Plasma cell dyscrasias include monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, myeloma, and plasmacytomas. Myeloma is diagnosed based on clonal plasma cells ≥10% or plasmacytoma, monoclonal protein, and end-organ damage like hypercalcemia, renal insufficiency, anemia, or bone lesions. Staging systems include Durie-Salmon based on cell mass and organ damage, and International Staging System (ISS) based on β2 microglobulin and albumin levels, which is currently preferred. Newer systems incorporate cytogenetics and LDH. Future risk stratification aims to include additional markers from techniques

1. Plasma Cell Dyscrasia : Grading

2. Introduction : Definition
•Plasma cell neoplasms (PCNs) are derived from the expansion of
mutated, terminally differentiated, postgerminal center B cells.
• These neoplasms include
•monoclonal gammopathy of undetermined significance (MGUS)
and monoclonal gammopathy of renal significance (MGRS)
•smoldering myeloma
•myeloma
•solitary plasmacytomas
•plasmacytomas with minimal marrow involvement
• light-chain amyloidosis

3. Criteria for diagnosis of Myeloma :
• All 3 criteria must be met except as noted:
• Clonal marrow plasma cells ≥10% and/or presence of a biopsy- proven
plasmocytoma
• Presence of serum and/or urinary monoclonal protein
• Evidence of end-organ damage specifically: ( CRAB )
• Hypercalcemia: serum calcium ≥11.5 mg/100 mL or
• Renal insufficiency: serum creatinine >2 mmol/L)
• Anemia: normochromic, normocytic with a hemoglobin value of >2 g/100 mL
below the lower limit of normal or a hemoglobin value <10 g/100 mL
• Bone lesions: lytic lesions, severe osteopenia, or pathologic fractures

4. Staging of Myeloma : Durie Salmon Grading
• Multiple attempts have been made to define clinical and laboratory
parameters that have prognostic significance in myeloma.
• The Durie-Salmon staging system was historically the most commonly
used
• It relates myeloma cell mass to the extent of bony disease, hemoglobin,
and calcium levels, as well as the monoclonal Ig levels in serum and
urine
• Disadvantage : measurement of bone disease by skeletal survey in
myeloma is observer dependent and potentially subjective

5. Durie Salmon staging
:

6. Current method : The ISS system
• Based on two widely available parameters—serum β2 Microglobulin and
albumin
• It recognizes 3 stages

7. Why ISS preferred ?
• β2 M correlates with tumor mass and impairment in renal function, whereas
low albumin reflects the effect of IL-6 produced by the microenvironment of
myeloma cells on the liver.
• This helped to predict the outcome of the patients in different stages of the
disease when offered the appropriate treatment
• Disadvantage : Lack of inclusion of cytogenetics and other markers of tumor
burden, such as LDH
• Current : Revised ISS — ———includes LDH values and Chromosomal
abnormalities

8. R-ISS score :

9. mSMART score : Cytogenetic risk based scoring

10. Future outlook :
• To include other novel methods for further high risk
assessment and stratification
• iFISH method to be replaced with Seq-FISH which
has validated the prognostic power of the R-ISS and
increased the sensitivity and reproducibility of
identifying chromosomal anomalies .

11. References :
•Wintrobe’s CLINICAL HAEMATOLOGY 14th edition
•Williams Hematology 10th edition
•Jain, A., Malhotra, P. Plasma Cell Dyscrasias in India-2017 Updates. Indian J
Hematol Blood Transfus 34, 1–4 (2018). https://doi.org/10.1007/s12288-017-
0910-0
•Hagen, P., Zhang, J. & Barton, K. High-risk disease in newly diagnosed multiple
myeloma: beyond the R-ISS and IMWG definitions. Blood Cancer J. 12, 83
(2022). https://doi.org/10.1038/s41408-022-00679-5