Chapter12- WBC: Plasma Cell Neoplasms and Related Disorders

Question 1

What are Plasma Cell Neoplasms?

Answer 1

These B-cell proliferations contain neoplastic plasma cells that virtually always secrete a
monoclonal Ig or Ig fragment.

Collectively, the plasma cell neoplasms (often referred to as dyscrasias) account for about 15% of the deaths caused by lymphoid neoplasms.

The most
common and deadly of these neoplasms is multiple myeloma, of which there are about 15,000
new cases per year in the United States

Question 2

What is the other name for plasma cell neoplasms?

Answer 2

Collectively, the plasma cell neoplasms (often referred to as dyscrasias) account for about 15% of the deaths caused by lymphoid neoplasms.

Question 3

What is the most
common and deadly of the plasma neoplasms

Answer 3

multiple myeloma, of which there are about 15,000
new cases per year in the United States

Question 4

A monoclonal Ig identified in the blood is referred to as what component, in reference to myeloma.

Answer 4

M component

Question 5

Why are complete M components restricted to the plasma and extracellular fluid and excluded from the urine in the absence of glomerular damage?

Answer 5

Since complete M components have molecular weights of 160,000 or higher, they are
restricted to the plasma and extracellular fluid and excluded from the urine in the absence of
glomerular damage.

Question 6

What are Bence-Jones proteins?

Answer 6

However, unlike normal plasma cells, in which the production and coupling
of heavy and light chains are tightly balanced, neoplastic plasma cells often synthesize excess
light or heavy chainsalong with complete Igs.

Occasionally only light chains or heavy chains
are produced.

The free light chains are small enough to be excreted in the urine, where they
are called Bence-Jones proteins.

Free light chains can be detected and measured in the urine or the blood, the latter with new, highly sensitive tests that are in the process of being
evaluated.

Question 7

Terms used to describe the abnormal Igs include monoclonal gammopathy, dysproteinemia, and
paraproteinemia. The following clinicopathologic entities are associated with monoclonal
gammopathies

Answer 7

• Multiple myeloma (plasma cell myeloma)
• Waldenström macroglobulinemia
• Heavy-chain disease
• Primary or immunocyte-associated amyloidosis
• Monoclonal gammopathy of undetermined significance (MGUS)

Question 8

What is Multiple myeloma (plasma cell myeloma) ?

Answer 8

• most important monoclonal gammopathy
• presents as tumorous masses scattered throughout the skeletal system.

Question 9

What is Solitary myeloma( plasmacytoma)?

Answer 9

• infrequent variant of multiple myeloma that presents as a single mass in bone or soft tissue

Question 10

Smoldering myeloma

Answer 10

refers to another uncommon variant of Multiple Myeloma defined by a lack of symptoms and a high plasma M component.

Question 11

What is Waldenström macroglobulinemia

Answer 11

is a syndrome in which high levels of IgM lead to
symptoms related to hyperviscosity of the blood.

It occurs in older adults, most
commonly in association with lymphoplasmacytic lymphoma

Question 12

What is heavy chain disease?

Answer 12

rare monoclonal gammopathy that is seen in association with a
diverse group of disorders, includinglymphoplasmacytic lymphomaand anunusual
small bowel marginal zone lymphomathat occurs inmalnourished populations (so-called
Mediterranean lymphoma).

The common feature is the synthesis and secretion of free heavy-chain fragments.

Question 13

Heavy-chain disease is a rare monoclonal gammopathy that is seen in association with a
diverse group of disorders, including what?

Answer 13

• lymphoplasmacytic lymphoma and an
• unusual small bowel marginal zone lymphoma that occurs in malnourished populations (so-called Mediterranean lymphoma).

Question 14

What is the common feature in these diseases:

lymphoplasmacytic lymphoma

small bowel marginal zone lymphoma (so-called
Mediterranean lymphoma)

Answer 14

The common feature is the synthesis and secretion of free

heavy-chain fragments.

Question 15

Primary or immunocyte-associated amyloidosis results

Answer 15

from a monoclonal proliferation of plasma cells secreting light chains (usually of γ isotype) that are deposited as
amyloid.

Some patients have overt multiple myeloma, but others have only a minor
clonal population of plasma cells in the marrow.

Question 16

Monoclonal gammopathy of undetermined significance (MGUS) is applied to patients who are:

Answer 16

without signs or symptoms who have small to moderately large M components in their
blood.

