25. Plasma cell neoplasms and related disorders Flashcards
What are plasma cell dyscrasias
neoplastic proliferation of plasma cells which secrete monoclonal intact immunoglobulin or Ig fragments (free light chain)
Classification of plasma cell neoplasm (dyscrasias)
I. multiple myeloma
II. smoldering multiple myeloma
III. solitary myeloma (plasmocytoma)
IV. monoclonal gammaopathy of undetermined significance
V. lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinaaemia)
VI. other rare entities
What is multiple myeloma
multifocal bone marrow disease characterized by malignant proliferation of plasma cells with skeletal destruction
- monoclonal B cells profuce a single type of Ig
- usually adults > 50 years
Causes of multiple myeloma
- previous exposure to irradiation
- exposure to asbestos, petroleum products, rubber or plastic products
- Human herpes virus 8
Pathogenesis of multiple myeloma
myeloma cells bind to bone marrow stromal cells via cell surface adhesion molecules -> myeloma cell growth -> survival -> drug resistance and migration in the bone marrow milieu
- myeloma cells produce cytokines (e.g. IL6)
- interaction with bone marrow stromal cells -> osteolast activation (RANK receptors) and osteoblast inhibition
- plasma cells produce intact monoclonal Ig (M component) and light chain
- intact monoclonal Ig has high molecular weight - not present in urine if no glomerular disease
- IgG, IgA, light chain
- light chain excreted in urine - can be filtered (Bence-Jones protein)
How is multiple myeloma diagnosed
- radiology
- bone marrow examination
- serum and urine electrophoresis and immunoglobulin levels
What can you see on bone marrow examination for someone who has multiple myeloma
- plasma cell increased
- perinuclear clearing and eccentric nucleus
- atypical cells with bi-, tri- or multinucleated forms
- immature blasts
- intracytoplasmic inclusion (Russell bodies)
- Mott cells
- intranuclear inclusions (Dutcher bodies)
- immunohistochemistry: single type of Ig and single type of light chain (kappa/lambda)
Serum and urine analysis of multiple myeloma
- serum
- monoclonal globulin spike on serum electrophoresis
- M spike most commonly IgG or IgA - urine
- proteinuria (light chain)
- kappa/lambda
Clinical features of multiple myeloma
CRAB C- calcium (elevated) R - renal failure A - anaemia B - bone lesion
What is bone lesion
proliferation of tumour cells which infiltrate the bone
-production of IL6/osteoclast activating factor
How is bone lesion presented
- bone pain
- lytic lesions
- pathological fractures
- diffuse osteoporosis
- hypercalcaemia (confusion, weakness, lethargy, abdominal pain, constipation, polyuria, depression, renal stones)
- spinal cord compression (lumbar vertebrae)
- tumour cell replace bone marrow -> anaemia, thrombocytopenia, leucopenia
Type of anaemia in multiple myeloma
normocytic or normochromic
What causes anaemia in multiple myeloma
-replacement of normal bone marrow by tumour cells
-inhibition of normal RBC production by cytokines
-decrease in erythropoietin production
decrease charge of RBC -> Rouleaux formation on blood smear
Why does bleeding occur in multiple myeloma
- monoclonal immune proteins interfere with normal coagulation
- infiltration of the bone marrow -> thrombocytopenia
Why does hyperviscosity occur in multiple myeloma
high volume of monoclonal protein -> blood viscosity increases -> complications: stroke, MI, myocardial ischaemia
-blood becomes sticky and thick
Why does sepsis occur in multiple myeloma
- decreased productin of normal Ig -> recurrent bacterial infection
- leucopenia
Clinal features of renal failure in multiple myeloma
- myeloma kidney = myeloma cast nephropathy
- Bence-Jones toxic to renal tubular epithelial cells - amyloidosis
- amyloid light chain type - light chain nephropathy
- hypercalcaemia and hyperuricaemia
- pyelonephritis
- drug induced
How to determine amyloidosis in multiple myeloma
systemic deposition of amyloid light chain type in:
kidneys - nephrotic syndrome
heart - restrictive cardiomyopathy
tongue enlargement
-require tissue biopsy from rectum
-congo red staining with apple green birefringence under polarised light
How does neurological symptoms occur in multiple myeloma
hyperviscosity, hypercalcaemia, nerve compression
Prognosis of multiple myeloma
-6 to 12 months if untreated
-medial survival 4 to 7 years
Cause of death:
-infection
-renal failure
Treatment of multiple myeloma
- currently not curable
- immunomodulatory, proteasome inhibitors
- bisphosphonates
- bone marrow transplantation: autologous, allogenic
What is smoldering multiple myeloma
- asymptomatic
- highly likely to progress to multiple myeloma
What is solitary plasmacytoma of bone
- involve spine, pelvis and femur
- single symptomatic area of bone destruction
- progression to multiple myeloma in 10-20 years
What is extramedullary plasmacytoma
- involve lung, oropharynx and nasal sinuses
- extra-ossesous lesions can be cured by local resection or radiotherapy
- progression to multiple myeloma is rare
What is monoclonal gammopathy of undetermined significance
- starts out as a relatively benign condition
- most common cause of monclonal gammopathy
- asymptomatic
- increased serum protein with M spike on spectrum electrophoresis
- plasma cells less than 10%
- no Bence-Jones protein, bone lesions, hypercalcaemia or amyloid
- early stage of myeloma
What is lymphoplasmacytic lymphoma
low-grade B cell lymphoproliferative neoplasm characterized by small lymphocytes and monoclonal IgM monoclonal gammopathy
-elderly
-males more than female
-neoplastic cells produce monoclonal IgM
(macroglobulin = Waldenstrom’s macroglobulinaemia)
-mean survival is 4-5 years
Clinical features of lymphoplasmacytic lymphoma
- no bone lesions
- weakness, weight loss
- lymphadenopathy, hepatosplenomegaly
- increased serum protein with M spike (IgM)
- autoimmune haemolysis (IgM binds to RBC)
- hyperviscosity syndrome
Clinical features of hyperviscosity syndrome
- visual impairment
- distension of retinal veins and haemorrhage - neurological symptoms
- headaches, dizziness due to sluggish blood flow - bleeding
- macroglobulins bind to clotting factors and interfere with platelet function - cryoglobulinaemia
- precipitation of macroglobulins at low temp -> Raynaud’s phenomenon
Treatment of hyperviscosity syndrome
Plasmapheresis
-removal, treatment, and return or exchange of blood plasma or components thereof from and to the blood circulation
