Info

🌱 來自：Diffuse large B-cell lymphoma

Genetics and Molecular Subtypes of Diffuse large B-cell lymphoma

• DNA expression analysis identifies three distinct subtypes:

  • germinal-center B-cell type (GCB),
  • activated B-cell type (ABC or non-GBC subtype),
  • & type 3 DLBCL (NEJM 2002;346:1937; Nature 2000;403:503).
  • ABC phenotype a/w older age, worse prognosis

• Immunohistochemical algorithms of DLBCL can be used in lieu of GEP classifying cases into GCB & non-GCB (w/o unclassifiable; Figure 23-1) (Blood 2004;103:275)

  • 👉 Immunohistochemical algorithms of Diffuse large B-cell lymphoma

• High-grade B-cell lymphoma w/ MYC & BCL2 &/or BCL6 translocations by FISH (formerly “double-hit in DLBCL”) represent ∼8% of all DLBCL & have poorer prog.

  • Almost always GCB.
  • IHC detected double expressors (MYC >40% BCL2 >70%) may be assoc w/ ↓ prog (JCO 2012;30:3460).
  • Burkitt typically BCL-2(−) vs. DLBCL nearly always BCL2(+)

• t(14:18) occurs in ∼30% of DLBCLs (common in follicular lymphoma); juxtaposes BCL-2 gene to the IgH gene. BCL-2+ IHC may be seen w/ or w/o this translocation

Pathology Evaluation

“Double-hit” – Double-hit lymphoma is a colloquial term for high-grade B cell lymphoma MYC and BCL2 and/or BCL6 rearrangements, which is a distinct category of aggressive lymphoma in the World Health Organization (WHO) classification [1] and the International Consensus Classification [2]. This is not a type of DLBCL, per se, and although it can resemble DLBCL histologically, it is associated with inferior prognosis and requires distinctive treatment, as described below. (See ‘High-grade lymphoma with rearrangements of MYC plus BCL2 and/or BCL6 (“double-hit”)’ below.)

Double-hit status is determined by fluorescence in situ hybridization (FISH). Immunohistochemistry (IHC) is not an acceptable alternative to FISH, as IHC can detect double expressor status (ie, expression of MYC, BCL2, and/or BCL6) but not double-hit status (ie, rearrangements of those genes). (See “Prognosis of diffuse large B cell lymphoma”, section on ‘MYC, BCL2, BCL6 abnormalities’.)

•Cell of origin (COO) – COO status is determined using an IHC algorithm (figure 1). COO status can also be assessed with the LymphCx platform, but this is less-widely available. (See “Prognosis of diffuse large B cell lymphoma”, section on ‘Cell of origin studies’.)

We assign COO as:

-Germinal center B cell (GCB) DLBCL – GCB status is generally associated with more favorable prognosis.

-Non-GCB DLBCL – Cases with non-GCB status generally have higher rates of relapse and a less favorable prognosis.

COO status does not influence the choice of initial treatment for advanced stage DLBCL.

Hans and Tally 汗濕和他瀝

• 

• 尚方寶劍：CD10; 二審：BCL6; MUM1: 丹書鐵卷

• 1. Measure GCB markers: CD10 (+ or -)and GCET1 (+ or -)
• 2. Measure ABC markers: MUM1 (+ or -)and FOxP1 (+ or -) (For each of the above, score 1 point for •+” and O points for ”-”)
• 3. Compare GCB score versus ABC score:

• i GCB >ABC, then dassify as GCB

• if GCB <ABC, then dassify as ABC

• if GCB = ABC, then measure LMO2:

  • if LMO2 ≥30%, then dassify as GCB
  • if LMO2 <30%, then dassify as ABC

References

• Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103:275.
• Meyer PN, Fu K, Greiner TC, et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B cell lymphoma treated with rituximab. J Clin Oncol 2011; 29:200.