ASCO 2017 | Understanding the Revised 4th Edition WHO Classification of Lymphoid Malignancies – Educational Session 

At the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, an educational session on “Understanding the New World Health Organization Classification of Lymphoid Malignancies”. The session, chaired by Sonali Smith of the University of Chicago, consisted of three parts: describing what has changed since the 2008 classification was published, how the new classification impacts histopathologic evaluation and treatment decisions, and the impact on clinical trials.

Elaine Jaffe, from the National Cancer Institute Center for Cancer Research, Bethesda,  explained during the first talk that the main reasoning for this new “Revised 4th Edition WHO Classification” was the large advances in understanding and diagnosis of lymphoid malignancies. The presentation was structured in three parts: what’s new in early lesions, what’s new in B-cell lymphomas, and what’s new in Peripheral T-Cell Lymphomas.

Early Lesions:

• The main change highlighted here was the renaming of Follicular Lymphoma in situ (FLIS) and Mantle Cell Lymphoma in situ to in situ follicular neoplasia and in situ mantle cell neoplasia
• Rationale: This change is to reflect data which shows that, in the case of FL, 70% of adults over age 50 have BCL2/IGHV mutations which increase with age; however, there is a low risk of progression from FL in situ to FL of <5%. Due to this data, no therapeutic intervention is required

B-Cell Lymphoma:

• The main changes highlighted in this section were:
  • High-grade BCL with MYC rearrangement and either BCL2 or BCL6 rearrangements to be classified first by molecular pathology, and then morphology to identify the high-risk double- and triple-hit lymphoma patients
  • DLBCL, NOS (Not Otherwise Specified) to be classified as either a GCB or an ABC type
  • Cases with blastoid features are now included in high-grade B-cell lymphoma, NOS
• Rationale:
  • DHL has a poor prognosis that is worse than DEL (Double Expressor Lymphoma; MYC >40% and BCL2 >50% by IHC) and DHL cases are almost always GCB whereas DEL are ABC by gene expression profiling and IHC. This was discussed during another Education session at 2017 ASCO Annual Meeting, also covered by the Lymphoma Hub. ABC types are also typically MUM1+ (>30% expression in nucleus)
  • DEL’s poor prognosis compared with non-DEL DLBCL may relate to ABC category, so it’s important not to categorize DEL and DHL together
• Guidelines for diagnosis of DHL or THL in DLBCL:
  • FISH to detect MYC rearrangement and BCL2 is recommended but not required as it’s important to use what means are available most commonly IHC

Peripheral T-Cell Lymphoma:

• ALK- ALCL (Anaplastic Large Cell Lymphoma) is now a recognized entity whose prognostic outcome is between ALK+ ALCL and PTCL
• GEP can result in the reclassification of 14% of PTCL, NOS patients to Angio-Immunoblastic T-Cell Lymphoma (AITL)
• IDH2 is the most specific mutation associated with AITL, with TET2, RHOA, and DNMT3A mutations and ITK-SYK translocations being common to AITL and TFH derived lymphomas

Dr. Jaffe stated that it is hoped that the full new revised 4th edition WHO classification for lymphoid malignancies will be published in 2017, with summaries already being available (Swerdlow et al. Blood 2016, Arber et al. Blood 2016).

During the questions section at the end of this session it was asked how DEL should be classified. Dr. Jaffe replied that although most DHL are going to be DEL, the DEL term should only include tumors that do not have DHL mutations as described, otherwise you would be mixing two different biological entities. Dr. Jaffe also reiterated that DEL tends to not be in GCB samples based on IHC, and that it is worth remembering that DEL is not a recognized subtype under the WHO classification, but is rather an “observational phenomenon” in more aggressive disease.

The second part of this session was presented by Prof. Paul Barr and an interview with Prof. Paul Barr on this subject can be found here.