Question 17

MGUS is very common to what age group?

Answer 17

in the elderly and has a low but constant rate of
transformation to symptomatic monoclonal gammopathies, most often multiple myeloma.

Question 18

What is Multiple myeloma?

Answer 18

Multiple myeloma is a plasma cell neoplasm characterized by multifocal involvement of the
skeleton.

Although bony disease dominates,

it can spread late in its course to lymph nodes and
extranodal sites such as the skin.

Question 19

What is the epidemiology of Multiple myeloma?

Answer 19

• causes 1% of all cancer deaths in Western countries.
• incidence is higher in men and people of African descent.
• It is chiefly a disease of the elderly, with a peak age of incidence of 65 to 70 years

Question 20

What is the molecular pathogenesis of Multiple myeloma ?

Answer 20

The Ig genes in myeloma cells always show evidence of somatic hypermutation.

On this basis,
the cell of origin is considered to be a post-germinal center B cell that homes to the bone
marrowandhas differentiated into a plasma cell.

Of interest, some studies suggest that the
tumor originates in and is maintained by stem-like cells resembling small B lymphocytes that rely
on signals generated by the “hedgehog” pathway for self-renewal

Question 21

The proliferation and survival of myeloma cells are dependent on several cytokines, most
notably what?.

Answer 21

IL-6

IL-6 is an important growth factor for plasma cells that is produced by the tumor cells themselves and resident marrow stromal cells.

• *High serum levels of IL-6** are seen in
• *patients with active disease and are associated with a poor prognosis**.

Myeloma cell growth and
survival are also augmented by direct physical interactions with bone marrow stromal cells,
which is a focus of new therapeutic approaches

Question 22

What is the major pathologic
feature of multiple myeloma?

Answer 22

Factors produced by neoplastic plasma cells mediate bone destruction

Question 23

Explain how does the neoplastic cells of multiple myeloma mediate bone destruction?

Answer 23

Of particular importance, myeloma-derived MIP1α upregulates the
expression of the receptor activator of NF-κB ligand (RANKL) by bone marrow stromal cells,
which in turn activates osteoclasts.

[36] Other factors released from tumor cells, such as
modulators of the Wnt pathway, are potent inhibitors of osteoblast function.

The net effect is a

• marked increase in bone resorption**, which leads to **hypercalcemia and pathologic
  fractures. ***

Question 24

Many myelomas have rearrangements involving the Ig heavy-chain gene on chromosome14q32.

What are the Common translocation partners?

Answer 24

​

• include FGFR3 (fibroblast growth factor receptor 3) on chromosome 4p16, a gene encoding a tyrosine kinase receptor implicated in the control of cellular proliferation;
• the cell cycle–regulatory genes cyclin D1 on chromosome 11q13 and cyclin D3 on chromosome 6p21;
• the gene for the transcription factor c-MAF on chromosome 16q23;
• and the gene encoding the transcription factor MUM1/IRF4 on chromosome 6p25.

As may be gathered from the involvement of two different D cyclin genes, dysreglation of D cyclins is a common feature. [38]

The other most frequent karyotypic

abnormalities are deletions of 13q.

Consistent with the diversity of chromosomal aberrations,

gene expression profiling studies suggest that myeloma is molecularly quite

heterogeneous

Question 25

What is the usual morphological presentation of Multiple myeloma?

Answer 25

Multiple myeloma usually presents as destructive plasma cell tumors
(plasmacytomas) involving the axial skeleton.

Question 26

What are the bones most commonly affected in Multiple myeloma (in
descending order of frequency)?

Answer 26

AXIAL SKELETON

• vertebral column,
• ribs,
• skull,
• pelvis,
• femur,
• clavicle,
• scapula.

Question 27

In the bone that is affected by Multiple myeloma, where does the lesion begins?

Answer 27

Lesions begin in the medullary cavity, erode cancellous bone, and progressively destroy the bony cortex, often leading to pathologic fractures; these are most common in the vertebral column, but may occur in any affected bone.

The bone lesions appear
radiographically as punched-out defects, usually 1 to 4 cm in diameter ( Fig. 13-16 ),
and grossly consist of soft, gelatinous, red tumor masses.

Less commonly, widespread
myelomatous bone disease produces diffuse demineralization (osteopenia) rather than focal
defects.

Question 28

What is the appearance of the bone lesions radiographically in Multiple myeloma?

