Fig. 5.43 Amyloidosis.(A)AsectionofliverstainedwithCongoredrevealspink-reddepositsofamyloidinthewallsofbloodvesselsandalongsinusoids.
(B)Notetheyellow-greenbirefringenceofthedepositswhenobservedbyapolarizingmicroscope.(B, Courtesy of Dr.Trace Worrell and Sandy Hinton, Department of Pathology,University of Texas Southwestern Medical School,Dallas,Texas.) http://ebooksmedicine.net
Amyloidosis may be found as an unsuspected anatomic change, having produced no clinical manifestations, or it may cause serious clinical problems and even death. The symptoms depend on the magnitude of the deposits and on the sites or organs affected. Clinical manifestations at first are often entirely nonspecific, such as weakness, weight loss, lightheadedness, or syncope. Somewhat more specific findings appear later and most often relate to renal, cardiac, and gastrointestinal involvement.
Renal involvement gives rise to proteinuria that may be severe enough to cause the nephrotic syndrome (Chapter 14). Progressive obliteration of glomeruli in advanced cases ultimately leads to renal failure and uremia. Renal failure is a common cause of death. Cardiac amyloidosis may present insidiously as congestive heart failure. The most serious aspects of cardiac amyloidosis are conduction disturbances and arrhythmias, which may prove fatal. Occasionally, cardiac amyloidosis produces a restrictive pattern of cardiomyopathy and masquerades as chronic constrictive pericarditis (Chapter 11). Gastrointestinal amyloidosis may be asymptomatic, or it may present in a variety of ways. Amyloidosis of the tongue may cause sufficient enlargement and inelasticity to hamper speech and swallowing. Depositions in the stomach and intestine may lead to malabsorption, diarrhea, and disturbances in digestion. Vascular amyloidosis causes vascular fragility that may lead to bleeding, sometimes massive, that can occur spontaneously or following seemingly trivial trauma. Additionally, in some cases AL amyloid binds and inactivates factor X, a critical coagulation factor, leading to a life-threatening bleeding disorder.
The diagnosis of amyloidosis depends on the histologic demonstration of amyloid deposits in tissues. The most common sites biopsied are the kidney, when renal manifestations are present, or rectal or gingival tissues in patients suspected of having systemic amyloidosis. Examination of abdominal fat aspirates stained with Congo red can also be used for the diagnosis of systemic amyloidosis. The test is quite specific, but its sensitivity is low. In suspected cases of AL amyloidosis, serum and urine protein electrophoresis and immunoelectrophoresis should be performed. Bone marrow aspirates in such cases often show a monoclonal population of plasma cells, even in the absence of overt multiple myeloma. Scintigraphy with radiolabeled serum amyloid P (SAP) component is a rapid and specific test, since SAP binds to the amyloid deposits and reveals their presence. It also gives a measure of the extent of amyloidosis and can be used to follow patients undergoing treatment. Mass spectroscopy is a useful tool for identification of the protein component of amyloid. It can be performed on paraffin embedded tissues.
The prognosis for individuals with generalized amyloidosis is poor. Those with AL amyloidosis (not including multiple myeloma) have a median survival of 2 years after diagnosis. Individuals with myeloma-associated amyloidosis have an even poorer prognosis. The outlook for individuals with reactive systemic amyloidosis is somewhat better and depends to some extent on the control of the underlying condition. Resorption of amyloid after treatment of the associated condition has been reported, but this is a rare occurrence. New therapeutic strategies aimed at correcting protein misfolding and inhibiting fibrillogenesis are being developed.