Douglas Krakower
Gillian Lieberman, MD
Amyloidosis: Imaging a Zebra
Douglas Krakower
Harvard Medical School Year III
Gillian Lieberman, MD
Douglas Krakower
Gillian Lieberman, MD
July 2002
2
Douglas Krakower
Gillian Lieberman, MD
Goals of this Presentation
• Outline a patient work-up that leads to a
diagnosis of amyloidosis
• Define amyloidosis
• Outline basic facts about the epidemiology,
classification, etiology, and prognosis of
amyloidosis
• Illustrate briefly two other presentations of
amyloidosis
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Douglas Krakower
Gillian Lieberman, MD
Initial Presentation of Our
Patient: “Mr. M”
• Mr. M → 52-year-old man
• History → HTN, hypercholesterolemia, s/p
cholecystectomy
• Presentation → abdominal pain x 4 hours
radiating to his back
• DDx:
– Pancreatitis
– Abdominal aortic aneurysm
– Perforation
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Douglas Krakower
Gillian Lieberman, MD
• The work-up of Mr. M’s
presentation…
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Douglas Krakower
Gillian Lieberman, MD
Step 1 in Work Up:
Radiographs and Labs
• Abdominal supine and erect
radiographs → within normal limits
• Labs → within normal limits, incl.
normal amylase/lipase
• Step 1 tests are inconclusive
∴ Step 2 → Abdominal CT
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Douglas Krakower
Gillian Lieberman, MD
Step 2 in Work Up: Abdominal CT
…Reveals Finding #1
Finding #1
•3.5 x 4.9 cm
rounded soft tissue
mass located in the
inferior portion of the
porta hepatis
•Extends into caudate
lobe of liver
BIDMC-PACS
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Douglas Krakower
Gillian Lieberman, MD
Abdominal CT
…Slice at Level of Paragastric and Paracaval Lymph
Nodes Reveals Finding #2
Finding #2
•Paragastric
lymphadenopathy
•Paracaval
lymphadenopathy
…other slices reveal
lymphadenopathy in
the celiac nodes as
well
BIDMC-PACS
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Douglas Krakower
Gillian Lieberman, MD
Abdominal CT
…Liver Window Reveals Finding #3
Finding #3
•Diffuse,
heterogeneous,
low attenuation
of liver
BIDMC-PACS
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Douglas Krakower
Gillian Lieberman, MD
• An anatomy review will help to
place Mr. M’s findings in
context…
10
Douglas Krakower
Gillian Lieberman, MD
Anatomy of Lymph Nodes in the Region
of the Porta Hepatis and the Pancreas
•From Netter, FH. The Ciba Collection of Medical Illustrations/prepared by Frank
H. Netter. West Caldwell, NJ: Ciba, 1983.
Finding #1
Soft tissue
mass near
porta
hepatis/
head of
pancreas
Finding #3: Diffuse, heterogeneous low attenuation of liver
Finding #2
Lymphadeno-
pathy of
paragastric,
paracaval,
and celiac
nodes
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Douglas Krakower
Gillian Lieberman, MD
• What are the differential
diagnoses for Mr. M’s findings?
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Douglas Krakower
Gillian Lieberman, MD
Differential Diagnoses for Mr. M’s Findings
DDx for Mass in the Region of the Pancreas on CT
• Abcess
• Carcinoma of liver, bile duct, pancreas
• Metastasis
• Lymphadenopathy
DDx for Generalized Low Attenuation Lesions on Non-
contrast CT
• Diffuse malignancy
• Fatty infiltration
• Amyloidosis (uncommon)
…No clear diagnosis → CT-guided biopsies
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Douglas Krakower
Gillian Lieberman, MD
• As imaging studies yield no clear
diagnosis for Mr. M, the work-up
requires a biopsy of Mr. M’s
lesions.
• The biopsy is performed under CT
guidance…
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Douglas Krakower
Gillian Lieberman, MD
Step 3 in Work Up:
Biopsy of Lesions
• CT-guided biopsies
(1) mass near porta hepatis
(2) liver tissue in area of low
attenuation
• Congo red stain → Green bi-refringence
∴ Dx → AMYLOIDOSIS
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Douglas Krakower
Gillian Lieberman, MD
• The pathological diagnosis is
amyloidosis.
