LYMPHOMAS

Mousa Qasim Hussein

21th Dec.2015
 Neoplasms arise from lymphoid tissue, and are
Diagnosed from pathological finding on biopsy
.As Hodgkin or non-Hodgkin lymphoma

.the majority are of B-cell origin*

: Hodgkin lymphoma
The histological hallmark is the presence of
Reed-Sternberg cells, which are malignant lymphoid cell
. Of B-cell origin
They are often only present in small numbers but are
,Surrounded by large numbers of reactive normal T-cells
.Plasma cells and eosinophils
Reed-Sternberg cell. Reed-Sternberg cells are large,
abnormal lymphocytes that may contain more than
one nucleus. These cells are found in Hodgkin
lymphoma.
In the center of the photomicrograph is a classic Reed-Sternberg cell,a binucleate
cell with large “owl’s eyes” eosinophilic nucleoli.
: Epidemiology

.Incidence :approximately 4 new cases/ 100 000 population/ year

.Sex ratio :slight male excess (1.5: 1)

Age :median age 31 years; first peak at 20-35 year and second at
.years 50-70
: Aetiology

.Unknown-
More common in patients from well-educated-
.Background and small families

- Three times more likely a past history of infectious

Mononucleosis but no causal link to Epstein-Barr virus
.Infection proven
: WHO pathological classification and incidence

Type histology incidence

Nodular lymphocyte- 5%
Predominant

Classical HL *nodular sclerosing 70%

Mixed cellularity 20%*
Lymphocyte-rich 5%*
lymphocyte-depleted Rare*
Nodular sclrosis H.L.is the most common subtype and is composed of
large tumor nodules showing scattered lacunar classical RS cells set in
a background of reactive lymphocytes, eosinophils and plasma cells with
varying degrees of collagen fibrosis/sclerosis.
 Is a common subtype and is composed of numerous
classic RS cells admixed with numerous inflammatory
cells including lymphocytes, histiocytes, eosinophils,
and plasma cells without sclerosis.

Mixed cellularity Hodgkins lymphoma

 )

Nodular lymphocyte predominance showing characteristic

L and H cells(popcorn cells
Lymphocyte rich H.L.Is a rare subtype, show many features which may
cause diagnostic confusion with nodular lymphocyte predominant B-cell
Non-Hodgkin's Lymphoma (B-NHL). This form also has the most favorable
prognosis.
Nodular lymphocyte predominant HL is a slow-growing , localised
.And rarely fatal

the nodular sclerosing type accounts for the initial peak in young *
.Patients and is more common in women

