Papillary renal cell carcinoma: current and controversial issues.
Current opinion in urology
PURPOSE OF THE REVIEW:Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15-20% of all RCC. Classification of pRCC is changing because novel tumour entities have been discovered in the last years. In this review, we summarise recent studies relevant for the understanding of the molecular complexity and the broader differential diagnosis of pRCC. RECENT FINDINGS:It has been 25 years ago, that pRCC was morphologically subdivided into type 1 and type 2. Recently described tumour entities in the 2022 WHO classification challenged this concept and allow a new view on the molecular background in pRCC. Biphasic hyalinizing psammomatous RCC and papillary renal neoplasm with reversed polarity are emerging tumour entities derived from the new concept of molecularly defined RCC subtypes. Immune checkpoint inhibition and tyrosine kinase inhibitors have been introduced as the new backbone in the first-line treatment of advanced pRCCs. To identify novel targeted treatments for patients with pRCC it is crucial to investigate the specific molecular background of pRCC considering emerging pRCC subtypes. SUMMARY:In the future, a deeper understanding of the correlation between molecular aberrations and new pRCC subtypes may improve the classification of pRCC patients and could reveal potential predictive biomarkers for each subgroup.
10.1097/MOU.0000000000001000
Papillary renal cell carcinoma: Review.
Mendhiratta Neil,Muraki Peter,Sisk Anthony E,Shuch Brian
Urologic oncology
Kidney cancer is the 13th most common malignancy globally, and the incidence is rising. Papillary renal cell carcinoma is the second most common subtype, comprising 10-15% of renal cell carcinomas. Though the histologic features of this subtype were initially described in the 1990's, our understanding of the genetic and molecular characteristics of this disease have rapidly evolved over the past decade. In this review, we summarize the contemporary understanding of the clinical, morphologic, radiographic, and genetic characteristics of papillary renal cell carcinoma, as well as clinical considerations, current options for management, and prognosis.
10.1016/j.urolonc.2021.04.013
WHO 2022 landscape of papillary and chromophobe renal cell carcinoma.
Histopathology
The 5th edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems contains relevant revisions and introduces a group of molecularly defined renal tumour subtypes. Herein we present the World Health Organization (WHO) 2022 perspectives on papillary and chromophobe renal cell carcinoma with emphasis on their evolving classification, differential diagnosis, and emerging entities. The WHO 2022 classification eliminated the type 1/2 papillary renal cell carcinoma (pRCC) subcategorization, given the recognition of frequent mixed tumour phenotypes and the existence of entities with a different molecular background within the type 2 pRCC category. Additionally, emerging entities such as biphasic squamoid alveolar RCC, biphasic hyalinising psammomatous RCC, papillary renal neoplasm with reverse polarity, and Warthin-like pRCC are included as part of the pRCC spectrum, while additional morphological and molecular data are being gathered. In addition to oncocytomas and chromophobe renal cell carcinoma (chRCC), a category of 'other oncocytic tumours' with oncocytoma/chRCC-like features has been introduced, including emerging entities, most with TSC/mTOR pathway alterations (eosinophilic vacuolated tumour and so-called 'low-grade' oncocytic tumour), deserving additional research. Eosinophilic solid and cystic RCC was accepted as a new and independent tumour entity. Finally, a highly reproducible and clinically relevant universal grading system for chRCC is still missing and is another niche of ongoing investigation. This review discusses these developments and highlights emerging morphological and molecular data relevant for the classification of renal cell carcinoma.
10.1111/his.14700
First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: a phase II study (SUPAP) by the French Genitourinary Group (GETUG)†.
