Cancer Division
Contributions
Type: Publication Only
Background
Bone involvement by Waldenstroms macroglobulinaemia (WM) is very uncommon. The presence of bony lesions may point towards possible high-grade transformation, or the diagnosis of a different IgM paraprotein-producing disorder (e.g. IgM myeloma).
Aims
We describe symptomatic skeletal involvement in 4 cases of previously diagnosed WM patients and evaluate the diagnostic value of bone biopsy to allow tailored management decisions to be made.
Methods
Four patients with WM were evaluated when they developed progressive bony pain, using MRI, PET-CT and bone biopsy. An image-guided biopsy of affected bone was performed in each case and the results were correlated with their bone marrow histology and other clinical and laboratory data.
Patient characteristics are shown below:
Patient ID | Age/ Sex | IPSSWM | ECOG | Isotype | Genetics | Time from diagnosis | Prior therapy |
A | 53/M | 1 | 0 | IgMk | N/A | New diagnosis | None |
B | 60/M | 2 | 1 | IgMk | N/A | 2 years | DRC x 6 to VGPR |
C | 57/F | 2 | 1 | IgMk | L265P Glu343Valfs*2 | 1 year | DRC x 6 to MR |
D | 44/F | 2 | 0 | IgGK | L265P | 3 years | DRC x 6 to PR |
Results
In all cases, patients were investigated due to unrelenting bone or joint pains, including shoulder & upper arm (24 months); knee (6 months); ankle and lower limb (6 months); knees (8 months) with limitation of movement and/or joint swelling. The bone disease was evident at the outset, at 12, 18 and 38 months from diagnosis respectively; 1 patient had newly diagnosed WM needing treatment, 2 had evidence of progressive disease 6 and 14 months post last treatment and the 4th patient had achieved a minor response to therapy at the time of bone disease.
MRI scans demonstrated abnormal intraosseous signal characteristics in the affected bones in all cases which enhanced with contrast and showed low signal intensity on the T1 weighted sequences and areas of high signal intensity on the T2 weighted sequences.
PET-CT scans were performed in 3 cases and showed patchy diffuse uptake correspomding with MRI signal abnormality in 2 cases, but no focal tracer uptake in the third case. There was no evidence of osteolysis on the CT component.
Biopsy of affected bones demonstrated a heavy infiltrate (70-90%) of lymphoplasmacytic lymphoma with identical characteristics to the iliac crest biopsy. In all cases, the bones were diffusely infiltrated by CD20+ cells, with a scattering of CD138+ cells. There was no evidence of transformation to high grade disease in any case.
Blood work showed a median Hb of 120 g/L, median platelets 270 x 109/L, median M-protein of 17 g/L (range 5-22 g/L), raised alkaline phosphatase and LDH in 1 patient, and normocalcaemia in all.
All 4 went on to receive chemoimmunotherapy (patient A also had radiotherapy to the humerus) which improved the bone symptoms in 2, but too early to assess in 2, and are alive with a median follow up is 7 months (range 1-20).
Summary
In our cohort of 4 patients who developed symptomatic bone disease there was appendicular skeletal infiltration by lymphoplasmacytic lymphoma; the possibility of skeletal disease in WM should be considered patients with bone or joint pain and the significance of bone disease in WM deserves further characterisation. Image-guided bone biopsy helps to confirm the diagnosis and rule out transformation to high grade lymphoma or an alternative diagnosis of IgM myeloma.
Keyword(s): Bone disease, Lymphoplasmacytic lymphoma, Waldenstrom's macroglobulinemia
Session topic: Publication Only
Type: Publication Only
Background
Bone involvement by Waldenstroms macroglobulinaemia (WM) is very uncommon. The presence of bony lesions may point towards possible high-grade transformation, or the diagnosis of a different IgM paraprotein-producing disorder (e.g. IgM myeloma).
Aims
We describe symptomatic skeletal involvement in 4 cases of previously diagnosed WM patients and evaluate the diagnostic value of bone biopsy to allow tailored management decisions to be made.
Methods
Four patients with WM were evaluated when they developed progressive bony pain, using MRI, PET-CT and bone biopsy. An image-guided biopsy of affected bone was performed in each case and the results were correlated with their bone marrow histology and other clinical and laboratory data.
Patient characteristics are shown below:
Patient ID | Age/ Sex | IPSSWM | ECOG | Isotype | Genetics | Time from diagnosis | Prior therapy |
A | 53/M | 1 | 0 | IgMk | N/A | New diagnosis | None |
B | 60/M | 2 | 1 | IgMk | N/A | 2 years | DRC x 6 to VGPR |
C | 57/F | 2 | 1 | IgMk | L265P Glu343Valfs*2 | 1 year | DRC x 6 to MR |
D | 44/F | 2 | 0 | IgGK | L265P | 3 years | DRC x 6 to PR |
Results
In all cases, patients were investigated due to unrelenting bone or joint pains, including shoulder & upper arm (24 months); knee (6 months); ankle and lower limb (6 months); knees (8 months) with limitation of movement and/or joint swelling. The bone disease was evident at the outset, at 12, 18 and 38 months from diagnosis respectively; 1 patient had newly diagnosed WM needing treatment, 2 had evidence of progressive disease 6 and 14 months post last treatment and the 4th patient had achieved a minor response to therapy at the time of bone disease.
MRI scans demonstrated abnormal intraosseous signal characteristics in the affected bones in all cases which enhanced with contrast and showed low signal intensity on the T1 weighted sequences and areas of high signal intensity on the T2 weighted sequences.
PET-CT scans were performed in 3 cases and showed patchy diffuse uptake correspomding with MRI signal abnormality in 2 cases, but no focal tracer uptake in the third case. There was no evidence of osteolysis on the CT component.
Biopsy of affected bones demonstrated a heavy infiltrate (70-90%) of lymphoplasmacytic lymphoma with identical characteristics to the iliac crest biopsy. In all cases, the bones were diffusely infiltrated by CD20+ cells, with a scattering of CD138+ cells. There was no evidence of transformation to high grade disease in any case.
Blood work showed a median Hb of 120 g/L, median platelets 270 x 109/L, median M-protein of 17 g/L (range 5-22 g/L), raised alkaline phosphatase and LDH in 1 patient, and normocalcaemia in all.
All 4 went on to receive chemoimmunotherapy (patient A also had radiotherapy to the humerus) which improved the bone symptoms in 2, but too early to assess in 2, and are alive with a median follow up is 7 months (range 1-20).
Summary
In our cohort of 4 patients who developed symptomatic bone disease there was appendicular skeletal infiltration by lymphoplasmacytic lymphoma; the possibility of skeletal disease in WM should be considered patients with bone or joint pain and the significance of bone disease in WM deserves further characterisation. Image-guided bone biopsy helps to confirm the diagnosis and rule out transformation to high grade lymphoma or an alternative diagnosis of IgM myeloma.
Keyword(s): Bone disease, Lymphoplasmacytic lymphoma, Waldenstrom's macroglobulinemia
Session topic: Publication Only