Dr James Wittig, MD Orthopedic Oncologist
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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



25% involve flat bones (pelvis, sacrum, ribs)
Mixed lysis/sclerosis in 28%
Aggressive or nonaggressive PR common

 

 

Permeative Lesion



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


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


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


Permeative/Motheaten Lesion with Pathologic Fracture

X-ray: Primary Lymphoma of Humerus

 

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


Reactive Inflammatory Infiltrate of Plasma Cells
and Lymphocytes

 

Large Malignant B-cells

 

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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