1.2. Complications of Oncologic Treatments: Focus on Lymphedema
Among the most significant complications of surgical and radiotherapeutic treatments is secondary upper-limb lymphedema, a condition characterized by protein-rich fluid accumulation in the interstitial tissue with physical, functional, and aesthetic repercussions. Lymphedema may arise even years after undergoing an oncologic treatment and, if not recognized early, tends to become chronic, causing pain, functional limitations, and psychological distress. It is more accurate to refer to chronic edema (not to be confused with acute edema, a temporary post-traumatic fluid accumulation), defined as interstitial fluid accumulation lasting at least 3 months due to dynamic or mechanical lymphatic insufficiency. Dynamic (functional) lymphatic insufficiency refers to conditions where fluid accumulation results from increased capillary filtration despite a structurally intact lymphatic system. Causes include venous insufficiency, inflammatory processes, and conditions altering oncotic pressure (e.g., hypoalbuminemia). Dynamic insufficiency may evolve into mechanical insufficiency. Mechanical lymphatic insufficiency refers to structural damage—primary or acquired—of the lymphatic system. Beyond a critical threshold of capillary filtrate, intrinsic lymphatic dysfunction prevents adequate reabsorption. Persistent interstitial stagnation triggers mechanotransduction processes stimulating fibroblasts to produce collagen fibers, leading to tissue sclerosis and preadipocyte proliferation.
1.2.1. Classification
Several classification systems exist, each emphasizing different aspects. When the etiology is considered, lymphedema may be classified as primary, secondary, or mixed. From a pathogenetic perspective, it may be classified as functional/overload (dynamic insufficiency) or mechanical insufficiency.
1.2.2. Staging
Multiple staging systems have been proposed, though none has achieved universal consensus, as no single system is considered fully comprehensive. The most widely used is the International Society of Lymphology staging system, which divides lymphedema into four stages based on clinical and instrumental criteria:
• Stage 0 / Ia: Subclinical stage in which edema is not clinically detectable, although patients may report suggestive symptoms and instrumental findings may be present. This stage may persist for months or years before becoming clinically evident.
• Stage I / Ib: Edema is visible and may regress during the day or with limb elevation; pitting may be present.
• Stage II: Persistent, non-reversible edema with pitting; tissue changes and fibrosis modify skin consistency.
• Stage III: The limb is markedly deformed by lymphostasis, with non-pitting edema due to advanced tissue fibrosis; cutaneous alterations may also be present.
1.2.3. Diagnosis
Diagnostic work-up should include detailed medical history, careful physical examination, and instrumental support. Risk factors such as previous malignancies, adjuvant or neoadjuvant radio-chemotherapy, and potential exposure to infectious agents (e.g., tropical travel) must be investigated. A positive family history may suggest hereditary forms, while associated signs and symptoms can indicate syndromic presentations. Patients with lymphedema report symptoms varying with severity, including heaviness, swelling, tightness, discomfort, and functional limitations. In severe cases, skin discoloration, thickening, and pruritus may also occur. A thorough clinical evaluation involves the assessment of morphological contours: reduced visibility of extensor tendons, superficial venous network, and bony prominences (e.g., knuckles, styloid processes in the upper limb). Surgical scars must be examined, as dystrophic or adherent scars may impede lymphatic return. Factors such as radiotherapy, aromatase inhibitors, surgical technique, weight gain, and age can affect one’s range of motion, particularly at the shoulder. In advanced stages, cutaneous signs of fibrosis may develop, including hyperkeratosis, lymphatic cysts, lichenification, and accentuation of the dermal papillae (peau d’orange). Potential complications should also be carefully assessed.
