|You are here: Home: Meet The Professors Vol. 3 Issue 1 2005: Case 5
Edited excerpt from the discussion:
DR LEONARD: We have a patient who
has skin-only involvement with follicular
lymphoma. In general, I think skin involvement
of lymphoma is among the more difficult
pathologic diagnoses to make. This is
one scenario in which eliciting an opinion
from an experienced hematopathologist
or dermatopathologist is important. Pathologists often have different opinions
in this situation. The type of lymphoma isn’t
always clear because lymphoid proliferations
can arise in the skin for many reasons.
That being said, an interesting issue is
MALT lymphoma (MALToma) of the skin,
which is one of the more common B-cell
subtypes. Some association has been made
between MALToma of the skin and infectious
agents; therefore, it’s something I
always consider. Although this patient has
a follicular lymphoma, not a MALToma, I
wonder whether we should chase after that
a little bit.
With those kinds of sidebars, I think a
patient with a follicular lymphoma of the
skin who has no disease elsewhere is likely
to do well in the long term. Often these
patients will have disease that, for whatever
reasons, recurs only in the skin. These
are four-millimeter lesions, so I would be
inclined to do relatively little — topical
steroid treatment, local radiation or no
Whether or not you chase after the skin
lesions is a clinical judgment based on the
scenario. I’m not sure systemic therapy,
whether it is rituximab or chemotherapy,
is going to change the big picture for this
patient. I don’t know that we have any
randomized trials showing that systemic
therapy makes a difference. My inclination
would be to do less, rather than more.
DR LOVE: From a psychosocial perspective,
do you think the patient and his wife would
have been able to accept watchful waiting?
DR GULATI: No. That was the major issue.
Watchful waiting was offered to them, but
they are clearly the nervous type. They
chose rituximab, which we gave weekly for
four weeks followed by monthly for four
months, for a total of five months.
DR LOVE: What happened to the lesions?
DR GULATI: The lesions disappeared by the
second treatment. The patient was doing
fine, but he was obviously worried. Every
time he came in, we would discuss the
issue. An episode occurred during which the
patient said he felt like fainting. He was
rushed to the emergency room where he had
a full coronary workup, but everything was
I called him before this conference and he
said he has a few new skin lesions near the
initial site. The patient was anxious; he
did not want these lesions on his skin. If
a remission occurred, it lasted only about
nine or 10 months. This is a Bcl-2-positive
lymphoma, so I don’t think that it is follicular
or lymphoid hyperplasia. He’s going to
come in and have a biopsy, and the question
will arise: What will be the next treatment?
DR C FARBER: I would be inclined to utilize
electron beam radiation therapy with a wide
field and an adequate margin in this patient.
That would probably prevent at least a local
recurrence. The lesions may keep recurring
just outside the field, in which case
it’s almost like spot welding. Electron beam therapy offers a low morbidity and it should
DR LOVE: What about electron beam therapy
in this situation, Dr Leonard?
DR LEONARD: I think it’s certainly reasonable
if the lesions are in the same area. It is
probably not going to change his long-term
outcome. You’re not going to prevent recurrence
elsewhere by removing these lesions.
It’s a matter of just chasing after them. It
may reach a point at which you question
whether it is worth the effort. If you treat
him and then a month later a lesion pops
up somewhere else, you start to wonder if
it may be easier for him to receive a couple
“squirts” of rituximab and go into remission,
rather than undergo re-treatment.
Again, that’s a clinical judgment. I’d be
inclined to do less, rather than more. If
you’re forced to treat him, I think it’s a
matter of the time and effort involved in
chasing after this, which is really psychological
palliation more than anything.
DR RADER: At some of the breast cancer
meetings, we discuss immunohistochemistry
for ER and how unreliable it is.
In patients with lymphoma, I’ve seen
multiple different opinions on whether cells
have been transformed — whether they’re
large or small cells — or whether the flow
cytometry agrees with the histological
picture. Do you believe that, routinely, most
lymphomas should have a second pathology
opinion. When the second opinions are
widely divergent, what type of evidence do
you evaluate next?
