Bone
Hematologic neoplasms
Lymphoma - general

Author: Sheren Younes, M.D. (see Authors page)

Revised: 8 November 2016, last major update October 2013

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

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

Cite this page: Bone - Lymphoma - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/bonelymphomageneral.html. Accessed December 7th, 2016.
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)
Epidemiology
  • 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
Sites
  • 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
Pathophysiology
  • 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
Diagnosis
  • Clinical, radiologic, and biopsy
Laboratory
  • 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
Treatment
  • 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
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Femur



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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
Micro 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
Micro Images
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Dense nuclei and "histiocyte-like" cells



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Sacral diffuse large B cell lymphoma

Anaplastic large cell lymphoma

Anaplastic large
cell lymphoma is
CD30+, EMA+,
granzyme B+, ALK1+

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