• Here is an example of the
histology of amyloidosis…
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Douglas Krakower
Gillian Lieberman, MD
Step 3 in Work Up:
Biopsy of Lesions
• Histology of amyloidosis in liver tissue
• Note amyloid deposits in blood vessel walls
Liver tissue:H&E stain Congo Red stain
From Robbins Pathologic Basis of Disease, 6th ed, by Ramzi S Cotran,
Vinay Kumar, and Tucker Collins, eds, 1425 pp. Philadelphia, Pa: WB
Saunders & Co, 1998.
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Douglas Krakower
Gillian Lieberman, MD
• Are there any other findings in
Mr. M that support the
diagnosis of amyloidosis?
• Thoracic CT reveals supportive
findings…
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Douglas Krakower
Gillian Lieberman, MD
Support of Diagnosis in Mr. M:
CT and Pathology Findings in Thorax
•Mediastinal and
hilar
lymphadenopathy
•Ultrasound-guided
biopsy of lymph
nodes → amyloid
deposits
BIDMC-PACS
19
Douglas Krakower
Gillian Lieberman, MD
• Mr. M has amyloidosis.
• What is amyloidosis?
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Douglas Krakower
Gillian Lieberman, MD
Amyloidosis: Definition
• Not a single disease entity
• Term for diseases that lead to extracellular
deposition of insoluble fibrillar proteins in tissues
• Fibrills are all beta-pleated sheets
21
Douglas Krakower
Gillian Lieberman, MD
Amyloidosis:
Most Common Presentations
• Heart → CHF
• Kidneys → Nephrotic syndrome
• Liver → Hepatomegaly
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Douglas Krakower
Gillian Lieberman, MD
Amyloidosis:
Incidence and Classification
• Incidence: 1275-3200 patients/year in USA
Subtype Underlying Disease
Process
Prognosis
(Median survival
after diagnosis)
Primary
amyloidosis
Plasma cell
dyscrasias 1-2 yrs
Secondary
amyloidosis
Chronic
inflammation Variable
Familial
amyloidosis Mutated proteins Up to 15 yrs
Adapted from Falk RH, Comenzo, RL, Skinner, M. The Sustemic Amyloidoses. N Engl J Med 1997; 337: 898-909.
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Douglas Krakower
Gillian Lieberman, MD
• Let’s look at another patient’s
presentation of amyloidosis…
24
Douglas Krakower
Gillian Lieberman, MD
Another Presentation of
Amyloidosis: Patient #2
• Patient #2 → 19-year-old man with a 9 year
history of progressive wheezing
• Chest radiographs were obtained
25
Douglas Krakower
Gillian Lieberman, MD
Patient #2 → PA Chest Radiograph
• Region of increased radio-opacity in tracheal lumen suggestive of a
mass
•Left tracheal deviation
Note
increased
radio-
opacity in
tracheal
lumen
Courtesy of Dr. Phillip Boiselle, BIDMC
26
Douglas Krakower
Gillian Lieberman, MD
• What is the differential
diagnosis for an intratracheal
mass as seen in Patient #2?
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Douglas Krakower
Gillian Lieberman, MD
Patient #2 → Differential Diagnosis
• DDx of Intratracheal Mass
– Adenoma
– Neoplasm, primary or secondary
– Amyloidosis
– Hamartochondroma
– Lymphoma
– Many more…
• Next step in work up →MRI
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Douglas Krakower
Gillian Lieberman, MD
• An MRI is needed to
characterize further the
intratracheal mass…
29
Douglas Krakower
Gillian Lieberman, MD
MRI of Tracheobronchial
Amyloidosis
•Coronal view of trachea
•Exophytic mass
•Biopsy → amyloid
Courtesy of Dr. Phillip Boiselle, BIDMC
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Douglas Krakower
Gillian Lieberman, MD
• Biopsy of the intratracheal mass
revealed amyloid deposits, solidifying
a diagnosis of amyloidosis for Patient
#2.
