Plasma Cell Disorders Flashcards
2 key features of monoclonal gammopathy
Presence of a monoclonal immunoglobulin or a monoclonal immunoglobulin light chain in the serum
Absence of evidence for overt malignancy of B cells or plasma cells
Demographics of pts affected with essential monoclonal gammopathy
Age 50-80 increasing risk
2-3x more common in African descent
Implications of essential monoclonal gammopathy and indications for tx
Tx only considered when pt is symptomatic
Symptoms occur when Ig interacts with plasma proteins, blood cells, kidney, ocular structures, or neural tissue, and can cause serious dysfunction (i.e., acquired bleeding d/o, renal insufficiency, neuropathy) — in such cases plasmapheresis to remove Ig and to suppress its production by immune or cytotoxic therapy may be indicated
Must also monitor for progression to lymphoma or myeloma
Demographics and presentation of multiple myeloma
7th decade
Anemia, bone pain, osteopenia/osteoporosis, pathologic fracture, lytic bone lesions, hypercalcemia, recurrent infections (particularly pneumococcal) or kidney failure
Classic triad of MM
Marrow plasmacytosis
Lytic bone lesions
Serum and/or urine M component
MGUS Implications and indications for tx
Pts with MGUS are asymptomatic; they have smaller amts of M protein and normal amts of other Igs
Pts with MGUS should not be treated
Workup for pt with MM
CBC - anemia, thrombocytopenia, leukopenia
Peripheral smear - rouleaux formation
Serum calcium - hypercalcemia
Serum creatinine - elevated d/t myeloma kidney, dehydration, hyperuricemia
Serum protein electrophoresis -M protein
Immunofixation of serum - M protein
Quantitative Ig measurement - monoclonal gammopathy
B2microglobulin - establishes tumor burden
24 hr urine protein electrophoresis with immunofixation - M protein
Radiographic bone survey
Bone marrow bx — plasma cells make up >10%
Bone marrow plasma cell labeling index
Cytogenetic and FISH studies (del of 13 = bad px)
General approaches available for MM tx
Autologous stem cell transplant
Induction chemo — melphalan, dexamethasone, thalidomide, lenalidomide, bortezomib
Common findings associated with hypercalcemia with MM
Hypercalcemia may cause AKI and amyloidosis is often associated with nephrotic syndrome and azotemia
Can see kidney stones too
Treatment for hypercalcemia in MM
Bisphosponates, hydration
Demographics and presentation of waldenstrom macroglobulinemia
Slightly more common in men
Increased incidence in increasing age (median age 64)
Pts present with weakness, fatigue, and recurrent infections as wel as epistaxis, visual disturbance, neuro symptoms like peripheral neuropathy, dizziness, HA, and transient paresis
Role of MYD88 L265P in pts with waldenstrom macroglobulinemia
Presence of MYD88 mutation is used as a dx test to dscriminate WM from marginal zone lymphomas, IgM-secreting myeloma, and CLL with plasmacytic differentiation
MYD88 also triggers BTK, hemopoeitic cell kinase growth, and survival signaling (important therapeutic targets)
Pts with wild type MY88 have lowerbone marrow disease burden
General approaches to tx of waldenstrom macroglobulinemia
Acute tx with plasmapheresis
Indolent dz does not require therapy
Ibrutinib targets BTK — used in symptomatic pts
Other first line agents: rituximab alone or with alkylators — bendamustine and cyclophosphamide — or proteasome inhibitors (bortezomib); fludarabine and cladribine
Autologous transplant
Features of POEMS syndrome
Polyneuropathy Organomegaly Endocrinopathy M-protein Skin changes
4 criteria for POEMS dx
- Polyneuropathy
- Monoclonal plasma cell proliferative d/o
- Any one of the following: sclerotic bonelesions, castlemans dz, elevated VEGF
- Any one of the following: organomegaly, volume overload, endocrinopathy, skin changes, thrombocytosis/polycythemia, papilledema
