ORIGINAL ARTICLE Calcium Oxalate Deposition in Renal Cell Carcinoma Associated With Acquired Cystic Kidney Disease A Comprehensive Study Norbert Sule, MD,*§ Ulkem Yakupoglu, MD,*§ Steven S. Shen, MD, PhD,*§ Bhuvaneswari Krishnan, MD,*§ Guang Yang, MD, PhD,† Seth Lerner, MD,† David Sheikh-Hamad, MD,‡ and Luan D. Truong, MD*‡§ Abstract: The main complication of acquired cystic kidney disease (ACKD) is frequent development of renal tumors, including renal cell carcinoma (RCC). Intratumoral deposition of calcium oxalate (CaOx) is a distinct feature of ACKD-associated RCCs, but several features of this type of RCC are not known. Features of the 30 end-stage renal disease (ESRD)-associated RCCs identified within a 13-year period, including eight with CaOx deposition, were analyzed. Pathologic and clinical features of CaOx positive (+) and negative (2) RCCs were evaluated and compared. The CaOx+ RCCs showed higher tendency for bilaterality and multifocality. Seven tumors displayed distinctive morphologic features characterized by tumor cells with ill-defined cell membrane, abundant granular eosinophilic cytoplasm, large nuclei, and prominent nucleoli. One tumor was of clear cell type. Regardless of histologic type, all tumors displayed a proximal tubular differentiation. No significant difference was noted for tumors’stage, proliferation, and apoptosis rate between the CaOx+ and CaOx2 RCCs. CaOx+ RCCs account for a significant portion of all ESRD- associated RCCs. The majority of these RCCs display a distinctive morphologic profile. Proximal tubular cell differentiation in con- junction with ESRD-mediated high serum level may be pathogeneti- cally important for intratumoral CaOx deposition. These RCCs seems to have a relatively good prognosis. Key Words: acquired cystic kidney disease, renal cell carcinoma, end-stage kidney disease, calcium oxalate, cell kinetics (Am J Surg Pathol 2005;29:443–451) A cquired cystic kidney disease (ACKD) is characterized by small cysts randomly distributed throughout the renal cortex and medulla of patients with end-stage renal disease (ESRD) unrelated to polycystic kidney disease. 4,7,15,17,23,35 Both the prevalence and severity of ACKD increase with the duration of ESRD and ACKD have been reported in almost all patients after more than 10 years of dialysis. 15,23 Renal neoplasm is noted in 4.2% to 5.8% of ESRD patients, reflecting a marked increase in its incidence com- pared with the general population. 11,17,23,35 Although these neoplasms were rarely reported in a shrunken kidney without cystic changes, most of them develop from the background of ACKD. 12,17,35 The involvement is usually bilateral/multifocal and displays a spectrum of closely associated lesions, includ- ing simple cysts, cyst lined by hyperplastic epithelium with or without atypia, adenoma, and renal cell carcinoma (RCC) with or without metastasis. 4,11 Some previous studies have sug- gested that the histologic types of RCCs in this context are similar to those in the general population but with overrep- resentation of the papillary RCC. 4,13,16,35 Indeed, the histologic features of ACKD-associated RCCs are not well studied, and many of these tumors do not fit in any categories in the current classification of renal neoplasms. 1,34 One of the distinctive features of ACKD-associated RCCs is intratumoral deposition of calcium oxalate (CaOx), which was previously reported in 4 cases and briefly men- tioned in a recent abstract. 3,28,34 This feature, to the best of our knowledge, has not been described in RCCs in the general population. Although this finding seems unique for ACKD- associated renal neoplasms, many pertinent features, including its frequency, pathogenesis and biologic implications, and the histologic type of the involved RCCs, are not known. MATERIALS AND METHODS Review of the pathology reports of 346 RCCs acces- sioned at the Department of Pathology, Methodist Hospital between 1990 and 2003 identified 29 RCCs in 22 nephrectomy specimens from 20 ESRD patients. One of these RCCs was noted in an atrophic kidney without cysts, nd the other 28 were associated with ACKD. One additional ACKD-associated RCC was found at autopsy during that period. Among these 30 RCCs, CaOx deposition was noted in eight tumors (27%) in seven kidneys (30%) from 5 patients (24%). Glass slides were reviewed for the background renal changes and the histologic features of the tumors, including growth patterns and cell types, nuclear grade, and pathologic stage. The severity of CaOx deposition in each nephrectomy specimen was separately semi-quantified for tumors, cysts, and the renal parenchyma. The severity of CaOx deposition in each nephrectomy specimen was separately semi-quantified From the Departments of *Pathology, †Urology, and ‡Medicine, Renal Section, Baylor College of Medicine, Houston, TX; and §Methodist Hospital, Houston, TX. Reprints: Luan D. Truong, MD, Department of Pathology, MS 205, Methodist Hospital, 6565 Fannin Street, Houston, TX 77030 (e-mail: ltruong@bcm. tmc.edu). Copyright Ó 2005 by Lippincott Williams & Wilkins Am J Surg Pathol  Volume 29, Number 4, April 2005 443