Correspondence

Easy to See but Hard to Find

N Engl J Med 2003; 348:1931-1932May 8, 2003

Article

To the Editor:

The clinical problem that was easy to see (Jan. 2 issue)1 could have been less hard to find if the diagnostic approach had been slightly different. When myeloma is likely, the first step should be to look for a paraprotein. Serum and an aliquot from a 24-hour urine collection should be subjected to immunofixation because small quantities of paraprotein may be missed on gel electrophoresis2 and because analysis of a random urine sample may not reveal paraprotein. A new serum free-light-chain assay may detect paraprotein in instances in which the results of immunofixation are negative.3

Marrow infiltration with plasma cells is often patchy. A marrow sample without plasmacytosis may still indicate a malignant process if there are morphologic abnormalities or if clonal plasma cells are detected on flow cytometry or immunohistochemical examination.1

If adequate blood, urine, and marrow studies fail to indicate myeloma under such clinical circumstances, a biopsy of a bone lesion should be the next step, rather than whole-body computed tomography, in search of an unknown primary cancer. (Intravenous contrast material can precipitate renal failure in patients with myeloma.) Skeletal magnetic resonance imaging can identify marrow abnormalities and focal lesions that are not obvious on conventional films in patients with myeloma and can help physicians choose potential sites for a biopsy.

Finally, before a patient with renal insufficiency is given a diagnosis of nonsecretory or light-chain myeloma, an IgD monoclonal protein should be sought. IgD is not estimated in the standard quantitative serum immunoglobulin assay, and the immunofixation plate in common use detects IgG, IgA, and IgM, but not IgD.

Seema Singhal, M.D.
Jayesh Mehta, M.D.
Northwestern University, Chicago, IL 60611
s-singhal@northwestern.edu

3 References

1. 1

   Reilly BM, Clarke P, Nikolinakos P. Easy to see but hard to find. N Engl J Med 2003;348:59-64
   Full Text | Web of Science | Medline

2. 2

   San Miguel JF, Almeida J, Orfao A. Laboratory investigations. In: Mehta J, Singhal S, eds. Myeloma. London: Martin Dunitz, 2002:243-68.
   

3. 3

   Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001;97:2900-2902
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Drs. Singhal and Mehta about methods to find paraproteins. Immunofixation electrophoresis of serum and aliquots of 24-hour urine is the gold-standard procedure in our laboratory as well. The new serum immunoassay for free light chains may be more sensitive than immunofixation, especially in patients with Bence Jones (light-chain) myeloma.1 Thus, it may also help in the diagnosis of IgD myeloma (which typically resembles light-chain myeloma2). However, the specificity of the new immunoassay remains undefined. Studies to date have used, as controls, normal volunteers, who have lower (though detectable) levels of free light chains than patients with myeloma. Further studies in a broader spectrum of patients are needed.

We disagree about how to find the correct diagnosis in our patient. Bone marrow abnormalities other than plasmacytosis do not meet currently accepted diagnostic criteria for myeloma. Certainly, magnetic resonance imaging can help identify potential sites for bone biopsy, as it did in our patient. However, we are not aware of any data supporting the respondents' contention that bone biopsy “should” take precedence over whole-body computed tomography in evaluating patients such as ours. In fact, it seems to us injudicious to insist on invasive, potentially harmful biopsies before noninvasive, standard studies for likely alternative diagnoses (metastatic lung, renal, intraabdominal, or thyroid cancer) are performed. Given our patient's fragile clinical condition and minimal risk of radiocontrast-induced renal failure,3 we endorse the approach taken by her physicians. Even with 20/20 hindsight, we think that what they saw was indeed hard to find.

Brendan M. Reilly, M.D.
Peter Clarke, M.D.
Petros Nikolinakos, M.D.
Cook County Hospital, Chicago, IL 60612
breilly@cchil.org

3 References

1. 1

   Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003;361:489-491
   CrossRef | Web of Science | Medline

2. 2

   Blade J, Lust JA, Kyle RA. Immunoglobulin D multiple myeloma: presenting features, response to therapy and survival in a series of 53 cases. J Clin Oncol 1994;12:2398-2404
   Web of Science | Medline

3. 3

   McCarthy CS, Becker JA. Multiple myeloma and contrast media. Radiology 1992;183:519-521
   Web of Science | Medline