Large B cell Lymphoma with IRF4 Rearrangement

Question 1

What is the definition of

this entity ?

Answer 1

• uncommon subtype of large B cell lympoma
• usually in children and young adults
• head and neck region, Waldeyer’s ring
• strong expression of IRF4/MUM1
  
  • usually with the IRF4 rearrangement
• can have a variable growth pattern
  
  • entirely diffuse
  • diffuse and follicular
  • entirely follicular
• IMP:
  
  • this entity is separate from pediatric FL

Question 2

What is the epidemiology of this lymphoma ?

Answer 2

• very rare, accounts for <0.05% of diffuse large B cell lymphomas
• patient age range is 4-79 years old
  
  • median age of 12
  • equal sex distribution
  • rare in adults

Question 3

What is the typical location of this large cell lymphoma ?

Answer 3

• head and neck
• Waldeyer’s ring
• gastrointestinal tract

Question 4

What is the typical clinical presentation ?

Answer 4

• isolated lymph node enlargement
• tonsillar enlargement (stage I-II)

Question 5

What are the key microscopic features of

large cell lymphoma with IRF4 rearrangement ?

Answer 5

• cells are medium to large in size with more open chromatin
  
  • centrocyte like but with small, basophilic nucleoli
• mitotic figures are infrequent and starry sky pattern is not seen
• when there is a follicular pattern
  
  • no serpiginous growth is seen
  • follicles are back to back with attenuated mantle zones
• many cases have a diffuse growth pattern

Question 6

What is the immunophenotype of

this large cell lymphoma ?

Answer 6

• mature B cell phenotype
  
  • (+) CD20, CD79a, and Pax-5
• IMP:
  
  • IRF4/MUM1 is typically strongly expressed
  • BCL6 is also positive
• 66% of cases are positive for CD10 and BCL2
• High proliferation index
• IMP
  
  • cass with CD10, BCL6 and IRF4/MUM1 should be screened for IRF4 rearrangments

Question 7

What is the normal counterpart

for this lymphoma ?

Answer 7

• germinal centre B cell with IRF4 rearrangement causing MUM1 expression

Question 8

What is the genetic profile of the entity ?

Answer 8

• Immunoglobulin genes are clonally rearranged
• Cryptic gene rearrangement usually identified
  
  • IRF4 with IGH locus
    
    • Break apart probe by FISH
  • light chains are rarely ever involved in the translocation
  • rarely current techniques may not detect IRF4 translocation but will pick up the IGH rearrangement
• BCL6 locus breakpoints may be seen in some cases
• IMP
  
  • MYC and BCL2 rearrangments cannot be present

Question 9

What is the gene expression profile of this

lymphoma ?

Answer 9

• most cases are found to be germinal center in origin but their gene signature is different from both germinal centre B cells and activated B cells
• they often show a complex pattern of genetic changes including loss of TP53
  • not likely to be a predictor of clinical behavior

Question 10

What are the prognostic and predictive factors

of large cell lymphoma with IRF4 rearrangement ?

Answer 10

• patients have favorable outcome after treatment
  
  • combination of chemotherapy with or without radiation
• this is in contrast to pediatric type FL where local treatment is usually all that is needed.