B-cell Lymphoma Unclassifiable With Features Intermediate Btw DLBCL And CHL

Question 1

What is the definition of B cell lymphoma unclassifiable (grey zone lymphoma, GZL) ?

Answer 1

• shows overlapping clinical, morphological and immunophenotypic features between CHL and DLBCL (particularly primary mediastinal large B)
• lymphomas are most often seen in the mediastinum (Grey-zone lymphoma)
  
  • have been reported in peripheral lymph nodes

Question 2

What is the epidemiology of GZL ?

Answer 2

• most common in young men (20-40 years)

* rare in children and the elderly

Question 3

What is the etiology of GZL ?

Answer 3

• unknown

- genetic studies show it has similarities to CHL and primary mediastinal large B cell lymphoma

Question 4

What sites can be involved by GZL ?

Answer 4

• usually a large anterior mediastinal mass with/without supraclavicular lymphadenopathy
• peripheral and intra-abdominal LN are rarely involved
• spread to the lung (via direct extension) as well as liver, spleen and bone marrow has been described

Question 5

What are the clinical features of GZL ?

Answer 5

• bulky mediastinal masses
• non-mediastinal often seen in older patients with less of a male predominance
• sometimes there is sequential development of CHL and primary mediastinal large B
  
  • IMP: usually CHL is the initial presentation followed by PMLB

Question 6

What are the microscopic features of GZL ?

Answer 6

• broad morphological spectrum, some cases resemble CHL and other PMLB (varies within the mass itself)
  IMP:
  
  • discordance between morphology and IHC is common in these lesions
• will have sheet like growth with fibrotic stroma most often
  -fibrous bands can also be seen
• cells are larger and more pleomorphic than primary mediastinal large B
• Necrosis is frequent but unlike CHL necrotic areas do not contain neutrophilic infiltrates

Question 7

What is the immunophenotype of GZL ?

Answer 7

• it is an aberrant immunophenotype based on the morphology
• Positive:
  
  • CD45, CD20, CD79a, CD30, CD15 (sometimes)
  • sometimes can have loss of B cell antigens and positive for CD15 and CD30
  • transcription factors usually positive: Pax5, OCT2, BOB1
  • BCL6 variable
• Negative
  
  • CD10 usually
  • ALK
• background lymphocytes, CD3 and CD4+, like in CHL

Question 8

What is the expression pattern of MAL in GZL ?

Answer 8

• MAL is a marker often seen in primary mediastinal large B cell lymphoma
• expressed in at least a subset of GZL

Question 9

Is GZL positive for EBV?

Answer 9

• no it should be negative

- if positive, especially in an elderly patient, it should prompt suspicion of an EBV DLBCL

Question 10

What is the postulated normal counterpart of GZL ?

Answer 10

• thymic B cell

Question 11

What is the genetic profile of GZL ?

Answer 11

• many of the genetic aberrations are similar to those seen in PMLB
• > 50% of cases have gains and amplification of JAK2 and PDCD1LG2 loci at 9p24.1
  • seen more in the mediastinal cases
  • increased expression of PD-L1 (CD274) occurs as a result
• Gains in MYC have been observed in 20-30% of cases

Question 12

What is the prognosis and predictive factors of patients with GZL ?

Answer 12

• poor outcome when compared to CHL and PMLBs
• more aggressive clinical course
• multimodal therapy including radiation to the mass
• a decrease in the absolute lymphocyte count (like in CHL) is associated with worse outcome