Tubulocystic Renal Cell Carcinoma Research Articles

MP59-11 CYSTIC RENAL CELL CARCINOMA PORTENDS EXCELLENT PROGNOSIS – RESULTS OF A LARGE POPULATION-LEVEL OUTCOME STUDY

You have accessJournal of UrologyKidney Cancer: Localized IV1 Apr 2014MP59-11 CYSTIC RENAL CELL CARCINOMA PORTENDS EXCELLENT PROGNOSIS – RESULTS OF A LARGE POPULATION-LEVEL OUTCOME STUDY Jaimin R. Bhatt, Sarah Kawaguchi, Patrick O. Richard, Shabbir Alibhai, Narhari Timilshina, Michael Jewett, and Antonio Finelli Jaimin R. BhattJaimin R. Bhatt More articles by this author , Sarah KawaguchiSarah Kawaguchi More articles by this author , Patrick O. RichardPatrick O. Richard More articles by this author , Shabbir AlibhaiShabbir Alibhai More articles by this author , Narhari TimilshinaNarhari Timilshina More articles by this author , Michael JewettMichael Jewett More articles by this author , and Antonio FinelliAntonio Finelli More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1807AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Renal cell carcinoma (RCC) makes up 3-5% of all cancers. Of these, cystic RCCs constitute between 3-14%, and are often detected incidentally as complex enhancing renal cysts on imaging. Since 2004, there has been a pathological reclassification of cystic clear RCC leading to description of multilocular cystic RCC (mcRCC) as a subtype of clear cell RCC. Other types include tubulocystic RCC. We aimed to study the histologic patterns and survival outcomes of all recorded cystic RCCs using a province-wide cancer registry database for Ontario. Methods A retrospective review of all histologically-proven cases of cystic RCC treated by partial or radical nephrectomy (PN or RN) between 1995 and 2004 identified from the Ontario Cancer Registry was performed. Patient demographics, type of surgery, histologic features and survival outcomes were evaluated. Results A total of 107 cystic RCCs were identified in 106 patients. Mean age was 55 years, with a male preponderance of 58%. RN was performed in 55% with adrenalectomy in 25%. Mean lesion size at histology was 4.16cm(1-18cm). Vast majority (106) were cystic clear-cell or multilocular cystic RCC (mcRCC) with one case of tubulocystic RCC. Ninety-five % were low grade (Fuhrman grade 1-2). There was only 1 case of vascular invasion and none of lymphatic invasion. None of the cases involved the renal pelvis or adrenal gland where removed. There were 2 small renal vein thrombi, and 3 cases of perinephric fat invasion. All cases were margin-negative. Patients had a median post-operative follow up of 5 years. Twelve deaths were reported but none were caused by RCC. Conclusions We believe that our study is the largest series of cystic RCCs to date. It confirms a favourable histology and an excellent prognosis of mcRCC. Given that this series excludes patients who underwent surgery and had a final pathological diagnosis which was benign, the magnitude of this favourable prognosis is under-represented. This makes a strong case for nephron-sparing, adrenal-saving approach for cystic renal masses suspicious of being RCCs. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e654 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Jaimin R. Bhatt More articles by this author Sarah Kawaguchi More articles by this author Patrick O. Richard More articles by this author Shabbir Alibhai More articles by this author Narhari Timilshina More articles by this author Michael Jewett More articles by this author Antonio Finelli More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Advances in Renal Neoplasia: Recommendations From the 2012 International Society of Urological Pathology Consensus Conference

The International Society of Urological Pathology (ISUP) 2012 Consensus Conference made recommendations regarding the classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. There was consensus that 5 entities should be recognized as novel tumors: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell papillary RCC, microphthalmia transcription factor-family translocation RCC [in particular t(6; 11) RCC], and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, 3 rare epithelial carcinomas were considered emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC, and anaplastic lymphoma kinase translocation RCC. There were also a number of suggested modifications to existing World Health Organization 2004 categories, with the new classification to be known as the ISUP Vancouver Classification. Tumor morphotype, sarcomatoid/rhabdoid differentiation, and tumor necrosis were identified as significant prognostic parameters for RCC. The ISUP Grading System was accepted with grades 1-3 of clear cell and papillary RCC being based on nucleolar prominence, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed that chromophobe RCC should not be graded. Consensus guidelines were formulated for specimen handling, and it was agreed that renal sinus invasion is present when tumor is in direct contact with fat or loose connective tissue of the sinus or if there is involvement of endothelial-lined spaces within the renal sinus, regardless of the size. The role of biomarkers in the diagnosis and assessment of prognosis of renal tumors was considered, and panels of immunohistochemical markers were identified for use in specific differential diagnostic scenarios.

