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NON HODGKIN
LYMPHOMA
Dr Vijay Shankar S
LEARNING OBJECTIVES
 Introduction
 Classification systems
 B cell lymphomas
 Burkitt lymphoma
Classification Systems
 Recognized as neoplasms in early 1900
 Chaotic terminology
 Descriptive vs cell lineage classif...
Lymphoma Classification
 Morphology
 Morphology + Clinical outcomes + ? Markers
 Morphology + Immunophenotype + Chromos...
Morphology
Markers
CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11,
CD14, CD15, CD19, CD20, CD21, CD25, CD30, CD33,
CD79A, C...
Classification Criteria - WF-NCI Classification (1982)
Criteria
 Pattern of Growth
 Cells & Cellular
Features
 Prognost...
Small Cells Intermediat
e
Large Cells
Pathologic / Morphologic Criteria – WF/NCI Classification, 1982
Nodular / Follicular...
Small Cells Intermediate Large Cells
Lymphoma Classification
Working Formulation (WF-NCI) Classification
 Pattern of Growth
 Follicular or Diffuse
 Cells
 ...
WF-NCIClassification (1982)
 Limitations
 Works well for B-cell lymphomas
 Mixed small and large cell lymphomas ?
 IPX...
Revised European & American
Lymphoma Classification (1996)
 WF-NCI system enhanced by Ancillary studies ?
 IHC
 Flow, c...
Criteria for WF-NCI and REAL/WHO
REAL-WHO
 Cells
 Pattern
 Immunophenotype
 Grade (not graded*)
*grading is under deve...
REAL-WHO, 2001
Cells and Cellular Features
 Cell size (S, M & L), cleaved
 Lymphoblasts, large/small
lymphocytes, mantle...
REAL-WHO – 2001: Classification – Biologic Groups ?
 Precursor B-cell
 ALL / lymphoblastic
lymphoma
 Mature (peripheral...
Relative Frequency of Lymphomas REAL .. N. Harris et al
 B-cell > 85%
 T-cell < 15%
Types
 Diffuse large B-cell – 31%
...
WHO Classification of Hematopoietic
and Lymphoid Tumors: B-cell Neoplasms
Indolent
 Chronic lymphocytic
leukemia (CLL)/sm...
B-Cell Lymphoma (85%)
 B-Cells help make antibodies, which are proteins that
attach to and help destroy antigens
 Lympho...
Precursor B or T Lymphoblastic
Leukemia/lymphoma
 High grade B or T cell
neoplasm
 Common in children
 Leukemic or
lymp...
B-Cell Small Lymphocytic /
CLL
 Small lymphoid cells &
“pseudo growth centers”
 Immunophenotype
 CD20+ dim, CD19+,
CD5+...
Follicular Lymphoma
 Most common form of NHL
 Middle age. M:F:: 1:1
 Rare in Asian population
 Neoplastic cells resemb...
Follicular Lymphoma
 Predominantly follicular,
focal diffuse or pure diffuse
 Small cleaved cells
(centrocytes)
 Larger...
Follicular Lymphoma
Histopathology
Centrocytes:Small cells with irregular / cleaved nuclear contours
& scant cytoplasm
Cen...
•Bone marrow involvement occurs in 85 % of cases
•Characteristically takes the form of paratrabecular
aggregates
bcl2 posi...
Immunophenotype
CD19+, CD20+, CD10+, k or l +, CD 5-, CD23+/-
Also expresses bcl-2 protein in more than 90 %
of cases.
Cyt...
Clinical features.
 Painless, generalised lymphadenopathy
 Indolent waxing and waning course
 Incurable
 Median surviv...
Diffuse large B-cell lymphoma
 most common type of “aggressive” lymphoma
 usually symptomatic,presents with rapidly
enla...
Diffuse Large Cell Lymphoma (B-
cell)
 Diffuse pattern of
growth.
 Large cell size(4 -5
times the diameter of
a small ly...
BURKITT LYMPHOMA
 Aggressive B- cell neoplasm
 Types
1. African ( Endemic) Burkitt lymphoma
2. Sporadic ( Non Endemic) B...
Died 23 Mar 1993 (born 28 Feb 1911)
Irish surgeon and medical researcher who
first identifiedBurkitt's lymphoma.
In 1957, ...
A group of Burkitt's Lymphoma cases in Dr Burkitt's care.
