papillary renal cell carcinoma presenting with hemoptysis
TRANSCRIPT
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Papillary Renal Cell Carcinoma Presenting with Hemoptysis
Michael Dougan, PhD, HMSIIIGillian Lieberman, MD
July 2009
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Our patient
• 57 y.o. man with a previous smoking history, and an 8 month
history of COPD presenting with worsening dyspnea
on
exertion, cough, and wheezing
• A chest X‐ray was performed to look for lung processes that
could be acutely exacerbating his condition– Pneumonia
– Obstruction/collapse– Pneumothorax
– Pleural effusion
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Our patient’s initial evaluation by chest X-ray is shown below
BIDMC PACS
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
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ABCs of CXR : quality control
Is this our patient? Do we have the standard views?Is the entire region of interest covered? Exposure?
BIDMC PACS
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
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ABCs of CXR : aberrant air
ABCs of CXR : bonesBIDMC PACS
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
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ABCs of CXR : cardiac silhouette
ABCs of CXR : diaphragmBIDMC PACS
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
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ABCs of CXR : cardiac silhouette
depressed diaphragm
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
BIDMC PACS
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ABCs of CXR : cardiac silhouette
small effusion
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
BIDMC PACS
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ABCs of CXR : extras
BIDMC PACS
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
outside the patient
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ABCs of CXR : fields
ABCs of CXR : gastric bubble and hilaBIDMC PACS
Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray
Increased markings
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Our patient’s course: worsening COPD
• Our patient was released with a diagnosis of worsening COPD– no acute lung problem
• 2 months later, he returned with a new COPD exacerbation, this time complicated by hemoptysis
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• Because of his acutely worsening condition, a CT scan was ordered
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Chest CT for to evaluate hemoptysis
yellow oval: airspace filling
DDx: water, blood, cells, protein
orange oval: focal densitycould this be malignant?
BIDMC PACS
axial chest CT: lung window
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Right bronchial mass on CT
BIDMC PACS
Yellow circle:density in the right bronchus
malignancy?mucus plug?
coronal reconstruction CT of the chest: soft tissue window
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Incidental finding in the abdominal portion of the CT
axial CT through the abdomen: soft tissue window
post-contrast
yellow circle: exophytic posterior left kidney cyst
pre-contrast
BIDMC PACS
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Overview of normal renal anatomy
www.nlm.nih.gov/medlineplus/ency/imagepages/1101.htm
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Exophytic kidney cyst
www.nlm.nih.gov/medlineplus/ency/imagepages/1101.htm
common incidental findings
DDxBenign Cyst (common)Renal Tumor (RCC, TCC, other)AbscessVascular AbnormalityMetastasisCystic Kidney Syndrome
follow-up is determined by specific radiographic features
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Bosniak Classification System• Bosniak I: hairline thin wall; no septa, calcification, or solid components.
Water density, no enhancement.
• Bosniak II: a few hairline thin septa, fine calcification in wall or septa.
• Bosniak IIF: more hairline septa. Minimal septa or wall enhancement, minimal wall thickening. Nodular or thick calcifications. No soft tissue enhancement.
• Bosniak III: cystic masses with thickened irregular walls, or septa with enhancement
• Bosniak IV: Cystic lesions with enhancing soft-tissue elements
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Generally Benign Cysts (I, II)• Bosniak I: hairline thin wall; no septa, calcification, or solid components.
Water density, no enhancement.
• Bosniak II: a few hairline thin septa, fine calcification in wall or septa.
• Bosniak IIF: more hairline septa. Minimal septa or wall enhancement, minimal wall thickening. Nodular or thick calcifications. No soft tissue enhancement.
• Bosniak III: cystic masses with thickened irregular walls, or septa with enhancement
• Bosniak IV: Cystic lesions with enhancing soft-tissue elements
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Potentially Malignant (IIF – IV)• Bosniak I: hairline thin wall; no septa, calcification, or solid components.
Water density, no enhancement.
• Bosniak II: a few hairline thin septa, fine calcification in wall or septa.
• Bosniak IIF: more hairline septa. Minimal septa or wall enhancement, minimal wall thickening. Nodular or thick calcifications. No soft tissue enhancement.
• Bosniak III: cystic masses with thickened irregular walls, or septa with enhancement
• Bosniak IV: Cystic lesions with enhancing soft-tissue elements
Follow-up Required
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Evidence that Bosniak
criteria are clinically meaningful
BosniakClassification
% Malignant
I 1.8% (2/114)
II 18.5% (20/108)
III 33% (218/660)
IV 92.5% (148/160)
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Analyzing our patient’s cyst using the Bosniak criteria
pre-contrast post-contrast
yellow circles: exophytic cyst, soft tissue density, some regions of inhomogeneity, question of rim enhancement, calcified rim, accessory nodule.
axial CT through the abdomen: soft tissue window
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How should we classify our patient’s cyst?
