Microscopic description:

Low power view of H&E stained slides show eosinophilic tumor in sheets/nests with a rim of uninvolved kidney parenchyma.

High power view shows tumor cells with abundant eosinophilic vacuolated cytoplasm, prominent nucleoli arranged in cribriform or sieve-like, papillary, cystic and tubular patterns. Adjacent to this tumor, a small focus of tubular or tubulopapillary tumor with small benign cuboidal cells with basophilic scant cytoplasm. This smaller tumor corresponds to a diagnosis of papillary adenoma.

Based on the histologic features, the differential diagnosis of the large tumor includes clear cell papillary renal cell carcinoma, papillary renal cell carcinoma, acquired cystic disease associated renal cell carcinoma, chromophobe renal cell carcinoma and Fumarate hydratase (FH) deficient renal cell carcinoma.

On immunohistochemical staining, the larger tumor showed positive staining for AMACR, CD10, FH, SDHB and RCC, and focal positive staining for CAIX (CAIX is negative in adjacent papillary adenoma) and CK7 and negative staining for CD117. Focal positive staining for CK7 rules out papillary RCC (CK7 strong positive), FH and SDHB retention rules out FH deficient RCC and SDHB deficient RCC, respectively. Negative staining for CD117 rules out eosinophilic tumors like oncocytoma and chromophobe renal cell carcinoma. These features along with history of ESRD and young age corresponds to a diagnosis of acquired cystic disease associated renal cell carcinoma.

Discussion:

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a unique subtype of renal cell carcinoma only found in patients with end-stage renal disease. It is the most common subtype of RCC present in end-stage kidneys (36%), and is present in 46% of kidneys with acquired cystic kidney disease (ACKD)

ACD-RCC is more prevalent in men, and length of dialysis is a prominent risk factor, as incidence of ACD-RCC increases significantly with a dialysis duration of 10 years or longer.

The pathogenesis is unclear, though current theories include multi factorial explanations, such as immunosuppression, oncogenic viruses, dialysis, and end stage renal disease. Papillary adenoma and associated cysts have been considered as putative precursors of ACD-RCC

The current literature suggests ACD-RCC is more prevalent in higher grade tumors than other renal cell carcinoma subtypes seen in end stage renal disease, but show more favorable prognosis, therefore being possibly less aggressive

Majority of tumors are well circumscribed and appear to arise in a cyst and generally completely fills the cystic space. The cells lining the cysts are typically morphologically similar to those in the rest of the tumor. A sieve-like appearance, intratumoral oxalate crystal deposits, and prominent nucleoli are characteristic features

ACD-RCC displays a variety of architectural patterns, presenting with solid, acinar, cystic, and papillary growth. Most tumor cells have granular eosinophilic cytoplasm, with round to oval nuclei and prominent nucleoli. Clear to vacuolated cytoplasm can also be present.

ACD-RCC frequently occurs in association with other renal tumor subtypes within the same kidney

IHC: Non-specific. Typically CD10, PAX8 and AMACR positive, and CD117 negative. Variable negativity to CK7. Molecular FISH studies have shown some gains on varying chromosomes, though more studies need to be done

Overall, ACD-RCC has a lower risk for metastasis and more favorable prognosis compared to other RCCs not associated with ACKD. Nephrectomy is recommended, including laparoscopic bilateral nephrectomy, as carcinoma in ACKD is often multi centric and bilateral

References:

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Kondo T, Sasa N, Yamada H, Takagi T, Iizuka J, Kobayashi H, Yoshida K, Fukuda H, Ishihara H, Tanabe K, Tsuzuki T. Acquired cystic disease-associated renal cell carcinoma is the most common subtype in long-term dialyzed patients: Central pathology results according to the 2016 WHO classification in a multi-institutional study. Pathol Int. 2018 Oct;68(10):543-549. doi: 10.1111/pin.12718. Epub 2018 Sep 6. PMID: 30187581.

Sun Y, Argani P, Tickoo SK, Epstein JI. Acquired Cystic Disease-associated Renal Cell Carcinoma (ACKD-RCC)-like Cysts. Am J Surg Pathol. 2018 Oct;42(10):1396-1401. doi: 10.1097/PAS.0000000000001124. PMID: 30001236

Torres VE, Grantham JJ. Cystic diseases of the kidney. In: Taal MW, ed. Brenner & Rector's The Kidney. 9th ed. Philadelphia: W.B. Saunders; 2011: 1626–1667.

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