Professional Documents
Culture Documents
Plasma Cell Disorders
Plasma Cell Disorders
Lymphoplasmacyte
IgM
SOMATIC
Lymphoblast
HYPERMUTATION
Plasmablast
SWITCH
RECOMBINATION Virgin B cell
V(D)J
Bone G,A,E Plasma cell RECOMBINATION
Marrow Pre-B cell
B cell Development As a Framework for Malignancies
Lymphoplasmacyte
IgM WALDENSTROM’S
SOMATIC
Lymphoblast
HYPERMUTATION
Plasmablast FOLLICULAR BURKITT’S
LYMPHOMA
LYMPHOMA
Virgin B cell
CLL
Bone MULTIPLE
G,A,E Plasma cell ALL
MYELOMA
Marrow Pre-B cell
Case Presentation
• 48 yo Jamaican male
• Admitted with 2 wk history of fatigue and diffuse
bone pain
• Evaluation:
– Increased serum creatinine 5.5 mg/dl (normal < 1.2
mg/dl)
– Increased serum calcium 12 mg/dl (normal < 10.5 mg/dl)
– Increased serum globulin 5.0 g/dl (normal < 3 g/dl)
Evaluation of Abnormal Serum Globulins
Serum
Urine
• Stable intramedullary
expansion
• Asymptomatic.
MGUS
(premalignant)
Normal Transformed
cell Cell
• Progressive intramedullary
expansion.
• Anemia, bone pain, infections
• Lytic bone disease.
• Incurable, limited survival.
(malignant)
Diagnostic Criteria in Monoclonal Gammopathies
• MGUS
– < 10% bone marrow plasma cells and M spike < 3 g/dl
– Monoclonal protein / clonal plasma cell population
– No End organ damage
• Myeloma
– > 10% marrow plasma cells
– End Organ Damage
• Indolent / Smoldering Myeloma
– > 10% marrow plasma cells or M spike > 3 g/dl
– No End organ damage
Criteria for End-Organ Damage
in Monoclonal Gammopathies
• CRAB
– Calcium > 1 mg/dl above ULN
– Renal Insufficiency (> 2 mg/dl)
– Anemia (< 10 g/dl)
– Bone Lesions (lytic lesions or osteopenia)
A Model for Pathogenesis of Myeloma
Monoclonal Gammopathy of Undetermined
Significance (MGUS)
• Common, age-related
• Prevalence: 3.2% in persons over 50 yrs old (Minnesota)
– ~5% in age >70
• Risk factors for progression: %PC, level M spike, Free light chain,
IgA protein, ?Decline in uninvolved Ig’s
Smoldering Myeloma (SMM)
• Patients with PC > 10% or M spike > 3 g/dl, but lacking CRAB
symptoms.
• Uncontrolled proliferation of Ig
secreting plasma cells
– most commonly IgG (57%),
IgA (21%) or light chain only
(18%)
• Twice as frequent in men as
women, and in blacks as whites
• 1% of all cancers
– 2% in African Americans
• Incurable
• Median survival 4-6 years
5 year survival (SEER)
Work-up in suspected myeloma
Osteoclast Ig deposition
Osteoblast Cast nephropathy
LYTIC BONE DZ RENAL FAILURE
HYPERCALCEMIA
Immune-paresis
Erythropoiesis Hypogamm
ANEMIA INFECTION
Historical aside…
At age 39, developed fatigue and bone pain from several fractures. She died 4
years later; autopsy showed that her marrow was replaced by a red, gelatinous
substance
Multiple Myeloma: Skeletal Complications
Original Article
Romosozumab in Postmenopausal Women with
Low Bone Mineral Density
Michael R. McClung, M.D., Andreas Grauer, M.D., Steven Boonen, M.D., Ph.D.,
Michael A. Bolognese, M.D., Jacques P. Brown, M.D., Adolfo Diez-Perez, M.D., Ph.D.,
Bente L. Langdahl, Ph.D., D.M.Sc., Jean-Yves Reginster, M.D., Ph.D., Jose R.
Zanchetta, M.D., Scott M. Wasserman, M.D., Leonid Katz, M.D., Judy Maddox, D.O.,
Yu-Ching Yang, Ph.D., Cesar Libanati, M.D., and Henry G. Bone, M.D.
N Engl J Med
Volume 370(5):412-420
January 30, 2014
Renal Pathology in MM
Light Chain Deposition Disease
• Glucocorticoids - 1966
– Prednisone, dexamethasone
• IMiDs - 1999
– Thalidomide
– Revlimid
– Pomalidomide
MGUS Pancytopenia
Stable MM Plasma cell leukemia
M protein
Treatments
IgM pentamer
Macroglobulinemia: Principles of Therapy
AL Amyloid
Light chain deposition dz
Neuropathy
Cryoglobulinemia
Acquired vWD
Clinical Settings Where Ig Deposition Diseases (Including AL
Amyloid) Should Be Suspected In Pts With Monoclonal Ig