Amyloid for pathology

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Patient presenting with amyloid in multiple biopsies.

Transcript of Amyloid for pathology

Unknown case conferenceMay 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

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)

Exam and testing

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 Moderate to severe antral erythema and erosions and friability. Mostly prepyloric

EGD:

TAH-BSOLarge fibroid and..

Liver biopsy

Congo

Contr

Liver biopsy

Whats Amyloid?

Amorphous, eosinophilic, hyaline, extracellular substance Congo red stain Apple green birefringence Pathologic misfolded proteinIntrinsic 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 light chains Associated with monoclonal B cell proliferation. Non-immunoglobulin protein made by liver Circulates in association with HDL3 subclass of lipoproteins Reactive to chronic infection or inflammation Alzheimers Cerebral plaques and blood vessel walls Derived from amyloid precursor protein

Amyloid associated (AA)

A amyloid

Biochemical-clinical classification

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

Organ involvement

Merlini G, Bellotti V. Molecular Mechanisms of Amyloidosis. N Engl J Med 2003;349:583-96.

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 Hoarseness of voice.

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.

Serum free light-chain assay Cardiac magnetic resonance imaging Serologic Fine-needle biomarkers. Ansari-Lari MA, Ali SZ. cardiac aspiration of abdominal fat pad for amyloid detection: aclinically useful test? Diagn Cytopathol. 2004 Mar;30(3):178-81.

Recent diagnostic and prognostic advances

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.