Bone Tumors
Lymphoma of Bone
James C. Wittig, MD Sarcoma Surgeon Orthopedic Oncologist
GENERAL INFORMATION
Primary lymphoma of bone is defined as lymphoma arising within the medullary cavity of a bone in the absence of lymph node or organ involvement for at least 6 months after diagnosis Primary lymphoma of bone is rare (3% of primary bone tumors) and most lymphomas that involve bone are metastatic from lymph node. If a lymphoma of bone is diagnosed one must look for another site. Most primary lymphomas of bone are Non Hodgkin's, large cell lymphomas In U.S. majority are B-cell proliferations Must rule out presence of extraskeletal disease May be misdiagnosed as chronic osteomyelitis
CLINICAL PRESENTATION
Signs/Symptoms: Localized dull or aching pain May have palpable mass or swelling Usually no general symptoms and appear healthy Pathological fractures in 25% of cases Prevalence: Male predilection (1.5:1)
Age: Broad age range Most occur after second decade with 50% occurring above 40 years Rare in children
Sites: Any bone can be involved Lower extremities involved most often especially femur and pelvis More common in appendicular than axial skeleton (opposite of metastatic lymphoma)
RADIOGRAPHIC PRESENTATION
Permeative or moth eaten bone destruction (55%) Geographic (11%); Blow out (1%); Blastic (2%); Normal XR (5%) Metadiaphysis (75%) Periosteal reaction—may look benign Interrupted or solid single layer (66%) Onion Skin 10% Sunburst 2% Soft tissue mass— by CT (80%); by MRI (100%)
Pathologic Fracture (22%) Sequestra (16%) Cross Joint (5%) Diff Dx: Metastatic Lymphoma Ewings Neuroblastoma Rhabdomyosarcoma Osteomyelitis Eosinophilic Granuloma
Permeative or moth eaten lytic lesion Often barely perceptible on X-ray Reactive sclerosis (28%) Metaphysis or metadiaphysis of long bones No Mineralization Soft tissue mass common Femur/tibia/humerus |
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25% involve flat bones (pelvis, sacrum, ribs) Mixed lysis/sclerosis in 28% Aggressive or nonaggressive PR common
Permeative Lesion |
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Increased activity on bone scan Increased activity on scintigraphy and normal XR highly suggestive of lymphoma Marrow replacement, cortical destruction and ST mass on CT Sequestra formation in 11-16%
Marrow Replacement |
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Variable SI MR Intermediate on T1 High on T2
ST mass common (permeation of tumor cells through small vascular channels in the cortical bone without frank cortical breakthrough (also seen with Ewing/PNET)
Intrasseous Lesion
Soft Tissue Mass |
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Radiographic Presentation: Primary Lymphoma of Bone
Cortex Appears Inteact (top) Soft Tissue Mass (bottom) T2 Weighted MRI
 TI Weighted MRI |
 T2 Weighted MRI |
MRI: Primary Lymphoma of Bone
Permeative/Moth eaten lesion Reactive sclerosis (mixed lysis and sclerosis) Slight periosteal reaction |
 | X-ray: Primary Lymphoma of Femur
Permeative Lesion
X-ray: Primary Lymphoma of Distal Humerus

X-ray: Primary Lymphoma of Tibia Permeative Moth eaten Lesion
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Permeative/Motheaten Lesion with Pathologic Fracture | X-ray: Primary Lymphoma of Humerus
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Permeative Lesion of Proximal Tibia with Pathological Fracture | X-Ray: Primary Lymphoma of Proximal Tibia
GROSS PATHOLOGY
Diffuse infiltrative growth pattern with soft tissue extension Intraosseous component Mixture of bone spicules and marrow fat as lesion permeates through the medullary canal and has an indistinct margin Extraosseous tissue Tan or white, resembles lymphomatous lymph nodes Areas of necrosis, hemorrhage, and cystic degeneration are present
MICROSCOPIC PATHOLOGY
Diffuse growth pattern Mixture of small lymphocytic cells and larger histiocytic components (Large Malignant B Cells in most cases) Cells and no matrix Nuclei Vary in shape and size Grooved vesicular nuclei Prominant nucleoli Cytoplasmic glycogen is absent Complex reticulin framework Prominent fibroblastic component CD5 and Leukocyte Common Antigen Positive CD3+ and CD45+ for B Cell Lymphoma; CD3+ for Rare T-Cell
Small Round Blue Cell Tumor Cells without Matrix Crush artifact Cells are different sizes and shapes |
 | Microscopic Pathology: Lymphoma

Microscopic Pathology: Lymphoma
Small round blue cells No matrix Extensive reticulin fibers |
 | Microscopic Pathology: Lymphoma
Mixture of small round blue cells of different sizes and shapes No Matrix production Large B-Cells mixed with reactive inflammatory infiltrate leads to different cell types |
 | Microscopic Pathology: Lymphoma
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Reactive Inflammatory Infiltrate of Plasma Cells and Lymphocytes
Large Malignant B-cells
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Microscopic Pathology: Lymphoma
 Microscopic Pathology: Lymphoma
 Microscopic Pathology: Lymphoma

Microscopic Pathology: Lymphoma
DIFFERENTIAL DIAGNOSIS
Ewing Sarcoma Chronic Osteomyelitis Leukemia
TREATMENT
Chemotherapy and radiation If truly an isolated primary lymphoma of bone, limb sparing surgery may be considered instead of or in conjunction with radiation Surgical resections to treat residual or recurrent tumors after radiation Amputation only recommended when lesions are unresponsive to radiation or recur and are not amenable to limb sparing surgery for various reasons
PROGNOSIS
Patients with: Monostotic disease & no soft tissue involvement 58% 5-year and 53% 10-year survival
Multifocal bony disease 42% 5 year and 35% 10 year survival
Osseous lymphoma with lymph node involvement 22% 5-year and 12% 10-year survival
Chemotherapy increases survival rates (88% disease free survival at 7 years) of patients with primary lymphoma of bone Has best prognosis of all osseous malignancies except for low grade intraosseous and parosteal osteosarcoma Possible better prognosis for lymphomas with cleaved nuclei as compared to noncleaved, immunoblastic or pleomorphic variants
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