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From www.bloodjournal.org by guest on March 17, 2016. For personal use only.
Prepublished online March 15, 2016; doi:10.11...
2008 WHO Lymphoma classification
Follicular lymphoma
Pediatric follicular lymphoma*
Primary cutaneous follicle centre lymp...
What prompted the change ……….
• NGS
• New clinical, pathological and genetic/molecular data concerning the
“small B-cell” ...
2016 WHO classification of Lymphoma
• MATURE B-CELL NEOPLASMS
• Chronic lymphocytic leukemia /small lymphocytic lymphoma
•...
• MATURE T-AND NK-NEOPLASMS
• T-cell prolymphocytic leukemia
• T-cell large granular lymphocytic leukemia
• Chronic lympho...
In situ Follicular Neoplasm(ISFN)
• Preserved tissue architecture and confined to the germinal centers,
without evidence o...
Pediatric FL
• large expansile highly proliferative follicles with prominent blastoid
follicular center cells
• BCL2 rearr...
Large B-cell lymphoma with IRF4
rearrangement
• Around Waldeyer ring and/or cervical lymph nodes and low stage.
• follicul...
Duodenal-type FL
• localized overt low grade FL, is distinct from other GI tract FL
• Overlap with ISFN and extranodal mar...
Monoclonal B-cell lymphocytosis (MBL)
• The 2008 :monoclonal B-cell populations in the peripheral blood (PB)
of up to 5x10...
CLL/SLL-LN variant of MBL
• lymph node involvement by “SLL”
• No significant rate of progression
• proliferation centers w...
Leukemic non-nodal mantle cell lymphoma
and in situ mantle cell neoplasia (ISMCN)
• IGHV mutated /SOX11
negative /CYCD11+B...
IgM MGUS IgG/IgA MGUS
• Related to LPL/B NHL
• MYD88+ve
• CCXR4 mutation+
• Related to myeloma
• MYD 88-ve
• CCXR4mutation...
Monoclonal immunoglobulin deposition
diseases(MIDD)
• Renal involvement is almost always present
• Renal insufficiency and...
DLBCL NOS
Hans algorithm :CD10,
BCL6 and IRF4/MUM1
Germinal center B-cell type
Activated B-cell type
High grade B-cell lymphoma [HGBL], with
rearrangements of MYC and BCL2 and/or BCL6
• 5-15% of DLBCL, NOS
• “starry sky” ap...
Double Expressed Lymphoma
• MYC protein expression (30-50%) and BCL2 in 20-35%
• cut-off of 40% MYC , >50% for BCL2.
• Mos...
High grade B cell Lymphoma NOS
• intermediate between DLBCL and
BL
• lack a MYC and BCL2 and/or BCL6
rearrangement
•
Indic...
Epstein-Barr virus positive (EBV+) DLBCL NOS
• >50 years old
• worse prognosis than EBV-negative tumors
• in younger patie...
Burkitt-like lymphoma with 11q aberration
• phenotypically and by GEP like BL but which lack MYC
rearrangements.
• chromos...
Follicular T-cell related Lymphoma
• Angioimmunoblastic T-cell lymphoma
• Follicular T-cell lymphoma
• Nodal peripheral T-...
ALCL
CD30+Lymphoma
Alk+ALCL>Alk-ve ALCL>CD30+VE PTCL
JAK-STAT Mutation
Breast implant associated ALCL
• Both saline and silicone filled
implants
• Median interval from implant to the
lymphoma 1...
Indolent T-cell lymphoproliferative disorder (LPD)
of the GI tract and
Primary cutaneous acral CD8+ T-cell lymphoma
• CD8p...
EBV-positive T-cell lymphomas
chronic active EBV-infection (CAEBV)
• Asians, and in indigenous
populations from Central an...
Enteropathy-associated T-cell lymphoma
(EATL)
Type I
• closely linked to celiac disease
• northern European origin
• TCR α...
