Bone
Hematologic neoplasms
Burkitt lymphoma (BL)

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

Revised: 2 December 2016, last major update November 2016

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

PubMed search: burkitt [title] lymphoma bone

Cite this page: Burkitt lymphoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/boneburkitt.html. Accessed December 9th, 2016.
Definition / General
  • Defined by WHO as an aggressive B cell NHL
  • See also Lymphoma chapter
  • Often presents at extranodal sites
  • Characterized by high degree of proliferation of malignant cells
  • MYC chromosomal translocation is almost always present
  • Most are related to EBV
Epidemiology
Three variants:
  • Endemic BL
    • In equatorial Africa, correspond to malaria endemic regions
    • Mean age 7 years old, range 2 - 16 years
    • Male to female ratio 2:1
    • Most are EBV+
    • Commonly affects jaw, facial bones and orbit
    • Less common in kidney, GI tract, ovaries, breast
  • Sporadic BL
    • No specific geographic or climatic association
    • Children and young adult
    • Male to female ratio 2:1
    • < 30% are EBV+
    • Most common in ileocecal valve, other extranodal sites and lymph nodes; also reported in jaw
  • Immunodeficiency associated lymphoma
    • Associated with HIV infection or immune suppression
    • 20% - 40% associated with EBV
Etiology
  • MYC translocation is the most important genetic abnormality in BL; is "gold standard" for diagnosis, although not sufficient alone, and not specific
  • Only a few BL cases with no MYC translocation have been reported (J Pathol 2008;216:440)
    • t(8;14) juxtaposes MYC to Ig gene, with loss of control over MYC gene expression
    • Other non immunoglobulin translocations involving MYC gene are t(8;9) - juxtaposes MYC to PAX5 gene, and t(3;8) - juxtaposes MYC to BCL6 gene
  • EBV infection
    • Found in > 95% of endemic BL, less common in sporadic and immunodeficiency related BL
    • A gamma herps virus capable of establishing different types of latency in B cells
    • May produce latency genes of EBNA and LMP
  • Malaria
    • Its role in endemic BL is unknown - may be due to chronic B cell stimulation
Clinical Features
  • Younger age in endemic areas, broader age range in nonendemic areas
  • Commonly affects jaw and facial bones; less commonly affects cranial vault, tibia, ribs
  • Symptoms include swelling of the mandible or maxilla, bone pain, tumor mass
  • Early sign is loosening of child's molar or premolar
  • Also causes ulceration of mouth mucosa; proptosis may be marked but usually not painful
  • Extradural lesions cause spinal cord compression and paraplegia
Diagnosis
  • Clinical, radiologic, histologic, immunophenotype and MYC translocation
Laboratory
  • CBC may show abnormalities
  • Serum lactate dehydrogenase (LDH) levels are elevated
  • Beta2 microglobulin predicts extent of disease and is used as a surrogate marker for early relapse
  • Serum uric acid levels are high due to the high grade nature of the disease and tumor lysis syndrome with chemotherapy
Radiology Description
  • Disease has rapidly proliferation, leading to rapid bone destruction with cortical bone destruction and soft tissue mass
  • Floating teeth sign seen on radiographs
  • Other facial bones may be involved and may develop extradural extension
  • Long bones (femur, tibia) are less frequently affected
    • Lesion can be multiple, bilateral; can affect diaphysis, metaphysis, epiphysis
    • Lesion may be osteolytic with periosteal reaction and soft tissue mass
Radiology Images
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Various images

Prognostic Factors
  • Poorer prognosis: Older age, lower performance status, high LDH, advanced stage, bone marrow involvement
Case Reports
Treatment
  • Poor prognosis, but curable
  • Chemotherapy; rituximab improves survival
Micro Description
  • Diffuse growth, rarely focal nodular pattern
  • Areas of necrosis and hemorrhage are usually seen
  • "Starry sky" or "moth eaten" appearance, due to blue neoplastic cells and histiocytes engulfing debris from apoptotic tumor cells
  • Neoplastic cells are motonous, medium sized, with squared-off basophilic cytoplasm, which may be plasmacytoid
  • Nuclei are uniform, round to oval, slightly indented, with coarse chromatin, 2 - 5 small centrally located basophilic nucleuoli
  • Numerous mitotic figures
  • Epithelioid granulomas can be seen especially with EBV+e cases
  • Atypical cytologic features and plasmacytic differentiation seen in HIV+ cases
Micro Images
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Lymph node

Cytology Description
  • Medium sized lymphoid cells with histiocytes interspersed
  • Lymphocytes are uniform in size
  • Cytoplasm is deeply basophilic, non granular, contains small vacuoles corresponding to lipid droplets
  • Nuclei are slightly indented with distinct small nucleoli, coarse chromatin and mitoses
Cytology Images
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Site unspecified

Peripheral Smear Description
  • Medium sized cells with basophilic vacuolated cytoplasm and indented nuclei
Positive Stains
  • Mature B cell markers: CD20, CD19, CD22, CD79a
  • IgM
  • Germinal center markers: CD10, BCL6
  • CD21 (receptor for C3d component of human complement and EBV) in endemic cases
  • Ki67 is > 95% positive
Negative Stains
Electron Microscopy Description
  • Rounded to slightly indented nucleus
  • Prominent multiple nucleoli
  • Endoplasmic reticulum and golgi apparatus are poorly developed
  • Mitochondria are few and grouped into pole of cell
Molecular / Cytogenetics Description
  • MYC translocations
    • t(8;14)
    • Other non Immunoglobulin translocations involving MYC gene are t(8;9) and t(3;8)
  • EBV EBER detected by FISH, depending on type of BL
  • BL Gene Expression Profiling
    • An accurate, quantitative method for distinguishing Burkitt lymphoma from diffuse large B cell lymphoma
    • High level of expression of c-myc target genes, the expression of a subgroup of germinal center B cell genes and the low level of expression of major histocompatibility complex class I genes and nuclear factor kappaB target genes (N Engl J Med 2006;354:2431)
Molecular / Cytogenetics Images
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3 translocations

Translocation of c-Myc gene

Differential Diagnosis
  • Lymphoid tumors
    • Lymphoblastic lymphoma:
      • Intermediate cells with starry sky pattern, leukemic pattern of infiltration with crush artifact, scanty to barely visible cytoplasm, round or convoluted nuclei, fine dusty chromatin, inconspicuous nucleoli, 90% are T cell phenotype and TdT+, 10% are B cell phenotype with BCL6− and variable CD10
    • Diffuse Large B cell lymphoma:
      • Large cells, mainly centroblastic and immunoblastic
      • BCL2+, Ki67 proliferation index < 90%, negative MYC rearrangement; BCL2 or BCL6 rearrangement are features favoring DLBCL
    • Myeloid sarcoma:
      • Intermediate cells with finely granular cytoplasm, fine chromatin, no starry sky pattern; may show Indian file pattern, clue is admixed immature eosinophils, CD43+, MPO+, CD15+, CD68+, MYC translocation negative
    • Other small cell lymphomas affecting bone
  • Round blue cell tumors of bone: all lack immunoreactivity to lymphoid markers
  • Osteosarcoma, small cell variant: osteoid is present
  • Mesenchymal chondrosarcoma: foci of chondroid differentiation, S100+
  • Metastatic small cell carcinoma: CK+, neuroendocrine markers+
  • Myeloma may arise in jaw
  • Odontogenic tumors