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National Cancer Institute (NCI)

WHO Clinical Advisory Committee for Lymphoid Neoplasms
March 8 – 9, 2007 • Warrenton, VA

Participants Workshop Summary


Thursday, March 8
8:00 a.m. Welcome, Introduction, Goals of Meeting, Ground Rules
N. L. Harris and Steering Committee
8:30 a.m. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chairs: S. Swerdlow and E. Montserrat
  B-Cell Prolymphocytic Leukemia
Chairs: S. Swerdlow and E. Montserrat
Questions/Issues for CLL/SL/PLL
E. Campo
  1. What are the minimal criteria for the diagnosis of CLL? When is the diagnosis of CLL appropriate versus “clonal lymphocytosis”?
  2. Is the mutational status of the Ig gene (+/- expression of CD38 or ZAP70) a defining criterion for two subtypes of CLL or is this a prognostic factor?
    a. Is this testing required for clinical diagnosis?
    b. Should we maintain the CLL morphological variants? (Atypical/CLL/PLL)?
  3. What is expected in terms of prognostic indices for CLL in terms of clinical practice (and how should they be used)? Are CLL and SLL the same entity? What do we know about mutational status and ZAP70 in SLL?
  4. Richter syndrome refers to the clinical situation of aggressive lymphoma in CLL, which may be either DLBCL or cHL—agreed?
  5. Is PLL a distinct entity? How is it defined (what to do with cases that are t(11;14)+?
  CAC Prepared Responses
E. Montserrat
K. Rai
M. Keating
  General Discussion of CLL/SLL
9:15 a.m. Splenic Lymphoma/Leukemias
  • Splenic marginal zone lymphoma
  • Hairy cell leukemia
  Questions/Issues Regarding SMZL, HCL, and Splenic Lymphomas
M. A. Piris
H. Stein
  1. Are the reported diffuse types of SMZL in the red pulp included as SMZL or are they unclassifiable?
  2. Should we have a category of B-cell lymphoma associated with mixed cryoglobulinemia and hepatitis C infection? or is this a subtype of SMZL?
  3. Should we include a category of splenic lymphoma/leukemia, unclassifiable?
  4. What is hairy cell leukemia variant and where does it belong in our classification? Is it related to the so-called SMZL of the red pulp?
  CAC Prepared Reponses
B. Coiffier
B. Falin
10:15 a.m. Mantle Cell Lymphoma
Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT-type)
Nodal Marginal Zone Lymphoma
  • Pediatric marginal zone lymphoma
Chairs N. L. Harris and B. Coiffier
Questions/Issues Regarding Mantle Cell Lymphoma
  1. Should cyclin D1 negative mantle cell lymphoma be specifically reported? What are the criteria for diagnosing this subtype?
  2. Is it important to recognize grades/blastoid variants of MCL and are there prognostic features that should be included in a standard pathology report (e.g., blastoid variants, Ki67 fraction)?
  3. Are there indolent cases of MCL and should we try to recognize/define them?
CAC response
B. Coiffier
Discussion of Mantle Cell Lymphoma
10:45 a.m. MALT and Nodal Marginal Zone Lymphomas
Questions/Issues Concerning MALT Lymphoma
P. G. Isaacson
  1. What information is important to provide for MALT lymphomas, in addition to the basic diagnosis?
    a. Should cytogenetic abnormalities be studied and reported? Specifically should t(11;18) be studied in all cases? In gastric cases?
    b. Should putative pathogens be studied in all MALT lymphomas from gastric and other sites?
    c. Should the number or distribution (clusters) of large B-cells be reported? Currently we just report clusters large enough to call DLBCL. Any new data to suggest otherwise?
  2. Is there sufficient basis to look at distinguishing extraosseous plasmacytoma from MALT lymphoma with extreme plasma cell differentiation? Is it clinically relevant to do so?
CAC Responses
E. Zucca
Discussion of MALT Lymphomas
Questions/Issues Regarding Nodal MZL
E. S. Jaffe
  1. Do we need to grade or subclassify nodal MZL?
  2. What criteria are needed to exclude nodal involvement by MALT lymphoma?
  3. Are nodal MZL indolent or aggressive neoplasms?
  4. Are pediatric NMZL a distinct entity or a variant that need special mention?
    a. Could be related to pediatric FL?
CAC Responses
B. Coiffier
1:00 p.m. Discussion of NM7L
  • Lymphoplasmacytic lymphoma
  • Heavy chain diseases
  • Plasma cell myeloma, including heavy and light chain deposition diseases
  • Solitary plasmacytoma of bone
  • Extraosseous plasmacytoma
    Chairs: R. McKenna and S. Treon
  • Questions/Issues for Lymphoplasmacytic Lymphoma
    S. Swerdlow
    1. What criteria should be used for lymphoplasmacytic lymphoma?
      a. Is it always associated with Waldenstrom macroglobulinemia?
      b. Is the resultant lymphoma both a distinct entity and inclusive enough?