Cystic renal oncocytoma and tubulocystic renal cell carcinoma: morphologic and immunohistochemical comparative study

Renal oncocytoma (RO) may present with a tubulo-cystic growth pattern in 3–7% of cases. In such cases its morphology may significantly overlap with tubulocystic renal cell carcinoma (TCRCC). We compared the morphological and immunohistochemical characteristics of these tumors aiming to clarify the differential diagnostic criteria and facilitating their discrimination. Twenty-four cystic RO (CRO) and 17 TCRCC were selected and analyzed for architectural pattern, stromal features, cytological criteria, necrosis, nuclear grade and mitotic activity. Immunohistochemical panel including various cytokeratins, vimentin, CD10, AMACR, antimitochondrial antigen (MIA), EMA and Ki-67. The islands of tumor cells, myxoid stroma, lower nuclear grade, absence of necrosis and mitotic figures were strongly suggestive of diagnosis of CRO while the absence of islands of tumor cells, fibrotic stroma, higher nuclear grade and presence of necrosis and mitoses were strongly suggestive of TCRCC. Immunohistochemical analysis of vimentin, CK7, CD10, AMACR and Ki-67 may discriminate between CRO and TCRCC. Islands of tumor cells and type of stroma may be major morphologic criteria for differentiating between CRO and TCRCC. In difficult cases, or cases when limited specimen availability precludes the assessment of morphologic criteria, immunohistochemical markers such as vimentin, CK7, CD10, AMACR and CK7 could lead to correct diagnosis.

A rare co-occurrence of tubulocystic and clear cell type renal cell carcinoma

Tubulocystic renal cell carcinoma (TC-RCC) is a recently described rare subtype of RCC. Less than 70 cases have been reported until date. The concurrent papillary RCC (P-RCC) and TC-RCC has been documented many times in the literature, but the co-occurrence of clear cell RCC (CC-RCC) and TC-RCC is very rare. We are probably describing the third case of TC-RCC occurring with CC-RCC in a 62-year-old male who presented with heaviness of left upper abdomen and dull intermittent pain in the left flank. Grossly, there was two distinct parts in the total nephrectomy specimen. The larger solid part displayed the histopathological features of CC-RCC and the smaller spongy part revealed the features of TC-RCC.

New and emerging renal tumors

The International Society of Urological Pathology (ISUP) 2012 Consensus Conference on Adult Renal Neoplasia made recommendations regarding the diagnosis and classification of new and emerging adult renal tumors. There was consensus that five entities should be recognized as new histological types: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubule) papillary RCC, MiT family translocation RCC [in particular t(6;11) RCC] and hereditary leiomyomatosis-associated RCC. In addition, three rare epithelial carcinomas were considered emerging or provisional entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK-translocation RCC. There were also a number of suggested modifications to existing WHO 2004 categories with the new classification. This new classification of renal neoplasia is known as the ISUP Vancouver Classification. These new renal tumor types have clinicopathological and molecular features that are distinct from those included in 2004 WHO classification. Correct diagnosis and classification of these new renal tumor entities have important implications for patient management.

Bilateral Tubulocystic Renal Cell Carcinomas in Diabetic End-Stage Renal Disease: First Case Report with Cytogenetic and Ultrastructural Studies

Tubulocystic renal cell carcinoma (TC-RCC) is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.

The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia

The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, advances in our understanding of angiomyolipoma, including the epithelioid and epithelial cystic variants, were considered. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumor was discussed, with the consensus that these tumors form a spectrum of neoplasia. Finally, it was thought that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia.

Tubulocystic carcinoma of the kidney with poorly differentiated foci: a series of 3 cases with fluorescence in situ hybridization analysis

We identified 3 consult cases of tubulocystic renal cell carcinoma with poorly differentiated areas. Two lesions measuring 9.5 and 3.8 cm were described as partly solid and cystic. One case was grossly a 14.0-cm cyst with a granular lining. Microscopically, all had classic areas of circumscribed tubulocystic renal cell carcinoma occupying 30%, 80%, and 90% of the tumor; 2 cases had small components of papillary renal cell carcinoma, and 1 case had a central large cystic component. In 2 cases, proliferations of small tubules infiltrated away from the main mass with typical features of collecting duct carcinoma. In the third case, a focus of poorly differentiated carcinoma was seen adjacent to the tubulocystic renal cell carcinoma. In 2 cases, tumor invaded perirenal tissue. The third case was organ confined with vascular invasion. One patient died 9 months postoperatively with metastases to the abdominal wall and femur. The second case developed a recurrence in the renal bed 3 years postoperatively. The third patient was lost to follow-up. Fluorescence in situ hybridization studies results showed some features overlapping with papillary renal cell carcinoma in both the tubulocystic and collecting duct-like components and with 1 exception showed identical cytogenetic findings between the 2 components. Morphologically, in 2 cases, the collecting duct-like areas were also indistinguishable from collecting duct carcinoma suggesting a relationship between the 2 entities. This is the first series and only the second report of tubulocystic renal cell carcinoma with poorly differentiated components and documents the increased the risk of aggressive behavior above that of usual tubulocystic renal cell carcinoma.

