Lymph node malignancies

• Roll no- 1936, 1937

Lymphomas
- these are malignant neoplasms originating
into the bone marrow and lymphatic
structures resulting in the proliferation of the
lymphocytes .
Hodgkin’s lymphoma
Non-hodgkin’s lymphoma
 Hodgkin lymphoma
Etiology
• Mostly idiopathic.
• Associated with EBV.
• HIV patients are at higher risk.
• Exposure to Benzene
• Males are affected more than female with 1.5:1
• Seen in 20-35 yrs of age and 50-70 yrs of age
• More common in the patients from well
educated backgrounds and small families.
 Classical Reed sternberg cell
- histological hallmark of HL
- these are large malignant lymphoid cells of B
cell origin
- Present in small numbers but are surrounded
by large no. of reactive non malignant cells T
cells, plasma cells and eosinophils.
- shows Owl eye appearance
- CD15+ / CD30+ (markers of lymphocyte
activation)
 Variants of Reed sternberg cells
1)Mononuclear cell-
with single large nucleus
2)Lacunar type-
single hyperlobated cell,
cytoplasm is retracted
around the nucleus creating
an empty space.
3)Pleomorphic RS cell
Multiple irregular nuclei
4)Lympho-histiocytic RS cell
small cell, with a very lobulated
nucleus, small nucleoli
 Classification of HL
• Classical HL and Non classical HL
Classical HL involves :-
1) Nodular seclerosis
-most common subtype globally
-female and male are equally affected
-Seen in young adults
-Lacunar cells are seen and prognosis is good
2) Mixed cellularity
-Most common type in India
-seen in young adults and >55 yr of age
-RS cells plasma cells eosonophil mononuclear cells
3)Lymphocyte rich
-seen in elderly peopl
-mononuclear cells are seen in this variant
-prognosis is good
4) Lymphocyte depleted HL
-seen in elderly patients especially who are infected with
HIV.
-Atypical hodgkin’s cells are present .
-prognosis is worst.
Non classical variant:-
: -lymphocyte predominant HL
-CD15/CD30 (-) but CD20 (+)
-not associated with EBV
Clinical features
Patients most commonly present with
- painless rubbery lymphadenopathy in the
neck and supraclavicular fossae
- half of the patients develop spleenomegaly
during the course of the disease.
- liver enlargement too may occur.
constitutional symptoms like pel-ebstein fever
with night sweats and weight loss , fatigue
malaise and pruritus.
Ann arbor staging of hodgkin’s lymphoma
Stage l
I – involvement of a single lymph node region
IE- involvement of single extra lymphatic organ or site
Stage ll
II involvement of two or more lymph node regions on
the same side of the diaphragm
IIE with localised contigous involvement of an
extranodal organ or site.
• Stage III
III- involvement of lmphnode regions on the
both sides of the diaghragm
IIIE- with localised contiguous involvement of
an extranodal organ or site
IIIES-both the featues of IIIE and IIIES present
Stage IV
Multiple or disseminated involvement of one
or more extra lymphatic organs or tissues with
or without lymphatic involvement
 INVESTIGATIONS
1)CBC may be normal. If a normochromic
normocytic anaemia or lymphopenia is
present, this is a poor diagnostic factor.
2)ESR may be raised
3)LFT may be abnormal reflecting the hepatic
infiltration .An obstructive pattern may be
caused by nodes at the porta hepatis
4)LDH are ussualy raised.
5)Chest X-ray may show a mediastinal mass.
6)CT scan of chest ,abdomen and pelvis for the
staging
7)Flowcytometery- CD15+and CD30+

