Chapter 21 : Multiple Myeloma and Related Plasma cell Disorders Flashcards
Fill in the blanks. “ _____________ reflects the increased synthesis of a specific type of immunoglobulin from a single expanded clone of plasma cells.”
A monoclonal immunoglobulin band (M-protein), or paraprotein
Fill in the blanks. “ When a monoclonal antibody is detected in the blood it is called __________.”
Paraproteinaemia
What is Multiple myeloma?
Multiple myeloma, also termed plasma cell myeloma, is a neoplastic disease characterized by plasma cell accumulation in the bone marrow , the presence of monoclonal protein in the serum or urine or both and in symptomatic patients related tissue damage.
What is the peak age incidence for Multiple myeloma?
65 - 70 years old
What is the pathogenesis of Multiple myeloma?
The myeloma neoplastic cell is a POST - GERMINAL CENTRE plasma cell that has undergone immunoglobulin class switching and somatic hypermutation and secretes the paraprotein that is present in serum.
What is the most frequent finding of clonal rearrange heavy and light chains immunoglobulins in multiple Myeloma?
Translocations involving the heavy chain on chromosome 14q
What genetic mutations are considered EARLY Unifying genetic events associated with Multiple myeloma?
Dysregulated or increased expression of the cyclin D1, D2 or D3 genes.
What genetic mutations are considered LATER Unifying genetic events associated with Multiple myeloma?
Secondary translocations of MYC, point mutations, e.g. of RAS or TP53, deletions, e.g. TP53, or epigenetic abnormalities.
True or False? Multiple Myeloma is most common in people of European descent.
FALSE!! It is most common in people of African Descent
Fill in the blanks. “ In Multiple myeloma , Osteolytic lesions are caused by osteoclast activation resulting from high serum levels of ___________.”
Nuclear factor-κB (NF-κB) ligand (RANKL)
Nuclear factor-κB (NF-κB) ligand (RANKL) is produced by which cells?
Plasma cells and bone marrow stroma
When does a Asymptomatic or Smouldering Myeloma increases its risk of becoming Symptomatic myeloma?
- If there is more than 60% of plasma cells in the marrow
- If there are circulating plasma cells
- If there is a greatly unbalanced free light chain ratio
- If there are Focal lesions on MRI
- If there are any cytogenetic abnormalities.
When is symptomatic myeloma diagnosed?
- If there is a Monoclonal protein in serum, urine, or both .
- Increased clonal plasma cells in the bone marrow
- Disease-related organ or tissue impairment.
What are the clinical features of Multiple Myeloma ?
C - Hypercalcaemia
R - Renal impairment
A - Anaemia
B - Bone disease
Additionally,
- Recurrent infections
- Abnormal bleeding tendency
- Amyloidosis (light chain) occurs in 5% with features such as macroglossia, carpal tunnel syndrome, heart failure, peri-orbital purpura and diarrhoea.
- Hyperviscosity syndrome, with purpura, haemorrhages, visual changes, cen- tral nervous system (CNS) symptoms, neuropathies and heart failure.
- Deep Vein Thrombosis
- Peripheral Neuropathy
- PUNCHED OUT LESIONS
What are the Laboratory Findings in Multiple Myeloma?
- Presence of a paraprotein- IgG (60%) , IgA(20%) & Light chain only ( The rest ) , less than 1% IgD & IgE
- Elevated serum immunoglobulin free light chains.
- Immunoparesis ( Normal serum immunoglobulin levels (IgG, IgA and IgM) are reduced)
- BENCE JONES Proteins
- There is usually a normochromic normocytic or macrocytic anaemia.
- ROULEAUX formation
- Neutropenia & Thrombocytopenia
- Abnormal Plasma cells
- High ESR - due to reduction in the normal red cell–repelling ‘zeta potential’ by immunoglobulin coating of erythrocyte surfaces.
- More than 20% of marrow cells in bone marrow
- Malignant plasma cells CD38 positive, CD 138 positive & LOW CD45
- Bone lesions
- Increase in Serum Calcium
- Increase in Serum Creatinine
- Normal ALP - except following pathological fractures.
- Increase LDH
- LOW Serum Albumin occurs with advanced disease = poor prognosis
- Raised Serum β2-microglobulin = poor outcome if high