On palpation, characteristic findings include:
• Consistency:
Texture varies with severity. Early stages show soft tissue due to fluid accumulation. With fibrosis affecting skin and subcutis, tissue becomes firm or woody. A grading scale may be used:
Grade 0: normal
Grade 1: elastic
Grade 2: fibro-elastic
Grade 3: fibrotic
• Pitting Edema Scale:
Assessed by maintaining pressure for at least 10 seconds and evaluating the depth and persistence of the indentation:
Grade 1: <2 mm, immediate rebound
Grade 2: 2–4 mm, disappears within seconds
Grade 3: 4–6 mm, disappears within 10–12 seconds
Grade 4: 6–8 mm, persists >20 seconds
Skin Foldability: also known as the Stemmer test, it consists of assessing the increase in cutaneous foldability—normally difficult to detect—at the dorsal aspect of the proximal phalanx of the second toe or finger. In the early stages of lymphedema, foldability appears increased due to the presence of fluid layers within the dermis and subcutis; in more advanced stages, however, fibrotic degeneration leads to reduced foldability. In some cases, the assessment of foldability may be extended to the entire limb
Figure 2.
Stemmer test a-b.
Figure 2.
Stemmer test a-b.
Volumetric measurements: that is, the assessment—using a measuring tape—of any increase in the size of the body region affected by lymphedema. The assessment involves multiple anatomical reference points. For the upper limb, the first measurement is performed at the level of the hand, using the figure-of-eight measurement technique.
The second measurement is taken at the level of the distal wrist crease, used as a reference point because it tends not to disappear even in the most severe cases of obesity. From this landmark, subsequent measurements are taken every 5 cm in a distal-to-proximal direction. According to the new guidelines, however, other parameters are now preferred. Regarding simple circumferential measurements, an increase of at least 2 cm compared with the healthy contralateral limb at any single reference point is considered indicative of lymphedema. These measurements also make it possible to compare the percentage volumetric variations—again relative to the healthy contralateral side. Instrumental examinations: Although medical history and physical examination are generally sufficient for the diagnosis of lymphedema, integrating first- or second-level instrumental assessments is often valuable—particularly to clarify ambiguous cases, better define disease severity, and differentiate among potential etiologies.
The most commonly used instrumental examinations include:
• High-resolution ultrasound
• Doppler ultrasound: useful for evaluating the deep venous system
• Lymphoscintigraphy: useful for assessing superficial and deep lymphatic vessels and lymph nodes and therefore considered the gold standard for diagnosing lymphatic abnormalities
For the diagnosis of lymphedema, at least one clinical criterion and one suggestive lymphoscintigraphic finding are required. This technique involves the injection of a radiotracer into the subcutaneous tissue at the first interdigital space of both hands or feet, depending on the location of lymphedema; the radiopharmaceutical is typically administered in two low-dose injections (thus carrying very low risk of ionizing radiation exposure and allergies). As it follows the lymphatic pathways, it reveals outflow obstructions through gamma-camera detection. The main limitation of this technique is insufficient standardization, as protocols differ regarding the radiotracer dose, injection site, and physical activity required during the exam. For preventive purposes, lymphoscintigraphy is recommended for patients at high risk of subclinical secondary lymphedema (e.g., after major lymphadenectomy at the limb root) and for relatives of patients with primary lymphedema.
• Lymphography: usually performed with direct oily contrast; rarely used today except in specific situations such as congenital or acquired disorders of the chylous vessels, cisterna chyli, or thoracic duct
• Bioimpedance analysis: a technique that correlates variations in electrical conduction velocity with tissue composition; it enables the detection of subclinical lymphedema by identifying even minimal compositional changes in the limb. Recent studies suggest that bioimpedance analysis, when normalized to limb length, may provide a standardized outpatient protocol for the quantitative assessment of unilateral lymphedema, offering greater reliability than simple circumferential measurements.
