Tumor biology and incidence

  • May affect skeletal system either as primary or secondary disease (metastasis)
    • Distinction is important prognostically: primary lesions potentially curable, secondary lesions associated with high mortality rate
  • Primary lesions characterized by histologic proof of bony disease preceding systemic involvement by at least 6 months
  • May be considered primary lesion if thorough search for alternate site of origin is negative
  • Primary lesions (restricted to bone) also known as reticulum sarcoma of bone
  • Cells arrested at different stages of differentiation
  • 25% of non-Hodgkin’s lymphoma cases involve bone
  • Combined with Hodgkin’s lymphoma, accounts for approximately 10% of malignant bone lesions


  • Average age is 45 years at diagnosis; rarely occurs before age 20
  • Peak ages of incidence is 50s and 60s


M:F = 2:1


  • Pain, pathologic fracture
  • Patients with advanced disease may be systemically unwell with weight loss, fatigue, fevers, or chills

Physical findings

  • Palpable mass or swelling may be present
  • Disseminated disease may present with lymphadenopathy and/or hepatosplenomegaly
  • Juxta-articular lesion may cause joint effusion

Blood work

  • CBC, blood chemistry analysis, LDH, and urinalysis indicated
  • Examination of peripheral blood necessary to rule out leukemia and disseminated lymphoma

Bone marrow aspiration

Examination of bone marrow necessary to rule out leukemia and disseminated lymphoma

Plain films

  • Bones usually involved (roughly in descending order): femur, tibia, humerus, pelvis, ribs, and vertebrae
  • Any bone may be affected


Tumor effect on bone
  • Majority of lesions are lytic with a “moth-eaten” permeative border
  • Lytic lesions often coalesce to form larger lytic lesions
  • Regional osteoporosis often present
Bone response to tumor
  • May be varying degrees of sclerosis: Lower-grade lesions often sclerotic, high-grade lesions rarely sclerotic
  • Vertebrae may have sclerosis leading to “ivory vertebra” radiographically


  • Cortical involvement common; usually see erosion and thickening
  • Periosteal reaction common; usually of lamellar type

Soft tissue mass

  • May be present
  • Significant number of patients with higher-grade lesions have cortical breakthrough with soft tissue mass
    • Similar to osteosarcoma and Ewing’s sarcoma, soft tissue mass may develop on top of intact cortex

Bone and gallium scans

Important for detection of polyostotic involvement or identification of visceral or lymphatic involvement on gallium scan.

CT and MRI

  • MRI optimal for evaluating extent of bone marrow involvement and presence of a soft tissue mass
  • CT necessary for staging mediastinal and retroperitoneal nodes

Differential diagnosis

In patients > 40 years of age
  • Multiple myeloma
  • Fibrosarcoma
  • Malignant fibrous histiocytoma
  • Metastasis
  • Paget’s disease
In younger patients
  • Eosinophilic granuloma
  • Infection
  • Ewing sarcoma
  • Osteosarcoma (especially in sclerotic lymphoma)
  • If the patient is < 10 years of age, consider metastatic neuroblastoma


  • Gross: Firm, tan tissue
  • Microscopic: Infiltrate of atypical lymphocytes
  • Grading depends on architecture, cell size, and nuclear and cytoplasmic morphology
  • Grade corresponds well with prognosis, with high-grade lesions having poorest prognosis
  • Immunohistochemistry, flow cytometry, and/ or molecular analysis used to identify whether lymphoma is of B cell or T cell lineage
  • Bone marrow aspirate used for staging

Diagnosis and treatment

  • Prior to bone biopsy, evaluate whether soft tissue site may be biopsied with less morbidity
  • Lymphoma is radiosensitive; bone resection generally not needed
  • Solitary lesions may be treated with radiation, often with chemotherapy
  • Staging should proceed with medical oncologist as part of treating team
  • Resection may be necessary for local symptoms in rare cases of local recurrence
  • 5-year survival for solitary bony lesions greater than 50%
  • Survival depends on extent of skeletal, visceral, and nodal disease evident at presentation, as well as tumor grade
  • Systemic chemotherapy is required for disseminated disease
  • Pathologic fracture often requires open reduction and internal fixation