Diagnostic Radiology and Nuclear Medicine Imaging in Hodgkin`s

Brett Cox
Gillian Lieberman, MD
March 2001
Diagnostic Radiology and
Nuclear Medicine Imaging in
Hodgkin’s Disease
Brett Cox, Harvard Medical School, Year III
Gillian Lieberman, MD
Brett Cox
Gillian Lieberman, MD
Agenda
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Introduction to radiological regions of the mediastinum.
Differential diagnosis of an anterior mediastinal mass.
Brief review of Hodgkin’s disease.
Radiological imaging for Hodgkin’s disease.
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Menu of tests
Diagnostic potential and limitations of tests
Role in treatment monitoring and follow-up
Introduction to gallium scanning
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Brett Cox
Gillian Lieberman, MD
Patient Clinical History
• A previously healthy 26-year-old white male was
referred to the BIDMC infectious disease department for
evaluation of:
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Anorexia with weight loss of 173 to 148 pounds over 8 months
Occasional headaches
Nonproductive cough
Prolonged unexplained fevers to 1032
Worsening drenching night sweats
• Entire infectious disease work-up was negative.
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Brett Cox
Gillian Lieberman, MD
Chest P A and Lateral
BIDMC
BIDMC
• Done as part of the FUO work-up and revealed:
– A right mediastinal opacity.
– Obliteration of the retrosternal clear space.
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Brett Cox
Gillian Lieberman, MD
Areas of the Mediastinum
• Anterior: Bounded by the
clavicles, diaphragm, sternum,
and the pericardium and
trachea.
• Middle: Between the anterior
and posterior mediastinum.
Includes the heart, great
vessels, and pulmonary roots.
A
M
P
• Posterior: Bounded by the
thoracic inlet, diaphragm,
vertebral bodies/paravertebral
gutters, and the pericardium.
Novelline, RA. Squire’s Fundamentals of Radiology.
Cambridge, Harvard University Press, 1997.
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Brett Cox
Gillian Lieberman, MD
Regions of the Anterior
Mediastinum
I
• Region I
II
• Region II
III
• Region III
Novelline, RA. Squire’s Fundamentals of Radiology.
Cambridge, Harvard University Press, 1997.
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Brett Cox
Gillian Lieberman, MD
Differential Diagnosis: Adult
Anterior Mediastinal Mass
• Region I
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• Region III
Retrosternal goiter
Tortuous innominate artery
Lymph nodes
Thymic tumors
Ascending aortic aneurysms
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Pericardiac fat pad
Diaphragmatic hump
Morgagni hernia
Pericardial cysts
I
• Region II
– Germ cell neoplasms
– Thymic tumors
– Sternal tumors (usually mets)
Novelline, RA. Squire’s Fundamentals of Radiology.
Cambridge, Harvard University Press, 1997.
II
III
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Brett Cox
Gillian Lieberman, MD
Definitive Diagnosis
• A Chamberlain procedure (mediastinotomy) was
performed.
• Multiple biopsies of the large anterior mediastinal
mass were taken.
• Histology and flow cytometry revealed Hodgkin’s
Disease, nodular sclerosing type.
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Brett Cox
Gillian Lieberman, MD
Hodgkin’s Disease
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7500 new cases per year.
20% of all lymphomas.
Mean age of diagnosis is 32.
Arises in a single node and spreads characteristically
to anatomically contiguous nodes.
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Brett Cox
Gillian Lieberman, MD
Hodgkin’s Disease
• Often associated with distinctive “B symptoms”:
– Unexplained fevers > 38oC.
– Drenching night sweats in past month.
– Weight loss >10% over 6 months.
• Histology: Reed-Sternberg cell
admixed with a variable
inflammatory infiltrate.
Cotran RS, Kumar V, Robbins SL. Pathologic Basis of Disease.
Philadelphia, W.B. Saunders Company, 1994.
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Brett Cox
Gillian Lieberman, MD
Imaging in Hodgkin’s Disease
• Staging is of utmost clinical importance because
therapy, prognosis, and clinical course are all intimately
related to the distribution of disease.
• Diagnostic radiology and nuclear medicine play a
pivotal role in:
– Initial staging.
– Intra-treatment surveillance.
– Post-treatment surveillance.
