Transcript lymphoma 15

Lymphoid Tumors (Blood
cancers)
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Overview
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Concepts, classification, biology
Epidemiology
Clinical presentation
Diagnosis
Staging
Important types
Bone Marrow
• Present in the soft inner part of some bones
such as the skull, shoulder, ribs, pelvis, and
backbones. (Occupies central cavity of bone)
• The bone marrow is made up of blood-forming
stem cells, lymphoid tissue, fat cells, and
supporting tissues that aid the growth of blood
forming cells.
Bone Marrow
• Spongy tissue where development of all
types of blood cells takes place
• All bones have active marrow at birth
• Adulthood - vertebrae, hip, shoulders,
ribs and skull contain marrow
Bone Marrow Aspiration/Biopsy
Hematopoietic Malignancies
􀂄 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series.
􀂄 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series.
Conceptualizing lymphoma
• neoplasms of lymphoid origin, typically
causing lymphadenopathy
• leukemia vs lymphoma
• lymphomas as clonal expansions of
cells at certain developmental stages
What is Lymphoma
• Lymphomas are cancers that begin by
the “malignant transformation” of a
lymphocyte in the lymphatic system
• Many lymphomas are known to be due
to specific genetic mutations
• Follicular lymphoma due to
overexpression of BCL-2 (gene that
blocks programmed cell death)
What is the Lymphatic System?
• Made up of organs, such as the tonsils,
spleen, liver, bone marrow and a network of
lymphatic vessels that connect glands, called
lymph nodes
• Lymph nodes located throughout the body
• Lymph nodes filter foreign particles out of the
lymphatic fluid
• Contain B and T lymphocytes
Lymphatic System
• Lymph nodes act as a filter to
remove bacteria, viruses, and
foreign particles
• Most people will have had “swollen
glands” at some time as a response
to infection
Blood Cell and Lymphocyte
Development
STEM CELLS
Multipotential
myeloid cells
Differentiate & mature into 6
Types of blood cells
Multipotential
lymphocytic cells
Differentiate & mature into 3
Types of lymphocytes
red cells basophils
neutrophils monocytes
eosinophils platelets
T lymphocytes
B lymphocytes
Natural Killer Cells
Lymphocytes
• Most lymphocytes are in lymph nodes,
spleen, bone marrow and lymphatic vessels
• 20% of white blood cells in blood are
lymphocytes
• T cells, B cells, natural killer cells
• B cells produce antibodies that help fight
infectious agents
• T cells help B cells produce antibodies and
they fight viruses
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
CLL
Lymphomas
MM
naïve
B-lymphocytes
Lymphoid
progenitor
AML
Hematopoietic
stem cell
Myeloid
progenitor
Plasma
cells
T-lymphocytes
Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
B-cell development
CLL
stem
cell
mature
naive
B-cell
germinal
center
B-cell
memory
B-cell
lymphoid
progenitor
MM
progenitor-B
ALL
pre-B
immature
B-cell
DLBCL,
FL, HL
plasma cell
Classification
Biologically rational
classification
Clinically useful
classification
Diseases that have distinct
• morphology
• immunophenotype
• genetic features
• clinical features
Diseases that have distinct
• clinical features
• natural history
• prognosis
• treatment
Classification
• Usually classified by how the cells look
under a microscope and how quickly
they grow and spread
– Aggressive lymphomas (high-grade
lymphomas)
– Indolent Lymphomas (low-grade
lymphomas)
Lymphoma classification
(2001 WHO)
• B-cell neoplasms
– precursor
– mature
• T-cell & NK-cell neoplasms
– precursor
– mature
• Hodgkin lymphoma
NonHodgkin
Lymphomas
Three common lymphomas
• Follicular lymphoma
• Diffuse large B-cell lymphoma
• Hodgkin lymphoma
Relative frequencies of
different lymphomas
Non-Hodgkin Lymphomas