• Perometry: a technique that uses infrared light beams to assess limb volume; it is extremely rapid, accurate, and reproducible, and is primarily used in specialized centers
• MR lymphangiography: particularly when using fat-suppression digital subtraction techniques, it can provide important information in advanced obstructive cases where lymphatic pathways appear dilated and filled with lymph
• CT lymphangiography: also used in complex cases involving vessel or cisterna chyli abnormalities
• Water-displacement plethysmography: considered the gold standard for calculating limb volume and the only reliable method for measuring edematous hands and feet. The principle is that a submerged body displaces a volume of water equal to its own. However, practical limitations—such as hygiene concerns — restrict its use
• Filarial antigen card test: used to detect Wuchereria bancrofti infection (Bancroftian filariasis), and therefore a possible infectious etiology of lymphedema, by identifying antibodies in individuals who live in or have traveled to endemic areas
• Genetic testing: identifies the most frequent mutations associated with familial primary lymphedema (e.g., FOXC2, VEGFR-3, SOX18).
1.5. Basics of Ultrasound
Ultrasound imaging is a highly versatile and easy-to-use diagnostic technique that employs mechanical waves—ultrasound—to generate digital images. Diagnostic ultrasound typically uses frequencies ranging from 2–3 MHz to 20 MHz. These waves propagate through tissues via cycles of compression and rarefaction at speeds determined by the physical properties of the medium. They are generated by the transducer, a component of the ultrasound machine that contains a piezoelectric material, which changes shape in response to an applied electrical potential.
When ultrasound waves encounter tissues with different impedance—a physical property related to tissue density—a portion of the waves is reflected and captured by the ultrasound system. In other words, impedance variations, known as interfaces, are detected, and converted into an analog signal, with depth represented on the x-axis and signal amplitude (in dB) on the y-axis. The analog trace is then converted into a digital signal in which each characteristic corresponds to white, black, or a shade of gray in the final image.
Figure 3.
Schematic representation of the ultrasound image acquisition process.
Figure 3.
Schematic representation of the ultrasound image acquisition process.
1.5.1. Ultrasound of Healthy Superficial Tissues
Typically, probes used for the assessment of the skin and subcutis operate at a frequency of 20 MHz, although an accurate ultrasound examination can be performed with any probe of at least 15 MHz. Frequencies higher than 20 MHz, despite offering potentially greater detail, allow for reduced tissue penetration. Standard ultrasound systems are used, without requiring dedicated software.
Ultrasound imaging of superficial tissues allows for the visualization of:
• Epidermis, the outermost layer, which appears as a thin, uniform hyperechoic line.
• Dermis, located deeper, which appears as a hyperechoic band (although less hyperechoic than the epidermis), with thickness varying according to the anatomical region. The dermis comprises a more superficial papillary dermis, which is more hypoechoic due to its high water content, and a deeper reticular dermis, which is more hyperechoic because of the density and orientation of collagen fibers. The epidermis, papillary dermis, and reticular dermis together form the dermo-epidermal complex (DEC).
• Hypodermis/subcutis (SUBC), the innermost layer, clearly separated from the DEC by the dermo-hypodermal junction, a continuous, well-defined line reflecting the structural differences between the dermis and hypodermis. The hypodermis appears hypoechoic, organized into lobules, and intersected by thin horizontal or oblique hyperechoic lines representing connective-tissue septa (scaffolds) through which lymphatic vessels run. These septa tend to be parallel to the muscular fascia and may form interconnections with it. The end of this layer is marked by the beginning of the muscular layer, and its thickness varies according to anatomical site and adipose-tissue content.
A proper evaluation of superficial tissues should also include the generous application of gel and the use of minimal pressure during probe manipulation. These precautions help prevent excessive deformation of the underlying tissues, allowing for an accurate visualization of structures without operator-induced artifacts.
Figure 4.
Ultrasound of superficial tissues in a healthy subject. The hyperechoic epidermis, the hypoechoic papillary dermis, and the hyperechoic reticular dermis can be identified, as well as the hypoechoic hypodermis traversed by hyperechoic fibrous septa.
Figure 4.
Ultrasound of superficial tissues in a healthy subject. The hyperechoic epidermis, the hypoechoic papillary dermis, and the hyperechoic reticular dermis can be identified, as well as the hypoechoic hypodermis traversed by hyperechoic fibrous septa.
