Showing papers on "Papillary renal cell carcinomas published in 2010"

Usefulness of diffusion-weighted imaging in the evaluation of renal masses.

Abstract: OBJECTIVE. The objective of our study was to assess the value of diffusion-weighted imaging in differentiating among the various subgroups of renal masses.MATERIALS AND METHODS. This retrospective study measured the apparent diffusion coefficients (ADCs) of renal masses. Malignant lesions were confirmed with surgical pathology results. Benign cystic lesions were stable without treatment for a minimum follow-up of 24 months.RESULTS. There were 20 and 22 patients, respectively, with benign lesions (three abscess, 31 cysts) and malignant lesions (17 clear cell, five papillary, one chromophobe, and two transitional cell cancers). The malignant lesions were larger than the benign lesions (mean diameter, 4.2 vs 2.6 cm, respectively; p = 0.01, Student's t test). The ADC values of the benign lesions were significantly higher than those of the malignant lesions (mean, 2.72 vs 1.88 × 10–3 mm2/s; p < 0.0001). The ADCs of the 31 benign cysts were significantly higher than those of the seven cystic renal cancers (2.77...

Clear cell tubulopapillary renal cell carcinoma: a study of 36 distinctive low-grade epithelial tumors of the kidney.

Abstract: Recently several low-grade renal cell tumors, distinct from those recognized by the 2004 World Health Organization classification of renal tumors, have been described. These tumors had similar clinicopathologic features, being low-stage tumors with cystic, tubuloacinar, and/or papillary architecture. The tumor cells were low grade with variable amounts of clear cytoplasm that was positive for cytokeratin 7 (CK7), but negative for CD10. Genetic changes characteristic of clear cell or papillary renal cell carcinoma were not seen in these tumors. We investigated the morphologic, immunohistochemical, and genetic features of 36 additional tumors. Immunohistochemistry was carried out for CK7, carbonic anhydrase 9, α-methylacyl-CoA racemase, CD10, TFE-3, and desmin. Interphase fluorescence in situ hybridization was carried out with centromeric probes for chromosomes 3, 7, 17, and a subtelomeric probe for 3p25. Sequencing of von Hippel-Lindau gene and analysis of the methylation status of the promoter region was also carried out in 2 tumors. Thirty-six tumors from 33 patients (mean age: 60.4 , range: 26 to 88; 17 men and 16 women) were studied. Three patients had bilateral tumors and 1 patient had von Hippel-Lindau disease. Follow-up was available in 60% (20/33) of the patients for a mean of 27.4 (range 1 to 85) months. No patient had evidence of the disease after surgery except for the patient with von Hippel-Lindau disease, who was alive with stable disease in the contralateral kidney. All 36 tumors were small (mean size 2.4 cm; range 0.9 to 4.5 cm) and low stage (pT1). The majority was cystic and had prominent fibrous capsule and stroma. The tumors were composed of variable amount of cysts, papillae, tubules, acini, and solid nests. The most characteristic histologic features were branching tubules and acini and anastomosing clear cell ribbons with low-grade nuclei. All tumors were strongly positive for CK7 and variably positive for CA9, but largely negative for CD10, and negative for α-methylacyl-CoA racemase and TFE-3. All but 1 tumor had no gains of chromosomes 7 and 17 and deletion of 3p. Only 1 tumor had low copy number gains of chromosomes 7 and 17. VHL gene mutation and promoter methylation were negative in 2 tumors analyzed. We show that these tumors, which we term as "clear cell tubulopapillary renal cell carcinoma," constitute a unique subtype in the spectrum of renal epithelial neoplasia based on their characteristic morphologic and immunohistochemical features.

Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer

Abstract: Background Fibronectin 1 (FN1) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of FN1 in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.

