Unknown case

conference
May 2008
 Chief complaint and
history
 59 year old woman
 Worsening abdominal pain, Weight loss
(↓30 lb) past 4 months
 Pain: right sided, no radiation, dull,
constant, eating worsens, also nausea,
vomiting and “bloating”.
 ROS: Fatigue, loss of appetite, short of
breath, frequent urination, ear pain.
 Seen in 2003 for pain.
 CT showed kidney cysts
 Exam and testing
 PAST MEDICAL HISTORY: Reflux
Chronic knee pain
History of breast cyst
 EXAM: RUQ tenderness.  Liver is palpated at the
costal edge.
 CT: Complex mass in the left ovary (4.7 x 6.9 x
4.9 cm)
Left and right kidneys with simple cysts.
Liver is “fatty”
 U/S: left hypoechoic ovarian mass, no free fluid in
pelvis, normal endometrium
 LABS:
 Hyperlipidemia with LDL of 332, triglycerides 294,
and total cholesterol 410
 Microscopic hematuria.
 Proteinuria 3+ on UA
 CA-125 was 13 U/mL (0-35)

 Colonoscopy:
 Patchy erythema right
colon near IC valve
 Patchy changes seen
throughout the remainder
of the colon, extending
down into the sigmoid
colon. 
 2 diminutive colon polyps
in sigmoid colon
 EGD:
 Moderate to severe antral
erythema and erosions
and friability.  Mostly pre-
pyloric
 TAH-BSO

Large
fibroid
and..
 Liver
biopsy

Congo Contr
 Liver
biopsy
 What’s Amyloid?
 Amorphous, eosinophilic,
hyaline, extracellular substance
 Congo red stain
 Apple green birefringence
 Pathologic misfolded protein
 Intrinsic property to assume pathologic
configuration
 Replacement of amino acid
 Proteolytic remodeling of protein
precursor
 “Apple Green
Birefringence”
 What you need
 Polarized light
 Congo red stained slide
Merlini G, Bellotti V. Molecular Mechanisms of Amyloidosis. N Engl J Med
 Amyloid types
 21 biochemically distinct forms
 Amyloid light chain (AL)
 Most are composed of λ light chains
 Associated with monoclonal B cell
proliferation.
 Amyloid associated (AA)
 Non-immunoglobulin protein made by liver
 Circulates in association with HDL3 subclass
of lipoproteins
 Reactive to chronic infection or inflammation
 Aβ amyloid
 Alzheimer’s
 Cerebral plaques and blood vessel walls
 Derived from amyloid precursor protein
 Biochemical-clinical
classification

Merlini G, Bellotti V. Molecular Mechanisms of Amyloidosis. N Engl J Med

 Organ involvement
 Nephrotic syndrome
 Restrictive cardiomyopathy
 Hepatomegaly
 Autonomic nervous system
 Orthostatic hypotension
 Early satiety as a result of delayed
gastric emptying
 Erectile dysfunction
 Intestinal motility issues
 Peripheral nervous system
 Painful, bilateral, symmetric, distal
sensory neuropathy
 Progresses to motor neuropathy
 Other soft tissue involvement
 Macroglossia
 Carpal tunnel syndrome
 Skin nodules
 Arthropathy
 Alopecia
 Nail dystrophy
 Submandibular gland enlargement
 Periorbital purpura
Merlini G, Bellotti V. Molecular Mechanisms of Amyloidosis.
 Hoarseness of voice.
N Engl J Med 2003;349:583-96.
 Mechanism of damage
 The deposition of large amounts of
fibrillar material can subvert the
tissue architecture
 Interacting with local receptors,
leading to an inflammatory response
 Precursors mediate cellular toxicity
through a mechanism that causes
oxidative stress and activates the
apoptotic pathway.
 Amyloid light chain
 In our population, multiple myeloma should be at
the top of your list when you find amyloid in a
biopsy.
 Plasma cell burden can be low 5-10%
 12-15% of patients with myeloma
 Fat pad biopsy (FNAFP)
 Often not considered clinically conclusive
 Followed by further invasive procedures to detect
amyloid
 Estimated sensitivity 75% and specificity 92%
 Overall, the reliance on the results depended on the
degree of clinical suspicion.
 Recent diagnostic and prognostic advances
 Serum free light-chain assay
 Cardiac magnetic resonance imaging
 Serologic
Ansari-Lari MA, Ali SZ. cardiac biomarkers.
Fine-needle aspiration of abdominal fat pad for amyloid detection: a
clinically useful test? Diagn Cytopathol. 2004 Mar;30(3):178-81.
 Lambda
Kappa

Further
IHC
showed
Kappa >
Lambda Control
 Bone
marrow
biopsy
and flow
cytometry
were
 Abnormal plasma cell

population done:
Abnormal expression
 CD19(absent)
 CD45 (variable)
 Monoclonal kappa cytoplasmic
light chain restriction
 SPE: IgA kappa Monoclonal Est.
1.9 g/dL
 Monoclonal component
characterized as free kappa
light chain too small to
quantitate.
 Normal gammaglobulins are
depressed.
 References:
 Ansari-Lari MA, Ali SZ. Fine-needle aspiration
of abdominal fat pad for amyloid detection: a
clinically useful test? Diagn Cytopathol. 2004
Mar;30(3):178-81.
 Robbins and Cotran Pathologic Basis of
Disease (7th ed.)
 Merlini G, Bellotti V. Molecular Mechanisms of
Amyloidosis. N Engl J Med 2003;349:583-96.
 Sanchorawala V. Light-Chain (AL)
Amyloidosis: Diagnosis and Treatment Clin J
Am Soc Nephrol, Nov 2006;1:1331-1341.