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48
Lymphedema
Definition
Lymphedema is a very common and serious
condition, affecting at least 3 million Ameri-
cans. It occurs if the transport capacity (TC) of
the lymphatic system has fallen below the nor-
mal amount of lymphatic load (LL; see Chap-
ter 2, Mechanical Insufficiency), resulting in
the abnormal accumulation of water and pro-
teins principally in the subcutaneous tissues.
Lymphedema may be present in the ex-
tremities, trunk, abdomen, head and neck, ex-
ternal genitalia, and inner organs; its onset is
gradual in some patients and sudden in others.
Most patients in the Western Hemisphere
develop lymphedema after surgery and/or
radiation therapy for various cancers (breast,
uterus, prostate, bladder, lymphoma, mela-
noma), in which case it is referred to as sec-
ondary lymphedema. Other patients develop it
without obvious cause at different stages in life
(primary lymphedema), and still others deve-
lop it after trauma or deep vein thrombosis. In
third world countries, parasites (filariasis) ac-
count for millions of cases.
Lymphedema is serious because of its long-
term physical and psychosocial consequences
for patients; it continues to progress if left un-
treated. If lymphedema combines with other
pathologies (cardiac and venous insufficien-
cies, chronic arthritic conditions, etc.), the
pathophysiological effects are further exacer-
bated due to the additional stress placed on
the already compromised lymphatic system
(see Chapter 2, Combined Insufficiency). Its
cosmetic deformities are difficult to hide, and
complications do occur frequently (fibrosis,
cellulitis, lymphangitis, lymphorrhea, etc.).
Lymphedema is also serious because of the
pervasive lack of medical expertise in the diag-
nosis and treatment of this condition and the
tendency of clinicians to trivialize lym-
phedema in patients who have been treated
for cancer.
Incidence of Lymphedema
No specific studies on the incidence of lym-
phedema have been performed to date, and
estimated rates reported in the literature vary
widely. Worldwide, 140 million to 250 million
cases of lymphedema are estimated to exist,
with filariasis, a parasitic infestation (see Sec-
ondary Lymphedema later in this chapter),
being the most common cause.
In the United States, the highest incidence of
lymphedema is observed following breast
cancer surgery, particularly among those who
undergo radiation therapy following axillary
lymph node dissection.
Other than skin cancer, breast cancer is the
most common type of cancer among women in
the United States. All women are at risk for
developing breast cancer. A woman’s chance of
developing breast cancer increases with age.
The majority of breast cancer cases occur in
women over 50 years of age. Although breast
cancer is less common at a young age, younger
women tend to have more aggressive types of
breast cancer than older women, which may
explain why survival rates are lower among
younger women. Incidence also varies within
ethnic groups and geographical location
within the United States (Table 3−1).
Generally, it can be said that 1 out of 8
women in the United States will develop breast
cancer during the course of their lives. (More
information can be found on the National
Institute for Cancer Web site at
http://cancer.gov/cancerinformation.)
Other cancer survivors at risk for lym-
phedema include those who have undergone
surgery and/or radiation treatment for malig-
nant melanoma of the upper or lower extremi-
ties; prostate cancer; gynecologic cancers;
ovarian, testicular, and prostate cancers; and
colorectal, pancreatic, or liver cancers. Some
studies report an incidence of lower extremity
lymphedema (and/or genital lymphedema)
after radical lymph node dissection in prostate
cancer to be more than 70 %.
Table 3−1 Incidence of Breast Cancer by Age
By age 30
By age 40
By age 50
By age 60
By age 70
By age 80
Ever
1 out of 2212
1 out of 235
1 out of 54
1 out of 23
1 out of 14
1 out of 10
1 out of 8
Source: National Cancer Institute, 1999
3 Pathology
49
It is generally thought that the more lymph
nodes are removed during any surgical pro-
cedure, the higher the incidence of lym-
phedema. The true numbers of patients suffer-
ing from any form of lymphedema are un-
known.
