Download GP Training Course (Draft 2 -- June 06)

GP Training Course
Module 1
Premalignant and malignant Non Melanoma Skin Tumours
Topic 6 Cutaneous T Cell Lymphoma
Pre reading: Participants should read pages 450 to 453 of the text before
commencing this topic.
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Learning objectives: Participants will be able to:
Identify T cell lymphoma and have an understanding of the differential
diagnoses.
Differentiate and identify the different clinical subtypes of T cell lymphoma
Understand how to investigate suspected T cell lymphoma
Understand the range of treatment options for T cell lymphoma
Clinical Overview
Cutaneous T cell lymphoma is a rare occurrence in most practitioners’ rooms. When the
lesion presents at first it looks more like dermatitis of the skin because of its red colour
and overlying fine scaling. This is known as the patch stage of mycosis fungoides. The
lesions though, unlike dermatitis, do not ooze or weep. The edges are much better
defined than the fuzzy edges you see in a dermatitic reaction and the patches may assume
unusual shapes and occur in areas where you would not normally find dermatitis.
There may be a phase before this known as the pre mycosis fungoides stage when a
nonspecific itchy eruption occurs in the skin. This may take the form of a pink slightly
scaly patch with a wrinkled slightly atrophic surface. It may look like eczema or psoriasis
and is called large plaque parapsoriasis. Unlike psoriasis or eczema the lesions are fixed
and have sharp edges and grow very slowly. When you prescribe topical steroids you
may see an initial improvement but the lesions slowly recur in the same areas. At this
point you should then question your diagnosis and resort to biopsying the skin.
In early T cell lymphoma of the skin it is often very difficult for the pathologist to make a
histological diagnosis. The pathologist is relying on recognising atypical lymphocytes
invading into the epidermis. If he sees the phenomenon of Pautrier microabscesses which
are localised collections of atypical lymphocytes in the epidermis, then he can make a
diagnosis of T cell lymphoma with confidence, but in many of the early lesions he will in
fact sign it out as chronic superficial dermatitis or large plaque parapsoriasis.
The diagnosis of T cell lymphoma of the skin is much easier when the patches develop
into plaques because of an increasing number of lymphocytes in the skin and the plaques
assume more bizarre shapes. When you biopsy one of these, the pathology is much more
likely to show atypical lymphocytes and Pautrier microabscesses. If these plaques are
untreated then the lymphocytes become more and more atypical and evolve into nodules
and may spread elsewhere. The Sezary syndrome is the leukemic phase of mycosis
fungoides. In this condition the patient presents as a red man with erythema involving
the whole body and often hair loss.
T cell lymphoma of the skin is a malignancy of a single clone of CD4 positive T cells.
There is a circulation of lymphocytes between the areas of the skin and draining local
lymph glands. Many lymphocytes will stay within this circulation pathway and not
migrate into the general vascular or lymphatic system. Even when they become slightly
atypical and acquire the ability to invade the epidermis they will still maintain this skin
associated lymphatic system circulation. It is only when they become severely atypical
that they all spread out into the systemic circulation. What it is that causes these
lymphocytes to become atypical in the first place is not known.
To biopsy a suspected lesion of mycosis fungoides or T cell lymphoma you do a punch or
ellipse biopsy. Look for the thickest area of the patch or plaque and biopsy there. With a
patch it is useful to do three biopsies from different areas. Often one of these will show
some of the features of early T cell lymphoma.
T cell lymphoma of the skin progresses very slowly. The lesions may remain in the
patch or early plaque phase for many years, sometimes decades. However once the
tumour phase begins the patient’s survival time can be less than three years, hence it is
important to pick this disease in the early patch or plaque phase. It is important that
steroid therapy is stopped for at least two weeks before performing a skin biopsy. The
pathologist will perform special stains looking to see if the lymphocytes are T
lymphocytes or B lymphocytes. In T cell lymphoma they are all T lymphocytes and they
are usually T helper cells or CD4 cells. Because this is a clonal disease, gene
rearrangement studies can be carried out to show that all the lymphocytes in a particular
biopsy specimen come from the same genetic source. In other inflammatory diseases the
lymphocytes are polygenetic, but in T cell lymphoma they are all clonal and have exactly
the same gene pattern. Some of these studies are best done on fresh tissue although
others can use the formalin fixed tissue.
