Acquired Cystic Disease-associated Renal Cell Carcinoma (ACD-RCC)

Abstract

The incidence of renal cell carcinoma (RCC) is known to be higher in patients with end-stage renal disease, including those with acquired cystic kidney disease due to dialysis. Acquired cystic disease (ACD)-associated RCC was recently incorporated into the 2016 WHO Classification of Tumors of the Urinary System and Male Genital Tract as a distinct entity and is reportedly the most common RCC arising in end-stage renal disease. In this study, we sought to further describe clinicopathologic findings in a large series of ACD-RCC, emphasizing histologic features, immunophenotype, clinical outcome, and patterns of disease spread. We collected 40 previously unpublished cases of ACD-RCC with mean clinical follow-up of 27 months (median, 19 mo; range, 1 to 126 mo). Mean tumor size was 2.7 cm (median, 2.4 cm), and 32 tumors (80%) were confined to the kidney (pT stage less than pT3a). International Society of Urological Pathology grade was 3 in 37 cases (92.5%), grade 2 in 1 case (2.5%), and grade 4 in 2 cases (5%). Architectural variability among ACD-RCC was common, as 39 cases (98%) showed varying combinations of tubular, cystic, solid, and/or papillary growth. ACD-RCC frequently occurred in association with other renal tumor subtypes within the same kidney, including papillary RCC (14 patients), papillary adenomas (7 cases), clear cell papillary RCC (5 cases), clear cell RCC (1 case), and RCC, unclassified type (1 case). A previously undescribed pattern of perinephric and renal sinus adipose tissue involvement by dilated epithelial cysts with minimal or absent intervening capsule or renal parenchyma was identified in 20 cases (50%); these cysts were part of the tumor itself in 5 cases (25%) and were part of the non-neoplastic acquired cystic change in the background kidney in the remaining 15 cases (75%). Of the 24 cases (60%) with tissue available for immunohistochemical stains, 19 (79%) were positive for PAX8, 20 (83%) showed negative to patchy expression of cytokeratin 7, and 24 (100%) were both positive for AMACR and negative for CD117. Fumarate hydratase expression was retained in all tumors, including those with nuclear features resembling fumarate hydratase-deficient RCCs. Of the 36 patients (90%) with available follow-up information, 4 (11%) experienced adverse events: 2 patients developed a local recurrence, 1 patient experienced multiple visceral metastases and subsequently died of disease, and 1 patient developed metastases to regional lymph nodes only. One local recurrence and the lymph node only metastasis both had an unusual, exclusively cystic pattern of growth. In summary, we present the largest clinicopathologic series of ACD-RCC to date and describe previously unreported cystic patterns of local soft tissue involvement and recurrence/metastases.

WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies

“…They are typically AMACR positive, but CK7 and CA-IX negative. They frequently occur with other renal tumour types [ 43 ].…”

Papillary Renal Cell Carcinoma With Microcystic Architecture Is Strongly Associated With Extrarenal Invasion and Metastatic Disease

“…3 The classification of RCCs with papillary architecture has evolved since the Heidelberg and Rochester consensus meeting statements published in the late 1990s. 44,45 Some tumors classified as PRCC in the past are now recognized as separate distinct entities, including FH-deficient RCC, 30,31 MiT family translocation-associated RCC, 32,33 acquired cystic kidney disease-associated RCC, [46][47][48] and clear cell-papillary RCC. [49][50][51][52] In addition, the concept of PRCC subclassification as 'type 1" and "type 2" was proposed in 1997, 8 but has fallen out of favor due to variable outcome results, intermediate forms, and recent molecular data.…”

An intracapsular nephrectomy for the acquired cystic disease-associated renal cell carcinoma in renal transplant allograft

“…The pathogenesis of ACRD-RCC so far has not been fully clarified. The existing theories include multifactorial reasons as immunosuppression, ESRD, oncogenic viruses, natural kidney evolution, dialysis, et al [ 6 , 7 ] First, several transplant and immunological factors might influence the risk of cancer after kidney transplantation, possibly owing to differences in rates of graft rejection and overall exposure to immunosuppression. [ 6 ] Continuous application of immunosuppressive drugs is a risk factor that cannot be ignored.…”