Heavy Chain Disease

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Heavy Chain Disease

• Masatoshi Kida, M.D.
• Dept. of Pathology
• University of Vermont

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heavy-chain diseases

• rare lymphoplasmacytic malignancies
• seen in lymphoplasma cell proliferative process
  (CLL/SLL, lymphoplasmacytic lymphoma)
• variable clinical manifestations with heavy chain
  isotype
• production of structurally altered monoclonal
  proteins (fragment of Ig heavy chain)
• three major subtypes
• ?-HCD
• ?-HCD
• ?-HCD

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heavy-chain diseases?-HCD

• age widely different age groups and countries
  of origin
• often with lymphoma-like illness
• Clinical feature
• diverse clinical findings (asymptomatic to
  aggressive)
• hepatosplenomegaly, lymphadenopathy (60)
• anemia (80 to 100), fever, malaise, weakness
• Treatment
• only for symptomatic cases
• many combinations have been tried, but
  inconsistent and disappointing
• Prognosis
• variable (indolent to rapidly aggressive)

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heavy-chain diseases?-HCD

• Dx
• demonstration of anomalous serum M component
  (often lt20g/L) that reacts with anti-IgG but not
  anti-light chain reagents
• M component is seen in both serum and urine (most
  of paraproteins are gamma, but others are also
  seen)
• BM non-diagnostic findings

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heavy-chain diseases?-HCD

• Clinical course and prognosis
• variable, but mostly rapid downhill course
• some survives 5 years with chemotherapy
• death from infection

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heavy-chain diseases?-HCD

• most common subtype of heavy chain disesase
• seen in Mediterranian and Middle East regions
• 10s and 20s, 60 male
• Clinical feature
• GI tract involvement (sever malabsorption with
  diarrhea, steatorrhea, loss of wt.)
• extensive mesenteric and para-aortic
  lymphadenopathy
• plasma cell infiltrate of jejunal mucosa
• rare respiratory tract involvement
• no light chains in serum or urine
• Treatment
• some response to chemotherapy, but most are
  progressive and fatal
• chemotherapy -- may produce long-term remissions
• chemotherapy antibiotics -- more effective
• antibiotics -- sometimes work (? chronic
  intestinal infection as etiologic stimulation)

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heavy-chain diseases?-HCD

• defect in assembly of light and heavy chains
• may seen with CLL/SLL
• Clinical feature
• Bence Jones proteinuria (kappa light chain in
  urine)
• increased number of lymphocytes, plasma cells and
  lymphoplasmacytoid cells in BM
• intracytoplasmic vacuoles (Russel body)
• variable clinical course
• Treatment
• corticosteroids and alkylating agents
• Prognosis
• same as CLL/SLL
• survival few months to many years

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