Diffuse large B-cell
Hodgkin
lymphoma
NHL
Follicular
Other NHL
~85% of NHL are B-lineage
Follicular lymphoma
• most common type of “indolent”
lymphoma
• usually widespread at presentation
• often asymptomatic
• not curable (some exceptions)
• associated with BCL-2 gene
rearrangement [t(14;18)]
• cell of origin: germinal center B-cell
• defer treatment if asymptomatic
(“watch-and-wait”)
• several chemotherapy options if
symptomatic
• median survival: years
• despite “indolent” label, morbidity and
mortality can be considerable
• transformation to aggressive lymphoma
can occur
Diffuse large B-cell lymphoma
• most common type of “aggressive”
lymphoma
• usually symptomatic
• extranodal involvement is common
• cell of origin: germinal center B-cell
• treatment should be offered
• curable in ~ 40%
Mechanisms of lymphomagenesis
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Genetic alterations
Infection
Antigen stimulation
Immunosuppression
Causes and Risk Factors
• The Exact causes are still unknown
– Higher risk for individuals who:
• Exposed to chemicals such as pesticides or
solvents
• Infected w/ Epstein-Barr Virus
• Family history of NHL (although no hereditary
pattern has been established)
• Infected w/ Human Immunodeficiency Virus
(HIV)
Lymphoma.org
Epidemiology of lymphomas
• males > females
• incidence
– NHL increasing
– Hodgkin lymphoma stable
• in NHL: 3rd most frequently diagnosed
cancer in males and 4th in females
• in HL: 5th most frequently diagnosed
cancer in males and 10th in females
0-1
1-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Incidence/100,000/annum
Age distribution of new NHL
100
80
60
40
20
0
Age (years)
Clinical manifestations
• Variable
• severity: asymptomatic to extremely ill
• time course: evolution over weeks, months, or
years
• Systemic manifestations
• fever, night sweats, weight loss, anorexia, pruritis
• Local manifestations
• lymphadenopathy, splenomegaly most common
• any tissue potentially can be infiltrated
Other complications of lymphoma
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bone marrow failure (infiltration)
CNS infiltration
immune hemolysis or thrombocytopenia
compression of structures (eg spinal
cord, ureters)
• pleural/pericardial effusions, ascites
Non-Hodgkin’s Lymphoma
Staging
• Stage is the term used to describe the
extent of tumor that has spread through the
body ( I and II are localized where as III
and IV are advanced.
• Each stage is then divided into categories
A, B, and E
– A: No systemic symptoms
– B: Systemic Symptoms such as fever, night
sweats and weight loss
– E: Spreading of disease from lymph node to
another organ
Staging of lymphoma
Stage I
Stage II
Stage III
Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss
Staging
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Cancer Sourcebook
Diagnosis
Staging Studies
• Bone marrow aspiration and biopsy
• Radionuclide scans:
• GI x-rays
• Spinal fluid analysis
• CT scans
• Magnetic Resonance Imaging (MRI)
• Biopsy
Diagnosis requires an
adequate biopsy
• Diagnosis should be biopsy-proven
before treatment is initiated
• Need enough tissue to assess cells and
architecture
Treatment
• Non-Hodgkin’s Lymphoma is usually treated
by a team of physicians including
hematologists, medical oncologists and a
radiation oncologist.
• In some cases such as for Indolent
lymphomas, the Doctor may wait to start
treatment until the patient starts showing
symptoms, known as “watchful waiting”
Treatment Options
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Chemotherapy
Radiation
Bone Marrow Transplantation
Surgery
Bortezomib (Velcade)
Immunotherapy
• Using the bodies own immune system
combined with material made in a lab.
Survival Rates
• Survival Rates vary widely by cell type
and staging.
