Clasificación de la OMS de las neoplasias linfoides is about to begin! Please silence your cellphones, beepers, person sitting next to you….. When Dr. Campo asked me to provide this introduction, I had to think long and hard before agreeing to prepare it for this course & deciding how to do it but….. he is a good friend so …… Clasificación de los linfomas. Evolución conceptual. Please do not be disappointed The remainder of this presentation is in American Style English However, this is an international story not from just one family tree nor one side of the Atlantic So let’s begin!

S. Fairey classification over the last half- century: A tale of evolution & revolution The Rappaport classification

1966 1974 are neoplasms of the immune system and should be categorized as such! The “functional” lymphoma classifications Cells of the normal immune system Lukes & Collins, Cancer 34:1488, 1974 Morphology & immunophenotype R. D. Collins - Vanderbilt R. L. Lukes - USC

1974 K. Lennert Signing off on the Kiel classification

The 1970’s were very exciting but tumultuous times – not everyone was on the same page!

“It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness….” The 1970’s were very exciting but tumultuous times – not everyone was on the same page!

“It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness….” Lancet 1974 7;2(7880): 586 Lancet 1974 7;2(7880): 586

NCI Working Formulation Cancer 49:2112, 1982

Morphologic classification based in large part on survival data from the late 1970s. Some felt the Working Formulation was dead on arrival while others rallied behind it, but with growing perceptions of a continental divide, other classifications aging, and the need for an up-to-date biologically meaningful & clinically useful classification, …..

Enter the International Lymphoma Study Group (ILSG)

International Lymphoma Study Group -- 1992

ILSG And then soon afterward planning began for another exciting classification Classification Committees with Clinical Advisory Committee November, 1997 Basic philosophy of the modern WHO classification • Identify distinct clinicopathologic entities based on a combination of morphology, immunophenotype (remembering that not all cases will have a typical phenotype), molecular & cytogenetic findings, and clinical features. 2001

WHO CLASSIFICATION But time marched on – classification aged, monograph became unavailable Clinical Advisory Committee meetings

The myeloid group

The lymphoid group

The “lymphoid” editors More editorial meetings 2007 Lots of emails & help from Dr. Ohgaki & the IARC staff 2008

Chapter drafts And finally in September, 2008 our new monograph! So far, 45,000 copies sold! The 2008 WHO classification

• DLBCL associated with chronic inflammation • Lymphomatoid granulomatosis Precursor lymphoid • Primary mediastinal (thymic) large B-cell lymphoma • Intravascular large B-cell lymphoma • ALK positive large B-cell lymphoma neoplasms • Plasmablastic lymphoma • B lymphoblastic leukaemia/lymphoma • Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease – B lymphoblastic leukaemia/lymphoma, NOS • Primary effusion lymphoma – B lymphoblastic leukaemia/lymphoma with recurrent cytogenetic abnormalities • • B lymphoblastic leukaemia/lymphoma with t(9:22) (q34;q11.2); BCR/ABL • B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell • B lymphoblastic leukaemia/lymphoma with t(v;11q23); MLL rearranged lymphoma and Burkitt lymphoma • B lymphoblastic leukaemia/lymphoma with t(12;21) (p13;q22); • B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell TEL/AML1(ETV6-RUNX1) lymphoma and classical • B lymphoblastic leukaemia/lymphoma with hyperdiploidy • B lymphoblastic leukaemia/lymphoma with hypodiploidy (Hypodiploid ALL) Mature T-cell & NK-cell • B lymphoblastic leukaemia/lymphoma with t(5;14)(q31;q32)(IL3-IGH) • B lymphoblastic leukaemia/lymphoma with t(1;19)(q23;p13.3); E2A- PBX1;TCF3/PBX1) neoplasms • T lymphoblastic leukaemia/lymphoma • T-cell prolymphocytic leukaemia • T-cell large granular lymphocytic leukaemia Mature B-cell neoplasms • Chronic lymphoproliferative disorder of NK-cells • Aggressive NK cell leukaemia • Chronic lymphocytic leukaemia/small lymphocytic lymphoma • Systemic EBV positive T-cell lymphoproliferative disease of childhood • B-cell prolymphocytic leukaemia • Hydroa vacciniforme-like lymphoma • Splenic marginal zone lymphoma • Adult T-cell leukaemia/lymphoma • Hairy cell leukaemia • Extranodal NK/ lymphoma, nasal type • Splenic lymphoma/leukaemia, unclassifiable • Enteropathy-associated T-cell lymphoma – Splenic diffuse red pulp small B-cell lymphoma • Hepatosplenic T-cell lymphoma – Hairy cell leukaemia-variant • Subcutaneous panniculitis-like T-cell lymphoma • Lymphoplasmacytic lymphoma • – Waldenström macroglobulinemia • Sézary syndrome • Heavy chain diseases • Primary cutaneous CD30 positive T-cell lymphoproliferative disorders – Alpha heavy chain disease – – Gamma heavy chain disease – Primary cutaneous anaplastic large cell lymphoma – Mu heavy chain disease • Primary cutaneous gamma-delta T-cell lymphoma • Plasma cell myeloma • Primary cutaneous CD8 positive aggressive epidermotropic cytotoxic T-cell lymphoma • Solitary of bone • Primary cutaneous CD4 positive small/medium T-cell lymphoma • Extraosseous plasmacytoma • Peripheral T-cell lymphoma, NOS • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT • Angioimmunoblastic T-cell lymphoma lymphoma) • Anaplastic large cell lymphoma, ALK positive • Nodal marginal zone lymphoma • Anaplastic large cell lymphoma, ALK negative – Paediatric nodal marginal zone lymphoma • – Paediatric follicular lymphoma • Primary cutaneous follicle centre lymphoma Hodgkin lymphoma • • Nodular lymphocyte predominant Hodgkin lymphoma • Diffuse large B-cell lymphoma (DLBCL), NOS • Classical Hodgkin lymphoma – T-cell/histiocyte rich large B-cell lymphoma – classical Hodgkin lymphoma – Primary DLBCL of the CNS – Lymphocyte-rich classical Hodgkin lymphoma – Primary cutaneous DLBCL, leg type – Mixed cellularity classical Hodgkin lymphoma – EBV+ DLBCL of the elderly – Lymphocyte depleted classical Hodgkin lymphoma

Updating the 2008 WHO classification • 6 of the 8 WHO editors met in this hotel October 24, 2012 to discuss an electronic revision of the 4th Edition of the WHO Bluebook on haematopoietic/lymphoid tissues. • Current Bluebook has been uploaded into “PubCan”, an electronic database now under IARC who oversees the Bluebook series, and is being “fixed up”. • Work will then begin on revisions that will be available on a web-based version (no new hard-copy text at the current time). Date to be determined.

Let the real festivities begin!