Showing papers on "Papillary renal cell carcinomas published in 1997"
Heidelberg University1, Loma Linda University2, Institute of Cancer Research3, Wellington Management Company4, University of Edinburgh5, Umeå University6, City of Hope National Medical Center7, University of Basel8, Memorial Sloan Kettering Cancer Center9, University of Toronto10, University of Groningen11
TL;DR: This paper presents the conclusions of a workshop entitled ‘Impact of Molecular Genetics on the Classification of Renal Cell Tumours’, which was held in Heidelberg in October 1996 and is applicable to routine diagnostic practice.
Abstract: This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996. The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys. The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities. Benign tumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma. Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified. This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice.
1,288 citations
Journal Article•
TL;DR: Papillary renal cell carcinoma is the second most common carcinoma of the renal tubules and has been characterized genetically, and its morphologic features are incompletely characterized.
657 citations
TL;DR: Papillary RCC is a malignant tumor, with a tendency to present at a lower stage, but with a distinct potential for progression and aggressive behavior, and the better 5-year survival rate of papillary R CC compared with that of conventional RCC suggests that it is a tumor with lower malignant potential.
Abstract: For more than two decades, papillary renal cell carcinoma has been recognized as a possible distinct clinicopathologic subtype of renal cell carcinoma (RCC). However, the histologic criteria for its diagnosis and the clinical outcome are still debated. In an attempt to clarify the diagnostic criteria and resolve issues pertaining to biologic potential, we have evaluated the histologic spectrum of 62 papillary RCCs and assessed significance of conventional pathologic prognostic parameters (Fuhrrman's nuclear grade [NG], pathologic stage [Robson and TNM], tumor size, multifocality, necrosis, and foam cells) and correlated these with outcome. The mean age of patients was 61.8 years (range 22-83), and males were more commonly affected (1.8:1). Grossly, most tumors were well circumscribed, averaged 6.7 cm in size (range 1.8-18), and were predominantly localized to the renal poles (polar vs. mid-renal, 3:1). Multifocality was a prominent feature (24 cases), and in three cases tumors were bilateral. Microscopically, papillary RCCs were predominantly papillary or tubulopapillary, often with a thick fibrous capsule, foam cells, necrosis, hemorrhage, and multifocality. Thirty-five percent of these tumors were low grade (NG I and II) and 65% high grade (NG III and IV). Sixteen of these tumors presented in a higher stage (stages III and IV), and the overall stage correlated with NG (chi 2, p = 0.009). Tumors were further distinguished by cytoplasmic features: eosinophilic (42%), basophilic (34%) and mixed (24%). Eosinophilic tumors were predominantly high grade, and basophilic tumors low grade (chi 2, p = 0.000). A mean follow-up of 57 months showed progression (metastasis, recurrence, or death due to disease) in 21%, whereas 63% were free of disease. Eleven percent died of unrelated causes, and 5% were lost to follow-up. Kaplan-Meier survival analysis showed that both high NG and stage were strongly associated with decreased survival (p = 0.0000 each), as were decreased foam cell (p = 0.0025) and vascular invasion (p = 0.0002). Comparison of 196 reported cases of papillary RCC, including the current series, with reported large series of conventional RCC indicates that papillary RCC usually presents at an early stage, and stage I (Robson) papillary RCC has better 5 year survival rates (87%-100%) than does RCC of the same stage (65-75%). The overall 5 years survival rate for papillary carcinoma (82-90%) was also higher than that of conventional RCC (44-54%). In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable (p = 0.0000, hazard ratio 10.1) in predicting outcome among papillary RCC. Based on this experience, we conclude that (a) papillary RCC is a malignant tumor, with a tendency to present at a lower stage, but with a distinct potential for progression and aggressive behavior; (b) stratification of these tumors according to cell type, amount of foam cells, presence or absence of vascular invasion, nuclear grade, and pathologic stage provides useful prognostic information; (c) the better 5-year survival rate of papillary RCC (overall and for stage I tumors) compared with that of conventional RCC suggests that it is a tumor with lower malignant potential. Thus, histologic subcategorization of a renal carcinoma as papillary RCC appears to have prognostic implications.
314 citations
TL;DR: Renal oncocytoma is a benign neoplasm and therefore does not merit a nuclear grading scheme, and has unique histologic features including an organoid and tubulocystic architecture, myxoid or hyalinized stroma, and occasionally some atypical findings including nuclear pleomorphism.
