Hodgkin Lymphomas and Large B cell Lymphomas

Question 1

What is a basic IHC panel for CHL?

Answer 1

• CD3, CD20, Pax5, CD30, CD15, CD45, MUM1 and EBER-ISH

Question 2

If a strong B cell program is seen in CHL what should your differential diagnosis be?

Answer 2

• Strong B cell program/expression includes: CD20 strong and uniform, Pax5 strong, CD79a positive, OCT/BOB1 positive
• exclude: NLPHL, Gray Zone Lymphoma, PMBL, EBV+ DLBCL

Question 3

What additional markers may be performed to evaluate CHL?

Answer 3

• ALK - to exclude an ALCL
• EBER
• CD45

Question 4

Can MUM1 be helpful in identifying CHL?

Answer 4

• yes and no
• relatively non-specific marker and can be positive in a range of activated cell types and lymphomas of B and T cell origin such as ALCL, CHL, and plasma cell neoplasms
• BUT it should always be positive in HRS cells

Question 5

What are some pitfalls with T cell antigens in the diagnosis of CHL?

Answer 5

• HRS cells may be positive some T cells antigens, particularly CD4 and CD2 and less often CD3 in a subset of cases
• these cells should be negative for any T cell receptor gene rearrangements
• expression of T cell antigens shows a worse overall survival

Question 6

Expression of Pax5 in HRS cells of CHL is critically in the setting of aberrant T cell antigen expression. What is a pitfall of Pax5?

Answer 6

• ALCL is the main differential in this setting as it can express CD2, CD4 and typically lacks CD3
• BUT remember, rarely T cell lymphomas may express Pax5 due to amplification of Pax5

Question 7

If the differential diagnosis is between CHL and NLPHL, what additional IHC markers may be helpful?

Answer 7

• OCT2, BOB1, PD-1, CD57, and IgD

Question 8

What is the morphologic d/d of CHL?

Answer 8

• DLBCL, esp EBV related
• PMBCL
• NLPHL
• ALCL

Question 9

What does EBER in situ hybridization test for?

Answer 9

• it looks for non-coding RNA EBER
• this is typically present in all viral latency states

IMP: should be positive in the large cells

Question 10

What is EBV LMP1?

Answer 10

• this is an EBV gene product
• often seen in EBV+ CHL
• it is a transforming protein that can confer a growth advantage to HRS cells by activating NF-Kappa B, JAK/STAT, and PI3K/AKT pathways

Question 11

What is the differential diagnosis if you have EBV+ small lymphocytes and HRS-like scattered cells?

Answer 11

• Hodgkin-like LPD:
  
  • associated with immune deficiency
  • EBV+ DLBCL
  • Primary EBV infection (mono)

Question 12

Cyclin D1 expression may be seen in what cells sometimes?

Answer 12

• LP cells of NLPHL
• large cells of THRLBCL

Question 13

How can the T cell populations be helpful in distinguishing NLPHL from THRLBCL?

Answer 13

• NLPHL: T cells are CD4 positive with a germinal center phenotype with very rare CD8+ T cells
  *also increased #s of double CD4/CD8+ T cells can be seen in 50% of cases

-THRLBCL contains more CD8+ T cells

Question 14

What is the differential diagnosis for NLPHL?

Answer 14

• CHL, particularly lymphocyte rich
• TCHRLBCL
• EBV+ DLBCL (if EBV+)

Question 15

What is the differential diagnosis for TCHRLBCL?

Answer 15

• NLPHL
• If there is any EBV+
  
  • Infectious mononucleosis
  • EBV+ DLBCL
  • EBV mucocutaneous ulcer
• Carcinoma!!
  *undifferentiated sinonasal nasopharyngeal carcinoma

Question 16

What is the immunophenotype of the B immunoblasts that may be proliferating in acute EBV infection (mononucleosis)?

Answer 16

• can have HRS like morphology and sheets of immunoblasts
• post-GC phenotype (CD10 & BCL6 negative, MUM1 +)
• polyclonal for cytoplasmic kappa and lambda light chains

Question 17

What are some IHC that can be positive in carcinomas and HRS/hematolymphoid neoplasms?

Answer 17

• CD30
• BCL2
• BCL6
• CD138
• CD5
• CD7
• CD10
• CD15
• CD56

Question 18

What are additional markers that may evaluate whether a large cell lymphoma is from the germinal center or activated B cell subtype?

Answer 18

• Germinal center: CD10, GCET1, and LMO2
• Non-GCB type: MUM1 and FOXP1

Question 19

What cutoff of p53 IHC stain in DLBCL is considered to be clinically significant?

Answer 19

• > 10%
  *but, cases with >50% are more likely to have a TP53 mutation
• IMP: low or absent p53 staining with a high mitotic rate, may also indicate a TP53 mutation

Question 20

What is the main differential diagnosis of primary cutaneous DLBCL leg type?

Answer 20

• Primary follicle center lymphoma
• The DLBCL will show positivity for: BCL2 (strong), MUM1, FOXP1 and overexposes MYC
  *they also lack CD10
  
  • also show cytoplasmic IgM

Question 21

What are some ways that EBV+ DLBCL is different from Lymphomatoid granulomatosis?

Answer 21

• DLBCL patients will have an elevated EBV viral load as compared to those with LYG
• DLBCL may have sheets of EBV+ cells, but this is not a feature of LYG
• LYG is more likely to show angioinvasion and angiodestruction