Page 1598 - Hematology_ Basic Principles and Practice ( PDFDrive )

1424 Part VII Hematologic Malignancies

A B

Fig. 87.5 MARROW CLOT SECTION. (A) Tryptase-staining mast cells surrounding a nodule of lympho-
plasmacytic cells in a patient with Waldenström macroglobulinemia. (B) Mast cells in the same section exhibit
strong CD40 ligand signaling, which has been shown to support (at least in part) the growth and survival of
lymphoplasmacytic cells.

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syndrome. Thus molecular mimicry may play a role in this Urinary cast nephropathy, however, has occurred in WM. On the
condition. Antisulfatide monoclonal IgM proteins, associated with other hand, the IgM macromolecule is more susceptible to being
sensory-sensorimotor neuropathy, have been detected in 5% of trapped in the glomerular loops, where ultrafiltration presumably
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patients with IgM monoclonal gammopathy and neuropathy. contributes to its precipitation, forming subendothelial deposits of
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Motor neuron disease has been reported in patients with WM and aggregated IgM proteins that occlude the glomerular capillaries.
monoclonal IgM with anti-GM 1 and sulfoglucuronyl paragloboside Mild and reversible proteinuria may result, and most patients are
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activity. Polyneuropathy, organomegaly, endocrinopathy, M protein, asymptomatic. The deposition of monoclonal light chain as fibril-
and skin changes (the POEMS syndrome) are rare in patients lar amyloid deposits (AL amyloidosis) is uncommon in patients
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with WM. 89 with WM. The clinical manifestations and prognosis are similar
to those of other patients with AL amyloidosis, with involvement
Cold Agglutinin Hemolytic Anemia. Monoclonal IgMs may have occurring in the heart (44%), kidneys (32%), liver (14%), lungs
cold agglutinin activity; they recognize specific red cell antigens at (10%), peripheral or autonomic nerves (38%), and soft tissues
temperatures below 37°C, producing a chronic hemolytic anemia. (18%). The incidence of cardiac and pulmonary involvement is
This disorder occurs in less than 10% of patients with WM and is higher in patients with monoclonal IgM than in those with other
associated with cold agglutinin titers greater than 1 : 1000 in most immunoglobulin isotypes. The association of WM with reactive amy-
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cases. The monoclonal component is usually an IgMκ and reacts loidosis has been documented rarely. 100,101 Simultaneous occurrence
most commonly with red cell I/i antigens, resulting in complement of fibrillary glomerulopathy, characterized by glomerular deposits
fixation and activation. 91,92 Mild to moderate chronic hemolytic of wide noncongophilic fibrils and amyloid deposits, has been
anemia can be exacerbated after cold exposure. Hemoglobin levels described. 102
usually remain above 70 g/L. The hemolysis is usually extravascular,
mediated by removal of C3b opsonized red cells by the mononuclear Manifestations Related to Tissue Infiltration by
phagocytes, primarily in the liver. Intravascular hemolysis from Neoplastic Cells
complement destruction of red blood cell membrane is infrequent. Tissue infiltration by neoplastic cells is uncommon but can involve
The agglutination of red cells in the skin circulation also causes various organs and tissues, including the liver, spleen, lymph nodes,
Raynaud syndrome, acrocyanosis, and livedo reticularis. Macroglobu- lungs, gastrointestinal tract, kidneys, skin, eyes, and central nervous
lins with the properties of both cryoglobulins and cold agglutinins system.
with anti-Pr specificity can occur. These properties may have as a
common basis the binding of the sialic acid–containing carbohydrate Lung. Pulmonary involvement in the form of masses, nodules,
present on red blood cell glycophorins and on Ig molecules. Several diffuse infiltrate, or pleural effusions is uncommon; the overall inci-
other macroglobulins with antibody activity toward autologous dence of pulmonary and pleural findings is approximately 4%. 103–105
antigens (e.g., phospholipids, tissue and plasma proteins), and foreign Cough is the most common presenting symptom, followed by
ligands have also been described. dyspnea and chest pain. Chest radiographic findings include paren-
chymal infiltrates, confluent masses, and effusions.
IgM Tissue Deposition. The monoclonal IgM can deposit in several
tissues as amorphous aggregates. Linear deposition of monoclonal Gastrointestinal Tract. Malabsorption, diarrhea, bleeding, or
IgM along the skin basement membrane is associated with bullous obstruction may indicate involvement of the gastrointestinal tract at
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skin disease. Amorphous IgM deposits in the dermis result in IgM the level of the stomach, duodenum, or small intestine. 106–109
storage papules on the extensor surface of the extremities, referred
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to as macroglobulinemia cutis. Deposition of monoclonal IgM in Renal System. In contrast to myeloma, infiltration of the kidney
the lamina propria and/or submucosa of the intestine may be associ- interstitium with lymphoplasmacytoid cell can occur in WM, and
ated with diarrhea, malabsorption, and gastrointestinal bleeding. 95,96 renal or perirenal masses are not uncommon. 110,111
Kidney involvement is less common and less severe in WM than
in myeloma, probably because the amount of light chain that is Skin. The skin can be the site of dense lymphoplasmacytic infiltrates,
excreted in the urine is generally less in WM than in myeloma and similar to those seen in the liver, spleen, and lymph nodes, forming
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because of the absence of contributing factors, such as hypercalcemia. cutaneous plaques and, rarely, nodules. Chronic urticaria and IgM