Showing papers on "Papillary renal cell carcinomas published in 2002"
TL;DR: It is shown that the histologic categorization of adult renal epithelial neoplasms performed by routine light microscopic hematoxylin and eosin-based examination in accordance with the contemporary classification scheme has prognostic utility.
Abstract: Just two and a half decades ago adult renal cell neoplasms, i.e., those arising from the renal tubules or collecting duct epithelium, were subdivided into two major subtypes: "clear cell carcinoma" and "granular cell carcinoma." Subsequent detailed morphologic and/or cytogenetic studies have resulted in the recognition of several distinctive subtypes of adult renal epithelial neoplasms, which has led to the promulgation of a refined contemporary histologic classification of these tumors. This study examines the prognostic significance of histologic subtyping in accordance with the new classification in a consecutive series of 405 cases treated at a single institution. Cases were histologically classified into 28 (7%) benign tumors [27 (6.7%) renal oncocytomas, 1 (0.2%) metanephric adenoma] and 377 (93%) malignant tumors [255 (63%) conventional (clear cell) renal cell carcinoma, 75 (18.5%) papillary renal cell carcinoma, 24 (5.9%) chromophobe renal cell carcinoma, and 23 (5.7%) renal cell carcinoma, unclassified]. A total of 25 (6.6%) malignant tumors showed evidence of sarcomatoid change. Kaplan-Meier survival analysis with log-rank test showed histologic type (p = 0.002), Fuhrman's nuclear grade (p = 0.001), TNM stage (p = 0.001), vascular invasion (p = 0.001), and necrosis (p = 0.001) to be significantly associated with disease-specific survival and progression-free survival, based on follow-up of 368 patients (mean 64.5 months, median 56 months). The 5-year disease-specific survival for chromophobe renal cell carcinoma, papillary renal cell carcinoma, conventional (clear cell) renal cell carcinoma, and renal cell carcinoma, unclassified was 100%, 86%, 76%, and 24%, respectively; no patient with a benign tumor diagnosis progressed or died of disease. The 5-year progression-free survival for chromophobe renal cell carcinoma, papillary renal cell carcinoma, conventional (clear cell) renal cell carcinoma, and renal cell carcinoma, unclassified was 94%, 88%, 70%, and 18%, respectively. Malignant tumors with sarcomatoid change had a 35% and 27%, 5-year disease-specific and progression-free survival, respectively. Cox proportional hazards regression analysis showed TNM stage (p = 0.001), nuclear grade (p = 0.01), and necrosis (p = 0.05) to be significant predictors of disease-specific survival. In conclusion, our study shows that the histologic categorization of adult renal epithelial neoplasms performed by routine light microscopic hematoxylin and eosin-based examination in accordance with the contemporary classification scheme has prognostic utility.
696 citations
TL;DR: The reappraisal of genetically defined subsets of renal tumors can help to highlight the key pathologic features of specific neoplastic entities and there is experimental evidence suggesting that these tumors may show differential sensitivity to certain chemotherapeutic agents.
