ACD-associated Renal Cell Carcinoma Research Articles

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.

New pathological subtypes of renal cell carcinoma (RCC) were designated in the 2016 World Health Organization (WHO) classification corresponding to the features commonly seen in patients with end-stage renal disease (ESRD). To determine the clinicopathological findings of new subtypes, we reanalyzed all sections from 315 kidneys in 291 ESRD patients bearing RCC tumors surgically resected in three Japanese institutes by the central pathologist. Clear cell RCC was diagnosed in 144 kidneys (45.7%), acquired cystic disease (ACD)-associated RCC in 100 (31.7%), papillary RCC in 41 (13.0%), and other minor subtypes in 30 (9.52%). Multivariate analysis showed that longer duration of dialysis, young age, and male sex were independent prognostic clinical factors for the occurrence of ACD-associated RCC. ACD-associated RCC included more WHO/International Society of Urologic Pathology (ISUP) grade 3/4 cases compared to other RCCs. In contrast, other unfavorable findings were less frequent in ACD-associated RCC, including the presence of a sarcomatoid component, lymphovascular invasion, and necrosis. In conclusion, ACD-associated RCC is a common histology in Japanese patients with ESRD. In addition, ACD-associated RCC showed more cases with a higher WHO/ISUP grade, but fewer cases with other unfavorable pathological features, suggesting a favorable prognosis of ACD-associated RCC.

Pathologic spectrum of cysts in end-stage kidneys: possible precursors to renal neoplasia.

Acquired cystic disease (ACD) is common in patients with end-stage renal disease. Given the significant increased risk of renal cell carcinoma (RCC) in these patients, we characterized the pathologic spectrum of cysts in end-stage kidneys to determine the possible relationship with coincidental neoplasms. Twenty-one native end-stage kidneys contained multiple cysts (0.1-4 cm), which could be categorized into 3 groups based on the cytoplasm of the predominant cell type: clear, eosinophilic, or foamy. Clear cell cysts showed strong staining with carbonic anhydrase IX (CA9) in a cup-shaped manner. Of 7 kidneys with CA9-positive clear cell cysts, 3 had at least 2 foci of RCC (0.5-8 cm), which all demonstrated the morphologic features and immunoprofile of clear cell papillary RCC. Eight kidneys contained foamy cysts, and 4 of these contained ACD-associated RCC, but 1 papillary RCC was also encountered. Six kidneys had eosinophilic cysts, which were negative for CA9, and 3 of these were associated with papillary RCC. Clear cell cysts, although few in number, are common in end-stage nephrectomy specimens. These cysts were present in all kidneys with clear cell papillary RCC and a few kidneys without an obvious mass. In specimens with ACD-associated RCC or papillary RCC, cysts lined by epithelial cells with predominantly eosinophilic or foamy cytoplasm were identified. These data support the idea that the cysts in end-stage kidneys could represent the earliest precursor lesion of renal neoplasia.

Genomic profiling of renal cell carcinoma in patients with end‐stage renal disease

The purpose of the present study was to determine the genomic profile of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) by analyzing genomic copy number aberrations. Seventy-nine tumor samples from 63 patients with RCC-ESRD were analyzed by array comparative genomic hybridization using the Agilent Whole Human Genome 4 × 44K Oligo Micro Array (Agilent Technologies Inc., Palo Alto, CA, USA). Unsupervised hierarchical clustering analysis revealed that the 63 cases could be divided into two groups, Clusters A and B. Cluster A was comprised mainly of clear cell RCC (CCRCC), whereas Cluster B was comprised mainly of papillary RCC (PRCC), acquired cystic disease (ACD)-associated RCC, and clear cell papillary RCC. Analysis of the averaged frequencies revealed that the genomic profiles of Clusters A and B resembled those of sporadic CCRCC and sporadic PRCC, respectively. Although it has been proposed on the basis of histopathology that ACD-associated RCC, clear cell papillary RCC and PRCC-ESRD are distinct subtypes, the present data reveal that the genomic profiles of these types, categorized as Cluster B, resemble one another. Furthermore, the genomic profiles of PRCC, ACD-associated RCC and clear cell papillary RCC admixed in one tissue tended to resemble one another. On the basis of genomic profiling of RCC-ESRD, we conclude that the molecular pathogenesis of CCRCC-ESRD resembles that of sporadic CCRCC. Although various histologic subtypes of non-clear cell RCC-ESRD have been proposed, their genomic profiles resemble those of sporadic PRCC, suggesting that the molecular pathogenesis of non-CCRCC-ESRD may be related to that of sporadic PRCC.