1.5.3. Ultrasound of Superficial Tissues in Patients with Lymphedema
The rationale for the ultrasound assessment of superficial tissues in patients with lymphedema does not lie in identifying intrinsic damage to the lymphatic system itself, as the resolution of standard ultrasound equipment used for this type of examination does not allow direct visualization of lymphatic vessels. Specifically, when affected by disease, the deeper canalicular component containing lymphatic collectors may become visible due to dilation and disruption of the fibrous scaffold; however, the subepidermal lymphatic plexus cannot be directly evaluated.
The objective, therefore, is to identify indirect tissue alterations that reflect lymphatic dysfunction, such as differences in echogenicity and thickness of the various layers of the skin and subcutis. In unilateral lymphedema, the healthy contralateral limb is always used as a point of comparison; in bilateral cases, previous examinations serve as the reference point.
Although the number of studies evaluating the role of ultrasound in lymphedema is still limited, several have laid the groundwork for its systematic use in clinical assessment. Of particular relevance is the study by Tassenoy et al. (2011), an observational study involving seven women with unilateral breast cancer who developed lymphedema. Limb volume increase was measured using water-displacement plethysmography, and ultrasound findings were correlated with MRI to assess tissue-structure changes [
20].
Similarly, the retrospective study by Suehiro et al. (2013) examined 35 patients with secondary lower-limb lymphedema by evaluating the skin and subcutis at eight standardized points. In the subcutaneous tissue, three grades of echogenicity were identified. This study highlighted that variations in tissue echogenicity correlate with lymphedema stage according to the International Society of Lymphology, and that such evaluation is feasible using probes operating at 11 MHz.
One of the most influential studies demonstrating the feasibility of a standardized ultrasound assessment protocol in lymphedema was conducted by Mander et al. (2019). This study precisely identified distinct ultrasonographic patterns representing progressive histological degeneration in the dermo-epidermal complex (DEC) and subcutis (SUBC) of the upper limb after mastectomy. These findings laid the foundation for a more objective evaluation of lymphatic-system compromise [
20].
Based on Mander’s work, characteristic ultrasound patterns can be identified in both the dermo-epidermal complex and the subcutis, each reflecting progressive stages of histological alteration. Specifically, for the dermo-epidermal complex, the following patterns may be observed:
• Dermal edema
This condition is characterized by increased DEC thickness and reduced echogenicity (hypoechoic dermis). It is caused by the dilation of the subepidermal lymphatic plexus, leading to leakage of fluid into the dermal interstitium and the formation of vessel-like structures between collagen bundles lacking endothelial lining (a phenomenon known as dermal backflow). The papillary dermis is typically affected earlier than the reticular dermis due to differences in vascular and lymphatic distribution and collagen architecture.
Some authors suggest an association between dermal edema and paresthesias, attributed to stretching and irritation of sensory nerve endings.
This acute-stage pattern is sonographically identified as F-DEC (fluid dermo-epidermal complex).
• Dermal sclerosis with infiltrative changes
This pattern shows a marked increase in DEC thickness, increased echogenicity (hyperechoic dermis), and loss of the typical trilaminar DEC structure. These findings are due to cellular infiltration and early collagen-fiber deposition.
This pattern reflects a subacute or evolving stage and is identified as S-DEC (sclerotic dermo-epidermal complex). It is considered partially reversible.
• Dermal sclerosis with fibrotic involution
This condition is characterized by the loss of the dermo-hypodermal interface, resulting in a homogeneous echogenic appearance across tissues, making it difficult or impossible to accurately measure individual layers. These changes are due to chronic collagen deposition, ultimately leading to dermal fibrosis.
This chronic, irreversible stage is identified as M-DEC (mixed or markedly sclerotic dermo-epidermal complex).
The normal pattern of the dermo-epidermal complex is labeled N-DEC.
Regarding the subcutaneous tissue, the following patterns may be observed:
• Dilation of lymphatic ducts
In this condition, the hyperechoic signal of the fibrous connective septa disappears and the subcutis becomes globally thickened. This disappearance is due to the dilation of the lymphatic collectors running within the fibrous strands, which leads to a marked separation of the adipose lobules (a cobblestone appearance). In some cases, dilated lymphatic collectors may cause a rupture of the fibrous septa, resulting in the formation of so-called lymph lakes. Unlike dilated lymphatic collectors, lymph lakes collapse under pressure from the ultrasound probe.