Answer 28

The bone lesions appear
radiographically as punched-out defects, usually 1 to 4 cm in diameter ( Fig. 13-16 ),
and grossly consist of soft, gelatinous, red tumor masses.

Question 29

In Multiple myeloma even away from overt tumor masses, the marrow contains an increased number of what which constitute more than 30% of the cellularity?

Answer 29

of plasma
cells

The plasma cells may infiltrate
the interstitiumor bepresent in sheets that completely replace normal elements.

Question 30

What is the histological apperance of Multiple myeloma malignant plasma cells like their benign counterparts?

Answer 30

Like their
benign counterparts, malignant plasma cells have a perinuclear clearing due to a prominent
Golgi apparatus and an eccentrically placed nucleus ( Fig. 13-17 ).

Relatively normalappearing
plasma cells,plasmablasts with vesicular nuclear chromatin and a prominent
single nucleolus, or bizarre, multinucleated cells may predominate.

Other cytologic
variants stem from the dysregulated synthesis and secretion of Ig, which often leads to
intracellular accumulation of intact or partially degraded protein.

Such variants include flame
cells with fiery red cytoplasm,

Mott cells with multiple grapelike cytoplasmic droplets, and
cells containing a variety of other inclusions, including fibrils, crystalline rods, and
globules.

The globular inclusions are referred to as Russell bodies (if cytoplasmic) or
Dutcher bodies (if nuclear).

In advanced disease, plasma cell infiltrates may be present in
the spleen, liver, kidneys, lungs, lymph nodes, and other soft tissues.

Question 31

In Multiple myeloma other cytologic variants stem from the dysregulated synthesis and secretion of Ig,which often leads to intracellular accumulation of intact or partially degraded protein.

What are these variants?

Answer 31

• flame cells with fiery red cytoplasm,
• Mott cells with multiple grapelike cytoplasmic droplets, and
• cells containing a variety of other inclusions, including :
  
  • fibrils,
  • crystalline rods, and
  • globules.

Question 32

In the other cytologic variants of Multiple myeloma, what do you call the globular inclusions?

Answer 32

• Russell bodies* (if cytoplasmic) or
• *Dutcher bodies** (if nuclear).

RC cola

DNky

Question 33

What is the reason for the other cytologic variants of Multiple myeloma?

Answer 33

Stems from the dysregulated synthesis and secretion of Ig, which often leads to
intracellular accumulationofintact or partially degraded protein

Question 34

In multiple myeloma, the high level of M proteins causes what?

Answer 34

Commonly, the high level of M proteins causes red cells in peripheral blood smears to stick to
one another in linear arrays, a finding referred to as rouleaux formation

. Rouleaux
formation is characteristic but not specific, in that it may be seen in other conditions in which
Ig levels are elevated, such as lupus erythematosus and early HIV infection.

Rarely, tumor
cells flood the peripheral blood, giving rise to plasma cell leukemia.

Question 35

In multiple myeloma, rarely, tumor
cells flood the peripheral blood, giving rise to what?

Answer 35

plasma cell leukemia

Question 36

What is myeloma kidney?

Answer 36

Bence Jones proteins are excreted in the kidney and contribute to a form of renal disease
called myeloma kidney

Question 37

Answer 37

FIGURE 13-16 Multiple myeloma of the skull (radiograph, lateral view). The sharply
punched-out bone lesions are most obvious in the calvarium.

Question 38

Answer 38

FIGURE 13-17 Multiple myeloma (bone marrow aspirate). Normal marrow cells are largely
replaced by plasma cells, including forms with multiple nuclei, prominent nucleoli, and
cytoplasmic droplets containing Ig

Question 39

What are the clinical features of multiple myeloma stem from?

Answer 39

• (1) the effects of plasma cell growth in tissues, particularly the bones;
• (2) the production of excessive Igs, which often have abnormal physicochemical properties; and
• (3) the suppression of normal humoral immunity.

Question 40

What is the reason for the pathologic fracture and chronic pain in multiple myeloma?

Answer 40

Bone resorption

Question 41

The attendant hypercalcemia in Multiple myeloma can give rise to what manifestations?

Answer 41

neurologic manifestations such as:

• confusion,
• weakness,
• lethargy,
• constipation, and
• polyuria, and
• contributes to renal dysfunction.

Question 42

In multiple myeloma the Decreased production
of normal Igs sets the stage for what?

Answer 42

recurrent bacterial infections

Cellular immunity is relatively
unaffected.