Abstract: The reappraisal of genetically defined subsets of renal tumors can help to highlight the key pathologic features of specific neoplastic entities. We report the morphologic, immunophenotypic, ultrastructural, and molecular features of 11 renal carcinomas bearing a t(X;1)(p11.2;q21) and/or the resulting PRCC-TFE3 gene fusion. The male/female ratio was 4:7. Ten patients were in the age range of 9-29 years and one was 64 years old (mean 21.3 years, median 15 years). The predominant histologic pattern was nested, with islands of tumor cells compartmentalized by thin-walled capillary vasculature. Minor variations on this pattern yielded solid, acinar, alveolar, and tubular architecture. Papillary architecture was seen in nine cases, usually as a minor component. Neoplastic cells were typically characterized by irregularly shaped nuclei with vesicular chromatin and small nucleoli not visible with a 10x objective, and cytoplasm that ranged from clear to densely granular and eosinophilic. Mitoses were extremely rare; 5 were found in 900 high power fields examined from the 11 neoplasms. The most distinctive immunohistochemical feature of these neoplasms was moderate to intense nuclear labeling for TFE3 protein. These tumors were also consistently immunoreactive for the RCC antigen (10 of 11) and CD10 (9 of 9), whereas cytokeratin and epithelial membrane antigen were negative in four cases and were positive focally in the others. Ultrastructurally, all of the six neoplasms examined showed features consistent with conventional-type (clear cell) renal carcinoma, although two demonstrated distinctive intracisternal microtubules. Both tumors tested contained PRCC-TFE3 fusion transcripts. The differential diagnosis includes conventional-type papillary renal cell carcinoma, conventional-type (clear cell) renal carcinoma, and the ASPL-TFE3 renal carcinomas associated with the t(X;17)(p11.2;q25), with the latter two being morphologically the most similar to the t(X;1) renal carcinomas. Aside from their distinctive clinicopathologic features described here, there is experimental evidence suggesting that these tumors may show differential sensitivity to certain chemotherapeutic agents.
304 citations
TL;DR: Papillary renal cell carcinomas are typically hypovascular and homogeneous, and a high tumor-to-parenchyma enhancement ratio essentially excludes the possibility of a tumor being papillary renal Cell carcinoma.
Abstract: OBJECTIVE. The purpose of this study was to determine whether renal tumor enhancement or heterogeneity on triphasic helical CT scans is predictive of the papillary cell subtype or nuclear grade of renal cell carcinoma.MATERIALS AND METHODS. We reviewed the CT scans of 90 consecutive patients with renal masses who had undergone triphasic renal helical CT before a complete or partial nephrectomy (12 with papillary renal cell carcinomas, 66 with nonpapillary renal cell carcinomas, and 12 with benign lesions). Three radiologists who were unaware of the patients' diagnoses retrospectively and independently measured the attenuation of each patient's tumor, abdominal aorta, and normal renal parenchyma on the scans obtained during all three phases. Ratios of tumor-to-aorta enhancement and tumor-to-normal renal parenchyma enhancement were calculated for both of the phases performed after contrast material had been administered. Tumor heterogeneity was calculated as the difference between the highest and lowest att...
220 citations
TL;DR: Standardized nuclear grades were more predictive of death due to RCC than nonstandardized grades for all subtypes studied.
Abstract: We compared the ability of original nuclear grades from surgical pathology reports and grades reviewed by a urologic pathologist to predict death due to renal cell carcinoma (RCC) for 2,042 patients treated with radical nephrectomy between January 1970 and December 1998. Reviewed grade I tumors had small, round nuclei with inconspicuous nucleoli visible at x400; grade 2 contained round to slightly irregular nuclei with mildly enlarged nucleoli visible at x200; grade 3 had round to irregular nuclei with prominent nucleoli visible at x100; grade 4 contained enlarged pleomorphic or giant cells. Predictive abilities were compared using R2 values from Cox proportional hazards models. There were 1,733 (84.87%) clear cell, 222 (10.87%) papillary, and 87 (4.26%) chromophobe tumors. Reviewed grades were more predictive of death due to RCC than original grades for clear cell (R2, 21% vs 16%), papillary (R2, 16% vs 13%), and chromophobe (R2, 39% vs 27%) RCC. Among patients with clear cell and papillary RCC, this difference was apparent even after adjusting for the 1997 TNM stage. Standardized nuclear grades were more predictive of death due to RCC than nonstandardized grades for all subtypes studied.
129 citations
TL;DR: It is confirmed that the morphologic sub-typing and Fuhrman grade are valuable factors of outcome of papillary renal cell carcinomas and that MUC1 immunostaining is useful in differentiating Type 1 and Type 2 tumors.
88 citations
TL;DR: It is concluded that PTEN/MMAC1 inactivation may play a role in the progression of cRCC, and biallelic in activation may preferentially occur by nonmutational mechanisms, or, alternatively, haploinsufficiency of PTEN or MMAC1 may be sufficient to affect tumor progression in cR CC.
