Translocation Carcinoma of the Kidney

Pathology Page Translocation Carcinoma of the Kidney enal carcinoma accounts for less than 5% of renal neoplasms in children. Recent studies confirm that approximately a third of renal carcinomas in young patients fall into the category of translocation carcinoma, a recently recognized, distinct type of renal cell carcinoma.1 The majority of patients are younger than 18 years. Translocation carcinoma accounts for less than 3% of renal carcinomas in patients 18 to 45 years old, and is infrequent in patients older than 45 years.1,2 Males and females are approximately equally affected. Intriguingly approximately 15% of patients have a history of chemotherapy. The most common of these carcinomas demonstrate translocations that involve a breakpoint on chromosome Xp11.2 and result in fusion of one of several translocation partners with the TFE3 transcription factor gene at this locus. Translocation partners identified to date include the ASPL and CLTC genes from chromosome 17, and the PRCC and PSF genes from chromosome 1. The best characterized Xp11 carcinomas are PRCC-TFE3 carcinoma and ASPL-TFE3 carcinoma.1 Nearly a dozen examples of another distinct translocation carcinoma, Alpha-TFEB, have been reported. Alpha-TFEB is characterized by a different translocation, t(6,11)(p21;q12), which results in fusion of a portion of the Alpha gene with the transcription factor gene TFEB at 6p21.3 Patients present with abdominal or flank pain, or hematuria. Some tumors are found incidentally. Grossly PRCC-TFE3 and ASPL-TFE3 carcinomas are tanyellow or gray, well circumscribed, sometimes associated with necrosis and/or hemorrhage (fig. 1). PRCC-TFE3 tumors typically have a fibrous pseudocapsule that may be sufficiently calcified to impart an eggshell consistency, whereas ASPL-TFE3 tumors are unencapsulated.1,2 Microscopically tumor cells with distinct cell membranes and abundant clear to finely granular to eosinophilic

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FIG. 2. PRCC-TFE3 carcinoma with nested and papillary architecture. Inset, abundant psammomatous calcifications in ASPL-TFE3 carcinoma.

cytoplasm are arranged to form nests and papillary structures (fig. 2). The nuclei are wrinkled and usually have prominent nucleoli. Calcified psammoma bodies are often present and may be abundant in ASPL-TFE3 carcinoma (fig. 2, inset). Due to the papillary architecture and clear cell morphology, Xp11 carcinoma may be difficult to distinguish from conventional clear cell and papillary renal carcinoma.1,2 The distinction can be made with immunostains such as CK7, CA-IX, AMACR, CD10 and TFE3. TFE3 immunostain highlights the nuclear presence of the dysregulated and over expressed TFE3 protein, which is considered distinctive, sensitive and specific for Xp11 translocation carcinoma. Prognosis information is limited. ASPL-TFE3 cancer tends to present at a higher stage and behaves more aggressively than PRCC-TFE3 carcinoma.1,2 Alpha-TFEB carcinoma is often tan-yellow-brown, solid with focal cyst formation and confined within a pseudocapsule.3 Microscopically tumor cells form solid nests. A biphasic cell population is present, with the majority having abundant clear or eosinophilic cytoplasm and the minority consisting of smaller cells clustered around nodules of basement membrane material. Tumor cells of this neoplasm do not express epithelial markers but show positive immunostaining for melanocytic markers and TFEB, which, like TFE3, is a member of the MiT transcription factor family. Alpha-TFEB carcinoma tends to be biologically indolent.3 Francisco A. Paras, Jr. and Gregory T. MacLennan Institute of Pathology University Hospitals of Cleveland Case Western Reserve University Cleveland, Ohio 1.

FIG. 1. Translocation carcinoma with thick capsule. Courtesy of Dr. Rodolfo Montironi, Ancona, Italy. 0022-5347/08/1795-2007/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION

Argani P and Ladanyi M: Translocation carcinomas of the kidney. Clin Lab Med 2005; 25: 363. 2. Argani P, Olgac S, Tickoo SK, Goldfischer M, Moch H, Chan DY et al: Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. Am J Surg Pathol 2007; 31: 1149. 3. Argani P, Hawkins A, Griffin CA, Goldstein JD, Haas M, Beckwith JB et al: A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosomal translocation. Am J Pathol 2001; 158: 2089.

2007

Vol. 179, 2007, May 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.02.013