Abstract: Renal oncocytoma has several features that overlap with other renal neoplasms with a preponderance of granular cytoplasm, such as chromophobe, granular, and papillary renal cell carcinomas. Lack of knowledge of this entire spectrum of eosinophilic renal cell neoplasms has led to several misconceptions in the literature regarding renal oncocytoma. These include the "grading of oncocytomas," "metastatic oncocytomas," and the impression that renal oncocytoma is usually low grade and lacks prominent nucleoli. In order to further characterize the histologic features and embelLish diagnostic criteria, we evaluated 93 tumors from 80 patients. Four tumors were bilateral and two were multifocal. The mean age was 67.2 years (32-89 years), men were more commonly affected (3.1:1), and 82.7% tumors were incidental findings. Grossly, the tumors were mahogany brown, lacked necrosis, and averaged 4.4 cm in size (range 0.6-15 cm). Histologically, renal oncocytoma was composed of an exclusive or predominant component of acidophilic cells with three architectural patterns of disposition: (a) The "classic" pattern (57.5%), composed of a characteristic nested or organoid arrangement of cells, each surrounded by a distinct reticulin framework; (b) a "tubulocystic pattern" (6.3%) with numerous closely packed cystically dilated tubular structures; and (c) "mixed pattern" (36.2%), which had both the organoid and tubulocystic patterns. A gross or microscopic scar was noted in 53.8% cases, and histologically a distinctive myxoid and/or hyalinized stroma separated nests of cells. Generally, the nuclei of renal oncocytoma were round with uniform nuclear contours. Nearly half of the tumors had prominent nucleoli (42.5% had prominent nucleoli equivalent to Fuhrman's grade III or IV). Pleomorphism was absent in 50% of cases but was conspicuous in 12.5% of cases including foci of bizarre cells. Other atypical features included perinephric fat involvement (11.3%), renal parenchymal invasion not associated with desmoplasia (10%), and hemorrhage (31.3%). Renal oncocytoma by definition lacks areas of clear cell carcinoma, significant lesional necrosis, or conspicuous papillary formations. Ancillary features noted included normal-appearing renal tubules within the lesion (15%), intranuclear holes (20%), psammoma bodies (7.5%), and foam cells (7.5%). 15% of tumors were locally excised, and 85% resulted in radical nephrectomy. Mean follow-up of 7.6 years (range 15-200 months) showed no evidence of recurrence, metastasis, or death due to tumor. In conclusion, renal oncocytoma, herein described, is a benign neoplasm and therefore does not merit a nuclear grading scheme. It has unique histologic features including an organoid and tubulocystic architecture, myxoid or hyalinized stroma, and occasionally some atypical findings including nuclear pleomorphism, prominent nucleoli, and adjacent renal parenchymal and perinephric fat involvement.
289 citations
TL;DR: It is concluded that solid variants of papillary RCCs lack true papillae but have characteristic histologic, immunohistochemical, and genetic features.
Abstract: Papillary renal cell carcinomas (RCCs) traditionally have been defined histologically as tumors with at least 50% true papillae. However, these tumors also have characteristic immunohistochemical and genetic features that separate them from other RCCs. We identified six tumors composed of solid sheets of cells without true papillae but that otherwise resembled papillary RCCs, which we feel represent solid variants of papillary RCCs. All six tumors were primary lesions of the kidney, all were strongly reactive for epithelial membrane antigen, cytokeratin 7, and callus keratin, and all were negative for the high molecular weight keratin antibody 34BE12. Four of four tumors tested showed trisomies for chromosome 7, chromosome 17, or both by either cytogenetic analysis or fluorescence in situ hybridization. Four cases were composed of solid sheets of cells containing distinct micronodules that in some cases resembled abortive papillae. The cells composing the micronodules had abundant eosinophilic cytoplasm, open chromatin, and in some cases prominent nucleoli. The intervening cells had similar nuclei, but the amount of cytoplasm was variable. In three of these micronodular cases, multiple tumors diffusely replaced the kidney; in the fourth case two typical clear cell RCCs and a typical papillary RCC were also present in the same kidney, but the micronodular tumor was unifocal. The two remaining cases were solitary tumors consisting of solid sheets of cells forming ill-defined tubules. These cells had scant clear cytoplasm and small round to elongate nuclei with occasional nuclear grooves but only rare small nucleoli. Limited follow-up has shown no evidence of disease in any patient thus far. The differential diagnosis includes "renal adenoma," renal adenomatosis, metanephric adenoma, and clear/granular cell RCC. We conclude that solid variants of papillary RCCs lack true papillae but have characteristic histologic, immunohistochemical, and genetic features.
