24. Plasma Cell Proliferation Flashcards
What are plasma cell dyscrasias?
Neoplastic proliferation of plasma cells (ie. mature B cells) that secrete monoclonal immunoglobulins
What is the structure of an immunoglobulin?
2 heavy and 2 light chains
Classify plasma cell dyscrasias
Multiple myeloma Smoldering multiple myeloma Solitary myeloma Monoclonal gammopathy of undetermined significance Waldenstrom's macroglobulinaemia
What is multiple myeloma?
Multifocal bone marrow disease
Malignant proliferation of plasma cells and skeletal destruction
What immunoglobulins are usually produced in multiple myeloma?
IgG and IgA
What is the name of the light chain protein excreted in urine in multiple myeloma?
Bence Jones protein
What is the appearance of plasma cells?
Eccentric nucleus
‘Clock face’ appearance
What are the possible causes of multiple myeloma?
Irradiation
Asbestos
Herpes virus 8
Genetics
What results from the cytokines produced by myeloma cells?
Growth of myeloma cells
Increase osteoclast activation
Eg. IL6
How is multiple myeloma diagnosed?
Radiology
Bone marrow examination
Serum and urine electrophoresis
Ig levels
How do skeletal lesions appear in multiple myeloma?
‘soap bubble’
In axial skeleton
Multifocal
What features are found in bone marrow examination in multiple myeloma?
Increased plasma cells
-Atypical and blasts
Russel bodies, Mott cells and Dutcher bodies
Only one type of Ig and light chain on IHC
What is a Russel body?
Cell with Ig within cytoplasm
What is a Mott cell?
Lots of Ig in cytoplasm
What is a Dutcher body?
Ig in nucleus
What finding is present in serum analysis of multiple myeloma?
Monoclonal globulin spike on electrophoresis
What finding is present in urine electrophoresis of multiple myeloma?
Proteinuria with Bence Jones protein
What are the clinical features of multiple myeloma?
CRAB Hypercalcaemia Renal failure Anaemia Bone lesions and bleeding
What 3 factors cause anaemia in MM?
bone marrow is replaced by tumour
Reduced RBC production due to cytokines
Reduced erythropoietin production
What is the most common cause of death for MM?
Sepsis
-reduction in normal Ig and leukocytes
What is the second most common cause of death for MM?
Kidney failure
What are the causes of kidney failure in MM?
Myeloma kidney AL type amyloidosis Light chain nephropathy Increased calcium and uric acid Pyelonephritis
What is the difference between myeloma kidney and light chain nephropathy?
Myeloma kidney is due to Bence Jones protein in epithelial cells
Light chain nephropathy takes place in the glomerulus
What is a Rouleaux formation?
Ig reduces the charge on RBCs so they stick together
What is the treatment for multiple myeloma?
Immunomodulatory and proteasome inhibitor therapies
Bisphosphonates
Bone marrow transplant
What are the symptoms of smoldering MM?
None
What is solitary plasmacytoma?
Solitary lesions on bone or soft tissue
What is monoclonal gammopathy of undetermined significance?
Early, benign stage of MM
What age group is lymphoplasmacytic lymphoma most common in?
Elderly
Why is lymphoplasmacytic lymphoma also known as?
Waldenstrom’s macroglobulinaemia
Produces IgM which is the biggest Ig
What are the symptoms of Waldenstrom’s lymphoma?
Weakness and weight loss Lymphadenopathy Hepatosplenomegaly M spike Autoimmune haemolytic anaemia Hyperviscosity syndrome
What are the symptoms of hyperviscosity syndrome?
Visual impairment
CNS symptoms
Bleeding
Cryoglobulinaemia
What causes visual impairment in hyperviscosity syndrome?
Distension and haemorrhage of retinal veins
Why is there bleeding in hyperviscosity syndrome?
IgM binds to clotting factors and interfere with platelet function
What is cryoglobulinaemia?
In cold macroglobulins stick together
Known as Raynaud’s phenomenon
