Question

John is a 48yo African-American male and was seen in the ER suffering from diarrhea, vomiting, abdominal cramps and fever that had not subsided for in the past 2 days. Microbiological studies identified Salmonella typhimurium as the cause of the gastroenteritis. In the course of his hospitalization, a complete physical exam was done including lab tests. The results are in Tables 1 and 2.

Table #1: CBC and ESR

John

Adult male reference range

Ref range for absolute cell counts (x 10E9/L)

WBC count

11.1

5-10 x 10E9/L

RBC count

2.94

5-6 x 10E12/L

Hb

93

135-175 g/L

Hct

0.28

.41-.53 L/L

MCV

95

80-100 fL

MCH

31.6

26-34 pg

MCHC

33.3

31-37 g/dL

RDW-CV

15

11.5-14.5%

Plt

128

150-400 x10E9/L

Differential:

PMN

32

25-60%

1.10-6.05

Bands

5

0-10%

0.10-2.1

Lymphs

54

20-50%

1.5-4.0

Monocutes

5

2-11%

0.2-.095

Eosinophils

0

0-8%

0-0.7

Basophils

0

0-2%

0-1.5

Metamyelocytes

3

0

0

plasma cells

1

0

0

Morphology: 1+ toxic granulation, Dohle bodies, slight anisocytosis, rouleaux

ESR: 135 (normal is 0-6 mm/hr)

John

Adult reference range

Creatinine

15

0.5-1.4mg/dL

BUN

114

5-25mg/dL

Total protein

12

5.5-7.5g/dL

Albumin

2.6

3.4-4.5 g/dL

Calcium

8.2

8.5-10.5mg/dL

phosphorous

>10

2.5-4.5

  1. The patient has a bacterial infection. What findings in the CBC reflect this fact?
    1. Given John’s CBC, describe his blood picture in proper hematological terminology.
    2. List some conditions that might be associated with the above CBC
  2. What other tests could be performed to narrow the differential diagnosis and what would be the expected results for each condition?

Table 3 Special Chemistry Tests

Serum protein electrophoresis

John

Reference range

Total protein

11.2

5.5-7.5g/dL

Albumin

2.8

3.4-4.5 g/dL

Alpha-1-globulin

0.34

0.1-0.3 g/dL

Alpha-2-globulin

0.78

0.5-1.0 g/dL

Beta-globulin

0.67

0.6-1.1 g/dL

Gamma

6.61

Immunoglobulins

IgA

<40

88-397 mg/dL

IgM

<35

54-220 mg/dL

IgG

6500

800-1800 mg/dL

Serum immunofixation electrophoresis

IgG and kappa light chains; monoclonal spike in urinary protein electrophoresis

Table 4: Bone Marrow Biopsy

Uniform confluent sheet of plasma cells consisting predominantly of mononuclear cells but occasionally exhibiting binuclear plasma cells. Myeloid and erythroid element are virtually obliterated by the plasma cell proliferation that is also obliterating the fatty content of the marrow and thinning the osseous trabecula.

  1. What diagnosis is suggested by these results?
  2. What does “ Myeloid and erythroid element are virtually obliterated by the plasma cell proliferation that is also obliterating the fatty content of the marrow and thinning the osseous trabecula” mean in layman’s terms?
    1. Describe the etiology and pathogenesis of John’s condition
    2. How does this relate to the appearance of the bones on x-ray?
    3. Which of John’s lab results is not typical of this condition?
  3. Discuss the mechanisms of immunosuppression in multiple myeloma
  4. Discuss the epidemiology of multiple myeloma.
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Answer #1

#. The diagnosis suggested by these results is Multiple Myeloma.

#. Etiology of Multiple myeloma is unknown . Some of the causes are :-

- genetic

- environmental

- MGUS

- chronic inflammation

- viral infection

#. Pathogenesis of Multiple Myeloma :-

-Exogenous stimuli induce cytogenetic changes in the B-cell lineage at the lymph node.
-50% pts have abnormal karyotypes
Hyperploidy chr 3, 5, 7, 9, 11, 15, 19
Hypoploidy chr 8, 12, 14
Sex chr X, 13
-Myeloma cells attach to bone marrow stromal cells causing growth - spread to cavities of large bones, forming mult small lesions.
-Myeloma cells produce growth factors that promote angiogenesis providing O2 and nutrients necessary for tumor growth. Able to inactivate immune system and produce substances that decrease the body's normal immune response to a foreign body. Thus, the cells can grow unchecked.

#. Bone destruction caused by myeloma cells can be detected with x-rays. This is called a bone survey or skeletal survey.

Disseminated multiple myeloma has two common radiological appearances, although it should be noted that initially, radiographs may be normal, despite the presence of symptoms. The two main diffuse patterns are:

  1. numerous, well-circumscribed, lytic bone lesions (more common)
    • punched out lucencies
      • raindrop skull
    • endosteal scalloping
  2. generalized osteopenia (less common)
    • often associated with vertebral compression fractures/vertebra plan

#. Patients with multiple myeloma are at increased risk of severe bacterial infection. A variety of immune deficits has been described in such patients, including a decreased primary antibody response and defects in complement and granulocyte function. The depressed humoral response appears to result primarily from the activity of suppressor monocytes.

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