From physical to ultrasound examination in lymphedema: a novel dynamic approach

Abstract

In daily practice, medical history and physical examination are commonly coupled with anthropometric measurements for the diagnosis and management of patients with lymphatic diseases. Herein, considering the current progress of ultrasound imaging in accurately assessing the superficial soft tissues of the human body; it is noteworthy that ultrasound examination has the potential to augment the diagnostic process. In this sense/report, briefly revisiting the most common clinical maneuvers described in the pertinent literature, the authors try to match them with possible (static and dynamic) sonographic assessment techniques to exemplify/propose an ‘ultrasound-guided’ physical examination for different tissues in the evaluation of lymphedema.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40477-021-00633-4.

Introduction

Lymphedema (LE) is a disorder characterized by the accumulation of protein-rich lymphatic fluid in the (sub)cutaneous tissues [1, 2]. In daily practice, volumetric increase of the limb, dorsal hump of the foot/hand, ‘square toes’ and Kaposi-Stemmer sign are considered as the most valuable physical findings. Coupled with the pinching and pitting tests, they allow the examiner to propose a clinical diagnosis of LE (Jayaraj, Keo) [3, 4]. Herewith, in the pertinent literature, several authors have clearly demonstrated the poor diagnostic performance of the aforementioned classical physical examination as regards the correct diagnosis of lymphatic diseases [3, 5–8].

Considering the potentialities of high-frequency ultrasound (US) imaging in promptly scanning the superficial (soft) tissues and their pathologies, [9–13] the authors strongly propose to couple physical and US examination in clinical practice—to better understand/define the diagnoses in several types of edematous disorders. Indeed, together with the classical physical findings, the US probe allows the examiner to promptly perform ‘sono-inspection’ of the swollen limb and ‘sono-palpation’ of a specific edematous region in LE [9, 14]. Likewise, in this report, we have briefly discussed the most commonly applied clinical signs/tests used for the diagnosis of lymphatic diseases and tried to match them with several sonographic patterns in order to construct an integrated clinical—ultrasonographical approach.

Pitting test

Pitting test is commonly performed in order to promptly assess the presence/amount of water content in the skin [3, 5, 7]. It is characterized by the application of sustained (5–10 s) thumb pressure on the skin whereby the presence of indentation after the release of the pressure indicates pitting edema [3, 5–7]. The depth of the skin indentation is usually considered as an index of the amount of (extra) interstitial fluid located in the skin and, for the same reason, as an indirect sign of edema severity [5, 7]. Histologically, the pitting maneuver induces mechanical effects on the surface of human body causing fluid displacement—i.e. movement of the excess interstitial water in response to pressure—and deformation of the superficial soft tissues (Fig. 1) [7].

Fig. 1.

Sonographic patterns of dermal edema. Applying external forces over the skin surface, mechanical effects are induced at the level of the dermo-epidermal complex during the pitting test (A). The “external” inspection of the macroscopic features of the skin indentation during physical examination may not be sufficient to fully characterize the different patterns/stages of dermal edema (double yellow arrow). Ultrasound examination of the dorsal surface of the forearm (B, C) and the anterolateral surface of the leg (D, E), can be considered an “internal” inspection of the superficial tissues. [Linear Probe, 5–11 MHz]

Unfortunately, the pitting test is not specific for LE; in other words, the superficial indentation of the cutis can be associated with several types of edematous diseases and might display false positivity/negativity due to several pathological conditions [3, 7]. Actually, a weakly positive pitting test may be related to an initial phase of dermal edema (Video 1) with selective involvement of the papillary dermis or, to a “complex” dermal edema with concomitant presence of fluid and cellular infiltration (Fig. 1) [9, 12, 13]. In the former case, physical examination alone can not be sufficient to achieve an early diagnosis of LE. In the latter case, however, the examiner may not correctly identify an advanced phase of the dermal pathology due to the (high-density, weakly compressible) cellular component.