Transition of Organizational Category on Renal Cancer

The incidence of kidney cancer is gradually increasing, with a rate of 2-3% per decade. The kidney develops various kinds of neoplasms, some of which are associated with familial cancer syndromes. Such cases have provided clues to identify the cancer-responsible genes. In 2004, the World Health Organization published a new classification system of renal neoplasms, incorporating recent knowledge obtained in the cytogenetic and molecular biological fields, i.e. genes responsible for each histologic subtype (von Hippel-Lindau for clear cell renal cell carcinoma, c-met for papillary renal cell carcinoma type 1, etc.). Subsequently, the Japanese classification system in 'the General Rule for Clinicopathological Study of Renal Cell Carcinoma' has been revised as the 4th edition, according to the World Health Organization system. Several novel subtypes have been introduced, i.e. mucinous tubular and spindle cell carcinoma, and Xp11.2/TFE3 translocation-associated renal cell carcinoma. Even after the publication of the classification, other novel subtypes have emerged, i.e. acquired cystic disease-associated renal cell carcinoma and tubulocystic renal cell carcinoma. Additionally, some of the subtypes seem to form families based on morphological transition, immunohistochemical features and gene expression profile. In future, the classification of renal cell carcinoma should be reorganized on the basis of molecular biological characteristics to establish personalized therapeutic strategies.

Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases

Generally, patients with renal cell carcinoma (RCC) are viewed as potential candidates for antiangiogenic targeted therapy. Tubulocystic RCC (TCRC) is a recently described entity which may behave aggressively, and the rationale for antiangiogenic therapy in this group of renal tumors has yet to be determined. Seven TCRCs and five non-tumor tissue samples from seven patients were subjected to relative expression analysis of mRNA levels of 16 genes involved in three angiogenic signal pathways: (1) VHL/HIF, (2) RTK/mitogen-activated protein kinase (MAPK), and (3) PI3K/Akt/mTOR. Two of them, pathways (2) and (3), are often targeted by antiangiogenic agents. We also determined the mutation and methylation status of the VHL gene. Finally, the levels of vascular endothelial growth factor A (VEGFA), HIF-1α, HIF-2α proteins, and phosphorylated mTOR protein were also determined. The comparison of tumor and control samples revealed no changes of mRNA levels of the following genes: VHL, HIF-1α, HIF-2α, PTEN, Akt2, Akt3, mTOR, VEGFA, KDR, HRas, C-Jun, EGFR, and FGF2. Significantly elevated mRNA level of TP53 was found, while the mRNA levels of FLT1 and C-FOS were reduced in tumor samples. No mutations or methylation in the VHL gene were found. Changes in levels of studied proteins VEGFA, HIF-1α, HIF-2α, and increased phosphorylation of mTOR protein were not found. Three studied angiogenic pathways (VHL/HIF, RTK/MAPK, and PI3K/Akt/mTOR) seem not to be upregulated in TCRC samples, so there appears to be no rationale for a general recommendation of antiangiogenic targeted therapeutic protocols for patients with these tumors.

Novel molecular aberrations and pathologic findings in a tubulocystic variant of renal cell carcinoma

Tubulocystic renal cell carcinoma (TRCC) is an indolent type of renal cell carcinoma with a good prognosis based on the limited number of published cases. Herein, we describe the unusual clinical, pathologic and molecular findings in a case of TRCC. Our patient with TRCC had two local recurrences and a brain metastasis following radical nephrectomy. Unusual histologic findings included focal solid growth pattern and cytologic atypia. A genome-wide molecular inversion probe assay identified copy number (CN) loss in three chromosome regions and one region with copy-neutral loss of heterozygosity (copy-neutral LOH). Copy number variations (CNVs) were observed (chromosomes 4p16.1 and 17q21.31-q21.32) in both the tumor and the normal tissue, and most likely represents benign variations. The loss of entire chromosomes 9, 18 and 15 and copy-neutral LOH involving 6p22.1 was observed only in the tumor. The presence of these clinical, pathologic and molecular findings could be related to an increased risk for tumor recurrence and poor prognosis. The novel molecular findings described in TRCC might represent new targets for novel therapies.

Update on renal tumours

This presentation will give an update on renal tumours encompassing new entities [including tubulocystic renal cell carcinoma (RCC), acquired cystic disease associated RCC, clear cell tubulopapillary RCC, t(6;11) translocation carcinoma, and hereditary leiomyomatosis and RCC] and emerging entities [thyroid-like follicular RCC, succinate dehydrogenase B (SDHB) mutation associated RCC, and ALK-translocation associated RCC]. A summary of the entities accepted in these categories by consensus at the International Society of Urological Pathology meeting in Vancouver in March 2012 will be given. Discussion of important familial tumours involving the kidney will be included.

Bilateral Tubulocystic Renal Cell Carcinomas Associated With Acquired End-Stage Renal Disease: The First Case Report With Cytogenetic and Ultrastructural Studies

Bilateral Tubulocystic Renal Cell Carcinomas Associated With Acquired End-Stage Renal Disease: The First Case Report With Cytogenetic and Ultrastructural Studies

Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma

Tubulocystic renal cell carcinoma (TCRCC) is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC) and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.