Latest WHO Description of multiple myeloma

1. MULTIPLE
MYELOMA
DR NIDHI RAI

2. PLASMA CELL NEOPLASM
Group of lymphoid neoplasms of terminally differentiated
B - cells associated with the monoclonal proliferation of
immunoglobulin secreting plasma cells and a resultant
increase in serum levels of a single homogeneous
(monoclonal) Ig or it’s fragments.

4. PLASMA CELLS
• Plasma cells are terminally
differentiated activated B-cells,
which have the ability to produce
antibodies against a variety of
antigens.
• Not normally found in peripheral
blood
• Account for less than 3.5% of
nucleated cells in the bone marrow
• Oval cells with low N:C
ratio.Cytoplasm is basophilic blue.
Nucleus
• (30-40% of the cell) is oval or round
and typically placed eccentrically (to
one side) of the cell.
• A clear, colorless area adjacent to
the nucleus contains Golgi apparatus

5. EPIDEMIOLOGY
• As per most recent data of SEER (Surveillance epidemiology
& End Result Programme )
 Males are affected more than Females
 1% of all Malignancy
 10% of all Haematological malignancy
 2nd common after NHL among haematological malignancy
 Median age of diagnosis -70 yrs
 Median age of death -75 yrs
 Blacks are affected more than Whites.

6. CLASSIFICATION OF PLASMA CELL
NEOPLASM ( WHO 2016)
1. Non-IgM (plasma cell) monoclonal gammopathy of undetermined significance
(MGUS).
2. Plasma cell myeloma: Clinical variants:
• Smoldering (asymptomatic) myeloma.
• Non-secretory myeloma.
• Plasma cell leukaemia.
3. Plasmacytoma:
• Solitary plasmacytoma of bone.
• Extraosseous (extramedullary) plasmacytoma.
4. Monoclonal immunoglobulin déposition diseases:
• Primary amyloidosis.
• Systemic light chain and heavy chain deposition diseases.
5. Plasma cell neoplasms with associated paraneoplastic syndrome:
• POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal
gammopathy and Skin lesions).
• TEMPI syndrome (Telangectasias, Elevated erythropoietin/erythrocytes,
Monoclonal gammopathy, Perinephric fluid collection and Intrapulmonary
shunting) (provisional).

7. MONOCLONAL GAMMOPATHY OF
UNDETERMINED SIGNIFICANCE
(MGUS)
• Pre-Neoplastic condition.
MGUS is the designation for a monoclonal immunoglobulin in the
serum or urine of a patient in whom there is no evidence of
PCM, amyloidosis, Waldenstrom macroglobulinemia or other
lymphoproliferative disorder, or any other disease known to
produce monoclonal immunoglobulins

8. TYPES
THERE ARE TWO DISTINCTIVE CATEGORIES OF
MGUS: IGM MGUS AND NON-IGM MGUS.
NON-IGM MGUS
 85% of cases.
 plasma cell features.
 Myeloma-type genetics.
 It may progress to a
malignant plasma cell
neoplasm (PCM or
amyloidosis).
IGM MGUS
 15% of cases.
 lymphoplasmacytic features.
 Lacks myeloma-type genetics.
 It can progress to lymphoma,
Waldenstrom
macroglobulinemia, or
occasionally to light chain
amyloidosis.

9. DIAGNOSTIC CRITERIA:
THE 2016 WHO DIAGNOSTIC CRITERIA FOR MGUS
(ADAPTED FROM THE INTERNATIONAL MYELOMA WORKING
GROUP UPDATED DIAGNOSTIC CRITERIA FOR MGUS):
1. Serum M-protein (IgA or IgG) < 30g/L.
2. Clonal BM plasma cells < 10%.
3. Absence of end-organ damage (CRAB: hypercalcemia, renal
insufficiency, anemia, bone lesions) or amyloidosis
attributable to the plasma cell proliferative disorder.
For light chain MGUS:
Abnormal free light chain ratio (<0.26 or >1.65).
Increased level of the involved free light chain.
No immunoglobulin heavy chain expression on IFE.
Urinary M-protein <500 mg/24 hr.
Clonal plasma cells < 10%.
Absence of end-organ damage (CRAB) or amyloidosis.

