Papillary Renal Cell Carcinoma Subtypes Research Articles

Morphological subtyping of papillary renal cell carcinoma: Clinicopathological characteristics and prognosis

The aim of the study was to evaluate the clinicopathological and prognostic significance of morphological subtyping of papillary renal cell carcinoma (PRCC). The patients treated for renal cell carcinoma in our department from January 1985 to March 2006 were evaluated retrospectively. Thirty-two of the 591 patients (5.4%) were diagnosed with PRCC. To determine the prognostic factors, we re-evaluated the pathological stage according to the 2002 TNM classification of malignant tumors, and the tumor type of renal cell carcinoma according to the 2004 World Health Organization histological classification. Survival was analysed using the Kaplan-Meier method and the log-rank test. The age at diagnosis ranged from 33 to 81 years (median: 63 years old) and the follow-up time after the surgical treatment ranged from 4 to 191 months (median: 54 months). The cancer-specific 5-year survival rate of the 32 PRCC patients was 74%. Pathologically, 17 patients (53%) and 15 patients (47%) were diagnosed with type 1 and type 2 PRCC, respectively. The type 2 PRCC patients had a significantly higher tumor grade (P < 0.001), a more advanced stage (P < 0.001), more frequent vascular invasion (P < 0.001), and a higher sarcomatoid component (P = 0.038) compared to the type 1 PRCC patients. The type 1 patients had a better cancer-specific 5-year survival rate than the type 2 patients (94% vs 50%) (P = 0.008). The morphological subtyping of PRCC is significantly associated with clinicopathological features and the prognosis. Our results provide evidence of the clinical utility of dividing PRCC into two subtypes.

Survival Analysis of 130 Patients with Papillary Renal Cell Carcinoma: Prognostic Utility of Type 1 and Type 2 Subclassification

To evaluate the prognostic significance of subtyping papillary renal cell carcinoma (PRCC) into type 1 and type 2 tumors. From 1995 to 2004, 1358 patients underwent surgery for renal cell carcinoma, of whom 130 had PRCC alone on the specimen. The tumor characteristics, including their subtype, were analyzed; small basophilic cells and large eosinophilic cells were defined type 1 and type 2 tumors, respectively. Survival analyses were performed retrospectively. Of the 130 patients (110 men and 20 women, mean age 60.6 +/- 15.3 years) with PRCC, 102 underwent radical nephrectomy (78.4%) and 28 underwent partial nephrectomy (21.6%). The median tumor size was 4.5 cm (range 0.5 to 21). The comparison of the 68 (52.3%) type 1 PRCCs and 62 (47.7%) type 2 PRCCs revealed that type 2 tumors were associated with a greater stage and grade and microvascular invasion significantly (P <0.001) more often. The median follow-up was 48 months (range 2 to 111). Of the 130 patients, 22 died of cancer-specific causes, 5 (7%) with type 1 and 17 (27%) with type 2 tumors (P = 0.002). The overall and disease-free survival rate was 89% and 92% in type 1 tumors and 55% and 44% in type 2 tumors, respectively. Univariate analysis identified tumor type, stage (P <0.001), grade (P <0.001), microvascular invasion (P <0.001), an absence of foam cells (P <0.001), the presence of sarcomatoid cells (P = 0.001), and tumor necrosis (P = 0.007) as prognostic factors. Multivariate analysis retained tumor type (P = 0.034) and TNM stage (P <0.001). The results of our study have shown that histologic subtyping of PRCC allows for the identification of an independent prognostic factor.

Are Small Renal Tumors Harmless? Analysis of Histopathological Features According to Tumors 4 Cm or Less in Diameter

Small renal tumors detected incidentally are considered to have less aggressive potential. This assumption is mainly based on the low tendency to increase in size on serial imaging studies, but histopathological parameters of progression in larger patient series are scant. We reviewed data of 287 tumor bearing kidneys in which solid tumors 4 cm or less in diameter were detected by cross-sectional imaging and subsequently removed surgically. Tumor size as documented by preoperative computerized tomography was correlated to histological diagnosis, and in cases of malignancy correlated to tumor type, pathological TNM stage and nuclear (Fuhrman) grade. With multifocal lesions the largest single tumor was considered the reference lesion but multifocality was also considered a separate parameter. At a mean tumor diameter of 2.94 +/- 0.87 cm 65 (22.6%) tumors were 2 cm or less, 103 (35.9%) were 2.1 to 3.0 cm and 119 (41.5%) were 3.1 to 4 cm in diameter. A total of 56 (19.5%) tumors were benign with no correlation to tumor size (Pearson test p = 0.660). Renal cell cancer was found in 227 (79.1%) patients with 159 (70.0%) clear cell, 47 (20.7%) papillary, 11 (4.8%) chromophobe and 10 others with no correlation to tumor diameter. Of the kidneys 31 (13.6%) had multifocal renal cell carcinoma, with a significant correlation to larger tumor diameter (linear regression p = 0.048) and papillary renal cell carcinoma subtype (linear regression p = 0.018). Two (4.2%), 4 (5%) and 25 (25.5%) cases of renal cell carcinoma 2 cm or less, 2.1 to 3 cm and 3.1 to 4 cm in diameter had Fuhrman grade G3/4, respectively (Pearson p = 0.0007). Advanced stage (pT3a or greater) was documented in 2 (4.2%), 12 (14.9%) and 35 (35.7%) cases for the same categories, respectively (p = 0.0023). Whereas distant metastases were diagnosed in only 4 patients with renal cell carcinoma with tumors 3 cm or less, distant metastases were in 10 (8.4%) patients with tumors 3.1 to 4 cm (p = 0.045). The aggressive potential of small renal cell carcinoma increases dramatically beyond a tumor diameter of 3 cm. Given the difficulty in measuring tumor diameters reliably with sequential imaging studies, the threshold for selecting patients for a surveillance strategy should be set well under this parameter.

