Non-Malignant Plasma Cell Disorders Flashcards
Monoclonal Gammopathy of Undetermined Significance, AL Amyloidosis, Waldenstrom’s Macroglobulinaemia
What is Monoclonal Gammopathy of Undetermined Significance (MGUS)?
DMGUS is defined by a
(1) paraprotein level <30 g/L
(2) Bone marrow plasma cells <10%
(3) No evidence of myeloma end-organ damage
What is the pathophysiology of MGUS?
MGUS involves an isolated finding of a monoclonal paraprotein in the serum or urine that does not meet the diagnostic criteria for smouldering or symptomatic myeloma
What is AL amyloidosis?
A clinical disorder caused by extracellular deposition of monoclonal immunoglobulin light chains, forming amyloid fibrils that alter tissue function
What is the most common type of systemic amyloidosis in developed countries?
AL amyloidosis
What are the most common presenting symptoms of AL amyloidosis?
Weakness and dyspnoea
What are the renal manifestations of AL amyloidosis?
(1) Heavy proteinuria
(2) nephrotic syndrome
(3) impaired renal function in half of the patients.
How is AL amyloidosis diagnosed?
Organ biopsy confirming amyloid deposition with Congo red stain showing ‘apple-green’ birefringence under polarised light
How is AL amyloidosis managed?
chemotherapy to stop the production of faulty light chains
What is the main adverse prognostic factor in AL amyloidosis?
The presence and severity of amyloid heart disease
What is the pathophysiology of AL amyloidosis?
In AL amyloidosis, clonal plasma cells produce unstable light chains that form insoluble amyloid fibrils, depositing in tissues and causing organ damage
What is Waldenstrom’s macroglobulinaemia?
A chronic disorder where abnormal B-cells produce an IgM paraprotein and invade the bone marrow
What are the risk factors for Waldenstrom’s macroglobulinaemia?
(1) Personal or family history of autoimmune, inflammatory, or infective disorders, especially Sjögren’s syndrome
(2) Autoimmune haemolytic anaemia
What is the pathophysiology of Waldenstrom’s macroglobulinaemia?
A clonal disorder of lymphoplasmacytic cells, intermediate between lymphocytes and plasma cells, producing a characteristic IgM paraprotein
What are the B symptoms in Waldenstrom’s macroglobulinaemia?
Night sweats and weight loss
What is the management for Waldenstrom’s macroglobulinaemia?
chemo
How is hyperviscosity treated in Waldenstrom’s macroglobulinaemia?
Plasmapheresis
= which removes paraprotein from circulation to reduce viscosity.
A 65-year-old male presents to the GP practice with worsening fatigue and weight loss. His past medical history includes a long-standing paraproteinaemia which he has had for the last ten years.
On examination, he appears cachectic. He has a very large tongue and a purple discolouration of his upper and lower eyelids.
Urine dip shows: protein ++
What is the most likely cause of this patient’s proteinuria?
AL Amyloidosis
How would you know that Congo red staining would be used to diagnose amyloidosis?
(1) Clinical signs like nephrotic syndrome, unexplained proteinuria, organ dysfunction, and the presence of amyloid deposits in soft tissues
(eg, enlarged tongue, yellow waxy deposits around the eyelids)
(2) Apple-green birefringence: Amyloid deposits show a distinctive apple-green birefringence under polarised light when stained with Congo red
(3) Renal involvement: Amyloid deposits in the kidneys can lead to nephrotic syndrome or kidney dysfunction, which is why a renal biopsy with Congo red staining is typically performed
What are the key indicators of amyloidosis?
- Organomegaly
= hepatomegaly, splenomegaly - Macroglossia
= enlarged tongue - Xanthelasma
=yellow, waxy deposits around eyelids - Fatigue, weight loss, and malaise
- Nephrotic syndrome
= proteinuria, low albumin, oedema
What are the key indicators for Waldenström’s macroglobulinaemia (WM)?
- Hyperviscosity symptoms
= Epistaxis, headache, blurred vision - Fatigue, weight loss, cachexia
- Organomegaly
= Splenomegaly, hepatomegaly - Lymphadenopathy
= Enlarged lymph nodes - Monoclonal IgM antibodies on serum protein electrophoresis
An 85-year-old man presents to the Emergency Department with 6 hours of right facial drop, slurred speech and left-sided hemiparesis. MRI head confirms a right-sided middle cerebral artery infarct.
Blood tests show the following:
1. Haemoglobin 100 g/L (115-165 g/L)
- Total protein 90 g/L (60-78 g/L)
- Albumin 38 g/L (35-50 g/L)
- Corrected calcium 2.50 mmol/L (2.20-2.60 mmol/L)
- Protein electrophoresis: monoclonal
- IgM paraprotein band
Bone marrow aspirate shows infiltration with lymphoplasmacytoid cells.
What is the best management for this patient? and why?
Plasmapheresis
= Hyperviscosity syndrome can present with an array of neurological symptoms, including headache, confusion, reduced consciousness or stroke. Hyperviscosity is treated as an emergency with plasmapheresis
If a patient doesn’t have hyperviscosity syndrome symptoms, the focus would shift to managing Waldenström’s macroglobulinaemia (WM) with no urgent need for plasmapheresis. The most appropriate treatment would be what?
- Chemotherapy
= Rituximab often in combination with:
Bortezomib or
Cyclophosphamide - supportive care
What are the key differences between MGUS and Waldenström’s Macroglobulinaemia (WM)?
Symptoms:
MGUS = Asymptomatic.
WM = Symptoms like hyperviscosity (headache, blurred vision), organomegaly.
Monoclonal Protein:
MGUS = Any monoclonal protein, often low levels.
WM = IgM monoclonal protein at higher levels.
Bone Marrow:
MGUS = Few plasma cells.
WM = Lymphoplasmacytoid cell infiltration.
A 72-year-old patient presents for a diabetes review. He has a background of T2DM and hypertension. He takes metformin, lisinopril, and amlodipine. His routine monitoring blood tests are unremarkable, except for an abnormal full blood count which prompts a serum protein electrophoresis. A prominent IgM paraprotein band is seen. His bone profile and renal function are normal. He has no other symptoms and his physical examination is normal
What is the diagnosis?
MGUS (Monoclonal Gammopathy of Unknown Significance)
= no symptoms therefore not Waldenström’s Macroglobulinaemia
A 68-year-old man presents with weakness, fatigue, and bone pain. Laboratory investigations reveal hypercalcaemia, anaemia, and renal impairment. Serum protein electrophoresis (SPEP) shows a monoclonal gammopathy.
What is the most likely diagnosis?
Multiple myeloma
A 65-year-old man comes with sudden onset headache, blurry vision and weakness in his right arm. He previously had multiple episodes of fleeting blindness. He was diagnosed with diabetes mellitus 20 years ago. Physical examination shows generalised lymphadenopathy, splenomegaly, reduced tone and power in the right arm compared to the left. Fundoscopy shows blurred disc margins and engorged retinal veins. Investigations show an increased erythrocyte sedimentation rate and plasma viscosity. Serum electrophoresis shows a monoclonal spike.
An increase in which of the following plasma components is most likely responsible for his clinical features?
IgM
