Bone & joints

Other tumors


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Last staff update: 18 January 2022

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PubMed search: lymphoma [title] bone, general [all fields]

Sheren Younes, M.D., Ph.D.
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Cite this page: Younes S. Lymphoma. website. Accessed September 25th, 2023.
Definition / general
  • 40% of bone tumors are hematologic neoplasms, usually myeloma or lymphoma
  • Primary bone lymphoma (PBL): defined as lymphoma presenting in an osseous site with no evidence of disease elsewhere for at least 6 months
  • Presence of regional lymph nodes does not exclude the diagnosis of PBL (Joint Bone Spine 2000;67:446)
  • PBL accounts for < 5% of extranodal lymphoma and < 1% of all non-Hodgkin lymphoma (Am J Surg Pathol 1990;14:329)
  • Slight male preponderance
  • Can occur at any age, common in adults, mean age 48 years (range 11 - 83 years)
  • 80% are diffuse large B cell lymphoma
  • PBL is classified into four groups:
    • Group 1: solitary bone lymphoma
    • Group 2: multifocal bony lesions
    • Group 3: cases with distant nodal disease
    • Group 4: cases with visceral disease
  • Secondary involvement of bone by lymphoma is more common than primary, considered to be stage IV
  • Any bone can be involved
  • Usually sites of bone marrow, axial skeleton (spine), femur
  • Common in metaphysis; presence in diaphysis or epiphysis probably means progressive disease
  • Unknown why bone marrow develops into PBL; may be due to osteoclast activating factor has been
  • Strong tendency to spread and relapse suggests homing properties of lymphoma
Clinical features
  • Most commonly bone pain
  • Also palpable mass, pathologic fracture, neurologic symptoms with spine involvement
  • LDH may be elevated
  • B symptoms are uncommon
  • May relapse and involve other bones, lymph nodes, adjacent soft tissue, lung, bone marrow, CNS
  • Clinical, radiologic, and biopsy
  • Elevated LDH and B2 microglobulin
  • CBC, ESR and CRP
Radiology description
  • Most are permeative, mixed lytic sclerotic bone lesions
  • Usually large portion of bone is affected
  • May be unifocal, monostotic, or polystotic
  • Cortex is destroyed without reactive periosteal new bone formation
  • Variable sclerosis
  • Cystic, commonly mixed
  • Lymph node and soft tissue involvement is common
  • MRI shows signal abnormalities in bone marrow
Prognostic factors
  • Relatively good prognosis: 5 years survival > 80%
  • Factors associated with poor prognosis include: polystotic type, advanced disease, age > 60 years, site of mandible / maxilla
  • Also high IPI score, performance status < 2, normal LDH
  • Also combined modality therapy, higher radiation dose, > 3 cycles of chemotherapy, non germinal center phenotype of diffuse large B cell lymphoma
Case reports
  • Combination of radiotherapy and chemotherapy (Clin Orthop Relat Res 2013;471:2684)
  • Surgery has limited role - may delay start of chemotherapy
  • In children, chemotherapy alone is treatment of choice - gives better response
  • Radiotherapy may cause bone sarcoma
Clinical images

AFIP images


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Imaging of sacral lymphoma

Gross description
  • Usually small biopsy to avoid pathologic fracture disabilities
  • Fish flesh appearance of lymphoma
  • Extraosseous extension and indistinct margins
Microscopic (histologic) description
  • Most common type is diffuse large B cell lymphoma (80%)
    • Similar to morphology at other sites: diffuse growth pattern, infiltrating between bone trabeculae
    • Large atypical cells, abundant cytoplasm
    • Centroblasts, immunoblasts, or large bizarre cells
    • Nuclei show clumped chromatin, prominent nucleoli
    • Component of small lymphocytes is admixed with large cells
    • May have marked spindling and fibrosis
  • Also Burkitt lymphoma, lymphoblastic lymphoma, follicular lymphoma, other low grade B cell lymphoma, Hodgkin lymphoma, T cell lymphomas
Microscopic (histologic) images

AFIP images

Dense nuclei and histiocyte-like cells

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Sacral diffuse large B cell lymphoma

Cytology description
  • Variable combination of centroblasts, immunoblasts
  • May show large bizarre cells
Peripheral smear description
  • Lymphoma cells are rarely present in peripheral blood; when centroblasts are present, cells are very large and pleomorphic with abundant cytoplasm, often lobulated nucleus containing one or more fairly prominent nucleoli
Positive stains
  • CD45, B cell and T cell markers vary with lymphoma type
  • Diffuse large B cell lymphoma can have germinal center phenotype (CD10+, BCL2+ ), post-germinal center phenotype (CD10−, BCL2− ), or undetermined
  • Often CD30, ALK
Negative stains
Flow cytometry description
  • Shows clonal rearrangement, helps determine phenotype
Electron microscopy description
  • Centroblasts have cleaved nuclei, immunoblasts have large, round nuclei with coarse chromatin and one to three prominent nucleoli
  • Rough endoplasmic reticulum with dilated cisternae and prominent Golgi apparatus are also apparent
  • The degree to which these features are present reflects the cellular degree of plasmacytoid differentiation
Molecular / cytogenetics description
  • Clonally rearranged immunoglobulin genes (BCL2, BCL6, MYC)
  • 80% of Non Hodgkin lymphoma have chromosomal abnormalities
  • Usually Epstein-Barr virus negative
Molecular / cytogenetics images

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FISH: diffuse
large B cell
lymphoma with
MYC translocation

Differential diagnosis
  • Sample size, fibrosis, crush artifacts, and admixed small cells can cause diagnostic problems
  • Metastatic carcinoma:
    • Cells may have cytoplasmic clearing or be arranged in Indian file pattern; keratin+ (other epithelial markers), negative for lymphoid markers
  • Osteosarcoma:
    • Due to reactive bone formation associated with lymphoma
  • Reactive inflammatory conditions:
    • Polymorphous infiltrate, no large neoplastic cells, mixed B and T cells, not clonal
  • Spindle cell sarcoma:
    • When neoplastic cells are spindled, or caused by fibrosis; are negative for CD45, lymphoid markers
  • Other hematopoietic neoplasms, including poorly differentiated plasmacytoma, myeloid sarcoma
  • Other round blue cell tumors of bone, all lack immunoreactivity to lymphoid markers
Staging / staging classifications
  • Ann Arbor staging system is preferred until a better system is available
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