Papillary Renal Cell Carcinoma Presenting with Hemoptysis

eradiology.bidmc.harvard.edu

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

– Pneumonia

– Obstruction/collapse

– Pneumothorax

– Pleural effusion


Our patient’s initial evaluation by

BIDMC PACS

chest X-ray is shown below

Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray


ABCs of CXR : quality control

BIDMC PACS

Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray

Is this our patient? Do we have the standard views?

Is the entire region of interest covered? Exposure?


BIDMC PACS

ABCs of CXR : aberrant air

Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray

ABCs of CXR : bones


ABCs of CXR : cardiac silhouette

Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray

BIDMC PACS

ABCs of CXR : diaphragm


ABCs of CXR : cardiac silhouette

BIDMC PACS

Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray

depressed diaphragm


ABCs of CXR : cardiac silhouette

BIDMC PACS

Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray

small effusion


BIDMC PACS

ABCs of CXR : extras

Frontal Upright Chest X-Ray Left Lateral Upright Chest X-Ray

outside the patient


BIDMC PACS

ABCs of CXR : fields

Frontal Upright Chest X-Ray 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

BIDMC PACS

orange oval: focal density

could this be malignant?

yellow oval:

airspace filling

DDx: water,

blood, cells,

protein


Yellow circle:

density in the

right bronchus

malignancy?

mucus plug?

Right bronchial mass on CT

coronal reconstruction CT of the chest: soft tissue window

BIDMC PACS


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

BIDMC PACS


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.

• 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


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


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


Evidence that Bosniak

clinically meaningful

criteria are

Bosniak

% Malignant

Classification

I 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

Sagittal abdominal MRI: T1 pre-contrast

fat suppressed

yellow circle: posterior exophytic left kidney mass

high signal regions suggest focal hemorrhage

BIDMC PACS

Sagittal abdominal MRI: T1 post-

contrast fat suppressed

orange circle: hyper-intensity in the posterior

renal fat

malignant invasion? inflammation?

pink arrows: enhancing papillary nodules


Coronal MRI of the kidney

coronal abdominal MRI: T1 pre-contrast,

fat suppressed

BIDMC PACS

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

BIDMC PACS

pink arrows: enhancing papillary nodules


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


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)

Clear Cell RCC

http://pathologyoutlines.com

Papillary RCC

http://pathologyoutlines.com


• Staging

RCC staging and prognosis

– 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

Post contrast axial CT through the abdomen: soft tissue window

Yellow circle: complex cystic mass (Bosniak IV)

Orange rectangle: area of detail (next slide)

BIDMC PACS


Magnification view

Post contrast axial CT through the abdomen centered on IVC:

soft tissue window

complex cystic mass

(Bosniak IV)

Yellow oval: tumor thrombus in the IVC (stage III disease)

BIDMC PACS


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


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 intra-

bronchial metastases

• Poor prognosis, limited response to current therapies

• Entered into a clinical trial investigating a novel small

molecule inhibitor


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


• Erica Gupta

• Maryellen Sun

• Gillian Lieberman

• Glenn Dranoff

• Richard Haspel

• Adam Jeffers

• Jay Pahade

• Rich Rana

• Aarti Sekhar

• Jennifer Son

Acknowledgments


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