Differential diagnosis of plasma cell dyscrasias in rheumatological practice

Plasma cell dyscrasias (PCD) present certain difficulties in differentially diagnosing with autoimmune rheumatic diseases (RD) as they have some clinical and laboratory manifestations that are characteristic of the latter.
Objective: to generalize the experience in diagnosing PCD at the Research Institute of Rheumatology (RIR), Russian Academy of Medical Sciences (RAMS).
Subjects and methods. Nineteen patients admitted to the RIR, RAMS, for rheumatological referral diagnoses were diagnosed as having different types of PCD, both PCD in the presence of RD (n = 10) and primary PCD without RD (n = 9). Immunochemical studies of serum and urinary proteins and bone marrow trepanobiopsy were performed in all the patients. Histological studies were made of the minor salivary glands (n = 12), lymph nodes (n = 3), parotid salivary glands - PSG (n = 5), spleen (n = 1), cranial bones (n = 2) and humerus (n = 1). The immunophenotype of tumor lymphocytes in the biopsy and trepanobiopsy specimens were determined by an immunoflurenscence method with standard monoclonal antibody panels and the paraffin sections of biopsy specimens were examined by an immunoperoxidase technique. Biopsy and trepanobiopsy speciments and myelograms were assessed by the researchers of the N.N. Blokhin Russian Cancer Research Center, RAMS. Results. Over 10 years of follow-up, 19 patients (13 females and 6 males) were diagnosed as having different types of PCD: multiple myeloma (MM) (n = 9), extramedullary plasmacytoma of lymph nodes (n = 2), solitary plasmacytoma (SP) of bone (n = 2), Bence-Jones myeloma
(BJM) (n = 2), primary amyloidosis (PA) (n = '), lymphoplasmacytic lymphoma (n = '), Waldenström's macroglobulinemia (WM) (n = 2). In the presence of RA, '0 patients with PCD developed Sjogren's disease (SD) (n = 7), rheumatoid arthritis (RA) + SD (n = 2), RA (n = '); and 9 patients had primary PCD (MM (n = 5), BJM (n = '), WM (n = '), SP (n = '), and PA (n = ')). These 9 patients with different rheumatological diagnoses were long followed up and referred to the RIR, RAMS, to specify these.
One third of the patients had recurrent conjunctivitis, enlarged PSG and xerostomia (55%). Arthralgias, arthritis of minor and large joints, flexion contractures of hands, ossalgias, and pains in the lumbar spine and ribs were present in '0-45% of the patients. Vascular lesions, such as Reynaud's phenomenon, recurrent purpuras, lower extremity ulcerative lesions, and toe gangrenes, were observed in '0-35% of the patients with PCD. Lesions in the reticuloendothelial system, such as lymphadenopathy, splenomegaly ('5%), hepatomegaly (45%), and fever (25%), were also detected.
Conclusion. Many clinical and laboratory manifestations of primary PCD and RD are similar and only the absence of classical laboratory markers of autoimmune disease, as well as the presence of serum monoclonal immunoglobulins and urinary Bence Jones protein suggest the presence of PCD, both primary PCDs and those with RD.

