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The arrow points to:
- A. Albumin
- B. a 1 globulin
- C. a 2 globulin
- D.b globulin
- E. monoclonal protein
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| A 78-year-old black man, a retired chemistry professor, comes to you
because of lumbosacral vertebral pain. There is no hepatomegaly. Cardiac
exam is normal and there is no evidence of arthritis. His Hct, MCV, WBC
and differential are normal. Liver enzymes are normal, but total serum
protein is mildly elevated. The serum Ca is normal. You find no protein
in his urine. A marrow aspirate&biopsy showed 6% plasma cells (normal=0-5%).
A roetgenographic survey was negative. His serum protein electrophoresis
is shown at right.
What is the most likely diagnosis based on the history and laboratory
findings?
- A. Waldenstrom's macroglobulinemia
- B. Amyloidosis
- C. Myeloma
- D. Monoclonal Gammopathy of Unknown Significance
- E. Heavy Chain Disease
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| A 72-year-old black woman, a retired school teacher, who you see for
hypertension and mild arthritis, complains of mid-back and hip pain for
4-5 months. Two days ago she fractured her arm trying to lift her 15 month
old grandson. Her Hct is 0.30; the WBC 3.8 x109/L with a normal
differential. Serum Ca is elevated at > 12 mg/dL.Urine protein is 3+
positive. Her serum protein electrophoresis is shown at right. Physical
examination shows no hepatosplenomegaly, nor lymphadenopathy.
What is the most likely primary diagnosis based on the history and laboratory
findings?
- A. Waldenstrom's macroglobulinemia
- B. Amyloidosis
- C. Myeloma
- D. Monoclonal Gammopathy of Unknown Significance
- E. Heavy Chain Disease
What additional studies are needed to confirm your differential diagnosis?
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Immunosecretory Disorders: Myeloma
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| Immunoelectrophoresis (IEP)is important to confirm and define
an apparent monoclonal band seen on SPEP.
| Observe the shape of the IgG, IgA, & IgM precipitin arcs
between the anti polyvalent Ig and the Control. Compare the arcs
of the Pt with the Control looking for the presence of abnormal
arcs and matching the abn arcs with those on the type specific
heavy & light antisera.
Abn-Igs usually have skewed* or split arcs compared to normal
(symmetrical due to Ig molecule heterogeneity). Usually abn-Igs
are in excess and/or to the exclusion of normal. Here the Pt has
an IgG in excess, but little IgA, or IgM. The k arc is in exess
and matches the abn *arc seen against the anti polyvalent Ig.
This is a k monoclonal IgG. |
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Immunoelectrophoresis (IEP) of a second case in which a
monoclonal band was seen on SPEP.
| Again compare the shape of the IgG, IgA, & IgM precipitin
arcs between the anti polyvalent Ig and the Control.Look for abnormal
arcs and match them with those on the type specific heavy &
light antisera.
Here the abn-Ig has a split* arc compared to the Pts normal protein#
(symmetrical due to Ig molecule heterogeneity). The *arc is identical
to the l arc and the #arc with the k arc. The l arc is in exess
and matches the abn *arc seen against the anti polyvalent Ig.
This is a l monoclonal IgG.
This should be confirmed with immunofixation electrophoresis.
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Immunosecretory Disorders
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| Immunofixation electrophoresis (M-fix) is useful for confirmation
and specific identification of monoclonal bands. Antibodies against immunoglobulins,
in this case IgG, k, and l, are used to identify the protein bands in
the serum protein electrophoresis (SPEP) as an IgG l monoclonal band.
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HEMATOPATHOLOGY
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| A 24-year-old woman, recently returned from graduate religious
studies in India, comes to you because of soft tissue swelling of her
lower extremities. She was treated with phenacetin for "arthritis" while
in India. She also noted tenderness of both wrists and some numbness/sensation
loss in her hands. On physical exam the soft tissue of her wrists is slightly
swollen and firm. Laboratory studies show the Hct is 0.38 and the WBC
8.4x109/L with a normal differential. Her urine is 3+ positive
for protein. There is no lymphadenopathy or hepatosplenomegaly. A skeletal
survey is normal.