.Mixed cellularity is more common in the elderly peak*

.lymphocyte rich HL usually present in men*

Lymphocyte-depleted HL is rare and probably represents large cells

.Or anaplastic non-Hodgkin lymphoma
: Clinical features

There is painless rubbery Lymphadenopathy , usually in the neck

.Or supraclavicular fossa; the lymph nodes may fluctuate in size
Young patients with nodular sclerosing disease
may have large Mediastinal mass which are
surprisingly asymptomatic but may cause Dry
.cough and some breathlessness
This patient presented with neck swelling, shortness of breath on
exertion and stridor.
Chest x-ray shows widening of the mediastinum.
CT scan shows Hodgkin's lymphoma surrounding the trachea and
narrowing its lumen.
 Biopsy of the neck mass
revealed Hodgkin's
lymphoma. The patient
was treated with radiation.
Isolated subdiaphragmatic nodes occur in
fewer than 10% at diagnosis.
Hepatosplenomegaly may be present but does
not alwaysindicate disease in those organs.
Spread is contiguousfrom one node to the
next and extranodal disease, such
as bone, brain or skin involvement, is rare.
: Clinical stages (ANN ARBOR classification)
stage I :involvement of a single lymph node region (I) or*
. extralymphatic site (IA E)
stage II :involvement of two or more lymph node regions( II)*
or an extralymphatic site and lymph node regions
on the same side of (above or below )the
.diaphragm(II E )
stage III :involvement of lymph node regions on both sides of*
Diaphragm with (III E) or without (III ) localised extralymphatic
Or involvement of the spleen (III S) or both (III SE)
stage IV diffuse involvement of one or more extralymphatic*
.tissue, e.g. liver or bone marrow
A no systemic symptoms
B weight loss, drenching sweats
,The lymphatic structures are defined as the lymph nodes
Spleen, thymus, Waldeyers ring, appendix and peyers patches
 Ann Arbor staging
 Stage I
Involvement of a
single lymph node
region or of a
single extranodal
organ or site(ⅠE)
 Ann Arbor staging
 Stage II:
 two or more lymph
node regions on the
same side of the
diaphragm
 localized extranodal
organ and one or more
lymph node regions
on the same side of
the diaphragm(ⅡE)
 Ann Arbor staging
 Stage III
lymph node regions on
both sides of the diaphragm
or with localized
extranodal organ (III E) or
spleen (IIIs)or both (III ES).
 Ann Arbor staging
 Stage IV:
Diffused or
disseminated
involvement of one
or more extranodal
organs, with or
without associated
lymph node
enlargement.
BM,LIVER,CNS,
EFFUSION
 Ann Arbor staging
Group A
 Without general symptoms

Group B
 With general symptoms
• unexplained fever , >38C, lasting over 3 days
• night sweating
• weight loss, >10% of body weight within 6 months
Investigations
The aim of investigations not only to diagnose lymphoma but also
.To determine the extent of disease

full blood count may be completely normal. A normochromic, normorcytic*

Anaemia may be present and , together with lymphopenia , is a bad
.Prognostic factor
.ESR may be raised*
Renal function test are required to ensure function is normal prior to *
.Treatment
Liver function may be abnormal in the absence of disease or reflect*
Hepatic infiltration. An obstructive pattern may be caused by nodes
.At the porta hepatis
.LDH measurement , as raised levels are an adverse prognostic factor *
.Chest X-ray may show mediastinal mass*
CT scan of chest and abdomen to permit staging. Bulky*
Disease (greater than10 cm in a single node mass) is an
.Adverse prognostic factor
Lymph node biopsy may be undertaken surgically or by*
.Percutaneous needle biopsy under radiological guidance
: Management
Treatment options include radiotherapy, chemotherapy
. Or a combinations of the two

: Radiotherapy
: Indications for radiotherapy
. stage I disease*
.stage II A disease with three or fewer areas involved*
.after chemotherapy to sites where there was originally bulk disease *
.to lesions causing serious pressure problems *
 RADIOTHERAPY
 Disease above the diaphragm
 mantle field
 covering the mediastinum and
the supraclavicular and cervical
lymph nodes.

 Disease below the diaphragm

 inverted- Y field
 covering the periaortic lymph
nodes, the inguinal lymph nodes,
and the splenic area.
Careful planning is required to limit the dose delivered*
.To normal tissues
.Fertility is usually preserved after radiotherapy*
women receiving breast irradiation during the treatment*
.Of chest disease have an increased risk of breast cancer
patients continuing to smoke after lung irradiation are at *
.Particular risk of lung cancer
 HODGKIN’S LYMPHOMA:
Treatment
 Chemotherapy
1. All patients with B symptoms
2. Stage II disease with more than three areas
involved
3. Stages III and IV disease

 Patients should receive at least six cycles of

chemotherapy to complete response
 ABVD (doxorubicin [Adriamycin], bleomycin,
vinblastine, and dacarbazine
 ChlVPP
Standard therapy of early-stage patients usually .
includes additional treatment with radiotherapy to the
involved lymph nodes after four courses of ABVD.
Treatment response is assessed clinically and by
repeat CT and newer scanning modalities such as
.positron emission tomography (PET)
ABVD chemotherapy can cause cardiac and
pulmonary toxicity, due to doxorubicin and
.bleomycin, respectively
The incidence of infertility and secondary
.myelodysplasia/AML is low with this regime
Patients with advanced-stage disease are most
commonly managed with chemotherapy alone.
Standard treatment in the UK is 6–8 cycles of
ABVD, followed by an assessment of response.
As with early disease, achieving PET-negative
remission predicts a better long-term
remission rate. Overall, the long-term disease
control/cure rates are lower with advanced
disease
Patients with disease which
is resistant to therapy
may be considered for
autologous HSCT
: Combined modality therapy
Radiotherapy may be given to the original sites of bulky disease
.After treatment by chemotherapy to reduce the risk of relapse
This form of treatment carries the greatest risk of long –term
.Complications
 Prognosis