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Brett Cox
Gillian Lieberman, MD
Hodgkin’s Disease Staging
Ann Arbor Classification
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Mauch PM, Armitage JO, Diehl V, Hoppe RT, Weiss JM (ed). Hodgkin’s Disease. Philadelphia, Lippincott Williams & Wilkins, 1999.
Brett Cox
Gillian Lieberman, MD
Radiographic work-up in initial
staging
• Mandatory radiological work-up includes:
– Chest PA/lateral
– CT of thorax
– CT of abdomen and pelvis ( replaces Bipedal lymphangiogram)
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Brett Cox
Gillian Lieberman, MD
CT Scan
– Done with IV contrast, early phase imaging, 1 cm slices.
– Detects intrathoracic disease not detected on CXR in 20% of
patients.
– Between 10-60% of patients have management change post-CT.
– Sensitivity of abdominal node detection equal to bipedal
lymphangiography and is noninvasive and gives added
information.
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Brett Cox
Gillian Lieberman, MD
Characteristics
CT findings:
General rule: nodes >1 cm are concerning.
– Often see Asymmetric, anterior mediastinal soft tissue mass.
– Pleural effusions in 30% of cases (lymphatic/venous obstruction).
– Benign pericardial effusions common.
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Brett Cox
Gillian Lieberman, MD
Out Patient: Chest CT
• Large, well
circumscribed
anterior
mediastinal
mass.
BIDMC
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Brett Cox
Gillian Lieberman, MD
Out Patient: Chest CT
• Small pericardial
effusion.
• Small right pleural
effusion.
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BIDMC
Brett Cox
Gillian Lieberman, MD
Radiographic work-up in initial
staging – optional tests
• Liver and spleen ultrasonography
– If clinical suspicion for involvement.
– Specificity & sensitivity similar to CT or MRI.
• Technetium bone scanning
– If bony pain, questionable lesions on other studies.
• MRI
– If suspected occult liver, spleen, thymus, bone marrow lesions.
– Specificity & sensitivity similar to CT for liver or spleen involvement.
• Gallium scanning
– Useful in differentiating scarring from active mediastinal lymphoma.
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Brett Cox
Gillian Lieberman, MD
Gallium radionuclide tumor
imaging
• Main indication:
– Staging of lymphomas, assessment of their response to therapy, and
relapse detection.
• Technique:
67Ga-citrate
administered I.V.
– Acquire delayed images.
– SPECT = rotation of a photon detector array around the body to
acquire data from multiple angles.
– Determines position and concentration of radionuclide distribution.
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• Imaging Mechanism
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Rough surrogate marker for tumor metabolic activity.
Increased permeability of tumor vessels
Large extracellular fluid space
Tumor up-regulation of iron-binding proteins such as ferritin
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Brett Cox
Gillian Lieberman, MD
Gallium radionuclide tumor
imaging
• Contraindications:
– None.
• Radiopharmaceutical: 67Ga-Gallium citrate
– 8-10 mCi, γ−emitter.
– Half-life = 78 hours.
– Binds to transferrin (in plasma), lactoferrin (in tissue), and ferritin.
• Equipment:
– Gamma camera w/ whole body and tomographic abilities, medium
or high energy collimator, imaging computer.
• Patient Preparation:
– Bowel regimen may be given after injection to clear activity.
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Brett Cox
Gillian Lieberman, MD
Gallium radionuclide tumor
imaging
• Images:
– Acquired at 48 and 72 hours.
– Sensitivity for detecting HD is about 85%, specificity of 90%.
– Sensitivity for mediastinal disease is 95%, specificity of 90%.
• Aftercare:
– None.
• Complications:
– None.
• Cost:
– The cost of SPECT imaging is around $700.
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Brett Cox
Gillian Lieberman, MD
Gallium radionuclide tumor
imaging
• Normal gallium activity:
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Renal cortex: First 24 hours.
Liver: Greatest uptake of gallium.
Spleen.
Bone marrow & blood pool: behavior as
an iron analog.
– Skeleton: Incorporated into the Cahydroxyapatite crystal as a Ca2+ analog.
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Children: physeal and thymic activity.
Glands: Nasopharynx, salivary & lacrimal.
Bowel: 1o colonic activity on delayed images.
Breasts & breast milk.
External genitalia.
BIDMC
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Brett Cox
Gillian Lieberman, MD
Our Patient: SPECT Imaging
• Large area of intense
tracer accumulation in
anterior mediastinum.