Reduced Notch Signaling Leads to Renal Cysts and Papillary Microadenomas

Abstract: The formation of proximal nephron segments requires canonical Notch2 signaling, but other functions of Notch signaling during renal development are incompletely understood. Here, we report that proximal tubules forming with reduced Notch signaling, resulting from delayed conditional inactivation of Notch1 and/or Notch2, are prone to cyst formation and tubular epithelial stratification. Conditional inactivation of the DNA binding factor RBP-J, which mediates Notch signaling, also resulted in multiple congenital cysts arising from the proximal tubule. Moreover, a few stratified foci/microadenomas containing hyperproliferative cells, resembling precursors of papillary renal cell carcinoma, formed in these proximal tubules. Epithelial stratification correlated neither with reduced expression of the transcriptional regulator of ciliary proteins TCF2/HNF1β nor with loss of apical-basal polarity. Instead, Notch signaling helped to restrict the orientation of epithelial mitotic spindles to a plane parallel to the basement membrane during nephron elongation. In the absence of Notch, random spindle orientation may explain the epithelial stratification and cyst formation. Furthermore, post hoc analysis of human class 1 papillary renal cell carcinoma revealed reduced Notch activity in these tumors, resulting from abundant expression of a potent inhibitor of canonical Notch signaling, KyoT3/FHL1B. In summary, these data suggest that canonical Notch signaling maintains the alignment of cell division in the proximal tubules during nephrogenesis and that perturbations in Notch signaling may lead to cystic renal disease and tumorigenesis.

Thyroid cancer of follicular cell origin in inherited tumor syndromes.

Abstract: Well-differentiated thyroid cancer accounts for 95% of thyroid malignancies. In contrast to medullary thyroid carcinoma, in which about 25% are familial, only 5% of follicular cell-derived thyroid carcinomas are a component of a familial cancer syndrome. The familial follicular cell-derived tumors or nonmedullary thyroid carcinoma encompass a heterogeneous group of diseases, and are classified into 2 distinct groups: syndromic-associated tumors, occurring in syndromes in which nonmedullary thyroid carcinomas are the predominant tumor encountered, and nonsyndromic tumors, those occurring in tumor syndromes in which thyroid involvement is a minor component. The first group, syndromic-associated tumors, includes phosphase and tensin (PTEN)-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis/Gardner syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome. Other syndromes, as McCune Albright syndrome, Peutz-Jeghers syndrome, and Ataxia-teleangiectasia syndrome may be associated with the development of follicular cell-derived tumors, but the link is less established than the above syndromes. The syndromic-associated tumors are the focus of this review. The second group of familial follicular cell-derived tumors syndromes or nonsyndromic tumors, in which nonmedullary thyroid carcinomas are the major findings, include pure familial papillary thyroid carcinoma, with or without oxyphilia, familial papillary thyroid carcinoma with papillary renal cell carcinoma, and familial papillary thyroid carcinoma with multinodular goiter. This review will discuss the clinical and pathological findings of the patients with familial syndrome-associated tumors: PTEN-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome.

Small (≤4 cm) cortical renal tumors: characterization with multidetector CT

Abstract: To determine if the pathology of small (≤4 cm) solid renal tumors can be predicted from findings on multidetector CT. This retrospective study included 46 patients (median age, 60 years; range, 32–91 years; 27 males, 19 females) with 47 tumors who underwent triphasic renal CT with pathology correlation. Two radiologists reviewed CT studies blinded to pathology results and recorded the morphologic and enhancement features of the tumors. The 47 tumors (median diameter, 2.5 cm; range, 0.6–4.0 cm) included: 26 (55%) clear cell renal cell carcinomas; 9 (19%) oncocytomas; 7 (15%) papillary renal cell carcinomas; 2 (4%) chromophobe renal cell carcinomas; 2 (4%) inflammatory pseudotumors; and 1 (2%) angiomyolipoma with minimal fat. Amongst the three commonest tumors, heterogeneity was seen in 23/26 (88%) clear cell renal cell carcinomas, 6/9 (67%) oncocytomas, and 2/7 (29%) papillary renal cell cancer. Median (minimum–maximum) absolute nephrographic phase enhancement (nephrographic minus unenhanced phase) was: clear cell renal cell carcinomas 65 HU (34–120), oncocytomas 80 HU (51–111), and papillary renal cell carcinomas 16 HU (7–32). Absolute nephrographic phase enhancement of ≤32 HU distinguished papillary renal cell carcinomas from clear cell renal cell carcinomas and oncocytomas.

Sunitinib in papillary renal cell carcinoma (pRCC): Results from a single-arm phase II study.

Abstract: 4604 Background: Frontline sunitinib has been shown to produce a high response rate (RR), and improved progression-free survival (PFS) and overall survival (OS) in patients (pts) with clear cell RC...

The application of cytogenetics and fluorescence in situ hybridization to fine-needle aspiration in the diagnosis and subclassification of renal neoplasms.

