1) The patient presented with fever, vomiting and back pain and has a history of hypertension, chronic pancreatitis and kidney disease. Imaging showed a lytic lesion in the vertebrae. 2) Laboratory tests showed normocytic normochromic anemia with eosinophilia. A bone marrow biopsy found increased plasma cells. 3) Differential diagnoses included reactive plasmacytosis, multiple myeloma, solitary plasmacytoma, lymphoplasmacytic lymphoma, monoclonal gammopathy of undetermined significance and smoldering myeloma.

1. PLASMA CELL DYSCRASIAS
Dr. ANJALY S
IIⁿᵈ YEAR PG
INSTITUTE OF
PATHOLOGY, MMC

2. CASE HISTORY
❏ 64 Years old male patient, presented with fever,
vomiting and back pain. He is a known case of
systemic hypertension, chronic pancreatitis and
CKD on conservative management. History of a
lytic lesion in vertebrae present.

3. ❖ COMPLETE BLOOD COUNT:
➢ WBC : 10.7 × 10³ / microlitre
➢ RBC : 2.43 × 10⁶ / mL
➢ Hb% : 7.2 g/dL
➢ MCV : 94.2 fL
➢ MCH : 29.6 pg/dL
➢ PC : 178×10³ / microlitre
➢ RDW-CV : 19.8%
➢ ESR : 28
INVESTIGATIONS(Contd.)

4. INVESTIGATIONS(Contd.)
❏ NORMOCHROMIC,
NORMOCYTIC
ANEMIA. NO
ROULEAUX
FORMATION

5. ❖ PERIPHERAL SMEAR:
➢ RBC:
■ Normal count
■ Normocytic, normochromic RBC with some
macrocytes
■ No rouleaux formation seen
■ Anisopoikilocytosis present composed of
tear drop cells
■ No nRBC / Inclusions / Hemoparasites
INVESTIGATIONS(Contd.)

6. ❖ PERIPHERAL SMEAR(Contd.):
➢ WBC:
■ Normal count
■ NEUTROPHILS - 79%
■ LYMPHOCYTES - 21%
■ EOSINOPHILS - 10%
■ AEC - 1170 cells/mm³
➢ PLATELETS:
■ Normal count
■ Distribution - singles
➢ IMPRESSION:
■ Normocytic, Normochromic Anemia with
eosinophilia
INVESTIGATIONS(Contd.)

7. PLASMA CELLS
❖ Identified in bone marrow based on morphology
and immunophenotype.
❖ Multi parametric flow cytometry that can detect
six or more antigens (commonly CD38, CD45,
CD56, CD19, KAPPA & LAMBDA)

8. PLASMA CELLS(Contd.)
★ MORPHOLOGIC FEATURES OF PLASMA CELLS
★ DEPENDING ON THEIR MATURITY
★ MATURE PLASMA CELLS ★ IMMATURE PLASMA CELLS
Oval with abundant basophilic
cytoplasm, nucleus is round and
eccentrically located,perinuclear
hoff or cytoplasmic clearing,
“clock face” or “spoke wheel”
chromatin without nucleoli.
Dispersed nuclear chromatin,
prominent nucleoli and a high
nuclear to cytoplasmic ratio.
Morphologically indistinguishable
from myeloblasts.

9. PLASMA CELLS(Contd.)

10. INVESTIGATIONS(Contd.)
❖ BONE MARROW ASPIRATION:
➢ Cellular, Adequate
➢ Trilineage hematopoiesis present
➢ Myeloid Erythroid Ratio - 5:1
➢ ERYTHROID:
■ Present, Reduced
■ Binucleate, Budding Present
➢ MYELOID:
■ Present, Increased
➢ Neutrophils - 34%
➢ Lymphocytes - 7%

11. INVESTIGATIONS(Contd.)
❖ BONE MARROW ASPIRATION(Contd.):
➢ Band forms - 18%
➢ Eosinophilis - 2%
➢ Metamyelocytes - 12%
➢ Myelocyte - 24%
➢ Plasma cells - 3%
➢ IMPRESSION:
■ Trilineage hematopoiesis with myeloid
hyperplasia with 3% plasma cells.