• Consistent with
history of mediastinal
lymphoma.
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BIDMC
Brett Cox
Gillian Lieberman, MD
Patient Treatment
• Chemotherapy: 5 cycles of ABVD
• Radiation therapy: Modified mantle
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Brett Cox
Gillian Lieberman, MD
Radiographic intra-treatment
surveillance
• Repeat studies with detectable lesions at presentation.
• Determines therapeutic response, therapy modification.
• Follow:
– Tumor volume decrease.
– New lesions.
– Therapy-induced lesions.
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Brett Cox
Gillian Lieberman, MD
Our Patient: Chest P A and Lateral
BIDMC
BIDMC
• Large right mediastinal mass has resolved.
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Brett Cox
Gillian Lieberman, MD
Frontal CXR Comparison
BIDMC
Pre-treatment
BIDMC
Intra-treatment
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Brett Cox
Gillian Lieberman, MD
Lateral CXR Comparison
BIDMC
Pre-treatment
BIDMC
Intra-treatment
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Brett Cox
Gillian Lieberman, MD
Our Patient: Chest CT
• Homogeneous
soft tissue mass
in the anterior
mediastinum
• 3.6 x 2.4 cm
BIDMC
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Brett Cox
Gillian Lieberman, MD
Chest CT Comparison
BIDMC
Pre-treatment
BIDMC
Intra-treatment
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Brett Cox
Gillian Lieberman, MD
Radiographic intra-treatment
surveillance
• Residual fibrotic mass often visible on CXR and CT.
• Further investigations determine nature of residual
abnormality.
• Gallium imaging after 3 cycles of chemotherapy is an
excellent prognostic indicator of clinical outcome.
• A complete response is achieved in 70% of patients.
– Longer disease free survival.
– Lower mortality.
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Brett Cox
Gillian Lieberman, MD
Our Patient: SPECT Imaging
• No abnormally
gallium-avid region
in the anterior
mediastinum.
BIDMC
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Brett Cox
Gillian Lieberman, MD
SPECT Comparison
BIDMC
Pre-treatment
BIDMC
Intra-treatment
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Brett Cox
Gillian Lieberman, MD
Radiographic post-treatment
surveillance
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Repeat investigations that were abnormal at presentation.
25% of relapses occur at new sites.
Regression of disease may be slow.
Residual fibrotic mass may still be visible on chest
radiograph and CT.
• Further investigations may be necessary to define nature
of residual abnormality, can also follow over time.
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Brett Cox
Gillian Lieberman, MD
References
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Castellino RA. 1992. Diagnostic imaging studies in patients with newly diagnosed Hodgkin's disease.
Annals of Oncology. 3 Suppl 4:45-7.
Chapman S, Nakielny R. Aids to Radiological Differential Diagnosis, 3rd edition. Philadelphia, W.B.
Saunders Company, 1995, 166-177.
Chapman S, Nakielny R. A Guide to Radiological Procedures. Philadelphia, W.B. Saunders Company,
1993, 298-299.
Cotran RS, Kumar V, Robbins SL. Pathologic Basis of Disease. Philadelphia, W.B. Saunders
Company, 1994, 643-648.
Front D, Israel O. 1995. The role of Ga-67 scintigraphy in evaluating the results of therapy of
lymphoma patients. Seminars in Nuclear Medicine. 25(1): 60-71.
Kramer EL, Sanger JJ (ed). Clinical SPECT imaging. New York, Raven Press, 1995, 7-38, 129-135,
197-201.
Mauch PM, Armitage JO, Diehl V, Hoppe RT, Weiss JM (ed). Hodgkin’s Disease. Philadelphia,
Lippincott Williams & Wilkins, 1999, 223-261.
McLaughlin AF, Magee MA, Greenough R, Allman KC, Southee AE, Meikle SR, Hutton BF, Joshua
DE, Bautovich GJ, Morris JG. 1990. Current role of gallium scanning in the management of lymphoma.
European Journal of Nuclear Medicine. 16(8-10):755-71.
Novelline, RA. Squire’s Fundamentals of Radiology. Cambridge, Harvard University Press, 1997.
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Brett Cox
Gillian Lieberman, MD
The End!
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Acknowledgements
• Beverlee Turner for her support and PowerPoint expertise
• Larry Barbaras and Ben Crandall our Web Masters
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