Lymphoma
Zhongshan Hospital,Fudan University
Zou Shanhua
Definition,A group of neoplastic diseases of
lymphoid tissues
Classification,
Hodgkin′ s Disease,HD
(Hodgkin′ s Lymphoma)
Non Hodgkin ′ s Lymphoma,NHL)
General considerations
Clinical Features,
Painless,progressive lymphadenectasis
Fever,wasting,night seat； cachexia
Splenohepatomegalia
Epidemiology,
Incidence,urban / rural;male/female;age
HD 8～ 11％； NHL 90%
General Considerations
Virulogy,
EB virus→ Burkitt lymphoma,HD
HTLV-Ⅰ →ATL
HTLV-Ⅱ →Mycosis fungoides
Etiology and Pathogenesis
Immune States of Host,
Immune deficiency/immune suppression
Mechanism,Antigenic stimulction →
lymphadenosis(modulation↓ )
→ infinite proliferation
→ lymphoma
Etiology and Pathogenesis
HD,Reed-Sternberg(R-S) Cell
Rye Classification, 1966
Lymphocyte predominance
Nodular sclerosis
Mixed cellularity
Lymphocyte depletion
Classification of Lymphoma
NHL,
IWF,1982
REAL,1994
WHO,2000
Classification of Lymphoma
Working formulation
Low-grade lymphoma
A,small lymphocytic,consistent with
chronic lymphocytic leukemia
plasmacytoid
B,follicular,predominantly small cleaved cell
diffuse areas
sclerosis
C,follicular,mixed small cleaved and large cell
diffuse areas
sclerosis
Working formulation
Intermediate-grad lymphoma
D,follicular,predominantly large cell
diffuse areas
sclerosis
E,diffuse,small cleaved cell
sclerosis
F,diffuse,mixed small and large cell
sclerosis
epithelioid cell component
G,diffuse,large cell
cleaved cell
noncleaved cell
sclerosis
Working formulation
High-grade lymphoma
H,mmunoblastic,large cell
plasmacytoid
clear cell
polymorphous
epithelioid cell component
I,lymphoblastic,convoluted or nonconvoluted cell
J,small noncleaved cell,Burkitt's or non-Burkitt's
Working formulation
Miscellaneous
composite
mycosis fungoides
histiocytic
extramedullary plasmacytoma
unclassifiable
other
REAL Classification
? B-cell neoplasms
I,Precursor B-cell neoplasm,precursor B-lymphoblastic
leukemia/lymphoma
II,Peripheral B-cell neoplasms
A,B-cell chronic lymphocytic leukemia/prolymphocytic
leukemia/small lymphocyticlymphoma
B,Lymphoplasmacytoid lymphoma/immunocytoma
C,Mantle cell lymphoma
D,Follicle center cell lymphoma,follicular
1,Provisional cytologic grades,
I small cell,
II mixed small and large cell,
III large cell
2,Provisional subtype,diffuse,predominantly
small cell type
REAL Classification
E,Marginal zone B-cell lymphoma
1,Extranodal (MALT-type +/- monocytoid B cells)
2,Provisional subtype,nodal (+/- monocytoid B cells)
F,Provisional entity,splenic marginal zone lymphoma
(+/- villous lymphocytes)
G,Hairy cell leukemia
H,Plasmacytoma/plasma cell myeloma
I,Diffuse large B-cell lymphoma
1,Subtype,primary mediastinal (thymic) B-cell
lymphoma
J,Burkitt’s lymphoma
K,Provisional entity,high-grade B-cell lymphoma,
Burkitt-like
REAL Classification
T-cell and putative NK-cell neoplasms
I,Precursor T-cell neoplasm,precursor T-
lymphoblastic lymphoma/leukemia
II,Peripheral T-cell and NK-cell neoplasms
A,T-cell chronic lymphocytic leukemia /
prolymphocytic leukemia
B,Large granular lymphocyte leukemia
1,T-cell type 2,NK-cell type
C,Mycosis fungoides/Sezary’syndrome
?