– 1 Year Survival Rate: 77%
– 5 Year Survival Rate: 56%
– 10 Year Survival Rate: 42%
Cancer.org
Hodgkin lymphoma
Thomas Hodgkin
(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
• cell of origin: germinal centre B-cell
• Reed-Sternberg cells (or RS variants)
in the affected tissues
• most cells in affected lymph node are
polyclonal reactive lymphoid cells, not
neoplastic cells
Reed-Sternberg cell
RS cell and variants
classic RS cell
(mixed cellularity)
lacunar cell
popcorn cell
(nodular sclerosis)
(lymphocyte
predominance)
A possible model of
pathogenesis
loss of apoptosis
transforming
event(s)
EBV?
cytokines
germinal
centre
B cell
RS cell
inflammatory
response
Hodgkin lymphoma
Histologic subtypes
• Classical Hodgkin lymphoma
– nodular sclerosis (most common subtype)
– mixed cellularity
– lymphocyte-rich
– lymphocyte depleted
Epidemiology
• less frequent than non-Hodgkin
lymphoma
• overall M>F
• peak incidence in 3rd decade
0-1
1-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
incidence/100,000/annum
Age distribution of new Hodgkin
lymphoma cases
6
5
4
3
2
1
0
Age (years)
Associated (etiological?)
factors
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EBV infection
smaller family size
higher socio-economic status
caucasian > non-caucasian
possible genetic predisposition
other: HIV? occupation? herbicides?
Clinical manifestations
• lymphadenopathy
• contiguous spread
• extranodal sites relatively uncommon
except in advanced disease
• “B” symptoms
Treatment and Prognosis
Stage
Treatment
I,II
ABVD x 4
& radiation
III,IV
ABVD x 6
Failurefree
survival
70-80%
Overall 5
year
survival
80-90%
60-70%
70-80%
Long term complications
of treatment
• infertility
– MOPP > ABVD; males > females
– sperm banking should be discussed
– premature menopause
• secondary malignancy
– skin, AML, lung, MDS, NHL, thyroid,
breast...
• cardiac disease
A practical way to think of lymphoma
Category
NonHodgkin
lymphoma
Hodgkin
lymphoma
Survival of
untreated
patients
Curability
To treat or
not to treat
Indolent
Years
Generally
not curable
Generally
defer Rx if
asymptomatic
Aggressive
Months
Curable in
some
Treat
Very
aggressive
Weeks
Curable in
some
Treat
All types
Variable –
months to
years
Curable in
most
Treat
Lab Diagnostic Studies
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Lymph node biopsy
Bone marrow aspiration and biopsy
Immunohistochemistry
Flow cytometry
Molecular Genetic studies
FISH
Cytogenetics
Histology Lab
RS cell and variants
classic RS cell
(mixed cellularity)
lacunar cell
popcorn cell
(nodular sclerosis)
(lymphocyte
predominance)
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Leukemia
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Definition: It is a group of malignant disorder, affecting
the blood and blood –forming tissue of the bone marrow
lymph system and spleen.
Aetiology
 Combination of predisposing factors including genetic
and environmental influences.
 Chronic exposure to chemical such as benzene
 Radiation exposure.
 Cytotoxic therapy of breast, lung and testicular cancer.
Classification of leukaemia
1. Acute lymphatic leukaemia (ALL)
Usually occurs before 14 years of age peak
incidence is between 2-9 years of age, older
adult
Pathophysiology
It arising from a single lymphoid stem cell, with
impaired maturation and accumulation of the
malignant cells in the bone marrow.
Acute lymphatic leukaemia
Cont.
Signs and symptoms
Clinical manifestation Clinical manifestation
Fever
Pallor
Bleeding
Anorexia
Fatigue
Weakness
Bone, joint and abdominal
pain
Increase intracranial
pressure
Generalized
lymphadenopathy
Infection of respiratory tract
Anaemia and bleeding of
mucus membrane
Ecchymoses
Weight loss
Hepatomegaly
Mouth sore
Acute lymphatic leukaemia
Cont.
Management
Diagnosis
 Low RBCs count, Hb, Hct, low platelet count ,
low normal or high WBC count.
 Blood smear show immature lymph blasts.
Acute Myelogenous Leukaemia
(AML)
It occurs at any age but occurs most often at
adolescence and after age of 55
Pathophysiology
Characterized by the development of immature
myeloblasts in the bone marrow.
Clinical manifestation
Similar to ALL plus sternal tenderness.
Management
Diagnosis
Low RBC, Hb, Hct, low platelet count, low to high
WBC count with myeloblasts.