84 citations
TL;DR: This study indicates that c-met over expression may be associated with an aggressive phenotype in these tumors, and this association is not associated with Fuhrman nuclear grade.
77 citations
TL;DR: The findings identify genetic differences between the recently proposed type 1 and type 2 PRCCs, and support the premise that these subtypes arise from distinct genetic pathways.
Abstract: The molecular genetic correlates of a recently proposed subclassification of papillary renal cell carcinoma (PRCC) that designates tumors as type 1 and type 2 based on histological features have not yet been established. Alterations of known genes in PRCC include missense mutations in the MET oncogene (7q31) and rare translocations fusing TFE3 at Xp11.2 with a variety of other loci. Previous cytogenetic and allelic loss studies of PRCC cases revealed gain of chromosome 3q, 7, 8, 12q, 16, 17, and 20q, and loss of 1p, 6q, 9p, 11p, 13q, 14q, 18, 21q, X, and Y. We analyzed a series of sporadic type 1 and type 2 PRCC cases for MET mutations, TFE3 rearrangements, and allelic imbalance (AI) on 3p, 6, 7q, 9p, 11, 13q, 14q, 17q, 18, 20q, and 21q and compared selected results with a series of conventional renal cell carcinomas. A somatic mutation M1149T was identified in MET exon 17 in 1 of 35 PRCC cases whereas TFE3 rearrangements were not detected in 22 PRCC cases examined. Significant differences in AI frequency between PRCCs and conventional renal cell carcinoma cases were seen on 3p (37.5% versus 77.8%, P = 0.01), 7q (42.9% versus 5.6%, P = 0.01), and 17q (54.5% versus 20.0%, P = 0.03). Significant differences in AI frequency between type 1 and type 2 PRCCs were noted on 17q (78.6% versus 12.5%, P = 0.006) and 9p (0% versus 37.5%, P = 0.02). Additional analyses suggested that the relationship between 17q AI and PRCC type may be independent of histological grade and stage. Our findings identify genetic differences between the recently proposed type 1 and type 2 PRCCs, and support the premise that these subtypes arise from distinct genetic pathways.
73 citations
TL;DR: There is a good agreement of cytogenetic and histopathologic criteria of malignancy in papillary renal cell tumors.
Abstract: Previous studies have indicated that a combined trisomy of chromosomes 7 and 17 is a constant finding in papillary renal cortical adenomas and that papillary renal cell carcinomas are marked by additional trisomies such as trisomy 12, 16, and 20. The aim of our study was to compare this cytogenetic classification of papillary renal cortical tumors with conventional histopathologic classification. We performed interphase cytogenetics with enumeration probes for chromosomes 7, 12, 16, 17, and 20 on 41 papillary tumors found in 21 nephrectomy and 10 autopsy kidneys. A total of 38 tumors harbored gains of chromosomes 7 or 17, and most of these showed a trisomic signal distribution. The three tumors with normal copy numbers for chromosomes 7 and 17 were a papillary grade-2 carcinoma, a small adenoma (both with distinctive oxyphilic cytoplasm), and a papillary carcinoma with focally clear cells. Gains for chromosomes 12, 16, or 20 were found in 21 tumors and were significantly associated with the presence of histologic criteria of malignancy (P<0.0001). Histopathologic and cytogenetic features of malignancy were found in eight tumors smaller than 10 mm. There is a good agreement of cytogenetic and histopathologic criteria of malignancy in papillary renal cell tumors. Interphase cytogenetics might give useful additional information in cases of doubt or when only small biopsy specimens are available.
23 citations
TL;DR: This report discusses the new cytogenetic classification of renal cell carcinoma (RCC) and its biological and clinical significance, and describes the four major types (clear cell, chromophil [papillary], chromophobe, and collecting duct) as well as rarer entities, such as small cell carcinomas, cystic RCC, rhabdoid variant of RCC.
