Solitary Plasmacytoma of the Bone SPB

1
Solitary Plasmacytoma of the Bone (SPB)

• Michael Gu, MD
• May 9, 2003

2
Case 1

• 30 y.o.A.A.F., healthy, presented with
  progressive bilateral LE weakness for 2 months
  PTA.
• MRI of the spine
• T7 vertebral body lesion with epidural soft
  tissue mass. Positive for cord compression.
• Core biopsy atypical plasma cell
• Lab
• CBC, CMP normal. Ca 9.
• SPEP Gamma 1.4 Restr Pk 0.3g/dl IF IgG
  lambda.
• UPEP (-) for M-protein. IF (-).
• Quantitative immunoglobulin normal range
• ?2-microglobulin 2.2 LDH 163

3
(No Transcript)
4
Case 1

• 30 y.o.A.A.F., healthy, with progressive
  bilateral LE weakness for 2 months PTA.
• MRI of the spine
• T7 vertebral body lesion with epidural soft
  tissue mass. Positive for cord compression.
• Lab
• CBC, CMP normal. Calcium 9.
• SPEP Gamma 1.4 Restr Pk 0.3g/dl IF IgG
  lambda.
• UPEP (-) for M-protein. IF (-).
• Quantitative immunoglobulin normal range.
• ?2-microglobulin 2.2 LDH 163.
• Core biopsy atypical plasma cell

5
Case 1 (continued)

• Bone marrow biopsy
• 1 plasma cell. No evidence of plasma cell
  dysplasia.
• Further Imaging
• Skeleton survey no other lytic lesions
• CT scan of the chest/abdomen/pelvis no other
  lesions
• Final diagnosis
• Solitary plasmacytoma of the bone.
• Management
• Local RT
• Lost follow up

6
Case 2

• 48 y.o. healthy w.f. presented with left
  hip/thigh pain for 11 months PTA.
• Plain X-ray and CT scan
• A large marrow-centered mass at left ilium with
  adjacent tissue invasion.
• Initial diagnosis
• Metastatic malignancy/solitary plasmacytoma/chondr
  osaarcoma
• Lab
• CBC, BMP normal
• SPEP TP7.7 Gamma 2.5 Restr Pk 2.2
  IF IgG Kappa
• UPEP no Resr Pk IF IgG Kappa.
• ?2-microglobulin 2.1
• LDH 152
• Quantitative immunoglobulin IgG 1580 IgA and
  IgM normal

7
(No Transcript)
8
(No Transcript)
9
Case 2

• 48 y.o. healthy w.f. with left thigh/hip pain for
  11 months.
• Plain X-ray and CT scan
• A large marrow-centered mass at left ilium with
  adjacent tissue invasion.
• Initial diagnosis
• Metastatic malignancy/chondrosaarcoma /solitary
  plasmacytoma
• Lab
• CBC, BMP normal
• SPEP TP7.7 Gamma 2.5 Restr Pk 2.2
  IF IgG Kappa
• UPEP (-) Restr Pk IF IgG Kappa.
• ?2-microglobulin 2.1
• LDH 152
• Quantitative immunoglobulin IgG 1580 IgA and
  IgM normal.

10
Case 2 (Continued)

• Exploratory surgery with biopsy
• Pathology diffuse sheets of slightly atypical
  plasma cell. 98 cells are CD 38 and ()
  cytoplasmic kappa light chain.
• Left total hip arthroplasty, partial excision of
  pelvis and acetabular reconstruction.
• Bone marrow biopsy
• Plasma cell 5. No diagnostic feature for plasma
  cell dyscrasia.
• Skeleton survey
• ? Two small lytic lesions at right ilium
• CT scan of the chest/abdomen/pelvis
• no other lytic lesions
• MRI of the spine
• no marrow replacement or focal osseous lesion

11
Case 2 (Continued)

• Final diagnosis
• Solitary plasmacytoma of the bone
• Post-surgery management
• Local adjuvant RT total 4000cGy in 20
  fractions
• Physical therapy.

3
Surgery
Radiation
?
2
Paraprotein Level (g/dl)
?
?
1
0
0 1 2 3 4 5
Months after 1st SPEP
12
Questions

• Prognosis?
• Observation or adjuvant therapy?

