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?
2. 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
3. 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.

4. What diagnosis is suggested by these results?
5. 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?
6. 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?
7. Discuss the mechanisms of immunosuppression in multiple myeloma
8. Discuss the epidemiology of multiple myeloma.

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.