112 citations
TL;DR: It is suggested that genetic markers at the above‐mentioned chromosomal sites can predict the clinical outcome of non‐papillary RCCs.
Abstract: In this study, 105 non-papillary renal cell carcinomas (RCCs) have been examined for allelic loss at the chromosome 8p12-21.1, 9p21, and 14q24.2-qter regions, each by two highly polymorphic microsatellites. Loss of heterozygosity (LOH) was detected at both chromosome 8p and 9p in 33 per cent of the cases and at chromosome 14q in 45 per cent of the tumours. A correlation of variables such as size, grade, and stage of tumours with these specific genetic alterations showed that loss of chromosomes 8p and 9p, and especially loss of chromosome 14q regions, is significantly associated with a higher grade of tumour and the combined LOH at these chromosomal sites with advanced tumour stage. These genetic alterations did not show any correlation with the size of non-papillary RCCs. This study suggests that genetic markers at the above-mentioned chromosomal sites can predict the clinical outcome of non-papillary RCCs.
106 citations
TL;DR: FISH analysis of renal metanephric adenoma identified frequent chromosome 7 and 17 gain and sex chromosome loss, consistent with a clonal neoplastic disorder in which chromosomes 7, 17, X and Y are likely to be involved in the pathogenesis of this tumor.
92 citations
TL;DR: It is concluded that, in addition to distinct cytoarchitectural features, immunostaining patterns with antimitochondrial antibody 113-1 appear to be a useful discriminatory adjunct in the complex differential diagnosis of granular renal cell tumors.
Abstract: Abundant granular eosinophilic cytoplasm is a common feature of renal oncocytoma, chromophobe renal cell carcinoma, eosinophilic variant of papillary renal cell carcinoma, and the granular variant of clear cell renal cell carcinoma (RCC). Each of these entities has a unique architectural pattern and a distinctive molecular or cytogenetic profile. The chief reason for their distinction from one another is the difference in their biologic behavior. Careful and thorough light microscopic examination distinguishes most cases based on individual characteristic architectural and cytomorphologic features. However, precise characterization may be difficult in some cases because of overlapping morphologic features. We evaluated the antimitochondrial antibody 113-1 in an attempt to ascertain differences in immunostaining patterns in 57 cases of granular renal tumors, including 20 renal oncocytomas, 15 chromophobe RCCs, 13 granular variants of clear cell RCC, and nine eosinophilic variants of papillary RCC. Distinctive, and nearly exclusive, staining patterns were observed among the groups, with chromophobe RCC showing peripheral accentuation of coarse cytoplasmic granules (15 of 15), renal oncocytoma with diffuse and fine granularity (20 of 20), and granular variant of clear cell RCC with irregular cytoplasmic distribution of coarse granules (11 of 13). Staining was most intense in the eosinophilic variant of papillary RCC and was generally coarsely granular and diffuse. Staining patterns also differed in clear cell areas within chromophobe RCC and the granular variant of clear cell RCC. Although clear cells in the former group showed granular staining with peripheral accentuation, most of the clear cells in the latter lacked any staining. We conclude that, in addition to distinct cytoarchitectural features, immunostaining patterns with antimitochondrial antibody 113-1 appear to be a useful discriminatory adjunct in the complex differential diagnosis of granular renal cell tumors.
66 citations
TL;DR: It is concluded that metanephric adenoma has unique cytologic features that may allow distinction from other renal neoplasms on fine-needle aspiration material and in difficult cases, ancillary studies may be helpful.
Abstract: Metanephric adenoma is a recently described renal neoplasm. Because follow-up to date has been benign, accurate diagnosis on fine-needle aspiration material may be important for appropriate clinical management. A retrospective analysis of fine-needle aspiration material from two metanephric adenomas was performed. The aspirates were cellular and composed of many small to large tightly packed clusters of cells and short papillae. Occasional tubules, rosettes, and glomeruloid-like structures were seen. The tumor cells had very scant cytoplasm; small, oval to round, uniform, overlapping nuclei with fine delicate chromatin; and minute or absent nucleoli. Rare psammoma bodies were noted. Atypia, pleomorphism, necrosis, and mitoses were absent. Cytogenetic analysis showed normal karyotypes in both cases. The cytologic differential diagnosis included Wilms' tumor, renal-cortical adenoma, papillary renal cell carcinoma, and neuroendocrin, and metastatic tumors. We conclude that metanephric adenoma has unique cytologic features that may allow distinction from other renal neoplasms on fine-needle aspiration material. In difficult cases, ancillary studies may be helpful.