REAL Classification
D,Peripheral T-cell lymphomas,unspecified
1,Provisional cytologic categories,
medium-sized cell,mixed medium and
large cell,large cell,lymphoepithelioid cell
2,Provisional subtype,hepatosplenic gamma
/delta T-cell lymphoma
3,Provisional subtype,
subcutaneous panniculitic T-cell
lymphoma
E,Angioimmunoblastic T cell lymphoma
F,Angiocentric lymphoma
REAL Classification
G,Intestinal T-cell lymphoma
(+/- enteropathy associated)
H,Adult T-cell lymphoma/leukemia
I,Anaplastic large cell lymphoma
1,CD30+ -cell type
2,T-cell type
3,Null-cell types
J,Provisional entity,anaplastic large cell
lymphoma,Hodgkin's-like
Clinical Features
HD
NHL
Age
Young people
More often in middle-aged people
Superficial lymph nodes
60～ 80％
50%
(first observed as tumefaction of cervical or supraclavicular lymph nodes)
Mediastinal lymph nodes
50%
20%
Retroperitoneal lymph nodes
Seldom invaded
Often invaded
Fever
Often occurred
Seldom in early period
Itch of skin
Often occurred in some young female
patients
Seldom occurred
Specific skin lesion
Seldom occurred
Often occurred
Extranodal sites
Seldom occurred
Often occurred
(Waldeyer’s ring,gastrointestinal tract,bone marrow,CNS,liver,lung,pleura,bone,skin,kidney)
Way of dissemination
Metastasis to nearby lymph nodes
In a jumping way
Bone marrow involvement
Seldom occurred
Often accompanied with leukemia
Progress
Slower
Faster
Prognosis
Better
Worse
Lab and Other Findings
Peripheral Blood and Bone Marrow
HD,Eosinophilia； R－ S cell
NHL,Lymphocytosis;Complicated leukemia
LDH,β2 -MG,Coombs test,globulin
Immunophenotype
Cytogenetic and Molecular Studies
Radiologic studies
Chest X-ray
CT,MRI
Radioactive nuclide
B-ultrasound
Biopsy
Diagnosis
Painless,progressive lymphadenectasis →
Biopsy
Skin Lesion → Biopsy
Bone Marrow Aspiration and Biopsy
Biopsy of Other Sites
Diagnosis and
Differential Diagnosis
Staging of lymphoma
Stage Definition
Ⅰ Involvement of a single lymph node region or of a single
extranodal organ or site(ⅠE)
Ⅱ Involvement of two or more node regions on the same side
of the diaphragm,or localized involvement of an
extranodal site or organ(ⅡE ) and one or more lymph
node regions on the same side of the diaphragm
Ⅲ Involvement of lymph node regions on both sides of the
diaphragm which may also be accompanied by localized
involvement of an extranodal organs or site(ⅢE ) or
spleen (Ⅲs ) or both (ⅢsE )
Ⅳ Diffuse or disseminated involvement of one or more distant
extranodal organs with or without associated lymph node involvement
B symptoms Fever> 38℃,night sweats,and/or weight loss > 10% of body in
the 6 months
Differential Diagnosis
Lymphadenectasis,
Chroniclymphadenitis
Tuberculous lymphadenitis
Tumour node metastases
Fever,Septicaemia,tuberculosis,
rheumatic disease
Extranodal Lymphoma:Other malignant tumer
Diagnosis and
Differential Diagnosis
Radiation Therapy
60Co,accelerator linear
Dosage:30～ 40GY,3～ 4W
Methods,
Local field irradiation(LFI)
Mantle or inverted Y irradiation
Total nodal irradiation(TNI)
Treatment
Indication,
HD Ⅰ A,Ⅱ A, Extended field irradiation(EFI)
Ⅰ B,Ⅱ B,Ⅲ A, TNI and/or combination
chemotherapy
Ⅲ B Ⅳ, Combination chemotherapy mainly
( or add local irradiation)
NHL Low-Grade Ⅰ, Ⅱ,Mid-GradeⅠ, EFI or local
irradiation
Ⅲ, Ⅳ, Combination chemotherapy mainly
( or add local irradiation)
Treatment
Chemotherapy
HD,MOPP CR,85％
ABVD CR, 75～ 80％
NHL,
Low -Grade:CB-1348,CTX; COP,CHOP
Mid or High-Grade:CHOP,m-BACOD,
MACOP-B
Relapsed:ESHAP
