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Liang et al. Plast Aesthet Res 2019;6:23 I http://dx.doi.org/10.20517/2347-9264.2019.33 Page 3 of 9

As edema persists, difficulty of fitting clothing, joint dysfunction and musculoskeletal agony may appear.
Characteristic skin changes including peau d’orange (pitted or dimpled skin texture), Kaposi-Stemmer
sign (the inability to pinch the fold of skin at the base of the second toe) and squared off appearance of
toes assists to identify lymphedema. Hyperkeratosis and fibrosis with verruca and nodules usually indicate
advanced stages. Lymphedematous extremity is prone to recurrent infection, cellulitis lymphangitis,
lymphorrhea and skin ulceration. Angiosarcoma that initially presents itself as red-purple nodules with/
without satellite lesions is a rare but lethal complication.

Laboratory examinations such as routine blood test, thyroid function or urinalysis are in need to rule out
other causes of edema, including renal, heart or hepatic failure etc. Though thorough history, physical and
laboratory examinations could help to diagnosis > 90% lymphedema patients, lymphedema in early stages
could be surprisingly challenging to diagnose, making assistant methods necessary for early detection and
confirmation.

STAGING
It’s widely accepted that lymphedema progresses through 4 stages. Stage 0 is the subclinical stage where
swelling is absent but with impaired lymph transport and possible complaints of discomfort or heaviness.
Stage 1 is spontaneously reversible edema that subsides with limb elevation, while the swelling of stage 2
could not be relieved by elevation. Stage 3, also known as lymphostatic elephantiasis, describes nonpitting
[2,9]
edema, fibrosis, hyperkeratosis and the aforementioned complications .

DIAGNOSTIC TECHNIQUES
Lymphoscintigraphy
Lymphoscintigraphy has been regarded as the gold standard for the diagnosis of lymphedema since its first
introduction. It involves the intradermal or subcutaneous injection into the hand or feet of radiolabeled
particles usually under the size of 100 nmol/L, such as 99m Tc (Technetium) human serum albumin
nanocolloid, 99m Tc sulfur colloid and 99m Tc albumin colloid. Gamma camera systems are applied to
capture the radiopharmaceutical emission as it is taken up and transported by the lymphatic vasculature.
Lymphoscintigraphy demonstrates the lymphatic vessels efferent from the injected sites and lymph nodes
along the pathway. Typical abnormalities include formation of collateral lymphatic channels, asymmetric
visualization of lymphatic channels, delayed or asymmetric node uptake, absent or delayed visualization of
lymph nodes, unusual visualization of the popliteal or antecubital lymph nodes (compensatory mechanism
involving deeper lymph pathways) [10,11] .

Dermal backflow, accumulation of tracer outside the main lymph routes and in cutaneous lymphatices,
and lymphangiectasia are considered major diagnostic findings for lymphedema. Other than morphologic-
qualitative information, lymphoscintigraphy provides us with quantitative information of the lymphatics.
Commonly used parameters consist of TAT (tracer appearance time, the time from injection to the
appearance of the tracer in the inguinal or axillary lymph nodes, normally < 10 min) and TI (Transport
Index, normally ranges from 1 to 10).

[12]
Hassanein et al. in their study including 227 patients (454 limbs) suggested the sensitivity and
the specificity of lymphoscintigraphy for lymphedema is 96% and 100% respectively. Early primary
lymphedema may result in false-negative lymphoscintigrams so repeat lymphoscintigraphy is
[12]
recommended . The recently developed Taiwan Lymphoscintigraphy Staging might provide a new angle
[13]
of assessing the severity of lymphedema . Lymphoscintigraphy is also valuable in early detection and
treatment selection, especially surgical planning as it allows to seek out possible functional lymphatic
vessels for vessels to use for lymphatic-venous anastomosis (LVA). Compared to lymphangiography, the