- A. Waldenstrom's macroglobulinemia
- B. Amlyoidosis
- C. Myeloma
- D. Monoclonal Gammopathy of Unknown Significance
- E. Heavy Chain Disease
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Immunosecretory Disorders
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| A 57 yr-old woman presents with headache & dizziness; numbness
& blanching of her fingers. The IEP is at right. The PB smear shows
4+ rouleaux. You find enlarged axillary & inguinal lymph nodes &
splenomegaly. X-rays show no lytic bone lesions.
| In comparing the precipitin arcs of the Pt with the Control
you see an abnormal arc in the Pt-antiPV and a matching arc on
the IgM and k antisera.
The abn-Ig has a skewed or asymetrical arc and is in excess compared
to normal. Here the Pt has an IgM in excess, but little IgG, or
IgA. This is interpreted as a k monoclonal IgM, but should be
confirmed with immunofixation as shown NEXT. |
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HEMATOPATHOLOGY
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| The immunofixation of this patient is shown at right. Does this confirm
your interpretation of the IEP?
Based on the history and these results which of the following is the
best diagnosis?
- A. Waldenstrom's macroglobulinemia
- B. Amlyoidosis
- C. Myeloma
- D. Monoclonal Gammopathy of Unknown Significance
- E. Heavy Chain Disease
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Multiple myeloma is generally characterized by all of the following
EXCEPT:
- A. Monoclonal gammopathy
- B. Rouleaux formation
- C. Anemia
- D. Splenomegaly
- E. Hypercalcemia
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In multiple myeloma the immunoglobulin most commonly elevated is:
- A. IgA
- B. IgG
- C. IgM
- D. IgD
- E. IgE
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Multiple myeloma is often associated with:
- A. Decreased ESR (erythrocyte sedimentation rate)
- B. Excretion of both kappa & lambda light chains in the urine
- C. Osteoblastic skeletal lesions
- D. Renal excretory impairment
- E. Hyperalbuminemia
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Which feature is more characteristic of Waldenstrom's macroglobulinemia
than multiple myeloma?
- A. Discrete lytic bone lesions
- B. Bence-Jones protein in the urine
- C. Rapid clinical course
- D. Spleen and lymph node enlargement
- E. IgA M-spike
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Hyperviscosity is a complication of which of the following diseases:
- A. Waldenstrom's macroglobulinemia
- B. Sickle cell anemia
- C. IgA Myeloma
- D. Polycythemia vera
- E. All of the above
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All of the following are complications associated with multiple myeloma EXCEPT:
- A. Pathologic fractures
- B. Increased susceptibility to infections
- D. Hypergammaglobulinemia
- E. Cryoglobulinemia
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Characteristic features of various heavy chain diseases include
all of the following EXCEPT:
- A. Increased levels of IgG kappa or lambda light chains
- B. Association with AIHA, Sjogren's syndrome, SLE, etc.
- C. Anemia, fever, lymphadenopathy, splenomegaly
- D. abdominal mass; malabsorption; diarrhea
- E. Mediterranean lymphoma
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All of the following features of B cell gene rearrangements
are true EXCEPT:
- A. Two attempts at k rearrange ment must take place before an attempt
at l rearrangement can take place
- B. The Cm gene is physically closest to the JH region on chromosome
14
- C. A heavy chain class switch allows identical VH/DH/JH antigen
specificity to be expressed with different constant regions
- D. Rearrangement
translation
transcription
- E. The gene for k light chains is located on chromosome 2 and has
a single constant region
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All of the following are true EXCEPT:
- A. Maternal IgG can cross the placenta
- B. Waldenstrom's macroglobulinemia is associated with mature B lymphocytes
that have not yet undergone a heavy chain class switch
- C. IgA is a major immunoglobulin in GI tract and respiratory secretions
- D. The Fab portion of IgG is important in the activation of complement
- E. a2-macroglobulin is a protease inhibitor
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