Treatment
Haemopoietic Stem Cell Transplantation,
Operation
Interferon
Anti-CD20 Monoclonal Antibody
Treatment
1,HD, Histology,clinical stage
2,NHL,Age *
Stage *
B symptoms
Performance status *
Mass size
Number of extranodal sites *
Bone marrow involvement
LDH *,β2 -MG
Histology
International Prognostic Index〔 IPI〕
Prognosis
Zhongshan Hospital,Fudan University
Zou Shanhua
Definition,A group of neoplastic diseases of
lymphoid tissues
Classification,
Hodgkin′ s Disease,HD
(Hodgkin′ s Lymphoma)
Non Hodgkin ′ s Lymphoma,NHL)
General considerations
Clinical Features,
Painless,progressive lymphadenectasis
Fever,wasting,night seat； cachexia
Splenohepatomegalia
Epidemiology,
Incidence,urban / rural;male/female;age
HD 8～ 11％； NHL 90%
General Considerations
Virulogy,
EB virus→ Burkitt lymphoma,HD
HTLV-Ⅰ →ATL
HTLV-Ⅱ →Mycosis fungoides
Etiology and Pathogenesis
Immune States of Host,
Immune deficiency/immune suppression
Mechanism,Antigenic stimulction →
lymphadenosis(modulation↓ )
→ infinite proliferation
→ lymphoma
Etiology and Pathogenesis
HD,Reed-Sternberg(R-S) Cell
Rye Classification, 1966
Lymphocyte predominance
Nodular sclerosis
Mixed cellularity
Lymphocyte depletion
Classification of Lymphoma
NHL,
IWF,1982
REAL,1994
WHO,2000
Classification of Lymphoma
Working formulation
Low-grade lymphoma
A,small lymphocytic,consistent with
chronic lymphocytic leukemia
plasmacytoid
B,follicular,predominantly small cleaved cell
diffuse areas
sclerosis
C,follicular,mixed small cleaved and large cell
diffuse areas
sclerosis
Working formulation
Intermediate-grad lymphoma
D,follicular,predominantly large cell
diffuse areas
sclerosis
E,diffuse,small cleaved cell
sclerosis
F,diffuse,mixed small and large cell
sclerosis
epithelioid cell component
G,diffuse,large cell
cleaved cell
noncleaved cell
sclerosis
Working formulation
High-grade lymphoma
H,mmunoblastic,large cell
plasmacytoid
clear cell
polymorphous
epithelioid cell component
I,lymphoblastic,convoluted or nonconvoluted cell
J,small noncleaved cell,Burkitt's or non-Burkitt's
Working formulation
Miscellaneous
composite
mycosis fungoides
histiocytic
extramedullary plasmacytoma
unclassifiable
other
REAL Classification
? B-cell neoplasms
I,Precursor B-cell neoplasm,precursor B-lymphoblastic
leukemia/lymphoma
II,Peripheral B-cell neoplasms
A,B-cell chronic lymphocytic leukemia/prolymphocytic
leukemia/small lymphocyticlymphoma
B,Lymphoplasmacytoid lymphoma/immunocytoma
C,Mantle cell lymphoma
D,Follicle center cell lymphoma,follicular
1,Provisional cytologic grades,
I small cell,
II mixed small and large cell,
III large cell
2,Provisional subtype,diffuse,predominantly
small cell type
REAL Classification
E,Marginal zone B-cell lymphoma
1,Extranodal (MALT-type +/- monocytoid B cells)
2,Provisional subtype,nodal (+/- monocytoid B cells)
F,Provisional entity,splenic marginal zone lymphoma
(+/- villous lymphocytes)
G,Hairy cell leukemia
H,Plasmacytoma/plasma cell myeloma
I,Diffuse large B-cell lymphoma
1,Subtype,primary mediastinal (thymic) B-cell
lymphoma
J,Burkitt’s lymphoma
K,Provisional entity,high-grade B-cell lymphoma,
Burkitt-like
REAL Classification
T-cell and putative NK-cell neoplasms
I,Precursor T-cell neoplasm,precursor T-
lymphoblastic lymphoma/leukemia
II,Peripheral T-cell and NK-cell neoplasms
A,T-cell chronic lymphocytic leukemia /
prolymphocytic leukemia
B,Large granular lymphocyte leukemia
1,T-cell type 2,NK-cell type
C,Mycosis fungoides/Sezary’syndrome
?