Question 43

In multiple myeloma, does the Cellular immunity is relatively unaffected?

T or F

Answer 43

TRUE

Question 44

Of the great significance in Multiple myeloma clinical manifestations is what?

Answer 44

Of great significance is renal insufficiency, which trails only infections as a cause of
death.

The pathogenesis of renal failure (discussed in Chapter 20 ), which occurs in up to 50%
of patients, is multifactorial.

However, the single most important factor seems to be Bence Jones proteinuria, since the excreted light chains are toxic to renal tubular epithelial cells. Certain light chains (particularly those of the γ6 and γ3 families) are prone to cause amyloidosis of the AL
type( Chapter 6 ), which canexacerbate renal dysfunction and deposit in other tissue as well.

Question 45

In the pathogenesis of renal failure which occurs in up to 50% of patients, is multifactorial. However, what is the single most important factor seems to be ?

Answer 45

Bence Jones proteinuria, since the excreted light chains are toxic to renal tubular epithelial cells.

Certain light chains (particularly those of the γ6 and γ3 families) are prone to cause amyloidosis of the AL
type (Chapter 6 ), which can exacerbate renal dysfunction and deposit in other tissue as well.

Question 46

In 99% of patients in Multiple myloma, laboratory analyses reveal increased levels of what?

Answer 46

Igs in the blood and/or light
chains (Bence Jones proteins) in the urine.

Question 47

In multiple myeloma the monoclona IGs are usually detected as what?

Answer 47

• *abnormal protein “spikes”** in serum or urine electrophoresis and then further characterized by
• *immunofixation** ( Fig. 13-18 ).

Most myelomas are associated with more than 3 gm/dL of serum Ig and/or more than 6 gm/dL of urine Bence Jones protein.

Question 48

Wha is the most common monoclonal Ig in Multiple myeloma?

Answer 48

• (“M protein”) is IgG (∼55% of patients), followed
• by IgA (∼25% of cases).
• Myelomas expressing IgM, IgD, or IgE occur but are rare.

Question 49

In multiple myeloma the excessive production and aggregation of M proteins, usually of the IgA and or IgG3 subtype, in about 7% of patients.

Answer 49

leads to symptoms related to hyperviscosity (described under

lymphoplasmacytic lymphoma

Both free light chains and a serum M
protein are observed together in 60% to 70% of patients.

However, in about 20% of patients
only free light chains are present.

Around 1% of myelomas are nonsecretory; hence, the
absence of detectable M proteins does not completely exclude the diagnosis

Question 50

Why does in Multiple myeloma, absence of detectable M proteins does not completely exclude the diagnosis?

Answer 50

Around 1% of myelomas are nonsecretory; hence, the
absence of detectable M proteins does not completely exclude the diagnosis

Question 51

Answer 51

FIGURE 13-18 M protein detection in multiple myeloma. Serum protein electrophoresis (SP)
is used to screen for a monoclonal immunoglobulin (M protein).

Polyclonal IgG in normal
serum (denoted by the arrow) appears as a broad band; in contrast, serum from a patient
with multiple myeloma contains a single sharp protein band (denoted by the arrowhead) in
this region of the electropherogram.

The suspected monoclonal Ig is confirmed and
characterized by immunofixation. In this procedure, proteins separated by electrophoresis
within a gel are reacted with specific antisera.

After extensive washing, proteins that are
cross-linked by antisera are retained and detected with a protein stain.

Note the sharp band
in the patient serum is cross-linked by antisera specific for IgG heavy chain (G) and kappa
light chain (κ), indicating the presence of an IgGκ M protein. Levels of polyclonal IgG, IgA
(A), and lambda light chain (γ) are also decreased in the patient serum relative to normal, a
finding typical of multiple myeloma

Question 52

The clinicopathologic diagnosis of multiple myeloma rests on what?

Answer 52

on radiographic and laboratory
findings.

It can be strongly suspected when the distinctive radiographic changes are present,
but definitive diagnosis requires a bone marrow examination.

Marrow involvement often gives
rise to a normocytic normochromic anemia, sometimes accompanied by moderate leukopenia
and thrombocytopenia.

Question 53

What is the definitive diagnosis in Multiple myeloma and what is seen?

Answer 53

bone marrow examination.

Marrow involvement often gives
rise to a normocytic normochromic anemia, sometimes accompanied by moderate leukopenia
and thrombocytopenia.