• Bosniak IIF: follow-up recommended– MRI can provide greater soft tissue detail
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Further diagnostic steps for our patient
• Multiple pulmonary/bronchial nodules identified– Concern for primary pulmonary malignancy– Bronchial nodule was resected and sent to pathology
• Follow-up MRI of the kidneys was performed to further characterize the mass
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Follow-up MRI was ordered
Sagittal abdominal MRI: T1 pre-contrastfat suppressed
Sagittal abdominal MRI: T1 post- contrast fat suppressed
yellow circle: posterior exophytic left kidney masshigh signal regions suggest focal hemorrhage
orange circle: hyper-intensity in the posterior renal fatmalignant invasion? inflammation?
pink arrows: enhancing papillary nodules
BIDMC PACS
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BIDMC PACS
Coronal MRI of the kidney
coronal abdominal MRI: T1 pre-contrast, fat suppressed
coronal abdominal MRI: T1 post-contrast, fat suppressed
pre-contrast images can be mathematically subtracted from post-contrast images to confirm regions of enhancement, outlining areas of blood flow
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BIDMC PACS
Further analysis of blood flow by MRI
coronal abdominal MRI: post-contrast subtraction view
pink arrows: enhancing papillary nodules
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MRI aided diagnosis• MRI imaging findings are characteristic of papillary RCC
– Cystic mass– Well encapsulated– Relatively low/homogenous enhancement with gadolinium– Enhancing, papillary projections into lumen
• Diagnosis was confirmed by bronchoscopy– The mass in his bronchus was confirmed to be papillary RCC
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Renal cell carcinoma• Most common tumor of the kidney
• Subtypes of RCC– Clear Cell (75% – 85%)– Chromophilic/papillary (10% – 15%)– Chromophobic (5% – 10%)– Oncocytic (rare)– Collecting Duct (rare)
http://pathologyoutlines.com
Clear Cell RCC
http://pathologyoutlines.com
Papillary RCC
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RCC staging and prognosis
• Staging– Stage I: < 7 cm– Stage II: > 7 cm but limited to kidney– Stage III: invasion into veins, adrenal, perirenal space– Stage IV: invasion beyond perirenal fascia, including distant
metastases
Stage Prognosis (5 year survival)
I 91% ‐
100%
II 74% ‐
96%
III 59% ‐
70%
IV 16% ‐
32%
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Use of CT for staging RCC
• Detect invasion of perirenal structures (Stage III disease)– Veins (renal, IVC)– Adrenal Gland– Perirenal fasica
• Identify distant metastases (Stage IV disease)– e.g. the pulmonary masses in our patient?
• Other modalities include:– MRI, metabolic bone scan, PET
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• Clear cell RCC is more common than the papillary variant, and has a more typical, malignant presentation by CT using the Bosniak criteria as demonstrated by companion patient 1
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Companion patient 1: typical presentation of clear cell RCC
Yellow circle: complex cystic mass (Bosniak IV)Orange rectangle: area of detail (next slide)
BIDMC PACS
Post contrast axial CT through the abdomen: soft tissue window
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Magnification view
complex cystic mass(Bosniak IV)
Yellow oval: tumor thrombus in the IVC (stage III disease)
BIDMC PACS
Post contrast axial CT through the abdomen centered on IVC: soft tissue window
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Renal cell carcinoma treatment• Surgical Resection (Stage I – III only)
• Standard chemotherapy has not been found to be effective
• Immune Therapy– IL-2, Interferon alpha, bevacizumab
• Targeted Therapy (Stage III, IV)– mTOR (temsirolimus), VEGF Receptor (sunitinib, sorafenib)
• Clinical Trials– response rates to current therapeutic regimens are poor
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Immune therapy for RCC• Tumors often express proteins that can be recognized as
foreign by the immune system– Mutated proteins, developmental/tissue restricted proteins, etc.
• Spontaneous anti-tumor immune responses do occur, but are rare and often insufficient to clear tumors
• Immune therapy is used to augment nascent anti-tumor immune responses– cytokines, monoclonal antibodies
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Cytokine therapy mechanism of action
• Both IL-2 and interferon alpha are important factors in promoting immune responses
• IL-2: potent T cell growth factor
• Interferon alpha: critical in for anti-viral responses, makes infected cells (or tumors) more susceptible killing by cytotoxic cells (CD8 T cells, and NK cells)
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Cytokine therapy efficacy and side effects
• Objective response rates are currently low (~10%), and durable responses are rare
• Adverse effects are significant, and resemble those of influenza infection– Malaise, fever, night sweats, joint pain, nausea
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Monoclonal antibody therapy for RCC
• Vascular Endothelial Growth Factor (VEGF) is an important growth factor in RCC– important in renal tumors associated with VHL disease
• VEGF can be directly targeted by monoclonal antibody therapy (bevacizumab)– Also targeted by new small molecule inhibitors (currently the
treatment of choice for many patients due to improved tolerability)
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Follow up on our patient• Diagnosed with Stage IV papillary RCC with intra-
bronchial metastases
• Poor prognosis, limited response to current therapies
• Entered into a clinical trial investigating a novel small molecule inhibitor
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Conclusion• Incidental renal cysts are a common finding
• Renal cysts are classified radiographically using the Bosniak system to separate benign findings from probable malignancies
• MRI can play an important role in correctly diagnosing cysts with indeterminate features on CT
• RCC is the most common tumor of the kidney, and, in early stage disease (stage I and II), can be treated by surgery alone
• Advanced RCC has a poor prognosis, and is managed using immune therapy or using targeted molecular therapy
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Acknowledgments• Erica Gupta• Maryellen Sun• Gillian Lieberman
• Glenn Dranoff• Richard Haspel• Adam Jeffers• Jay Pahade• Rich Rana• Aarti Sekhar• Jennifer Son
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