Chronic Lymphoproliferative Disorders, Plasma Cell Myeloma And Amyloidosis Flashcards
How does one class chronic lymphoproliferative disorders?
Are either B or T cell malignancies.
*some are more leukaemic and some are more lymphomatous.
What is the difference between a lymphoma and leukaemia?
Lymphoma- solid lymph node mass.
Leukaemia- circulating cells in peripheral blood.
List the types of B Cell chronic leukaemias.
Chronic lymphocytic leukaemia (common)
Hairy cell leukaemia
Prolymphocytic leukaemia
Some typical Non-Hodgkin lymphomas may spill into peripheral blood when advanced
Types of chronic T cell leukaemias?
T prolymphocytic leukaemia
Large granular lymphocytic leukaemia
Adult T cell leukaemia/lymphoma
Some of the methods used to diagnose chronic leukaemias?
Blood tests - chronic persistent lymphocytosis Morphology Immunophenotype Cytogenetics Genetics
Who are most at risk with regards to chronic lymphocytic leukaemia (CLL)?
Older age group (60-80)
There is a genetic predisposition
What is the problem in chronic lymphocytic leukaemia (CLL)?
Accumulation of monoclonal mature B Lymphocytes in the:
- blood
- bone marrow
- liver
- spleen
- lymph nodes
- is due to reduced apoptosis
Clinical features or chronic lymphocytic leukaemia?
Males affected 2:1 Lymph node enlargement --> non-tender, symmetrical Anaemia Thrombocytopenia Splenomegaly Immunosuppression
Which sex is more affected with regards to chronic lymphocytic leukaemia?
M:F 2:1
Lab features of chronic lymphocytic leukaemia?
Lymphocytosis
Normocytic anaemia/autoimmune haemolysis (spherocytes)
Sometimes neutropenia/thrombocytopenia
Decreased serum Ig
Features of a peripheral blood smear regarding chronic lymphocytic leukaemia?
WCC - lymphocytosis
Small round lymphocytes
Smear cells (due to fragile B cells)
Which staging system is used to stage CLL?
Which end of the scale indicates a poorer prognosis?
Rai staging system.
Rai 0 or 1 - good prognosis.
2-4 associated with more advanced disease.
How to treat CLL?
Will partially respond to chemo but more about managing symptoms:
- treat problamatic organomegaly
- bone marrow suppression(anaemia, thrombocytopenia, neutropenia)
- haemolytic episodes
Ehat are the aims of treatment with regards to CLL?
Support not cure (cure is rare)
Control symptoms and limit extent of leucocytosis (using chemo).
What group of people does one see Hairy Cell Leukaemia in?
More in males of older age (40-60yo).
Is rare!
How do people with Hairy Cell Leukaemia present?
Severe infectons.
Anaemia.
Splenomegaly.
What does hairy cell leukaemia NOT present with?
Lymphadenopathy.
Why is it called hairy cell leukaemia?
Affected B cells appear ‘hairy’ beneath a microscope due to radial projections from their surface.
Where do abnormal cells accumulate in hairy cell leukaemia?
Bone marrow–> anemia, thrombocytopenia, infections
How does one diagnose hairy cell leukaemia?
Peripheral blood morphology.
Flow cytometry.
Bone marrow biopsy.
Prognosis of hairy cell leukaemia?
May respond well to certain chemotherapies.
Characteristics of B cell prolymphocytic leukaemia?
Very rare.
Aggressive.
Poor prognosis.
Some characteristics of T prolymphocytic leukaemia?
Very high WCC.
Skin invlovement.
Serous effusions.
Some characteristics of large granular lymphocyte leukaemia?
Cytopenias - anaemia, neutropenia
Associated with rheumatoid arthritis.
Characteristics of adult T-cell leukaemia?
Commonly seen in Caribbean and Japan. Associated with HTLV1 virus associaton. Signs+symptoms: - skin lesions - hepatosplenomegaly - lymphadenopathy - hypercalcaemia
What is multiple myeloma (plasma cell myeloma)?
A neoplasm of plasma cells that infiltrate the bone marrow and disrupt regular function of the bone marrow. Tissue damage may be a feature.
Group of people in which MM is mostly seen?
Develop after 40y.o.a.
Peak in the 60’s
What is thought to be a key factor in the development of MM?
Overexpression of cyclin D.
What may be a common complaint that is associated with MM?
An elderly patient who complains about persistent bone pain/back pain.
What are the clinical features of MM?
Bone pain - RANKL activation–> stimulates osteoclast activity (bone lesions).
Anaemia - lethargu, weakness, pallor, dyspnoea, tachycardia.
Recurrent infections- neutropenia, lack of normal Ig.
Renal- failure (calculi due to hypercalcaemia, Ig’s), polyuria, polydipsia, anorexia.
Bleeding- paraprotein interferes with platelets and coagulation factors.
Amyloidosis.
Hyperviscosity- haemorrhage, loss of vision, CNS sx, neuropathies, cardiac failure.
Diagnosis of MM?
Serum and urine protein electrophoresis looking for monoclonal protein.
Increased clonal plasma cells in bone marrow.
Increased serum calcium.
Cytogenetics and FISH
Pneumonic for MM symptoms?
C - hypercalcaemia
R - renal impairment
A - anaemia
B - bone involvement
What is seen in a trephine biopsy in MM?
Diffuse infiltrate of plasma cells.
Immunophenotyping of MM?
Monoclonal Ab staining. (Light chain)
Other investigations to diagnose MM?
Presence of paraproteins (mostly IgG).
Urine BJP - bence jones protein (monoclonal globulin protein)
Anaemia (normochromic/normocytic)
Neutropenia/thrombocytopenia
High ESR and rouleaux formation
Skeletal survey - osteolytic lesions or osteoporosis.
Management (supportive) of MM?
Renal: rehydrate, management of hypercalcaemia and hyperuricaemia
Bone disease: biphosphonates
Anaemia and infections: transfusions, antibiotics, Ig, antifungals
Bleeding: plasmapheresis
Management(specific) of MM?
Intensive - younger patients- intensive chemo
Non-intensive: oral chemo, steroids, thalidomide
Prognosis of MM?
Depends on genetics and disease burden.
A few years with non-intense chemo.
Variable.
What is MGUS?
Monoclonal gammopathy of undetermined significance.
Is a precursor of myeloma.
No clinical complications at this stage.
What is plasma cell leukaemia?
When large amounts of circulating plasma cells.
Rare + poor prognosis.
What is amyloidosis?
A group of disorders –> deposition of protein in fibrillar form extracellularly.
*disrupts organ/tissue function.
Amyloidosis: inheritance? Pattern of spread?
Is congenital or acquired.
Focal or systemic.
Systemic effects of amyloidosis?
Heart - failure
Nerves - neuropathy, carpal tunnel
Kidneys - failure
Tongue - macroglossia