Chronic lymphocytic Leukaemia
(CLL)
The incidence of CLl increases with age and
is rare under the age of 35.It is common in
men.
Pathophysiology
It is characterized by proliferation of small,
abnormal , mature B lymphocytes, often leading
to decreased synthesis of immunoglobulin and
depressed antibody response.
The number of mature lymphocytes in peripheral
blood smear and bone marrow are greatly
increased
Chronic lymphocytic Leukaemia (CLL)
Cont
Clinical Manifestation
Usually there is no symptoms.
Chronic fatigue , weakness , anorexia,
splenomegaly , lymphadenopathy,
hepatomegaly.
Signs and Symptoms
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Pruritic vesicular skin lesions .
Anaemia
Thrombocytopenia.
The WBC count is elevated to a level between
20,000 to 100,000.
 Increase blood viscosity and clotting episode.
Chronic Myelogenous
Leukaemia(CML)
Occurs between 25-60 years of age. Peak
45 year. It is caused by benzene exposure
and high doses of radiation.
Clinical Manifestation
There is no symptoms in disease. The
classic symptoms of chronic types of
leukaemia, include:
Fatigue, weakness, fever, sternal
tenderness.
Weight loss, joint & bone pain.
Chronic Myelogenous Leukaemia(CML) Cont.
Clinical Manifestation Cont.
Massive splenomegaly and increase in
sweating.
 The accelerated phase of disease(blastic
phase) is characterized by increasing
number of granulocytes in the peripheral
blood.
There is a corresponding anaemia and
thrombocytopenia.
Cancer Screening & Early
detection
.
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CANCER IS PREVENTABLE
80 – 90% CANCER ARE DUE TO OUR
HABITS AND ACTIVITIES
CANCER INVOLVES ALMOST EVERY
PARTS OF THE BODY
FACTS ABOUT
CANCER
 70 – 80 % CANCER CASES ARE DETECTED AT
LATE STAGE WHEN TREATMENT IS NOT
POSSIBLE.
 EARLY DETECTION OF CANCER HELPS IN
COMPLETE CURE OF SOME CANCER.
 PREVENTION
BY
TAKING
SOME
PRECAUTIONARY MEASURES IS THE BEST
WAY TO PREVENT CANCER.
Causes of Cancer
• Alcohol, Tobacco, Betel nut ,animal fat,
grilled food at high temp; air
pollution(industry).
• Water pollution.
• X-rays (diagnostic, on pregnant lady
may lead to fetal anomalies,).
• Viruses( Hbs,HCV,HPV, EBV, HIV).
• Heredity( retinoblastoma, colon, breast).
Definition of SCREENING
• Some types of cancer can be found
before they cause symptoms. Checking
for cancer (or for conditions that may
lead to cancer) in people who have no
symptoms is called screening.
WHY EARLY DETECTION IS
IMPORTANT ?
• DISEASE DETECTED AT EARLY STAGE
PRODUCES BETTER RESULTS ON TREATMENT
AND EVEN CURE .
• ADVANCED DISEASE SHOWS POOR RESULT ON
TREATMENT.
• ADVANCED DISEASE LEADS TO FINANCIAL
AND PSYCHOLOGICAL BURDEN.
Role of DOCTOR
• Not all types of cancer have screening
tests and some tests are only for people
with specific genetic risks.
• Types of Tests for Screening
• Visual Inspection by doctor& clinical
examination may rule out Skin, oral
cavity, breast, testicular tumors, thyroid
and lymph glands.
Oral cancer
• Screening for Specific Types of
Cancer
• Breast Cancer
• Cervical Cancer
• Colon and Rectal Cancer
• Lung Cancer
• research shows that using certain
screening tests carried regularly will
reduce deaths from above cancer.
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• Screening methods are in use or being
studied, but their ability to reduce the
number of deaths from cancer has not
been established.
Usefulness & limitations of
screening
• Mammography.
• Harmful Ionizing Radiation.
• Sensitivity and Specificity: May wrongly
indicate cancer in a healthy person.
