Elderly Man With Fatigue and Backache

A

70-year-old African American man, who is a retiredelectrician, presents with increasing fatigue anddull back pain of 4 months' duration. Although he usuallywalks about 2 miles a day, he now becomes exhaustedafter half a block. He reports exertional dyspnea but noparoxysmal nocturnal dyspnea or orthopnea. Recently, henoticed ankle edema.He has no cough, chest pain, palpitations, fever, chills,rigors, night sweats, weight loss, or history of back injury.In the past 2 months, he has noticed polydipsia and polyuriaand wakes up once or twice each night to urinate.His only medication is aspirin, 81 mg/d, and he takesa multivitamin supplement. During the past year, he wastreated twice for pneumonia with oral antibiotics. He doesnot smoke or drink alcohol.

Examination.

The patient is a well-built, well-nourishedbut pale man. Temperature is 37

^o

C (98.6

^o

F); heartrate, 90 beats per minute and regular; respiration rate,24 breaths per minute; blood pressure, 145/86 mm Hg.No rash, icterus, or candidal infection is evident. Thyroidgland is not palpable. No palpable adenopathy or jugularvenous distention is observed; there is 1+ ankle swelling.Apex is well localized and heart sounds are normal. Lungsare clear. Abdomen is soft and benign with no organomegalyor tenderness. The prostate is mildly enlargedwith no nodules; stool guaiac test results are negative.Neurologic examination is unremarkable. Spine examinationreveals tenderness in the lower thoracic region.

Laboratory studies.

Initial results include hemoglobin,10.2 g/dL; hematocrit, 32%; mean corpuscular volume,88 fL; mean corpuscular hemoglobin, 30 pg/cell;mean corpuscular hemoglobin concentration, 34 g/dL;rouleaux formation, +++; white blood cell count, 7200/μL,with 70% polymorphonuclear leukocytes, 24% lymphocytes,3% eosinophils, 3% monocytes; platelet count,210,000/μL; erythrocyte sedimentation rate (ESR), 110mm/h. Urinalysis reveals protein, 2+; no glucose or redor white blood cells. Serum sodium, 135 mEq/L; potassium,4 mEq/L; chloride, 102 mEq/L. Blood urea nitrogenlevel, 50 mg/dL; serum creatinine, 2.6 mg/dL.Glucose (fasting), 90 mg/dL; serum calcium, 12.8 mg/dL.Total protein, 9 g/dL; albumin, 3.0 g/dL. Electrophoresisshows an M spike between the α

₂

and the γ region. Alkalinephosphatase, 100 IU/L.A chest radiograph shows that the heart is of normalsize and no infiltrates are present. A spinal radiograph revealslytic lesion and osteoporosis.You order a bone marrow aspiration.

What abnormalities are evident on this image,and what do you suspect is the cause?

A.

Aleukemic leukemia

B.

Hodgkin lymphoma

C.

Multiple myeloma

D.

Prostate cancer

E.

Monoclonal gammopathy

MULTIPLE MYELOMA:
AN OVERVIEW

Multiple myeloma is a progressive malignant neoplasmthat results from monoclonal proliferation of plasmacells and overproduction of a monoclonal immunoglobulin(eg, IgA, IgG, or IgE) or Bence Jones protein.The cause of this disorder remains unclear. Exposureto radiation, herbicides, pesticides, or herpesvirus 8 maybe a factor.Multiple myeloma is the most common primary malignancyof the skeletal system in adults. The annual incidencein the United States is 3 or 4 cases per 100,000 population.It is generally a disease of elderly persons (medianage at diagnosis is 65 years) and accounts for 1% ofall cancers and 10% of all hematologic malignancies diagnosedin the United States. Multiple myeloma is twice ascommon in African Americans (9.6 per 100,000 population)as in whites and affects men slightly more thanwomen (1.6:1).

