Imaging findings of papillary renal cell carcinoma
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1 Imaging findings of papillary renal cell carcinoma Poster No.: C-0286 Congress: ECR 2015 Type: Educational Exhibit Authors: J. Praia, R. Dias, C. Macedo, J. Albuquerque, M. Certo ; Barreiro/PT, Porto/PT Keywords: Cancer, Staging, Diagnostic procedure, Ultrasound, MR, CT, Oncology, Kidney, Abdomen DOI: /ecr2015/C-0286 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 34
2 Learning objectives - Overview of the epidemiology, pathology and biology of renal cell carcinoma (RCC) and its different subtypes. - Description and discussion of the imaging findings of the papillary subtype (prcc) and its impact on the treatment, prognosis and follow-up of this pathology. Page 2 of 34
3 Background - RCC is not a single disease but an entity with different distinct genetic, molecular, and histologic subtypes having varying clinical behavior and outcomes. The 2004 World Health Organization histologic classification of renal tumors acknowledges this concept and defines a number of subtypes whose recognition has a bearing on treatment and outcome. Clear cell (conventional) RCC Multilocular clear cell RCC Papillary RCC Chromophobe RCC Carcinoma of the collecting ducts of Bellini Renal medullary carcinoma Xp11 translocation carcinoma Carcinoma associated with neuroblastoma Mucinous tubular spindle cell carcinoma Unclassified RCC Table World Health Organization Classification of RCC Page 3 of 34
4 Fig. 1: Papillary renal cell carcinoma - we can observe a well- circumscribed neoplasm composed of papillae (a) that compresses the adjacent normal renal parenchima (b). References: Department of Pathology, Centro Hospitalar do Porto, EPE - Porto/PT - The incidence of RCC is gradually increasing, partly due to increased use of imaging and partly due to the increasing incidence of obesity in the general population, a risk factor associated with increased incidence of RCC. - RCC accounts for about 3% of cancers in adulthood, and the prcc 10-15% of all RCC (the predominant subtype is clear cell (crcc))., - Patients are typically years of age at presentation with a moderate male predilection of around 2:1. - Most RCCs are incidentally diagnosed at imaging, with the ammount of cases diagnosed by using the classic triad of hematuria, flank pain, and a mass in the abdomen continues to decline. Page 4 of 34
5 Fig. 2: Papillary renal cell carcinoma - We can observe the neoplasm composed by malignant cells forming papillae. The tumour cells cells have eosinophilic cytoplasm and pseudostratified nuclei on papillary cores - being, then, classified as a papillary renal cell carcinoma type 2. In the inset, on the left upper corner of the picture we can, also, see the nuclei details wich puts the neoplasm in a grade 2 of Fuhrman classification. References: Department of Pathology, Centro Hospitalar do Porto, EPE - Porto/PT - The majority of the solid enhancing renal masses found at imaging tend to be RCC, with other benign entities such as oncocytomas and lipid-poor angiomyolipomas being less common. - Although most prccs are unilateral, it is the most common multifocal or bilateral renal tumor, with a male predominance by 5:1. - Papillary RCC has no significant prognostic differences compared to crcc, with fiveyear survival rates ranging from 64% (stage II) and 11% (stage IV). Page 5 of 34
6 - There is an inherited predisposition to papillary RCC, of the autosomal dominant type, expressing itself as multiple bilateral renal tumors. Page 6 of 34
7 Images for this section: Fig. 1: Papillary renal cell carcinoma - we can observe a well- circumscribed neoplasm composed of papillae (a) that compresses the adjacent normal renal parenchima (b). Department of Pathology, Centro Hospitalar do Porto, EPE - Porto/PT Page 7 of 34
8 Fig. 2: Papillary renal cell carcinoma - We can observe the neoplasm composed by malignant cells forming papillae. The tumour cells cells have eosinophilic cytoplasm and pseudostratified nuclei on papillary cores - being, then, classified as a papillary renal cell carcinoma type 2. In the inset, on the left upper corner of the picture we can, also, see the nuclei details wich puts the neoplasm in a grade 2 of Fuhrman classification. Department of Pathology, Centro Hospitalar do Porto, EPE - Porto/PT Page 8 of 34
9 Findings and procedure details - Imagiologically speaking, prcc manifests as a solid mass, distinguishing itself from other more common types by its relative avascularity. - Two morphologic types of prcc are described, with different clinical behavior - type 2 tumour carry a worse prognosis than do type 1 tumour. Imaging is not able by itself to differentiate between the two. - Sarcomatoid dedifferentiation is seen in roughly 5% of prccs, being associated with both types and with a worse prognosis. Imaging is not able by itself to differentiate between the two. IMAGING FEATURES COMPUTED TOMOGRAPHY - CT is frequently used to both diagnose and stage renal cell carcinomas. - prcc is less vascular than crcc, due to differences in the intratumoral vascularity. Page 9 of 34