WHO 2016 lymphoma classification
WHO 2016 lymphoma classification
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WHO 2016 lymphoma classification

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WHO lymphoma classification, Blood,mar 2015

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WHO 2016 lymphoma classification

  1. 1. From www.bloodjournal.org by guest on March 17, 2016. For personal use only. Prepublished online March 15, 2016; doi:10.1182/blood- 2016-01-643569 The 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms Steven H. Swerdlow, Elias Campo, Stefano A. Pileri, Nancy Lee Harris, Harald Stein, Reiner Siebert, Ranjana Advani, Michele Ghielmini, Gilles A. Salles, Andrew D. Zelenetz and Elaine S. Jaffe Dr CK Das, MD
  2. 2. 2008 WHO Lymphoma classification Follicular lymphoma Pediatric follicular lymphoma* Primary cutaneous follicle centre lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma (DLBCL), NOS T-cell/histiocyte rich large B-cell lymphoma Primary DLBCL of the CNS Primary cutaneous DLBCL, leg type EBV-positive DLBCL of the elderly* DLBCL associated with chronic inflammation Lymphomatoid granulomatosis Primary mediastinal (thymic) large B-cell lymphoma Intravascular large B-cell lymphoma ALK-positive large B-cell lymphoma Plasmablastic lymphoma Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease Primary effusion lymphoma Burkitt lymphoma B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma • Mature B-cell neoplasms • Mature T-cell and NK-cell neoplasms T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Chronic lymphoproliferative disorder of NK cells* Aggressive NK-cell leukemia Systemic EBV-positive T-cell lymphoproliferative disease of childhood Hydroa vacciniforme-like lymphoma Adult T-cell leukemia/lymphoma Extranodal NK/T-cell lymphoma, nasal type Enteropathy-associated T-cell lymphoma Hepatosplenic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides Sézary syndrome Primary cutaneous CD30+ T-cell lymphoproliferative disorders Lymphomatoid papulosis Primary cutaneous anaplastic large cell lymphoma Primary cutaneous γδ T-cell lymphoma Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma* Primary cutaneous CD4+ small/medium T-cell lymphoma* Peripheral T-cell lymphoma, NOS Angioimmunoblastic T-cell lymphoma Anaplastic large cell lymphoma, ALK-positive Anaplastic large cell lymphoma, ALK-negative* Hodgkin lymphoma Nodular lymphocyte predominant Hodgkin lymphoma Classical Hodgkin lymphoma Nodular sclerosis classical Hodgkin lymphoma Lymphocyte-rich classical Hodgkin lymphoma Mixed cellularity classical Hodgkin lymphoma Lymphocyte-depleted classical Hodgkin lymphoma Histiocytic and dendritic cell neoplasms Histiocytic sarcoma Langerhans cell histiocytosis Mature B-cell neoplasms Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocytic leukemia Splenic marginal zone lymphoma Hairy cell leukemia Splenic lymphoma/leukemia, unclassifiable* Splenic diffuse red pulp small B-cell lymphoma* Hairy cell leukemia variant* Lymphoplasmacytic lymphoma Waldenström macroglobulinemia Heavy chain diseases α Heavy chain disease γ Heavy chain disease μ Heavy chain disease Plasma cell myeloma Solitary plasmacytoma of bone Extraosseous plasmacytoma Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma) Nodal marginal zone lymphoma Pediatric nodal marginal zone lymphoma*
  3. 3. What prompted the change ………. • NGS • New clinical, pathological and genetic/molecular data concerning the “small B-cell” lymphomas. • Cooperative Multicentric trials
