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LYMPHOMA
Dr Irshad Ali
Lymphoma
• Clonal malignant disorders that are derived from
lymphoid cells: either precursor or mature T-cell
or B-cell
• Majority are of B- cell origin
• Divided into 2 main types :
1. Hodgkin’s lymphoma
2. Non - Hodgkin’s lymphoma
Blood Cell and Lymphocyte
Development
STEM CELLS
Multipotential
myeloid cells
Multipotential
lymphocytic cells
Differentiate & mature into 6
Types of blood cells
red cells basophils
neutrophils monocytes
eosinophils platelets
Differentiate & mature into 3
Types of lymphocytes
T lymphocytes
B lymphocytes
Natural Killer Cells
T-Cells and B-Cells
􀂄 Immature lymphocytes that travel to the
thymus differentiate into T-Cells
– “T” is for thymus
􀂄 Immature lymphocytes that travel to the
spleen or lymph nodes differentiate into B
cells
– "B" stands for the bursa of Fabricius, which is
an organ unique to birds, where B cells
mature.
ALL MMCLL Lymphomas
Hematopoietic
stem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor
Myeloproliferative disordersAML
Lymphoid
progenitor T-lymphocytes
Plasma
cells
B-lymphocytes
naïve
Lymphoma classification
(2001 WHO)
• B-cell neoplasms
– precursor
– mature
• T-cell & NK-cell neoplasms
– precursor
– mature
• Hodgkin lymphoma
Non-
Hodgkin
Lymphomas
A 25 year old lady
1 month of evening rise of temperature, night
sweats and noticed a lump in her neck
On examination pallor, generalized
lymphadenopathy, hepatosplenomegaly
Hodgkin lymphoma
Thomas Hodgkin
(1798-1866)
Etiology
• ? Infection – EBV
• ? Environmental factors
REAL* Classification
• Classic:
– Nodular Sclerosis-MOST COMMON IN WORLD
– Lymhocyte rich
– Mixed Cellularity-MOST COMMON IN INDIA
– Lymhocyte depleted
• Non-Classic
– Nodular Lymphocyte predominant
*REAL – Revised European,American,lymphoma
Classical Hodgkin Lymphoma
Clinical features
• Bimodal age distribution :
– young adults ( 20-30 yrs) & elderly (> 50yrs) May
occur at any age
• M > F
• Lymphadenopathy:
– most often cervical region
– asymmetrical, discrete
– painless, non-tender
– elastic character on palpation ( rubbery)
– not adherent to skin
– fluctuate in size
• Contiguous spread via the lymphatic chain
eg.involvement of abdominal & thoracic LNs
• Extra nodal disease - rare
• Hepatospleenomegaly
• Constitutional symptoms ( B symptoms )
–Night sweats,
–sustained fever > 38 degree celsius,
–loss of weight >10% of body weight in 6 mo
• Fever sometimes cyclical (‘Pel-Ebstein fever’)
• Pain at the site of disease after drinking alcohol
• Pallor
• Pruritis
• Symptoms of Bulky (>10 cm) disease
Investigations
• CBC : Anemia (normochromic / normocytic),
• eosinophilia, neutrophilia, lymphopenia
• ESR -raised
• LFT- (liver infil / obs at porta hepatis)
• RFT- prior to treatment
• Urate , Ca,
• LDH - adverse prognosis
• CXR- mediastinal mass
• CT thorax / abdomen / pelvis-for staging
• Other: Gallium scan, PET, Lymphangiography ,
Laporotomy
• LN FNAC / biopsy :
– Malignant REED-STERNBERG ( RS) Cell: Bi-nucleate cell
with a prominent nucleolus. Derived from B cell, at an
early stage of differentiation
– Reactive background of eosinophils, lymphocytes,
plasma cells
– Fibrous tissue
REED-STERNBERG ( RS ) Cell
REED-STERNBERG ( RS) Cell
Lymphangiography
Staging
• Stage I : Involvement of single LN region (I) or extra
lymphatic site (IAE )
• Stage II : Two or more LN regions involved (II) or an extra
lymphatic site and lymph node regions on the same side of
diaphragm
• Stage III : Involvement of lymph node regions on both sides
of diaphragm, with (IIIE) or without (III) localized extra
lymphatic involvement or involvement of the spleen (IIS) or
both (IISE)
• Stage IV : Involvement outside LN areas (Liver, bone
marrow)
A : Absence of ‘B’ symptoms