CLINICAL MANIFESTATIONS

The disease usually has an insidious onset; it typicallypresents with skeletal pain, renal failure, anemia, and recurrentbacterial infections. Bone pain, commonly in thelow back or ribs, is the presenting complaint in two thirdsof cases. The pain of myeloma intensifies with movement;in contrast, the pain of metastatic cancer is not exacerbatedby movement but often worsens at night. A pathologicfracture is present in 30% of cases. Patients may seek medicalattention because of weakness and fatigue (a result of anemia or renal failure), recurrent infections, pulmonaryor genitourinary symptoms, or symptoms related to hyperviscosityand/or hypercalcemia (nausea, paresthesias,or mental status changes). Occasionally, multiple myelomais diagnosed after abnormalities are found on routinelaboratory studies.Pallor is the most common physical finding. Neurologicsigns related to neuropathy or spinal cord compressionmay be noted. Patients with amyloidosis, which is asecondary complication, may have an enlarged tongue,cardiomegaly, or hepatosplenomegaly.

DIAGNOSIS

A normocytic normochromic anemia is found innearly all patients with multiple myeloma. Leukocytecounts may be low or normal. Fifteen percent of patientshave thrombocytopenia. Rouleaux formation on peripheralsmear is present in 60% of cases. The ESR is usuallymarkedly elevated. Hypercalcemia is present in 10% to20% of patients at the time of diagnosis, and levels ofserum urea nitrogen, creatinine, and uric acid are oftenabnormal.Serum and urine protein electrophoresis are recommendedin all suspected cases of multiple myeloma. Nearlyall patients exhibit the characteristic monoclonal Mspike in the α or γ region. Approximately 20% of patientshave an electrophoretic pattern that is normal or consistentwith hypogammaglobinemia. In these cases, immunofixationmay be helpful to detect small monoclonal spikes or Bence Jones (light chain) proteins. Immunofixationis also used to distinguish the immunoglobulin type;IgG is found in 50% of cases and IgA in 20%; 15% of patientshave light chain or Bence Jones myeloma

(Table).

A skeletal survey, including radiographs of the skull,spine, ribs, and proximal long bones, reveals "punchedout" or lytic lesions in two thirds of patients with multiplemyeloma

(Figure 2).

Diffuse osteopenia or osteoporosisis also common. MRI or CT may be helpful when radiographsare normal. Radionuclide bone scanning is notrecommended.

PROGNOSIS

Multiple myeloma is rarely curable. Advances intreatment have resulted in a median survival of 2 to 2.5years. High levels of M protein, anemia, hypercalcemia,renal insufficiency, and extensive bony lesions are unfavorableprognostic signs. A poor prognosis is more reliablyindicated by elevation of the plasma cell labelingindex and elevated levels of C-reactive protein and uncorrectedβ

₂

-microglobulin.

TREATMENT

The treatment regimen of choice in newly diagnosedmultiple myeloma is somewhat controversial. The alkylatingagent melphalan and oral prednisone have been usedfor a number of years. Combination chemotherapy--eg, vincristine and doxorubicin with dexamethasone--produces better response rates but no change in survival.Thalidomide is used to treat relapsed or refractory multiplemyeloma. High-dose chemotherapy with stem celltransplantation has been effective in patients aged 65years and younger. The proteasome inhibitor bortezomibwas recently approved by the FDA and shows somepromise as a therapeutic agent.Radiation is effective for bone pain resulting frommyeloma infiltration. Bisphosphonates are given routinelyto improve bone density and reduce skeletal complications.Anemia is treated with erythropoietin.

References:

FOR MORE INFORMATION:

• Bataille R, Harousseau JL. Multiple myeloma. N Engl J Med. 1997;336:1657-1664.
• Kyle RA. Diagnostic criteria of multiple myeloma. Hematol Oncol Clin NorthAm. 1992;6:347-357.
• Rajkumar SJ, Greipp PR. Prognostic factors in multiple myeloma. HematolOncol Clin North Am. 1999;13:1295-1314.
• Riedel DA, Pottern LM. The epidemiology of multiple myeloma. HematolOncol Clin North Am. 1992;6:225-247.