Section 1 -

Benign Mimics and Tumor-Like Lesions of the Kidney Liliane Boccon-Gibod Professor of Surgical Pathology, Hôpital Armand Trousseau 75571 PARIS Cédex (France)

Going through the Medline and looking for what has been published in the last decades about renal pseudo-tumors tells you a lot about medical history and extraordinary progress of medical imaging. Prior to the era of CT scan and MRI, a large amount of non tumoral or benign lesions could be mistaken for a true renal tumor. In the literature from the 80's sonography proved to be a necessary complement to excretion urography in assessing cysts, pseudo-tumors and variants of the structure of the kidney, resembling space occupying lesions in the excretory urogram which was then the gold standard exam. One good example of Ultrasound importance is Bertin's columns hypertrophy, which could easily be mistaken for intra-renal tumor. Renal tumors are either more echo producing or less echogenic than adjacent normal renal parenchyma, whereas pseudo-tumors have the same echo characteristics as surrounding and adjacent normal renal parenchyma. Most of these differential diagnoses have nowadays disappeared, even prior to biopsy or surgery, and most of the present discussions take place around the CT scan and/or the MRI. Going back through our experience, we will focus on the issues which seem important to us, in adults and also for some of them in children. Xanthogranulomatous Pyelonephritis Xanthogranulomatous Pyelonephritis (XGPN) is a chronic suppurative inflammation of the renal parenchyma that may extend to contiguous retroperitoneal and intra-abdominal structures and be suggestive of renal malignancy. Grossly, the kidney is destroyed by large yellowish masses distributed within the renal parenchyma around the calices. This yellowish colour may be again misleading for a RCC. Histologically, large sheets of lipid laden macrophages are encountered, sometimes surrounding a true abcess with neutrophils. Surgery is curative, and most cases undergo nephrectomy, either with a presumed diagnosis of renal tumor either with diagnosis of XGPN. XGPN can be focal and /or cystic therefore making the diagnosis still more difficult with a renal tumor prior to surgery. Aspiration cytology or biopsy may be of help. Renal Malakoplakia Malakoplakia is a rare chronic inflammatory disease affecting predominantly the bladder, occurring occasionally in other organs from the genito-urinary tract (kidney, testis) and other organ systems. Renal malakoplakia usually affects women over 40 years of age and is associated with recurrent urinary tract infections. E. coli is the most common pathogen. Approximately 20% of patients have an immunocompromised state. Clinical presentation (hematuria, palpable mass) and radiological appearance often simulate a neoplasm, notably Renal Cell Carcinoma (RCC). Fever, flank pain, pyuria may be associated and suggest an infectious mass. US and CT scan can reveal uni or bilateral enlargement of the kidney. In the case of unilateral enlargement, nephrectomy has often been performed, with a preliminary diagnosis of malignancy. In the more recent cases, MRI and early renal biopsy have helped insure diagnosis; medical therapy has resulted in resolution of the lesions in some cases, although in unifocal cases, surgical excision is still the treatment of choice. Grossly, affected kidney present with soft tan yellow plaques and nodules, which can reach 3- 4 cm in diameter. Histologically, renal parenchyma is infiltrated by conglomerates of foamy histiocytes, containing abundant PAS positive granules (Von Hansemann cells) and diagnostic extra or intracytoplasmic basophilic inclusions with surrounding clear halos (Michaelis-Gutman bodies). Important differential diagnoses are post transplant lympho-proliferative disorders (PTLPD) and lymphoma, especially in the setting of immunocompromised patients. Renal malakoplakia seems medically treatable when detected in early stages. Inflammatory Myofibroblastic Tumor Inflammatory Myofibroblastic Tumor (IMT) is a well known, although rare, entity. First described in the lung, mainly in young adults and children, IMT has been now described at multiple extra pulmonary sites. In the GU tract, IMT are more frequent in the bladder than in the kidney. A sery of 12 cases have recently been reported by Kapusta et al: interestingly renal IMT occur later (mean age 57 y) in life than other localisations. Tumours are mainly localised into the renal sinus (6/12) and present the histological patterns described by Coffin et al in IMT: a) loosely organised spindle cells admixed with inflammatory cells in a myxoïd background b) spindle cell proliferation admixed with collagen, with lymphocytes and plasma cells c) hypo cellular fibrous tissue with fibrosis and few inflammatory cells. Immunostaining for