Acquired cystic disease-associated renal cell carcinoma: an immunohistochemical and fluorescence in situ hybridization study

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has been recently identified. However, there are only a few genetic studies to date. In this article, we performed an immunohistochemical and fluorescence in situ hybridization (FISH) study for six cases including one case with sarcomatoid change. As a result, we observed frequent immunohistochemical expression of AMACR. FISH of chromosome 3 showed trisomy for three cases, monosomy for two cases, and disomy for one case. Additionally, FISH of chromosome 16 showed trisomy for three cases, monosomy for two cases, and both trisomy and monosomy for one case. Furthermore, both the carcinomatous area and the sarcomatoid area of one ACD-associated RCC with sarcomatoid change revealed monosomy of chromosomes 3, 9, and 16 but showed disomy of chromosome 14. In conclusion, the numerical abnormalities of chromosomes 3 and 16, irrespective of gain or loss, may be characteristic of ACD-associated RCC.

Review of acquired cystic disease-associated renal cell carcinoma with focus on pathobiological aspects.

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently established entity. In this article, we introduce the general view of this new entity. Macroscopically, the disease exclusively occurs in ACD and may arise as a dominant mass or non-dominant masses. Histologically, the tumor is characterized by a microcystic pattern, neoplastic cells with an eosinophilic or oncocytic cytoplasm and frequent intratumoral oxalate crystal deposition. Prominent nucleoli of tumor cells are often observed. Immunohistochemically, neoplastic cells are generally positive for AMACR but negative for cytokeratin 7. Ultrastructurally, neoplastic cells contain abundant mitochondria in the cytoplasm. Genetically, the gain of chromosomes 3, 7, 17 and abnormality of the sex chromosome were frequently observed in several studies. In conclusion, ACD-associated RCC may be widely recognized as a distinct entity in the near future because this tumor is morphologically and genetically different from other renal tumor entities that have been previously established.

