Download Papillary Renal Cell Carcinoma Presenting with Hemoptysis

Papillary Renal Cell Carcinoma
Presenting with Hemoptysis
Michael Dougan, PhD, HMSIII
Gillian Lieberman, MD
July 2009
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
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Pneumonia
Obstruction/collapse
Pneumothorax
Pleural effusion
Our patient’s initial evaluation by
chest X-ray is shown below
Frontal Upright Chest X-Ray
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Left Lateral Upright Chest X-Ray
ABCs of CXR : quality control
Frontal Upright Chest X-Ray
Left Lateral Upright Chest X-Ray
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Is this our patient? Do we have the standard views?
Is the entire region of interest covered? Exposure?
ABCs of CXR : aberrant air
Frontal Upright Chest X-Ray
Left Lateral Upright Chest X-Ray
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ABCs of CXR : bones
ABCs of CXR : cardiac silhouette
Frontal Upright Chest X-Ray
Left Lateral Upright Chest X-Ray
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ABCs of CXR : diaphragm
ABCs of CXR : cardiac silhouette
Frontal Upright Chest X-Ray
Left Lateral Upright Chest X-Ray
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depressed diaphragm
ABCs of CXR : cardiac silhouette
Frontal Upright Chest X-Ray
Left Lateral Upright Chest X-Ray
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small effusion
ABCs of CXR : extras
Frontal Upright Chest X-Ray
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outside the patient
Left Lateral Upright Chest X-Ray
ABCs of CXR : fields
Frontal Upright Chest X-Ray
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Left Lateral Upright Chest X-Ray
Increased markings
ABCs of CXR : gastric bubble and hila
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
• Because of his acutely worsening condition, a CT scan
was ordered
Chest CT for to evaluate hemoptysis
axial chest CT: lung window
yellow oval:
airspace filling
DDx: water,
blood, cells,
protein
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orange oval: focal density
could this be malignant?
Right bronchial mass on CT
coronal reconstruction CT of the chest: soft tissue window
Yellow circle:
density in the
right bronchus
malignancy?
mucus plug?
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Incidental finding in the abdominal
portion of the CT
axial CT through the abdomen: soft tissue window
pre-contrast
yellow circle: exophytic posterior left kidney cyst
post-contrast
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Overview of normal renal anatomy
www.nlm.nih.gov/medlineplus/ency/imagepages/1101.htm
Exophytic kidney cyst
DDx
Benign Cyst (common)
Renal Tumor (RCC, TCC, other)
Abscess
Vascular Abnormality
Metastasis
Cystic Kidney Syndrome
follow-up is determined by
specific radiographic features
www.nlm.nih.gov/medlineplus/ency/imagepages/1101.htm
common
incidental
findings
Bosniak Classification System
•
Bosniak I: hairline thin wall; no septa, calcification, or solid components.
Water density, no enhancement.
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Bosniak II: a few hairline thin septa, fine calcification in wall or septa.
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Bosniak IIF: more hairline septa. Minimal septa or wall enhancement,
minimal wall thickening. Nodular or thick calcifications. No soft tissue
enhancement.
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Bosniak III: cystic masses with thickened irregular walls, or septa with
enhancement
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Bosniak IV: Cystic lesions with enhancing soft-tissue elements
Generally Benign Cysts (I, II)
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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
Potentially Malignant (IIF – IV)
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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.
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Bosniak III: cystic masses with thickened irregular walls, or septa with
enhancement
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Bosniak IV: Cystic lesions with enhancing soft-tissue elements
Follow-up Required
Evidence that Bosniak criteria are clinically meaningful
Bosniak
Classification
I
% Malignant
1.8% (2/114)
II
18.5% (20/108)
III
33% (218/660)
IV
92.5% (148/160)
Analyzing our patient’s cyst using
the Bosniak criteria
axial CT through the abdomen: soft tissue window
pre-contrast
post-contrast
yellow circles: exophytic cyst, soft tissue density, some regions of inhomogeneity, question
of rim enhancement, calcified rim, accessory nodule.
How should we classify our patient’s
cyst?
• Bosniak IIF: follow-up recommended
– MRI can provide greater soft tissue detail
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
Follow-up MRI was ordered
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Sagittal abdominal MRI: T1 pre-contrast
fat suppressed
yellow circle: posterior exophytic left kidney mass
high signal regions suggest focal hemorrhage
Sagittal abdominal MRI: T1 postcontrast fat suppressed
orange circle: hyper-intensity in the posterior
renal fat
malignant invasion? inflammation?
pink arrows: enhancing papillary nodules
Coronal MRI of the kidney
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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
Further analysis of blood flow by
MRI
coronal abdominal MRI: post-contrast subtraction view
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pink arrows: enhancing papillary nodules
MRI aided diagnosis
• MRI imaging findings are characteristic of papillary RCC
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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
Renal cell carcinoma
• Most common tumor of the kidney
Clear Cell RCC
• Subtypes of RCC
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Clear Cell (75% – 85%)
Chromophilic/papillary (10% – 15%)
Chromophobic (5% – 10%)
Oncocytic (rare)
Collecting Duct (rare)
http://pathologyoutlines.com
Papillary RCC
http://pathologyoutlines.com
RCC staging and prognosis
• Staging
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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%
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
• 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
Companion patient 1: typical
presentation of clear cell RCC
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Post contrast axial CT through the abdomen: soft tissue window
Yellow circle: complex cystic mass (Bosniak IV)
Orange rectangle: area of detail (next slide)
Magnification view
Post contrast axial CT through the abdomen centered on IVC:
soft tissue window
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complex cystic mass
(Bosniak IV)
Yellow oval: tumor thrombus in the IVC (stage III disease)
Renal cell carcinoma treatment
•
Surgical Resection (Stage I – III only)
•
Standard chemotherapy has not been found to be effective
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Immune Therapy
– IL-2, Interferon alpha, bevacizumab
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Targeted Therapy (Stage III, IV)
– mTOR (temsirolimus), VEGF Receptor (sunitinib, sorafenib)
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Clinical Trials
– response rates to current therapeutic regimens are poor
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
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)
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
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)
Follow up on our patient
• Diagnosed with Stage IV papillary RCC with intrabronchial metastases
• Poor prognosis, limited response to current therapies
• Entered into a clinical trial investigating a novel small
molecule inhibitor
Conclusion
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Incidental renal cysts are a common finding
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Renal cysts are classified radiographically using the Bosniak system
to separate benign findings from probable malignancies
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MRI can play an important role in correctly diagnosing cysts with
indeterminate features on CT
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RCC is the most common tumor of the kidney, and, in early stage
disease (stage I and II), can be treated by surgery alone
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Advanced RCC has a poor prognosis, and is managed using
immune therapy or using targeted molecular therapy
Acknowledgments
• Erica Gupta
• Maryellen Sun
• Gillian Lieberman
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Glenn Dranoff
Richard Haspel
Adam Jeffers
Jay Pahade
Rich Rana
Aarti Sekhar
Jennifer Son
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