Most statistics are available on the incidence
of upper extremity lymphedema following
breast cancer surgery in women. Studies show
incidences varying from 6 to 70% of breast
cancer patients (a report in the April 1984
issue of Breast Cancer Digest found that 苲50 to
70% of patients who have had axillary node
surgery will develop lymphedema). In general,
studies with longer follow-up show higher in-
cidence and more severe swelling. Some
authors feel that with the more conservative
surgical procedure (modified radical mas-
tectomy), the incidence has decreased. Sur-
geons hope that the sentinel node procedure
(see discussion in Secondary Lymphedema
later in this chapter) will reduce lymphedema
because it removes fewer nodes. Presently,
there is not enough follow-up information
available to state this with certainty.
Based on the numbers above and other
statistics, it is estimated that 2 million to 3 mil-
lion secondary and 1 million to 2 million pri-
mary lymphedema cases are currently in ex-
istence in the United States.
Lymphedema may develop anytime during
the course of a lifetime in primary cases. Sec-
ondary cases may occur immediately post-
operative, within a few months, a couple of
years, or twenty years or more after surgery.
Etiology of Lymphedema
Lymphedema can be classified as primary or
secondary, based on underlying etiology.
However, this classification usually has little
significance in determining the method of
treatment (Table 3−2).
Primary Lymphedema
Primary lymphedema represents a develop-
mental abnormality (dysplasia) of the lym-
phatic system, which is either congenital or
hereditary. It can present as a variety of abnor-
malities.
Hypolasia. This most common form of dys-
plasia refers to the incomplete development of
lymph vessels; that is, the number of lymph
collectors is reduced, and the diameter of ex-
isting lymph vessels is smaller than normal.
Hyperplasia. The diameter of lymph collec-
tors is larger than normal in this dysplasia
(lymphangiectasia or megalymphatics). The di-
lation of the lymph collectors results in a
malfunction of the valvular system within the
collectors, which often leads to lymphatic re-
flux.
Aplasia. The absence of single lymph collec-
tors, capillaries, or lymph nodes associated
with this abnormality may be a cause for the
development of primary lymphedema.
Table 3−2 Etiology of Lymphedema
Primary Lymphedema Secondary Lymphedema
쐌
Aplasia
쐌
Hypoplasia
쐌
Hyperplasia (lymphangiectasia/megalym-
phatics)
쐌
Fibrosis of lymph nodes
쐌
Agenesis of lymph nodes
쐌
Congenital
쐌
쏝 35 years of age: lymphedema praecox
쐌
쏜 35 years of age: lymphedema tarda
쐌
Dissection of lymph nodes
쐌
Radiation
쐌
Trauma
쐌
Surgery
쐌
Infection
쐌
Malignancies
쐌
Chronic venous insufficiencies
쐌
Immobility
쐌
Self-induced
Lymphedema
50
Fibrosis of the inguinal lymph nodes (Kin-
month syndrome) presents an additional
cause for the onset of primary lymphedema.
The fibrotic changes primarily affect the
capsular and trabecular area of the involved
lymph nodes. This may affect lymph transport
in the afferent lymph collectors.
With the understanding of basic lymphatic
system physiology, it becomes evident that the
transport capacity of the lymphatic system in
all the abnormalities listed above is reduced
(Fig. 3−1). As discussed in Chapter 2, lymph-
edema occurs if the transport capacity of the
lymphatic system falls below the normal
amount of lymphatic loads.
Although the developmental abnormalities
are present at birth, lymphedema may develop
at some point later in life. It may not develop at
all as long as the (reduced) transport capacity
of the lymphatic system is sufficient enough to
manage the lymphatic loads. Primary lym-
phedema is often classified by the age of the
patient at the onset of swelling.
Congenital lymphedema is clinically evident
at birth or within the first 2 years of life. A sub-
group of patients with congenital lym-
phedema has a familial pattern of inheritance,
which is termed Milroy’s disease. If primar y
lymphedema presents after birth but before
the age of 35, it is called lymphedema praecox,
which is the most common form of primary
lymphedema and most often arises during
puberty or pregnancy. Lymphedema tarda is
relatively rare and develops after the age of 35.