113 GENOMIC PROFILING OF RENAL CELL CARCINOMA IN PATIENTS WITH END-STAGE RENAL DISEASE

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011113 GENOMIC PROFILING OF RENAL CELL CARCINOMA IN PATIENTS WITH END-STAGE RENAL DISEASE Toru Inoue, Keiko Matsuura, Taichiro Yoshimoto, Takahiro Narimatsu, Fuminori Sato, Yoji Nagashima, Shingo Hatakeyama, Chikara Ohyama, Tomonori Habuchi, Masayuki Nakagawa, Masatsugu Moriyama, and Hiromitsu Mimata Toru InoueToru Inoue Oita, Japan More articles by this author , Keiko MatsuuraKeiko Matsuura Oita, Japan More articles by this author , Taichiro YoshimotoTaichiro Yoshimoto Tokyo, Japan More articles by this author , Takahiro NarimatsuTakahiro Narimatsu Oita, Japan More articles by this author , Fuminori SatoFuminori Sato Oita, Japan More articles by this author , Yoji NagashimaYoji Nagashima Yokohama, Japan More articles by this author , Shingo HatakeyamaShingo Hatakeyama Hirosaki, Japan More articles by this author , Chikara OhyamaChikara Ohyama Hirosaki, Japan More articles by this author , Tomonori HabuchiTomonori Habuchi Akita, Japan More articles by this author , Masayuki NakagawaMasayuki Nakagawa Kagoshima, Japan More articles by this author , Masatsugu MoriyamaMasatsugu Moriyama Oita, Japan More articles by this author , and Hiromitsu MimataHiromitsu Mimata Oita, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.179AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with end-stage renal disease (ESRD) show an increased incidence of renal cell carcinoma (RCC) compared with the general population. RCCs in patients with ESRD (RCC-ESRD) have a wide variety of histological subtypes. The copy number aberrations (CNAs) of these RCC-ESRD have not been fully investigated. Therefore, we performed array comparative genomic hybridization (array CGH) to determine the CNAs of RCC-ESRD. METHODS A total of 65 patients with RCCs in ESRD were analyzed. Genomic DNA was extracted selectively from formalin-fixed, paraffin-embedded tissues using laser microdissection. High resolution array CGH was performed using Agilent Whole Human Genome 4x44K Oligo Micro Array Kit. RESULTS We analyzed 65 cases of RCC in ESRD (32 clear cell RCCs, 9 papillary RCCs, 17 ACD-associated RCCs, 3 clear cell-papillary RCCs, 1 chromophobe RCC, 1 MTSCC, 2 unclassified RCCs) by array CGH. Unsupervised hierarchical cluster analysis revealed that RCC-ESRD could be subclassified into two main groups (Cluster A and B). The cluster A contained mainly papillary RCC, ACD-associated RCC, clear cell-papillary RCC. These 3 histologic subtypes did not constitute any independent cluster, suggesting that they shared similar CNAs. On the other hand, the cluster B mainly contained clear cell RCC. Next, we analyzed the patterns of CNAs on each cluster and found that the cluster A showed similar CNA patterns with sporadic papillary RCC, such as 7pq gain and 16 pq gain, suggesting that, as a whole, CNAs of papillary RCC-ESRD resemble those of sporadic papillary RCC. On the other hand, the cluster B had similar CNA patterns with sporadic clear cell RCC including 3p, 14q losses, and 5q gain. Next, we compared the CNAs of papillary RCC, ACD-associated RCC and clear cell-papillary RCC, all of which were categorized in the cluster A. Interestingly, we found that all the three histologic subtypes had similar patterns of CNAs, which resemble those of sporadic papillary RCC, suggesting that they shared similar molecular mechanisms of the carcinogenesis of these tumors, although their histologic phenotypes were clearly different. Moreover, duration of dialysis in cluster A was significantly longer than that of cluster B (p=0.015). CONCLUSIONS RCCs-ESRD can be classified into two categories based on their CNAs. Papillary RCC-ESRD, ACD-associated RCC, and clear cell-papillary RCC may share similar oncogenic mechanism. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e48 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Toru Inoue Oita, Japan More articles by this author Keiko Matsuura Oita, Japan More articles by this author Taichiro Yoshimoto Tokyo, Japan More articles by this author Takahiro Narimatsu Oita, Japan More articles by this author Fuminori Sato Oita, Japan More articles by this author Yoji Nagashima Yokohama, Japan More articles by this author Shingo Hatakeyama Hirosaki, Japan More articles by this author Chikara Ohyama Hirosaki, Japan More articles by this author Tomonori Habuchi Akita, Japan More articles by this author Masayuki Nakagawa Kagoshima, Japan More articles by this author Masatsugu Moriyama Oita, Japan More articles by this author Hiromitsu Mimata Oita, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Acquired cystic disease-associated renal cell carcinoma with gain of chromosomes 3, 7, and 16, gain of chromosome X, and loss of chromosome Y

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has been recently described. To date, there are no reports on genetic findings of G-band karyotype of ACD-associated RCC. In this article, we report the first report of G-band karyotype of ACD-associated RCC. A 66-year-old Japanese man was found to have a left renal tumor during the follow-up of hemodialysis consequent to chronic renal failure. Left nephrectomy was performed. Histological examination of three tumors in the left kidney showed the cribriform or microcystic growth pattern of neoplastic cells with eosinophilic cytoplasm, and many oxalate crystals were observed. The G-band karyotype of ACD-associated RCC showed 49, X, +X, -Y, +3, +7, +16. These chromosomal abnormalities resemble those of sporadic papillary RCC that has been previously reported. Finally, we suggest that this tumor may show a close relationship between ACD-associated RCC and papillary RCC, but a large-scale study will be needed to clarify the relationship between ACD-associated RCC and papillary RCC.