  4. 4. 2016 WHO classification of Lymphoma • MATURE B-CELL NEOPLASMS • Chronic lymphocytic leukemia /small lymphocytic lymphoma • Monoclonal B-cell lymphocytosis* • B-cell prolymphocytic leukemia • Splenic marginal zone lymphoma • Hairy cell leukemia • Splenic B-cell lymphoma/leukemia, unclassifiable • Splenic diffuse red pulp small B-cell lymphoma • Hairy cell leukemia-variant • Lymphoplasmacytic lymphoma • Waldenström macroglobulinemia • Monoclonal gammopathy of undetermined significance (MGUS), IgM* • Mu heavy chain disease • Gamma heavy chain disease • Alpha heavy chain disease • Monoclonal gammopathy of undetermined significance (MGUS), IgG/A* • Plasma cell myeloma • Solitary plasmacytoma of bone • Extraosseous plasmacytoma • Monoclonal immunoglobulin deposition diseases* • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) • Nodal marginal zone lymphoma • Pediatric nodal marginal zone lymphoma • Follicular lymphoma • In situ follicular neoplasia* • Duodenal-type follicular lymphoma* • Pediatric-type follicular lymphoma* • Large B-cell lymphoma with IRF4 rearrangement* • Primary cutaneous follicle center lymphoma • Mantle cell lymphoma • In situ mantle cell neoplasia* • Diffuse large B-cell lymphoma (DLBCL), NOS • Germinal center B-cell type* • Activated B-cell type* • T cell/histiocyte-rich large B-cell lymphoma • Primary DLBCL of the CNS • Primary cutaneous DLBCL, leg type • EBV positive DLBCL, NOS* • EBV+ Mucocutaneous ulcer* • DLBCL associated with chronic inflammation • Lymphomatoid granulomatosis • Primary mediastinal (thymic) large B-cell lymphoma • Intravascular large B-cell lymphoma • ALK positive large B-cell lymphoma • Plasmablastic lymphoma • Primary effusion lymphoma • HHV8 positive DLBCL, NOS* • Burkitt lymphoma • Burkitt-like lymphoma with 11q aberration* • High grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements* • High grade B-cell lymphoma, NOS* • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
  5. 5. • MATURE T-AND NK-NEOPLASMS • T-cell prolymphocytic leukemia • T-cell large granular lymphocytic leukemia • Chronic lymphoproliferative disorder of NK cells • Aggressive NK cell leukemia • Systemic EBV+ T-cell Lymphoma of childhood* • Hydroa vacciniforme-like lymphoproliferative disorder* • Adult T-cell leukemia/lymphoma • Extranodal NK/T-cell lymphoma, nasal type • Enteropathy-associated T-cell lymphoma • Monomorphic epitheliotropic intestinal T-cell lymphoma* • Indolent T-cell lymphoproliferative disorder of the GI tract * • Hepatosplenic T-cell lymphoma • Subcutaneous panniculitis- like T-cell lymphoma • Mycosis fungoides • Sézary syndrome • Primary cutaneous CD30 positive T-cell lymphoproliferative disorders • Lymphomatoid papulosis • Primary cutaneous anaplastic large cell lymphoma • Primary cutaneous gamma-delta T-cell lymphoma • Primary cutaneous CD8 positive aggressive epidermotropic cytotoxic T-cell lymphoma • Primary cutaneous acral CD8+ T-cell lymphoma* Primary cutaneous CD4 positive small/medium T-cell lymphoproliferative disorder* Peripheral T-cell lymphoma, NOS Angioimmunoblastic T-cell lymphoma Follicular T-cell lymphoma* Nodal peripheral T-cell lymphoma with TFH phenotype* Anaplastic large cell lymphoma, ALK positive Anaplastic large cell lymphoma, ALK negative * Breast implant-associated anaplastic large cell lymphoma HODGKIN LYMPHOMA Nodular lymphocyte predominant Hodgkin lymphoma Classical Hodgkin lymphoma Nodular sclerosis classical Hodgkin lymphoma Lymphocyte-rich classical Hodgkin lymphoma Mixed cellularity classical Hodgkin lymphoma Lymphocyte-depleted classical Hodgkin lymphoma POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS (PTLD) Plasmacytic hyperplasia PTLD Infectious mononucleosis PTLD Florid follicular hyperplasia PTLD* Polymorphic PTLD Monomorphic PTLD (B- and T/NK-cell types) Classical Hodgkin lymphoma PTLD HISTIOCYTIC AND DENDRITIC CELL NEOPLASMS Histiocytic sarcoma Langerhans cell histiocytosis Langerhans cell sarcoma Indeterminate dendritic cell tumour Interdigitating dendritic cell sarcoma Follicular dendritic cell sarcoma Fibroblastic reticular cell tumour Disseminated juvenile xanthogranuloma Erdheim/Chester disease