50 citations
TL;DR: The differential diagnosis includes Wilms' tumor, renal adenoma, papillary renal cell carcinoma, and metastatic tumors, and both immunohistochemistry and FISH may be of help in distinguishing some of these lesions.
Abstract: Metanephric adenoma is a recently described benign renal neoplasm with distinctive histologic features. The cytologic appearance and fluorescence in situ hybridization (FISH) studies of this tumor have not been described. We present a case from a 48-yr-old woman. Cytologically, the cells were arranged in tight, short papillae and loose sheets. The cells had scant cytoplasma, round monotonous nuclei with fine even chromatin and rare small nucleoli. Immunohistochemistry revealed no reactivity for epithelial membrane antigen (EMA), keratins (AE1/AE3, callus, 34BE12), or carcinoembryonic antigen (CEA). FISH showed a disomic pattern for chromosomes 7, 17, and for the chromosome 3 short arm. The differential diagnosis includes Wilms' tumor, renal adenoma, papillary renal cell carcinoma, and metastatic tumors. Both immunohistochemistry and FISH may be of help in distinguishing some of these lesions.
43 citations
Journal Article•
TL;DR: PRCCs represent a histologically and genotypically heterogeneous group of tumors, and if PRCAs consistently exhibit +7, +17, and -Y, it is uncertain whether PRCCs always evolve directly from such lesions.
TL;DR: The clinical and pathologic features of collecting duct carcinoma are reviewed based on the reported cases and place them into perspective with the putative widening histologic spectrum.
Abstract: Collecting duct carcinoma is a distinctive hislologic subtype of renal cell carcinoma which has recently gained acceptance as a clinicopathologic entity. Approximately 50 cases have been described, with the largest series to date reports 12 cases. Based on the literature experience certain key characteristics regarding this tumor emerge, including predilection for younger age, epicenter in renal medulla, high grade nuclear features with desmoplasia and mucin production, and aggressive clinical course. Origin from the collecting duct is based on the observation of dysplastic changes in the adjacent collecting ducts as well as immunohistoehemical reactivity for Ulex europaeus agglutinin-1 lectin, peanut lectin agglutinin and high molecular weight cytokeratin. Recently there is evidence that the histologic spectrum of collecting duct carcinoma may be wider than that published. In this article we review the clinical and pathologic features of collecting duct carcinoma based on the reported cases and place them into perspective with the putative widening histologic spectrum.
TL;DR: Analysis of paired normal and tumor DNA obtained from short‐term cultures of 104 non‐papillary RCCs with 29 microsatellite markers uncovered multiple hemi‐ and homozygous interstitial deletions at chromosome 3p, providing evidence for terminal deletion.
Abstract: Multiple hemi- and homozygous interstitial deletions at chromosome 3p have been found in different types of cancer, including non-papillary renal cell carcinoma (RCC). To determine the frequency and size of deletions, we have analyzed paired normal and tumor DNA obtained from short-term cultures of 104 non-papillary RCCs with 29 microsatellite markers covering the entire chromosome 3p region. Deletion mapping provided evidence for terminal deletion, with the most distal breakpoint between loci D3S1606 and D3S3666 in 94 cases, whereas constitutional heterozygosity was retained at all loci in 4 RCCs. In 6 cases, interstitial deletions were detected. Deletion mapping detected the smallest overlapping region between loci D3S3666 and D3S1560, which corresponds to an approx. 55 cM genetic distance.
TL;DR: The constitutive fragile site at chromosomal band 3p14.2, FRA3B, is the most active common fragile site in the human genome and localized aphidicolin-induced breakpoints to two distinct clusters, separated by 200 Kb, in FRA1B, demonstrating that FRA2B does play a role in chromosome breakage and loss in RCC.