12. INVESTIGATIONS(Contd.)
❖ BONE MARROW BIOPSY (9775/22):
➢ GROSS:
■ Received three grey white, grey brown bony
fragments each measuring 0.3 cm in length.
➢ MICROSCOPY:
■ Cellular marrow
■ Adequate
■ Trilineage hematopoiesis - present
■ Erythroid - present

13. ❖ BONE MARROW BIOPSY(Contd.):
➢ MICROSCOPY(Contd.):
■ Myeloid - present
■ Maturing myeloid - present
■ Megakaryocytes - Adequate
■ Blasts - Not increased
■ Lymphocytes - Not increased
■ Plasma cells - Increased
■ Granuloma - Absent
■ Reticulin - Grade I
INVESTIGATIONS(Contd.)

14. ❖ BONE MARROW BIOPSY(Contd.):

15. ❖ BONE MARROW
BIOPSY(Contd.):
➢ IMMUNO
HISTOCHEMISTRY:
■ CD138 - Positive
in plasma cells
in singles and in
clusters
INVESTIGATIONS(Contd.)

16. INVESTIGATIONS(Contd.)
❖ BONE MARROW BIOPSY(Contd.):
➢ DISCUSSION:
■ 64 year old male with lytic lesion in
vertebrae with history of anemia and renal
failure. Bone marrow aspiration shows
trilineage hematopoiesis with myeloid
hyperplasia and 3% plasma cells. Bone
marrow biopsy shows CD138 positive
plasma cells in singles and in clusters.
➢ IMPRESSION:
■ Bone marrow plasmacytosis.suggested
clinical correlation.

17. INVESTIGATIONS(Contd.)
❖ CT GUIDED BIOPSY OF L3 VERTEBRAL BODY(FROM
THE LYTIC LESION)
➢ GROSS:
■ Received multiple grey white linear bony
fragments largest measuring 1.2cm in length,
smallest measuring 0.5cm in length.
➢ MICROSCOPY:
■ Section studied shows multiple fragments of
mature bony trabeculae with intervening
marrow spaces exhibiting normal trilineage
hematopoiesis along with few plasma cells.
➢ IMMUNO HISTOCHEMISTRY:
■ CD38 - Positive in 15% of plasma cells.

18. ❖ LYTIC BONE LESION BIOPSY :

19. ❖ IMMUNO
HISTOCHEMISTRY:
➢ CD38 - Positive in
plasma cells.
INVESTIGATIONS(Contd.)

20. INVESTIGATIONS(Contd.)
➢ Serum Calcium level - 8.1 mg/dL
➢ Urine Bence Jones proteins - Negative
➢ Serum protein electrophoresis shows normal
electrophoretic pattern. No para protein band
detected.
➢ Free light chain assay - Report awaited

21. ❏ REACTIVE PLASMACYTOSIS
❏ MULTIPLE MYELOMA
❏ SOLITARY PLASMACYTOMA
❏ LYMPHOPLASMACYTIC LYMPHOMA
❏ MGUS
❏ SMOULDERING MYELOMA
DIFFERENTIAL DIAGNOSIS

22. ❏ Clonality should be established by showing a
kappa/lambda light chain restriction on flow
cytometry, immuno histochemistry or immuno
flureoscence.
❏ Bone marrow plasma cell percentage should be
estimated from a core biopsy specimen when
possible.
❏ Approximately 4% of patients may have fewer
than 10% bone marrow plasma cells, since
marrow involvement maybe focal rather than
diffuse.