Over 90% of patients with early-stage HL achieve

complete remission when treated with
chemotherapy followed by involved field
radiotherapy, and the great majority are cured.
The major challenge is how to reduce treatment
intensity, and hence long-term toxicity, without
.reducing the excellent cure rates in this group

Between 50 and 70% of those with advanced-stage HL

can be cured
Patients who fail to respond to initial
chemotherapy have a poor prognosis but
some may achieve long-term survival after
autologous BMT. Patients relapsing within a
year of initial chemotherapy have a good
salvage rate with autologous HSCT.
Patients relapsing after 1 year may obtain
long-term survival with further
.chemotherapy alone
The Hasenclever index
can be helpful in assigning
approximate chances of
cure when discussing
treatment plans with
patients
 Non-Hodgkin lymphoma (NHL)
Represents a monoclonal proliferation of lymphoid cells
.And may be of B-cell(70%) or T-cells (30%) origin
NHL are classified as low or high grade on the basis of
. Their proliferation rate
High grade tumours are dividing rapidly , have only being present for a matter
.of weeks before diagnosis and may be life-threatening
Low-grade tumours are dividing slowly, may have been present
.For many months before diagnosis and have an indolent fashion
Epidemiology
Incidence
.new cases /100 000 people per year 12*

Sex ratio
.slight male excess*

Age
.median age 65-70 years*
Aetiology
. no single causative abnormality described*
.lymphoma is a late manifestation of HIV Infection*
specific lymphoma types are associated with EBV, human*
.Herpesvirus8(HHV8) and HTLV infection
the development of gastric lymphoma can be associated*
.With Helicobacter pylori infection
some lymphomas are associated with specific chromosome*
Lesions; the t(14:18) translocation in follicular lymphoma
Result in the desregulated expression of the BCL-2 gene
.Product which inhibits apoptotic cell death
lymphoma occurs in congenital immunodeficiency states*
.And in immunosuppressed patients post organ transplantation
Of all cases of NHL ,85% are either high-grade diffuse
.Large cell NHL or low grade follicular NHL
Other forms of NHL , including mantle cell lymphoma
.And malt lymphomas , are less common
The current WHO classification stratifies according to
.Cell lineage
Clinically the most important factor is grade, which is
. A reflection of proliferation rate
HIGH –GRADE NHL has high proliferation rates , rapidly
Produces symptoms, is fatal if untreated ,but potentially
.Curable
LOW GRADE NHL has low proliferation rates, may be
Asymptomatic for many months before presentation, run
An indolent course, but is not curable by conventional
.Therapy
 Follicular lymphoma is the 2nd most common B- .]FOLLICULAR LYMPHOMA[
cell non-Hodgkin lymphoma after diffuse large B-cell lymphoma. It comprises
up to 20% of lymphoma in adults in the USA and in Western Europe. As the
name implies the lymphoma takes a “follicular” or nodular pattern of growth with
.or without diffuse areas
Diffuse large B-cell lymphoma
Peripheral T-cell lymphoma
: Clinical features
Patients present with lymph node enlargement which may
,Be associated with systemic upset ; weight loss, sweat
.Fever and itching
.Hepatosplenomegaly may be present
Extranodal disease is more common in NHL ,with involvement
Of bone marrow , gut ,thyroid , lung ,skin, testis, brain and
. More rarely , bone
Extranodal disease is more common in T-cell disease, whilst
Bone morrow involvement is more common in Low-grade
.than high grade(10%) disease )50-60%(
Compression syndromes may occur; gut obstruction
Ascites, superior vena caval obstruction and spinal cord
.Compression may all be presenting features
Staging
The same staging system is
used for both HL and NHL but
NHL is more likely to be stage
.III or IV at presentation
:Investigations
These are as for HL but in addition the following should
: Be performed
.routine bone marrow aspiration and trephine*
Immunophenotyping of surface antigens to distinguish*
.T-and B-cell tumours
this may be done on
-blood.
marrow-
Cytogenetic analysis to detect chromosomal
translocations and molecular testing for T cell
receptor or immunoglobulin gene rearrangements,
if available-Nodal material.
.
*Immunoglobulin determination. Some lymphomas
are associated with IgG or IgM praroteins serve as
.as marker for treatment response
.Measurement of uric acid levels*
some very aggressive high-Grade NHL are
associated with very high urate levels, which can
.Precipitate renal failure when treatment is started
HIV testing .this may be appropriate if risk factors*
are present
: Management
:Low-grade NHL
Asymptomatic patients may not require therapy*