Mulago Hospital, Kampala, Uganda, in 1960
Clinical features
Both endemic & sporadic are found in children and young adults.
Endemic Burkitt lymphoma : often present...
Morphology
Immunophenotype: Mature B cell markers – Surface IgM, CD19,
CD20,CD10.
Cytogenetic Features
In most of the cases of Burkit...
prognosis
 Very aggressive , but responds well to short-
term, high dose chemotherapy.
 Most children and young adults c...
THANK YOU
Non hodgkin lymphoma
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Non hodgkin lymphoma

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non Hodgkin lymphoma, Classification of NHL, Burkitt lumphoma

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Non hodgkin lymphoma

  1. 1. NON HODGKIN LYMPHOMA Dr Vijay Shankar S
  2. 2. LEARNING OBJECTIVES  Introduction  Classification systems  B cell lymphomas  Burkitt lymphoma
  3. 3. Classification Systems  Recognized as neoplasms in early 1900  Chaotic terminology  Descriptive vs cell lineage classification systems Classification based on:  Morphology (H&E)  Clinical Outcomes  Morphology + markers + Molecular techniques
  4. 4. Lymphoma Classification  Morphology  Morphology + Clinical outcomes + ? Markers  Morphology + Immunophenotype + Chromosome data  Morphology + IPX + Molecular studies + Chr (biologic subgroups)  Morphology + Clinical + IPX + Mol. Sty + Gene arrays  +Proteomics 1900 2010 Reticulum Cell Tumors & HD Lymphoma Rappaport 1950 WF / NCI 1982 REAL - WHO
  5. 5. Morphology Markers CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11, CD14, CD15, CD19, CD20, CD21, CD25, CD30, CD33, CD79A, CD99, CD117 etc. Molecular T & B cell gene rearrangement studies In-situ (FISH etc.), HUMARA, Gene/tissue arrays, CGH, Proteomics etc.
  6. 6. Classification Criteria - WF-NCI Classification (1982) Criteria  Pattern of Growth  Cells & Cellular Features  Prognostic Categories Classification  Low Grade  Intermediate Grade  High Grade Pathology - 1180 cases independently reviewed by panel of hematopathologists (US, Europe and Japan) Clinical data – Survival/response analyzed by statisticians NCI funded study, 1982
  7. 7. Small Cells Intermediat e Large Cells Pathologic / Morphologic Criteria – WF/NCI Classification, 1982 Nodular / Follicular Diffuse
  8. 8. Small Cells Intermediate Large Cells
  9. 9. Lymphoma Classification Working Formulation (WF-NCI) Classification  Pattern of Growth  Follicular or Diffuse  Cells  Cell size - Small, medium & large  Lymphocytes, plasma cells, immunoblasts  Prognostic Categories  Low grade  Intermediate & High grade  Low Grade  A. Small cell  B. Follicular small cell cleaved  C. Follicular mixed small and large  Intermediate Grade  D. Follicular large cell  E. Diffuse small cell cleaved  F. Diffuse mixed small & large cell  G. Diffuse large cell  High Grade  H. Immunoblastic  I. Lymphoblastic  J. Small cell non-cleaved
  10. 10. WF-NCIClassification (1982)  Limitations  Works well for B-cell lymphomas  Mixed small and large cell lymphomas ?  IPX, Flow & molecular data not applicable  Marginal zone (MALT) and mantle types not classifiable  Newer subtypes (T, NK cell etc.) cannot be adequately classified under WF-NCI system  Strengths  Grading system and high clinical acceptance  Many Rx protocols are based on WF-NCI