8)Lymph node biopsy may be undertaken

surgically or by percutaneous needle biopsy
under radiological guidance.
9)Whole body PET scan for staging and follow up
 TREATMENT
Treatment involves radiotherapy and chemotherapy
depending on the stage
drugs used – Adriamycin
Bleomycin
Vinblastine
Dacarbazine
For stage I and II
2-4 cycles of ABVD or Radiotherapy
Stage III and IV
6-8 cycles + radiation
• Make sure to monitor PFT and ECHO of the
patient as the bleomycin can cause pulmonary
fibrosis and doxorubicin can cause
cardiomyopathy
if the patient is resistant to the therapy –
autologous HSCT (hemopoietic stem cell
transplant)
Relapsed after chemotherapy or transplant -
Brentuximab which is monoclonal antibody
against CD30
Non Hodgkin lymphoma
Deepika
Roll no - 1937
• Non-Hodgkin
lymphoma (NHL)
represents a
monoclonal
proliferation of
lymphoid cells of B-
cell (90%) or T-cell
(10%) origin. The
incidence of these
tumours increases
with age, to
62.8/million population
per annum at age 75
years, and the overall
rate is increasing at
about 3% per year.
• Previous classifications were based principally on histological appearances.
The current WHO classification stratifies according to cell lineage (Tor B
cells) and incorporates clinical features, histology, genetic abnormalities and
concepts related to the biology of the lymphoma. 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 is potentially curable.
• Low-grade NHL has low proliferation rates, may be asymptomatic for many
months or even years before presentation, runs an indolent course, but is
frequently disseminated at diagnosis and not curable by conventional
therapy.
• Of all cases of NHL in the developed world, over 50% are either diffuse large
B-cell NHL (high-grade) or follicular NHL (low-grade).
• Other forms of NHL, including Burkitt lymphoma, mantle cell lymphoma,
mucosa-associated lymphoid tissue (MALT) lymphomas and T-cell lymphomas,
are individually less common.
 Clinical features -
• Unlike Hodgkin lymphoma, NHL is often widely
disseminated at pres-entation, including in
extranodal sites. Patients present with lymph
node enlargement, which may be associated
with systemic upset:
• weight loss, sweats, fever and itching.
Hepatosplenomegaly may be present. Sites of
extranodal involvement include the bone
marrow, gut, thyroid, lung, skin, testis, brain
and, more rarely, bone. Bone marrow
involvement is more common in low-grade
(50%-60%) than high-grade (10%) disease.
• Other extranodal sites tend to be more
common in high grade diseases, particularly
CNS involvement. Compression symptoms may
 Investigations -
• These are as for HL, but in addition the following
should be performed:
• Bone marrow aspiration and trephine to identify
bone marrow involvement.
• Immunophenotyping of surface antigens to
distinguish 7-cell from B-cell tumours. This may
be done on blood, marrow or nodal material.
• Cytogenetic analysis to detect chromosomal
translocations, particularly rearrangements of the
oncogene c-MYC and molecular testing for T-cell
receptor or immunoglobulin gene
rearrangements.
• Immunoglobulin determination. Some lymphomas
are associated with IgG or IgM paraproteins,
which serve as markers for treatment response.
• Measurement of urate levels.
Some very aggressive high-
grade
• NHLs are associated with very
high rate levels, which can
precipitate renal failure when
treatment is started as a
consequence of tumour lysis
syndrome.
• HIV testing. HIV is a risk factor
for some lymphomas and
affects treatment decisions.
• Hepatitis B and C testing. This
 Management-
• Low-grade NHL-
• The majority of patients (80%) present with advanced
stage disease and will run a relapsing and remitting
course over several years. Overall survival has
improved in recent years with more treatment options.
• Asymptomatic patients may not require therapy and
are managed by "watching and waiting’.
• Indications for treatment include marked systemic
symptoms, lymphadenopathy causing discomfort or
disfigurement,bone marrow failure & compression
symptoms.
In follicular lymphoma the options are-
• Radiotherapy, this can be used for localised stage I
disease , which is rare. FDG PET-CT-confirmed stage I
disease has a 70% cure rate with radiotherapy.