When the pathologist tells you the patient has T cell lymphoma you should refer this
patient to a specialist for further work up and the staging procedures. The initial staging
involves a full clinical examination looking for lymph gland enlargement and hepato
splenomegaly. Blood is examined looking for Sezary cells and CT scans are done of the
chest, abdomen and pelvis.
For patch stage T cell lymphoma with less than 10% of the body surface covered, the
prognosis is similar to that for normal age matched controls.
For those with greater than 10% of the body surface with patches or plaques or early
tumour stage who are older than 60 years of age, then the median survival is
approximately three years but this can be subdivided further looking at area involved,
patch or plaque and local lymph gland involvement. The five years’ survival for the
tumour or erythrodermic Sezary phases is less than 40%.
There are some rarer variants of T cell lymphoma described:
Patients presenting with a netlike or reticulated pattern of red slightly pigmented lesions
with telangiectasia are said to have the Poikilodermatous variant.
Some patients present with obviously follicular involvement .This may show hair loss
and the skin feels boggy because of mucin in the follicular sheath. A small bead of clear
mucin may appear on squeezing the skin. A patient with multiple follicular lesions has a
worse prognosis than the equivalent plaque stage.
Lymphomatoid papulosis is a rare T cell tumour which looks clinically and histologically
aggressive but which behaves in many cases as a benign process with lesions resolving
spontaneously in a few weeks. However up to 20% may evolve into a lymphoma
including T cell lymphoma.
Teaching Clinical Scenarios
CASE 1
A patient presents with a long standing history of two patches of dermatitic looking skin
on the trunk. There is associated itch. There is some improvement after applying topical
steroids but the lesion recurs in the same area each time.
Question 1 What are your differential diagnoses for this rash?
Question 2 How do you investigate this patient?
Question 3 How do you treat this patient?
ANSWERS FOR CASE 1
Question 1. Eczema, Psoriasis, Tinea corporis. These conditions should be considered
in all red scaly rashes. Bowens Disease, Pagets disease and BCC could also be
considered with long standing red scaly rashes in this area.
Question 2 A skin scraping is the test for tinea but if considering the possibility of T cell
lymphoma then several punch biopsies are taken from the involved area and the clinical
diagnosis of early T cell lymphoma is suggested to the pathologist. Often however this is
not the primary diagnosis and a single biopsy is taken to help. If the result comes back as
possible T cell lymphoma then further biopsies may be necessary to sort it out.
Question 3 Topical steroids may be effective on their own at first but they have to be
strong topical steroids such as Diprosone or Novasone. They should be applied twice
daily to the involved plaque until it disappears and then gradually tailed off.
CASE 2
Question 1 What clinical features of T cell lymphoma of the skin are shown in this
image?
Question 2. Do you think this is an early stage T cell lymphoma or a late stage?
ANSWER FOR CASE 2
Question 1
The image shows marked dusky infiltration of the skin with extension on to the upper
arm. There is early plaque formation and some features of poikiloderma with
pigmentation and telangiectasia.
Question 2.
This is a late stage and the presence of poikiloderma and plaques is worrying.
CASE 3
These lesions have been present for two years and have been slowly growing.
Question 1 What clinical features suggest T cell lymphoma of the skin?
Question 2 What is the best treatment option for this stage tumour?
ANSWERS
Question 1 The shape of thee lesions is unusual and fixed. The lesions have been slowly
growing and joining together to form these unusual shapes.
Question 2 This is patch stage T cell lymphoma. If strong topical steroids have been
tried already and failed then some ultraviolet therapy with oral psoralens and UVA light
or narrow band UVB will be helpful. Treatment should be given initially three times a
week and reduced to maintenance therapy once every week or two to keep the skin clear.