B : B symptoms present
Treatment - Guidelines
• Indications for RT:
– Stage I disease
– Stage II disease with 3 or lesser areas involved
– For Bulky disease
– For pressure problems
• Indications for CT
– All with B symptoms
– Stage II disease with >3 areas involved
– Stage III and IV disease
Treatment
• Stage IA , Stage IIA with 3 or < 3 areas involved:
Radiotherapy
• Stage IB, Stage II A with > 3 areas , Stage IIB:
Chemotherapy every 3-4 weeks, 6-8 cycles; either
alone, or in combination with radiotherapy
• Stage III & IV : Chemotherapy +
Radiotherapy ( for bulky disease or palliation of
symptoms)
Irradiation fields used in Hodgkin’s Lymphoma
Chemotherapy
• MOPP :
Nitrogen Mustard,
Vincristine (Oncovin),
Procarbazine,
Prednisolone
• ABVD:
Adriamycin,
Bleomycin,
Vinblastine,
Dacarbazine
• Higher dose for relapse or younger pts with poor
prognostic features
Prognosis
• Overall 10 yr survival – 80%
• In long term survivors there is a risk of
– secondary malignancy: (leukemia , NHL), Solid tumors-
Lung, breast
– Infections
– Cardiac, pulmonary, endocrinal abnormalities
International Prognostic Index (IPI)
• Age
• Advanced stage disease
• Performance status
• Elevated LDH
• Presence of Extra nodal disease
Non Hodgkin’s lymphoma
• Incidence is increasing
• NHL>HD
• Median age of presentation is 65-70 yrs
• M>F
• More often clinically disseminated at
diagnosis
• B-cell-70% ; T-cell-30%
Relative frequencies of different
lymphomas
Hodgkin
lymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85% of NHL are B-lineage
Specific types
• Precursor B cell lymphoblastic
leukemia/lymphoma
Most common cancer in chilhood is B cell ALL
Cells are hetrogenous insize and
round/convoluted nuclei,high
nuclear/cytoplasmic ratio and absence of
cytoplasmic granules
Mature B cell neoplasm
• B ell chronic lymphoid leukemia/small
lymphocytic lymphoma
Cells expressing CD-5 ANTIGEN
PS-SMUDGE/BASKET CELLS
Autoimmune hemolytic
anemia/thrombocytopenia/hypogamma
globulinemia
• Young pt-bone marrow transplatation
• Chlorambucil alone or with cyc,rituximab
• Fludarabine
• CVP-CYC,VINCRISTINE
MALT-LYMPHOMA
Extra nodal marginal zone
Associated with H.pylori
CD-5 negative
Can occur in
stomach,orbit,intestine,lung,thyroid,salivary
gland,skin,soft tissue,bladder,kidney,CNS
AUTOIMMUNE PROCESS-
• SJOGRENS Syndrome-salivary gland
• Hashimoto’s thyroiditis-thyroid MALT
• C.psittaci conjunctivitis-ocular MALT
• Borrelia skin infection-cutaneous MALT
• MANTLE CELL LYMPHOMA
CD-5 POSITIVE
irregular nuclear contours of the medium-sized lymphoma cells and the presence of a
pink histiocyte. By immunohistochemistry the lymphoma cells expressed CD20, CD5
and Cyclin D1
FOLLICULAR LYMPHOMA
• Classic appearance of spleen involved by
follicular lymphoma, namely the presence of
discrete, miliary, small, white "pearly" nodules
throughout the whole parenchyma.
T(14,18),BCL-2 POSITIVE
DIFFUSE LARGE B CELL LYMPHOMA
• MOST COMMON NHL
LARGE CELLS WITH VESICULAR
CHROMATIN AND PROMINENT
NUCLEOLI
BURKITT’S LYMPHOMA
• RARE
• T(8;14)
• T(2;8),C-MYC and LAMDA LIGHT CHAIN GENE
• HIV Associated
• Most rapidly progressive human tumour
• The "starry sky" appearance seen under low
power is due to scattered tingible body-laden
macrophages (macrophages containing dead
apoptotic tumor cells).
Hairy cell leukemia
• B –CELL
• Presents as Pancytopenia
• Hairy projections on light/electron microscopy
Hair like projections
T –CELL LYMPHOMA/LEUKEMIA
• PRECURSOR T-cell lymphoblastic
leukemia/lymphoma
Presents as ALL
AGGRESSIVE
MATURE/PERIPHERAL T cell disorders
• Mycosis fungoides-cutaneous T cell lymphoma
Presents as eczematous skin lesions
52 Yr old male with mycosis fungoides(Alibert-
Bazin syndrome ) - common form of cutaneous
T-cell lymphoma.
