Table 2

Highlights of changes in 2016 WHO classification of lymphoid, histiocytic, and dendritic neoplasms

Entity/categoryChange
CLL/SLL• Cytopenias or disease-related symptoms are now insufficient to make a diagnosis of CLL with <5 × 109/L PB CLL cells.
• Large/confluent and/or highly proliferative proliferation centers are adverse prognostic indicators.
• Mutations of potential clinical relevance, such as TP53, NOTCH1, SF3B1, ATM, and BIRC3, have been recognized.
Monoclonal B-cell lymphocytosis• Must distinguish low-count from high-count MBL.
• A lymph node equivalent of MBL exists.
Hairy cell leukemiaBRAF V600E mutations in vast majority of cases with MAP2K1 mutations in most cases that use IGHV4-34 and lack BRAF mutation.
Lymphoplasmacytic lymphoma (LPL)MYD88 L265P mutation in vast majority of cases impacting diagnostic criteria even though finding is not specific for LPL.
• IgM MGUS is more closely related to LPL and other B-cell lymphomas than to myeloma.
Follicular lymphoma (FL)• Mutational landscape better understood but clinical impact remains to be determined.
In situ follicular neoplasia• New name for in situ follicular lymphoma reflects low risk of progression to lymphoma.
Pediatric-type FL• A localized clonal proliferation with excellent prognosis; conservative therapeutic approach may be sufficient.
• Occurs in children and young adults, rarely in older individuals.
Large B-cell lymphoma with IRF4 rearrangement• New provisional entity to distinguish from pediatric-type FL and other DLBCL.
• Localized disease, often involves cervical lymph nodes or Waldeyer ring.
Duodenal-type FL• Localized process with low risk for dissemination.
Predominantly diffuse FL with 1p36 deletion• Accounts for some cases of diffuse FL, lacks BCL2 rearrangement; presents as localized mass, often inguinal.
Mantle cell lymphoma (MCL)• Two MCL subtypes recognized with different clinicopathological manifestations and molecular pathogenetic pathways: one largely with unmutated/minimally mutated IGHV and mostly SOX11+ and the other largely with mutated IGHV and mostly SOX11 (indolent leukemic nonnodal MCL with PB, bone marrow (BM), ±splenic involvement, may become more aggressive).
• Mutations of potential clinical importance, such as TP53, NOTCH 1/2, recognized in small proportion of cases.
CCND2 rearrangements in approximately half of cyclin D1 MCL.
In situ mantle cell neoplasia• New name for in situ MCL, reflecting low clinical risk.
Diffuse large B-cell lymphoma, NOS• Distinction of GCB vs ABC/non-GC type required with use of immunohistochemical algorithm acceptable, may affect therapy.
• Coexpression of MYC and BCL2 considered new prognostic marker (double-expressor lymphoma).
• Mutational landscape better understood but clinical impact remains to be determined.
EBV+ DLBCL, NOS• This term replaces EBV+ DLBCL of the elderly because it may occur in younger patients.
• Does not include EBV+ B-cell lymphomas that can be given a more specific diagnosis.
EBV+ mucocutaneous ulcer• Newly recognized entity associated with iatrogenic immunosuppression or age-related immunosenescence.
Burkitt lymphomaTCF3 or ID3 mutations in up to ∼70% of cases.
Burkitt-like lymphoma with 11q aberration• New provisional entity that closely resembles Burkitt lymphoma but lacks MYC rearrangement and has some other distinctive features.
High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations• New category for all “double-/triple-hit” lymphomas other than FL or lymphoblastic lymphomas.
High-grade B-cell lymphoma, NOS• Together with the new category for the “double-/triple-hit” lymphomas, replaces the 2008 category of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU).
• Includes blastoid-appearing large B-cell lymphomas and cases lacking MYC and BCL2 or BCL6 translocations that would formerly have been called BCLU.
T-cell large granular lymphocyte leukemia• New subtypes recognized with clinicopathologic associations.
STAT3 and STAT5B mutations in a subset, latter associated with more clinically aggressive disease.
Systemic EBV+ T-cell lymphoma of childhood• Name changed from lymphoproliferative disorder to lymphoma due to its fulminant clinical course and desire to clearly distinguish it from chronic active EBV infection.
Hydroa vacciniforme–like lymphoproliferative disorder• Name changed from lymphoma to lymphoproliferative disorder due to its relationship with chronic active EBV infection and a spectrum in terms of its clinical course.
Enteropathy-associated T-cell lymphoma (EATL)• Diagnosis only to be used for cases formerly known as type I EATL, typically associated with celiac disease.
Monomorphic epitheliotropic intestinal T-cell lymphoma• Formerly type II EATL; segregated from type I EATL and given a new name due to its distinctive nature and lack of association with celiac disease.
Indolent T-cell lymphoproliferative disorder of the GI tract• New indolent provisional entity with superficial monoclonal intestinal T-cell infiltrate, some cases show progression.
Lymphomatoid papulosis• New subtypes described with similar clinical behavior but atypical histologic/immunophenotypic features.
Primary cutaneous γ δ T-cell lymphoma• Important to exclude other cutaneous T-cell lymphomas/lymphoproliferative disorders that may also be derived from γ δ T cells such as mycosis fungoides or lymphomatoid papulosis.
Primary cutaneous acral CD8+ T-cell lymphoma• New indolent provisional entity, originally described as originating in the ear.
Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder• No longer to be diagnosed as an overt lymphoma due to limited clinical risk, localized disease, and similarity to clonal drug reactions.
• Remains a provisional entity.
Peripheral T-cell lymphoma (PTCL), NOS• Subsets based on phenotype and molecular abnormalities being recognized that may have clinical implications but are mostly not a part of routine practice at this time.
Nodal T-cell lymphomas with T-follicular helper (TFH) phenotype• An umbrella category created to highlight the spectrum of nodal lymphomas with a TFH phenotype including angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, and other nodal PTCL with a TFH phenotype (specific diagnoses to be used due to clinicopathologic differences).
• Overlapping recurrent molecular/cytogenetic abnormalities recognized that potentially could impact therapy.
ALK anaplastic large-cell lymphoma• Now a definite entity that includes cytogenetic subsets that appear to have prognostic implications (eg, 6p25 rearrangments at IRF4/DUSP22 locus).
Breast implant–associated anaplastic large cell lymphoma• New provisional entity distinguished from other ALK ALCL; noninvasive disease associated with excellent outcome.
Nodular lymphocyte–predominant Hodgkin lymphoma• Variant growth patterns, if present, should be noted in diagnostic report, due to their clinicopathologic associations.
• Cases associated with synchronous or subsequent sites that are indistinguishable from T-cell histiocyte-rich large B-cell lymphoma (THRLBCL) without a nodular component should be designated THRLBCL-like transformation.
Lymphocyte-rich classical Hodgkin lymphoma• Features recognized that are intermediate between NLPHL and other types of classical Hodgkin lymphoma.
Erdheim-Chester disease• Should be distinguished from other members of the juvenile xanthogranuloma family; often associated with BRAF mutations.
Other histiocytic/dendritic neoplasms• Clonal relationship to lymphoid neoplasms recognized in some cases.