Abstract: BACKGROUND: Percutaneous fine-needle aspiration (FNA) cytology is an important diagnostic test for the evaluation and management of selected renal masses. Cytogenetic analysis of cytology specimens can serve as an adjunct for precise classification because certain tumors are associated with specific chromosomal aberrations. This study summarizes our experience with the application of conventional cytogenetics and fluorescence in situ hybridization (FISH) to renal FNA specimens. METHODS: All percutaneous renal FNAs performed during 2005 through 2008 were identified from the electronic pathology database. Results of cytogenetic and FISH analyses were correlated with the final diagnoses of the renal FNAs. RESULTS: A total of 303 renal FNAs were performed. During an onsite assessment, a portion of the cytology specimen was allocated for cytogenetic analysis in 74 cases. Karyotypic analysis or FISH was successful in 44 (59%) of these. Characteristic chromosomal abnormalities were observed in 27 cases. In 17 cases, a karyotype revealed a combination of trisomies/tetrasomies and in another 5 cases, FISH revealed trisomy 7 and 17, both of which are consistent with papillary renal cell carcinoma (RCC). Two cases showed 3p deletions consistent with clear cell RCC. Trisomy 3 was observed in 1 case of clear cell RCC. Monosomy 1 and 17 was observed in a case of papillary RCC comprised oncocytic cells. In 1 case of primary renal synovial sarcoma, FISH revealed a rearrangement at the SYT locus (18q11.2). CONCLUSIONS: Renal FNA specimens are amenable to analysis by cytogenetics and FISH in the diagnosis and subclassification of renal neoplasms. Cancer (Cancer Cytopathol) 2010;118:137–45. V C 2010 American Cancer Society.

The utility of PAX-2 and renal cell carcinoma marker immunohistochemistry in distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with papillary features.

Abstract: PAX-2, a homeogene expressed during kidney development, has been studied as a marker of renal origin in both primary and metastatic clear cell renal cell carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24 papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%) were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10 (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%) uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas, 1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%) choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features, and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There is significant overlap between the expressions of these markers in PRCC and NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC and may prove useful in the initial work up of metastases of unknown primary. PAX-2 and RCCma immunohistochemistry should be interpreted with caution in papillary neoplasms, with particular attention to the possibility of ovarian and uterine papillary serous carcinomas, which can express both PAX-2 and RCCma.

Renal cell carcinoma with mixed features of papillary and clear cell cytomorphology: a fluorescent in situ hybridization study

Abstract: We performed fluorescent in situ hybridization (FISH) to investigate the numeric change of chromosomes 7, 17, and Y and loss of chromosome 3p in “papillary renal cell carcinomas (RCC) with extensive clear cell changes (CCC)” Consecutive cases of RCC over a 12-year period were reviewed to identify “papillary RCC with extensive CCC” Immunostaining for cytokeratin 7 and alpha-methylacyl-CoA racemase (AMACR) and FISH for chromosomes 7, 17, Y, and 3p were applied Of the total of 521 RCC retrieved, there were 49 RCC with papillary architecture and clear cell areas that could be divided into: Group 1 (12 cases), typical clear cell RCC with focal areas of papillary formation; Group 2 (28 cases), focal typical papillary RCC having papillary architecture with extensive CCC; and Group 3 (nine cases), RCC with an admixture of eosinophilic/clear cytoplasm and solid/papillary architecture Group 1 showed negative immunoreactivity for CK7 and AMACR and absence of numeric chromosomal gain or loss of chromosomes 7/17 and Y Groups 2 and 3 showed variable reactivity for CK7 and AMACR Tumors in group 2 and five in group 3 showed trisomies of chromosomes 7 and/or 17 with or without loss of chromosome Y Loss of small arm 3p was observed in groups 1 and 3 but not in group 2 tumors In conclusion, papillary RCC may show phenotypical CCC mimicking clear cell RCC In a small number of cases with mixed histopathological features, FISH is helpful in subtyping RCC

Chromosomal abnormalities of clear cell renal cell carcinoma: frequent gain of chromosome 7.

