Page 1599 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 87 Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma 1425

gammopathy are the two cardinal features of the Schnitzler syndrome, into many clinical laboratories and may help in clarifying the
which is not usually associated initially with clinical features of WM, diagnosis of WM from other IgM-secreting entities. 35–39 The use of
113
although evolution to WM is not uncommon. Thus close follow-up peripheral blood B cells may also permit determination of MYD88 L265P
of such patients is important. status by allele-specific PCR assays, particularly in untreated patients
with WM.
Joints. Invasion of articular and periarticular structures by WM
malignant cells is rarely reported. 114
IMMUNOLOGIC ABNORMALITIES
Eye. The neoplastic cells can infiltrate the periorbital structures,
lacrimal gland, and retroorbital lymphoid tissues, resulting in ocular High-resolution electrophoresis combined with immunofixation of
nerve palsies. 115,116 serum and urine is recommended for identification and characteriza-
tion of the IgM monoclonal protein. The light chain of the mono-
Central Nervous System. Direct infiltration of the central nervous clonal IgM is κ in 75% to 80% of patients. More than one M
system by monoclonal lymphoplasmacytic cells as infiltrates or as component may be present. The concentration of the serum mono-
tumors constitutes the rarely observed Bing-Neel syndrome, charac- clonal protein is very variable, but in most cases it lies within the
terized clinically by confusion, memory loss, disorientation, and range of 15–45 g/L. Densitometry should be adopted to determine
117
motor dysfunction (reviewed by Civit et al. ). IgM levels for serial evaluations because nephelometry is unreliable
and shows large laboratory variation. The presence of cold agglutinins
or cryoglobulins may affect determination of IgM levels, and therefore
LABORATORY FINDINGS testing for cold agglutinins and cryoglobulins should be performed
at diagnosis. If present, subsequent serum samples should be analyzed
Blood Abnormalities at 37°C for determination of serum monoclonal IgM level. Although
Bence Jones proteinuria is frequently present, it exceeds 1 g/24 h in
Anemia is the most common finding in patients with symptomatic only 3% of cases. Whereas IgM levels are elevated in patients with
WM and is caused by a combination of factors: decrease in red WM, IgA and IgG levels are most often depressed and do not recover
cell survival, impaired erythropoiesis, moderate plasma volume after successful treatment. 123
expansion, hepcidin production leading to an iron reuse defect, and
blood loss from the gastrointestinal tract. 16,118,119 Blood films are
usually normocytic and normochromic, and rouleau formation is SERUM VISCOSITY
often pronounced. Mean red cell volume may be elevated spuri-
ously owing to erythrocyte aggregation. In addition, the hemoglobin Because of their large size (molecular weight almost 1 million), most
estimate can be inaccurate (i.e., falsely high) because of interaction IgM molecules are retained within the intravascular compartment
64
between the monoclonal protein and the diluent used in some and can exert an undue effect on serum viscosity. Serum viscosity
120
automated analyzers. Leukocyte and platelet counts are usually can be measured if the patient has signs or symptoms of hyperviscos-
within their reference ranges at presentation, although patients may ity syndrome, though levels are often slow to be reported and erratic
16
occasionally present with severe thrombocytopenia. Monoclonal B owing to a lack of standardization in most clinical laboratories. As
lymphocytes expressing surface IgM and late-differentiation B-cell such, serum IgM levels may be more expedient and relied upon.
markers are uncommonly detected in blood by flow cytometry. Patients typically become symptomatic at serum viscosity levels of
A raised erythrocyte sedimentation rate is almost always present 4.0 cp and above, which relate to serum IgM levels above 6000 mg/
and may be the first clue to the presence of macroglobulinemia. dL. 124,125 Patients may be symptomatic at lower serum viscosity and
The clotting abnormality detected most frequently is prolongation IgM levels, and in these patients cryoglobulins may be present. Recur-
of thrombin time. AL amyloidosis should be suspected in all patients ring nosebleeds, headaches, and visual disturbances are common
16
with nephrotic syndrome, cardiomyopathy, hepatomegaly, or periph- symptoms in patients with symptomatic hyperviscosity. Fundus-
eral neuropathy. Diagnosis requires the demonstration of green copy is an important indicator of clinically relevant hyperviscosity.
birefringence under polarized light of amyloid deposits stained with Among the first clinical signs of hyperviscosity are the appearance
Congo red. of peripheral and midperipheral dot- and blotlike hemorrhages in
the retina, which are best appreciated with indirect ophthalmoscopy
68
and scleral depression. In more severe cases of hyperviscosity, dot,
MARROW FINDINGS blot, and flame-shaped hemorrhages can appear in the macular
area along with markedly dilated and tortuous veins with focal
Central to the diagnosis of WM is the demonstration, by trephine constrictions resulting in “venous sausaging,” as well as papilledema
biopsy, of marrow infiltration by a lymphoplasmacytic cell population (Fig. 87.4).
characterized by small lymphocytes with evidence of plasmacytoid
and plasma cell maturation (Fig. 87.1). 1,14 The pattern of marrow
infiltration may be diffuse, interstitial, or nodular, usually with an IMAGING
intertrabecular pattern of infiltration. A solely paratrabecular pattern
of infiltration is unusual and should raise the possibility of fol- Magnetic resonance imaging (MRI) of the spine in conjunction with
1
licular lymphoma. The marrow cell immunophenotype should be computed tomography (CT) of the abdomen and pelvis are useful in
126
confirmed by flow cytometry and/or immunohistochemistry. The evaluating disease status. Marrow involvement can be documented
+
+
+
+
+
cell immunoprofile sIgM CD19 CD20 CD22 CD79 is character- by MRI studies of the spine in more than 90% of patients; CT of
istic of WM. 14,120,121 Up to 20% of cases may express either CD5, the abdomen and pelvis demonstrates enlarged nodes in approxi-
19
CD10, or CD23. In these cases, chronic lymphocytic leukemia and mately 20% of patients with WM at diagnosis, but this proportion
mantle cell lymphoma should be excluded. “Intranuclear” periodic may be higher at relapse. 126
122
acid-Schiff–positive inclusions (Dutcher-Fahey bodies) consist-
ing of IgM deposits in the perinuclear space, and sometimes in
intranuclear vacuoles, may be seen occasionally in lymphoid cells. LYMPH NODE BIOPSY
An increased number of mast cells, usually in association with the
lymphoid aggregates, is commonly found, and their presence may Lymph node biopsy may show preserved architecture or replacement
help in differentiating WM from other B-cell lymphomas (see Fig. by infiltration of neoplastic cells with lymphoplasmacytoid, lympho-
14
87.3). MYD88 L265P testing of BM samples has been incorporated plasmacytic, or polymorphous cytologic patterns.