Second opinions are often 180 degrees
different. These opinions influence therapy
— like CHOP versus watchful waiting — so
should second opinions be routine?
DR SMITH: I see a lot of patients who were
referred to me for a second opinion, and
when I discuss the case with the referring
doctor, it’s clear that I’m going to not
change the oncologist’s opinion. However,
whether it’s low grade or aggressive
lymphoma, the key to a second opinion is a
review of the pathology.
Approximately a third of the time we will
have a change regarding pathology. Often
the change is minor; however, sometimes it
is major, making it low grade versus aggressive
— particularly when the lymphoma is
in extranodal sites, such as the stomach or
skin. Second opinions are critical, but then
what do you do? Is it best two out of three?
In community practices, I find that the
slides are usually analyzed locally, and the
flow goes to someone at an outside lab who
knows nothing about the patient or the
physician. At our place, after I’ve seen the
patient, I sit down with my hematopathologist,
who also does the flow. We discuss the
issues, and come up with something. It’s not
so much that the stain or the flow is wrong,
but that you have to put the whole picture
together before it can make sense. That’s
one of the concerns, particularly if you’re in
a small hospital.
DR LEONARD: I agree; it is easy to ascertain
a pathologic second opinion — it’s simply
a matter of sending the slides; the patient
doesn’t have to go. Generally, pathologists
will discuss it with you over the phone,
even if you’re at another institution. It’s
not a big deal to do, and the pathology is
key. I believe a pathologic second opinion
is more important than another lymphoma
subspecialist’s opinion. We re-evaluate a
situation based on our pathologist giving
us information that the primary oncologist
didn’t have; therefore, I encourage patients
to ascertain a pathologic second opinion. It
is a relatively easy thing to do, and it gives
the patients some reassurance.
I think all patients diagnosed with mantle
cell lymphoma should also have a second
pathology opinion. That’s a hard diagnosis
to make and the implications, as far as the
prognosis, are enormous. Additionally, if the
disease is acting like one type of lymphoma,
but the pathologist is telling you it’s
another type of lymphoma, maybe that’s a
red flag that you ought to have it evaluated
by someone else.
Finally, gray areas exist when you see
follicular and diffuse lymphomas, and you
are trying to decide if transformation has occurred and whether you need to use an
anthracycline — this is an area in which I
would encourage a second opinion from the
DR BHARDWAJ: Some changes have
occurred in terms of how the insurance
companies are reimbursing for second
opinions. At some institutions, the
Pathology Department is now billing the
hospital Pathology Department, and not the
patient. That puts a crimp in terms of where
the patients’ slides are being sent.
DR LEONARD: Second-opinion slides are the
best spent $300 or $500 that a patient will
invest. Even if you have to tell the patient,
“Insurance isn’t going to cover it,” this
has such important implications, at least
in lymphoma, that if the patient can do it,
even if they have to pay out of pocket, I
DR SMITH: A more difficult situation is
when patients have large cell lymphoma
isolated to the skin, because it looks ugly
but often behaves indolently. Can you give
rituximab as a single agent or local radiation
to a patient who, histologically, has
large cell lymphoma? According to the literature,
large cell lymphoma in the skin tends
to behave more indolently. That is a second
opinion that we see often, and my reply is,
“Maybe you need to be aggressive with this
DR LOVE: Any hints in terms of pathophysiology
of cutaneous lymphoma in terms of
why it has this natural history?
DR SMITH: As John mentioned, the
MALTomas of the skin might be infection-driven.
We don’t know much about the
lymphocytes that are normally in the skin,
why they home there and how they behave
day to day. There is probably something
there that we should be learning about, but
we don’t know that much about it.
DR LOVE: Dr Gulati, how are you going to
treat this patient?
DR GULATI: My previous experience with
electron beam, especially for large cell
lymphoma, has not been good. This is
the first time I’ve seen a follicular Bcl-2-
positive, so I’m open-minded. Rituximab
worked; therefore, I am tempted to give
more rituximab although the remission
didn’t last more than seven months. The
story is incomplete. I think the workup
will be important. If he has positive lymph
nodes, then he’s going to receive chemotherapy.