This pattern is identified as F-SUBC (fluid subcutaneous).
• Edema and infiltrative phenomena of adipose lobules
This condition is characterized by increased echogenicity of the subcutaneous tissue, poor visualization of the fibrous framework, and overall thickening of the subcutis. It is caused by an infiltration of fluid and cells into the stromal component of adipose lobules—i.e., at the intercellular level— resulting in a sclerotic-edematous appearance known as “snow-fall”. In addition, mechanical pressure within the lobules may lead to the formation of a network of microscopic fissures in which fluid can accumulate.
• Subcutaneous sclerosis with fibrotic involution
This condition shows increased echogenicity and reduced thickness of the subcutis. It results from the replacement of adipose lobules with fibrotic tissue and collagen fibers, producing a fibro-sclerotic pattern. When the subcutis reaches this stage, and when a dermo-epidermal complex already shows dermal fibrosis, the dermo-hypodermal interface may become indistinguishable.
These latter two patterns are classified as S-SUBC (sclerotic subcutaneous).
The normal pattern of the subcutis is labeled N-SUBC.
In clinical practice, differentiation between patterns is not always clear-cut, and features of different patterns may coexist within the same ultrasound image, producing blended or transitional appearances.
1.5.4. Ultrasound Examination Protocol
As noted previously, the ultrasound evaluation was performed several weeks after the outpatient visit, within the National Health Service framework for patients with suspected chronic secondary lymphedema after mastectomy for breast cancer. The examination—always conducted by the same operator—required several technical precautions, such as the use of abundant gel, positioning the probe perpendicular to the skin, and stabilizing the grip by resting the little finger on the patient’s skin.
Figure 5.
Technique for the correct execution of ultrasound examination of skin and subcutis.
Figure 5.
Technique for the correct execution of ultrasound examination of skin and subcutis.
The standardized approach to the ultrasound examination, as outlined by Mander et al. and later by Ricci et al., involved dividing the upper limb into 17 total sectors: one sector on the dorsal surface of the hand near the third metacarpal ray, four anterior and four posterior sectors below the elbow, and four anterior and four posterior sectors above the elbow.
Figure 6.
Division of the upper limb into 17 total sectors.
Figure 6.
Division of the upper limb into 17 total sectors.
Each sector was then analyzed both qualitatively and quantitatively.
From a qualitative standpoint, the patterns previously described by Mander et al. and later by Ricci et al. were used to classify the findings. Specifically, for the dermo-epidermal complex (DEC):
• N-DEC: normal dermo-epidermal complex
• F-DEC: fluid dermo-epidermal complex
• S-DEC: sclerotic dermo-epidermal complex
• M-DEC: undifferentiated dermo-epidermal complex
For the subcutis (SUBC):
• N-SUBC: normal subcutis
• F-SUBC: fluid subcutis
• S-SUBC: sclerotic subcutis
From a quantitative standpoint, it was possible to measure dermal and subcutaneous thickness and compare these values with those of the healthy contralateral limb. Dermal thickness was measured from the deep surface of the epidermis to the dermis–subcutis transition; subcutaneous thickness was measured from the dermis–subcutis junction to the deep fascia.
(Tassenoy et al., 2011; Suehiro et al., 2013; Mander et al., 2019; Ricci et al., 2021)
1.5.5. International Guidelines and Dermo-Aesthetic Recommendations
Recent multidisciplinary recommendations highlight the need for an integrated approach to the management of patients with breast cancer. In particular, the international article by González et al. (2024) provides clinical guidelines for aesthetic medicine and oncologic rehabilitation.
These interventions must be incorporated into a multidisciplinary pathway involving oncologists, dermatologists, physiotherapists, nutritionists, and specialists in aesthetic and reconstructive medicine.