  6. 6. In situ Follicular Neoplasm(ISFN) • Preserved tissue architecture and confined to the germinal centers, without evidence of disseminated disease • low rate of progression, but are more often associated with prior or synchronous overt lymphomas • D/D:partial involvement by FL • ISFN does have fewer chromosomal copy number abnormalities than focal and especially overt FL • higher levels of circulating t(14;18)-positive lymphocytes (>10-4 of total cells) indicate a higher risk for FL
  7. 7. Pediatric FL • large expansile highly proliferative follicles with prominent blastoid follicular center cells • BCL2 rearrangements must not be present, but there may be some BCL2 protein expression. • lack BCL6 and MYC rearrangements • D/D FL G3
  8. 8. Large B-cell lymphoma with IRF4 rearrangement • Around Waldeyer ring and/or cervical lymph nodes and low stage. • follicular, follicular and diffuse or pure diffuse growth pattern resembling FL grade 3B or a DLBCL. • Strong IRF4/MUM1 expression with BCL6 and a high proliferative fraction. • Germinal center type:on gene expression profiling • More aggressive than other pediatric-type FL but patients, • Good response to chemotherapy Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults- German High-Grade Lymphoma Study Group, and the Berlin-Frankfurt-Münster-NHL trial grou July 7, 2011; Blood: 118 (1)
  9. 9. Duodenal-type FL • localized overt low grade FL, is distinct from other GI tract FL • Overlap with ISFN and extranodal marginal zone lymphoma • excellent outcome • watch and wait strategy
  10. 10. Monoclonal B-cell lymphocytosis (MBL) • The 2008 :monoclonal B-cell populations in the peripheral blood (PB) of up to 5x109/l either with the phenotype of CLL, atypical CLL or non-CLL (CD5-) B-cells in the absence of other lymphomatous features. • 12% of healthy individuals • MBL precedes virtually all cases of CLL • “low count” MBL , defined as a PB CLL count of <0.5 x109/l • “high count” MBL 0.5-5 x109 because low count MBL • NO CLL with <5x109/l PB CLL cells in the absence of extramedullary disease even if there are cytopenias or disease-related symptoms Landgren O, Albitar M, Ma W, et al. B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med. 2009;360(7):659-667.
  11. 11. CLL/SLL-LN variant of MBL • lymph node involvement by “SLL” • No significant rate of progression • proliferation centers were not observed • Adenopathy was <1.5cm based on CT scans • Non-CLL type MBL: Early stage of splenic marginal zone lymphoma
  12. 12. Leukemic non-nodal mantle cell lymphoma and in situ mantle cell neoplasia (ISMCN) • IGHV mutated /SOX11 negative /CYCD11+B- cells,Ki67<30% • peripheral blood, bone marrow and often spleen. • clinically indolent • Observation • ISMCN: cyclin D1+ cells in the inner mantle zones of follicles, preserved architecture
  13. 13. IgM MGUS IgG/IgA MGUS • Related to LPL/B NHL • MYD88+ve • CCXR4 mutation+ • Related to myeloma • MYD 88-ve • CCXR4mutation-ve Advances in the Diagnosis, Classification, Risk Stratification, and Management of Monoclonal Gammopathy of Undetermined Significance: Implications for Recategorizing Disease Entities in the Presence of Evolving Scientific Evidence S. Vincent Rajkumar, MD, Robert A. Kyle, Mayo Clin Proc. 2010 Oct; 85(10): 945–948
  14. 14. Monoclonal immunoglobulin deposition diseases(MIDD) • Renal involvement is almost always present • Renal insufficiency and proteinuria,nephrotic syndrome. • light chain deposition disease (LCDD) light and heavy chain deposition disease (LHCDD) heavy chain deposition disease (HCDD) MC 92% k Y light chain deposition disease (LCDD) light and heavy chain deposition disease (LHCDD) heavy chain deposition disease (HCDD) MC 92% k k/y y
