Plasma Cell Disorders

Question 1

2 key features of monoclonal gammopathy

Answer 1

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

Question 2

Demographics of pts affected with essential monoclonal gammopathy

Answer 2

Age 50-80 increasing risk

2-3x more common in African descent

Question 3

Implications of essential monoclonal gammopathy and indications for tx

Answer 3

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

Question 4

Demographics and presentation of multiple myeloma

Answer 4

7th decade

Anemia, bone pain, osteopenia/osteoporosis, pathologic fracture, lytic bone lesions, hypercalcemia, recurrent infections (particularly pneumococcal) or kidney failure

Question 5

Classic triad of MM

Answer 5

Marrow plasmacytosis

Lytic bone lesions

Serum and/or urine M component

Question 6

MGUS Implications and indications for tx

Answer 6

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

Question 7

Workup for pt with MM

Answer 7

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)

Question 8

General approaches available for MM tx

Answer 8

Autologous stem cell transplant

Induction chemo — melphalan, dexamethasone, thalidomide, lenalidomide, bortezomib

Question 9

Common findings associated with hypercalcemia with MM

Answer 9

Hypercalcemia may cause AKI and amyloidosis is often associated with nephrotic syndrome and azotemia

Can see kidney stones too

Question 10

Treatment for hypercalcemia in MM

Answer 10

Bisphosponates, hydration

Question 11

Demographics and presentation of waldenstrom macroglobulinemia

Answer 11

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

Question 12

Role of MYD88 L265P in pts with waldenstrom macroglobulinemia

Answer 12

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

Question 13

General approaches to tx of waldenstrom macroglobulinemia

Answer 13

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

Question 14

Features of POEMS syndrome

Answer 14

Polyneuropathy
Organomegaly
Endocrinopathy
M-protein
Skin changes

Question 15

4 criteria for POEMS dx

Answer 15

1. Polyneuropathy
2. Monoclonal plasma cell proliferative d/o
3. Any one of the following: sclerotic bonelesions, castlemans dz, elevated VEGF
4. Any one of the following: organomegaly, volume overload, endocrinopathy, skin changes, thrombocytosis/polycythemia, papilledema

Question 16

Presentation of gamma heavy chain dz (franklin dz)

Answer 16

LAD, fever, anemia, malaise, HSM, weakness

Most distinct symptom is palatal edema

Associated with autoimmune dz like RA

Question 17

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

Answer 17

Alpha chain heavy chain dz (seligmann)

Question 18

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

Answer 18

Mu

Question 19

General tx of POEMS syndrome

Answer 19

Treated similar to myeloma

Local therapy for plasmacytoma with radiotherapy

Novel agents and highdose therapy with autologous stem cell tranplant in select pts

Question 20

Relationship of alpha heavy chain dz to immunoproliferative small intestinal disease (IPSID) and implications for tx

Answer 20

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

Question 21

Primary vs. secondary amyloidosis

Answer 21

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

Question 22

Common complaints and clinical manifestations of AL amyloidosis

Answer 22

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

Question 23

Treatment for amyloidosis

Answer 23

Melphalan
Prednisone/dexamethasone
Stem cell transplant

Consider cardiac transplant, diuretics, support stockings, diuretics, amiodarone, anticoagulation, midodrine, motility agents, nutritional supplements

Question 24

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

Answer 24

C. Polyclonal gammopathy

[this is the most common of the answer choices]

Question 25

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

Answer 25

C. Serum protein electrophoresis

Question 26

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?

Answer 26

Observation — this is MGUS

Concern is 20% risk of transition into malignancy

Question 27

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?

Answer 27

Radiation therapy

Question 28

In pts with an albumin:globulin ratio of less than 1, what should be on your DDx?

Answer 28

Plasma cell disorder!