Case 8 -

Xanthogranulomatous Pyelonephritis Eva M. Wojcik Loyola University Medical Center Maywood, IL

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Clinical Summary A 64 year old man, as part of his work-up for microhematuria, was found to have a large, partially cystic right kidney mass. CT-guided FNA of the renal lesion was performed. Case 8 - Figure 1 - Aspirate shows a two-dimensional cluster of large cells with abundant granular cytoplasm, ovoid nuclei with fine chromatin and small distinct nucleoli. (Papanicolaou stain, high power). Case 8 - Figure 2 - A papillary-like cluster of cells with high nuclear/ cytoplasmic ratio and varying in size round to oval nuclei. The chromatin is fine and small nucleoli can be appreciated. (Diff- Quik stain, high power) Case 8 - Figure 3 - A loose cluster of cells with abundant delicate granular cytoplasm and oval nuclei. Some of the nuclei appear indented. (Diff-Quik stain, high power). Case 8 - Figure 4 - A loose sheath of degenerated/necrotic large cells with abundant cytoplasm admixed with inflammatory cells. (Diff- Quik stain, high power). Xanthogranulomatous pyelonephritis (XGP) is an inflammatory sequel of chronic suppurative renal infection and is often associated with an obstruction. Generally, the infection is caused by Proteus or E.coli. The exact pathogenesis and etiology of XGP are unknown but, most probably, an inflammatory process is due to defect in the processing of bacteria by macrophages. XGP was first described by Schlagenhaufer in 1916. Although it is an uncommon disorder but it can clinically, radiographically and pathologically be confused with renal cell carcinoma. The peak age incidence is between 4th and 6th decades, however, XGP can be seen in infants. It is more common in females. Patients present with symptoms overlapping those of renal cell carcinoma. Often they complain of flank pain, fever, malaise, loss of appetite, and weight loss. The most common physical finding is a tender flank mass. XGP begins with suppurative inflammation and edema within the pelvic lamina propria and adjacent sinus fat leading to ulceration and fat necrosis. The necrotic process extends to medulla, cortex (Stage I), perinephric fat (Stage II) and retroperitoneal tissue (Stage III). Depends upon the extension of the destructive process, three patterns of XGP are recognized: diffuse, segmental and focal. The diffuse form is most common. It usually arises in a completely obstructed kidney usually due to calculi, often of staghorn form. The treatment of choice is nephrectomy. The segmental and focal forms are the ones most often radigraphically and grossly confused with carcinomas. Segmental XGP is polar and is more common in children. The focal (or tumefactive) form is a cortical variant, it lacks communication with the pelvis and is not associated with obstruction. The segmental and focal forms can be treated with partial nephrectomy. There are even reports of a successful antibiotic therapy. In general, less then 50% of XGPs are correctly diagnosed pre-operatively. Although, most cases contain a large staghorn calculus, its sonographic demonstration is difficult. Grossly, XGP is unilateral, tumor-like forming process. Kidney may be partially involved or be almost completely replaced by golden-yellow confluent masses. In addition, extension of the mass into a pernephric fat is often seen. Gross evidence of obstruction either by a presence of a calculus or by a deformity of the ureteropelvic junction are often appreciated. Microscopically, XGP also resembles renal cell carcinoma. The hallmark of the XGP is an abundance of foamy macrophages (xanthoma cells) that are intermixed with inflammatory cells including lymphocytes, plasma cells, neutrophils and multinucleated giant cells. The distribution of inflammatory cells may not be even leading to the formation of almost pure aggregates of foamy macrophages. In addition, the periphery of the tumor is usually surrounded by histiocytes transformed into spindled fibroblastic cells. Therefore extensive sampling of the lesion is very important to avoid false diagnoses of either clear cell carcinoma when mostly xanthoma cells are sampled or a sarcomatoid renal cell carcinoma or even a spindle cell neoplasm when peripheral spindled fibroblastic cells are sampled. The vascular pattern characteristic for renal cell carcinoma is absent and this is an important clue to the proper diagnosis. In addition, there is lack of cytologic atypia and mitoses. Also, cytoplasm of the foam cells contain numerous fat microvesicles as compared to cleared out cytoplasm of renal carcinomas. Ultrastructurally, macrophages contain numerous phagolysosomes containing rests of phagocytosed polymorphonuclear lekocytes and bacteria. Cytology findings also depend upon what area has been aspirated. In general, aspirates are composed of histiocytes with foamy or eosinophilic cytoplasm, round to oval nuclei and distinct nucleoli. The background may appear necrotic and inflammatory cells and giant cells are seen. Importantly, similarly to histology specimens, vascular network, characteristic for renal cell carcinoma, is absent. However, we have to remember that histiocytes can occasionally artificially cluster together adding to difficulties in distinguishing XGP from renal carcinoma. In problematic cases, special studies can be utilized.   XGP Renal cell carcinoma, clear cell type PAS Negative Positive Low Molecular Weight Cytokeratin Negative Positive EMA Negative Positive Vimentin Positive Positive CD 10 ?Positive Positive CD 68 Positive Negative References Sease WC, Elyaderani MK, Belis JA: Ultrasonography and needle aspiration in diagnosis of xanthogranulomatous pyelonephritis. Urology 29:231-235;1987 Kumar N, Jain S: Aspiration cytology of focal xanthogranulomatous pyelonephritis: a diagnostic challenge. Diagn Cytopathol 30:111-114; 2004 Nguyen GK: Percutaneous fine-needle aspiration biopsy cytology of the kidney and adrenal. Pathol Annu 22:163-191;1987 Bosch-Princep R, Salvado-Usach MT, Martinez-Gonzalez S, Alvaro-Naranjo T: Xanthogranulomatous pyelonephritis: urinary and fine needle aspiration cytology. Acta Cytol 42:1062-1064;1998 Antonakopoulos GN, Chapple CR, Newman J, Crocker J, Tudway DC, O'Brien JM, ConsidineJ: Xanthogranulomatous pyelonephritis: A reappraisal and immunohistochemical study. Arch Pathol Lab Med 112:275-281;1988