  15. 15. DLBCL NOS Hans algorithm :CD10, BCL6 and IRF4/MUM1 Germinal center B-cell type Activated B-cell type
  16. 16. High grade B-cell lymphoma [HGBL], with rearrangements of MYC and BCL2 and/or BCL6 • 5-15% of DLBCL, NOS • “starry sky” appearance with a high MiB-1 (which is consistent with BL), but with larger cells with irregular nuclei and more prominent nucleoli (which is consistent with DLBCL). • Aggressive clinical course:extranodal sites:bone marrow and CNS • The median survival time is reported to be about 5 months BCL-2, BCL-6, c-MYC gene rearrangements as a break-apart FISH
  17. 17. Double Expressed Lymphoma • MYC protein expression (30-50%) and BCL2 in 20-35% • cut-off of 40% MYC , >50% for BCL2. • Most of these tumors do not carry MYC/BCL2 chromosomal alteration • worse outcome than DLBCL, NOS but they are not as aggressive as Double hit/Tripple hit A prognostic indicator in DLBCL, NOS but not a separate category.
  18. 18. High grade B cell Lymphoma NOS • intermediate between DLBCL and BL • lack a MYC and BCL2 and/or BCL6 rearrangement • Indication of MYC, BCL2 and BCL6 rearrangements study GCB phenotype and/or high grade morphology cases with >40% MYC+ cells.
  19. 19. Epstein-Barr virus positive (EBV+) DLBCL NOS • >50 years old • worse prognosis than EBV-negative tumors • in younger patients, with a broader morphological spectrum and better survival. EBV+ mucocutaneous ulcer • self-limited growth potential and • response to conservative management • advanced age or with iatrogenic immunosuppression
  20. 20. Burkitt-like lymphoma with 11q aberration • phenotypically and by GEP like BL but which lack MYC rearrangements. • chromosome 11q alteration characterized by proximal gains and telomeric losses. • More complex karyotypes, lower levels of MYC expression, a certain degree of cytological pleomorphism • frequently nodal presentation. • The clinical course similar to BL
  21. 21. Follicular T-cell related Lymphoma • Angioimmunoblastic T-cell lymphoma • Follicular T-cell lymphoma • Nodal peripheral T-cell lymphoma with TFH phenotype • express at least two or three TFH-related antigens, including CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5 • contain EBV+B-cell blasts, simulate Hodgkin-Reed Sternberg (HRS) cells • Progression to EBV positive B-cell neoplasms may occur
  22. 22. ALCL CD30+Lymphoma Alk+ALCL>Alk-ve ALCL>CD30+VE PTCL JAK-STAT Mutation
  23. 23. Breast implant associated ALCL • Both saline and silicone filled implants • Median interval from implant to the lymphoma 10 yr • Trt: removal of the implant and capsule. • If invasion through the capsule:systemic chemotherapy
  24. 24. Indolent T-cell lymphoproliferative disorder (LPD) of the GI tract and Primary cutaneous acral CD8+ T-cell lymphoma • CD8positive T cells • indolent clinical course • Localized to a single site:Ear • Managed conservatively
  25. 25. EBV-positive T-cell lymphomas chronic active EBV-infection (CAEBV) • Asians, and in indigenous populations from Central and South America and Mexico. • indolent, localized forms like hydroa vacciniforme-like lymphoproliferative disorder Systemic EBV+ T-cell lymphoma of childhood • fever, hepatosplenomegaly and lymphadenopathy with or without cutaneous manifestations • usually associated with a hemophagocytic syndrome
  26. 26. Enteropathy-associated T-cell lymphoma (EATL) Type I • closely linked to celiac disease • northern European origin • TCR αβ. Type II Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL • no association with celiac disease • Asians, and Hispanic • monomorphic, and usually positive for CD8, CD56, and MAPK • Gains in chromosome 8q24 involving MYC From γδ T-cells,

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