Page 1126 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1090 Part eight Immunology of Neoplasia

with mu HCD have increased free light chain secretion, and they LIGHT CHAIN AMYLOIDOSIS
may develop cast nephropathy or amyloidosis. 23
Amyloidosis refers to the deposition of fibrils composed of
Diagnosis low-molecular-weight subunits of normal serum proteins. AL
The diagnosis of the HCDs can be made on histopathological amyloidosis is a specific form of amyloidosis caused by the
examination of affected tissues and/or analysis of serum or urine deposition of monoclonal light chains. These light chains undergo
samples by electrophoresis and immunofixation electrophoresis. transformation to a beta-pleated fibrillar configuration. Deposi-
A typical M-spike in the serum or urine may not always be tion of these light chains in various organs results in organ failure.
present. On serum or urine immunofixation electrophoresis or AL amyloidosis is an uncommon disorder of older adults,
immunohistochemical staining of affected tissues, the abnormal and the exact incidence is unknown. In the United States, the
protein consists of a heavy chain without an associated light incidence is approximately 6–10 cases per million person-years.
chain. Immunohistochemical staining of affected tissue shows Age-specific incidence rates increase in each decade of life after
the presence of a clonal population of cells staining positively age 40 years. The median age at diagnosis is 64 years, and less
for a heavy chain but negative for both kappa and lambda light than 5% of patients are under the age of 40. There is a male
chains. 23 predominance, with men accounting for 65–70% of patients. AL
Alpha HCD most commonly involves infiltration of the jejunal amyloidosis occurs in all races and all geographic locations. 24
mucosa with plasmacytoid cells, whereas the duodenum and
ileum are affected less often. The diagnosis depends upon the Clinical Presentation
recognition of a monoclonal alpha heavy chain without an AL amyloidosis is a systemic disorder that can present with a
associated light chain in the serum, urine, intestinal secretions, variety of symptoms, including significant proteinuria, edema,
or the cells infiltrating the intestinal mucosa. The serum protein hepatosplenomegaly, otherwise unexplained heart failure, and
electrophoretic pattern is normal in one-half of cases, and in carpal tunnel syndrome. Although virtually all patients have
the remainder an unimpressive broad band may appear in the multisystem amyloid deposition, it is not uncommon for a patient
alpha-2 or beta mobility regions. The amount of alpha heavy to present with evidence of mainly one organ involvement.
chain in the urine is small. 23 Nonspecific systemic symptoms, including fatigue and
Gamma HCD is typically associated with a polymorphous unintentional weight loss, are common in patients with AL
infiltrate, including admixtures of lymphocytes, plasmacytoid amyloidosis. Renal involvement occurs in approximately 70%
lymphocytes, plasma cells, immunoblasts, and eosinophils. of patients and most often presents as asymptomatic proteinuria
The electrophoretic pattern often shows a broad-based band or nephrotic syndrome. Cardiac involvement is seen in approxi-
more suggestive of a polyclonal increase, but the gamma chains mately 60% of patients and typically is characterized by thickening
are monoclonal. The diagnosis is established by immunofixa- of the interventricular septum and ventricular wall. This can
tion electrophoresis, which shows that the abnormal protein lead to systolic or diastolic dysfunction with symptoms of heart
consists only of gamma heavy chains without associated light failure. Other manifestations that may be seen include sudden
chains. 23 death or syncope due to arrhythmia or heart block and, rarely,
Mu HCD is characterized by vacuolated plasma cells or angina or infarction due to accumulation of amyloid in the
lymphoid cells observed in the bone marrow, together with coronary arteries. 24
panhypogammaglobulinemia. The serum protein electrophoretic Hepatomegaly with or without splenomegaly is seen in as
pattern is usually normal, except for hypogammaglobulinemia. 23 many as 70% of patients. Potential gastrointestinal manifestations
include bleeding, gastroparesis, constipation, bacterial overgrowth,
Management and Prognosis malabsorption, and intestinal pseudo-obstruction resulting from
Initial treatment of alpha HCD consists of eradication of any dysmotility. 24
concurrent infection with appropriate antibiotics. Those with Mixed sensory and motor peripheral neuropathy and/or
symptomatic disease who do not respond adequately to antibiotics autonomic neuropathy is a prominent feature in AL amyloidosis.
may be treated with chemotherapy similar to that used for non- Symptoms of numbness, paresthesia, and pain are frequently
23
Hodgkin lymphoma, such as the CHOP regimen. Treatment noted, as in peripheral neuropathy of many other causes. Com-
of gamma HCD is indicated only for symptomatic patients. pression of peripheral nerves, especially the median nerve within
Appropriate chemotherapy includes melphalan plus prednisone the carpal tunnel, can cause more localized sensory changes.
or regimens used to treat B-cell lymphoma, such as the combina- Symptoms of bowel or bladder dysfunction and findings of
tion of cyclophosphamide, vincristine, and prednisone, with or orthostatic hypotension may be due to autonomic nervous system
without doxorubicin, or rituximab if the abnormal cells express damage. 24
23
CD20. Treatment for symptomatic patients with mu HCD is Amyloid infiltration of skeletal muscles may cause visible
similar to that employed in patients with CLL (e.g., glucocorti- enlargement. Macroglossia, or lateral scalloping of the tongue
coids, alkylating agents, fludarabine). 23 from impingement on the teeth, is characteristic of AL amyloid.
In the absence of therapy, alpha HCD typically is progressive Arthropathy may be due to amyloid deposition in joints and
and fatal. The prognosis of gamma HCD is variable and ranges surrounding structures. The “shoulder pad“ sign is visible
from the asymptomatic presence of a stable monoclonal heavy enlargement of the anterior shoulder due to fluid in the gleno-
chain in the serum or urine (e.g., MGUS) to a rapidly progressive humeral joint and/or amyloid infiltration of the synovial
downhill course over a short duration (e.g., highly aggressive membrane and surrounding structures. 24
lymphoma). Median survival is 7.4 years with an extremely wide Purpura, characteristically elicited in a periorbital distribution
23
range from 1 month to more than 21 years. The course of mu (raccoon eyes) by a Valsalva maneuver or minor trauma, is present
HCD is variable, and survival ranges from a few months to many in only a minority of patients, but it is highly characteristic of
years. 23 AL amyloidosis. Other signs of skin involvement include waxy