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Waldenstrom's macroglobulinemia

serum monoclonal IgM paraprotein > 3gm/dl Epidemiology: 1) disease of old age 2) presents in the 6th & 7th decades of life Pathology: 1) bone marrow shows a diffuse infiltrate of lymphocytes & plasma cells comprising > 10% of bone marrow 2) secretion of abnormal macroglobulin results in hyperviscosity syndrome 3) can be seen in association with - lymphoplasmacytic lymphoma - splenic marginal zone lymphoma - B-cell chronic lymphocytic leukemia - extranodal marginal zone B-cell lymphoma of MALT type 4) may resemble CLL more than multiple myeloma 5) malignant cells derive from postgerminal B-cell with somatic hypermutation, but not switch recombination [6] 6) impaired platelet function 7) dysfibrinogenemia Clinical manifestations: 1) chief complaints are generally non-specific a) weakness b) fatigability c) B symptoms of fever, night swears, & weight loss 2) hyperviscosity syndrome is a medical emergency (31%) a) visual impairment, blurred vision b) tinnitus, dizziness, hearing loss c) mucosal bleeding d) headache e) heart failure f) altered mentation 3) neurologic signs, neuropathy 4) deafness 5) excessive oozing from wounds 6) ecchymosis 7) lymphadenopathy [7] 8) hepatosplenomegaly [7] Laboratory: 1) serum & urine protein electrophoresis - immunofixation electrophoresis (monoclonal IgM) - M spike > 3 g/dL 2) bone marrow biopsy & aspirate 3) viscosity of serum if IgM > 4 g/dL or hyperviscosity syndrome suspected [7] 4) negative findings a) serum complement levels are normal b) antinuclear antibody (ANA) is negative c) rheumatoid factor (RF) is negative Special laboratory: - ophthalmoscopy may reveal evidence of hyperviscosity - dilated retinal veins (images [11]) - papilledema - flame hemorrhages [7] Radiology: - Chest X-ray a) no distinct radiologic lesions b) pleural effusion (50%) c) parenchymal infiltrates may be seen Complications: - hyperviscosity syndrome is a medical emergency - immediate plasmapheresis is indicated to remove excess IgM [7] - hyperviscosity-related retinopathy [11] Management: 1) plasmapheresis to remove IgM for hyperviscosity syndrome 2) chemotherapy a) rituximab with or without cytotoxic chemotherapy [7] - rituximab with nucleoside analogs with or without alkylating agents - rituximab + thalidomide [9] b) cyclophosphamide-based therapy - cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) [9] - cyclophosphamide + dexamethasone c) chlorambucil d) fludarabine e) 2-chlorodeoxyadenosine (cladribine) 3) salvage therapy - add bortezomib, alemtuzumab [9] - bortezomib associated with peripheral neuropathy 4) stem cell therapy, autologous vs allogeneic [9] 3) prognosis: average survival is 2-5 years

Interactions

disease interactions

Related

multiple myeloma; plasmacytoma/plasma cell myeloma

General

lymphoid leukemia paraproteinemia (monoclonal gammopathy) peripheral B-cell lymphoid neoplasm plasma cell dyscrasia

Database Correlations

OMIM 153600

References

  1. Cotran et al Robbins Pathologic Basis of Disease, W.B. Saunders Co, Philadelphia, PA 1989 pg 743
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 430, 790
  3. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1307
  4. Schiller G, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  5. WHO Classification Tumours of Haematopoietic and Lymphoid Tissues. IARC Press 2001
  6. Chng WJ et al, Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. Blood 2006, 108:2499 PMID: 16804116 - Wiestner A Gene expression relates WM to CLL. Blood 2006, 108:2755
  7. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  8. Treon SP. How I treat Waldenstrom macroglobulinemia. Blood. 2009 Sep 17;114(12):2375-85 PMID: 19617573
  9. Dimopoulos MA, Gertz MA, Kastritis E et al Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. J Clin Oncol. 2009 Jan 1;27(1):120-6. PMID: 19047284
  10. Gertz MA Waldenstrom macroglobulinemia: 2013 update on diagnosis, risk stratification, and management. Am J Hematol. 2013 Aug;88(8):703-11. PMID: 23784973
  11. Kim W, Kweon E (images) Hyperviscosity-Related Retinopathy in Waldenstrom's Macroglobulinemia. N Engl J Med 2016; 374:73. January 7, 2016 PMID: 26735995 http://www.nejm.org/doi/full/10.1056/NEJMicm1501103
  12. Castillo JJ, Garcia-Sanz R, Hatjiharissi E et al Recommendations for the diagnosis and initial evaluation of patients with Waldenstrom Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenstrom Macroglobulinaemia. Br J Haematol. 2016 Oct;175(1):77-86. PMID: 27378193 Free PMC Article
  13. Waldenstrom's Macroglobulinemia http://cis.nci.nih.gov/fact/6_4.htm