Objectives
• To introduce the terminology used in describing
the plasma cells neoplasm.
• To explain the physiology of the normal cells & the
pathological effects of their neoplastic growth.
• To describe the classification of plasma cells neoplasm.
• To discuss the relationship with amyloidosis and its
pathology.
Plasma cells
Terminally differentiated B- Lymphocytes that are
capable of producing immunoglobulins.
• Paraprotein :
Structurally identical & homologous ig.of the same clone i.e
monoclonal.
• Lymphoplasmacytic Neoplasm :
Neoplasm of the plasma cells producing excess paraprotein.
Classification of plasma cell neoplasms
• Monoclonal gammopathy of undetermined significance.
• Multiple myeloma.
• Macroglobulinemia.
Monoclonal gammopathy of undetermined
significance ( MGUS)
• M protein presence, stable
• levels of M protein: IgG < 3,5g IgA < 2g LC<1g/day
• normal immunoglobulins - normal levels
• marrow plasmacytosis < 5%
• complete blood count - normal
• no lytic bone lesions
• no signs of disease
Monoclonal gammopathy of undetermined
significance ( MGUS)
• M protein
– 3% of people > 70 years
– 15% of people > 90 years
– MGUS is diagnosed in 67% of patients with an M
protein
– 10% of patients with MGUS develop multiple
myeloma
Macroglobulinemia
Tumour of lymphoplasmacytoid cells producing
Monoclonal ig most commonly ( Igm )
Types : - Essential macroglobulinemia.
- waldenstrom macroglobulinemia.
Clinical Features :
• Weight loss, fatigue.
• Bleeding usually epistaxis.
• Bone marrow infiltration by the lymphoplasmcytic cells “less
mature than plasma cells” presenting as anemia thrombocytopenia
or leucopenia.
Multiple Myeloma
• Definition:
B-cell malignancy characterised by
abnormal proliferation of plasma cells able to
produce a monoclonal immunoglobulin ( M protein )
• Incidence:
3 - 9 cases per 100000 population / year
more frequent in elderly
modest male predominance
Multiple Myeloma
• Clinical forms:
multiple myeloma
solitary plasmacytoma
plasma cell leukemia
• M protein:
- is seen in 99% of cases in serum and/or urine
IgG > 50%, IgA 20-25%, IgE i IgD 1-3%
light chain 20%
- 1% of cases are nonsecretory
Multiple Myeloma
Clinical manifestations are related to malignant
behavior of plasma cells and abnormalities produced
by M protein
• plasma cell proliferation:
multiple osteolytic bone lesions
hypercalcemia
bone marrow suppression ( pancytopenia )
• monoclonal M protein
decreased level of normal immunoglobulins
hyperviscosity
Multiple Myeloma
Clinical symptoms:
• bone pains, pathologic fractures
• weakness and fatigue
• serious infection
• renal failure
• bleeding diathesis
Multiple Myeloma
Laboratory tests:
• ESR > 100
• anaemia, thrombocytopenia
• rouleaux in peripheral blood smears
• marrow plasmacytosis > 10 -15%
• hyperproteinemia
• hypercalcemia
• proteinuria
• azotemia
Diagnostic Criteria for Multiple Myeloma
Major criteria
I. Plasmacytoma on tissue biopsy
II. Bone marrow plasma cell > 30%
III. Monoclonal M spike on electrophoresis IgG > 3,5g/dl,
IgA > 2g/dl, light chain > 1g/dl in 24h urine sample
Minor criteria
a. Bone marrow plasma cells 10-30%
b. M spike but less than above
c. Lytic bone lesions
d. Normal IgM < 50mg, IgA < 100mg, IgG < 600mg/dl
Diagnostic Criteria for Multiple Myeloma
Diagnosis:
• I + b, I + c, I + d
• II + b, II + c, II + d
• III + a, III + c, I II + d
• a + b + c, a +b + d
Staging of Multiple Myeloma
Clinical staging
• is based on level of haemoglobin, serum calcium,
immunoglobulins and presence or not of lytic bone
lesions
• correlates with myeloma burden and prognosis
I. Low tumor mass
II. Intermediate tumor mass
III. High tumor mass
• subclassification
A - creatinine < 2mg/dl
B - creatinine > 2mg/dl
Multiple Myeloma
Poor prognosis factors
• cytogenetical abnormalities of 11 and 13
chromosomes
• beta-2 microglobulines > 2,5 ug/ml
Treatment of Multiple Myeloma
• Patients < 65 - 70 years
– high-dose therapy with autologous stem cell
transplantation
– allogeneic stem cell transplantation ( conventional
and „mini”)
• Patients > 65 years
– conventional chemotherapy
– non-myeloablative therapy with allogeneic
transplantation („mini”)
Treatment of Multiple Myeloma
• Conventional chemotherapy
– Melphlan + Prednisone
– M2 ( Vincristine, Melphalan, Cyclophosphamid,
BCNU, Prednisone)
– VAD (Vincristin, Adriamycin, Dexamethasone)
• Response rate 50-60% patients
• Long term survival 5-10% patients
Treatment of Multiple Myeloma
• Autologous transplantation
– patients < 65-70 years
– treatment related mortality 10-20%
– response rate 80%
– long term survival 40-50%
• Conventional allogeneic transplantation
– patients < 45-50 years with HLA-identical donor
– treatment related mortality 40-50%
– long term survival 20-30%
Treatment of Multiple Myeloma
• New method
– non-myeloablative therapy and allogeneic
transplantation
– thalidomid
Treatment of Multiple Myeloma
• Supportive treatment
– biphosphonates, calcitonin
– recombinant erythropoietin
– immunoglobulins
– plasma exchange
– radiation therapy
Disorder Associated with Monoclonal Protein
• Neoplastic cell proliferation
– multiple myeloma
– solitary plasmacytoma
– Waldenstrom macroglobulinemia
– heavy chain disease
– primary amyloidosis
• Undetermined significance
– monoclonal gammopathy of undetermined significance (MGUS)
• Transient M protein
– viral infection
– post-valve replacement
• Malignacy
– bowel cancer, breast cancer
• Immune dysregulation
– AIDS, old age
• Chronic inflammation
Amyloidosis
• Primary amyloidosis :
Deposition of light chain of Ig as in multiple myeloma sites
: Tongue, GIT, Heart, Connective tissue.
• Secondary Amyloidosis :
Deposition of amyloid -A- substance
Sites : Spleen, Liver, Kidney
• Familial Amyloidosis:
Due to genetic mutation
Causing deposition of unmetalised prealbumin.