23. ❖ Polyclonal plasma cells
❖ Bone Marrow:
➢ hypercellularity
➢ Trilineage hematopoiesis with normal
morphology
❖ Immuno histochemistry:
➢ Positive for CD38, CD138,CD45,CD19
➢ Kappa and Lambda light chains
➢ Negative for CD 56
REACTIVE PLASMACYTOSIS:

24. MULTIPLE MYELOMA:
❖ Clonal bone marrow plasma cell percentage
≥10% or biopsy-proven plasmacytoma and
❖ ≥1 of the following myeloma-defining events:
➢ END ORGAN DAMAGE ATTRIBUTABLE TO THE
PLAMSA CELL PROLIFERATIVE DISORDER:
■ Hyper calcemia : Serum calcium >0.25
mmol/L (>1mg/dL) higher than the upper
limit of normal or >2.75 mmol/L (>11mg/dL)
■ Renal insufficiency : Creatinine clearance
<40 mL/min or serum creatinine >177
micromol/L (>2 mg/dL)

25. ■ Anemia : a hemoglobin value of >20 g/L
below the lower limit of normal or a
hemoglobin value <100 g/L
■ Bone lesions : ≥ 1 osteolytic lesion on
skeletal radiography, CT or PET/CT
➢ ≥1 OF THE FOLLOWING BIOMARKERS OF
MALIGNANCY:
■ Clonal bone marrow plasma cell percentage
≥60%
■ An involved-to-uninvolved serum free light
chain ratio ≥100
■ >1 focal lesion on MRI
MULTIPLE MYELOMA(Contd):

26. ❖ CONDENSED OR CRYSTALLISED IMMUNOGLOBULIN :

27. ❖ IMMUNOPHENOTYPE:
❏ Immunohistochemical
staining,
immunofluorescent flow
cytometry.
❏ Expression of some normal
plasma cell markers( eg:
CD79a, VS38c, CD138 &
CD138)
❏ Either kappa or lambda light
chains, not both.
❏ Absence of surface
immunoglobulin.
❏ Absence of CD19 in most
instances.
❏ Variable expression of
CD45(usually negative), CD56
(usually positive)
❏ The kappa/lambda ratio of
more than 4:1 or less than 1:2.

28. SOLITARY PLAMSACYTOMA:
❖ Biopsy proven solitary lesion of bone or soft
tissue consisting of clonal plasma cells.
❖ Normal random bone marrow biopsy with no
evidence of clonal plasma cells.
❖ Normal skeletal survey and MRI or CT except for
the solitary lesion.
❖ Absence of end organ damage attributable to a
plasma cell proliferative disorder.

29. PLAMSACYTOMA:

30. ❖ Single focus of plasma cells occuring in either
bone or soft tissue.
❖ Males
❖ Sixth decade
❖ MICROSCOPY:
➢ Very vascular with a minimal stromal
component and consists of sheets of plasma
cells of varying degree of differentiation.
SOLITARY PLAMSACYTOMA:

31. ❖ Lymphoplasmacytic lymphoma in the bone with
an IgM monoclonal gammopathy in blood
(Walden Strom macroglobulinemia).
❖ Predominant cells are small lymphocytes or a
mixture of small lymphocytes and plasma cytoid
lymphocytes.
❖ Small lymphocytic component that express a
clonal surface immunoglobulin, CD19 and CD20.
LYMPHOPLASMACYTIC LYMPHOMA

32. MONOCLONAL GAMMOPATHY OF
UNDETERMINED SIGNIFICANCE(MGUS):
❖ M protein in serum < 30 g/L
❖ Bone marrow clonal plasma cells < 10%
❖ No evidence of other B cells proliferative
disorders.
❖ No myeloma-related organ or tissue impairment
(no end organ damage, including bone lesions)

33. SMOULDERING MYELOMA:
❖ Serum M protein > 30g/L, Urine M protein > 500
mg per 24 hours and/or clonal marrow plasma
cells of 10% - 60%, and
❖ Absence of myeloma defining events or
amyloidosis

34. THANK
YOU