Abstract: Gain of chromosome 7 is well known to be a characteristic abnormality of papillary renal cell carcinoma (RCC). The purpose of the present study was to perform cytogenetic analysis of G-band karyotype in 16 clear cell RCC obtained from nephrectomy. The age of patients ranged from 50 to 79 years and the tumor size in largest dimension ranged from 1.8 to 6.2 cm. As a result, the structural abnormality of chromosome 3 was most frequently observed (eight clones). Loss of chromosome 3 and gain of chromosome 7 followed (four clones). Among four clones showing gain of chromosome 7, two were associated with the abnormality of chromosome 3 and the remaining two were devoid of the abnormalities of chromosome 3. In addition, none of all four tumors showing gain of chromosome 7 demonstrated any foci of papillary growth pattern. The present study shows that gain of chromosome 7 is not exclusive to papillary RCC, but it can be found in clear cell RCC as well, and this finding may represent a diagnostic pitfall in distinguishing clear cell RCC from papillary RCC.

Type 2 and clear cell papillary renal cell carcinoma, and tubulocystic carcinoma: a unifying concept.

Abstract: The clinical and pathological features of multiple different renal neoplasms arising in a setting of end-stage renal disease in a 72-year-old male are described. The kidney showed features of renal oncocytosis with multiple oncocytomas, hybrid tumours and chromophobe renal carcinoma. In addition, the kidney contained a type 2 papillary renal cell carcinoma, clear cell papillary and cystic renal cell carcinoma, and tubulocystic carcinoma. The occurrence of these three tumours in a setting of end-stage kidney disease is unique and suggests a common pathogenesis. Immunostaining of these tumours further suggests they are derived from similar stem cells which show immunophenotypic features of both the proximal and distal nephron.

Metanephric adenoma of the kidney: an unusual diagnostic challenge

Abstract: Although metanephric adenoma (MA) is a rare, benign neoplasm of epithelial cells, it is often difficult to distinguish this entity from other malignant neoplasms preoperatively. We report a case of a large renal mass for which preoperative diagnosis was indeterminate, with the differential diagnosis including Wilm’s tumor, MA, and papillary renal cell carcinoma (PRCC). Accurate postoperative differentiation of MA from PRCC is critical because adjuvant therapy is considered after surgical resection of PRCC tumors.

A unique renal cell carcinoma with features of papillary renal cell carcinoma and thyroid-like carcinoma: a morphological, immunohistochemical and genetic study.

Abstract: described, usually in association with inflammatory bowel disease, none of these cases were associated with inflammation and endocrine cell hyperplasia. Gastric enterochromaffin-like (ECL) carcinoid tumours arise sporadically or in association with ECL-cell hyperplasia induced by hypergastrinaemia. Type 1 neoplasms due to autoimmune gastritis in association with pernicious anaemia are the most common of these hypergastrinaemia-driven tumours. As features of atrophic gastritis, including intestinal metaplasia, endocrine cell hyperplasia, inflammation and mild, low-grade dysplasia, were present in the adjacent stomach these would appear to be the obvious histogenetic factors in this case. Because atrophic gastritis is also a factor in the aetiology of gastric adenomas, and as endocrine cells may form a component of gastrointestinal adenomas, the two components might occur not unexpectedly under these circumstances. In addition, while none of the gastric or colonic lesions have been associated with metastases, the single case reported in the terminal ileum had liver, peritoneal and lymph node metastases of the carcinoid component, highlighting the significance of this component. However, the well-differentiated Grade G1 endocrine component of this mixed tumour has a low propensity to metastize with the conservative treatment indicated. John D Coyne Barry O’Connor Department of Pathology, Royal Liverpool Hospital, Prescot Street, Liverpool, L7 8XP, UK and Shanakiel Hospital, Cork, Co. Cork, Ireland

Strength of molecular cytogenetic analyses for adjusting the diagnosis of renal cell carcinomas with both clear cells and papillary features: a study of three cases

Abstract: Histological features are usually sufficient for providing an accurate diagnosis of renal cell carcinomas (RCC). However, the morphological appearance might sometimes be misleading. For instance, RCC with papillary areas and extensive clear cell changes may be difficult to classify either as clear cell renal carcinoma or as papillary renal cell carcinoma (pRCC). We used the combination of immunohistochemistry, conventional cytogenetics, fluorescence in situ hybridization (FISH), bacterial artificial chromosomes comparative genomic hybridization arrays and high-density single nucleotides polymorphism arrays (SNP arrays) to characterize three cases of RCC showing a predominant cytology of cells with clear cytoplasm and variable amounts of papillary areas. In accordance with the 2004 World Health Organization (WHO) classification, we initially assessed the diagnosis of clear cell RCC for one of the cases and unclassified RCC for the two remaining cases. However, because of a strong immunohistochemical labeling for α-methylacyl-CoA racemase, as well as the presence of a gain of chromosomes 7 and 17, we concluded that two of these tumors were actually pRCC. As for the third case, because of the presence of both pCCR and ccCCR molecular cytogenetic aberrations, including gains of chromosomes 7 and 17, loss of chromosome Y and whole chromosome 3 loss of heterozyosity (isodisomy), the final diagnosis was hybrid tumor cc-pRCC, so-called “unclassified RCC” according to the WHO classification. Our observations demonstrate the necessity to use immunohistochemical and cytogenetic tools in all cases of RCC showing unusual features. The combination of FISH and SNP arrays is prevailing for characterizing cases with hybrid features.