10 Fig. 5: Axial view of the unenhanced phase of a renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a hypodense lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 10 of 34
11 - prcc presents as an enhancing lesion, but with less contrast enhancement than the surrounding renal parenchyma. Non-enhanced sequences show iso, hypo or even hyperdense masses. - At nonenhanced CT, calcification is seen slightly more often in prcc (roughly 30% of cases) than in crcc. However, the presence or absence of this feature is not of value in making this differentiation. Page 11 of 34
12 Fig. 6: Coronal view of the arterial phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT - prcc enhances to a lesser degree than does crcc in all phases of postcontrast imaging: if a heterogeneous mass enhances to a degree similar to the renal cortex, it more likely is a crcc; to a lesser degree, is likely to represent a prcc or a chromophobe RCC. - Generally speaking, prccs can be classified on the basis of their CT appearance as solid or cystic masses. Solid tumors can appear homogeneous and uniform or heterogeneous with areas of necrosis. Page 12 of 34
13 Fig. 7: Zoomed-in sagittal view of the arterial phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT - At CT, prcc is more likely to be homogeneous in comparison with crcc, particularly in cases of smaller tumors (<3 cm in diameter). prccs larger than 3 cm in diameter Page 13 of 34
14 may be heterogeneous with areas of necrosis and hemorrhage; this may be a useful finding, particularly in differentiating between prcc and chromophobe RCC at CT, since chromophobe RCCs tend to be homogeneous even when large. - Nephrographic phase images are more useful than corticomedullary ones on identifying small tumours (<3 cm in diameter). Fig. 8: Axial view of the arterial phase of the abovementioned renal CT-scan. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 14 of 34
15 - The relative hypovascularity of prcc can cause it to be mistaken for a simple renal cyst. Simple cysts do not enhance by more than 10 HU from precontrast to postcontrast imaging. Enhancement of HU is considered suspicious and should alert the radiologist to look for other suspicious signs of malignancy, such as a solid nodule or enhancing septa. Fig. 9: Sagittal view of the venous phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. Page 15 of 34
16 It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT - When precontrast images are not available, the presence of de-enhancement or contrast material washout at delayed phase imaging, such as during the excretory phase, is also an indicator of vascularity. - prccs can also and occasionally manifest as cystic masses. The cystic nature may be due to their inherent architecture or secondary to cystic degeneration and extensive necrosis. Page 16 of 34
17 Fig. 10: Coronal view of the venous phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 17 of 34
18 - Although cystic RCCs may belong to any subtype, a unilocular cystic RCC tends to be of the papillary subtype. It is characterized by a single cyst with a nodule within it or tumor growth filling part of the cyst. - Cystic degeneration is almost as likely to occur in prcc as in crcc. MAGNETIC RESSONANCE IMAGING (MRI) - MRI is used for the characterization of renal lesions on an occasional fashion (e.g., allergies to iodinated contrast material). - However, owing to the superior tissue contrast provided, it may also be used in differentiating solid from cystic lesions. - The pattern of contrast enhancement is similar to CT. - prcc frequently shows a pseudocapsule and frequently has low signal intensity on both T1- and T2-weighted images, whereas crcc has higher signal intensity on T2weighted images. ULTRASONOGRAPHY - No know US technique validated for the differentiation between different RCC subtypes. - Replaced mostly by CT and MRI as a diagnostic and staging tool for renal masses. Page 18 of 34
19 Fig. 3: Renal US, demonstrating on the upper pole of the left kidney a nodular hyperchoic solid complex, with a linear calcification, which are suspicious findings. A CT scan and biopsy were consequently performed, revealing a type 1 papillary renal cell carcinoma. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT - However, US is still useful in differentiating cystic from solid masses, particulary the ones that show borderline enhancement at CT and for for high-attenuation lesions that show little or no enhancement at CT. Page 19 of 34