Primary lymphedema almost exclusively af-
fects the lower extremity (unilateral and bi-
lateral) and involves mostly females. The swel-
ling usually starts at the foot and ankle and
gradually involves the remainder of the ex-
tremity. It may occur without any known im-
petus or may develop after minor trauma (in-
sect bites, injections, sprains, strains, burns,
cuts), infections, or immobility. These trigger-
ing factors produce additional stress to the al-
ready impaired lymphatic system, resulting in
mechanical insufficiency (Fig. 3−2).
Secondary Lymphedema
The mechanical insufficiency present in sec-
ondary lymphedema is caused by a known in-
sult to the lymphatic system.
Most common causes for secondary lym-
phedema include surgery and radiation,
trauma, infection, malignant tumors, immo-
bility, and chronic venous insufficiencies.
Lymphedema may also be self-induced.
Surgery and radiation: As outlined earlier,
this is by far the most common cause for sec-
ondary lymphedema in the United States. Sur-
gical procedures in cancer therapy commonly
include the removal (dissection) of lymph
nodes. The goal of these procedures is to elimi-
nate the cancer cells and to save the patient’s
life.
A side effect in lymph node dissection is the
disruption in the lymph transport. If the re-
maining lymphatics are unable to manage the
lymphatic load, secondary lymphedema will
develop.
TC
(reduced)
TC (normal)
LL
(normal)
LTV max
Figure 3−1 Reduced trans-
port capacity in the subclinical
stage of lymphedema. LL, lym-
phatic loads or lymph volume;
LTV, lymph time volume (TC =
LT V
max
); TC, transport capacity
of the lymphatic system.
3 Pathology
51
In the early years of breast cancer surgery,
radical mastectomy was the only option availa-
ble for patients. Radical mastectomy includes
the removal of the entire mammary gland, the
axillary lymph nodes, and the pectoralis
muscles under the breast. Although common
in the past, radical mastectomy is now rarely
performed and is recommended only if the
cancer cells have spread to the muscles under
the mammary gland. Modified radical mas-
tectomy is now more commonly performed.
This procedure includes the removal of the
breast and part of the axillary lymph nodes. In
certain forms of breast cancer, a simple or total
mastectomy is performed, in which only the
mammary gland, but not the axillary lymph
nodes, is removed.
Today, many women with breast cancer are
given the choice between mastectomy and
lumpectomy. In lumpectomy, also referred to as
breast-conserving surgery, only the part of the
mammary gland containing the malignant
tumor and some of the normal surrounding
tissue are removed. Most women after breast
surgery, especially after lumpectomy, receive
radiation treatments (Fig. 3−3).
Sentinel lymph node biopsy, a relatively new
technique, was developed to determine if
cancer cells have spread to the axillary nodes
and trunks, without having to perform a tradi-
tional axillary lymph node dissection during
which, on average, 苲 10 to 15 axillary lymph
nodes are removed. A sentinel lymph node
Figure 3−2 Primary lymphedema of the left lower
extremity.
Figure 3−3 A. Secondary lymphedema of the left
upper extremity. B. Secondary lymphedema of the left
upper extremity following bilateral mastectomy.
A
B
Lymphedema
52
biopsy requires the removal of only those
lymph nodes to which the mammary gland
drains first (sentinel nodes) before reaching
the rest of the axillary lymph nodes. A patholo-
gist then closely reviews these one to three
lymph nodes. If they do not contain malignant
cells, the chance that the remaining axillary
nodes are cancer free is 苲 95 %, and removal of
additional axillary nodes may be avoided.
Radiation (or radiotherapy) is the treatment
of cancer and other diseases with ionizing
radiation. The goal of this therapy is to destroy
cancer cells that may linger after surgery. It
uses either precisely aimed, high-energy, ex-
ternal beam radiation or radioactive seeds that
are implanted in the tumor area. Malignant
cells often grow at a faster rate than normal
cells; this makes many cancers very sensitive;
that is, vulnerable to radiation.
Although radiation damages both cancer
cells and normal cells, the normal cells are
able to repair themselves and continue to
function properly. Radiation is usually admin-
istered 5 days a week for several weeks and
may also contribute to the onset of lymph-
edema. Rays can cause fibrosis in the tissues,
leading to an impaired lymph transport, and
hinder the regeneration of lymph vessels.