: Indications for treatment

.marked systemic symptoms*
lymph node adenopathy causing discomfort or*
.dysfigerment
.bone marrow failure*
.compression syndrome*
: I-Radiotherapy
.Can be used for localised stage I disease

: II-Chemotherapy
most patients will respond to oral therapy with chlorambucil
Which is well tolerated .more intensive I.V chemotherapy in
Younger patients produce better quality of life but no
.Survival benefit. neither therapy will cure patients

: III-Monclonal antibody therapy

Humanised monoclonal antibodies can be used to target
Surface antigen on tumour cells, and induce tumour cell
.Apoptosis directly
Rituximab :anti-CD20 antibody has been shown to induce
Durable clinical response in up to 60%of patients. at present
Only recommended as last-line therapy for stage III and IV
Follicular lymphoma. synergistic effect are seen when treatment
.Is combined with standard chemotherapy
IV-Transplantation. Particular interest centres
on the role of high-dose chemotherapy and
HSCT in patients with relapsed disease.
Such high-dose therapy improves disease-free
survival but longer follow-up is awaited before
conclusions can be drawn about cure.
High-grade lymphoma
Patients with diffuse Large B-cell NHL need treatment at
.initial presentation

:I CHEMOTHERAPY
The majority (more than 90%)will need I.V combination
.Chemotherapy
: The CHOP regimen
C : cyclophosphamide
H :doxorubicin
O :VINCRISTINE
P: Prednisolon
.This regimen remain the mainstay of therapy
When combined with CHOP chemotherapy,
the biological therapy rituximab (R) increases
the complete response rates and improves
overall survival.
R-CHOP is currently recommended as first-
line therapy for those with stage II or greater
diffuse large B-cell lymphoma .
: II RADIOTHERAPY
A few stage I patients without bulky disease may be
.Suitable for radiotherapy
It is also indicated for a residual localised site of bulk
Disease after chemotherapy , and for spinal cord and
.Other compression syndromes

III-Transplantation
Autologous stem cell transplantation benefits
.patients With relapsed chemosensitive disease
Prognosis
Low-grade NHL runs an indolent remitting and
relapsing course, with an overall median
survival of 10 years.
Transformation to a high-grade NHL occurs in
3% per annum and is associated with poor
survival.
In diffuse large B-cell high-grade NHL treated
with R-CHOP, some 75% of patients overall
respond initially to therapy and 50% will have
disease-free survival at 5 years.
 Prognosis is further refined according to the
.international prognostic index (IPI)
*for high-grade NHL, 5 year survival ranges from 75% in
those With low risk scores:
age less than 60-1
.stage I or II, one or Fewer extranodal sites -2
normal LDH-3
.good performance Status-4
for high-grade NHL, 5 year survival 25%in
those With high risk scores
.increasingAge-1
.advanced stage -2
. concomitant disease -3
. ) araisedLDH-4
Relapse is associated with a poor
response to further chemotherapy
(< 10% 5-year survival), but in
patients under 65 years, bone
marrow transplantation improves
.survival