    2. Is there a biological borderline between stage IV MALT lymphoma and LPL?
    CAC Prepared Responses
    S. Treon
    M. A. Dimopoulos
    Discussion of LPL
    Brian Brooks
    Questions/Issues Regarding Plasma Cell Neoplasms
    N. Harris
    R. McKenna
    1. Are the heavy chain diseases distinct entities or expression of specific types of lymphoid/plasmacytic neoplasms? If the latter, should they still be mentioned in one chapter and/or broken out in the classification? Or just subsets of other neoplasms (CLL, LPL, MZL)?
    2. Is there anything that needs to be revisited in terms of criteria for myeloma and its variants and those for MGUS?
      a. Should we refine the criteria for these situations? Is it clinically useful to separate smoldering and indolent myeloma? Could they be merged under the designation "asymptomatic myeloma"?
    3. What is the current role for conventional cytogenetic, FISH, and molecular studies in terms of classification and clinical decision making?
    CAC Responses
    M. A. Dimopoulos
    S. Treon
    Discussion of Plasma Cell Neoplasms
    2:30 p.m.
  • Follicular lymphoma(s)
  • Pediatric follicular lymphoma
  • Primary cutaneous follicle center lymphoma
    Chairs: E. S. Jaffe and S. Horning
  • Questions/Issues Regarding Follicular Lymphomas
    N. L. Harris
    R. A. Warnke
    1. What specific types of FL should be recognized, and should they be described in the FL chapter or separate chapters/entities?
      a. Pediatric
      b. Specific sites of non-cutaneous extranodal FL (duodenum [intestinal?], testicular)?
    2. Do we need to revisit grading?
      a. Two grades or three?
      b. Should FL Grade 3B be considered a variant of DLBCL instead of a variant of FL?
      c. Should Ki67 be done in all cases, to substitute or complement morphological grading?
    3. Are there other biomarkers that should be studied for prognostic purposes?
      a. Histiocytes
      b. T-cell subsets
      c. P53 IHC or FISH?
    4. “In situ” follicular lymphoma
      a. Should “in situ” FL be diagnosed and reported?
      b. How should “in situ” FL be managed clinically? Staging to look for frank lymphoma? Follow-up?
    CAC Responses
    S. Horning
    A. Lister
    G. Salles
    3:15 p.m. Discussion of Follicular Lymphomas
    3:30 p.m. Do clinicians agree on definition and inclusion of cutaneous FCL (distinction from DLBCL-leg type)?
    R. Willemze
    3:35 p.m. Discussion of Cutaneous B-Cell Lymphomas
    3:45 p.m.
  • Diffuse large B-cell lymphoma, NOS
    • Germinal center B-cell type
      Activated B-cell type
      DLBCL associated with chronic inflammation
      EBV-positive DLBCL, NOS
      T cell/histiocyte rich large B-cell lymphoma
  • Primary mediastinal (thymic) large B-cell lymphoma
  • Primary DLBCL of the CNS
  • Primary cutaneous DLBCL, leg type
  • Intravascular large B-cell lymphoma
  • ALK-positive DLBCL
  • Plasmablastic lymphoma
  • Primary effusion lymphoma
  • Lymphomas associated with HHV8-associated multicentric Castleman disease
    Chairs: E. Campo and R. Fisher
  • Questions/Issues Regarding DLBCL
    H. Stein
    J. W. Chan
    1. What variants and subtypes of DLBCL need to be recognized?
      a. Is THRBCL a specific subtype or a morphological variant?
      b. Should certain anatomic localizations of DLBCL be recognized as specific entities (in addition to cutaneous FCL and mediastinal DLBCL e.g., CNS…)?
      c. Plasmablastic, ALK+ etc?
    2. How should new molecular information be integrated in clinical practice? What subtypes recognized by expression profile should be defined and recognized?
    3. What are the expectations for diagnostic evaluations of DLBCL?
      a. Prognostic factors (immunohistochemistry for GC versus ABC types, Ki67, cytogenetic/FISH, other)?
    CAC Responses
    M. Shipp
    J. Armitage
    B. Coiffier
    Discussion of DLBCL
    5:00 p.m.
  • Burkitt Lymphoma/Leukemia
  • High-grade B-cell lymphoma NOS (or intermediate between DLBCL and BL?)