13
Solitary Plasmacytoma

• Definition
• localized tumor containing monoclonal plasma
  cells
• Type
• Solitary Plasmacytoma of the Bone (SPB)
• Extramedullary Plasmacytoma (EMP)

14
Difference Between SPB and EMP
Bolek,TW.et al. Int J Radiat.Oncol. Biol.Phys.36(
2) 329-333
15
SPB

• Incidence
• 2-5 of plasma dysplasia disorders.
• Sex
• Malefemale 3-41 (MM 1-1.51)
• Age
• Median age 55 y/o (MM69y/o)
• Initial site of involvement
• thoracic spine gt lumbar spine gt pelvis gt rib

Vertebra 40 Pelvis 17 Rib 14
Scapula 9 Sternum 7 Skull 5
Others 8
16
SPB (Continued)

• Symptoms
• Pain bone destruction
• Neurologic symptom spinal cord / nerve
  compression
• Serum monoclonal protein
• Positive in 24-72 of the cases
• The level is much lower than MM
• Immunoglobulin
• The uninvolved immunoblobulin levels are
  preserved
• Standard therapy Local radiotherapy
• Dose 4000 cGy
• Field a normal tissue margin (in spine
  lesion, or gtone uninvolved vertebra)
• Outcome and prognostic factors

17
Criteria of the Diagnosis of SPB

• Single bone lesion
• Complete radiographic skeletal survey
• MRI scan of the axial skeleton (skull, spine,
  pelvis, proximal femora and humeri)
• Clonal plasmacytosis
• Biopsy of the tumor
• Flow cytometry or immunohistochemistry
• Normal bone marrow
• Morphology
• Lack of clonal plasma cells or aneuploidy on flow
  cytometry
• Absent or low, serum or urinary levels of
  monoclonal protein
• If present at diagnosis, should disappear within
  6-12 months of therapy
• Preserved levels of uninvolved immunoglobulins
• No anemia, hypercalcemia, or renal impairment
  attributable to myeloma

18
OUTCOME
19
Summary of the outcome with RT
32
6.3
9.9
Dimopoulos, MA et al. Blood 96(6) 2037-2044
(2000)
20
Pattern of Progression

• Local relapse (lt10)
• New focal bone lesions(lt10)
• Multiple Myeloma( gt80)

21
Prognostic Factors
22
Solitary Bone Plasmacytoma Outcome and
Prognostic Factors Following Radiotherapy
Liebross, RH et al Int J Radiat.Oncol.
Biol.Phys.(1998) Vol 41(5) 1063-1067

• 1965-1996. 57 previously untreated patient with
  SPB
• Treatment
• Megavoltage radiation
• Median dose 50 Gy (30-70 Gy)
• Median fraction size 2 Gy (1.3-5.0)

23
Results

• Local control 96
• Post RT myeloma protein level
• Disappeared from serum 9/33 (27)
• Disappearance of B-J protein 2/7 (29)
• Evolution of MM
• 29 Pts (53)
• Median time for progression 1.8 year
• Median survival 11 years

24
Prognostic Factors

• Dose of Radiotherapy

- No dose-response relationship for local
control, disappearance of M protein and
progression to MM
25
Prognostic Factors (Continued)

• Age, site of the disease and pretreatment
  paraprotien level no effect

26
Prognostic Factors (Continued)
- Post- radiotherapy paraprotein level
No.of Pts progression to MM
Post-treatment
No. of the patients
Pretreatment
Non-secretary 16 10 63 Secretary 41 11(27
) protein ? 2 18 30(73) protein? 17 57
27
Prognostic Factors (Continued)
-Disappearing of paraprotein after local RT was
associated with a long-term stability.
28
Prognostic Factors (Continued)

• Pretreatment imaging modality

8 staged with plain radiography alone
23 Pts with thoraco-lumbar spine diseases
7 progressed to MM
(P 0.08)
7 staged also with MRI
1 progressed to MM
29
Prognostic Factors (Continued)

• low level of uninvolved IG
• All 3 patients had early progression to MM
• Patient with ? uninvolved IG should not be
  considered to have SPB.
• Size of the Lesion
• Lesion gt5 cm is an adverse prognostic factor.
  (Holland, et al 1991)
• 82 of the conversion Pts had lesion gt5
  cm (median 7 cm)
• 28 of the Unconversion Pts had lesiongt5
  cm (median 3.75 cm)

30
Solitary Plasmacytoma of Bone Mayo Clinic
Experience
Frassica, DA et al. Int J radiat.Oncol.
Biol.Phys. Vol1643-48 1989

• 1950-1982. 46 cases with median follow up 90
  months.
• RT alone. Dose 20 Gy -70 Gy ( median 39.75 Gy)
• MM progression rate 54. Median time to
  progression 18 months.
• Survival

74
45
43
25
31
Prognostic Factors
- Pre- and Post-treatment M protein level did not
affect the development of MM and the survival.

