Table 2.

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

Entity/category	Change
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 leukemia	• BRAF 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 lymphoma	• TCF3 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.