Monoclonal gammopathy of undetermined significance

* The association of sarcoidosis with Hodgkin disease and non-Hodgkin lymphoma is well known. However, multiple myeloma also can occur rarely in association with sarcoidosis. We describe a patient with sarcoidosis who subsequently developed multiple myeloma. The patient was a 49-year-old woman with a 4-year history of severe, chronic, active sarcoidosis involving her lungs, lymph nodes, eyes, and bone marrow. During the initial clinical workup, a serum monoclonal paraprotein was detected and bone marrow examination revealed a slight increase in plasma cells (4%), in addition to noncaseating granulomas. Thus, the diagnoses of monoclonal gammopathy of undetermined significance and sarcoidosis were established simultaneously. She sought medical attention for her current illness when she developed low back pain and weakness of her lower extremities. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin (Ig) G kappa type, and quantification revealed an IgG level of 46.67 g/L (normal, 5.88-15.73 g/L). Bone marrow aspiration and biopsy revealed multiple myeloma and sarcoidosis. Including this patient, 11 cases of sarcoidosis and multiple myeloma have been reported to date, including 3 patients with monoclonal gammopathy of undetermined significance preceding the onset of multiple myeloma. In this case, as in most of the cases reported previously, sarcoidosis preceded the development of multiple myeloma.

(Arch Pathol Lab Med. 2002;126:365-368)

Sarcoidosis is a chronic systemic disorder of unknown etiology characterized histologically by the presence of nonnecrotizing granulomas.1 This disease most often affects young adults and is often more severe and acute in African Americans than in other racial groups. The clinical manifestations of sarcoidosis are protean and reflect the large number of organ systems that can be involved. Of these, the respiratory tract is almost invariably affected, and hilar lymph nodes are also enlarged in up to 90% of patients. Other organs commonly involved include the liver, heart, skin, and eyes. Sarcoidosis is associated with disturbances of the immune system, including decreased CD8-positive T-cell suppressor/cytotoxic cells, activation of CD4-positive T-cell helper/inducer cells, abnormal cytokine production, cutaneous anergy to particular antigens such as tuberculin purified protein derivative, and hypergammaglobulinemia.1,2

An association between sarcoidosis and malignant neoplasms has been suggested.3,4 In particular, patients with sarcoidosis may also develop a lymphoproliferative disorder. Usually, the lymphoproliferative disorder follows the onset of sarcoidosis by more than one year. Hodgkin disease is the most common lymphoid neoplasm; however, many different types of non-Hodgkin lymphomas and lymphoid leukemias also have been reported in patients with sarcoidosis. Brincker5 suggested the term sarcoidosis-lymphoma syndrome for this association in 1986.

References

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2. Karakantza M, Matutes E, MacLennan K, O'Connor NTJ, Srivastava PC, Catovsky D. Association between sarcoidosis and lymphoma revisited. J Clin Pathol. 1996;49:208-212.

3. Brincker H, Wilbek E. The incidence of malignant tumours in patients with respiratory sarcoidosis. BrJ Cancer. 1974;29:247-251.

4. Brincker H. Sarcoidosis and malignancy. Chest. 1995;108:1472-1474.

5. Brincker H. The sarcoidosis-lymphoma syndrome. Br J Cancer. 1986;54: 467-473.

6. Schafer A, Miller JB. Association of IgA multiple myeloma with pre-existing disease. Br J Haematol. 1979;41:19-24.

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8. Santos CP, Roca JR, Manero NG, et al. Mieloma multiple y sarcoidosis de presentation simultanea. Sangre. 1997;42:411-413.

9. Selroos O, Grander L, Virolainen M. Sarcoidosis and myeloma of lambda-- type IgG. Acta Med Stand. 1974;1-2:59-63.

10. Uchiumi H, Murakami H, Matsushima T, et al. Does sarcoidosis induce multiple myeloma? Am J Hematol. 1993;44:220.

11. Sailer M, Vykoupil K-F, Peest D, et al. Prognostic relevance of a histologic classification system applied in bone marrow biopsies from patients with multiple myeloma: a histopathological evaluation of biopsies from 153 untreated patients. EurJ Haematol. 1995;54:137-146.

12. Hunninghake GW, Crystal RG. Mechanisms of hypergammaglobulinemia in pulmonary sarcoidosis. J Clin Invest. 1981;67:86-92.

13. Bataille R, Harousseau JL. Multiple myeloma. N Engl J Med. 1997;336: 1657-1664.

Filiz Sen, MD; Karen P. Mann, MD, PhD; L. Jeffrey Medeiros, MD

Accepted for publication August 8, 2001.

From the Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Tex (Drs Sen and Medeiros); and the Department of Pathology and Laboratory Medicine, Emory University Medical Center, Atlanta, Ga (Dr Mann).

Reprints: L. Jeffrey Medeiros, MD, Division of Pathology and Laboratory Medicine, Box 72, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (e-mail: jmedeiro@mdanderson.org).

Copyright College of American Pathologists Mar 2002
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