• Let’s look briefly at one more way that
amyloidosis can present…
31
Douglas Krakower
Gillian Lieberman, MD
Yet Another Presentation of
Amyloidosis : Small Bowel Amyloidosis
•Barium study
of small bowel
•Nodular,
irregular
thickening of
bowel folds
•Biopsy →
amyloid
Courtesy of Dr. Jonathan Kruskal, BIDMC
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Douglas Krakower
Gillian Lieberman, MD
Take-Home Message
• Amyloidosis has a protean presentation
• Can affect almost any organ
• Uncommon disease that commonly appears on
DDx for imaging findings…Even though it is a
“zebra” diagnosis, it should be considered!
• If high clinical suspicion → biopsy to confirm
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Douglas Krakower
Gillian Lieberman, MD
References
• Carlson, HC, Breen, JF. Amyloidosis and Plasma Cell Dyscrasias: Gastrointestinal
Involvement. Seminars in Roentgenology 1986; XXI: 128-138.
• Falk RH, Comenzo, RL, Skinner, M. The Sustemic Amyloidoses. N Engl J Med 1997; 337: 898-
909.
• Gross, BH, Felson, B, Birnberg, FA. The Respiratory Tract in Amyloidosis and the Plasma Cell
Dyscrasias. Seminars in Roentgenology 1986; XXI: 113-127.
• Netter, FH. The Ciba Collection of Medical Illustrations/prepared by Frank H. Netter. West
Caldwell, NJ: Ciba, 1983.
• Pear, BL. Other Organs and Other Amyloids. Seminars in Roentgenology 1986; XXI: 150-164.
• Reeder, MM, Bradley, WG Jr. Reeder and Felson’s Gamuts in Radiology: Comprehensive
Lists of Roentgen Differential Diagnosis, 3rd Edition. New York: Springer-Verlag, 1998.
• Robbins Pathologic Basis of Disease, 6th ed, by Ramzi S Cotran, Vinay Kumar, and Tucker
Collins, eds, 1425 pp. Philadelphia, Pa: WB Saunders & Co, 1998.
• Scott, PP, Scott, WW Jr., Siegelman, SS. Amyloidosis: An Overview. Seminars in
Roentgenology 1986; XXI: 103-112.
• Yamada, CY. Radiology-Pathology Correlation Conference, Massachusetts General Hospital.
Jan 2, 1996. ACR 671.68.
References
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Douglas Krakower
Gillian Lieberman, MD
Acknowledgements
• Dr. Jonathan Kruskal
• Dr. Phillip Boiselle
• Dr. Dan Saurborn
• Dr. Gillian Lieberman
• Pamela Lepkowski
• Larry Barbaras and Cara Lyn D’amour
• The Members of BIDMC Radiology Core
Clerkship, July 2002
Amyloidosis: Imaging a Zebra
Goals of this Presentation
Initial Presentation of Our Patient: “Mr. M”
Slide Number 4
Step 1 in Work Up:�Radiographs and Labs
Step 2 in Work Up: Abdominal CT�…Reveals Finding #1
Abdominal CT�…Slice at Level of Paragastric and Paracaval Lymph Nodes Reveals Finding #2
Abdominal CT�…Liver Window Reveals Finding #3
Slide Number 9
Anatomy of Lymph Nodes in the Region of the Porta Hepatis and the Pancreas
Slide Number 11
Differential Diagnoses for Mr. M’s Findings
Slide Number 13
Step 3 in Work Up:�Biopsy of Lesions
Slide Number 15
Step 3 in Work Up:�Biopsy of Lesions
Slide Number 17
Support of Diagnosis in Mr. M:�CT and Pathology Findings in Thorax
Slide Number 19
Amyloidosis: Definition
Amyloidosis:�Most Common Presentations
Amyloidosis: �Incidence and Classification
Slide Number 23
Another Presentation of Amyloidosis: Patient #2
Patient #2 PA Chest Radiograph
Slide Number 26
Patient #2 Differential Diagnosis
Slide Number 28
MRI of Tracheobronchial Amyloidosis
Slide Number 30
Yet Another Presentation of Amyloidosis : Small Bowel Amyloidosis
Take-Home Message
References
Acknowledgements