Sezary syndrome
• Pt with cutaneous T cell leukemia presents
with generalized erythroderma and circulating
tumour cells
Adult T cell lymphoma/lekemia
• HTLV-1 retro virus manifestation
• Flower cells
• A 22-year-old female presented with 2 weeks
of fever, anemia, generalized
lymphadenopathy, hepatosplenomegaly, and
skin rashes. Her total leukocyte count was 306
× 109/L. Peripheral blood smear showed many
atypical lymphocytes with petal-shaped nuclei
like flowers as seen in the photograph..
Flower cells
• Peripheral blood immunophenotype noted
negative markers for myeloid and B lymphoid
lineage (CD10, CD19, CD3, CD5, CD7, cyto-
CD3, TCR, CD16, CD56) and strongly positive
for CD4 and CD25, and also CD2, which was
atypical. Bone marrow aspirate and biopsy
revealed involvement by acute leukemia.
Serology for HTLV-1 was positive and serum
calcium was normal
Anaplastic large T/null cell lymphoma
• ALK-ANAPLASTIC LYMPHOMA KINASE protein
positive
• t(2;5)
• CD-30 POSITIVE
PERIPHERAL T –CELL LYMPHOMA
• AGGRESSIVE
• MATURE T cells
NHL-TREATMENT
• R-CHOP-CD-20 POSITIVE
RITUXIMAB,CYCLOPHOSPHAMIDE,ADRIAMYCI
N,VINCRISTINE,PREDNISOLONE
• CHOP
Lymphoma like disordes
• Castle man disease-IL-6
• A 38-year-old lady was referred for FNAC of
multiple left axillary nodes, one of them in the
axillary tail of left breast, which appeared as a
breast lump in the upper outer quadrant. The
nodes ranged from 1 to 3 cm in size, were well
defined, mobile, firm and non-tender. s
• There were no systemic symptoms and no
other organomegaly. Peripheral blood counts
and erythrocyte sedimentation rate (ESR)
were within normal limit
Section of lymph node containing
vascularized germinal centres and
eosinophilic material
Rosai dorfman disease
• Rosai–Dorfman disease, also known as sinus
histiocytosis with massive lymphadenopathy,
is a rare disorder of unknown cause that is
characterized by abundant histiocytes in the
lymph nodes throughout the body.
ONE WORD ANSWER
• FLOWER CELLS SEEN IN-
• BASKET CELLS SEEN IN-
• T(14;18) seen in-
• STARRY SKY PATTERN SEEN IN-
• Mycosis fungoides is ……T/B cell lymphoma
• CD 15 AND CD 30 NOT SEEN IN……HODGKINS
TYPE LYMPHOMA
• Thank u

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Lymphoma

  • 2. Lymphoma • Clonal malignant disorders that are derived from lymphoid cells: either precursor or mature T-cell or B-cell • Majority are of B- cell origin • Divided into 2 main types : 1. Hodgkin’s lymphoma 2. Non - Hodgkin’s lymphoma
  • 3. Blood Cell and Lymphocyte Development STEM CELLS Multipotential myeloid cells Multipotential lymphocytic cells Differentiate & mature into 6 Types of blood cells red cells basophils neutrophils monocytes eosinophils platelets Differentiate & mature into 3 Types of lymphocytes T lymphocytes B lymphocytes Natural Killer Cells
  • 4. T-Cells and B-Cells 􀂄 Immature lymphocytes that travel to the thymus differentiate into T-Cells – “T” is for thymus 􀂄 Immature lymphocytes that travel to the spleen or lymph nodes differentiate into B cells – "B" stands for the bursa of Fabricius, which is an organ unique to birds, where B cells mature.