20 - At US, RCCs may appear hypo-, iso-, or hyperechoic relative to the surrounding renal parenchyma. Fig. 4: Renal US, demonstrating on the upper pole of the left kidney a nodular hyperchoic solid complex, with a linear calcification, which are suspicious findings. A CT scan and biopsy were consequently performed, revealing a type 1 papillary renal cell carcinoma. References: Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 20 of 34
21 - Twenty percent to 50% of small RCCs are found to be hyperechoic - similar to the more common angiomyolipoma. Therefore, noncalcified hyperechoic lesions are best characterized with CT or MR imaging. STAGING - Clinically, prcc is staged according to the TNM staging system, common to all subtypes of RCC and the most important prognostic factor. - It is worth noting that the predominance of crcc and the relatively small numbers of prcc mean that the utility of this staging system has been validated in crcc but not necessarily in other subtypes. - Tumor extension into the inferior vena cava, the renal vein, or its branches (stage T3b and T3c) is relatively less common in prcc (~ 8.2% of cases) than in crcc (~ 23.6%). However, venous extension is associated with a drastic decrease in survival compared with that of similarly staged crcc cases. - prcc is associated with an increased prevalence of nodal involvement (13%) than crcc (8.6%). However, unlike in crcc, where nodal involvement carries a poorer prognosis, prcc with regional nodal metastases is not necessarily associated with a poorer prognosis. Patients with prcc and nodal metastases show significantly improved survival compared with that of a similar cohort of crcc patients. - Once replaced by tumor cells, lymph nodes show enhancement characteristics similar to those of the primary tumor: metastatic prcc nodes enhance to a lesser degree than do metastatic crcc nodes. - Spread to mediastinal lymph nodes and supra-clavicular lymph nodes is not unusual considered distant metastases and classified as M1 disease. - prcc metastasize less frequently than crcc. - Patients with prcc and visceral metastases have a dismal prognosis. Such patients have a significantly lower median survival (9.1 months) than do patients with metastatic crcc (22 months). Page 21 of 34
22 - It is common for metastatic lesions prcc to show enhancement characteristics similar to those of the primary tumor and be hypovascular. Conversely, metastatic lesions from crcc are generally hypervascular. TREATMENT - Radical nephrectomy or the more recently developed nephron-sparing procedures such as partial nephrectomy or thermal tumor ablation remain the only effective method of cure for all subtypes of localized RCC. However, there have been several recent advances in systemic therapy for metastatic RCCs. - The first-line therapy is similar between metastatic prcc and crcc: antiangiogenesis agents such as bevacizumab, sunitinib, and sorafenib increase progression-free survival in patients with both clear cell and non-clear cell RCC. However, crcc tend to have better response. - Studies on some new agents are showing promise, such as the investigational agent temsirolimus, which appears to improve overall survival in patients with metastastic prcc compared with that in patients with metastatic crcc. Page 22 of 34
23 Images for this section: Fig. 3: Renal US, demonstrating on the upper pole of the left kidney a nodular hyperchoic solid complex, with a linear calcification, which are suspicious findings. A CT scan and biopsy were consequently performed, revealing a type 1 papillary renal cell carcinoma. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 23 of 34
24 Fig. 4: Renal US, demonstrating on the upper pole of the left kidney a nodular hyperchoic solid complex, with a linear calcification, which are suspicious findings. A CT scan and biopsy were consequently performed, revealing a type 1 papillary renal cell carcinoma. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 24 of 34
25 Fig. 5: Axial view of the unenhanced phase of a renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a hypodense lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 25 of 34
26 Fig. 6: Coronal view of the arterial phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 26 of 34
27 Fig. 7: Zoomed-in sagittal view of the arterial phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 27 of 34
28 Fig. 8: Axial view of the arterial phase of the abovementioned renal CT-scan. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 28 of 34
29 Fig. 9: Sagittal view of the venous phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 29 of 34