Presentation of gamma heavy chain dz (franklin dz)
LAD, fever, anemia, malaise, HSM, weakness
Most distinct symptom is palatal edema
Associated with autoimmune dz like RA
Most common heavy chain dz; presents in young persons in parts of the world where intestinal parasites are common; presents with chronic diarrhea, weight loss, and malabsorption and have extensive mesenteric and paraaortic adenopathy
Alpha chain heavy chain dz (seligmann)
The only features that may distinguish ____ heavy chain disease are presence of vacuoles in the malignant lymphocytes of CLL and the excretion of kappa light chains in the urine
Mu
General tx of POEMS syndrome
Treated similar to myeloma
Local therapy for plasmacytoma with radiotherapy
Novel agents and highdose therapy with autologous stem cell tranplant in select pts
Relationship of alpha heavy chain dz to immunoproliferative small intestinal disease (IPSID) and implications for tx
IPSID is associated with excessive plasma cell differntiation and produces truncated alpha heavy chains lacking the light chains as well as the first constant domain
Early stage IPSID responds to abx; if untreated progresses to lymphoplasmacytic and immunoblastic lymphoma
Primary vs. secondary amyloidosis
Primary amyloidosis = AL amyloid; arises from a clonal B cell or plsma cell disorder and can be associated with myeloma or lymphoma
Secondary amyloidosis = AA amyloid; occurs in setting of chronic inflamm or infectious disease
Common complaints and clinical manifestations of AL amyloidosis
fatigue, weight loss, kidney involvement (proteinuria, hypoalbuminemia, secondary hypercholesterolemia, hypertriglyceridemia, anasarca, edema); can also see cardiac involvement, nervous system, MACROGLOSSIA is pathognomonic, liver involvement, spleen, easy bruising, ecchymosis, RACOON EYE SIGN, nail dystrophy, alopecia, arthropathy
Treatment for amyloidosis
Melphalan
Prednisone/dexamethasone
Stem cell transplant
Consider cardiac transplant, diuretics, support stockings, diuretics, amiodarone, anticoagulation, midodrine, motility agents, nutritional supplements
69 y/o M presents for routine physical. No complaints or problems other than HTN. CMP shows total protein 9.8, albumin 4.1, CBC is normal. Elevated total protein most likely represents
A. Nephrotic syndrome B. Amyloidosis C. Polyclonal gammopathy D. Mulitple myeloma E. Inflammation
C. Polyclonal gammopathy
[this is the most common of the answer choices]
69 y/o M presents for routine physical. No complaints or problems other than HTN. CMP shows total protein 9.8, albumin 4.1, CBC is normal. The next step in evaluation is
A. Fat pad bx B. Renal bx C. Serum protein electrophoresis D. CRP E. Immunoglobulin electrophoresis
C. Serum protein electrophoresis
69 y/o M presents for routine physical. No complaints or problems other than HTN. CMP shows total protein 9.8, albumin 4.1, CBC is normal. Through further testing including protein and Ig electrophoresis, you diagnose him with an IgG monoclonal gammopathy. How should this pt be managed?
Observation — this is MGUS
Concern is 20% risk of transition into malignancy
62 y/o F c/o discomfort in left leg w/o hx of trauma/injury. PMH includes HTN and fibromyalgia. PSH includes TAH/BSO for benign dz, lap chole 2 yrs ago. Meds include lyrica, osteobiflex, and maxzide. Smokes 1 ppd x40yrs; 2-3 drinks/week. Family hx of COPD. PE reveals BMI 32.5, left mid-tibial region tender to palpation,mildly warm, with bony abnormality noted. CBC and CMP are normal; CXR shows COPD w/o mass or infiltrate. X ray shows lytic bone lesion with periosteal reaction.
She is eventually dx with solitary plasmacytoma. How should this pt be managed?
Radiation therapy
In pts with an albumin:globulin ratio of less than 1, what should be on your DDx?
Plasma cell disorder!