  • 5. ALL MMCLL Lymphomas Hematopoietic stem cell Neutrophils Eosinophils Basophils Monocytes Platelets Red cells Myeloid progenitor Myeloproliferative disordersAML Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve
  • 6. Lymphoma classification (2001 WHO) • B-cell neoplasms – precursor – mature • T-cell & NK-cell neoplasms – precursor – mature • Hodgkin lymphoma Non- Hodgkin Lymphomas
  • 7. A 25 year old lady 1 month of evening rise of temperature, night sweats and noticed a lump in her neck On examination pallor, generalized lymphadenopathy, hepatosplenomegaly
  • 9. Etiology • ? Infection – EBV • ? Environmental factors
  • 10. REAL* Classification • Classic: – Nodular Sclerosis-MOST COMMON IN WORLD – Lymhocyte rich – Mixed Cellularity-MOST COMMON IN INDIA – Lymhocyte depleted • Non-Classic – Nodular Lymphocyte predominant *REAL – Revised European,American,lymphoma
  • 12. Clinical features • Bimodal age distribution : – young adults ( 20-30 yrs) & elderly (> 50yrs) May occur at any age • M > F • Lymphadenopathy: – most often cervical region – asymmetrical, discrete – painless, non-tender – elastic character on palpation ( rubbery) – not adherent to skin – fluctuate in size
  • 13. • Contiguous spread via the lymphatic chain eg.involvement of abdominal & thoracic LNs • Extra nodal disease - rare • Hepatospleenomegaly
  • 14. • Constitutional symptoms ( B symptoms ) –Night sweats, –sustained fever > 38 degree celsius, –loss of weight >10% of body weight in 6 mo • Fever sometimes cyclical (‘Pel-Ebstein fever’) • Pain at the site of disease after drinking alcohol • Pallor • Pruritis • Symptoms of Bulky (>10 cm) disease
  • 15. Investigations • CBC : Anemia (normochromic / normocytic), • eosinophilia, neutrophilia, lymphopenia • ESR -raised • LFT- (liver infil / obs at porta hepatis) • RFT- prior to treatment • Urate , Ca, • LDH - adverse prognosis • CXR- mediastinal mass • CT thorax / abdomen / pelvis-for staging • Other: Gallium scan, PET, Lymphangiography , Laporotomy
  • 16. • LN FNAC / biopsy : – Malignant REED-STERNBERG ( RS) Cell: Bi-nucleate cell with a prominent nucleolus. Derived from B cell, at an early stage of differentiation – Reactive background of eosinophils, lymphocytes, plasma cells – Fibrous tissue
  • 17.
  • 18.
  • 21.
  • 22.
  • 23.
  • 25. Staging • Stage I : Involvement of single LN region (I) or extra lymphatic site (IAE ) • Stage II : Two or more LN regions involved (II) or an extra lymphatic site and lymph node regions on the same side of diaphragm • Stage III : Involvement of lymph node regions on both sides of diaphragm, with (IIIE) or without (III) localized extra lymphatic involvement or involvement of the spleen (IIS) or both (IISE) • Stage IV : Involvement outside LN areas (Liver, bone marrow) A : Absence of ‘B’ symptoms B : B symptoms present
  • 26.
  • 27. Treatment - Guidelines • Indications for RT: – Stage I disease – Stage II disease with 3 or lesser areas involved – For Bulky disease – For pressure problems • Indications for CT – All with B symptoms – Stage II disease with >3 areas involved – Stage III and IV disease
  • 28. Treatment • Stage IA , Stage IIA with 3 or < 3 areas involved: Radiotherapy • Stage IB, Stage II A with > 3 areas , Stage IIB: Chemotherapy every 3-4 weeks, 6-8 cycles; either alone, or in combination with radiotherapy • Stage III & IV : Chemotherapy + Radiotherapy ( for bulky disease or palliation of symptoms)
  • 29. Irradiation fields used in Hodgkin’s Lymphoma
  • 30. Chemotherapy • MOPP : Nitrogen Mustard, Vincristine (Oncovin), Procarbazine, Prednisolone • ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine • Higher dose for relapse or younger pts with poor prognostic features
  • 31. Prognosis • Overall 10 yr survival – 80% • In long term survivors there is a risk of – secondary malignancy: (leukemia , NHL), Solid tumors- Lung, breast – Infections – Cardiac, pulmonary, endocrinal abnormalities
  • 32. International Prognostic Index (IPI) • Age • Advanced stage disease • Performance status • Elevated LDH • Presence of Extra nodal disease
  • 33. Non Hodgkin’s lymphoma • Incidence is increasing • NHL>HD • Median age of presentation is 65-70 yrs • M>F • More often clinically disseminated at diagnosis • B-cell-70% ; T-cell-30%
  • 34. Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage
  • 35. Specific types • Precursor B cell lymphoblastic leukemia/lymphoma Most common cancer in chilhood is B cell ALL
  • 36. Cells are hetrogenous insize and round/convoluted nuclei,high nuclear/cytoplasmic ratio and absence of cytoplasmic granules
  • 37. Mature B cell neoplasm • B ell chronic lymphoid leukemia/small lymphocytic lymphoma Cells expressing CD-5 ANTIGEN PS-SMUDGE/BASKET CELLS Autoimmune hemolytic anemia/thrombocytopenia/hypogamma globulinemia
  • 38.
