Page 1816 - Williams Hematology ( PDFDrive )

1790 Part XI: Malignant Lymphoid Diseases Chapter 109: Macroglobulinemia 1791

surface of the extremities, referred to as macroglobulinemia cutis. Eye
94
Deposition of monoclonal IgM in the lamina propria and/or submucosa The neoplastic cells can infiltrate the periorbital structures, lacrimal
of the intestine may be associated with diarrhea, malabsorption, and gas- gland, and retroorbital lymphoid tissues, resulting in ocular nerve
trointestinal bleeding. 95,96 Kidney involvement is less common and less palsies. 115,116
severe in WM than in myeloma, probably because the amount of light
chain excreted in the urine is generally lower in WM than in myeloma Central Nervous System
and because of the absence of contributing factors, such as hypercalce- Direct infiltration of the central nervous system by monoclonal lymphop-
97
mia. Urinary cast nephropathy, however, has occurred in WM. On the lasmacytic cells as infiltrates or as tumors constitutes the rarely observed
other hand, the IgM macromolecule is more susceptible to being trapped Bing-Neel syndrome, characterized clinically by confusion, memory loss,
in the glomerular loops where ultrafiltration presumably contributes to disorientation, and motor dysfunction (reviewed in Ref. 117).
its precipitation, forming subendothelial deposits of aggregated IgM pro-
98
teins that occlude the glomerular capillaries. Mild and reversible pro- LABORATORY FINDINGS
teinuria may result and most patients are asymptomatic. The deposition
of monoclonal light chain as fibrillar amyloid deposits (AL amyloidosis) BLOOD ABNORMALITIES
is uncommon in patients with WM. Clinical expression and prognosis
99
are similar to those of other AL amyloidosis patients with involvement Anemia is the most common finding in patients with symptomatic WM
of heart (44 percent), kidneys (32 percent), liver (14 percent), lungs (10 and is caused by a combination of factors: decrease in red cell survival,
percent), peripheral or autonomic nerves (38 percent), and soft tissues impaired erythropoiesis, moderate plasma volume expansion, hepcidin
(18 percent). The incidence of cardiac and pulmonary involvement is production leading to iron reutilization defect, and blood loss from
higher in patients with monoclonal IgM than with other immunoglobu- the gastrointestinal tract. 16,118,119 Blood films are usually normocytic
lin isotypes. The association of WM with reactive amyloidosis has been and normochromic, and rouleaux formation is often pronounced (see
documented rarely. 100,101 Simultaneous occurrence of fibrillary glomer- Fig. 109–1). Mean red cell volume may be elevated spuriously owing
ulopathy, characterized by glomerular deposits of wide noncongophilic to erythrocyte aggregation. In addition, the hemoglobin estimate can
fibrils and amyloid deposits, has been described. 102 be inaccurate, that is, falsely high, because of interaction between the
monoclonal protein and the diluent used in some automated analyz-
ers. Leukocyte and platelet counts are usually within the reference
120
MANIFESTATIONS RELATED TO TISSUE range at presentation, although patients may occasionally present with
INFILTRATION BY NEOPLASTIC CELLS severe thrombocytopenia. Monoclonal B-lymphocytes expressing
Tissue infiltration by neoplastic cells is uncommon but can involve var- surface IgM and late-differentiation B-cell markers are uncommonly
detected in blood by flow cytometry. A raised erythrocyte sedimenta-
ious organs and tissues, including the liver, spleen, lymph nodes, lungs, tion rate is almost always present and may be the first clue to the pres-
gastrointestinal tract, kidneys, skin, eyes, and central nervous system.
ence of the macroglobulinemia. The clotting abnormality detected most
frequently is prolongation of thrombin time. AL amyloidosis should
Lung be suspected in all patients with nephrotic syndrome, cardiomyopa-
Pulmonary involvement in the form of masses, nodules, diffuse infil- thy, hepatomegaly, or peripheral neuropathy. Diagnosis requires the
trate, or pleural effusions is uncommon; the overall incidence of pul- demonstration of green birefringence under polarized light of amyloid
monary and pleural findings is approximately 4 percent. 103–105 Cough is deposits stained with Congo red.
the most common presenting symptom, followed by dyspnea and chest
pain. Chest radiographic findings include parenchymal infiltrates, con-
fluent masses, and effusions. MARROW FINDINGS
Central to the diagnosis of WM is the demonstration, by trephine
Gastrointestinal Tract biopsy, of marrow infiltration by a lymphoplasmacytic cell population
Malabsorption, diarrhea, bleeding, or obstruction may indicate involve- characterized by small lymphocytes with evidence of plasmacytoid
1,14
ment of the gastrointestinal tract at the level of the stomach, duodenum, and plasma cell maturation (see Fig. 109–1). The pattern of mar-
or small intestine. 106–109 row infiltration may be diffuse, interstitial, or nodular, usually with an
intertrabecular pattern of infiltration. A solely paratrabecular pattern of
Renal System infiltration is unusual and should raise the possibility of follicular lym-
In contrast to myeloma, infiltration of the kidney interstitium with lym- phoma. The marrow cell immunophenotype should be confirmed by
1
phoplasmacytoid cell can occur in WM, and renal or perirenal masses flow cytometry and/or immunohistochemistry. The cell immunoprofile:
+
+
are not uncommon. 110,111 sIgM CD19 CD20 CD22 CD79 is characteristic of WM. 14,120,121 Up to
+
+
+
20 percent of cases may express either CD5, CD10, or CD23. In these
19
Skin cases, chronic lymphocytic leukemia and mantle cell lymphoma should
The skin can be the site of dense lymphoplasmacytic infiltrates, similar be excluded. “Intranuclear” periodic acid-Schiff–positive inclusions
122
to that seen in the liver, spleen, and lymph nodes, forming cutaneous (Dutcher-Fahey bodies) consisting of IgM deposits in the perinuclear
112
plaques and, rarely, nodules. Chronic urticaria and IgM gammopathy space, and sometimes in intranuclear vacuoles, may be seen occasion-
are the two cardinal features of the Schnitzler syndrome, which is not ally in lymphoid cells. An increased number of mast cells, usually in
usually associated initially with clinical features of WM, although evolu- association with the lymphoid aggregates is commonly found, and their
113
tion to WM is not uncommon. Thus, close followup of these patients presence may help in differentiating WM from other B-cell lympho-
14
is important. mas (Fig. 109–5). MYD88 L265P testing of marrow samples has been
incorporated into many clinical laboratories, and may help in clarifying
Joints the diagnosis of WM from other IgM-secreting entities. 35–39 The use of
Invasion of articular and periarticular structures by WM malignant blood B cells may also permit determination of MYD88 L265P status by
cells is rarely reported. 114 allele-specific PCR assays, particularly in untreated WM patients.

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