Solitary Plasmacytoma
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Transcript of Solitary Plasmacytoma
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
3
2
1
0
Months after 1st SPEP
Par
apro
tein
Lev
e l (
g/d
l)
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.