Question 54

What is the prognosis of Multiple myeloma?

Answer 54

The prognosis is variable but generally poor.

Question 55

Wha tis the median surivival of multiple myeloma?

Answer 55

The median survival is 4 to 6 years, and cures
have yet to be achieved.

P atients with multiple bony lesions, if untreated, rarely survive formore than 6 to 12 months, whereas patients with “smoldering myeloma” may be asymptomatic for many years.

Translocations involving cyclin D1 are associated with a good outcome, whereas deletions of 13q, deletions of 17p, and the t(4;14) all portend a more aggressive
course. [

Question 56

In the prognosis of multiple myeloma which one of these may be asymptomatic for many years?

Answer 56

with “smoldering myeloma” may be asymptomatic for many years.

Question 57

In the prognosis of multiple myeloma which Translocations involved has a good outcome?

Answer 57

Translocations involving cyclin D1 are associated with a good outcome, whereas deletions of 13q, deletions of 17p, and the t(4;14) all portend a more aggressive
course.

Question 58

What can induce remission in Multiple myeloma?

Answer 58

Cytotoxic agents induce remission in 50% to 70% of patients, and new therapeutic approaches
are bringing hope.

Myeloma cells are sensitive to inhibitors of the proteasome, [42] a cellular
organelle that degrades unwanted and misfolded proteins.

You will recall from Chapter 1 that
misfolded proteins activate apoptotic pathways.

• *Myeloma cells are prone to the accumulation of**
• *misfolded, unpaired Ig chains.**

Proteasome inhibitors may induce cell death by exacerbating this inherent tendency, and also seem to retard bone resorption through effects on stromal
cells. [43]

Question 59

Thalidomide and related compounds also have activityagainst myeloma by what mechanism?

Answer 59

, apparently by altering interactions between myeloma cells and bone marrow stromal cells and by inhibiting angiogenesis. [35]

Question 60

What can Biphosphates do in the treatment of Multiple myeloma?

Answer 60

Biphosphonates, drugs that inhibit bone resorption, reduce pathologic
fractures and limit the hypercalcemia.

Question 61

In multiple myeloma Bone marrow transplantation prolongs life but has not yet
proven to be curative.

T or F

Answer 61

True

Question 62

What is Solitary Myeloma?

Answer 62

• About 3% to 5% of plasma cell neoplasms present as a solitary lesion of bone or soft tissue.
• The bone lesions tend to occur in the same locations as in multiple myeloma.
• Extra-osseous lesions are often located in the lungs, oronasopharynx, or nasal sinuses.
• Modest elevations of M proteins in the blood or urine may be found in some patients.
• Solitary osseous plasmacytoma almost inevitably progresses to multiple myeloma, but this can take 10 to 20 years or longer.
• In contrast, extra-osseous plasmacytomas, particularly those involving the upper respiratory tract, are frequently cured by local resection.

Question 63

Solitary osseous plasmacytoma almost inevitably progresses to multiple myeloma, but how long does it take?

Answer 63

but this can take 10 to 20 years or longer.

Question 64

In contrast, extra-osseous plasmacytomas, particularly those involving the upper respiratory tract, are frequently cured by local resection.

T or F

Answer 64

True

Question 65

What is smoldering myeloma?

Answer 65

Smoldering Myeloma.
This entity defines a middle ground between multiple myeloma and monoclonal gammopathy of
uncertain significance.

Plasma cells make up 10% to 30% of the marrow cellularity, and the serum M protein level is greater than 3 gm/dL, but patients are asymptomatic.

About 75% of
patients progress to multiple myeloma over a 15-year period

Question 66

What is MGUS?

Answer 66

MGUS is the most common plasma cell dyscrasia , [45] occurring in about 3% of persons older
than 50 years of age and in about 5% of individuals older than 70 years of age.

By definition,
patients are asymptomatic and the serum M protein level is less than 3 gm/dL.

Approximately
1% of patients with MGUS develop a symptomatic plasma cell neoplasm, usually multiple myeloma, per year , [46] a rate of conversion that remains roughly constant over time.

Question 67

Of pathogenic interest, the clonal plasma cells in MGUS often contain what?

Answer 67

the same chromosomal translocations and deletions that are found in full-blown multiple myeloma, [47] indicating that MGUS is an early stage of myeloma development.