  11. 11. Revised European & American Lymphoma Classification (1996)  WF-NCI system enhanced by Ancillary studies ?  IHC  Flow, cytogenetic  Several sub-categories  All neoplastic entities of reticuloendothelial system  Includes tissue based, BM and peripheral blood neoplasms  Grading system not used  Currently modified by Society of Hematopathology, European association of Hematopathology  Recent WHO publication (2001)
  12. 12. Criteria for WF-NCI and REAL/WHO REAL-WHO  Cells  Pattern  Immunophenotype  Grade (not graded*) *grading is under development WF-NCI  Pattern  Cells  Grade
  13. 13. REAL-WHO, 2001 Cells and Cellular Features  Cell size (S, M & L), cleaved  Lymphoblasts, large/small lymphocytes, mantle cells, monocytoid B-cells (marginal zone), immunoblasts, lymph- plasma cells Pattern of Growth  Follicular or diffuse Immunophenotype  IHC, Flow & Genotype  Lymphoid (B, T, NK), histocyte, myeloid and macrophages Several Categories  B-cell Neoplasms  T-cell Neoplasms  Hodgkin’s disease  Histiocytic/Dendritic cell neoplasms  Acute leukemia  Lymphoid or myeloid  Myelodysplasia  Chronic myeloproliferative disorders
  14. 14. REAL-WHO – 2001: Classification – Biologic Groups ?  Precursor B-cell  ALL / lymphoblastic lymphoma  Mature (peripheral) B-cell  CLL / SLL  B-prolymphocytic leukemia  Lymphoplasmacytic leukemia  Splenic marginal zone (SLVL)  Hairy cell leukemia  Plasma cell myeloma  Extranodal MALT  Nodal MALT  Follicular lymphoma  Diffuse large B-cell lymphoma  Burkitt lymphoma/leukemia  Precursor T-cell  ALL / lymphoblastic lymphoma  Blastoid NK-cell lymphoma  Mature (peripheral) T-cell  T-cell prolymphocytic  T-cell large granular lymph  Aggressive NK-cell leuk  ATLL (HTLV1+)  Extranodal NK/T-cell lymphoma  Enteropathy associate T lymp  Hepatosplenic lymphoma  Subcutaneous panniculitis T-cell lymphoma  MF/SS  Primary cutaneous large lymph  Angioimmunoblastic lymphoma  Primary systemic anaplastic large cell lymphoma (ALCL)
  15. 15. Relative Frequency of Lymphomas REAL .. N. Harris et al  B-cell > 85%  T-cell < 15% Types  Diffuse large B-cell – 31%  Follicular lymphoma – 22%  MALT lymphoma 8%  Mature T-cell lymphoma – 8%  CLL/SLL – 7%  Mantle cell lymphoma – 6%  Mediastinal large B-cell lymphoma – 2%  Anaplastic large cell lymphoma – 2%  Burkitt lymphoma – 2%  Nodal marginal zone lymphoma – 2%  Precursor T lymphoblastic – 2%  Lymphoplasmacytic lymphoma – 1%  Other types – 7%
  16. 16. WHO Classification of Hematopoietic and Lymphoid Tumors: B-cell Neoplasms Indolent  Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma  Lymphoplasmacytic/ Waldenstrom’s macroglobulinemia (WM)  Hairy cell leukemia  Marginal zone lymphoma  Extranodal mucosa- associated lymphoid tissue (MALT)  Nodal  Splenic  Follicle center lymphoma, follicular, grade I-II Aggressive  Prolymphocytic leukemia  Plasmacytoma/ multiple myeloma  Mantle cell  Follicle center lymphoma, follicular, grade III  Diffuse large B-cell lymphoma (DLBCL)  Primary mediastinal large B-cell lymphoma Very Aggressive  Precursor B-lymphoblastic lymphoma/leukemia  Burkitt lymphoma/ B-cell acute leukemia  Plasma cell leukemia Jaffe E, et al. IARC Press, World Health Organization, 2001.
  17. 17. B-Cell Lymphoma (85%)  B-Cells help make antibodies, which are proteins that attach to and help destroy antigens  Lymphomas are caused when a mutation arises during the B-cell life cycle  Various different lymphomas can occur during several different stages of the cycle  Follicular lymphoma, which is a type of B-cell lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2, which blocks apoptosis.
