An asymptomatic 41-year-old man presented for evaluation for a kidney transplant. He has a history of end-stage renal disease of unknown etiology and has been on hemodialysis for the past five years. On imaging, a 7.3 cm complex solid cystic mass (Bosniak IV) with thickened, irregular septations and soft tissue nodule was seen in the lower pole of the right kidney. Multiple bilateral renal cysts and renal atrophy were also noted. The patient underwent right radical nephrectomy. Grossly, 7.0 cm multiseptated encapsulated cystic mass with a solid soft tan brown nodule was seen in the lower pole. The rest of the kidney had multiple cysts. See below for microscopic images.
The correct answer is ...
The correct answer is: acquired cystic disease-associated renal cell carcinoma (ACD-RCC).
Microscopically, sections from the cystic mass showed a thick fibrous capsule and tumor arising from the capsule and filling up the cyst (Figure 1). The tumor showed variegated architecture with papillary and tubulocystic areas. Prominent intracellular and intercellular spaces imparting a distinct cribriform appearance were seen (Figure 2). The tumor cells are predominantly large, with abundant granular eosinophilic cytoplasm, ill-defined cell membranes, and Fuhrman grade 3 nuclei with prominent nucleoli (Figure 3). Refractile intratumoral calcium oxalate crystals with no foreign body giant cell reaction were present (Figure 4). The histological findings were consistent with the diagnosis of acquired cystic disease-associated renal cell carcinoma (ACD-RCC).
Because papillary architecture can be variably present in cases of ACD-RCC, these tumors are commonly misdiagnosed as type 2 papillary renal cell carcinoma (PRCC). Separating ACD-RCC from type 2 PRCC based on morphology can be challenging, as both have papillary architecture and large eosinophilic cells with high-grade nuclei. Helpful features to distinguish are the presence of foamy macrophages, psammoma bodies, and glassy hyaline globules in PRCC but are not seen in ACD-RCC. Papillary RCC also lacks the cribriform appearance and is not associated with polarizable calcium oxalate crystals.
The presence of clear cell areas with solid and acinar architecture may lead to confusion with clear cell renal cell carcinoma (CCRCC). The combination of papillary, cribriform, and/or tubulocystic features of ACD-RCC is more complex than in classic CCRCC, and the eosinophilic cells and high-grade nuclei are uncharacteristic of classic CCRCC.
Clear cell papillary renal cell carcinoma (CCPRCC) is an important differential diagnosis because of the variable papillary and tubulocystic features. Despite the architectural similarities, the papillary cores of CCPRCC are lined by low-grade cells with a characteristic subnuclear vacuolar appearance due to the reversed polarity of nuclei away from the basement membrane.
Although CCRCC, type 2 PRCC, and clear cell PRCC can occur in the same clinical setting of acquired cystic kidney disease with ESRD, and the morphologies of these entities overlap, careful attention to subtle histologic and cytologic details, such as the presence of cribriform architecture and intratumoral calcium oxalate crystals, is essential in deciphering the correct diagnosis. The key defining features of ACD-RCC lacking in the other entities is the mixture of eosinophilic and clear cells, cribriform morphology, and presence of polarizable calcium oxalate crystals.
Lagnajita Datta, M.B.B.S.
Resident, Surgical Pathology
Yajue Huang, M.D., Ph.D.
Consultant, Anatomic Pathology
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science