They include:
Dermatology: Prevention and management of cutaneous toxicities using emollients, photoprotection, and targeted treatments for alopecia, hand–foot syndrome, and nail alterations.
Physiotherapy: Manual lymphatic drainage, progressive exercise, prevention and treatment of lymphedema, mobilization techniques, and hydrotherapy.
Plastic Surgery: Breast reconstruction procedures.
Aesthetic Medicine: Scar treatments, fillers and botulinum toxin, laser, and radiofrequency devices, with specific recommendations regarding timing.
Nutrition: Mediterranean diet and body-weight management as prognostic factors.
Dentistry: Prevention and management of oral complications (mucositis, xerostomia, bisphosphonate-related osteonecrosis of the jaw).
Gynecology and Aesthetic Gynecology: Management of genitourinary syndrome of menopause (GSM) with non-hormonal or low-risk topical options.
The integration of these recommendations into clinical practice improves quality of life and reduces the side effects associated with cancer treatments.
Dermo-Aesthetic Interventions
• Fractional lasers (CO2, Er:YAG) and radiofrequency: improve skin texture and post-radiotherapy fibrosis
• Microneedling: stimulates dermal regeneration, useful for linear scars
• Botulinum toxin: reduces scar retraction and scar-related pain
- 2.
Regenerative Treatments
• PRP: stimulates fibroblasts and angiogenesis through growth factors
• Lipofilling: restores volume and improves skin trophism
• Nanofat: enhances skin texture and radiotherapy-induced dyschromias
- 3.
Fillers and Botulinum Toxin
• Hyaluronic acid fillers: correct scar depressions and contour irregularities
• Collagen stimulators: induce progressive improvement in skin quality
• Botulinum toxin: also beneficial for post-mastectomy neuropathic pain
- 4.
Laser and Energy-Based Devices
• CO2/Er:YAG lasers: surgical scars, fibrosis, radiotherapy tattoos
• IPL: treatment of skin dyschromias
• Carboxytherapy: improves microcirculation and reduces scar fibrosis
- 5.
Reconstructive Plastic Surgery
• DIEP flap and autologous flaps for breast reconstruction
• Implants with or without tissue expanders
• Mastopexy or mastoplasty for post-treatment asymmetries
- 6.
General Recommendations
• Timing: preferably 6–12 months after oncologic treatments
• Personalization: procedures should be calibrated based on clinical and ultrasound findings
• Multidisciplinarity: coordination among oncologists, plastic surgeons, dermatologists, and aesthetic physicians
Breast cancer patients frequently experience cutaneous and physical side effects resulting from oncologic treatments. For this reason, dermo-aesthetic care plays an important role in improving quality of life, body image, and overall well-being [
9,
11,
18]. Proper skin care for the face and body is essential, as treatments can lead to dryness, pruritus, and irritation. The use of gentle cleansers, emollients, fragrance-free creams, and consistent photoprotection, helps to maintain the integrity of the skin barrier. During treatment, the scalp and hair become fragile: scalp cooling can reduce the risk of alopecia by half, while wigs and headscarves provide valuable psychological and aesthetic support. Hand–foot syndrome may cause pain, swelling, and erythema, affecting daily activities; therefore, preventive and soothing treatments are recommended. Nail changes—including discoloration, fragility, and periungual infections—also require preventive and targeted management. All procedures must be carefully evaluated and coordinated with the oncologist to ensure safety and individualized care. In summary, dermo-aesthetic recommendations include tailored skincare, strategies against alopecia and nail fragility, and aesthetic and reconstructive support, always within a multidisciplinary framework involving oncology, dermatology, and aesthetic medicine.
The goal is to reduce treatment-related side effects, improve self-perception, and restore overall well-being. Aesthetic medicine procedures therefore represent fundamental rehabilitative tools for patients treated for breast cancer. When properly integrated, they improve quality of life, self-esteem, and adherence to therapeutic programs. The integration of high-resolution ultrasound further allows for the personalization of treatments based on clinical stage.