Middle-aged Woman With Malaise and GI Complaints

A 56-year-old African American woman complains of malaise, nausea, and vomitingof several weeks’ duration. In addition, urinary output is reduced, and shehas mild dyspnea. She denies abdominal pain, diarrhea, constipation, and bonepain; however, she has had a mild but persistent backache for several months.

A 56-year-old African American woman complains of malaise, nausea, and vomitingof several weeks' duration. In addition, urinary output is reduced, and shehas mild dyspnea. She denies abdominal pain, diarrhea, constipation, and bonepain; however, she has had a mild but persistent backache for several months.HISTORY
The patient was previously healthy. She takes no medications, has neversmoked, and does not drink alcohol.PHYSICAL EXAMINATION
Temperature is normal, blood pressure is 160/100 mm Hg, and oxygensaturation is 90% on room air. Jugular venous pressure is elevated to 4 cm abovethe clavicle. Conjunctival pallor is evident; there is no jaundice. Results of cardiacand abdominal examinations are normal. Bibasilar pulmonary crackles areaudible. Neurologic examination reveals subtle mental status changes but nofocal findings. Sphincter tone is intact.LABORATORY, IMAGING, AND BIOPSY RESULTS
Blood urea nitrogen level is 136 mg/dL; creatinine, 19.7 mg/dL; and calcium,11.8 g/dL. Albumin and liver enzyme levels are normal. Total protein levelis 8.5 g/dL. Hemoglobin level is 7.6 g/dL and mean corpuscular volume is90 fL. Ferritin level is 599 ng/mL. The corrected reticulocyte count is 1.3% andthe white blood cell count is 6500/μL. Urinalysis reveals 2+ proteinuria butno active sediment. Fractional excretion of sodium is greater than 1%. Serumprotein electrophoresis shows no monoclonal protein.Mild pulmonary vascular congestion is evident on a chest film. Anechocardiogram reveals normal left ventricular function and no left ventricularhypertrophy. A renal ultrasound scan shows that the kidneys are slightlysmaller than normal; no urinary tract obstruction is noted.A nephrologist is consulted, and dialysis is started because of the patient'svolume overload. A renal biopsy is performed; the findings are interpreted as"myeloma kidney."Which of the following tests is not useful in the workup ofmultiple myeloma?A. Urine electophoresis and immunofixation.B. Nuclear bone scan.C. Bone marrow aspiration and biopsy.D. CT scan.CORRECT ANSWER:B
Multiple myeloma is a neoplastic disorder characterizedby monoclonal proliferation of a single clone of B-cell-derived plasma cells. It is a common hematologic malignancythat occurs with greater frequency in elderly personsand is significantly more common in African Americansthan in whites or Asians. The underlying processesof multiple myeloma are marrow replacement by plasmacells, effects of circulating monoclonal protein, and cytokineeffects. These result in a great variety of clinicalmanifestations.Clinical features of myeloma. This patient's presentationwas not typical. Although renal insufficiency iscommon in myeloma (it occurs in 40% of patients at somestage of theirillness), it is unusualfor theprimary presentingsymptom tobe end-stagerenal failure. Themechanismsof renal failure inmyeloma arecomplex and variable.They includelight-chaindeposition, castnephropathy, hypercalcemia, and hyperuricemia; exposureto intravenous dye or NSAIDs can precipitate acutedeterioration. The average creatinine level at diagnosis is1.2 mg/dL; it was 19.7 mg/dL in this patient.The most common presenting symptom of multiplemyeloma is pain that results from bone tissue destruction,which is visible on plain radiographs in two thirds of patientsat diagnosis. Destructive bone disease affects 85% ofpatients with multiple myeloma during the course of theirillness. This patient had very mild bone pain, and a skeletalsurvey with plain radiography revealed no evidence ofbone disease.Characteristic features of multiple myeloma that areseen in this patient are:

  • Hypercalcemia (found in 15% of patients at presentation);it is caused by cytokine-induced bone resorption.
  • Mild anemia (usually normocytic and typically accompaniedat presentation by normal white blood cell and plateletcounts). Anemia in this setting is caused by marrow replacement,renal failure, and cytokine-mediated marrowsuppression.

Diagnostic tests.

The diagnosis of myeloma requires,at an absolute minimum, the following findings:

  • At least 10% marrow plasma cells (or a plasmacytoma).
  • Monoclonal protein in the serum or urine or evidence oflytic bone disease.

The screening test is serum protein electrophoresis,which reveals a monoclonal spike in more than 80% of patientswith multiple myeloma. In this patient, the testshowed no monoclonal protein; however, false-negativesare fairly common.If serum protein electrophoresis results are negativeand multiple myeloma is strongly suspected, order aserum immunofixation and a urine electrophoresis andimmunofixation (choice A). In this patient, these tests revealeda monoclonal


light chain.Further testing is required because the presenceof monoclonal protein does not necessarily confirmmyeloma. Manypatients have"monoclonalgammopathy ofunknown significance"(MGUS),which is characterizedby findingsof smallmonoclonal protein,less than10% marrowplasmacytosis,no bone disease,and normal calcium and creatinine levels. Patients withMGUS have a lifetime risk of progression to myelomaof only 11%. In addition, negative results of tests for monoclonalprotein do not rule out myeloma; 3% of patientswith myeloma have no detectable monoclonal protein ineither serum or urine (this is considered "nonsecretory"myeloma).Bone marrow aspiration and biopsy (choice C) canbe used to detect marrow plasma cells. In this patient, themarrow was infiltrated with 90% plasma cells.In patients who have a normal plain radiographicskeletal survey, either CT (choice D) or MRI may detectsigns of bone lesions, because both are more sensitivethan plain radiography. Generally, these studies are orderedonly if a patient has persistent pain but normalradiographs. In this patient, CT scans showed destructivelesions in the lumbar vertebrae. Nuclear bone scans, althoughvery helpful in the detection of blastic bone disease(eg, metastatic prostate cancer), are


useful in thelytic disease that is typical of myeloma. Thus, choice B iscorrect.


Myeloma is a highly treatable--althoughstill incurable--disease. In addition to chemotherapy, specificdisease complications are managed individually. Hypercalcemia is best managed with hydration and bisphosphonates;the latter also help reduce the risk of fracturefrom bone disease. Anemia can be treated with erythropoietin--to which this woman responded well. If renalinsufficiency develops, general supportive measures areused first. If these do not quickly and effectively reversethe condition, the best means of salvaging renal function(if this is possible) is plasmaphoresis and urgent institutionof effective myeloma treatment.


Average survival of patients with myelomahas remained unchanged over the last few decades atabout 3 years. Prognosis is estimated by parameters thatindicate:

  • Tumor burden (eg, number of lytic lesions; percentageof marrow plasma cells; calcium, creatinine, and hemoglobinlevels; platelet count; and beta2-microglobulin level).
  • Tumor biology (eg, plasma cell labeling index).
  • Patient well-being (eg, age, performance status).
  • Response to treatment

Outcome of this case.

The patient was given highdosedexamethasone therapy for the myeloma and respondedvery well. After 4 months, her creatinine level is2.4 mg/dL and her monoclonal


light-chain burden hasbeen reduced by 50%.



  • Child JA, Morgan GH, Davies FE, et al. High-dose chemotherapy withhematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875-1883.
  • Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosedmultiple myeloma. Mayo Clin Proc. 2003;78:21-33.
  • Rajkumar SV, Gertz MA, Kyle RA, et al. Current therapy for multiple myeloma.Mayo Clin Proc. 2002;277:813-822.
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