De novo concurrent papillary renal cell carcinoma and angiomyolipoma in a kidney allograft: evidence of donor origin

In the general population, renal cell carcinoma (RCC) is a relatively common neoplasm; however, the papillary RCC subtype is infrequent and represents only 10 to 15% of all RCC. Angiomyolipoma is a well-known common benign tumor. The occurrence of RCC in association with angiomyolipoma is a rare event, with only approximately 50 cases reported in the nontransplantation setting. In transplant recipients, RCC can develop in native kidneys, but its occurrence "de novo" in the renal allograft is very rare with an estimated incidence of less than 0.5%. We report here the case of a 39-year-old woman who underwent cadaveric renal transplantation in 1990. No lesion was observed in the allograft during the pre- and perioperative period or on early postoperative ultrasounds. No graft rejection occurred under a standard triple immunosuppressive therapy. Thirteen years later, during a routine ultrasonography, 2 solid masses were discovered in the allograft, both of them richly vascularized. She underwent allograft nephrectomy and the histologic findings revealed that one of the tumors was a chromophilic (type 1) papillary RCC (2.5 cm in diameter) and the other, an angiomyolipoma (1.5 cm). Microsatellite analysis of the allograft, as compared with the recipient peripheral blood leukocytes, demonstrated that the 2 tumors (1 malignant and 1 benign) were of donor origin. To our knowledge, this is the first report of de novo concurrent papillary RCC and angiomyolipoma in a renal allograft.

Review of papillary renal cell carcinoma with focus on clinical and pathobiological aspects.

Recent studies have shown that papillary renal cell carcinoma (RCC) is clinically and genotypically a distinct entity. Papillary RCCs account for about 10-15% of renal parenchymal neoplasms. Macroscopically, the cut surface is yellow or brown in color and large tumors frequently show cystic change. Hemorrhage and necrosis are common. Histologically, Delahunt and Eble have classified papillary RCCs into type 1 (small cells, single layer) and type 2 (large cells, pseudostratification) according to the cytoplasmic volume and thickness of the lining cells. In chromosomal analysis, gain of chromosomes 7 and 17, loss of Y chromosome and additional gains (chromosome 3q, 8p, 12q, 16q and 20q) are frequently found in type 1 papillary RCCs, but the chromosomal aberration of type 2 papillary RCCs seems to be more heterogenous than that of type 1 papillary RCCs. Mutations of MET proto-oncogenes in some cases of both hereditary and sporadic papillary RCCs have recently been detected. Furthermore, all hereditary and sporadic papillary RCCs with MET proto-oncogene show type 1 histological features. Type 1 papillary RCCs generally seem to have a favorable prognosis, but type 2 tumors have a worse prognosis than do type 1 tumors. Papillary RCCs with involvement of the X chromosome and cancer syndrome with predisposition to cutaneous/uterine leiomyomas and papillary RCCs, the histological features of which are basically different from those of usual papillary RCCs, have also been recently reported. Since papillary RCCs seem to constitute clinically, histologically, and even genetically more heterogenous groups than previously thought, further investigations are needed to characterize the subtype of papillary RCC.

Chromosomal Imbalances in Papillary Renal Cell Carcinoma: Genetic Differences between Histological Subtypes

Papillary renal-cell carcinoma (RCC) is a renal carcinoma variant with distinct gross, microscopic, and cytogenetic features. Recently, a type 1 (pale cytoplasm, small-cell) and a type 2 (eosinophilic cytoplasm, large-cell) subtype of papillary RCC have been described. Chromosomal alterations associated with these tumor types were examined in 25 papillary RCCs by comparative genomic hybridization. Relative copy number gains were frequently detected at chromosomes 7p (56%), 7q (44%), 12q (28%), 16q (32%), 17p (56%), 17q (76%), and 20q (32%). Chromosomal regions that were most often lost included 1p (24%), 4q (36%), 6q (40%), 9p (36%), 13q (36%), Xp (28%), Xq (36%), and Y (73%). There were clinical and genetic differences between the subtypes of papillary RCC. Type 2 tumors were of higher nuclear grade (P = 0.0012) and higher stage (P = 0.01) and had a worse prognosis (P = 0.03) than type 1 tumors. The number of DNA gains per tumor, especially gains of 7p and 17p, was significantly higher in type 1 than in type 2 tumors (P < 0.01). These data suggest the existence of two distinct morphological and genetic subgroups of papillary RCC. Losses of chromosome Xp were associated with short patient survival (P < 0.01). Despite the small number of cases, this finding suggests that a gene on chromosome Xp may contribute to papillary RCC progression.