Abstract: The constitutive fragile site at chromosomal band 3p14.2, FRA3B, is the most active common fragile site in the human genome. We have localized aphidicolininduced breakpoints to two distinct clusters, separated by 200 Kb, in FRA3B (Paradee et al., 1996). Sequence analysis of these regions identified two polymorphic microsatellite markers immediately adjacent to each of these breakpoint clusters. In this report we have used these two new microsatellites and 14 additional 3p microsatellites to analyse chromosome 3p breakage and loss in 94 sporadic RCC samples, including nonpapillary, papillary and oncocytomas. We have found heterozygous loss of 3p14 sequences in 460% of the RCC samples, including both clear cell and papillary renal cell carcinomas. We have found frequent breakage in the region immediately surrounding FRA3B, demonstrating that FRA3B does play a role in chromosome breakage and loss in RCC. In contrast to other reports, 450% of the papillary tumors also showed LOH of 3p markers. We also observed microsatellite instability (MIN) with most of the tested markers in seven of eight oncocytomas and one of 69 clear cell carcinomas. The MIN in some oncocytomas was of the RER+ (replication error) type I phenotype. None of the five 3p14.2 markers detected any homozygous deletions in tumor samples, but 69/94 (73%) of the tumors had LOH for the region, which includes the recently identified FHIT gene.
TL;DR: The pathomorphologic and immunohistochemical features suggested that it is possible to divide PRCCs into 2 types and thatPRCCs in type 1 confer an favorable prognosis and the results supported the possibility of adenoma-carcinoma sequence.
Abstract: BACKGROUND Papillary renal cell carcinomas (PRCCs) are genotypically distinct from nonpapillary renal cell carcinomas. METHODS We studied the clinical, pathomorphological, immunohistochemical features in 34 PRCCs and 7 papillary renal adenomas. Immunohistochemical studies were performed using lectins and antibodies against cytokeratins, epithelial membrane antigen and Tamm-Horsfall protein. RESULTS PRCCs were divided into two types based on the features of tumor cells and vascular stalks. Fifteen PRCCs displayed small cuboidal cells with basophilic cytoplasm and thin, short vascular stalks (type 1, micropapillary). Nineteen PRCCs displayed large columnar cells with eosinophilic cytoplasm and edematous or fibrous thick stalks (type 2, macropapillary). Infiltration of foam cells was more common in type 1. Co-existence of papillary renal adenomas was recognized in three cases among type 1, but in only case among type 2. In type 1, a male to female predominance was evident (13:2), and the majority of tumors in type 1 were in lower nuclear grade and lower stage. The 5-year survival rates of patients in type 1 and 2 were 87% and 46%, respectively. Immunohistochemically, 15 (100%) cases in type 1 were diffusely positive for cytokeratin 7 (CK7), 15 (100%) were positive for cytokeratin 19 (Progen 19) and 11 (73%) were positive for dolichos biflorus agglutinin (DBA). In type 2, only 4 (19%) cases focally stained for CK7, 10 (53%) were stained for Progen 19 and only 2 (10%) were positive for DBA. The staining pattern in papillary renal adenoma was similar to that of type 1, all cases were positive for CK7, four of five cases (80%) were positive for Progen 19 and five of seven cases (71%) were positive for DBA. CONCLUSION The pathomorphologic and immunohistochemical features suggested that it is possible to divide PRCCs into 2 types and that PRCCs in type 1 confer an favorable prognosis. Furthermore, our results supported the possibility of adenoma-carcinoma sequence.
01 Jan 1997
TL;DR: The cytogenetic features of renal and bladder cancers have been defined only over the past 10 yr, but it is already clear that these parameters have substantial diagnostic and prognostic relevance.
Abstract: The cytogenetic features of renal and bladder cancers have been defined only over the past 10 yr, but it is already clear that these parameters have substantial diagnostic and prognostic relevance. In fact, the clinical ramifications of chromosome aberrations in genitourinary tumors are in many respects a paradigm for the potential uses of cytogenetics in other types of solid tumors. Very characteristic chromosome aberrations have been identified in different histologic types of renal cancer, and these distinctive cytogenetic profiles are discussed at some length in this chapter (Table 1). Of particular note are the ubiquitous deletion of chromosome 3 short-arm material in nonpapillary clear cell and granular carcinomas (1–3), extra copy number—particularly trisomies—of several chromosomes in renal adenomas and papillary carcinomas (4–7), and hypodiploid karyotypes in chromophobe carcinomas (8). Likewise, many of the common pediatric renal tumors contain characteristic cytogenetic aberrations. Deletion of 11p is a very well-studied and well-publicized aberration in Wilms tumors, but several other aberrations are more frequent and might have greater prognostic relevance (9–13).