  18. 18. Precursor B or T Lymphoblastic Leukemia/lymphoma  High grade B or T cell neoplasm  Common in children  Leukemic or lymphomatous phase  CD19+, CD79a+, CD10+, CD24+, tDt+ (precursor B)  CD3+, CD5+, tDt+ (precursor T)
  19. 19. B-Cell Small Lymphocytic / CLL  Small lymphoid cells & “pseudo growth centers”  Immunophenotype  CD20+ dim, CD19+, CD5+, CD23+, k or l+ dim  Indolent process  Prolymphocytes (<30%)  High grade B-cell lymphoma (Richter’s transformation) SLL SLL CLL
  20. 20. Follicular Lymphoma  Most common form of NHL  Middle age. M:F:: 1:1  Rare in Asian population  Neoplastic cells resemble normal Germinal center B cells
  21. 21. Follicular Lymphoma  Predominantly follicular, focal diffuse or pure diffuse  Small cleaved cells (centrocytes)  Larger cells ( centroblasts)  Mixed small and large cells  Grade I, II & III a/b  Nodal or extranodal  BM + (85%) Small Cell Cleaved Follicular Lymphoma Grade I
  22. 22. Follicular Lymphoma Histopathology Centrocytes:Small cells with irregular / cleaved nuclear contours & scant cytoplasm Centroblasts: larger cells with open nuclear chromatin, several nucleoli & moderate cytoplasm Centrocytes Centroblasts
  23. 23. •Bone marrow involvement occurs in 85 % of cases •Characteristically takes the form of paratrabecular aggregates bcl2 positivity of bone marrow neoplastic cellsParatrabecular bone marrow infiltration by Follicular lymphoma
  24. 24. Immunophenotype CD19+, CD20+, CD10+, k or l +, CD 5-, CD23+/- Also expresses bcl-2 protein in more than 90 % of cases. Cytogenetics & Molecular Genetics Hallmark of follicular lymphoma is a (14 ;18 ) translocation that juxtaposes the IgH locus on Chr 14 and the bcl-2 locus on Chr 18
  25. 25. Clinical features.  Painless, generalised lymphadenopathy  Indolent waxing and waning course  Incurable  Median survival- 7-9 yrs  Histologic transformation to DLBCL in 30% - 50% of cases., rarely into burkitt like lymphoma.  Survival less than 1 yr after transformation
  26. 26. Diffuse large B-cell lymphoma  most common type of “aggressive” lymphoma  usually symptomatic,presents with rapidly enlarging, mass at a single nodal or extranodal site  extranodal involvement is common  cell of origin: germinal center B-cell  treatment should be offered  curable in ~ 40 – 50%.
  27. 27. Diffuse Large Cell Lymphoma (B- cell)  Diffuse pattern of growth.  Large cell size(4 -5 times the diameter of a small lymphocyte.  R-S like cells may be seen in more anaplastic variants. Large cell Lymphoma Immunoblastic Lymphoma
  28. 28. BURKITT LYMPHOMA  Aggressive B- cell neoplasm  Types 1. African ( Endemic) Burkitt lymphoma 2. Sporadic ( Non Endemic) Burkitt lymphoma 3. Aggressive lymphomas in individuals infected with HIV  EBV infection related. t(8;14)
  29. 29. Died 23 Mar 1993 (born 28 Feb 1911) Irish surgeon and medical researcher who first identifiedBurkitt's lymphoma. In 1957, in Uganda, Burkitt found several children suffering from fast-spreading tumours in the head and neck. When they died within weeks, Burkitt recognised this was a previously undescribed cancer disease. He showed that these and all cases were characterized by infiltration of the affected tissues by lymphocytes. With colleagues Edward Williams and Clifford Nelson, he plotted the geographical incidence of the disease, and found it in the same areas endemic with malaria. This survey is regarded as one of the pioneering studies of geographical pathology. Burkitt helped to develop chemotherapy for the disease. Later, he championed high fibre diets. Dr Denis (Parsons) Burkitt
  30. 30. A group of Burkitt's Lymphoma cases in Dr Burkitt's care. Mulago Hospital, Kampala, Uganda, in 1960
  31. 31. Clinical features Both endemic & sporadic are found in children and young adults. Endemic Burkitt lymphoma : often present as a mass involving mandible Unusual prediliction for abdominal viscera(kidneys, ovaries, adrenals). Sporadic Burkitt lymphoma: Most often presents as an abdominal mass involving the ileocecum and peritoneum
  32. 32. Morphology
  33. 33. Immunophenotype: Mature B cell markers – Surface IgM, CD19, CD20,CD10. Cytogenetic Features In most of the cases of Burkitt's lymphoma, a reciprocal translocation has moved the proto-oncogene c-myc from its normal position on chromosome 8 to a location close to the enhancers of the antibody heavy chain genes on chromosome 14. T(8;14)
  34. 34. prognosis  Very aggressive , but responds well to short- term, high dose chemotherapy.  Most children and young adults can be cured.  Outcome guarded in older adults.
  35. 35. THANK YOU

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