clinical and surgical management of vhl-related cysts and
TRANSCRIPT
10/11/2018
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Clinical and Surgical Management of VHL-Related Cysts and Cystic RCC
Mark W. Ball, MDAssistant Research Physician
Attending Surgeon
Urologic Oncology Branch, National Cancer Institute
@markballmd
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Outline
Prevalence of renal cysts and cystic RCC in VHL Biology of cystic VHL-related lesions Differentiating cysts from cystic RCC Surgical management
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VHL Renal Manifestations
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VHL Renal Manifestations
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VHL Renal Manifestations
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VHL Renal Manifestations
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Cyst vs Cystic RCC
Chen et al. 2012 Arch Pathol Lab Med
Atypical CystsBenign CystOne layer of clear cells Multiple layers and/or
focal papillary tufting
Cystic RCCCluster of clear cells associated with cyst
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CNS HB: central nervous system hemangioblastomas; RA: retinal angiomas, ELST: endolymphatic sac tumor; KS: kidney solid tumor;KC: kidney cyst, pheo: pheochromocytoma, PS: pancreatic solid tumor; PC: pancreatic cyst; ECA: epididymal cystadenoma
CNS HB RA ELST Kid Solid Kid Cyst Pheo PS PC ECA# evaluable 766 756 731 766 763 741 762 761 249
Total 606 (78.9) 400(52.9) 55 (7.5) 439 (57.3) 547 (71.7) 182 (24.6)
195 (25.6) 483 (63.5) 61 (24.5)
How prevalent are renal cysts in VHL?
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CNS HB RA ELST Kid Solid Kid Cyst Pheo PS PC ECA# evaluable 766 756 731 766 763 741 762 761 249
Total 606 (78.9) 400(52.9) 55 (7.5) 439 (57.3) 547 (71.7) 182 (24.6)
195 (25.6) 483 (63.5) 61 (24.5)
CNS HB: central nervous system hemangioblastomas; RA: retinal angiomas, ELST: endolymphatic sac tumor; KS: kidney solid tumor;KC: kidney cyst, pheo: pheochromocytoma, PS: pancreatic solid tumor; PC: pancreatic cyst; ECA: epididymal cystadenoma
How prevalent are renal cysts in VHL?
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CNS HB RA ELST Kid Solid Kid Cyst Pheo PS PC ECA# evaluable 766 756 731 766 763 741 762 761 249
Total 606 (78.9) 400(52.9) 55 (7.5) 439 (57.3) 547 (71.7) 182 (24.6)
195 (25.6) 483 (63.5) 61 (24.5)
Missense, n (%)n=376
262 (69.7) 195 (52.6) 16 (4.5) 180 (47.8) 234 (62.4) 150 (42.3)
109 (29.1) 171(45.6) 23 (19.7)
Partial Deletion, n (%)N=166
149 (89.8) 92 (56.1) 21 (13.2) 117 (79.5) 137 (83) 12 (7.3) 37 (22.4) 138 (83.6) 23 (36.)
Nonsense, n (%)N=64
62 (96.9) 42 (65.6) 9 (14.1) 48 (75) 55 (85.9) 5 (7.8) 16 (25.4) 58 (92.1) 7 (33.3)
Complete Deletion, n (%)N=49
40 (81.6) 9 (18.7) 0 17 (34.7) 29 (60.4) 0 7 (14.6) 36 (75) 1 (5.6)
Frameshift, n (%)N=60
51 (85) 35 (60.3) 4 (7.1) 43 (71.6) 49 (81.7) 3 (5) 15 (25) 39 (66.1) 5 (25)
Splice, n (%)N=31
26 (83.9) 16 (53.3) 4 (13.3) 20 (64.5) 24 (77.4) 8 (26.7) 8 (25.1) 24 (77.4) 2 (50)
AA Deletion, n (%)N=16
14 (87.5) 9 (56.3) 1 (6.25) 13 (81.3) 15 (93.8) 1 (6.25) 1 (6.25) 15 (93.7) 0
CNS HB: central nervous system hemangioblastomas; RA: retinal angiomas, ELST: endolymphatic sac tumor; KS: kidney solid tumor;KC: kidney cyst, pheo: pheochromocytoma, PS: pancreatic solid tumor; PC: pancreatic cyst; ECA: epididymal cystadenoma
How prevalent are renal cysts in VHL?
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Range of Phenotypes
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How do cystic lesions behave?
Limited published data on behavior of cystic VHL tumors Must extrapolate from: Sporadic cystic RCC
Solid VHL tumors
Institutional experience
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Cyst Biology: CAIX staining
Mandriota et al, Cancer Cell, 2002Are any cysts truly benign?
Normal Kidney (-) Tumor (+) Cyst lining (+)
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Evolution of a complex cystic lesion
2014 2016 2017 2018
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How do sporadic cystic lesions behave?
336 patients with complex renal cystsOnly 60 patients had surgeryMean cyst size 3.5 cm1 cancer-specific death
• 133 patients with resected complex renal cysts• 76% low grade, low stage• 1 local recurrence
Reese et al Urologic Oncology, 2012 Chandrasekar et al J Urol, 2017
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Growth Kinetics in VHL-Associated Solid Renal Tumors
Ball et al Under Review
240 tumors in 152 patients, comprising 1301 tumor measurements
Median GR: 3.7 mm/yr (IQR: 2.6-5.7)
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Solid tumors: No patients developed metastatic disease when managed by the 3 cm guideline.
Tumor Size # mets/ # pts (%)< 3 cm 0/178 (0%)3-4 cm 4/109 (3.7%)4-5 cm 8/62 (12.9%)5-6 cm 7/27 (25.9%)6-7 cm 6/12 (50%)> 7 cm 17/28 (60%)
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< 3 3-4 4-5 5-6 6-7 > 7PR
OPO
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TUMOR SIZE
Metastatic Potential by Tumor Size
Ball et al AUA 201818
Institutional Experience
The vast majority of lesions that appear to be simple cysts on imaging are benign cysts on final path.
Complex cystic lesions are often low grade (Fuhrman 1-2) ccRCC on final path.
Patients who have developed metastatic disease have had large (> 3 cm) solid tumors.
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Cyst behavior
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Surveillance and Treatment
MRI: workhorse Ultrasound: adjunct
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MRI
Both T2 and T1 contrast enhanced phases are useful
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Clinic-Based Ultrasound
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Ultrasound Adjunct
> 3 cm
2.5 cm
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When to intervene
Most interventions are based on solid tumors (i.e. when solid tumor reaches 3 cm)
For mixed cystic lesions with a discrete nodule, the solid portion can be used as a trigger.
For mixed honeycomb-like lesions, the proportion of solid tumor can be estimated.
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Operative Consideration
Cyst decortication: not recommended
Enucleation Less parenchymal compression
Intraoperative ultrasound is critical
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Preoperative Planning
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Enucleation
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Operative Approach
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Acknowledgements Clinical Team: W. Marston Linehan, MD Ramaprasad Srinivasan, MD, PhD Cris Leite• Caitlin Drew, RN• Debbie Nielsen, RN• Lindsay Middleton, RN Clinical Fellow George Washington U Residents Georgetown U Residents Walter Reed Residents
Genetics Team• Laura Schmidt, PhD
• Cathy Vocke, PhD• Chris Ricketts, PhD
• Caitlin Drew, RN
• Debbie Nielsen, RN
• Lindsay Middleton, RN
Laboratory of Pathology Maria Merino, MD
Radiology Ashkan Malyeri, MD Rabindra Gautam Kailash Daryanani
Data Management
James Peterson
Kristin Choo
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