Welcome to this lecture on the important topic of lymphoma.
In this lecture, you will learn a number of important points.
the malignant lymphoid cells accumulate in lymphoid tissue rather than blood.
There are two broad subtypes of lymphoma.
Hodgkin lymphoma and non-Hodgkin lymphoma.
Hodgkin lymphoma is diagnosed by the presence of the Reed-Sternberg cell.
Whereas non Hodgkin’s lymphomas
are an extremely heterogeneous group of disorders.
Now lymphoma is a disorder of malignant lymphoid cells.
But in lymphoma, these cells accumulate in lymphoid tissue,
whereas in leukemia, they are mainly in the bone marrow and blood.
If we look at the slide on the right,
you’ll see that this patient has a very large lymph node mass in the neck.
The incidents of lymphoma is increasing particularly non Hodgkin lymphoma.
We really don’t know the epidemiology behind this trend.
The treatment of lymphoma depends on the accurate diagnosis
of the disease subtype.
And during this lecture we'll spend time
working out how to make the correct diagnosis.
Let’s start with Hodgkin lymphoma.
This disorder which described by Thomas Hodgkin in 1832.
He worked at Guy’s Hospital in London.
And on the right, this very beautiful drawing,
shows the original description of Hodgkin lymphoma from that time.
And it actually shows one of the major features of Hodgkin lymphoma
which is it tends to spread down the lymphatic system,
in this case from the neck into the axillary lymph nodes.
The most common presentation of Hodgkin lymphoma
is with enlarged lymph nodes usually in the neck.
And as I said from the picture, it tends to spread
through the lymphatic system rather than through other tissues.
There may be additional symptoms
which are important in staging Hodgkin lymphoma.
These are fatigue, weight loss, and fever.
Now, the diagnosis of Hodgkin lymphoma, as with all diseases
depends on the history, examination, and investigations.
On the history, should focus on the time course
of the swelling of the lymph nodes
which may indicate any other systemic symptoms as well.
EBV infection is an implicated
as cause of many cases of Hodgkin lymphoma.
This is seen because there is evidence of EBV infection
in many of the tumor cases.
And also, interestingly, when some people get their first EBV infection,
they can get glandular fever or infectious mononucleosis.
Although that always clears up, many years later they do carry a high risk
of developing Hodgkin lymphoma.
The examination of the patient should be of the major lymph node groups.
In the neck, under the arms, and in the abdomen and groin.
Blood test may show anemia
and very often patient will have a CT or an MRI scan to look for evidence of disease.
On the right, you can see a chest x-ray
showing mediastinal lymphadenopathy.
But to make the diagnosis you need to get some lymph node tissue
and that biopsy is critical for looking for the Reed-Sternberg cell.
This is the characteristic feature of Hodgkin lymphoma,
the Reed-Sternberg cell.
It’s an unusual cell in histology.
It is large, generally has a bilobed nucleus
and has a very prominent nucleoli.
You can see some of the cells on that specimen
which have a white cytoplasmic halo and a very prominent nucleolus.
The Reed-Sternberg cell is derived from a B cell
and it’s expresses its mark such as CD15 and CD30.
And pathologists use these stains to make the diagnosis of Hodgkin lymphoma.
Pathologists also categorize Hodgkin lymphoma into 4 major types.
Nodular sclerosing, mixed cellularity,
lymphocyte depleted, and lymphocyte predominant.
And this will affect the outlook and prognosis of the patient in some cases.
Now when a patient is diagnosed with Hodgkin lymphoma
it’s very important to stage the disease.
And essentially what we’re doing here
is seeing how far the disease has progressed
because that will indicate the type of treatment that we need to give.
Hodgkin lymphoma is staged from I to IV.
Let’s look at this in more detail.
In stage I disease, there is swelling of a lymph node area in one region
perhaps in the neck as shown on this picture.
In stage II, there is involvement of two lymph node groups
but on the same side of the diaphragm, as you’ll see in the picture there,
in which case we have lymph node swelling and mediastinal swelling.
Stage III disease, shows disease of above and below the diaphragm.
Whereas stage IV, is disseminated disease
and involves non-lymphoid tissues perhaps the spleen
or the bone marrow.
In addition, we also have to stage the disorder
on whether the patients have systemic symptoms
such as fevers or weight loss.
A, indicates the absence of these
whereas B, indicates that these are present
and that represents a more challenging disease to treat.
So a patient may be categorized as stage IIA or IIIB for example.
Now the treatment of Hodgkin lymphoma
depends on the use of chemotherapy and radiotherapy
in various degrees of combination.
The standard chemotherapy regimen for many years
has been that ABVD regimen.
adriamycin, bleomycin, vinblastine, and dacarbazine.
And it’s a very effective treatment to Hodgkin Lymphoma.
Now one of the big questions
when you are thinking about treatment of Hodgkin Lymphoma is
the amount of chemotherapy and perhaps radiotherapy
which you might want to give to the patient.
And doctors are moving towards trying to minimize the amount of treatment
that is given so as to maintain a high cure rate
while it’s limiting the side effects of chemotherapy and radiotherapy.
Here I’ve shown some examples of regimens
that you might consider for different stages of disease.
So stage IA is very early disease, limited to one area
and with no systemic symptoms.
And here, relatively short courses of chemotherapy
or chemotherapy with small amounts of radiotherapy may be used.
For stage IB or II,
you might want to give 4 to 6 courses of ABVD every month.
And maybe, only give radiotherapy to very large lymph node groups.
Whereas for more advanced disease
you may wish to give a lot many more courses, 6 to 8 courses of ABVD
and with radiotherapy to lymph nodes that remain at the end of treatment.
But people are always trying to improve and advance treatment
and some centers use slightly different chemotherapy regimens,
and there’s an example there of one that is used for intensive—
for more intensive chemotherapy called BEACOPP
which incorporates some additional chemotherapy agents.
Now the PET scan,
the positron emission tomography scan is highly important
in the treatment of Hodgkin lymphoma.
The PET scan involves the injection of fluorodeoxyglucose
which is an analogue of glucose.
And it’s taken up by tumor cells,
in this case Hodgkin lymphoma cells and then admits gamma rays.
These are detected by an external scanner,
and it can be combined with the CT scan as a PETCT scan.
You can see that on the right.
Now PET scans are very useful for indicating areas of active tumor.
They can be useful for guiding the need for further treatment
and also for distinguishing between tumor and scar tissue.
That’s particularly important in Hodgkin Lymphoma,
because lymph nodes can remain large
even after treatment when there is no active disease.
And the other area where PET scans are quite interesting
is that they may be used to guide and potentially limit
the amount of treatment that are given to individual patients.
So to titrate a therapy against the response.
The outcome for patients with Hodgkin Lymphoma are very good,
Unfortunately relapse can occur, and this tends to be treated by
different course of chemotherapy, a stem cell transplant,
perhaps, using stem cells from the patient’s themselves
called an autologous transplant
or allogeneic transplant from another person.
Antibodies to block PD-L1 are emerging
as a very effective immune therapy for Hodgkin lymphoma.
It may actually come to be used in first line therapy in future years.
And antibodies against CD30
which we learned early on as expressed on those
Reed-Sternberg cells are also proving effective.
If we put all of these together,
we can see that overall survival is excellent
for patients with Hodgkin Lymphoma
and over 85% of patients can achieve a long-term cure.
But the major concern with therapy in Hodgkin lymphoma
is to avoid the complications of the treatment itself.
This could be seen as secondary malignancies many years later
or cardiac toxicity from the chemotherapy and radiotherapy.
And that has driven the move to limit the chemo and radiotherapy
to just a minimum needed for disease control.