• Chemotherapy. Most patients will respond to oral therapy

with chlor-ambucil, which is well tolerated, but not
curative and is reserved nowadays for older/trail patients.
More intensive intravenous chemotherapy in younger
patients produces better quality of life through long
periods of remission.

• Monoclonal antibody therapy. Humanised monoclonal

antibodies (biologic therapy’)can be used to target surface
antigens on tumour cells and to induce tumour cell
apoptosis directly. The anti-CD20 antibody rituximab, has
been shown to induce durable clinical responses in up to
60% of patients when given alone, and acts synergistically
when given with chemotherapy. Rituximab (R) in
combination with cyclophosphamide, vincristine and
prednisolone (R-CVP), cyclophosphamide, doxorubicin
• Targeted therapy. The PI3 kinase inhibitor
idealisib is approved for relapsed
follicular lymphoma and ibrutinib (Fig.
25.30) is approved for relapsed mantle
cell lymphoma (a poor-prognosis
lymphoma with low-grade histology, but
aggressive clinical behaviour) and for
relapsed Waldenstrom's
macroglobulinaemia (also known as lym-
Phoplasmacytic lymphoma.
• Transplantation. High-dose chemotherapy
and autologous HSCT
Can produce long remissions in patients
with relapsed disease.
Decisions on the timing of such
treatment are complex in the context of
rituximab maintenance and newer
targeted therapies.
However, younger patients with short first
 High grade NHL-
• Patients with diffuse large B-cell NHL need
treatment at initial presentation:
• Chemotherapy. The majority (>90%) are
treated with intravenous combination
chemotherapy, typically with the CHOP
regimen (cyclophosphamide, doxorubicin
(hydroxydaunorubicin), vincristine (oncovin)
and prednisolone).
Monoclonal antibody therapy. When combined
with CHOP chemo-therapy, rituximab (R)
increases the complete response rates and
improves overall survival. R-CHOP, 4-6 cycles,
is currently recommended as first-line therapy
for all relatively fit patients. Dose reduction
(R-mini CHOP) is preferable in those over 80
years of age and replacement of doxorubicin
with gemcitibine (R-GCVP) is considered in
• Radiotherapy. Stage I patients without
bulky disease are treated with four cycles
of CHOP or R-CHOP, followed by involved
site radio-therapy. Radiotherapy is also
indicated for a residual localised site of
bulk disease after chemotherapy and for
spinal cord and other compression
syndromes.
• HSCT. Autologous HSCT benefits patients
with relapsed disease that is sensitive to
salvage immunochemotherapy. As with HL,
achieving a negative FDG PTC-CT negativity
to autologous transplantation is desirable.
• CAR-T-cell therapy- is licensed for
certain patients with multiply
relapsed DBL or high-grade
transformation of follicular Imphoma
and can salvage patients from a
desparate situation.
 Prognosis -
• Low-grade NHL runs an indolent remitting and
relapsing course, with an overall median
survival of 12 years. Transformation to a high-
grade NHL occurs in 3% per annum and is
associated with poor survival.
• In diffuse large B-cell NHL treated with R-CHOP,
some 75% of patients overall respond initially to
therapy and 50% will have disease-free survival
at 5 years. The prognosis for patients with high
grade NHL is further refined according to the
international prognostic index (IPI). For high-
grade NHL, 5-year survival ranges from over
75% in those with low-risk scores (age <60
years, stage I or lI, one or fewer extranodal
sites, normal LDH and good performance status)
to 25% in those with high-risk scores
• Rearrangements of the c-MYC oncogene,
either alone (more commonly Burkitt
lymphoma) or with rearrangements of BCL-
2 and/or BCL-6 (double or triple hit high-
grade lymphomas) are recognised entities
in WHO classification with poor prognoses
and are increasingly treated more
aggressively.
• Relapse is associated with a poor
response to further chemotherapy (<10%
5-year survival), but in patients under 65
years HSCT improves survival.
Thank you !