Defects in Humoral Immunity (MML, Paraproteins, Hypogammaglobulinemia etc.) Flashcards
What is Multiple Myeloma?
Multiple Myeloma
- Neoplastic clonal proliferation of plasma cells producing a monoclonal immunoglobulin resutling in end organ dysfunction
- Usually single clone of plasma cells, although biclonal myeloma also occurs, rarely non-secretory
What diagnosis are these abnormal plasma cells associated with?
Plasma cells appear as “fried eggs” in MML.
What are some symptoms of MML?
MML symptoms
- Bone pain
- Anemia
- Hypercalcemia
- Renal failure
- Tumor masses
- Recurrent infection
Remember CRAB:
- Increased Calcium
- Renal failure
- Anemia
- Bony lesions (lytic lesions or osteoporosis felt to be caused by myeloma)
What is the name of this peripheral blood film finding? What is it associated with?
Anemia with rouleaux formation is associated with MML.
What are some of the common complications of MML?
Common Complications in MML
Skeletal Destruction
- Lytic lesions
- Pathological fractures
- Plasmacytomas
- Hypercalcemia
Marrow Infiltration
- Anemia
Monoclonal Protein
- Urine - renal failure
- Blood - cryoglobulins, hyperviscosity, bleeding disorders
- Tissue - amyloidosis
Reduction of Normal Immune Globulins
- Immune suppression resuling in infections
What clinical feature is shown in the image and what disease is it associated with?
MML classically results in bone disease (pain, usually back, bony tenderness, pathologic fractures). The image shows punched out lytic lesions.
If suspicious of MML what investigations would you conduct?
MML Investigations
- Serum protein electrophoresis, 25 hour urine (UPEP)
- Serum free light chains
- IgA, IgM, IgG
- CBC, albumin, Beta-2 microglobulin
- Calcium, creatinine
- Skeletal survey, MRI or other imaging as needed
- Bone marrow biopsy with cytogenetics
What treatment modalities are available for MML?
MML Treatment
- Chemotherapy (cyclophosphamide)
- Corticosteroids (prednisone, dexamethasone)
- Proteosome inhibitors (bortezomib)
- Immunological therapies (thalidomide, lenalidomide)
- Stem cell transplant
- Bisphosphonates (pamidronate, zometa) for bone disease
What is Monoclonal Gammopathy of Undetermined Significance (MGUS)?
MGUS
- Presence of M protein in serum in absence of any clinical or laboratory evidence of a plasma cell dyscrasia or lymphoproliferative disorders
How is MGUS diagnosed?
MGUS Diagnosis
- Presence of a serum monoclonal protein (M protein) at a concentration <30 g/L
- <10% plasma cells in bone marrow
- Absence of CRAB: hyperCalcemia, Renal insufficiency, Anemia, Bony disease related to plasma cell proliferative process
- 1%/year will transform into a lymphoproliferative disorder
What is Amyloidosis?
Amyloidosis
- Average age is 60
- Clinical syndrome caused by organ deposition of abnormal, insoluble protein in beta pleated sheets
- Often lambda light chain
- Serum monoclonal protein may be small
- Plasmacytosis of the marrow is usually <10%
- Can be found concurrently with multiple myeloma
Almost any organ can be involved:
- Liver: hepatomegaly
- Heart: congestive heart failure
- Kidney: nephrotic syndrome, renal failure
- Nerves: peripheral/autonomic neuropathy
- Skin: infiltration/bleeding
- GI tract: macroglossia, diarrhea
- Spleen: hyposlenism
What is the finding shown in the image?
This is macroglossia; amyloid infiltration of the tongue.
What is Waldenstrom’s Macrogloobulinemia (Lymphoplasmacytic Lymphoma)? What are some clinical featuers?
Waldenstrom’s Macroglobulinemia
- Proliferation of lymphoplasmacytoid cells
- Presence of monoclonal IgM paraprotein
Clinical Features
- Chronic disorder of elderly patients; median age 64 yrs
- Symptoms: weakness, fatigue, bleeding (oronasal), weight loss, recurrent infections, dyspnea, CHF (triad of anemia, hyperviscosity, plasma volume expansion), neurological symptoms, peripheral neuropathy, cerebral dysfunction
- Signs: pallor, splenomegaly, hepatomegaly, lymphadenopathy, retinal lesions
- Key complication to avoid: hyperviscosity syndrome
