COW-2021-33

1. d

Acquired cystic disease associated renal cell carcinoma

This 1.8cm well-circumscribed tumor is found in a background of an end-stage kidney with multiple simple cysts. It displays a variety of growth patterns, including acinar, alveolar, tubular, and papillary architectures, and has a sieve-like pattern. Intratumoral oxalate crystals are found throughout. The tumor cells have abundant pink cytoplasm with prominent nucleoli. IHC reveals positivity for AMACR, and focally positive CK7. These findings are consistent with acquired cystic disease-associated renal cell carcinoma (ACD-RCC).

Patients with end stage renal disease are prone to developing acquired cystic disease (ACD), which is seen in up to 60% of patients with 5+ years of dialysis, and in >90% of patients with 10+ years of dialysis. ACD cysts are a nidus for tumor formation, and though any type of RCC may form, ACD-RCC is the most common type occurring in up to 36% of patients. Fortunately, ACD-RCC typically presents as a radiologic incidentaloma during routine medical care, and therefore is usually found in a low clinicopathologic stage.

ACD-RCC arises from the proximal nephron cells. Factors contributing to tumorigenesis in ACD-RCC include oxalate crystal-induced tubular proliferation, increased reactive oxygen species and dysregulation of antioxidant defenses, immunosuppressive medications, and a depressed immune status in the renal failure patient. The tumor frequently fills the cyst it arises in and is well circumscribed by a thick fibrous capsule. Half of cases are multifocal, and more than 20% are bilateral. The cells in ACD-RCC are large with eosinophilic, granular cytoplasm (though clear cells are not uncommon) and have poorly-defined cell membranes. 98% of cases display a variety of growth architectures, and its intra- and intercytoplasmic microsciopic lumina give it a characteristic sieve-like appearance which helps distinguish it from other neoplasms. Most, but not all, cases have intratumoral oxalate crystals, which is postulated to occur as a consequence of the proximal tubular cell phenotype from which the tumor originates. ACD-RCC is most commonly positive for AMACR, CD10, and RCC-Ma; CK7 is negative to focally positive.

Importantly, this tumor should be distinguished from tubulocystic carcinoma (TCC). TCC has small to intermediate sized cystic dilated tubules with fibrous septate, and the tubules and cysts are lined by a single layer of flat, hobnail, or cuboidal cells with eosinophilic cytoplasm. TCC cells have larger nuclei, often with nuclear membranes and prominent nucleoli. Unlike TCC which tends to occur in association with papillary neoplasms, ACD-RCC is seen in patients with a history of dialysis and in the background of an end-stage kidney parenchyma with oxalate crystals.

Oncologic outcomes of ACD-RCC are favorable because most cases are found during early stage, and nephrectomy is largely curative. Worse outcomes are seen in patients with longer duration of dialysis, probably because these tumors are more likely to demonstrate the more aggressive sarcomatoid/rhabdoid phenotype. Tumor metastases may have features morphologically similar to the primary tumor, but may also form cystic structures which can cause clinical, radiographic, and histologic confusion. Interestingly, the metastases can also show calcium oxalate deposition.

Foshat M, Eyzaguirre E. Acquired Cystic Disease-Associated Renal Cell Carcinoma: Review of Pathogenesis, Morphology, Ancillary Tests, and Clinical Features. Arch Pathol Lab Med 2017;141:600-606.

Kojima F, Gandhi JS, Matsuzaki I, et al. Comprehensive Clinicopathologic Analyses of Acquired Cystic Disease-associated Renal Cell Carcinoma With Focus on Adverse Prognostic Factors and Metastatic Lesions. Am J Surg Pathol 2020;44:1031-1039.

Kondo T, Sassa N, Yamada H, Takagi T, Iizuka J, Kobayashi H, Yoshida K, Fukuda H, Ishihara H, Tanabe K, Tsuzuki T. Comparable survival outcome between acquired cystic disease associated renal cell carcinoma and clear cell carcinoma in patients with end-stage renal disease: a multi-institutional central pathology study. Pathology. 2021 May 1:S0031-3025(21)00098-2.

Lin X, Goyal R, Yang XJ. Pathologic characterization of renal epithelial neoplasms arising in nonfunctioning kidneys. Hum Pathol 2020;97:1-7.

Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2016;70:93-105.

Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2016;70:93-105.

Sun Y, Argani P, Tickoo SK, et al. Acquired Cystic Disease-associated Renal Cell Carcinoma (ACKD-RCC)-like Cysts. Am J Surg Pathol 2018;42:1396-1401.

Yang XJ, Zhou M, Hes O, et al. Tubulocystic carcinoma of the kidney: clinicopathologic and molecular characterization. Am J Surg Pathol 2008;32:177-187.

Maria F. Arisi, Ruihe Lin, Li Li
Thomas Jefferson University; Philadelphia, PA, USA

kidney

Kidney, acquired cystic disease associated renal cell carcinoma, oxalate, ACD-RCC, ACKD-RCC