Plasma Cell Disorders

Question 1

What common finding characterizes plasma cell disorders?

Answer 1

M spike (monoclonal protein production) +/- BM plasmocytosis (monoclonal or polyclonal)

• If population is both lamda and kappa then polyclonal
• If one or other - monoclonal (neoplastic)

Question 2

Plasmacytoma

Answer 2

• collection of monoclonal plasma cells outside BM - form tumor
• Cortical bone or soft tissue (commonly upper respiratory tract)
• Usually cure w/ radiation or curetage
• If boney involvement then often develop multiple myeloma while if in soft tissue usually do not

Question 3

Cryoglobinemia (3 types)

Answer 3

• Cryoglobulins - antibodies (either whole immunoglobulin or just light chain) that undergo reversible precipitation at temp below body temp –> occlusion or renal failure
• 3 Types
  • I - monoclonal Ig (plasma cell dyscresias or lymphoproliferative disorders)
  • II - mix (infections or Hep C)
  • III- polyclonal only (autoimmune)

Question 4

Plasma Cell Leukemia

Answer 4

• multiple myeloma in leukemic phase
• When # plasma cells in blood >20% and total plasma cells in peripheral blood > 2000/microL
• Aggressive form of disease

Question 5

POEMS Syndrome

Answer 5

• P- polyneuropathy
• O- organomegaly
• E- endocrinopathy (damage to hormone producing glands) / edema
• M - M protein
• S - skin abnormalities (hyperpigmentation, hypertrichosis)
• **Practically, polyneuropathy and myeloma is enough to make dx

Question 6

Waldenstroms Macroglobinemia (including genetics)

Answer 6

• IgM paraprotein and infiltration of BM w/ malignant cells that have morphological features of both plasma cells and lymphocytes
• Disease is combo of myeloma and NHL
• Genetics - MYD88 mutation
• Similar to myeloma but have lymphadenopathy and splenomegaly, no bone disease, high IgM –> inc viscosity, no evidence of myeloma
• Tx - similar to other indolent lymphomas (rituximab and chemo??)

Question 7

Amyloidosis (primary v secondary)

Answer 7

• Primary (AL) - plasma cell dyscrasia –> abnormal deposition of monoclonal light chains in various tissues
  - Tx w/ myeloma drugs and maybe stem cell transplant +/- organ transplant
• Secondary (AA)- chronic infection –> non-light chain deposition
  - Tx - treat underlying disease (anti-inflammatory) and rare solid organ transplant
• Presentation dep on organs of deposition
  - Kidney - renal disease
  - GI - hepatomegaly, splenomegaly, dismotility
  - Cardiomyopathy
  - Skin (waxy), bony lesions
  - Heme - BM infiltration –> cytopenias and M spike

Question 8

Multple Myeloma Spectrum

Answer 8

• MGUS (monoclonal gammopathy of unknown significance)
  
  • Risk of progression inc w/ inc M spike (amount and duration)
  • < 3 g M spike, <10% clonal plasma cells in BM, no end organ damage
  • No therapy, just monitor
• Smoldering Myeloma
  
  • > 3 g M spike OR > 10% clonal plasma cells in BM
  • STATIC myeloma (may not progress for mo to yrs)
  • Observation; only treated if progression
  • About 5% have smoldering at diagnosis
• Active Myeloma
  
  • Heme malignancy of neoplastic proliferation of plasma cells –> monoclonal Ig in blood and/or urine
  • M spike > 3 g /dl and BM plasma cells > 10%
  • AND end organ damage; need 1 part of CRAB (calcium inc, renal dysfunction by creatinine, anemia, bone disease w/ lytic lesions or overt osteoporosis)

Question 9

Presentation/Complications of Multiple Myeloma

Answer 9

• Anemia (fatigue), thrombocytopenia/leukopenia (rare)
  
  • IL-6 production is thought to be primary cause of anemia
• Renal failure (proximal or distal tubule destruction by protein casts, NSAIDs, infection, infiltration w/ myeloma cells or amyloid, contrast dye)
• Bone lesions (osteoporosis, osteopenia, osteolysis, pathological fractures, bone pain esp in back or chest)
  
  • X-ray first
  • If inconclusive or negative but high suspicion then MRI and CT more sensitive
  • 2/3 pts present w/ bone pain at diagnosis
  • 60% have fracture
• Hypercalcemia - from inc bone resorption and dec bone formation + renal impairment (rarely due to inc PTHrP)
  
  • Dry mouth, anorexia, renal stones, confusion, depression, polydipsia, polyuria, nausea and vomiting
• Presence of monoclonal protein (M protein)
• Inc risk infection
• Neuro - radiculopathy (usually thoracic or lumbosacral); bone growth –> compression in SC

Question 10

Multiple Myeloma Prognosis

Answer 10

• MGUS/smoldering myeloma (observation) –> if progresses to active disease w/ signs of end organ damage then initiate tx –> remission usually followed by relapse (additional tx)
• Ea interval to relapse gets smaller w/ time
• Avg length of survival is 5 yr even w/ tx

Question 11

Multiple Myeloma Workup

Answer 11

• Labs - CBC, BUN, electrolytes, LDH (indirect measure or tumor burden), quantitative Ig, beta-2-macroglobulin (non-specific measure of tumor burden), CRP (marker for IL-6), serum free light chains
• Serum protein electrophoresis (look for M spike - monoclonal Ig) then immunofixation to see what caused the spike (monoclonal or polyclonal - kappa or lamda)
  - May use urine - picks up light chain b/c readily excrete in urine
• BM biopsy
• Cytogenetics
• Flow cytometry
• MRI / PET scans to look at bone
• Serum viscosity (if IgA myeloma or high M protein)

Question 12

Multiple Myeloma Tx

Answer 12

• Chemotherapy
• Immunomodulatory drugs - thalidomide, lenalidomide, bortezomib
• Autologous stem cell transplant after high dose melphalan
  
  • Are they a candidate? Dep on age, performance and co-morbidities
• No allogenic stem cell transplant
• Supportive care (abx, renal replacement, bone meds, etc)
  
  • Vit D, Ca++, bisphosphonates, local radiation, rods to prevent fractures
  • Blood thinners (hyper-coag state)
  • Dialysis
  • Hydration, calcitonin, bisphosphonates for hypercalcemia
  • Plasmapheresis for kidney problems and high viscosity