Chapter 106. Plasma Cell Disorders (Part 10)

Heavy Chain Diseases The heavy chain diseases are rare lymphoplasmacytic malignancies. Their clinical manifestations vary with the heavy chain isotype. Patients secrete a defective heavy chain that usually has an intact Fc fragment and a deletion in the Fd region. Gamma, alpha, and mu heavy chain diseases have been described, but no reports of delta or epsilon heavy chain diseases have appeared. Molecular biologic analysis of these tumors has revealed structural genetic defects that may account for the aberrant chain secreted.Gamma Heavy Chain Disease (Franklins Disease)This disease affects individuals of widely different age groups and countries of origin. It...
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Chapter 106. Plasma Cell Disorders (Part 10) Chapter 106. Plasma Cell Disorders (Part 10) Heavy Chain Diseases The heavy chain diseases are rare lymphoplasmacytic malignancies. Theirclinical manifestations vary with the heavy chain isotype. Patients secrete adefective heavy chain that usually has an intact Fc fragment and a deletion in theFd region. Gamma, alpha, and mu heavy chain diseases have been described, butno reports of delta or epsilon heavy chain diseases have appeared. Molecularbiologic analysis of these tumors has revealed structural genetic defects that mayaccount for the aberrant chain secreted. Gamma Heavy Chain Disease (Franklins Disease) This disease affects individuals of widely different age groups andcountries of origin. It is characterized by lymphadenopathy, fever, anemia,malaise, hepatosplenomegaly, and weakness. Its most distinctive symptom ispalatal edema, resulting from involvement of nodes in Waldeyers ring, and thismay progress to produce respiratory compromise. The diagnosis depends on thedemonstration of an anomalous serum M component [often paraaortic adenopathy. Respiratory tract involvement occurs rarely. Patients mayvary widely in their clinical course. Some may develop diffuse aggressivehistologies of malignant lymphoma. Chemotherapy may produce long-termremissions. Rare patients appear to have responded to antibiotic therapy, raisingthe question of the etiologic role of antigenic stimulation, perhaps by some chronicintestinal infection. Chemotherapy plus antibiotics may be more effective thanchemotherapy alone. Immunoproliferative small intestinal disease (IPSID) isrecognized as an infectious pathogen–associated human lymphoma that hasassociation with Campylobacter jejuni. It involves mainly the proximal smallintestine resulting in malabsorption, diarrhea, and abdominal pain. IPSID isassociated with excessive plasma cell differentiation and produces truncated alphaheavy chain proteins lacking the light chains as well as the first constant domain.Early-stage IPSID responds to antibiotics (30–70% complete remission). Mostuntreated IPSID patients progress to lymphoplasmacytic and immunoblasticlymphoma. Mu Heavy Chain Disease The secretion of isolated mu heavy chains into the serum appears to occurin a very rare subset of patients with chronic lymphocytic leukemia. The onlyfeatures that may distinguish patients with mu heavy chain disease are thepresence of vacuoles in the malignant lymphocytes and the excretion of kappalight chains in the urine. The diagnosis requires ultracentrifugation or gel filtrationto confirm the nonreactivity of the paraprotein with the light chain reagents,because some intact macroglobulins fail to interact with these serums. The tumorcells seem to have a defect in the assembly of light and heavy chains, because theyappear to contain both in their cytoplasm. There is no evidence that such patientsshould be treated differently from other patients with chronic lymphocyticleukemia (Chap. 105). Further Readings Ghobrial IM et al: Waldenström macroglobulinaemia. Lancet Oncol 4:679,2003 [PMID: 14602248] Harousseau JL, Moreau P: Evolving role of stem cell transplantation inmultiple myeloma. Clin Lymphoma Myeloma 6:89, 2005 [PMID: 16231846] Hideshima T et al: Understanding multiple myeloma pathogenesis in thebone marrow to identify new therapeutic targets. Nature Rev Cancer 7:585, 2007[PMID: 17646864] The International Myeloma Working Group: Criteria for the classificationof monoclonal gammopathies, multiple myeloma and related disorders: A reportof the International Myeloma Working Group. Br J Haematol 121:749, 2003 Kuehl WM, Bergsagel PL: Multiple myeloma: Evolving genetic events andhost interactions. Nature Rev Cancer 2:175, 2002 [PMID: 11990854] Kyle RA, Rajkumar SV: Multiple myeloma. N Engl J Med 351:1860, 2004[PMID: 15509819] ——— et al: Prevalence of monoclonal gammopathy of undeterminedsignificance. N Engl J Med 354:1362, 2006 ——— et al: American Society of Clinical Oncology 2007 clinical practiceguideline update on the role of bisphosphonates in multiple myeloma. J ClinOncol 25:2464, 2007 Mitsiades CS et al: Focus on multiple myeloma. Cancer Cell 6:439, 2005 Munshi NC, Anderson KC: Plasma cell neoplasm, in Principles andPractice of Oncology, 7th ed, V DeVita, S Rosenberg, S Hellman (eds).Philadelphia, Lippincott–Raven Publishers, 2005 Treon SP et al: Update on treatment recommendations from the ThirdInternational Workshop on Waldenströms macroglobulinemia. Blood 107:3442,2006 [PMID: 16410453] Wahner-Roedler DL et al: Gamma-heavy chain disease: Review of 23cases. Medicine 82:236, 2003 [PMID: 12861101 ...