Acquired cystic disease–associated renal cell carcinoma with sarcomatoid change and rhabdoid features

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently described entity. To the best of our knowledge, there are no reports of ACD-associated RCC with sarcomatoid and rhabdoid changes. In this article, we present the first case of such a tumor. A 56-year-old Japanese man has received long-term hemodialysis and had a history of right renal cancer. Following the discovery of metastatic cancer in the thoracic wall, detailed imaging studies revealed a mass in the left kidney. The histologic examination of the left renal tumor showed ACD-associated RCC with sarcomatoid change and rhabdoid features. Immunohistochemically, intracytoplasmic globular inclusions in rhabdoid cells were positive for vimentin and cytokeratin CAM5.2. The G-band karyotype showed the following changes: 46, X, +X. -Y[1]/43, idem, add(2)(q31), -6, -9, -14, -15, +16, -22, +mar1[6]/46, XY[2]/abnormal cell[11]. In conclusion, pathologists and urologists should be aware that rhabdoid features may occur in ACD-associated RCC and that the loss of chromosomes 9 and 14 may occur during the process of sarcomatoid change in ACD-associated RCC.

Imaging of acquired cystic disease-associated renal cell carcinoma by contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography

The preoperative assessment of renal cell carcinoma (RCC) complicated with acquired renal cystic disease in a 63-year-old male patient on long-term hemodialysis (30 years and 8 months) that was difficult because of no or poor contrast enhancement by dynamic CT scan is reported. Contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography (PET-CT) with 18F-fluorodeoxy glucose (FDG) in addition to dynamic CT were effective and useful for preoperative assessment of this patient. The pathological subtype of RCC in this patient was acquired cystic disease-associated RCC (ACD-associated RCC), which has been newly defined by Tickoo et al. (Am J Surg Pathol 30:141-153, 2006).

Renal cell carcinoma in patients with end‐stage renal disease: relationship between histological type and duration of dialysis

To evaluate the clinical outcomes and histological types of renal cell carcinoma (RCC) arising in patients with end-stage renal disease (ESRD), and to analyse the relationship of histopathological features with the duration of dialysis. Clinical characteristics and outcomes of 34 patients who had a radical nephrectomy for RCC arising in ESRD between November 1994 and June 2008 were investigated. Archive paraffin-embedded tissue specimens obtained from 27 patients were histochemically and immunohistochemically analysed to determine the histopathological type. There was one death from cancer and one patient with local progression within a median observation period of 29.5 months. Acquired cystic disease (ACD)-associated RCC, clear cell-papillary RCC, mucinous tubular and spindle-cell carcinoma, and Xp11.2 translocation/TFE3 gene fusion were identified in eight, two, three and one patient, respectively. Conventional clear-cell RCC was the predominant histological type (nine of 15) in patients with a duration of dialysis of <10 years, while ACD-associated RCC was predominant (seven of 12) in those with dialysis for > or =10 years. Sarcomatoid foci were identified in three patients with dialysis for > or =10 years. Papillary adenoma was microscopically identified as a satellite tumour in 10 patients. The spectrum of histological types of RCCs arising in ESRD is distinct from that of sporadic RCCs. Patients with a longer duration of dialysis should have particular attention for progression and metastasis. Immunohistochemical profiling is efficient in the histological classification of RCCs arising in ESRD, although knowledge about genetic changes remains to be accumulated.

Sarcomatoid acquired cystic disease-associated renal cell carcinoma.

In this article, we report a rare case of hitherto undescribed acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) with sarcomatoid change. A 78-year-old woman had been receiving hemodialysis for fourteen years at the time when a renal tumor was encountered on the follow-up examination of the kidney. Microscopically, oncocytic cuboidal cells proliferated with tubular, cribriform or papillary growth patterns, and atypical columnar cells with abundant cytoplasm proliferated with papillary configuration. Oxalate crystal deposition was observed in the stroma and the tumor focally resembled translocation type (TFE3) RCC. Sarcomatous neoplastic cells were also seen. The cytoplasm of oncocytic and sarcomatous neoplastic cells was diffusely positive for anti-mitochondrial antibody and the ultrastructural examination detected many mitochondria in the cytoplasm of oncocytic carcinoma cells and sarcomatous neoplastic cells. The loss of chromosomes 1p, 2q11-22, 9 and 14 was observed using comparative genomic hybridization analysis. We thus report here a case of hitherto undescribed ACD-associated RCC intermingled with oncocytic cells, translocation type RCC-like area and sarcomatoid change. This is the sixth case of sarcomatoid RCC arising in end-stage kidney disease.