Abstract: This report discusses the new cytogenetic classification of renal cell carcinoma (RCC) and its biological and clinical significance. It describes the four major types (clear cell, chromophil [papillary], chromophobe, and collecting duct) as well as rarer entities, such as small cell carcinoma, cystic RCC, rhabdoid variant of RCC, and unclassified RCC. Sarcomatoid carcinomas are a diverse group representing high-grade transformation of the other types. In addition to a description of the pathologic findings, there is a discussion of tumor markers and prognostic indicators. The clinical significance of the classification is discussed, with reference to recent reports.
10 citations
TL;DR: An extended family in which 15 of 70 members over three generations exhibited multiple, small, grey skin coloured, dome shaped papules distributed over the face, neck, and upper trunk inherited in an autosomal dominant pattern is reported.
Abstract: In 1977, Birt, Hogg, and Dube described a kindred in which 15 of 70 members over three generations exhibited multiple, small, grey skin coloured, dome shaped papules distributed over the face, neck, and upper trunk inherited in an autosomal dominant pattern.1 Histological examination of these lesions showed fibrofolliculomas, trichodiscomas, and acrochordons. This triad has become known as Birt-Hogg-Dube (BHD) syndrome. Since the initial report, other cases have been described.2–13
The cutaneous manifestations of BHD, which typically appear during the third or fourth decade of life, have been associated with renal carcinoma,2,5 spontaneous pneumothorax,2,6 and colonic polyps.3,4 Toro et al 2 recently reported three extended kindreds in whom renal neoplasms and BHD segregated together. Two kindreds had renal oncocytomas and a third had a variant of papillary renal cell carcinoma. Renal neoplasms can be familial or sporadic. Four types of familial renal neoplasms have been well described: (1) clear cell renal carcinoma associated with haemangioblastomas of the brain, spine, and eye owing to mutations in the von Hippel-Lindau (VHL) disease tumour suppressor gene,4 (2) clear cell renal carcinoma associated with constitutional, balanced translocations involving the short arm of chromosome 3,15–17 (3) papillary renal cell carcinoma associated with germline mutations in the tyrosine kinase domain of the MET proto-oncogene,18 and (4) renal oncocytoma.19
In this study, we report an extended family that we evaluated for PTEN , CTNNB1 , and PTCH as candidate genes for BHD and renal cancer. These genes were selected for study because mutations in each are associated with a disorder that has clinical features that overlap BHD and because each of these disorders carries an increased risk for internal malignancy. We used a candidate gene approach. We first performed sequencing analysis, but no mutations …
TL;DR: Both FISH and microsatellite analyses are helpful to strengthen the diagnosis of conventional renal cell carcinoma, however, both techniques may have some disadvantage in a special setting.
Abstract: Aims: The new classification of renal cell tumours relies on tumour-specific genetic alterations, which can be detected by different techniques. For diagnosis of conventional renal cell carcinoma by FISH we have isolated BAC clones from the chromosomal regions of interest.
Methods and results: A BAC library was screened by microsatellites mapped to the smallest overlapping regions of loss of heterozygosity (LOH) at chromosomes 3p, 5q, 6q, 8p, 9p and 14q. Positive BACs were tested by carrying out FISH in normal cells for signal/noise ratio. Subsequently, 11 conventional and two papillary renal cell carcinomas were analysed by the new diagnostic BAC set and the results were compared with those obtained by microsatellite allelotyping. The diagnostic value of FISH was comparable to that of microsatellite analysis in nearly all tumours except those with extreme chromosomal polyploidization.
Conclusions: We conclude that both FISH and microsatellite analyses are helpful to strengthen the diagnosis of conventional renal cell carcinoma. However, both techniques may have some disadvantage in a special setting.
Journal Article•
TL;DR: A 60-year-old male was admitted with bilateral renal masses with a diameter of 50 mm (right kidney), and 15 mm (left kidney) found incidentally by computed tomography, the third case of renal oncocytoma with synchronous contralateral renal cell carcinoma reported in Japan.
