Pediatric-type Follicular Lymphoma

Question 1

What diagnosis are excluded from the category of

Pediatric type FL ?

Answer 1

• testicular FL
• Large B cell lymphoma with IRF4 rearrangement
  
  • these can often have partial or complete follicular growth pattern
• DLBCL

Question 2

What is the definition of pediatric follicular lymphoma ?

Answer 2

• uncommon, nodal FL that occurs primarily in children
  
  • can sporadically occur in older individuals but should not be used for cases of DLBCL
• usually involves LN of the head and neck and is stage I disease
• cytologically the lesions appear high grade with high proliferation rates
• usual translocations of other B cell lymphomas are absent (ie those of BCL2 and BCL6)

Question 3

What is the epidemiology of this disease?

Answer 3

• no known risk factors and no known associations with immunodeficiency or autoimmune disease
• most patients are aged 5-25 years old
• marked male predominance
  
  • M > F 10:1

Question 4

What is the localization of the disease ?

Answer 4

• enlarged lymph nodes in the head and neck region
• inguinal and femoral lymph nodes are less often the presenting site

IMP:

• virtually all patients present with isolated peripheral lymphadenopathy without involvement of paraortic or mesenteric lymph nodes

Question 5

What are the pertinent clinical findings ?

Answer 5

• isolated, asymptomatic lymph node enlargement
• occasional cases of FL have shown more extensive involvement and focal disease progression to DLBCL
  
  • However, it is thought that these reported cases were mis-classified as pediatric type FL
  • the nature of this diseases does not typically follow such a course

Question 6

What are the key staging features of this disease ?

Answer 6

• usually single site of lymph node enlargement
• bone marrow involvement has not been reported
• B symptoms such as fever and weight loss are absent

Question 7

What are the microscopic findings of

lymph nodes with this lymphoma ?

Answer 7

• partial or complete LN architectural loss
• large expansile follicles with serpiginous growth pattern
• partial involvement of the LN can be seen
• low power
  
  • starry sky pattern
  • thin or absent mantle zones
• evidence of marginal zone differentiation can be see peripheral to the neoplastic follicles
• the cells are typically blastoid and lack prominent nucleoli
  
  • mitotic figures are readily identifiable
  • some areas contain more centroblasts

Question 8

What is the grade of typical Pediatric-type FL ?

Answer 8

• typically cases have been reported out as grade 3A or 3B
• BUT
  
  • grading is not typically used as would be seen in usual follicular lymphoma

Question 9

What is the typical immunophenotype of

this lymphoma?

Answer 9

• mature B cells
  
  • (+) for CD20, CD79a, and Pax-5
  • (+) CD10 (strong) and BCL6
• IMP: BCL2 is negative or at best shows weak staining
• moderate to high proliferation index >30%
• CD21 and CD23 shows intact follicular dendritic cells
• IgD is negative in the absent or attenuated mantle cell cuffs
• MUM/IRF4
  
  • negative
  • if positive raises the possibility of Large B with IRF4 rearrangement

Question 10

Should you see an abundance of plasma cells

in pediatric-type FL ?

Answer 10

• No plasma cells should be sparse
• If there are abundant plasma cells it raises the possibility of a reactive follicular hyperplasia

Question 11

What is a potential pitfall by flow cytometry?

Answer 11

• In pediatric type follicular lymphoma usually a CD10+ CD5(-) clonal B cell population is identified
• BUT
  
  • rare cases of florid follicular hyperplasia in young boys can have small, clonal population of CD10 positive B cells that end up being monoclonal by IG rearrangement studies.

Question 12

What is the genetic profile for pediatric

type FL ?

Answer 12

• PCR detects IG gene rearrangments
  
  • helps rule out most follicular hyperplasia but not all
• No aberrations of
  
  • BCL2, BCL6 or IRF4 loci are detected
• No mutations of
  
  • KMT2D, CREBBP and EZH2 genes are detected
  • These are often seen in usual FL
• Negative for BCL2 gene rearrangement

Question 13

What are the most common genetic

changes in pediatric follicular lymphoma ?

Answer 13

• deletion at 1p36 and deletions or mutations affecting TNFRSF14
• IMP: MAP2K1 mutations are identified in approximately 40-50% of cases

Question 14

What is the prognosis of patients with pediatric

FL ?

Answer 14

• most patients with localized disease do not require radiation or chemotherapy
• IMP
  
  • areas of DLBCL exclude the diagnosis of pediatric type FL
  • diagnosis should be made with caution in patients that are >25 years of age
    
    • correlation with clinical features is essential in older individuals