plasma cell dyscrasias, rheumatic diseases, monoclonal immunoglobulins

1. <div><p>Osterland C. Monoclonal gammopathies - their identification and biological significance Clinica Chimica Acta 1989;180:1-22.</p><p>Kyle R., Rajkumar S. Monoclonal gammopathies of undetermined significance Best Pract Res Clin Haematol 2005;18:689-707.</p><p>Городецкий В.Р., Пробатова Н.А., Васильев В.И. и др. Первичная плазмоцитома лимфатических узлов. Гематол и трансфузиол 2006;51(5):3-8.</p><p>Васильев В.И., Городецкий В.Р., Седышев С.Х. и др. Клинические проявления васкулита в дебюте множественной миеломы. Науч-практ ревматол 2010;1:81-7.</p><p>Biologic and clinical significance of cryoglobulins. Review. A report of 86 cases Amer J Med 1974;57:775-87.</p><p>Naschitz J.E. Rheumatic syndromes: сlues to occult neoplasia. Curr Opin Rheumatol 2001;13:62-6.</p><p>Blade J., Kyle R.A. Monoclonal gammopathies of undertermined significance. Myeloma. Biology and management. Ed. Malpas J.S., Bersagel D.E., Kyle R.A., Anderson K.S. Oxford medical publications, 1998;514-41.</p><p>Rajkumar S.V., Kyle R.A. eds. Treatment of Multiple Myeloma and Related Disorders. Cambridge University Press, 2009;1-195.</p><p>Smedby K.E., Baecklund E., Askling J. Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics. Review. Cancer Epidem Biomarkers Prev 2006;15(11):2069-77.</p><p>Zintzaras E.,Voulgarelis M., Moutsopoulos H.M. The risk of lymphoma development in autoimmune diseases. A meta-analysis. Arch Intern Med 2005;165(14):2337-44.</p><p>Askling J., Bongartz T. Malignancy and biologic therapy in rheumatoid arthritis. Curr Opin Rheumatol 2008;20:334-9.</p><p>Кiltz U., Brandt J., Zochling J. et al. Rheumatic manifestations of lymphoproliferative disorders. Clin Exp Rheumat 2007;25:35-9.</p><p>Vital E.M., Emery P. Rheumatological manifestations of malignant haematological conditions. Reports on the rheumatic diseases series 5. Topical Reviews 2007;11:1-8.</p><p>Manganelli P., Fietta P., Quaini F. Hematologic manifestations of primary Sjogren's syndrome. Clin Exp Rheumatol 2006;24:438-48.</p><p>Leandro M.J., Isenberg D.A. Rheumatic diseases and malignancy - is there an association? Scand J Rheumatol 2001;30:185-8.</p><p>Васильев В.И., Пробатова Н.А., Тупицин Н.Н. и др. Лимфопролиферативные заболевания при болезни Шёгрена. Онкогематол 2007;3:16-27.</p><p>Saadoun D., Sellam J., Ghillani-Dalbin P. et al. Increased risks of lymphoma and death among patients with non-hepatitis C virus - related mixed cryoglobulinemia. Arch Intern Med 2006;166(23):2101-8.</p><p>Kurzrock R., Cohen P.R. Vasculitis and cancer. Clin Dermatol 1993;11(1):175-87.</p><p>Национальное руководство по ревматологии. Под ред. Е.Л. Насонова, В.А. Насоновой. М.: ГОЭТАР-Медиа, 2008; 714 с.</p><p>Андреева Н.Е., Балакирева Т.В. Множественная миелома. Руководство по гематологии. Т 2. Под ред. А.И. Воробьева. М.: Ньюдиамед, 2003;151-73.</p><p>Symmons D.P., Ahern M., Bacon P.A. et al. Lymphoproliferative malignancy in rheumatoid arthritis: a study of 20 cases. Ann Rheum Dis 1984;43(2):132-5.</p><p>Васильев В.И., Пробатова Н.А., Варламова Е.Ю. и др. Прогностическое значение смешанной моноклональной криоглобулинемии при болезни Шёгрена Тер арх 2004;8:61-8.</p><p>Васильев В.И., Пробатова Н.А., Тупицин Н.Н. и др. MALT-лимфомы при болезни Шёгрена Тер арх 2006;1:45-52.</p><p>Kojima M., Itoh H., Shimizu K. et al. Malignant lymphoma in patients with systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis): a clinicopathologic study of 24 Japanese cases. Int Surg Pathol 2006;14(1):43-8.</p><p>Городецкий В.Р. Иммуноглобулинсекретирующие лимфомы: Автореф. дис. канд. мед. наук. М., 2000; 22 с.</p><p>Cur H., Koren V., Ehrenfeld M. et al. Rheumatic manifestation preceding adult acute leukaemia: characteristics and implication in course and prognosis. Acta Haematol 1999;101(1):1-6.</p><p>Dispenzieri A., Merlini G., Comenzo R.L. Amyloidosis: 2008 BMT Tandem Meetings. Biology of blood and marrow transplantation 2008;14:6-11.</p><p>Городецкий В.Р., Пробатова Н.А., Логвиненко О.А. и др. Трудности диагностики лимфоидных неоплазий у больных ревматоидным артритом. Науч-практич ревматол 2009;3:94-100.</p><p>Варламова Е.Ю. Иммунохимическая диагностика парапротеинемий. Клиническая онкогематология. Под ред. М.А. Волковой. М.: Медицина, 2001;411-9.</p><p>Vasilyev V.I., Mitricov B.V., Kokosadze N.V. et al. B-cell neoplasms in primary Sjogren's syndrome. Abstract book. 10th Internacional symposium on Sjogren's syndrome. 2009; 125.</p></div><br />