Abstract: A 60-year-old male was admitted with bilateral renal masses with a diameter of 50 mm (right kidney), and 15 mm (left kidney) found incidentally by computed tomography. Renal angiography demonstrated neovascularization in the lower pole of the right kidney, but no remarkable findings in the left kidney. We could not deny the possibility of bilateral renal cell carcinoma. Right radical nephrectomy and left partial nephrectomy were performed. The histopathological finding revealed diagnosis of right papillary renal cell carcinoma and left oncocytoma. To our knowledge, this is the third case of renal oncocytoma with synchronous contralateral renal cell carcinoma reported in Japan.
Journal Article•
TL;DR: Nphron sparing surgery is as effective as radical nephrectomy for treatment of localised RCC, and the reduced incidence of complications associated with a minimum complexity of the procedure and the results make this technique approachable by surgeons of different technical experience.
Abstract: PURPOSE Partial nephrectomy is an effective method of treatment for renal cell carcinoma. The aim of this study is to compare our experience with international literature data METHODS Between January 1997 and December 2000 a total of 50 renal units in 30 males and 18 women, 27 to 77 years old (mean age 60.6) with renal solid lesion of < 4 cm diameter were treated at our institution with nephron sparing surgery (NSS). The indications for NSS was elective in 43 case, imperative in 5. So far no local metastases, or vascular involvement have been encountered. The procedure was performed by 4 surgeons alternatively. RESULTS In 25 patients histology revealed with clear renal cell carcinoma, one case of the chromophobe cell type, 6 papillary renal cell carcinoma, 8 oncocytomas, 8 angiomyolipomas, 1 multicystic and 1 simple cyst renal carcinoma. The complications were 1 acute reversible renal failure and 1 arteriovenous fistula. At the follow-up of 23 months no local or distant metastases were encountered. No significant differences in results were noted in regard to surgeon. CONCLUSIONS Our results suggest that nephron sparing surgery is as effective as radical nephrectomy for treatment of localised RCC. The reduced incidence of complications associated with a minimum complexity of the procedure and the results make this technique approachable by surgeons of different technical experience.
Journal Article•
TL;DR: It has become apparent that chromosome 3p14-25 3 has possible TSGs for RCC, and it was pointed out in April that germline mutation of fumarate hydratase, a Krebs cycle enzyme, is present in multiple cutaneous and uterine leiomyomatosis families that develop papillary RCC.
Abstract: Renal Cell Carcinoma (RCC) is classified into six cell pathological types by the Thoenes classification (5) Deletion of DNA (loss of heterozeigosity: LOH) is seen with a high frequency in human RCC of all 6 types at chromosome 3p 14-25 The presence of at least three tumor suppressor genes at this domain has been pointed out The VHL gene, one of the tumor suppressor genes (TSG), was identified in 1993 at chromosome 3p25-26 as the gene responsible for VHL disease As a consequence, it was demonstrated that inactivation of the von Hippel-Lindau (VHL) gene is responsible for sporadic clear cell RCC Activating mutations of c-Met receptor type tyrosine kinase has been demonstrated in papillary renal cell carcinoma families Possible involvement of the FHIT tumor suppressor gene, located at the fragile site (FRA3B) of chromosome 3p14, has been detected in sporadic RCC Recently, methylation of RASSF1A at chromosome 3p213 was pointed out in sporadic RCC Thus, it has become apparent that chromosome 3p14-25 3 has possible TSGs for RCC Furthermore, it was pointed out in April that germline mutation of fumarate hydratase, a Krebs cycle enzyme (FH), is present in multiple cutaneous and uterine leiomyomatosis families that develop papillary RCC The functional significance in these genes for the development of RCC is still not apparent, except for the VHL gene Thus, there is still a long way to go before we find all responsible TSGs in all pathological subtypes in sporadic RCC