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1774 Part XI: Malignant Lymphoid Diseases Chapter 108: Immunoglobulin Light-Chain Amyloidosis 1775

TABLE 108–1. Nomenclature of Amyloidosis is important for clinicians to have an operational approach to avoid
inappropriate resource utilization. Only 1 percent of patients with AL
Clinical Organ amyloidosis are younger than age 40 years. Consequently, it would be
Amyloid Type Subunit Protein Involvement unlikely for younger patients to have AL amyloidosis, although this age
AL (κ or λ) or AH Immunoglobulin light Heart group regularly can be seen with secondary systemic amyloidosis. The
or heavy chain Kidney majority of patients with AL amyloidosis are males (66 percent), unlike
May be localized or Liver myeloma, where the male-to-female is 52:48. 15
systemic The most common symptoms reported by patients with amyloido-
Nerve
sis are fatigue, weight loss, and lower-extremity edema. Unfortunately,
AA Secondary serum Kidney these symptoms are too nonspecific to be used as a trigger to screen
amyloid A Gastrointestinal patients, as the yield for these vague symptoms would be very low. The
Thyroid mechanism underlying fatigue in this disorder is usually amyloid heart
disease, which can be an extremely subtle diagnosis and is discussed
ATTR Senile systemic Heart further under the specific amyloid syndromes. Weight loss accompany-
(age relelated) transthyretin Carpal tunnel ing amyloidosis can be impressive, and may exceed 20 kg. This usually
ATTR (mutant) Familial transthyretin Heart results in an investigation for occult malignancy; but even if blind biop-
Nerve sies are performed, the diagnosis may be overlooked if a specific request
for amyloid stains is not made to the pathologist. Lower-extremity edema
A Lect-2 Leukocyte chemotac- Kidney may be attributable to nephrotic range proteinuria, hypoalbuminemia,
tic factor and transudation of serum into the extracellular space. Edema may also
No mutation found be seen from high filling pressures caused by the restrictive cardiomyo-
A Ins Insulin localized to Skin pathy, which, again, can easily be overlooked because of the subtle diag-
injection sites nostic testing required. These patients are often treated empirically with
A Fib Fibrinogen A-2 Kidney diuretics until cardiac dysfunction becomes more evident.
mutation The physical findings of amyloidosis are present in only one patient
in six. Periorbital purpura is frequently cited as a diagnostic finding
A β M β -Microglobulin Soft tissue
2 2 and, when present, is useful but is only seen in 15 percent of patients
Chronic dialysis Joints spine (Fig. 108–1). Sometimes, the purpura is subtle and can only be seen
with the patient’s eyes closed. Even when purpura is present, it may lead
to an evaluation of a coagulopathy or platelet dysfunction, which would
invariably be negative in this setting. Purpura not only is seen on the
are extracted from the urine of patients with myeloma and injected eyelids but also on the face, neck, and anterior chest above the nipple
into mice, amyloid deposits are not seen. However, when the light line. Enlargement of the tongue is seen in approximately one person in
chains from patients with amyloidosis are extracted from the urine and eight (Fig. 108–2). Dental indentations on the underside of the tongue
injected into mice, they will develop amyloidosis. The exact structural are characteristic. Often the patient will have sudden-onset of sleep
8
characteristics that lead to the misfolding of the α helical protein into apnea syndrome as a result of occlusion of the airway by the enlarged
16
the amyloid β-pleated sheet configuration are unknown. Patients with tongue when the patient is supine. Even when diagnostic findings
amyloidosis are classified into those with myeloma and those without are present, their significance is often missed, leading in many cases
myeloma. The percentage of plasma cells present in the marrow at the to tongue biopsy with a preoperative suspicion of tongue cancer. Most
time of diagnosis is prognostic and predicts outcome in patients with patients with enlargement of the tongue will also have palpable subman-
amyloidosis. As a result, the percentage of plasma cells in the marrow dibular lymphadenopathy, usually caused by displacement of the nodes
9
may dictate alternate therapeutic considerations at diagnosis (see “Ther- by the enlarged base of the tongue; although amyloid infiltration of the
apy” below). Overt myeloma with CRAB criteria (hypercalcemia, renal submandibular gland may also result in a firm palpable mass in the sub-
insufficiency, anemia, or bone disease) is uncommon in AL amyloidosis. mandibular region. Hepatomegaly is seen in approximately 20 percent
However, an elevation in the percentage of plasma cells in the marrow of
patients without CRAB criteria confers the same adverse prognosis as
observed in patients who have overt symptomatic myeloma, and these
groups can be considered as a single cohort of myeloma-associated
amyloidosis. Patients who do not have myeloma at presentation have
almost no chance of developing myeloma later in the course of their dis-
ease. The plasma cells in the marrow of patients with amyloidosis tend
10
to be nonproliferative and frequently lack the karyotypic abnormalities
typically seen in myeloma, such as –17p, t(4;14), and –13. A transloca-
tion 11;14 is commonly seen in amyloidosis and appears to confer an
inferior outcome. Circulating plasma cells detectable by flow cytometry
are uncommonly seen relative to their frequency in myeloma 12
CLINICAL FEATURES

Unfortunately, the symptoms of amyloidosis are vague and often non-
specific. Physical findings, when present, can be highly specific but
are only present in a minority of patients. For a disease this rare, it Figure 108–1. Amyloid purpura.

Kaushansky_chapter 108_p1773-1784.indd 1774 9/18/15 9:52 AM