott Williams & Wilkins, Philadelphia (1999), 1758-9.
4. Song, Erwin K. Mark Zwanger “Xanthogranulomatous Pyelonephritis” Journal of Emergency Medicine 2001 July 21(1), 63-4.
5. Stevens, S.A. “Malakoplakia of the Testis” British Journal of Urology (1995), 75, 111-2.
6. Sueki, Hirohiko et. al., “Adult-Onset Xanthogranuloma Appearing Symmetrically on the Ear Lobes” Journal of American Academy of Dermatology 1995;32:372-4.
7. Zelger, Bernhard et. al. “Juvenile and Adult Xanthogranuloma” American Journal of Surgical Pathology 18(2): 126-135 (1994)