CASE 4
This well circumscribed asymptomatic spotty patch has been present on this 45 year old
ladies buttock for several years.
Question 1 This is a particular morphological variant of T cell lymphoma of the skin.
Which one is it?
Question 2 What might be found on squeezing the skin?
Question 3 Does this variant have a poorer prognosis?
Question 4 What treatments would you use sequentially in treating this patient?
ANSWERS
Questions 1 This is the follicular variant of T cell lymphoma of the skin
Question 2 Sometimes a small bead of clear mucin can be squeezed from the follicle
opening. Any hairs in the area may be lost so it can present as an area of alopecia in a
predominantly hair bearing area.
Question 3 Yes this variant does have apoor prognosis especially if there are multiple
lesions. These lesions should be treated aggressively.
Question 4 Initially a strong topical steroid twice daily for a month. If there is no
response and the area is localized try some intralesional steroid diluted Kenacort A10 and
review. The next step would be localized PUVA therapy and lastly localized Xray
therapy. T cell lymphomas are very susceptible to Xrays although the therapy is mainly
used for localized tumour stage lesions.
CASE 5
This young man presented with a nodule on his forehead which was biopsied and
said to be an insect bite reaction. It resolved over a four week period but he then
developed these lesions on his chest wall.
Question 1 What condition is he suffering from? Consider the rapid resolution of some
of his lesions without treatment.
Question 2 Can this condition evolve into a lymphoma?
Question 3 What is the prognosis for this condition?
ANSWERS
Question 1 This is lymphomatoid papulosis.
Question 2 It can evolve into various forms of lymphoma of the skin but in a majority of
cases it occurs in crops of lesions which resolve and then flare again.
Question 3 This condition is a form of T cell lymphoma of the skin where many of the
lesions actually resolve on their own. However a proportion of patients, about 20%, will
evolve into a lymphoma, either T cell lymphoma and sometimes Hodgkin’s disease. The
papules and nodules are usually a reddish brown in colour and can undergo central
necrosis and spontaneous healing with scar formation. The lesions often arise in crops
particularly on the trunk and extremities and can do so over months or years, but it is
important to remember that these lesions can evolve into a T cell lymphoma. They
respond well also to radiotherapy or to ultraviolet therapy.
CASE 6
This patient presents with skin that has apparently aged over the last few years
unexpectedly. There are varying areas of wrinkling of the skin with pigmentation and
telangiectasia. The skin surface has an atrophic appearance.
Question 1 What variant of T cell lymphoma of the skin is this and how would you
investigate it?
Question 2 What therapy would be best for this elderly lady?
ANSWERS
Question 1 This is the poikilodermatous variant. It can be slightly more aggressive than
the patch stage mycosis fungoides. It is diagnosed again by several biopsies being taken
and the pathologist being alerted to the possible diagnosis.
Question 2 The best therapy for this generalized variant of T cell lymphoma in an elderly
lady would be ultraviolet therapy using narrow band UVB or PUVA therapy using oral
psoralens and UVA light. This is given 3 times a week for 6 weeks to gain clearance and
then maintanence therapy is given once every one to two weeks to keep the condition
controlled.
Case 7
This 73 year old man has suffered from a chronic rash for many years but over the past 2
years there have been dramatic changes develop with significant thickening of the skin
and diffuse redness.
Question 1 What is this stage of T cell lymphoma called?
Question 2 Is this Sezary’s syndrome?
ANSWERS
Question 1 Tumour Stage Mycosis Fungoides. It is this stage that gives the name
mycosis fungoides to T cell lymphoma of the skin. Visceral metastasis can occur during
this stage to the spleen, lungs, liver or gastrointestinal tract. When the skin is
erythrodermic like this Sezary cells may be found circulating in the blood and comprising
between 5 and 20% of circulating lymphocytes.
Question 2 True Sezary syndrome is the leukemic form of T cell lymphoma of the skin
presenting with generalized itch, exfoliative dermatitis ,skin thickening,hair loss and the
finding of more than 1000 of these atypical circulating lymphocytes per cc of blood. In
Sezary’s syndrome the patients may not have any tumours in the skin.