SMA and muscle specific actin was positive in most cases. Interestingly ALK was negative in all the cases tested. This is again different form cases reported in the lung. Cystic Lesions When facing a large cystic or multicystic renal lesion in an adult the main question is: is it a true cystic lesion like a cystic nephroma (CN), a benign lesion with cysts like a cystic hamartoma of the renal pelvis, or is it a real malignant tumor, like a multicystic renal cell carcinoma? One can dispute the true nature of cystic nephroma. In children; this lesion has for a long time been considered as a malformative cyst (syn: multilocular cyst of the kidney, or renal cystadenoma); more recently the possibility of CN being the fully mature end of Cystic Partially Differentiated Nephroblastoma (CPDN) has been raised. The differential diagnosis between these 2 entities relies on the presence of immature metanephric elements (mainly tubules, rarely blastema) or heterologous components in the septa of CPDN, whereas the thin septa of a Cystic Nephroma contain only connective mature tissue. The treatment and prognosis issues for CN and CPDN are similar: surgery alone (nephrectomy) is followed by total cure; no relapse have been described in children. In the adult, when facing a putative CN, or others renal cysts, the multicystic variant of renal cell carcinoma is an important issue to raise. Tumor component with clear cells can be obvious, but more often, clear cancer cells are disposed in one layer and not present along most septa. A long search of the different slides may be necessary to prove the neoplastic nature of the multilocular cyst. Prognosis of this form of renal clear cell carcinoma is excellent, as surgery alone is curative, and can in some instances be limited to partial nephrectomy. . Three cases of sarcomatous transformation of cystic nephroma in adults have been reported on a poster at the 1997 USCAP meeting in Orlando , but these cases have never been published and looking back to the images, they were more suggestive of other diagnoses. Does Adult Mesoblastic Nephroma Exist ? Description of Congenital Mesoblastic Nephroma (CMN) CMN is the most frequent renal tumor in infants under 6 months of age and is not seen over 1 year of age. Cases published in older children have been recently identified as Mesoblastic Stromal Tumor (MST); Sex ratio M/F is 1:1; the renal mass is never encapsulated and is extremely infiltrative, invading sinus, hilar and perirenal fat; it is composed predominantly of spindled mesenchymal cells of fibroblastic or myofibroblastic lineage, admixed with a small number of tubules, seen at the periphery of the tumor (entrapped normal renal tubules). The cellular variant is associated with t(12;15) translocation and ETV6-NTRK3 gene fusion and is the renal counterpart of congenital (infantile) fibrosarcoma. The classical variant of CMN is not associated with any gene fusion and only exceptional chromosomal abnomalies have been associated with this lesion which is now considered by many as the renal counterpart of of soft tissue fibromatosis. No epithelial component is associated in true CMN. Tumors described in the adult as mesoblastic nephroma are totally different : Sex ratio M/F is 1:9, lesions are encapsulated and a columnar epithelial component, sometimes presenting with cilia is associated with the stromal component. Since Cystic Hamartoma of the renal pelvis has been described by Pawade in 1993 and Mixed epithelial and stromal tumor of the kidney by MIchal in 1998, these diagnoses are more and more frequent in the urological community, and less and less adult MN have been reported. It is our opinion that most of the previously published so-called "Adult" Mesoblastic Nephroma" are either Cystic Hamartoma of the renal pelvis or Mixed Epithelial and stromal tumors of the kidney, these last 2 entities being extremely close, not to say similar. Stromal estrogen and/or progesterone receptor positivity in the majority of cases of cystic nephroma is a novel finding which strongly support this view, which was already proposed by JB Beckwith in 1998 . The spectrum of Adult MN is shrinking and we foresee it's disappearance in the next future. References Xanthogranulomatous Pyelonephritis Hendrickson RJ, Lutfiyya WL, Karrer FM, Furness PD 3rd, Mengshol S, Bensard DD. Xanthogranulomatous pyelonephritis. J Pediatr Surg. 2006 ;41:e15-7. Hussain MS, Bhagat VK. Focal xanthogranulomatous pyelonephritis -- a diagnostic dilemma. J Coll Physicians Surg Pak. 2006 ;16:164-6. Khaira HS, Shah RB, Wolf JS Jr. Laparoscopic and open surgical nephrectomy for xanthogranulomatous pyelonephritis.J Endourol. 