Chronic LE can be regarded as a form of chronic inflammation sustained and stimulated by the accumulation of excess proteins in the interstitial spaces of the superficial tissues, activating the cellular pathways of inflammation [15, 16]. On the other hand, a positive pitting test does not allow a clear differentiation between partial/initial disorganization of the dermal architecture (with the presence of multiple fluid loci disseminated between the fringes of the extracellular matrix) and an advanced condition (with a linear hypoechoic pattern and widespread suppression of the dermal echogenicity—i.e. hypoechoic dermis) (Fig. 1). The latter condition—if not promptly managed—is more prone to progressive disruption of the subepidermal lymphovascular plexus [17] until the fibrotic involution of the dermis with the disappearance of the dermo-hypodermal junction [9, 12]. Similarly, it is worth pointing out that the pressure-induced indentation of the skin (i.e. positive pitting test) may be related to fluid accumulation also deep to the dermo-epidermal complex in the subcutaneous tissue. Interestingly, more than 95% of total tissue fluid retained in soft tissues is located in the subcutis and not in the lymphovascular plexus of the dermis [17]. As such, US examination of the superficial tissues may also be contributory to better define this condition [9–13].

The strength applied during this test is not standardized, and sustained thumb pressure can easily squeeze the dermo-epidermal complex and the subcutaneous layers at the same time—displacing the fluids located in both compartments [4–7]. Of note, the spatial distribution and the grade of the dilatation of the lymphatic collectors of the fibrous scaffold in the subcutaneous tissue are extremely variable (Video 2). Therefore, physical examination alone is not accurate enough to fully evaluate the subcutis involvement in patients with LE [3].

Deep epifascial collectors are usually involved during the early stages of the disease (Video 3) accompanied by progressive dilatation of the ascending oblique lymphatic channels with or without concomitant dermal edema (Fig. 2). Interestingly, in chronic LE, the patient may develop mechanical disruption of the lymphatic collector walls with fluids spreading inside the lax connective tissue [17] forming the lymphatic lakes (Video 4). At this stage, the high pressure inside the epifascial compartment of the limb (i.e. between the epidermis and the epimysium) may strongly reduce the compressibility of the superficial tissues as well as the response to the pitting test (Fig. 2). Accordingly, chronic LE can easily be misdiagnosed as chronic non-pitting edema related to fibrotic involution of the superficial tissues—if physical examination is not promptly supported by ‘sono-inspection’. In severe cases, patients can develop a clinical scenario similar to compartment syndrome, with possible compression of vascular and neural structures of the limb [18].

Fig. 2.

Sonographic patterns of subcutaneous tissue. Classical physical examination of a swollen limb (black arrows) may not be accurate enough to correctly define and map the involvement of the subcutaneous tissue (A). Selective dilatation of the deep lymphatic collectors (white arrowhead) (B) can progressively advance with distension of the ascending oblique lymphatic channels (yellow arrowhead) and severe dermal edema (red arrowhead) with linear pattern and complete involvement of the papillary and reticular dermis (C, D) at the level of the thigh. In advanced phases, lymphatic lakes (L) may completely change the histological architecture of the subcutaneous tissue resulting in hard, non-pitting edema at the level of the leg (E, F, G). [Linear Probe, 5–11 MHz]

Among the several presentations of lymphatic diseases, we should also keep in mind that non-pitting edema may be related to peculiar distribution of fluids at the level of the adipose lobules of the subcutis rather than into the interstitial space of the dermis and/or in the lumen of lymphatic collectors [9, 13, 19, 20]. In fact, fluid can be widely scattered inside the stromal matrix of the fatty lobule in the subcutaneous layer generating a swollen subcutis, which is tumescent and hardly compressible. Herein, the clinically evaluated non-pitting edema can be matched with a sclero-edematous sonographic pattern of the subcutaneous tissue [9, 12, 20] (Fig. 3).

Fig. 3.

Lipedema and fibrosclerosis: potential patterns of “Non-Pitting Edema”. Magnetic resonance imaging clearly shows the circumferential and uniform thickening of the subcutaneous adipose tissue (yellow arrowheads) in the lower limb (A) without fluid collections and/or dilatations of the lymphatic channels (B). The corresponding sonogram is characterized by a normal trilaminar structure of the dermo-epidermal complex (white arrowheads) and a sclero-edematous pattern of the subcutaneous tissue (double dotted arrow) with poor visualization of the fibrous scaffold and fatty lobulation at the level of the thigh (C). The fluids are mainly distributed in the stromal matrix (inset) of the fatty lobule (D). Comparative scanning (E) promptly shows the disappearance of the dermo-hypodermal junction (white arrowheads) and the lobulation loss of the subcutis in case of chronic lymphatic disease and non-pitting edema at the level of the forearm (F). [Linear Probe, 5–11 MHz]