End of Topic ASSESSMENT TASKS
CASE 1
This 55 year old man has had this rash slowly spreading over many years.
a) This is most likely a T cell lymphoma of the skin?
b) It is likely to show some response to strong topical steroids?
c) The condition may remain limited to the skin for years?.
d) It is a tumour of T suppressor cells?
e) The diagnosis is easily made on biopsy and histology?
(True)
(True)
(True)
(False)
(False)
Answers
This is a T cell lymphoma of the skin. There is little scale and the patches look fixed in
the skin. There will be some response to strong topical steroids but the lesions are likely
to slowly recur in the same areas. T cell lymphoma remains in the skin for many years
before spreading elsewhere. It is often difficult to make the diagnosis histologically early
in the piece and the report may come back as chronic superficial dermatitis.
CASE 2
This 68 year old man has widespread thickening and scaling and erythema of his skin
which has been progressively worsening in recent years.
Question 1This patient will respond to topical steroids?
(False)
Question 2 This patient is at risk of visceral metastases.
(True)
Question 3 The histology is likely to show Pautrier microabscesses
(True)
Question 4 He may suffer from alopecia in hairy areas
(True)
Question 5 This stage may respond to electron beam therapy
(True)
Answers
This man has a generalized infiltrative type of T cell lymphoma of the skin.It is very
unlikely to respond to topical steroids because of the thickness of the infiltrate. He is
equally unlikely to respond to phototherapy with PUVA again because of the thickness of
the infiltrate and the difficulty of light penetrating the infiltrate. Electron beam therapy
could be used here because the radiotherapists can dial up different thicknesses of
penetration. This man is at great risk of systemic metastases. Infiltration of hairy areas
will produce alopecia.
CASE 3
This patient has a T cell lymphoma of the skin.
Question 1 He is likely to have lymphadenopathy in his groin
(False)
Question 2 This is known as patch stage mycosis fungoides?
Question3 His histology is likely to be positive?
(False)
(True)
Question 4 He needs an extensive work up for staging ?
Question 5 Topical Nitrogen mustard could be used to treat this lesion?
(True)
(True)
Answers
This is plaque stage T cell lymphoma of the skin. If these are his only lesions it is
unlikely he will have groin lymphadenopathy. A punch biopsy of his skin is likely to
show a marked lymphocytic infiltrate with atypical lymphocytes extending into the
overlying epidermis forming Pautrier’s microabscesses. Despite the likliehood this is still
localized to the skin I would carry out a CAT scan for local and systemic
lymphadenopathy to stage him properly. Topical nitrogen mustard has been used
effectively in this condition but needs to be formulated specially by a pharmacist and is
not a first line treatment.
End of Module Assessment Task
CASE 4
This is a patient with patch and plaque stage mycosis fungoides involving more than 10%
of the body surface area with no local lymphadenopathy.
Question 1 He has a greater than 50% 5 year survival
(True)
Question 2 PUVA therapy would be good treatment for him?
(True)
Question 3 Any lymphadenopathy he has would definitely signify tumour
in the lymph nodes ?
(False)
Question 4 As plaques develop itching becomes less severe?
(False)
Answers
This is a more generalized case of patch and plaque stage T cell lymphoma of the skin. It
would be difficult to treat with topical steroids. It should respond well to UV therapy . If
any lesions are slow to respond they can be treated with localized radiotherapy. This is
stage 2b T cell lymphoma with more than 10% of the body surface involved by patch or
plaque lesions but with no lymphadenopathy. The 5 year survival would be 75% and the
10 year survival 50%. If there were just patches but no obvious plaques the 5 year
survival would be 90%. Itching is likely to become more severe rather than less as
plaques develop. Lymphadenopathy may be reactive rather than signify local gland
involvement but this can only be decided after needle biopsy and histopathology
examination. Reactive glands will disappear after local skin treatment.