2005;19:813-7. Pelage JP, Helenon O, Szagier C, Cornud F, Melki P, Belin X, Moreau JF: Pseudotumoral form of focal acute pyelonephritis. J Radiol 1996; 77: 271-4. Zorzos I, Moutzouris V, Petraki C, Katzou G : Xanthogranulomatous pyelonephritis- the "great imitator" justifies it's name. Scand J Urol Nephrol 2002; 36 : 74-6. Renal Malakoplakia Gupta M, Venkatesh SK, Kumar A, Pandey R. Fine-needle aspiration cytology of bilateral renal malakoplakia. Diagn Cytopathol. 2004;31:116-7. Hill GS, Droz D, Nochy D. The woman who loved well but not too wisely, or the vicissitudes of immunosuppression. Am J Kidney 2001; 37 :1324-9. McKeen SK, Tie ML. Renal parenchymal malakoplakia: an unusual cause of unilateral, diffuse renal enlargement. Australas Radiol. 2002 ;46:69-72. Wielenberg AJ, Demos TC, Rangachari B, Turk T. Malacoplakia presenting as a solitary renal mass. AJR Am J:Roentgenol. 2004 ;183:1703-5. Zimina OG, Rezun S, Armao D, Braga L, Semelka RC. Renal malacoplakia: demonstration by MR imaging. Magn Reson Imaging. 2002: 20:611-4. Inflammatory Myofibroblastic Tumor Coffin CM, Watterson J, Priest JR et al : Extrapulmonary pseudo-tumor (inflammatory pseudo-tumor) : a clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995 ; 19 : 859-72. Epaulard O, Fabre M, Barnoud R, Pasquier B, Massot C: Fièvre prolongée révélatrice d'une pseudotumeur inflammatoire rénale. Rev Med Interne 2000; 21: 889-92. Kapusta LR, Weiss MA, Ramsay J, Lopez-Beltran A, Srigley JR; Inflammatory myofibroblastic tumors of the kidney: a clinicopathologic and immunohistochemical study of 12 cases. Am J Surg Pathol 2003;27:658-66. Magro G, Cavallaro V, Torrisi A, Lopes M, Dell'Albani M, Lanzafame S: Intrarenal solitary fibrous tumor of the kidney report of a case with emphasis on the differential diagnosis in the wide spectrum of monomorphous spindle cell tumors of the kidney. Pathol Res Pract 2002 ; 198 : 37-43. Yoshida S, Watanabe T, Yoshinaga A, Ohno R, Ishii N, Terea T, Hayashi T, Yamada T: Inflammatory myofibroblastic tumor of the renal pelvis. Hinyokika Kiyo 2006; 52: 31-3. Adult Mesoblastic nephroma, Cystic Nephroma, Mixed epithelial and stromal tumor of the kidney . Renal Cysts, Multilocular cystic renal carcinoma Adsay NV, Eble JN, Srigley JR, Jones EC, Grignon DJ. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol. 2000;24:958-70. Antic T, Perry KT, Harrison K, Zaytsev P, Pins M, Campbell SC, Picken MM. Mixed epithelial and stromal tumor of the kidney and cystic nephroma share overlapping features: reappraisal of 15 lesions. Arch Pathol Lab Med. 2006 ;130 :80-5. Hora M, Hes O, Michal M, Boudova L, Chudacek Z, Kreuzberg B, Klecka J.: Extensively cystic renal neoplasms in adults (Bosniak classification II or III)-possible «common» histological diagnoses: multilocular cystic renal cell carcinoma, cystic nephroma, and mixed epithelial and stromal tumor of the kidney. Int Urol Nephrol 2005 ; 37 : 743-50. Jevremovic D, Lager DJ, Lewin M. Cystic nephroma (multilocular cyst) and mixed epithelial and stromal tumor of the kidney: a spectrum of the same entity? Ann Diagn Pathol. 2006 ;10 :77-82. Michal M, Syrucek M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract. 1998; 194:445-8. Michal M, Hes O, Bisceglia M, Simpson RH, Spagnolo DV, Parma A, Boudova L, Hora M, Zachoval R, Suster S. Mixed epithelial and stromal tumors of the kidney. A report of 22 cases. Virchows Arch. 2004 ;445:359-67 Pawade J, Soosay GN, Delprado W, Parkinson MC, Rode J. Cystic hamartoma of the renal pelvis.Am J Surg Pathol. 1993 ;17:1169-75. Romero Ortiz A, Lopez-Beltran, Lopez Luque A, Requena Tapia MJ : Multilocular cystic renal carcinoma : pathologic study of 14 cases. Arch Esp Urol 2005 ; 58 : 9-16. Truong LD, Choi YJ, Shen SS, Ayala G, Amato R, Krishnan : Renal cystic neoplasms and renal neoplasms associated with cystic renal diseases : pathogenetic and molecular links. Advances Anat Pathol 2003 ; 10 : 135-59. Miscellaneous Amouroux J, Michon J, Gurly R, Olivieri P, Michaud B, Roujeau J : Sarcoid pseudo-tumor of the kidney. Arch Anat Pathol 1967 ; 15 : 301-3. Azam FA, Oberson R, Anderegg A : Hypertrophy of columns of Bertin a case of renal pseudo-tumor Schweiz Rundsch Med Prax 1976 ; 65 : 235-8. Mandosse P, Bourg S, Paulhac P, Dumas JP, Colombeau P: Splenic lobulation and pseudo- cancer of the left kidney. Prog Urol 2000 ; 10 : 291-4. Michel JR, Rouleau P, Reboul F, Moreau JF, Affre J, Raust JV: Radiological diagnosis of tumoral lipomatosis of the renal sinus. The role of arteriography J Radiol Electrol Med Nucl 1977; 58: 505-12. Paslawski M, Zlomaniec J, Bienko-Baka G: Differential diagnosis of asymmetrical renal cortex thickening and solid renal tumours. Ann Univ Mariae Curie Sklodowska 2004 ; 59 : 417-23. Vaidyanathan S, Hughes PL, Mansour P, Soni BM, Singh G, Watt JW, Oo T, Sett P : Pseudo-tumours of the urinary tract in patients with spinal cord injury/spina bifida. Spinal Cord 2004 ; 42 : 208-12. Weisgerber G, Douvin D, Krulik M, Huguet C : Pseudo-tumoral suprarenal-renal dysgenesis. J Urol 1975 ; 81 : 371-8.