10. MGUS PROGRESSION
• Predictors of Progression :
Size of the M-protein at the time of recognition of MGUS
– most important predictor of progression
IgM & IgA monoclonal proteins have a greater risk of
progression than an IgG M-protein.
• Risk of progression 1% per year.
Therefore
• Periodic monitoring of serum protein electrophoresis
• Interval of monitoring based on initial M-Protein level
• Monitoring should be at least annually LIFELONG

11. WHAT IS MULTIPLE MYELOMA
 Plasma cell dyscrasia
 Characterized by
➔ Increase Plasma cell in marrow
➔ M-protein in serum or urine
➔ Lytic Bone lesion
➔ Renal Insufficiency
 The BM is the site of origin of nearly all myelomas and in
most cases there is disseminated BM involvement. Other
organs may be secondarily involved.

12. ETIOLOGY
• Radiation
• Organic chemical exposure
• Wood processing industry
• Familial occurrence
• Idiopathic

13. PATHOGENESIS

14. DIAGNOSTIC CRITEREIA
Recommended diagnostic studies for PCM patients according
to International Myeloma Working Group (IMWG)
I. History and physical examination.
II. Routine testing:
1. Complete blood count with leukocyte differential and blood
smear examination.
2. Chemistry panel: including calcium and creatinine.
3. Serum protein electrophoresis and immunofixation (IF).
4. Nephelometric quantification of immunoglobulins
(Quantitative immunoglobulin).
5. Measurement of free light chains (FLC).
6. 24-hour urine collection for electrophoresis and IF.

15. III. Bone marrow aspirate and trephine biopsy:
• Morphologic evaluation.
• Immunophenotyping.
• Cytogenetic studies.
IV. Radiologic skeletal bone survey:
• Spine, pelvis, skull, humeri, and femurs.
V. Other laboratory investigations:
- β2 microglobulin, C-reactive protein, and lactate
dehydrogenase(LDH).

16. HISTORY & CLINICAL EXAMINATION
1. Skeletal System:
• Bone pain in the back and ribs, which is aggravated by
movement, is the most common symptom.
• Punched out osteolytic lesions
• Osteoporosis
• hypercalcemia.
• Production of osteoclast-activating factor by myeloma
cells is responsible for skeletal destruction.
2. Neurological Dysfunction: spinal cord compression

17. 3. Renal Failure: due to
• Infiltration of MM cells in renal parenchyma (Myeloma
kidney)
• Formation of light-chain casts in renal tubules
• Hypercalcemia (results from bone resorption)
• Amyloid deposits.
• Pyelonephritis
4. Anaemia:Fatigue, weakness, and pallor
Causes:
• Replacement of BM by myeloma cells.
• Suppression of haematopoiesis.
• Renal failure.
• Bleeding.
• Infection.
• Haemolysis.

18. 5. Infections:
• Patients are susceptible to bacterial infections particularity of respiratory
and urinary tracts.
• Causes:
 Hypogammaglobulinemia due to suppression of normal B-lymphocytes by
myeloma cells.
 Neutropenia secondary to BM infiltration or chemotherapy.
6. Haemorrhagic Tendencies:
• These can occur such as purpura or mucosal bleeding.
• Causes:
 Thrombocytopenia (due to BM replacement or chemotherapy).
 Platelet dysfunction (due to coating of platelets by immunoglobulins which
interfere with platelet aggregation).
 Antibodies against clotting factors.
7. Hyper viscosity syndrome:
• A triad of visual changes, bleeding, and neurologic impairment results from
increase in blood viscosity by immunoglobulins.
8. Amyloidosis

