Plasma cell disorders Multiple myeloma o Malignant proliferation of plasma cells in the BM o Most common primary malignancy of bone

e Metastatic carcinoma is the most common malignancy to involve bone o High serum IL-6 is sometimes present GF for plasma cells o Clinical presentation is going to be based on what the cells are actually producing Bone pain w/ hypercalcemis Neoplastic plasma cells activate RANK receptors on osteoclasts o Also secrete IL-1 which is osteoclast activating factor Present w/ lytic punched-out lesions seen on x-ray o Esp of the vertebrae and skull Leading to an increased risk for bone fractures

Plasma cells of MM will produce immunoglobulin elevated serum protein There will be an M spike present on SPEP (serum protein electrophoresis) M spike = monoclonal immunoglobulin o Most commonly due to monoclonal IgG or IgA o Complication Increased infection Due to the monoclonality of the immunoglobulins which lack antigenic diversity o Most common cause of death in these pts Rouleaux formation on blood smear Increased serum protein decreases charge bw the RBCs o Cells start piling up on each other Primary AL amyloidosis Over production of light chain o Free light chain circulates in serum and deposits in tissues o Can lead to proteinuria Free-light chain is excreted in urine as Bence-Jones proteins Deposition in kidney tubules leads to risk for renal failure (myeloma kidney) MGUS (monoclonal gammopathy of undetermined significance) o Increased serum protein w/ M spike on SPEP o Other features of multiple myeloma are absent (no lytic lesions, hypercalcemia, AL amyloid, or Bence-jones proteinuria) o

o Common in elderly (seen in 5% of pts in their 70s) o 1% of pts w/ MGUS develop multiple myeloma each year Waldenstrom macroglobulinemia o B-cell lymphoma w/ monoclonal IgM production Macroglobulin = IgM bc its a pentamer o Clinical features Generalized LAD Lytic bone lesions are absent Increased serum protein w/ M-spike (comprised of IgM) Increases the viscosity of the blood leading to: o Visual and neurologic deficits (retinal hemorrhage or stroke) o Bleeding Due to defective platelet aggregation o Acute complications are treated w/ plasmapheresis Removes IgM from serum Langerhans cell histiocytosis Langerhans cells: o Specialized dendritic cell found predominantly in the skin o Derived from BM monocytes o Present antigen to nave T-cells Tumor of langerhans cells = langerhans cell histiocytosis o Neoplastic proliferation of langerhans cells o Characteristic birbeck (tennis racket) granules seen on EM o Cells are CD1a+ and S100+ by immunohistochem

3 subtypes of langerhans histiocytosis o Letterer-siwe disease Malignant proliferation of langerhans cells Classic presentation is skin rash and cystic skeletal defects in and infant (less than 2yrs) Multiple organs may be involved and its rapidly fatal o Eosinophilic granuloma Benign proliferation of langerhans cells in bone Classic presentation is pathologic fracture in an adolescent (ddx osteosarcoma) Skin is not involved Biopsy shows langerhans cells w/ mixed inflammatory cells (including eos) o Hand-Schuller-Christian disease Malignant proliferation of langerhans cells

Classic presentation is scalp rash, lytic skull defects, diabetes insipidus and exopthalmos in children (greater than 3 yrs)