Radiation may also affect nervous tissue,
which can result in numerous problems affect-
ing either the lymphedema itself or the
patient’s ability and compliance during the
treatment of the lymphedema (radiation plex-
opathy; see Complications in Lymphedema
later in this chapter).
Trauma: Traumatic insults involving the
lymphatic system may cause a significant re-
duction in lymph flow, resulting in secondary
lymphedema (burns, larger skin abrasions).
Scar tissue hinders regeneration (lympholym-
phatic anastomosis) of lymph collectors,
further exacerbating the problem. Post-trau-
matic secondary lymphedema develops from a
mechanical insufficiency of the lymphatic sys-
tem as a result of tissue lesions and should not
be confused with post-traumatic edema. Post-
traumatic edema is a local result due to
trauma, which usually recedes after a few days
(see Lipedema later in this chapter).
Infection: Recurrent acute or chronic inflam-
matory processes affecting the lymphatic sys-
tem may result in mechanical insufficiency. If
inflammation involves lymph nodes (lymph-
adenitis) or collectors (lymphangitis), the
walls tend to become fibrotic and the lymph
fluid coagulates and obliterates the lymphat-
ics, thus creating blockage to the lymph flow.
In addition to the existing mechanical insuffi-
ciency, there is an increase in the volume of
lymphatic load, resulting in combined insuffi-
ciency.
Lymph node and lymph vessel infections can
be caused by bacteria (especially Streptococ-
cus) and fungal infections. The inflammatory
process affecting intra and periarticular tissues
in rheumatoid arthritis may spread to the lym-
phatics, presenting another cause for mechani-
cal insufficiency (see Traumatic Edema later in
this chapter).
The most common cause for inflammation of
the lymphatic system and lymphedema in
general is filariasis (Fig. 3−4A).
Lymphatic filariasis is endemic in more than
80 countries in the tropics and subtropics and
is caused by threadlike, parasitic filarial
worms, Wuchereria bancrofti, that live almost
exclusively in humans.
Lymphatic filariasis is transmitted when an in-
fected mosquito bites a person, then goes on to
bite others, thus infecting them with the para-
sites. The worms live for 4 to 6 years lodged in
the lymphatic system, where they reproduce.
The toxicity of the waste products produced by
these worms results in inflammation and ob-
literation of the lymphatic system, leading to
swelling (often extreme) of the lower extremi-
ties and genitalia (Fig. 3−4B).
Lymphatic filariasis has been identified by
the World Health Organization as a leading
cause of permanent and long-term disability in
the world. It is estimated that over 120 million
people have some form of the disease, with
over 40 million people having recurrent infec-
tions and abnormalities. Lymphatic filariasis is
very rare in the United States, but it may be
contracted by visitors to the endemic areas.
The goal of the Global Alliance to Eliminate
Lymphostatic Filariasis is to stop the spread of
filarial infection, thus interrupting transmis-
sion. This is done through the distribution of
free medication in the endemic areas. Lymph-
edema caused by filariasis can be treated
successfully with complete decongestive ther-
apy.
3 Pathology
53
Malignant tumors: Malignant tumors may
mechanically block the lymph flow by pressing
against lymphatic structures from the outside
(see Complications in Lymphedema later in
this chapter). Malignant cells may also infil-
trate the lymphatic system and proliferate in
either lymph vessels (malignant lymphangio-
sis) or lymph nodes, thus blocking the flow of
lymph (Fig. 3−5). Modified CDT protocols may
be applied to address the symptoms associated
with malignancies (Fig. 3−6).
Chronic venous insufficiencies: Insufficient
venous return results in an increase in venous
blood pressure. The subsequent elevation in
blood capillary pressure causes an increase in
net filtrate (see Chronic Venous and Lym-
phovenous Insufficiency later in this chapter).
