Burkitt's lymphoma pathophysiology

Burkitt's lymphoma Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Burkitt's lymphoma from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study Of Choice
Staging
History and Symptoms
Physical Examination
Laboratory Findings
X Ray Findings
CT
MRI
Biopsy
Other Imaging Studies
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Burkitt's lymphoma pathophysiology On the Web
Most recent articles
cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Burkitt's lymphoma pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Burkitt's lymphoma pathophysiology
CDC on Burkitt's lymphoma pathophysiology
Burkitt's lymphoma pathophysiology in the news
Blogs on Burkitt's lymphoma pathophysiology
Directions to Hospitals Treating Burkitt's lymphoma
Risk calculators and risk factors for Burkitt's lymphoma pathophysiology

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]

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 the following B cells :
  • 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 (CD19, CD20, CD22), CD10, and 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. 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

Burkitt lymphoma, touch prep, wright stain

Video

{{#ev:youtube|CwsQ-wIbbK8}}

References

Template:WikiDoc Sources