19. II. ROUTINE LABORATORY
INVESTIGATIONS
RBCs:
Anemia develops with progression of disease in all patients
and is normocytic and normochromic.
WBCs:
Total leucocyte count may be normal or low.
Platelets:
Platelet count is usually normal.
Thrombocytosis in some patient due to IL6
Thrombocytopenia, when present, is usually mild.
1. CBC

20. BLOOD FILM MORPHOLOGY
• A characteristic feature on PB smear is bluish background and red
cell rouleaux formation due hypergammaglobulinemia. Rouleaux
formation may interfere with blood grouping.
• Differential count may show neutropenia (due to replacement of
hemopoietic cells by myeloma cell) with relative lymphocytic
predominance and few plasma cells.
• In plasma cell leukaemia, plasma cells are ≥ 20% in PB.
• A leucoerythroblastic blood picture is observed in a minority of
cases.

21. 2. CHEMISTRY SCREEN
1. Liver function tests:
• Total protein: increased.
• Serum alkaline phosphatase: is normal or slightly increased; this
is helpful in differentiating MM from skeletal involvement due to
hyperparathyroidism or metastatic carcinoma in which alkaline
phosphatase is markedly raised.
2. Kidney function tests:
• Serum creatinine: raised in the presence of renal insufficiency.
3.Serum Calcium:
• Hypercalcaemia.

22. 3. SERUM PROTEIN
ELECTROPHORESIS (SPE)

23. POLYCLONAL
GAMMOPATHY
• A wide band with
indistinct borders merging
into the background on
electrophoresis or broad
based peak in γ region
• Seen in chronic infections,
inflammation, connective
tissue disease,
lymphoproliferative
disease.
MONOCLONAL
GAMMOPATHY
• narrow-based, tall,
sharply defined spike– M-
Spike
• Also, note reduction in the
normal polyclonal gamma
band
• M band or spike in serum
is not observed in non
secretory myeloma, light
chain disease, and
primary amyloidosis
Urine sample must also be examined for the presence of M protein
because if only light chains are being produced then they are not
demonstrable in serum due to their rapid excretion in urine.

24. IMMUNOFIXATION
ELECTROPHORESIS (IFE)
• Gold standard for identification of nature of M protein.
• More sensitive than SPEP
• Immunofixation is performed when SPEP shows a sharp “peak” or
a plasma cell disorder is suspected despite a normal SPEP
• Particularly helpful for the identification of a small amount of
M protein.
• Done to confirm the presence of M-Protein and to determine the
type (IgM or IgG etc. and the light chain restriction : k or λ)
Why do both SPEP and IF ? Why not just IF in initial diagnosis ?
Unlike SPEP, immunofixation does not give an estimate of the
size of the M protein (i.e, its serum concentration), and thus
should be done in conjunction with electrophoresis

25. 4.24-HOUR URINE PROTEIN
ELECTROPHORESIS:
• Both serum and urine protein electrophoresis should be
performed in all suspected patients of plasma cell neoplasms.
• Bence Jones protein in urine refers to either κ or λ free
light chains synthesized by a neoplastic clone of plasma cells.
• Detected by :
1. Heat method at 55 degree C
2. Electrophoresis.
• Identification of light chain type (κ or λ) is done by
immunoelectrophoresis or immunofixation.

26. 5.QUANTITATIVE
IMMUNOGLOBULIN ASSAY
• Necessary to assess the disease severity and follow
response to treatment.
• The height of the peak on serum protein electrophoresis
(on densitometer tracing) is directly proportional to the
amount of M protein.
• Exact quantitation can be done by nephelometry.

27. • IgG is found in slightly more than half of patients with
myeloma, and IgA and monoclonal light chains only are
found in approximately 20%.
• IgD, IgE, IgM, and bi clonal myeloma are rare.
• Less than 3% of patients have a non-secretory myeloma by
IFE, but low quantities of monoclonal light chain are
detectable in a majority of these by serum free light chain
analysis.
• Kappa light chain is more common than lambda light chain
for all immunoglobulin types of myeloma except IgD.