In its primary function to actively prevent
edema, the lymphatic system tries to compen-
sate for the higher volume of the lymphatic
load of water by the activation of its safety fac-
tor (see Chapter 2, Safety Factor of the Lym-
phatic System). Without initiation of adequate
therapy for the venous problem, the lymphatic
system may develop a mechanical insuffi-
ciency (combined insufficiency) over time, due
to the constant strain (Fig. 3−7).
Immobility: If left without proper care, im-
mobility caused by injuries to the spinal cord,
stroke, or cerebral hemorrhage may eventually
result in similar problems as discussed earlier
(e.g., insufficient venous return with sub-
sequent lymphatic overload).
Self-induced lymphedema: By use of a tour-
niquet (bandages, rubber band), some in-
dividuals produce a combination of venous
and lymphatic obstruction on an extremity to
produce the signs and symptoms of lym-
phedema. The ligature mark is usually easily
identifiable just proximal to the swelling. This
Figure 3−4 A. Lymphatic filariasis endemic countries
(Used with permission from the World Health Organi-
zation). B. Lymphatic filariasis on both lower extremi-
ties.
A
B
Lymphedema
54
Figure 3−5 Malignant lymphedema of the left upper
extremity.
Figure 3−6 Therapeu-
tic approach in malig-
nant lymphedema.
Figure 3−7 Lymphedema in combination with
venous insufficiency (stage 2) on both lower extremi-
ties.
3 Pathology
55
condition is extremely rare. If a therapist sus-
pects self-induced lymphedema (also known
as artificial lymphedema), it is recommended
that he or she contact the referring physician
following the evaluation (Fig. 3−8).
Stages of Lymphedema
Currently, there is no cure or permanent rem-
edy for lymphedema. The transport capacity in
the damaged lymph vessels cannot be restored
to its original level (see Chapter 2, Fig. 2−13).
Table 3−3 Stages of Lymphedema with Typical Symptoms
Stages of Lymphedema Characteristics
쐌
Latency stage
쐌
Lymphangiopathy (also Stage 0/Prestage/
Subclinical stage)
쐌
No swelling
쐌
Reduced transport capacity (TC)
쐌
“Normal” tissue consistency
Stage 1 (reversible stage)
쐌
Edema is soft (pitting)
쐌
No secondary tissue changes
쐌
Elevation reduces swelling
Stage 2 (spontaneously irreversible stage)
쐌
Lymphostatic fibrosis
쐌
Hardening of the tissue (no pitting)
쐌
Stemmer sign positive
쐌
Frequent infections
Stage 3 (lymphostatic elephantiasis)
쐌
Extreme increase in volume and tissue tex-
ture with typical skin changes (papillomas,
deep skinfolds, etc.)
쐌
Stemmer sign positive
If lymphedema is present, the lymphatic sys-
tem is mechanically insufficient; that is, the
transport capacity has fallen below the normal
amount of lymphatic load.
Although the swelling may recede somewhat
during the night in some early-stage cases,
lymphedema is a progressive condition. Re-
gardless of genesis, lymphedema, in most
cases, will gradually progress through its
stages, if left untreated (Table 3−3).
Figure 3−8 Self-induced lymphedema of the left lower extremity (note the ligature mark on the left knee).
Lymphedema
56
There is no specific period of time for a
patient to remain in a particular stage. For ex-
ample, a patient will not be in stage 1 for 4
months and then progress to stage 2 for 6
months before moving to stage 3.
Stage 0
This stage is also known as the subclinical
stage, or prestage, of lymphedema. In this
stage, the transport capacity of the lymphatic
system is subnormal, yet remains sufficient to
manage the (normal) lymphatic load (Fig. 3−1).
This situation results in a limited functional re-
serve (FR) of the lymphatic system (see Chap-
ter 2, Lymph Time Volume and Transport
Capacity of the Lymphatic System).
Patients who underwent surgery (or had
trauma) involving the lymphatic system and
do not experience the onset of lymphedema
are said to be in a latency stage, which is a sub-
category of stage 0. For example, those women
who had surgery for breast cancer (with or
without lymph node dissection and radiation)
and do not present with postmastectomy/lum-
pectomy lymphedema are considered to be in
a latency stage. Again, in these cases, the TC is
subnormal but still sufficient to drain the nor-
mal LL.
