CH6 - 6) Plasma cell disorders, Histiocytosis Flashcards
What are the plasma cell disorders?
Dyscrasias: 1) multiple myeloma 2) MGUS 3) Waldenstrom Macroglobulinemia
What is multiple myeloma?
Malignant proliferation of plasma cells in the bone marrow
Whis the most common primary malignancy of bone?
metastatic cancer,
What is the most common malignant lesion of bone overall?
Multiple myeloma
In multiple myeloma what is usually present?
High serum IL-6 is sometimes present; stimulates plasma cell growth and immunoglobulin production
What are the clinical features for multiple myeloma?
1) Bone pain with hypercalcemia 2) Elevated serum protein 3) increased risk of infection 4) Rouleaux formation of RBC’s on blood smears 5) Primary AL amyloidosis 6) Proteinuria
Why is there bone pain with hypercalcemia in multiple myeloma?
Neoplastic plasma cells activate the RANK receptor on osteoclasts, leading to bone destruction.
With multiple myeloma what might you see on x-ray?
Lytic, ‘punched-out’ skeletal lesions are seen on x-ray, especially in the vertebrae and skull; increased risk for fracture
Why is there elevated serum protein in multiple myeloma?
Neoplastic plasma cells produce immunoglobulin;
In multiple myeloma, what is seen on electrophoresis?
M spike is present on serum protein electrophoresis (SPEP), most commonly due to monoclonal IgG or IgA
In multiple myeloma why is there increased risk of infection?
Monoclonal antibody lacks antigenic diversity
What is the most common cause of death in multiple myeloma?
infection
Why is there rouleaux formation of RBCs on blood smear?
increased serum protein decreases charge between RBCs
Why is there primary AL amyloidosis in multiple myeloma?
Free light chains circulate in serum and deposit in tissues.
Why is there proteinuria in multiple myeloma? What does this increase the risk for?
Free light chain is excreted in the urine as Bence Jones protein; deposition in kidney tubules leads to risk for renal failure (myeloma kidney).
What is monoclonalgammopathy of undetermined significance?
Increased serum protein with M spike on SPEP; other features of multiple myeloma are absent (no lytic bone lesions, hypercalcemia, AL amyloid, or Bence Jones proteinuria)
MGUS is common in what group of people?
elderly (seen in 5% of 70-year-old individuals);
What are the odds of a patient with MGUS developing multiple myeloma?
1% of patients with MGUS develop multiple myeloma each year.
What is Waldenstrom macroglobulinemia?
B-cell lymphoma with monoclonal IgM production
What are the clinical features for waldenstrom macroglobulinemia?
1) Generalized lymphadenopathy, lytic bone lesions are absent 2) Increased serum protein with M spike (comprised of IgM) 3) Visual and neurologic deficits (e.g., retinal hemorrhage or stroke) IgM (large pentamer) causes serum hyperviscosity. 4) Bleeding
Why is there bleeding in waldenstrom macroglobulinemia?
Viscous serum results in defective platelet aggregation
What are the complications for waldenstrom macroglobulinemia treated with?
plasmapheresis, which removes IgM from the serum
What are langerhans cells?
specialized dendritic cells found predominantly in the skin.
What are langerhans cells derived from?
bone marrow monocytes
What do langerhans cells present?
Present antigen to naive T cells
What is langerhans cell histiocytosis?
it is a neoplastic proliferation of Langerhans cells
What is seen on electron microscopy in langerhan cell histiocytosis?
Characteristic Birbeck (tennis racket) granules are seen on electron microscopy;
What is langerhan cell histiocytosis immunochemistry?
cells are CDla+ and S100+
What is Letterer-Siwe disease?
Malignant proliferation of Langerhans cells
What is the classic presentation of Letterer-Siwe?
it is a skin rash and cystic skeletal defects in an infant (< 2 years old).
Can Letterer-Siwe be fatal?
Multiple organs may be involved; rapidly fatal
What is eosinophilic granuloma?
Benign proliferation of Langerhans cells in bone
What is the classic presentation for eosinophilic granuloma?
it is a pathologic fracture in an adolescent; skin is not involved
What does biopsy of eosinophilic granuloma show?
Langerhans cells with mixed inflammatory cells, including numerous eosinophils
What is Hand-Schuller-Christian disease?
Malignant proliferation of Langerhans cells
What is the classic presentation of Hand-Schuller-Christian disease?
it is scalp rash, lytic skull defects, diabetes insipidus, and exophthalmos in a child.