  • Questions/Issues Regarding Burkitt Lymphoma/Leukemia and NOS Cases
    H. Stein
    P. H. Kluin
    1. What are the minimum criteria for the diagnosis of BL? What is the impact of the NEJM gene profiling studies on our approach to the diagnosis of what is and what isn’t a Burkitt lymphoma?
      a. Should FISH for MYC be required in all cases?
      b. Should absence of bcl2 and bcl6 rearrangements be required?
      c. Can you make the diagnosis if case is otherwise typical and no MYC (some cases in both NEJM papers lacked MYC)?
    2. What to call double/triple hit cases with MYC, BCL2, BCL6?
    3. Can/should we try to define an immunohistochemistry and FISH panel that should be standard on all cases?
    CAC Responses
    S. J. Horning
    M. Link
    Discussion of Burkitt and Borderline Cases
    Friday, March 9
    8:00 a.m. B-Cell Proliferations of Uncertain Malignant Potential
    Chairs: P. G. Isaacson and W. Wilson
    • Lymphomatoid granulomatosis Grades 1 and 2
    • Polymorphic EBV-associated lymphoproliferations
    • Polymorphic B-cell PTLD
    • Polymorphic B-cell LPD associated with other iatrogenic immunosuppression
    • EBV-associated B-cell LPD not associated with known immunodeficiency
      • EBV-associated B-cell LPD of the elderly
    Questions/Issues Regarding B-Cell Proliferations of Uncertain Malignant Potential
    E. S. Jaffe
    S. Swerdlow
    S. Nakamura
    1. Does LyG belong in this category? Only grades 1 and 2?
    2. Should we have a category of immunodeficiency-associated LPD that would include the spectrum of reactive to neoplastic (polyclonal to clonal) lesions?
    3. When a PTLD is diagnosed, what clinical information is required for clinical purposes (e.g., categorization according to current classification, EBV status, other)?
    4. Should “low grade” lymphomas in the post-transplant setting be considered a form of PTLD?
    5. What iatrogenic immunodeficiencies should be included
      a. Methotrexate?
      b. TNF inhibitors?
    6. What is the best term and spectrum of EBV-associated LPD of the elderly? Do we need this category?
    CAC Responses
    W. Wilson
    8:45 a.m. Mature T-Cell and NK Cell Neoplasms
    Leukemic Mature T-Cell Neoplasms
    Chairs: P. H. Gaulard and R. Liang
    • T-cell prolymphocytic leukemia
    • T-cell large granular lymphocytic leukemia
    • Indolent large granular NK-cell lymphoproliferative disorder
    • Aggressive NK/T cell leukemia/lymphoma
    • Fulminant EBV+T-cell LPD of childhood
    • Adult T-cell leukemia/lymphoma
    Questions/Issues Regarding Leukemic Mature T-Cell Neoplasms
    J. W. Chan
    J. C. K. Chan
    1. Given the problems with documenting clonality with NK disorder, what are the minimum criteria for the diagnosis of indolent large granular NK-cell lymphoproliferative disorder?
      a. When should genotypic studies be performed and when are flow cytometric studies sufficient?
      b. Is it expected to include KIR expression in the diagnosis of the entity?
    2. Should we recognize indolent LG NK disorder as a neoplastic entity?
    3. Should we include the term "lymphoma" in the aggressive NK/T–cell leukemia as in adult T-cell leukemia/lymphoma?
      a. Are all these cases EBV positive?
      b. Is EBV a defining criterion?
      c. Is the fulminant EBV+ T-cell LPD of childhood a subtype of this entity?
    4. Is anything new in ATLL that needs to be included?
    CAC Response
    M. Yamaguchi
    K. Tsukasaki
    Discussion of Leukemic Mature T-Cell Neoplasms
    9:30 a.m. Extranodal Mature T-Cell Neoplasms
    • Extranodal NK/T-cell lymphoma, nasal type
    • Enteropathy-type intestinal T-cell lymphoma
    • Hepatosplenic T-cell lymphoma
    • Subcutaneous panniculitis-like T-cell lymphoma
    • Mycosis fungoides
    • Sezary syndrome
    • Primary cutaneous anaplastic large-cell lymphoma
    • Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma
    • Mucocutaneous gamma-delta T-cell lymphoma
    • Primary cutaneous small/medium CD4+ T-cell lymphoma
    Questions/Issues Regarding Extranodal T-Cell Neoplasms
    P. G. Isaacson
    P. H. Gaulard
    1. Enteropathy/Intestinal
      a. What are the lower limits of diagnosing enteropathy type T-cell lymphoma (e.g., versus refractory sprue)?
      b. How do we distinguish between ETCL and other intestinal PTCL? Should testing for sprue be done in all intestinal PTCL? What tests are definitive? Is the term "enteropathy-type intestinal T-cell lymphoma" the most appropriate for these tumors?