Of note, fluids are not displaceable upon pressure application because they are neither contained inside cavitated collecting structures (e.g. lymphatic collectors) nor located inside a soft and superficial environment (e.g. the interstitial space of the dermis); but they are rather “entrapped” inside the extracellular matrix of the adipose lobule [9, 12]. The infiltrating edema among the adipocytes produces multiple reflective interfaces inside the fat lobules. This peculiar histological condition is probably related to the reduced visualization of the fibrous scaffold of the subcutis (i.e. blurred visibility of the fat compartmentalization) with a coarse echotexture of the subcutaneous tissue—“snowfall pattern” (Video 5) [9, 12]. Mechanical disruption of the fibrous scaffold is induced from the edematous fatty lobules, and the spatial disorganization of the connective tissue often generates peculiar sonographic artifacts presenting as acoustic shadows with irregular morphology (Video 5) [21].

Chronic deposition of protein-rich lymphatic fluid in the intercellular space of the subcutaneous lobules induces progressive adipocyte hypertrophy until the fibrotic involution of the subcutis [15, 16]. In this sense, early identification of the sclero-edematous pattern can be paramount to avoid the transition to a fibro-sclerotic pattern (Video 6) [9, 12]. Lastly, non-pitting edema can (also) be related to the fibrotic involution of the dermis and/or subcutaneous fat in patients with chronic LE [22] whereby US examination can promptly confirm the clinical scenario (Fig. 3) [9, 12]. Lobulation loss and lamellar pattern of the subcutis, hyperechogenicity of the different tissue layers, and poor visualization of the dermo-hypodermal junction are the most common US findings in patients with fibro-sclerotic pattern [9, 12]. Combined with the clinical features of the soft tissues during superficial/deep palpation, US examination can definitely help to better characterize long-lasting non-pitting edema.

Dorsal hump and pinching test

Dorsal hump is usually referred as focal swelling of the superficial soft tissues on the dorsum of the hand/foot in patients with LE [3, 6]. During physical examination, the hump can be palpated to assess its consistency (e.g. soft, hard, elastic) and compressibility [3, 4]. As previously mentioned, clinical tests alone are not accurate enough to fully define the morphological features of the hump [3, 4]. For instance, non-pitting hump of the foot can be related to different pathological conditions. Poor compressibility of the dorsum of the foot can be related to a fibro-sclerotic pattern of the subcutaneous tissue (e.g. chronic lymphatic disease) or to distal high-pressure edema located in between the fascial layers (Video 7). Indeed, due to the peculiar anatomy of this region, local fluids can dissociate the adipose lobules in the deep layers (i.e. ‘cobblestone’ pattern) and separate the dorsal fasciae in the more superficial layers (i.e. striped pattern) (Fig. 4) [23]. Due to the restraining-compressive effect provided by multiple fascial layers, a high-pressure compartment can develop over the dorsum of the foot which is hardly compressible and distinguishable from fibrotic involution of the subcutis upon classical palpation. Of note, the differential diagnosis between the two aforementioned conditions is paramount in order to accurately manage the patient and correctly define the conservative and/or surgical approach.

Fig. 4.

Sonographic patterns of the dorsal hump and ultrasound guidance for the pinching test. Non-pitting dorsal hump of the foot (A) may be related to selective fibro-sclerotic pattern of the subcutaneous tissue (double white arrow) (B)—without the involvement of the dermo-epidermal complex (white arrowheads)—as well as to complex edema (C) with a combination of ‘striped’ pattern (double red arrow) in the superficial compartment and ‘cobblestone’ pattern (double yellow arrow) in the deep compartment. The inability of the examiner in pinching and lifting the soft tissues of the limb from the deep layers, generating a superficial plication (D) is a test not sensitive enough to differentiate loss of the dermo-hypodermal junction in the early phase (with dilatation of the lymphatic collectors) (E) from an advanced phase of the disease (with fibrotic involution of the subcutis and lobulation loss) at the level of the forearm (F). [Linear Probe, 5–11 MHz]. MT metatarsal bone, V vein