A condition known as lymphangiopathy pre-
sents if the TC is reduced by congenital malfor-
mations (dysplasia) of the lymphatic system.
As long as the subnormal TC can manage the
LL, lymphedema is not clinically present.
Patients in a prestage are “at risk” to develop
lymphedema. The reduction in functional re-
serve results in a fragile balance between the
subnormal TC and the LL. The onset of lym-
phedema correlates to the ability of the lym-
phatic system to compensate for any added
stress to the system or the frequency of certain
occurrences that may cause an increase in
lymphatic load of water (or water and protein)
in the limb at risk.
Patient information and education, espe-
cially following surgical procedures, can
dramatically reduce the risk of developing
lymphedema (see Chapter 5, Precautions and
Lymphedema and Air Travel).
Stage 1
This stage, also known as the reversible stage,is
characterized by soft tissue pliability without
any fibrotic alterations. Pitting is easily in-
duced, and the swelling retains the indenta-
tion produced by the (thumb) pressure for
some time (Fig. 3−9). In early stage 1, it is
possible for the swelling to recede overnight.
With proper management in this early stage,
it is possible for the patient to expect reduction
of the extremity to a normal size (compared
with the uninvolved limb). Without proper
care, progression into stage 2 in the vast major-
ity of the cases is inevitable.
It is difficult to distinguish stage 1 lymph-
edema from edemas of other geneses. The clini-
cian needs to rely on the patient’s history and
whether the swelling resolves with conven-
tional management (compression, elevation)
or not (refer to Diagnosis and Evaluation of
Lymphedema later in this chapter).
Stage 2
Stage 2, also known as spontaneously irreversi-
ble lymphedema, is primarily identified by
tissue proliferation and subsequent fibrosis
(lymphostatic fibrosis). Over time the tissue
becomes more indurated, and pitting is diffi-
cult to induce. In stage 2, the Stemmer sign is
positive (Fig. 3−10). A Stemmer sign is positive
if the skin from the dorsum of the fingers and
toes cannot be lifted, or lifted only with diffi-
culty (compared with the uninvolved side). A
positive Stemmer sign is considered accurate
to diagnose lymphedema of the extremities;
the absence of a Stemmer sign, however, does
not exclude the presence of lymphedema
(false-negative Stemmer sign).
Figure 3−9 Pitting lymphedema (stage 1) on the
right hand.
3 Pathology
57
Figure 3−10 Positive Stemmer sign on the second
toe of the right foot in lower extremity lymphedema.
In many cases, the volume of the swelling
increases, which exacerbates the already com-
promised local immune defense (increased
diffusion distance). Because of this, infections
(cellulitis) in this stage are common.
Volume reduction can be expected if proper
treatment is initiated in this stage of lym-
phedema. In most cases, the indurated tissue
will not completely recede in the intensive
phase of Complete Decongestive Therapy (see
Chapter 4). Reduction of fibrotic tissue is
achieved mainly in the second phase of CDT
with compression and good patient compli-
ance (Fig. 3−11).
Lymphedema often stabilizes in stage 2. In
those patients suffering from recurrent infec-
tions, the lymphedema may develop into stage
3, lymphostatic elephantiasis.
Stage 3 (Lymphostatic Elephantiasis)
Typical for this stage are an increase in volume
of the lymphostatic edema and further pro-
gression of the tissue changes. Lymphostatic fi-
brosis increases in firmness, and other skin al-
terations, such as papillomas, cysts, and fistu-
las, hyperkeratosis, mycotic infections of the
nails and skin, and ulcerations, develop
frequently. Pitting may or may not be present.
The natural skinfolds, especially on the dor-
sum of the wrist and ankle, deepen, and the
Stemmer sign becomes more prominent. In
many cases, cellulitis is recurrent (Fig. 3−12).
If lymphedema management starts in this
stage, reduction can still be expected. To
achieve good results, it is necessary to extend
the duration of the intensive phase of complete
Figure 3−11 Primary lymphedema of the right lower extremity before (left) and after (right) complete de-
congestive therapy.
Lymphedema