False Positive and False Negative
Results
• Screening is not normally useful for rare
cancers.
Limitations of tests
• The extent to which a cancer is treatable: if
a person has a low life expectancy or
otherwise is in the end stages of a chronic
condition, then such a patient may have a
better life by ignoring the cancer even if
one were found. If the diagnosis of cancer
would not result in a change in care then
cancer screening would not likely result in
a positive outcome.
Whole body imaging
• There is a significant risk of detection of
what has been recently called an
incidentaloma - a benign lesion that
may be interpreted as a malignancy and
be subjected to potentially dangerous
investigations.
Breast cancer
• population Screening mammography once
for every two years for all women aged
50–74, with decisions about screening
younger and older women being
determined by consideration of the
individual's risk factors and the benefits
and harms of screening.
• Clinical breast exam (CBE) about every 3
years for women in their 20s and 30s and
every year for women 40 and over.
Breast screening
• Digital mamograghy. The compression of
the breast that's required during a
mammogram can be uncomfortable.
• The compression also causes overlapping
of the breast tissue. A breast cancer can
be hidden in the overlapping tissue .
• Some tissue can not show up on the
mammogram.
• Mammograms take only one picture(2D).
Breast screening
• Breast tomosynthesis,
• Digital tomosynthesis. It takes multiple
x-ray pictures of each breast from many
angles.
• The x-ray tube moves in an arc around
the breast while 11 images are taken
during a 7-second .
Cervical cancers
• Cervical cancer screening (testing)
should begin at age 21. Women under
age 21 should not be tested.
• Women between ages 21 and 29
should have a Pap test every 3 years.
• Women between the ages of 30 and
65 should have a Pap test plus an HPV
test (called “co-testing”) every 5years.
Cervix
• Women over age 65 who have had
regular cervical cancer testing with
normal results should not be tested .
• A woman who has been vaccinated
against HPV should still follow the
screening recommendations for her age
.
Bowel cancer
• screening for colorectal cancer using
fecal occult blood testing,
sigmoidoscopy, or colonoscopy, in
adults, beginning at age 50 years and
continuing until age 75 years.
• A new method for colorectal cancer
screening is the M2-PK Test, which is
able to detect bleeding and none
bleeding colorectal cancers and polyps.
Bowel Ca
• Tests that find polyps and cancer
• Flexible sigmoidoscopy every 5 years,
or
• Colonoscopy every 10 years, or
• Double-contrast barium enema every 5
years, or
• CT colonography (virtual colonoscopy)
every 5 years.
continued
• Tests that primarily find cancer
• Yearly fecal occult blood test (FOBT), or
• Yearly fecal immunochemical test (FIT)
every year, or
• Stool DNA test (sDNA)
• If the test is positive, a colonoscopy
should be done.
Endometrial (uterine)
cancer
• at the time of menopause, all women
should be told about the risks and
symptoms of endometrial cancer.
Women should report any unexpected
bleeding or spotting to their doctors.
• Endometrial biopsy.
Prostate cancer
• When screening for prostate cancer, the
PSA test may detect small cancers that
would never become life threatening,
but once detected will lead to treatment.
• Starting at age 50, men should talk to a
doctor
Lung Cancer
• Genetic susceptibility testing of tobacco
users.
• Sputum cytology . DOTA LAN scan.
• Spiral C.T
Prevention of cancer
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Stay away from tobacco, Paan Naswar etc.
Stay at a healthy weight.
Get moving with regular physical activity.
Eat healthy with plenty of fruits and vegetables.
Avoid alcohol.
Protect your skin.
Know yourself, your family history, and your
risks.
• Have regular check-ups and cancer screening
tests.
Prevention
• An apple a day keeps doctor away.
• In our part of world hepatitis is common
hence hepatitis B vaccination may prevent
Liver tumors at least from HBV.
• Care in dental procedures, Endoscopes.
• Care at Barber shop prevents from HCV.
Prevention
• HIV aids,(restriction to spouse).
• HPV can give rise to Ca Cervix, where
it is common. Similarly Circumcision has
got a preventive role.
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