28. 6. FREE LIGHT CHAIN (FLC) ASSAY
• In these patients, the traditional methods of measuring circulating
monoclonal immunoglobulins (electrophoresis, IME, immunofixation
electrophoresis, and nephelometric measurement of Ig heavy
chains of serum) are not adequate.
Indications:
1. For the less than 3% of myeloma patients who are:
a. Non-secretory.
b. Oligo-secretory disease
c. Light chain only disease.
2. For the majority of patients with AL amyloidosis (AL).

29. • Involved FLC (iFLC) & Difference in FLC (dFLC):
If the abnormally elevated light chain is lambda then:
 Involved FLC (iFLC): lambda.
 Uninvolved FLC: kappa.
 dFLC: (involved – uninvolved) (lambda-kappa).
 dFLC is used more for monitoring.
• Free light chain assay measures free kappa to free lambda
ratio.
 Normal ratio : 0.26 – 1.65
 If <0.26 – monoclonal lambda chain
 >1.65 – monoclonal kappa chain
• FLC ratio (rFLC)- very important& Included in diagnostic criteria
of MM by IMMG
 Diagnosis (involved : uninvolved FLC ratio ≥ 100).
 Assessing response.

30. III. BONE MARROW
EXAMINATION:
• Hypercellular to Normocellular marrow
• plasmacytosis (>10%) - Hallmark
• BM involvement is often focal and percentage of plasma cells
aspirated from different sites is variable.
• On the basis of their cytologic features, myelomas have
been classified into mature, intermediate, immature, and
plasmablastic cytologic types (Griepp System)
1. Bone marrow aspiration (BMA)

31. A. THE MATURE-TYPE
MYELOMA:
• Cytoplasm: abundant, deeply
basophilic cytoplasm with a
perinuclear clear area or ‘hof’
representing Golgi zone.
• Nucleus: eccentrically-placed
nucleus with dense coarse
chromatin and no nucleoli.
B. THE IMMATURE-TYPE
MYELOMA:
• Size: Larger than typical plasma
cells.
• Nucleus: Larger nucleus, which
may be centrally or eccentrically
located with hof, finely
dispersed nuclear
chromatin(diffuse), one or two
prominent nucleoli.
• Cytoplasm: Abundant light blue
cytoplasm.
• Pleomorphism may be seen.

32. THE INTERMEDIATE-TYPE
MYELOMA
• The plasma cells exhibit
features intermediate between
mature and immature types of
myeloma.
• Condensed chromatin
• Occasional or absent nucleoli
• several have
• lobated nuclei, and two are
binucleate
THE PLASMABLASTIC
MYELOMA
• Considered plamablastic when
>2% of the marrow cells are
plasmablasts.
• Very high N:C ratio
• Scant cytoplasm
• Central immature large nucleus
with prominent nucleoli
• Reticular chromatin pattern
• Little/no hof

33. MYELOMA INCLUSIONS
• Intracellular accumulations of immunoglobulins may produce distinctive
morphological features such as:
1. Mott cells or morula cells (numerous ‘grape-like’ pale bluish
cytoplasmic inclusion)
2. Dutcher bodies(Intra nuclear inclusions)
3. Russel bodies (round hyaline inclusions in cytoplasm).
• Various cells:
1. Flame cells: cytoplasm flaming with peripheral free border showing
orange red colour (due to glycogen)
 Predominatly in myeloma with M spike of IgA
2. Pseudogoucher cells:Abundant cytoplasm with small nuclei
 Due to rapid turn over of myeloma cell in marrow
3. Thesaurocytes: large flaming cell with pyknotic nuclei

34. 2. BONE MARROW BIOPSY:
• BMB is of particular importance in
1. Asymptomatic MM where the plasma cells aree few in BMA ( <10%)
2. Cases with hypocellular narrow with inadequate marrow aspirate.
3. Myeloma associated fibrosis
4. For congo red staining in amyloidosis cases
5. BM necrosis( as BMA is dry tap)
• Large clusters or sheets of plasma cells on BM biopsy are highly
suggestive of a neoplastic rather than a reactive disorder.
• Infiltration pattern of MM
1. Interstitial
2. Focal/Nodular
3. Packed marrow
4. Para trabecular pattern- rare