• 25/46 Pts had M protein
• 15/25 Pts had follow up after
• treatment
• 7/15 Pts ? protein. 5/7(71)?MM
• 8/15 Pts?protein. 6/8(75)?MM

32
Summary of Prognostic Factors

• Post-radiotherapy M protein level
• Pretreatment imaging modality
• Uninvolved immunoglobulin level
• Original tumor size

33
How to prevent disease progression and improve
survival?

• Increase the sensitivity of diagnostic tool to
  fill out MM in evolution
• MRI, PET, Flow cytometry, plasma cell labeling
  index
• Strictly follow diagnostic criteria
• Adjuvant therapy for high risk patients

34
The Role of Adjuvant Chemotherapy in SPB
35
The role of radiation therapy in the treatment of
solitary plasmacytomas
Mayr, NA et al. Radioth Oncol 1990 17 293-303

• 1960-1985. Total 30 patients (SPB 17 EMP 13)
• Median follow up 12.8 years ( 39 mo - 25 y)
• Criteria for SPB . BM plasma cell lt10 IgG
  lt3.5 Ig Alt2.

9/12(75) ? MM in 36 mo.
12 RT alone
17 Patients. With SPB
5 RT Chemo (3 M alone 1 Cyto alone 1 MP.)
0/5 (0) ? MM in median 66 mo. follow up
36
Improved Outcome in Solitary Bone Plasmacytomata
with Combined Treatment
Aviles,A et al Hematol Oncol Vol. 14, 111-117
(1996)
28 Pts with RT( 4000-5000 cGY)
53 Pts with SPB (1982-1989)
Median follow up for 8.9 years
25 Pts with RT(4000-5000 cGy) followed by
adjuvant chemotherapy
Adjuvant chemotherapy Mephalan 6 mg/m2/day x
4 Prednisone 40 mg/m2/day x4 Each cycle Q 6 wks
for 3 years
37
(No Transcript)
38

• Results
• 15/28 (54) patients with RT alone progressed to
  MM
• 3/25 (12) patients with RTchemo progressed to
  MM
• No significant adverse effects. No leukemia.

39
Solitary Plasmacytoma of the Spine long-Term
Clinical Course
Delauche-Cavallier, MC, et al. Cancer
61-1707-1714, 1988.

• 1959-1979. 19 patients with SPB of the spine.
• 8/19 patients had RT chemotherapy
• 4/8 (50) progressed
• 4/8 developed leukemia (3/4 had progressed
  disease)

40
PlasmacytomaTreatment Results and Conversion to
Myeloma
Holland, J et al. Cancer 69(6) 1523. 1992

• 1961-1988. 46 patients (32 SPB 14 EMP)
• Adjuvant chemo and conversion to MM
• Chemotherapy did not prevent the conversion to
  MM.
• Chemotherapy may delay the time to conversion.
• The survival time after conversion was the same
  (14.5 mo)

41
The Disadvantage of Adjuvant Chemotherapy in SPB

• The benefit is still uncertain.
• May over-treat patients who are cured by RT.
• The chance to induce resistant subclones.
• Adverse effects such as leukemia.

42
American society of Clinical Oncology Clinical
Practice Guidelines The Role of Bisphosphonates
in Multiple Myeloma
Bruce, JR et al. JCO 203719-3736 (2002)

• Starting bisphosphonates for patients with
  solitary plasmacytoma is not suggested.

43
Summary

• Solitary plasmacytoma is a rare disease which
  consists of SPB and EMP. EMP has a better outcome
  then SPB.
• Local RT is still the standard treatment. With
  that, SBP has long-term overall survival (9.9Y).
  However 2/3 of the patients will progress to MM
  in 10 years. Most of the conversions occurred in
  first 4 years.
• The size of the tumor, the post-radiotherapy
  M-protein level and level of uninvolved IG may
  predict the outcome.

44
Summary (continued)

• Strictly following diagnostic criteria and using
  sensitive screening tools to exclude MM may
  increase the specificity for diagnosis of pure
  SPB. It may improve the outcome.
• The role of adjuvant chemotherapy in the
  prevention of MM conversion is still unclear.
  Generally, it is not recommended at the time.