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. |
| 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. |