Solitary Plasmacytoma of the Bone (SPB)

Michael Gu, MDMay 9, 2003

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

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”

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

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/chondrosaarcoma

• Lab:• CBC, BMP normal• SPEP: TP:7.7; 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

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: TP:7.7; 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.

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

Case #2 (Continued)• Final diagnosis:

• Solitary plasmacytoma of the bone

• Post-surgery management:• Local adjuvant RT: total 4000cGy in 20 fractions

• Physical therapy.

0 1 2 3 4 5

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Surgery Radiation

Questions

• Prognosis?

• Observation or adjuvant therapy?

Solitary Plasmacytoma

• Definition: – localized tumor containing monoclonal

plasma cells

• Type: – Solitary Plasmacytoma of the Bone (SPB)– Extramedullary Plasmacytoma (EMP)

SPB EMP

Incidence 2-5% 3%

Initial site Axial bone Sofe tissue oforonasopharyn andupper resperotory

Symptom Pain and cord/nervecompression

Bleeding andobstruction of nasal

passagersSurvival afterlocal XRT (10Y) 53% 85%

Progression toMM in 10 years 68% 20%

Difference Between SPB and EMP

Bolek,TW.et al. Int J Radiat.Oncol. Biol.Phys.36( 2): 329-333

SPB• Incidence:

• 2-5% of plasma dysplasia disorders.

• Sex: • Male:female = 3-4:1 (MM 1-1.5:1)

• Age: • Median age 55 y/o (MM=69y/o)

• Initial site of involvement:• thoracic spine > lumbar spine > pelvis > rib

Vertebra 40 %Pelvis 17 %Rib 14 %Scapula 9 %Sternum 7 %Skull 5 %Others 8 %

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 >one uninvolved vertebra)

• Outcome and prognostic factors:

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

OUTCOME

Summary of the outcome with RT

32%6.3% 9.9

Dimopoulos, MA et al. Blood 96(6) : 2037-2044 (2000)

Pattern of Progression

• Local relapse (<10%)

• New focal bone lesions(<10%)

• Multiple Myeloma( >80%)

Prognostic Factors

Solitary Bone Plasmacytoma: Outcome and Prognostic Factors Following Radiotherapy

• 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)

Liebross, RH et al Int J Radiat.Oncol. Biol.Phys.(1998) Vol 41(5): 1063-1067

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

Prognostic Factors

– Dose of Radiotherapy:

- No dose-response relationship for local control, disappearance of M protein and progression to MM

Prognostic Factors (Continued)

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

Prognostic Factors (Continued)

Pretreatment No. of the patients

Non-secretary 16 10 63%

Secretary 41 11(27%) protein 2 18%

30(73%) protein 17 57%

No.of Pts progression to

MM

Post-treatment

- Post- radiotherapy paraprotein level:

Prognostic Factors (Continued)

-Disappearing of paraprotein after local RT was associated with a long-term stability.

Prognostic Factors (Continued)

• Pretreatment imaging modality:

23 Pts with thoraco-lumbar spine diseases

8 staged with plain radiography alone

7 staged also with MRI

7 progressed to MM

1 progressed to MM

(P = 0.08)

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 >5 cm is an adverse prognostic factor. (Holland, et al 1991) 82 % of the conversion Pts had lesion >5 cm (median 7 cm)

28% of the Unconversion Pts had lesion>5 cm (median 3.75 cm)

Solitary Plasmacytoma of Bone: Mayo Clinic Experience

• 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:

Frassica, DA et al. Int J radiat.Oncol. Biol.Phys. Vol16:43-48 1989

74%

45%43%

25%

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 Ptsprotein. 6/8(75%)MM

Summary of Prognostic Factors

• Post-radiotherapy M protein level

• Pretreatment imaging modality

• Uninvolved immunoglobulin level

• Original tumor size

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

The Role of Adjuvant Chemotherapy in SPB

The role of radiation therapy in the treatment of solitary plasmacytomas

• 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 <10; IgG <3.5; Ig A<2.

Mayr, NA et al. Radioth Oncol 1990 : 17: 293-303

17 Patients. With SPB

12 RT alone

5 RT + Chemo (3 M alone; 1 Cyto alone; 1 M+P.)

9/12(75%) MM in 36 mo.

0/5 (0%) MM in median 66 mo. follow up

Improved Outcome in Solitary Bone Plasmacytomata with Combined Treatment

Aviles,A et al Hematol Oncol Vol. 14, 111-117 (1996)

53 Pts with SPB (1982-1989)

28 Pts with RT( 4000-5000 cGY)

25 Pts with RT(4000-5000 cGy) followed by adjuvant chemotherapy

Median follow up for 8.9 years

Adjuvant chemotherapy:

Mephalan 6 mg/m2/day x 4Prednisone 40 mg/m2/day x4

Each cycle Q 6 wks for 3 years

• Results:– 15/28 (54%) patients with RT alone progressed to MM– 3/25 (12%) patients with RT+chemo progressed to MM

– No significant adverse effects. No leukemia.

Solitary Plasmacytoma of the Spine long-Term Clinical Course

• 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)

Delauche-Cavallier, MC, et al. Cancer 61-1707-1714, 1988.

PlasmacytomaTreatment Results and Conversion to Myeloma

• 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)

Holland, J et al. Cancer 69(6): 1523. 1992

No. of thePts.

No. of PtsConversion

to MM

Median timeto conversion

(mo)

RT alone 32 13(41%) 29RT + chemo 14 9(64%) 59Total 46 22(48%)

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.

American society of Clinical Oncology Clinical Practice Guidelines:

The Role of Bisphosphonates in Multiple Myeloma

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

Bruce, JR et al. JCO 20:3719-3736 (2002)

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.

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.