30 Fig. 10: Coronal view of the venous phase of an enhanced renal CT scan,emphasizing in the posterior aspect of the upper half of the left kidney a lesion complex with grossly nodular morphology, measuring 4.2 cm in greatest diameter with discrete spontaneously hyperdense areas and multiple millimetric foci of calcification, which exhibits delayed enhancement, strongly suggestive of translating neoformative injury. It is associated with mild densification of the peri-renal fat planes, suspicious for invasion by contiguity. This lesion was later diagnosed by histologic analysis as a type 2 papillary renal cell carcinoma. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 30 of 34
31 Fig. 11: Axial view of the delayed phase of the abovementioned renal CT-scan, showing delayed enhancement. Department of Imagiology, Centro Hospitalar do Porto, EPE - Porto/PT Page 31 of 34
32 Conclusion RCC is an entity with different genetic, molecular, and histologic subtypes having varying clinical behavior and outcomes, specially prcc. The pattern and degree of enhancement appear to be the key in differentiating primary crcc from prcc. The relative hypovascularity of these tumors poses specific diagnostic pitfalls and challenges. There is also a great degree of overlap in the imaging appearances of non-clear cell RCCs. There are discriminating differences in the natural history of prcc and crcc based on the commonly used TNM staging criteria. Knowledge of the differences in prognostic significance unique to different subtypes while staging is essential to tailor appropriate treatment and follow-up programs. The changes in clinical management trickle down to the the expectations on the radiologist interpretation of the results of imaging and staging studies. Page 32 of 34
33 References American Cancer Society. Cancer facts & figures Atlanta, Ga: American Cancer Society, EbleJN, Sauter G, Epstein JI, Sesterhenn IA. WHO classification of tumours: pathology and genetics of tumours of the urinary system and male genital organs. Paris, France: International Agency for Research on Cancer, SchraderAJ, Olbert PJ, Hegele A, Varga Z, Hofmann R. Metastatic non-clear cell renal cell carcinoma: current therapeutic options. BJU Int2008; 101: ReuterVE. The pathology of renal epithelial neoplasms. Semin Oncol2006; 33: PatardJJ, Leray E, Rioux-Leclercq N, et al. Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. J Clin Oncol2005; 23: Van PoppelH, Nilsson S, Algaba F, et al. Precancerous lesions in the kidney. Scand J Urol Nephrol Suppl2000; 205: WildbergerJE, Adam G, Boeckmann W, et al. Computed tomography characterization of renal cell tumors in correlation with histopathology. Invest Radiol1997; 32: KimJK, Kim TK, Ahn HJ, Kim CS, Kim KR, Cho KS. Differentiation of subtypes of renal cell carcinoma on helical CT scans. AJR Am J Roentgenol2002; 178: ZhangJ, Lefkowitz RA, Ishill NM, et al. Solid renal cortical tumors: differentiation with CT. Radiology2007; 244: WangJH, Min PQ, Wang PJ, et al. Dynamic CT evaluation of tumor vascularity in renal cell carcinoma. AJR Am J Roentgenol2006; 186: RaghunandanV, et al. Papillary Renal Cell Carcinoma: Radiologic-Pathologic Correlation and Spectrum of Disease. RadioGraphics2009; 29: Page 33 of 34
34 JinzakiM, Tanimoto A, Mukai M, et al. Double-phase helical CT of small renal parenchymal neoplasms: correlation with pathologic findings and tumor angiogenesis. J Comput Assist Tomogr2000; 24: Ruppert-KohlmayrAJ, Uggowitzer M, Meissnitzer T, Ruppert G. Differentiation of renal clear cell carcinoma and renal papillary carcinoma using quantitative CT enhancement parameters. AJR Am J Roentgenol2004; 183: SzolarDH, Kammerhuber F, Altziebler S, et al. Multiphasic helical CT of the kidney: increased conspicuity for detection and characterization of small (<3-cm) renal masses. Radiology1997; 202: YamadaT, Endo M, Tsuboi M, et al. Differentiation of pathologic subtypes of papillary renal cell carcinoma on CT. AJR Am J Roentgenol2008; 191: MacariM, Bosniak MA. Delayed CT to evaluate renal masses incidentally discovered at contrast-enhanced CT: demonstration of vascularity with deenhancement. Radiology1999; 213: BrinkerDA, Amin MB, de Peralta-Venturina M, Reuter V, Chan DY, Epstein JI. Extensively necrotic cystic renal cell carcinoma: a clinicopathologic study with comparison to other cystic and necrotic renal cancers. Am J Surg Pathol2000; 24: RoyC, Sauer B, Lindner V, Lang H, Saussine C, Jacqmin D. MR imaging of papillary renal neoplasms: potential application for characterization of small renal masses. Eur Radiol2007; 17: FarrellyC, Delaney H, McDermott R, Malone D. Do all non-calcified echogenic renal lesions found on ultrasound need further evaluation with CT? Abdom Imaging2008; 33: Hyperechoic renal tumors: anechoic rim and intratumoral cysts in US differentiation of renal cell carcinoma from angiomyolipoma. Radiology1993; 188: Page 34 of 34
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