As in patients with smoldering myeloma,
progression to multiple myeloma is unpredictable; hence, periodic assessment of serum M
component levels and Bence Jones proteinuria is warranted.

Question 68

What is Lymphoplasmacytic Lymphoma?

Answer 68

• B-cell neoplasm of older adults
• usually presents in the sixth or seventh decade of life.
• Although bearing a superficial resemblance to CLL/SLL, it differs in that a substantial fraction of the tumor cells undergo terminal differentiation to plasma cells.

Question 69

In lymphoplasmacytic lymphoma Although bearing a superficial resemblance to CLL/SLL it differs in what aspect?

Answer 69

it differs in that a substantial fraction of the tumor cells undergo terminal differentiation to plasma cells.

Question 70

Most commonly, the plasma cell component of Lymphoplasmacytic Lymphoma secretes what?

Answer 70

monoclonal IgM, often in amounts
sufficient to cause a hyperviscosity syndrome known asWaldenström macroglobulinemia.

Question 71

What is Waldenström macroglobulinemia?

Answer 71

monoclonal IgM, often in amounts
sufficient to cause a hyperviscosity syndromeknown as Waldenström macroglobulinemia.

Question 72

What are the disctinctions of Lymphoplasmacytic Lymphoma from multiple myeloma?

Answer 72

Unlike multiple myeloma, heavy- and light-chain synthesis is usually balanced and complications
stemming from the secretion of free light chains (e.g., renal failure and amyloidosis) are rare.

A further important distinction is that bone destruction is not observed in this disease

Question 73

What is the morphology of Lymphoplasmacytic lymphoma?

Answer 73

Typically, the marrow contains a diffuse sparse-to-heavy infiltrate of lymphocytes, plasma cells, and plasmacytoid lymphocytes in varying proportions, often accompanied by mast cell hyperplasia ( Fig. 13-19 ).

Some tumors also contain a population
of larger lymphoid cellswith morevesicular nuclear chromatin and prominent nucleoli.

• *Periodic acid–Schiff-positive inclusions** containing Ig are frequently seen in the cytoplasm
• *(Russell bodies**) or the nucleus (Dutcher bodies) of some of the plasma cells.

At diagnosis
the tumor has usually disseminated to the lymph nodes, spleen, and liver.

Infiltration of the
nerve roots, meninges, and more rarely the brain can also occur with disease progression.

Question 74

Answer 74

FIGURE 13-19 Lymphoplasmacytic lymphoma. Bone marrow biopsy shows a characteristic
mixture of small lymphoid cells exhibiting various degrees of plasma cell differentiation. In
addition, a mast cell with purplish red cytoplasmic granules is present at the left-hand side
of the field.

Question 75

What are the dominant presenting complaints in Lymphoplasmacytic lymphoma?

Answer 75

• nonspecific and
• include weakness,
• fatigue, and
• weight loss.
• Approximately half the patients have lymphadenopathy, hepatomegaly, and splenomegaly .
• Anemia caused by marrow infiltration is common.
• About 10% of patients have autoimmune hemolysis caused by cold agglutinins, IgM antibodies that bind to red cells at temperatures of less than 37°C (described in Chapter 14 ).

Question 76

Patients with IgM-secreting tumors have additional complaints stemming from the
physicochemical properties of IgM. Because of its large size, at high concentrations IgM greatly
increases the viscosity of the blood, giving rise to a hyperviscosity syndrome characterized by
the following:

Answer 76

• Visual impairment associated with venous congestion, which is reflected by striking tortuosity and distention of retinal veins; retinal hemorrhages and exudates can also contribute to the visual problems
• • Neurologic problems such as headaches, dizziness, deafness, and stupor, all stemming from sluggish blood flow and sludging
• • Bleeding related to the formation of complexes between macroglobulins and clotting factors as well as interference with platelet functions
• • Cryoglobulinemia resulting from the precipitation of macroglobulins at low temperatures, which produces symptoms such as Raynaud phenomenon and cold urticaria

Question 77

What is the treatment for Lymphoplasmacytic lymphoma?

Answer 77

is an incurable progressive disease.

Since most IgM is
intravascular, symptoms caused by the high IgM levels(such as hyperviscosity and hemolysis)
can be alleviated by plasmapheresis.

Tumor growth can be controlled for a time with low doses of chemotherapeutic drugs and immunotherapy with anti-CD20 antibody.

Transformation to
large-cell lymphoma occurs but is uncommon.

Median survival is about 4 years.