Annals of oncology : official journal of the European Society for Medical Oncology
BACKGROUND:Papillary renal cell carcinoma (PRCC), type 1 and type 2, represents 10%-15% of renal cell carcinomas (RCC). There is no standard first-line treatment of metastatic PRCC (mPRCC). Anti-angiogenics have shown activity in retrospective studies but no prospective studies in pure papillary histology have been reported, but one with foretinib. PATIENTS AND METHODS:A prospective phase II study evaluated sunitinib in first-line treatment of mPRCC. The primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS:Fifteen and 46 patients, respectively, with type 1 and type 2 mPRCC were enrolled. Using the MSKCC scoring system: 12 (20%), 33 (55%) and 9 (15%) patients were, respectively, in the favourable, intermediate or poor risk group and 7 undetermined. Median follow-up is 51.4 months. In type 1, 2 patients 13% [95% confidence interval (CI) 0.1-30.5] had a partial response (PR), 10 had stable disease (SD) with 5 (33%) ≥12 weeks. In type 2, 5 patients 11% (95% CI 1.9-20.3) had a PR, 25 had SD with 10(22%) ≥12 weeks. Median PFS was 6.6 months (95% CI 2.8-14.8) in type 1 and 5.5 months (95% CI 3.8-7.1) in type 2. Median OS was 17.8 (95% CI 5.7-26.1) and 12.4 (95% CI 8.2-14.3) months, respectively, in type 1 and 2. Safety was as expected with sunitinib for metastatic RCC. CONCLUSION:Sunitinib showed activity in treatment of type 1 and 2 mPRCC but lower than in clear-cell mRCC. Both PFS and OS are longer in type I PRCC. Sunitinib represents an acceptable option in first-line treatment of mPRCC.
10.1093/annonc/mdv149
Comparison of clinicopathologic parameters and oncologic outcomes between type 1 and type 2 papillary renal cell carcinoma.
Le Xiang,Wang Xiang-Bo,Zhao Hao,Chen Ren-Fu,Ge Peng
BMC urology
BACKGROUND:To compare the clinicopathologic parameters and oncologic outcomes between type 1 and type 2 papillary renal cell carcinoma (PRCC). METHODS:This study was approved by the review board (NO.XYFY2019-KL032-01). Between 2007 and 2018, 52 consecutive patients who underwent surgery at a single tertiary referral hospital were included. Clinicopathologic and survival data were collected and entered into a database. The Kaplan-Meier method, and univariate and multivariate Cox proportional hazard regression analyses were performed to estimate progression-free survival (PFS) and cancer-specific survival (CSS). RESULTS:Of the 52 patients, 24 (46.2%) were diagnosed with type 1 PRCC, and 28 (53.8%) had type 2 PRCC. The mean tumor size was 4.8 ± 2.5 cm. The two subtypes displayed different morphological features: foamy macrophages were more common in type 1 PRCC, while eosinophils and microvascular angiolymphatic invasion were more frequent in type 2 PRCC. Type 2 cases showed higher tumor stage and World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade than type 1 cases (T3-T4: 43% vs 17%, P = 0.041; G3-G4: 43% vs 8%, P = 0.005). In univariate analysis, type 2 PRCC had a lower probability for PFS and CSS than patients with type 1 PRCC (P = 0.016, P = 0.049, log-rank test, respectively). In multivariate analysis, only WHO/ISUP grade (HR 11.289, 95% CI 2.303-55.329, P = 0.003) and tumor size (HR 1.244, 95% CI 1.034-1.496, P = 0.021) were significantly associated with PFS. CONCLUSIONS:PRCC subtype displayed different morphological features: foamy macrophages, eosinophils and microvascular angiolymphatic invasion are pathologic features that may aid in the distinction of the two subtypes. Histologic subtype of PRCC is not an independent prognostic factor and only WHO/ISUP grade and tumor size were independent predictors for PFS.
10.1186/s12894-020-00716-0
Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases.
Marsaud Alexandre,Dadone Bérengère,Ambrosetti Damien,Baudoin Christian,Chamorey Emmanuel,Rouleau Etienne,Lefol Cédrick,Roussel Jean-François,Fabas Thibault,Cristofari Gaël,Carpentier Xavier,Michiels Jean-François,Amiel Jean,Pedeutour Florence
Genes, chromosomes & cancer
Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinoma (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC. We studied the clinical, histological, immunohistological, and comprehensive genetic features of a series of 31 pRCC including 15 pRCC1 and 16 pRCC2. We aimed to determine whether pRCC represents a unique entity or several diseases. In addition, we compared the genetic features of pRCC2 to those of eight RCC showing various degrees of tubulo-papillary architecture, including three TFE-translocation RCC and five unclassified RCC. We demonstrate that pRCC is a heterogeneous group of tumors with distinct evolution. While most pRCC2 had genetic profiles similar to pRCC1, some shared genomic features, such as loss of 3p and loss of chromosome 14, with clear cell RCC, TFE-translocation RCC, and unclassified RCC. We identified variants of the MET gene in three pRCC1. A mutation in the BRAF gene was also identified in one pRCC1. In addition, using next-generation sequencing (NGS), we identified several variant genes. Genomic profiling completed by NGS allowed us to classify pRCC2 in several groups and to identify novel mutations. Our findings provide novel information on the pathogenesis of pRCC that allow insights for personalized treatment.