35. • A staging system has been
proposed based on percentage
of marrow space replaced by
myeloma in bone marrow
trephine biopsies:
Stage I: Less than 20% of BM is
replaced by plasma cells.
Stage II: 20 to 50% of BM is
replaced by plasma cells.
Stage III: More than 50% of BM
is replaced by plasma cells.
• The extent of involvement in
BM biopsy sections usually
reflects the overall tumor
burden.
• Angiogensis of marrow is
associated with worst prognosis.

36. 3. IMMUNOPHENOTYPIC ANALYSIS
• Normal Plasma Cells:
1. Bright CD38 expression.
2. Express CD138, and this antigen is essentially specific for plasma
cells among hematolymphoid cells.
3. Positive for CD19 and CD45.
4. Negative for CD20 and CD56.
5. Express polytypic cytoplasmic immunoglobulin, with kappa:lambda
ratios in the range of 1-2: 1, but occasionally as high as 4: 1 in reactive
plasma cell proliferations.
6. Others: bright expression of CD27 and CD81 and lack of CD28,
CD117, and CD200.

37. • Neoplastic Plasma Cells:
1. PCM cells express CD38 and CD138, but CD138 expression
tends to be brighter and CD38 dimmer than in normal plasma
cells.
2. CD19 is absent in about 95% of PCM cases.
3. CD56 is positive in 60% to 80%.
4. CD45 decreases with maturation of plasma cells, and variability
of CD45 expression is a common feature in myeloma; the plasma cells
with the brightest CD45 represent proliferative compartment.
5. Monoclonal kappa or lambda light chains
6. CD20 is expressed in approximately 10% to 20% of PCMs.
7. CD117 is positive in 30%.
8. CD200 is positive in 60% to 75%.

39. 4. IMMUNOHISTOCHEMISTRY
(IHC):
• Indications of IHC in PCM:
1. Assessment of exact plasma cell burden - can be estimated by
CD138 on biopsy.
2. Identification of a monoclonal (vs. polyclonal) plasma cell
proliferation ( By anti kappa and anti lamda Ab)
 In normal BM and in reactive plasma cell proliferations: there is
a polyclonal pattern of kappa and lambda staining plasma cells,
usually with a slight to moderate kappa predominance.
 In cases of myeloma: the plasma cells express a monoclonal
pattern of reactivity.
3. Identification of unusual morphologic variants of myeloma.
4. Distinction of myeloma from other neoplasms.

40. • IHC using CD138 is most sensitive marker to assess volume
pretreatment and post treatment myeloma.
• Presence of microaggregates of plasma cells (>10 plasma
cells in non-perivascular location) in a post remission BMB is
a predictor of early relapse.

41. 5. CYTOGENETIC STUDIES:
• There are two major groups of genetic abnormalities in PCM: hyper
diploid (60% of cases) and non-hyperdiploid (40% of cases):
1. Non-hyper diploid cases have structural chromosomal
abnormalities.
 The most frequent structural change in this group is
translocations involving the heavy chain locus (IGH) on
chromosome 14q32.
 They are usually associated with more aggressive disease and
shorter outcome.
2. Hyper diploid myelomas: lack recurrent translocations
 manifest trisomies of odd-numbered chromosomes: 3, 5, 7, 9, 11,
15, 19, 21.

