Burkitt's lymphoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Shivali Marketkar, M.B.B.S. [2] Sowminya Arikapudi, M.B,B.S. [3], Kamal Akbar, M.D.[4]

Overview

The c-myc gene is involved in the pathogenesis of Burkitt's lymphoma. On gross pathology, ulceration and discharge are characteristic findings of Burkitt's lymphoma. On microscopic histopathological analysis, "starry sky" appearance is a characteristic finding of Burkitt's lymphoma.

Pathology

Burkitt's lymphoma is an aggressive and rapidly growing tumor.. It can present in a wide variety of locations which include:

• Head and neck (facial bones and Waldeyer's ring)
• Pleural space (~70%)
• Gastrointestinal tract, especially ileocaecal region
• Mesentery, peritoneum, and retroperitoneum
• Kidneys
• Gonads (~75%)

Genetics

Translocation of chromosome 8 myc locus with 3 possible partners (accounting for 90% of translocations):

• The Ig heavy chain region on chromosome 14: t(8;14)
• The kappa light chain locus on chromosome 2: t(2;8)
• The lambda light chain locus on chromosome 22: t(8;22)
• WHO committees suggest the following:

• If morphologic features are intermediate, diagnosis of Burkitt's should only be made if the Ki-67 fraction of viable cells is at least 99 percent
• If morphologic features suggest diffuse large B cell lymphoma, but have with a high proliferation fraction or t(8;14), they should be classified as diffuse large B cell lymphoma

Gene targets

• Unique genetic alterations promote cell survival in Burkitt's lymphoma, distinct from other types of lymphoma
• These TCF3 and ID3 gene mutations in Burkitt's correspond to a cell survival pathway that may be found to be amenable to targeted therapy.

MicroRNA expression

• In 2014, it was described that short non-coding RNAs named microRNAs (miRNAs) have important functions in lymphoma biology
• In malignant B cells miRNAs participate in pathways fundamental to B cell development like B cell receptor (BCR) signaling, B cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of immunoglobulins
• MiRNAs influences B cells in the following manner:
  • Maturation
  • Generation of marginal zone
  • Follicular
  • Plasma
  • Memory B cells

Immunohistochemistry

The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation and they are the following:

• (CD19
• CD20
• CD22)
• CD10
• BCL6
• The tumor cells are generally negative for BCL2 and TdT. The high mitotic activity of Burkitt's lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.

Malignant B cell characteristics

Malignant B cells have identical DNA recombinations of the V(D)J region of the immunoglobin genes and there characteristics are the following:

• This means that no increase in specificity of antibody molecules is occurring in the malignant cells
• These malignant cells are thus clonal populations and can be assayed for by using DNA probes specific for the regions where recombination is expected
• Normal DNA will be characterized by two high concentration of identical germ line DNA V(D)J regions and endless, likely undetectable, non-germline Ig V(D)J DNA
• Lymphoma cells have an additional high concentration of V(D)J DNA that is unlike the germ line, indicating clonal populations of B Cells that are not undifferentiated B cells (germ line DNA cells)
• Assays typically use the process of electrophoresis and southern blot analysis to determine the existence of these characteristics

Gross Pathology

• 

  Seven-year-old Nigerian boy with a several-month history of jaw swelling which had been treated with antibiotics: The tumor was ulcerated and draining

• 

  Picture of a mouth of a patient with Burkitt lymphoma showing disruption of teeth and partial obstruction of airway

Microscopic Pathology

On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:

• Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells)
• Round nucleus
• Small nucleoli
• Relatively abundant cytoplasm (basophilic)
• Brisk mitotic rate and apoptotic activity
• Cellular outline usually appears squared off
• "Starry-sky pattern":

• The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells)

• The tumour cells are the sky

Video

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References

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