The role of surgery in clinical management of patients with metastatic papillary renal cell carcinoma.

Abstract: Patients with metastatic papillary renal cell carcinoma (RCC) show special clinical behavior compared to patients with other histologic subtypes of RCC. This study aimed to assess the relevance of surgical and systemic options used in treatment of these patients prior to the recent era of targeted therapies. Retrospectively, we assessed clinical data of 61 patients with metastatic papillary RCC who were treated at eight centers in Germany. Median follow-up was 20 (range 1–114) months and median age at time of diagnosis was 62 (range 24–85) years. Men were affected predominantly (50/61; 82%). Twenty-one patients (34%) showed metastases at time of diagnosis. In the remaining 40 patients, median time to development of metastases was 30.4 (range 3–143; mean 16.5) months. Sites of metastases were lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%), and local recurrence (17; 28%). Others sites of disease were brain metastases (6 patients/10%), peritoneal carcinosis (5 patients/8%), and others. A surgical approach with potentially curative intention was performed primarily in 11 patients (18%). 31 patients received an immuno- (interferon-α ± interleukin-2) or immunochemotherapy as first line treatment for metastatic disease. Overall, 42/61 patients (69%) received systemic therapy. Supportive care only was performed in 12 patients (20%) because of poor performance status. Median overall survival after diagnosis of metastatic disease was longer than 48 months in patients with tumor resection (n = 11) compared to 13.0 ± 4.3 months 95% CI 4.5–21.5 (n = 42) months in patients without surgical approach. Complete resection of metastases represents a valid option in management of patients with relapsing or metastatic papillary RCC.

Solid Variant of Papillary Renal Cell Carcinoma With Spindle Cell and Tubular Components

Abstract: The solid variant of papillary renal cell carcinoma, when strictly defined as a tumor in which no true papillae can be identified, is extremely rare, with only a few cases reported in the literature. This tumor is characterized histologically by solid sheets of cells without true papillae; nevertheless, immunohistochemical and genetic analysis supports the classification of this tumor as a variant of papillary renal cell carcinoma. We report a case of solid variant of papillary renal cell carcinoma affecting a young man and provide histologic and clinical follow-up data, adding an additional case of this extremely rare pathology to the literature. In addition, we describe the first case, to our knowledge, of a solid variant of papillary renal cell carcinoma to contain a high-grade (sarcomatoid) spindle cell component.

Metastatic renal cell carcinoma complicated with diffuse alveolar hemorrhage: a rare adverse effect of sunitinib

Abstract: We report the case of a 67-year-old man with metastatic papillary renal cell carcinoma (RCC) who developed bloody sputum after the administration of sunitinib. Chest computed tomography revealed diffuse ground-glass opacity lesions, and bloody bronchoalveolar lavage fluid was obtained by flexible bronchoscopy. The abnormal shadows promptly regressed after withdrawal of sunitinib. In four cycles of sunitinib treatment, he suffered from controllable diffuse alveolar hemorrhage. Finally, he died of respiratory failure 8 months after onset. This is the first case report of diffuse alveolar hemorrhage as an adverse effect of sunitinib in metastatic papillary RCC. Care should be taken with pulmonary hemorrhage in the use of anti-angiogenesis agents in not only squamous cell lung cancer, but also metastatic lung tumors.

Changes in Cell-Surface Peptidase Activity in Papillary Renal Cell Carcinoma

Abstract: Background: Renal cancer is one of the ten most common malignant tumours in humans and its histological classification, best clinical management and treatment strategies are continuously debated. Roughly 10% of renal carcinomas are papillary renal cell carcinomas (RCCs), a histologically well characterized tumour subtype that is linked to alterations on chromosomes 7 and 17. Peptidases are