42. INTERNATIONAL MYELOMA GROUP
CYTOGENETIC CLASSIFICATION

43. IV. RADIOLOGIC SKELETAL BONE
SURVEY:
• lytic lesions, osteoporosis, or fractures in 70% to 85% of cases of
myeloma at diagnosis.
• The vertebrae, pelvis, skull, ribs, femur, and proximal humerus are
most often affected.
• CT and MRI: Capable of detecting small osteolytic lesions in areas
not well visualized by conventional techniques.
• MRI imaging has prognostic significance in patients with symptomatic
myeloma. MRI findings also have significance in diagnosis of solitary
plasmacytoma and smoldering myeloma.
• PET-CT is superior in detection of extent of disease, including soft
tissue disease, and may be the best technique for assessment of
active or inactive disease following therapy.

44. V. OTHER LABORATORY
INVESTIGATIONS:
• ESR:
 A markedly increased (or rapid) ESR is a typical feature.
 due to increased immunoglobulins.
• β2 microglobulin:
 Provides useful prognostic information.
 β2 microglobulin level more than 6 μg/ml is associated with high
tumor mass and shorter survival as compared to patients with β2
microglobulin < 6 μg/ml.
 Serial estimation of β2 microglobulin is also helpful in assessing
the growth rate of myeloma.

45. DIAGNOSTIC CRITERIA:
• The 2016 WHO diagnostic criteria of Plasma cell myeloma (Adapted from International
Myeloma Working Group (IMWG) updated criteria for diagnosis of Plasma cell myeloma):
PLUS
1. Clonal BM plasma cells ≥ 10% or biopsy-proven plasmacytoma.
2. Any one or more of the following myeloma defining events:
Evidence of end organ damage that can be attributed to the underlying
plasma cell proliferative disorder specifically (CRAB)
Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the
upper limit of normal or > 2.75 mmol/L (> 11mg/dL).
Renal insufficiency: creatinine clearance <40 mL per min or serum
creatinine > 177 μmol/L (> 2 mg/dL).
Anemia: Hemoglobin value of > 2 g/dL below the lower limit of normal or a
hemoglobin value < 10 g/dL.
Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or
PET-CT.
3. Any one or more of the following biomarkers of malignancy:
 Clonal BM plasma cell percentage ≥ 60%.
 Involved : uninvolved serum free light chain ratio (kappa : lambda or lambda
to kappa ratio) ≥ 100 (provided that the absolute level of involved FLC is at
least 100 mg/L).
 More than one focal lesions on MRI studies.

46. STAGING & PROGNOSIS:

48. GENETIC RISK CATEGORIES
• Mayo Stratification of Myeloma and Risk-Adapted Therapy
(m-SMART):

49. PLASMA CELL MYELOMA
VARIANTS

50. SMOLDERING PLASMA CELL
MYELOMA (ASYMPTOMATIC
MYELOMA):
• Incidence:
• About 8% to 14% of patients with PCM are asymptomatic at the
time of diagnosis.
• Features:
• 10% or more bone marrow plasma cells and an M-protein at
myeloma levels but lack related end-organ impairment.
• Plasma cells are cytologically atypical in BM aspirate smears, and
focal aggregates of plasma cells, interstitial infiltration, or both
are found in BM biopsy sections.
• The immunophenotype and genetics appear to be similar to other
myelomas.

51. DIAGNOSTIC CRITERIA
The 2016 WHO diagnostic criteria (Adapted from International
Myeloma Working Group (IMWG) updated criteria for diagnosis of
Asymptomatic Plasma Cell Myeloma (Smouldering Myeloma):.
Both criteria must be met:
1. Clonal bon marrow plasmacytosis 10-60%
and /or
2. Serum M-protein (IgG or IgA) ≥ 30 g/L or urinary M-protein ≥
500 mg per 24hr.
3.Absence of myeloma defining events or amyloidosis

52. NON-SECRETORY PLASMA CELL
MYELOMA
• Incidence: 3% of PCMs.
• Features:The clinical features of non-secretory myeloma are also generally
similar to other PCMs, except for a lower incidence of renal insufficiency and
hypercalcemia and less depression of normal polyclonal Ig.
• Patients with secretory myeloma at the time of diagnosis may occasionally
become nonsecretory or oligosecretory at relapse.
• The neoplastic plasma cells appear to lack the capacity to secrete
immunoglobulin, and there is no M-protein in either the serum or urine by
immunofixation analysis.
• In about two thirds of these patients, however, elevated serum free light
chains or an abnormal free light chain ratio is detectable.
• Monoclonal light chains are demonstrated in the cytoplasm of the myeloma
cells in about 85% of cases by immunohistochemical staining (producer
myeloma).
• In 15% of cases, no staining is detected, suggesting that Ig is not produced
(non-producer myeloma).
• The cytologic and histologic features, immunophenotype, and genetics of non-
secretory myeloma appear to be similar to other myelomas.