REAL Classification
D,Peripheral T-cell lymphomas,unspecified
1,Provisional cytologic categories,
medium-sized cell,mixed medium and
large cell,large cell,lymphoepithelioid cell
2,Provisional subtype,hepatosplenic gamma
/delta T-cell lymphoma
3,Provisional subtype,
subcutaneous panniculitic T-cell
lymphoma
E,Angioimmunoblastic T cell lymphoma
F,Angiocentric lymphoma
REAL Classification
G,Intestinal T-cell lymphoma
(+/- enteropathy associated)
H,Adult T-cell lymphoma/leukemia
I,Anaplastic large cell lymphoma
1,CD30+ -cell type
2,T-cell type
3,Null-cell types
J,Provisional entity,anaplastic large cell
lymphoma,Hodgkin's-like
Clinical Features
HD
NHL
Age
Young people
More often in middle-aged people
Superficial lymph nodes
60～ 80％
50%
(first observed as tumefaction of cervical or supraclavicular lymph nodes)
Mediastinal lymph nodes
50%
20%
Retroperitoneal lymph nodes
Seldom invaded
Often invaded
Fever
Often occurred
Seldom in early period
Itch of skin
Often occurred in some young female
patients
Seldom occurred
Specific skin lesion
Seldom occurred
Often occurred
Extranodal sites
Seldom occurred
Often occurred
(Waldeyer’s ring,gastrointestinal tract,bone marrow,CNS,liver,lung,pleura,bone,skin,kidney)
Way of dissemination
Metastasis to nearby lymph nodes
In a jumping way
Bone marrow involvement
Seldom occurred
Often accompanied with leukemia
Progress
Slower
Faster
Prognosis
Better
Worse
Lab and Other Findings
Peripheral Blood and Bone Marrow
HD,Eosinophilia； R－ S cell
NHL,Lymphocytosis;Complicated leukemia
LDH,β2 -MG,Coombs test,globulin
Immunophenotype
Cytogenetic and Molecular Studies
Radiologic studies
Chest X-ray
CT,MRI
Radioactive nuclide
B-ultrasound
Biopsy
Diagnosis
Painless,progressive lymphadenectasis →
Biopsy
Skin Lesion → Biopsy
Bone Marrow Aspiration and Biopsy
Biopsy of Other Sites
Diagnosis and
Differential Diagnosis
Staging of lymphoma
Stage Definition
Ⅰ Involvement of a single lymph node region or of a single
extranodal organ or site(ⅠE)
Ⅱ Involvement of two or more node regions on the same side
of the diaphragm,or localized involvement of an
extranodal site or organ(ⅡE ) and one or more lymph
node regions on the same side of the diaphragm
Ⅲ Involvement of lymph node regions on both sides of the
diaphragm which may also be accompanied by localized
involvement of an extranodal organs or site(ⅢE ) or
spleen (Ⅲs ) or both (ⅢsE )
Ⅳ Diffuse or disseminated involvement of one or more distant
extranodal organs with or without associated lymph node involvement
B symptoms Fever> 38℃,night sweats,and/or weight loss > 10% of body in
the 6 months
Differential Diagnosis
Lymphadenectasis,
Chroniclymphadenitis
Tuberculous lymphadenitis
Tumour node metastases
Fever,Septicaemia,tuberculosis,
rheumatic disease
Extranodal Lymphoma:Other malignant tumer
Diagnosis and
Differential Diagnosis
Radiation Therapy
60Co,accelerator linear
Dosage:30～ 40GY,3～ 4W
Methods,
Local field irradiation(LFI)
Mantle or inverted Y irradiation
Total nodal irradiation(TNI)
Treatment
Indication,
HD Ⅰ A,Ⅱ A, Extended field irradiation(EFI)
Ⅰ B,Ⅱ B,Ⅲ A, TNI and/or combination
chemotherapy
Ⅲ B Ⅳ, Combination chemotherapy mainly
( or add local irradiation)
NHL Low-Grade Ⅰ, Ⅱ,Mid-GradeⅠ, EFI or local
irradiation
Ⅲ, Ⅳ, Combination chemotherapy mainly
( or add local irradiation)
Treatment
Chemotherapy
HD,MOPP CR,85％
ABVD CR, 75～ 80％
NHL,
Low -Grade:CB-1348,CTX; COP,CHOP
Mid or High-Grade:CHOP,m-BACOD,
MACOP-B
Relapsed:ESHAP
Treatment
Haemopoietic Stem Cell Transplantation,
Operation
Interferon
Anti-CD20 Monoclonal Antibody
Treatment
1,HD, Histology,clinical stage
2,NHL,Age *
Stage *
B symptoms
Performance status *
Mass size
Number of extranodal sites *
Bone marrow involvement
LDH *,β2 -MG
Histology
International Prognostic Index〔 IPI〕
Prognosis
