Case 1 -

Renal Cell Carcinoma, Acquired Cystic Kidney Disease Associated Subtype Jesse K. McKenney, Stanford University, Stanford, CA

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Clinical History The patient is a 41 year old dialysis dependent man who was found to have a renal mass at routine imaging surveillance. Case 1 - Figure 1 Gross kidney showing a renal mass with extensive cystic change in the background kidney. Case 1 - Figure 2 Papillary growth of eosinophilic neoplastic cells. The neoplastic cells bridge between adjacent papillae to form cribriform or sieve-like structures. Case 1 - Figure 3 Neoplastic cells form a cribriform/sieve- like architectural pattern. Case 1 - Figure 4 High power magnification of intratumoral oxalate crystal. Case 1 - Figure 5 Background kidney shows numerous cysts lined by similar appearing eosinophilic cells. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Grossly, this kidney shows numerous renal cysts and a solitary renal mass. The renal mass is characterized histologically by a proliferation of neoplastic cells with granular eosinophilic cytoplasm, which are arranged in a variety of architectural patterns including papillary, solid, and cribriform. The nuclei of the neoplastic cells are generally round with small nucleoli. There are also scattered oxalate crystals admixed within the neoplasm. In the background kidney, there are numerous cysts lined by a similar population of eosinophilic epithelial cells. Differential Diagnoses: 1) RCC, Papillary type 2) RCC, Collecting duct type 3) RCC, Acquired cystic kidney disease associated subtype 4) RCC, Xp11/TFE3 translocation subtype 5) RCC, Low grade tubulocystic Final Diagnosis: Renal cell carcinoma, acquired cystic kidney disease associated subtype Case Discussion: This renal neoplasm shows the characteristic morphologic features of ACKD- RCC that allow its recognition: 1) Background cystic kidney, often with eosinophilic lining cells 2) Cribriform or sieve-like architectural growth pattern in carcinoma 3) Admixed oxalate crystals An immunophenotypic analysis is usually not necessary to make the diagnosis of ACKD-RCC, but the neoplastic cells typically express AMACR, CD10, and RCCma. CK7 expression is usually negative or only focal. No immunostains were performed in this case. The differential diagnostic considerations for this renal neoplasm could potentially include Papillary RCC, Clear Cell RCC, Collecting Duct Carcinoma, Translocation Xp11/TFE3 RCC, and Low Grade Tubulocystic Carcinoma. 1) Papillary Renal Cell Carcinoma, Type 2 Papillary renal cell carcinoma (P-RCC) may be difficult to distinguish from ACKD-RCC, especially if it occurs in a patient with acquired cystic disease. P- RCC does not typically have the complex sieve-like growth pattern that is characteristic of ACKD-RCC. Psammoma bodies may be seen in association with P-RCC, but not oxalate crystals. P-RCC (Type II) may be diffusely CK7 positive, but (unlike Type I P-RCC) some may also be CK7 negative. 2) Clear Cell Renal Cell Carcinoma (with cytoplasmic eosinophilia) Clear cell renal cell carcinoma (CC-RCC) typically has vascular septae that divide the neoplastic cells into a nested/alveolar architecture. Even CC-RCC with prominent eosinophilic cytoplasm commonly retains the fibrovascular septae with an alveolar arrangement, unless very poorly differentiated or sarcomatoid foci are present. Oxalate crystals are not a feature of CC-RCC. 3) Translocation Associated (Xp11/TFE3) Renal Cell Carcinoma Translocation associated (Xp11/TFE3) renal cell carcinoma (TFE3-RCC) often has significant variation in morphology from case to case, but an unusual admixture of abundant granular and clear cytoplasm is common. Papillary or nested architecture is also common. Numerous associated psammoma bodies are seen in a subset of cases (but not oxalate crystals). TFE3-RCC is often negative (or only focally positive) for broad spectrum cytokeratin staining. A translocation may be confirmed by FISH testing. 4) Collecting Duct Carcinoma Collecting duct carcinoma may have a mixed cribriform and papillary architecture that could potentially mimic ACKD-RCC; however, collecting duct carcinomas are often high stage with more destructively infiltrative growth (often with associated stromal desmoplasia). In addition, lymph node or distant metastases are common. Collecting duct carcinoma is not common in end stage renal disease. 5) Low-grade Tubulocystic Renal Cell Carcinoma In low-grade tubulocystic carcinoma (LGTC-RCC), the individual cysts/tubules may have a very similar appearance to the background cysts of ACKD-RCC with both eosinophilic cytoplasm and enlarged nuclei; however, the individual cysts of LGTC-RCC are back-to-back and form a macroscopic mass lesion (with preserved background kidney). Complex intracystic proliferation and sieve-like architecture are not typical of LGTC-RCC. In addition, it is not a common RCC subtype in end stage renal disease. Review of the Literature/Treatment Options: The association between end-stage renal disease and renal cell carcinoma risk has been well documented for many years; the overall incidence of renal cancer in end stage kidneys is reported between 3-7%. However, the presence of specific subtypes of renal cell carcinoma arising in this setting has only recently gained attention. A large clinicopathologic series was published in 2006 by Tickoo et al that proposed ACKD-RCC as a specific subtype of renal cancer and distinguished it from other renal tumors arising in end-stage renal disease. Morphologically similar tumors have been previously reported in small descriptive case series in the modern literature going back at least to 1998. These ACKD-RCCs have likely been reported as papillary RCC in the past. ACKD-RCCs are often found at low stage (small size) because patients are under close imaging surveillance due to their underlying renal disease. Therefore, most reported cases of ACKD-RCC have had a non-aggressive course. Rare cases have presented with pT3 disease and/or sarcomatoid differentiation. The very few reported patient deaths have had sarcomatoid differentiation. Conclusion(s): ACKD-RCC is the most common renal cell carcinoma subtype in patients with acquired cystic renal disease, and is almost always seen in patients on dialysis. Most kidney tumors associated with end stage kidney disease are found incidentally on imaging for surveillance of chronic renal disease. ACKD-RCC is becoming a well-recognized subtype of renal cell carcinoma and can generally be recognized by the characteristic histologic appearance and the background cystic disease. References: Sule N, Yakupoglu U, Shen SS, Krishnan B, Yang G, Lerner S, Sheikh Hamad D, Truong LD. Calcium oxalate deposition in renal cell carcinoma associated with acquired cystic kidney disease: a comprehensive study. Am J Surg Pathol. 2005 Apr;29(4):443-51. PubMed PMID: 15767796. Tickoo SK, dePeralta-Venturina MN, Harik LR, Worcester HD, Salama ME, Young AN, Moch H, Amin MB. Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am J Surg Pathol. 2006 Feb;30(2):141-53. PubMed PMID: 16434887.