    2. Cutaneous/Other
      a. Do we still want to leave out the category of “CD30+ cutaneous LPD”?
      b. Do clinicians recognize the new entities?
      c. Should we still consider the rare subtypes as provisional entities, as in the EORTC/WHO?
      d. Nasal-type NK-cell: how to handle non-nasal cases?
    CAC Responses
    R. Willemze
    M. Yamaguchi
    R. Liang
    Discussion of Extranodal T-Cell Neoplasms
    10:30 a.m. Other T-Cell Neoplasms
    Chairs: J. C. K. Chan and J. Armitage
    • Peripheral T-cell lymphoma, unspecified
    • Angioimmunoblastic T-cell lymphoma
    • Anaplastic large-cell lymphoma, ALK+
    • Anaplastic large-cell ALK-M
    • T-cell proliferations of uncertain malignant potential
      • Lymphomatoid papulosis
      • ? Indolent NK-LGL
    Questions/Issues Regarding Nodal PTCL
    S. Pileri
    G. Delsol
    1. Are there specific subtypes/stratification of PTCL-NOS with clinical relevance?
    2. Should we keep the unspecified category? Does NK-LGL belong there?
    3. Should ALK+ ALCL be a specific entity?
    4. Should ALK- be a specific entity or included in PTCL-NOS?
    CAC Responses
    P. L. Zinzani
    J. Armitage
    B. Falini
    Discussion of Nodal PTCL and ALCL
    1:00 p.m. Hodgkin Lymphoma and Borderline Cases
    Chairs: H. Stein and A. Engert
    • Nodular lymphocyte predominant Hodgkin lymphoma
    • Classical Hodgkin lymphoma
      • Mixed cellularity Hodgkin lymphoma
      • Nodular sclerosis Hodgkin lymphoma
      • Lymphocyte-rich classical Hodgkin lymphoma
      • Lymphocyte-depleted classical Hodgkin lymphoma
    • B-cell lymphoma with features intermediate between DLBCL and cHL
    Questions/Issues Regarding Hodgkin Lymphoma
    S. Poppema
    H. Stein
    1. Are there clinically relevant morphological variants of NLPHL that should be recognized (e.g., T-cell rich nodular and diffuse patterns)?
    2. How should we report diffuse T-cell-rich areas in a patient with concomitant or prior NLPHL? Is this a diffuse area/progression of NLPHL or progression to THRLBCL?
      a. How should these diffuse areas be reported?
      b. What are the clinical implications?
      c. How should we report positive bone marrows, when there is typically a T-cell-rich background?
    3. What is the clinical importance of the subtypes of classical HL?
      a. Should MC and LD subtypes of Classical HL be merged, as grades of the same entity (analogous to Grades 1 and 2, NSHL)?
    4. Is it clinically relevant to report on the EBV status in cHL?
    5. Does T-cell HL exist? Is it clinically relevant?
    CAC Responses
    A. Engert
    R. Hoppe
    Discussion of Hodgkin Lymphoma
    Questions/Issues Regarding B-Cell Lymphoma with Features Intermediate Between DLBCL and cHL
    E. S. Jaffe
    1. Do we accept this as a category in the classification? Nomenclature OK?
    2. Should this be included as a variant of (mediastinal) large B-cell lymphoma or cHL? Does it matter?
    3. How should these patients be treated?
    CAC Response
    M. Shipp
    Discussion of Intermediate Lymphomas between DLBCL and cHL
    2:00 p.m. Histiocytic and Dendritic Cell Neoplasms
    Chair: S. Pileri
    • Precursor dendritic cell neoplasm
      • Plasmacytoid dendritic cell neoplasm
    • Mature histiocytic/dendritic cell neoplasms
      • Histiocytic sarcoma
      • Langerhans cell histiocytosis/sarcoma
      • Interdigitating dendritic cell tumor/sarcoma
      • Follicular dendritic cell tumor/sarcoma
      • Dendritic-cell tumor/sarcoma, not otherwise specified
      • Juvenile xanthogranuloma (disseminated)
    Questions/Issues Regarding Dendritic Cell and Histiocytic Neoplasms
    S. Pileri
    J.C.K. Chan

    1. Acute leukemia group wants plasmacytoid DC neoplasm to be a precursor lesion in the dendritic cell group. Do we agree?
    2. What are the clinical features and treatment for PLDC neoplasm?
    3. What do clinicians expect from a classification of tumors derived from mature histiocytes and accessory cells?
    4. How are these treated?
    5. Is it necessary to distinguish “sarcoma” from “tumor” in the histiocytic/dendritic proliferations?
    CAC Responses
    Discussion of Histiocytic and Dendritic Cell Neoplasms
    3:00 p.m. Conclusions and Future Plans
    E. Campo
    4:00 p.m. Adjourn

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    Last Reviewed: June 1, 2007
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