10.1002/gcc.22248
GCN2 is a potential prognostic biomarker for human papillary renal cell carcinoma.
Ge Liyuan,Chen Wei,Cao Wenmin,Liu Guangxiang,Zhang Qing,Zhuang Junlong,Zhang Mingxin,Yang Jun,Guo Suhan,Zhao Xiaozhi,Guo Hongqian
Cancer biomarkers : section A of Disease markers
Postoperative recurrence for papillary renal cell carcinoma (PRCC) remains a tough problem in clinic. Previous studies have shown that general control nonderepressible kinase 2 (GCN2) was critically involved in tumour development. However, its function and clinical significance in renal cancer remain unknown. In this study, we investigated the role of GCN2 in PRCC. GCN2 silencing suppressed the viability and proliferation, promoted apoptosis of renal cancer cells. We found that the protein level of GCN2 was increased in PRCC tissues. Immunohistochemistry was performed in 84 patients with PRCC to explore the association of GCN2 level with clinical significance. High GCN2 protein level was observed to be significantly correlated with adverse clinicopathological parameters, such as larger tumor size, higher TNM stage, higher Fuhurman Grade, and lymph node metastasis. We evaluated patient outcomes according to various clinical parameters as well as GCN2 expression by Kaplan-Meier curves. Multivariate analysis revealed that GCN2 overexpression can be a predictive factor correlated with reduced OS and PFS of postoperative PRCC patients. Collectively, GCN2 is potentially to play crucial roles in PRCC progression, and its overexpression may be used to predict poor prognosis and promising therapeutic strategy for PRCC patients.
10.3233/CBM-170922
High WHO/ISUP Grade and Unfavorable Architecture, Rather Than Typing of Papillary Renal Cell Carcinoma, May Be Associated With Worse Prognosis.
Yang Chen,Shuch Brian,Kluger Harriet,Humphrey Peter A,Adeniran Adebowale J
The American journal of surgical pathology
Conflicting data have been published on the prognostic significance of histologic parameters in papillary renal cell carcinoma (PRCC). We conducted a comprehensive evaluation of clinical and histologic parameters in PRCC in nephrectomies and their impact on prognosis, with an emphasis on World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade, tumor architecture (solid, micropapillary, and hobnail), and PRCC type. A total of 185 PRCC cases were evaluated, 117 (63.2%) type 1, 45 (24.3%) type 2, and 11 (5.9%) mixed type 1 and type 2. Using WHO/ISUP grading criteria, PRCCs were graded as follows: 6 (3.2%) grade 1; 116 (62.7%) grade 2; 61 (33.0%) grade 3; and 2 (1.1%) grade 4. The solid architecture was present in 3 cases (1.6%) and comprised 10%, 10%, and 30% of the tumor area. Micropapillary architecture was present in 10 cases (5.4%), ranging from 5% to 30% of the tumor (mean=11%; median=10%). Hobnail architecture was seen in 9 cases (4.9%), with mean percentage of 23% (median=15%; range: 5% to 50%) involvement of tumor area. Parameters associated with worse disease-free survival (DFS) and overall survival (OS) in the univariate analysis included WHO/ISUP grade, pathologic stage, tumor size, and solid, micropapillary, or hobnail architecture (P<0.05). The pathologic stage and WHO/ISUP grade were significantly associated with both DFS and OS in stepwise multivariate Cox regression analysis (P<0.05). In addition, micropapillary architecture and type 1 histology were linked with an adverse impact on OS (P<0.05). We found no difference in DFS (P=0.8237) and OS (P=0.8222) for type 1 versus type 2 PRCC in our patient cohort. In addition, we performed a meta-analysis with data from studies with reported hazard ratios (HRs) on PRCC type in relation to DFS and OS. We identified 5 studies that reported DFS and found no significant effect for type 2 PRCC (P=0.30; HR=1.43; 95% confidence interval: 0.73-2.80). We identified 7 studies that reported OS and found no significant association between type 2 PRCC and worse OS (P=0.41; HR: 1.21; 95% confidence interval: 0.77-1.91). Our findings suggest that high WHO/ISUP grade and unfavorable architecture (solid, micropapillary, or hobnail), rather than typing of PRCC, are associated with worse outcomes.
10.1097/PAS.0000000000001455