  • 39. • Young pt-bone marrow transplatation • Chlorambucil alone or with cyc,rituximab • Fludarabine • CVP-CYC,VINCRISTINE
  • 40. MALT-LYMPHOMA Extra nodal marginal zone Associated with H.pylori CD-5 negative Can occur in stomach,orbit,intestine,lung,thyroid,salivary gland,skin,soft tissue,bladder,kidney,CNS
  • 41. AUTOIMMUNE PROCESS- • SJOGRENS Syndrome-salivary gland • Hashimoto’s thyroiditis-thyroid MALT • C.psittaci conjunctivitis-ocular MALT • Borrelia skin infection-cutaneous MALT
  • 42.
  • 43. • MANTLE CELL LYMPHOMA CD-5 POSITIVE
  • 44. irregular nuclear contours of the medium-sized lymphoma cells and the presence of a pink histiocyte. By immunohistochemistry the lymphoma cells expressed CD20, CD5 and Cyclin D1
  • 46. • Classic appearance of spleen involved by follicular lymphoma, namely the presence of discrete, miliary, small, white "pearly" nodules throughout the whole parenchyma.
  • 48. DIFFUSE LARGE B CELL LYMPHOMA • MOST COMMON NHL
  • 49.
  • 50.
  • 51. LARGE CELLS WITH VESICULAR CHROMATIN AND PROMINENT NUCLEOLI
  • 52. BURKITT’S LYMPHOMA • RARE • T(8;14) • T(2;8),C-MYC and LAMDA LIGHT CHAIN GENE • HIV Associated • Most rapidly progressive human tumour
  • 53.
  • 54.
  • 55.
  • 56. • The "starry sky" appearance seen under low power is due to scattered tingible body-laden macrophages (macrophages containing dead apoptotic tumor cells).
  • 57. Hairy cell leukemia • B –CELL • Presents as Pancytopenia • Hairy projections on light/electron microscopy
  • 59. T –CELL LYMPHOMA/LEUKEMIA • PRECURSOR T-cell lymphoblastic leukemia/lymphoma Presents as ALL AGGRESSIVE
  • 60. MATURE/PERIPHERAL T cell disorders • Mycosis fungoides-cutaneous T cell lymphoma Presents as eczematous skin lesions
  • 61. 52 Yr old male with mycosis fungoides(Alibert- Bazin syndrome ) - common form of cutaneous T-cell lymphoma.
  • 62. Sezary syndrome • Pt with cutaneous T cell leukemia presents with generalized erythroderma and circulating tumour cells
  • 63.
  • 64.
  • 65. Adult T cell lymphoma/lekemia • HTLV-1 retro virus manifestation • Flower cells
  • 66. • A 22-year-old female presented with 2 weeks of fever, anemia, generalized lymphadenopathy, hepatosplenomegaly, and skin rashes. Her total leukocyte count was 306 × 109/L. Peripheral blood smear showed many atypical lymphocytes with petal-shaped nuclei like flowers as seen in the photograph..
  • 68. • Peripheral blood immunophenotype noted negative markers for myeloid and B lymphoid lineage (CD10, CD19, CD3, CD5, CD7, cyto- CD3, TCR, CD16, CD56) and strongly positive for CD4 and CD25, and also CD2, which was atypical. Bone marrow aspirate and biopsy revealed involvement by acute leukemia. Serology for HTLV-1 was positive and serum calcium was normal
  • 69. Anaplastic large T/null cell lymphoma • ALK-ANAPLASTIC LYMPHOMA KINASE protein positive • t(2;5) • CD-30 POSITIVE
  • 70. PERIPHERAL T –CELL LYMPHOMA • AGGRESSIVE • MATURE T cells
  • 72. Lymphoma like disordes • Castle man disease-IL-6
  • 73. • A 38-year-old lady was referred for FNAC of multiple left axillary nodes, one of them in the axillary tail of left breast, which appeared as a breast lump in the upper outer quadrant. The nodes ranged from 1 to 3 cm in size, were well defined, mobile, firm and non-tender. s
  • 74. • There were no systemic symptoms and no other organomegaly. Peripheral blood counts and erythrocyte sedimentation rate (ESR) were within normal limit
  • 75. Section of lymph node containing vascularized germinal centres and eosinophilic material
  • 76. Rosai dorfman disease • Rosai–Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare disorder of unknown cause that is characterized by abundant histiocytes in the lymph nodes throughout the body.
  • 77.
  • 78. ONE WORD ANSWER • FLOWER CELLS SEEN IN- • BASKET CELLS SEEN IN- • T(14;18) seen in- • STARRY SKY PATTERN SEEN IN- • Mycosis fungoides is ……T/B cell lymphoma • CD 15 AND CD 30 NOT SEEN IN……HODGKINS TYPE LYMPHOMA