53. PLASMA CELL LEUKEMIA (PCL):
• Definition:
 Plasma cell leukemia (PCL) is a myeloma in which the number of
neoplastic plasma cells in PB is > 20% of the total leukocytes or
the absolute plasma cell count exceeds 2 × 109/L.
 The neoplastic plasma cells are also commonly found in other
extramedullary sites including liver and spleen, body cavity
effusions, and spinal fluid.
• PCL may be:
1. Primary: present at the time of initial diagnosis.
2. Secondary: evolving during the course of disease in a patient
with previously diagnosed myeloma;
• approximately 60% to 70% of cases are primary.

54. • Incidence:
Primary PCL:2% to 4% of cases of myeloma.
Secondary PCL is a leukemic transformation that occurs in
approximately 1% of previously diagnosed PCM.
• Clinical Presentation:
• Most of the features are like MM, but there are several
features that distinguish it:
The median age at diagnosis is younger.
Lymphadenopathy, organomegaly, and renal failure are
significantly more common.
Lytic bone lesions and bone pain less common.

55. INVESTIGATIONS:
1. CBC:
• Anemia
• Thrombocytopenia in 50%.
• Nucleated red cells are frequently observed in
blood smears.
• The total leukocyte count may be in the normal
range but is usually elevated and may be as high
as 100 × 109/L.
• Plasma cells are > 20% of total WBCs or the
absolute plasma cell count exceeds 2 × 109/L.
Morphology:
• Often, many of the plasma cells are smaller than
usual with relatively little cytoplasm and may
resemble plasmacytoid lymphocytes.
• Large and pleomorphic plasma cells are
uncommon. Cases with these features may be
difficult to distinguish from a lymphoplasmacytic
lymphoma on blood smear examination.

56. 2. M-Protein:
• All types of M-proteins have been reported in PCL.
• a higher proportion of cases of light chain only and IgD myeloma
present with PCL than IgG or IgA.
3. Immunophenotyping:
• Similar to other myelomas, except for more frequent expression of
CD20 and less frequent expression of CD56,
• CD117 and HLA-DR are also less commonly expressed in PCL.
4. Cytogenetics:
• An abnormal karyotype is more frequently found in PCL than in other
myelomas.
• There is a higher incidence of high-risk genetics in both primary and
secondary PCL
• The t(11;14), usually associated with a favorable prognosis in PCM, is
also morefrequent in primary PCL.

57. DIFFERENTIAL DIAGNOSIS
1. Waldenstrom macroglobulinemia:
2. Reactive plasmacytosis:
Perivascular and plasma cell demonstrate both anti kappa and anti
lambda positivity
3.MGUS : Plamsa cell <10%
4. Lymphomas associated with monocloncal gammapathies:
IHC CD138/CD38
5. Matastatic deposit in BM
6. SLE with M –proteinemia
7. Plasmaplatic lymphome

58. SOLITARY PLASMACYTOMA
• Localized collection of tumor cell in soft tissue with plasma cell
differentiation but without the evidence of multiple myeloma or
lymphoma.
• Histologically: Presence of neoplastic proliferation with features
of clonal mature/immature plasma cells.
• Immunophenotyping:
CD138,anti kappa or anti lamda and CD 56 positive
• IMWG 2014 classified it into two groups
1.Solitary plasmacytoma
2.Solitary plasmacytoma with minimal marrow involvement

60. THANK YOU