Another clinical maneuver—commonly performed in daily practice to evaluate patients with lymphatic diseases—is the pinching test of the skin. The examiner’s ability to pinch and lift the superficial tissues of the affected anatomical region—dissociating them from the underlying anatomical planes—is considered as normal pinching test [8, 24]. Using the thumb and the index/middle finger, it is also possible to compare the texture of the superficial tissues between the healthy and pathological limbs, assessing whether the skin on the affected side is thicker and tighter than that on the unaffected side [24]. Unfortunately, the test is highly non-specific because it is not possible to exactly know which tissue layer (e.g. dermo-epidermal complex, subcutaneous tissue or both) we are pinching during the maneuver. Therefore, it is not possible to correctly define where the edematous/fibrotic changes are.

For instance, an abnormal pinching test can be related to severe thickening of the subcutaneous tissue with tensioning of the overlying skin (making it hardly pinchable) or to fibrotic adhesions between different layers of the superficial tissues. In the former case, US examination promptly allows the examiner to measure the thickness of the subcutis and check for the specific (e.g. ‘cobblestone’, sclero-edematous, double) sono-patterns. Likewise, in the latter case, US evaluation can confirm the disappearance of the dermo-hypodermal interface with an undifferentiated, fibrotic pattern involving the dermis and the subcutaneous tissue (Fig. 4) [9, 12]. On the contrary, in some patients, the fluids can infiltrate directly to the dermo-hypodermal junction, progressively dissociating the two histological planes and leading to a hypermobile dermis with respect to the underlying subcutaneous tissue (i.e. dermo-hypodermal dissociation) (Video 8). In that case, the dermo-epidermal complex can appear normal during the pinching test (i.e. dissociable from the deep planes) while the US assessment still shows pathological changes of the superficial tissues.

Ultrasound-Guided refill test

Considering the very superficial location of the US findings in LE, [9, 10, 12, 13] gentle compression/decompression using the probe (i.e. superficial sono-palpation) can be used to evaluate how the target tissues react to the phases of squeeze and release [14]. For instance, this US-guided maneuver can be promptly performed to dynamically image a cluster of dilatated lymphatic collectors in the subcutaneous tissue. During the first phase (gently pushing the probe over the skin surface), it is possible to induce collapse of the distended lymphatic channels, bringing the adipose lobules closer to each other. While slowly lifting the probe, it is possible to clearly observe the progressive dilatation of the lymphatic collectors in the fibrous scaffold of the subcutaneous tissue, coupled with rarefaction of the fatty lobules (i.e. refilling phase of the lymphatic network) (Video 9). Of note, mapping the spatial distribution of the fluid collections during the compression/decompression cycles allows the examiner to promptly differentiate the superficial veins from the lymphatic vessels. In fact, the latter present peculiar architecture arranged as a web between the subcutaneous adipose lobules.

In advanced stages of LE, high-pressure fluid collection may lead to the formation of a lymphocoele—i.e. lymphatic pseudocyst with a smooth endothelial wall [25]. In patients with chronic lymphatic diseases, the classical palpation alone would not suffice to correctly discriminate a lymphocoele from other pathological conditions characterized by focal swellings (e.g. lymphatic lakes or fatty lobules’ edema) [3, 6, 9]. Instead, combined US—physical examination can precisely confirm the presence and the shape of lymphatic pseudocysts with static (Supplementary Fig. 1) and dynamic (Video 10, 11) assessment. Posterior enhancement and lateral acoustic shadows are the classical US artifacts of cystic formation [21] and the high density of echoes suspended inside the lumen are quite characteristic for the protein-rich lymphatic fluid [25].

Conclusion

Cornerstones in the diagnosis of LE are medical history and physical examination. However, owing to the potentiality of US examination in evaluating the superficial tissues, it is possible/feasible/reasonable to combine physical and US examinations [26, 27] as an important strategy to augment the diagnosis of LE in daily practice. To this end, starting from the histo-anatomy of the (sub)cutis and getting acquainted with the US patterns of different pathological conditions, physicians can readily empower the above discussed clinical evaluations while dealing with LE patients.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

This research received no external funding.

Declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

No institutional review board (IRB) has been established to collect images necessary for the manuscript but, written permission was obtained from all the patients involved.